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The tectonic of the Middle and Late Ordovician in the western margin of the north China Platform is complex, and the accumulation models of organic matter of the Wulalike Formation formed during this period are still unclear. Total organic carbon (TOC) content, mineral composition, organic carbon isotope composition, as well as the major and trace elements in the shale samples were all measured in this study. The Wulalike Formation was formed during a tectonic transition from a passive continental margin to an active continental margin. Hydrocarbon-forming organisms are mainly algae. Primary productivity, terrigenous input, and sedimentation rates influence input, dilution, and degradation of organic matter. The degree of degradation, redox, and basin restriction control the preservation of organic matter. The TOC of the Wulalike Formation is determined by the input and preservation degree of organic matter at different sedimentary periods. The organic matter accumulation model in the Wulalike Formation is controlled by regional structures, dominated by sedimentation rate and preservation conditions., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Ethnopharmacological Relevance: HLA-B*35:01 has been identified as a risk allele for Polygonum multiflorum Thunb.-induced liver injury (PMLI). However, the immune mechanism underlying HLA-B*35:01-mediated PMLI remains unknown., Aim of the Study: To characterize the immune mechanism of HLA-B*35:01-mediated PMLI., Materials and Methods: Components of P. multiflorum (PM) bound to the HLA-B*35:01 molecule was screened by immunoaffinity chromatography. Both wild-type mice and HLA-B*35:01 transgenic (TG) mice were treated with emodin. The levels of transaminases, histological changes and T-cell response were assessed. Splenocytes from emodin-treated mice were isolated and cultured in vitro. Phenotypes and functions of T cells were characterized upon drug restimulation using flow cytometry or ELISA. Emodin-pulsed antigen-presenting cells (APCs) or glutaraldehyde-fixed APCs were co-cultured with splenocytes from emodin-treated transgenic mice to detect their effect on T-cell activation., Results: Emodin, the main component of PM, could non-covalently bind to the HLA-B*35:01-peptide complexes. TG mice were more sensitive to emodin-induced immune hepatic injury, as manifested by elevated aminotransferase levels, infiltration of inflammatory cells, increased percentage of CD8+T cells and release of effector molecules in the liver. However, these effects were not observed in wild-type mice. An increase in percentage of T cells and the levels of interferon-γ, granzyme B, and perforin was detected in emodin-restimulated splenocytes from TG mice. Anti-HLA-I antibodies inhibited the secretion of these effector molecules induced by emodin. Mechanistically, emodin-pulsed APCs failed to stimulate T cells, while fixed APCs in the presence of emodin could elicit the secretion of T cell effector molecules., Conclusion: The HLA-B*35:01-mediated CD8 + T cell reaction to emodin through the P-I mechanism may contribute to P. multiflorum-induced liver injury., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest regarding the publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The midcheek groove, a diagonal wrinkle in the infraorbital and infrazygomatic regions, disrupts the entire midface smooth lines and impacts facial aesthetics. Despite current treatments' limited effectiveness, including hyaluronic acid fillers and surgical risks, and the neglect of the medial orbicularis oculi muscle, this study explores the efficacy and safety of combining botulinum toxin type A with sodium hyaluronate injection for midcheek groove treatment, considering anatomical and clinical factors., Methods: In this prospective study, healthy participants with midcheek grooves (depth >3 mm) were treated with botulinum toxin type A combined with hyaluronic acid injections. Data were collected at baseline, 4, 12, and 32 weeks as well as 30 min after treatment, and at 1, 3, and 6 months follow-up. Changes in the depth of the midcheek groove were measured using a three-dimensional scanner and assessed using the Patient Satisfaction Assessment Scale. Subgroup analyses were performed to assess the impact of different clinical subtypes on treatment outcomes., Results: Thirty-six volunteers completed this study, and the midcheek groove depth was significantly reduced at 30 min after treatment and at 1, 3, and 6 months of follow-up (p < 0.001). The medial half of the midcheek groove had the best efficacy at 1 month after treatment, while the lateral half responded best at 30 min after treatment. Subgroup analyses showed that clinical subtypes affected treatment efficacy. No complications or severe adverse reactions were observed., Conclusions: Botulinum toxin type A combined with hyaluronic acid injection effectively improved the midcheek groove., Level of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

In this study, a dextran sodium sulfate-induced ulcerative colitis model in C57BL/6 mice was used to explore the effect of acceptable daily intake (ADI) of aspartame on inflammation in colonic tissues. The effects of aspartame on the inflammatory state of the colon in mice were comprehensively evaluated by comparing the body weight, colon length/colon length index, splenic index, disease activity index (DAI) score, histological activity index (HAI) score, the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, claudin-3, and occludin, the infiltration characteristics of macrophage and neutrophil and the composition of the gut microbiota in the control group, aspartame group, ulcerative colitis model group, and aspartame + ulcerative colitis group. We demonstrated that, in a mouse model of dextran sulfate-induced ulcerative colitis, ADI of aspartame caused a significant decrease in body weight, colon length/colon length index, DAI scores, and expression levels of the proteins claudin-3 and occludin. Moreover, ADI of aspartame caused an increase in the splenic index, HAI scores, the levels of proinflammatory factors TNF-α, IL-1β, and IL-6 both in intestinal tissue and serum and infiltration of macrophages and neutrophils in colon tissues. These results showed that ADI of aspartame promoted intestinal pathology and systemic inflammation in a mouse model of colitis., (© 2024 Institute of Food Technologists.)

Lactylation, a novel discovered posttranslational modification, is a vital component of lactate function and is prevalent in a wide range of cells, interacting with both histone and non-histone proteins. Recent studies have confirmed that lactylation as a new contributor to epigenetic landscape is involved in multiple pathological processes. Accumulating evidence reveals that lactylation exists in different pathophysiological states and leads to inflammation and cancer; however, few mechanisms of lactylation have been elaborated. This review summarizes the biological processes and pathophysiological roles of lactylation in cancer, as well as discusses the relevant mechanisms and potential therapeutic targets, aiming to provide new insights for targeted cancer therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhu, Liu, Luo, Xiao and Sun.)

The elevated levels of geogenic (natural) ammonium in groundwater have been frequently documented in recent years. Although improving insights have been achieved in understanding the genesis of ammonium in the subsurface environment, the vertical variability of the geogenic ammonium in groundwater remains poorly understood. Here, we selected typical multi-layered aquifer systems in the central Yangtze River plain and characterized the vertical heterogeneity of geogenic ammonium through the hydrogeochemical analysis. Subsequently, the controlling factors were identified by examining the molecular composition of dissolved organic matter (DOM) and aquifer sediment features. The results indicated that the ammonium concentration in groundwater increased from the deep to shallow aquifers (2.13 to 9.88 mg/L as N), accompanied by a transition in organic matter (OM) degradation towards the methanogenic stage (δ 13 C-DIC: -23.07 to -0.34‰). Compared to the deeper aquifers, the DOM in the shallow aquifer was characterized by a higher abundance of the N-containing OM (15.1% > 13.13% > 12.76%) with a lower molecular lability index, corresponding to more thorough degradation extent. The characteristics of the soluble OM in depth-matched sediments were similar to those of the DOM in groundwater, suggesting the persistent water-rock interactions. Besides, the pumping tests revealed that the hydraulic conductivity decreased from deep to shallow aquifers (2.28 to 0.62 m/d), which further facilitated the more retention of geogenic ammonium in the shallow aquifer. That is, the combined effects of the abundant N-containing OM in sediments, strong degradation of the bioactive DOM, and long retention governed by hydrodynamics contributed to the increased ammonium enrichment in the shallow aquifer, thereby generating the vertical variability. The findings underscore the significance of the complex coupled factors in controlling the vertical distribution of geogenic ammonium in multi-layered aquifer systems, which was crucial for understanding the spatial heterogeneity of geogenic contaminated groundwater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The electrochemical activation of inert CO 2 molecules through C─C coupling reactions under ambient conditions remains a significant challenge but holds great promise for sustainable development and the reduction of CO 2 emission. Lewis pairs can capture and react with CO 2 , offering a novel strategy for the electrosynthesis of high-value-added C2 products. Herein, an electron-beam irradiation strategy is presented for rapidly synthesizing a metal-organic framework (MOF) with well-defined Lewis pairs (i.e., Cu- N pyridinic ). The synthesized MOFs exhibit a total C2 product faradic efficiency of 70.0% at -0.88 V versus RHE. In situ attenuated total reflection Fourier transform infrared and Raman spectra reveal that the electron-deficient Lewis acidic Cu sites and electron-rich Lewis basic pyridinic N sites in the ligand facilitate the targeted chemisorption, activation, and conversion of CO 2 molecules. DFT calculations further elucidate the electronic interactions of key intermediates in the CO 2 reduction reaction. The work not only advances Lewis pair-site MOFs as a new platform for CO 2 electrochemical conversion, but also provides pioneering insights into the underlying mechanisms of electron-beam irradiated synthesis of advanced nanomaterials., (© 2024 Wiley‐VCH GmbH.)

The evidence on associations between ambient gaseous pollutants and conjunctivitis remains inconclusive, and limited research is available, particularly regarding children. Based on a case-crossover study conducted in ten Chinese cities from 2013 to 2023, we documented 418,027 outpatient visits for conjunctivitis in children. Of these visits, 256,525 were for boys and 161,502 for girls. A one standard deviation (SD) increase in daily concentrations of carbon monoxide (CO) was related to a 1.20 % rise in same-day outpatient visits for pediatric conjunctivitis (OR = 1.012, 95 % CI: 1.005, 1.018). Similar associations were found for nitrogen dioxide (NO 2 : 2.90 % increase; OR = 1.029, 95 % CI: 1.019, 1.040), sulfur dioxide (SO 2 : 1.70 % increase; OR = 1.017, 95 % CI: 1.007, 1.028), and ozone (O 3 : 1.30 % increase; OR = 1.013, 95 % CI: 1.006, 1.021). The positive associations remained significant in two-pollutant and mixed-effects models. Notably, we observed stronger associations in girls compared to boys, among children at 1-5 years of age compared to other age groups, and the relationships were more pronounced during the summer months. This study reveals a link between exposure to common gaseous air pollutants and increased risks of conjunctivitis in children, indicating the potential benefits of public health interventions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Polysaccharides serve as a source of energy for organisms and play a crucial role in various life activities, exhibiting a wide array of biological functions. To develop bioactive polysaccharides for combating cancer, PGP40-2B, a homogeneous polysaccharide with a molecular weight of 7.05 × 10 3  g/mol, has been isolated from Platycodon grandiflorum, which is a traditional medicinal and edible plant with multiple functions. PGP40-2B was found to be mainly formed from several fragments including →2)-α-l-Araf-(1→, →5)-α-l-Araf-(1→, →3,4)-α-l-Rhap-(1→, →4)-α-d-GalpA-(1→, →6)-α-d-Glcp-(1→, and α-d-Galp-(1→. In addition to the structural characteristics characterized by various techniques, PGP40-2B was biologically assessed using zebrafish models and was found to exhibit in vivo antitumor effects. Subsequent mechanism studies suggested that the antitumor activity in vivo of PGP40-2B was not caused by cytotoxic mechanisms but was related to its targeting of vascular endothelial growth factor (VEGF) and programmed cell death protein 1 (PD-1) to inhibit angiogenesis and activate immunity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

During the progression of metabolic dysfunction-associated steatohepatitis (MASH), the accumulation of auto-aggressive CD8 + T cells significantly contributes to liver injury and inflammation. Empagliflozin (EMPA), a highly selective inhibitor of sodium-glucose co-transporter 2 (SGLT2), exhibits potential therapeutic benefits for liver steatosis; however, the underlying mechanism remains incompletely elucidated. Here, we found that EMPA significantly reduced the hepatic accumulation of auto-aggressive CD8 + T cells and lowered granzyme B levels in mice with MASH. Mechanistically, EMPA increased β-hydroxybutyric acid by promoting the ketogenesis of CD8 + T cells via elevating 3-hydroxybutyrate dehydrogenase 1 (Bdh1) expression. The β-hydroxybutyric acid subsequently inhibited interferon regulatory factor 4 (Irf4), which is crucial for CD8 + T cell activation. Furthermore, the ablation of Bdh1 in T cells aggravated the manifestation of MASH and hindered the therapeutic efficacy of EMPA. Moreover, a case-control study also showed that SGLT2 inhibitor treatment repressed CD8 + T cell infiltration and improved liver injury in patients with MASH. In summary, our study indicates that SGLT2 inhibitors can target CD8 + T cells and may be an effective strategy for treating MASH., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Short-term exposure to ozone has been linked to multiple allergic diseases, but the relationship between ozone exposure and allergic conjunctivitis (AC) remains unclear. This study aimed to investigate the association between short-term exposure to ozone and the risk of AC. We conducted a time-stratified case-crossover study across five Chinese cities from 2014 to 2022. Daily outpatient visit records for AC were identified in five hospitals using either the diagnosis name or ICD-10 code H10.1. Data on air pollution and meteorological conditions were also collected. We first examined the city-specific association between short-term ozone exposure and AC using conditional logistic regression. A random-effects meta-analysis was then conducted to obtain overall estimates. During the study period, 130,093 outpatient visits for AC occurred, with 58.8% (76,482) being male and 41.2% (53,611) female. A one-standard-deviation (SD) increase in ozone was associated with an 8.3% increase (95% CI: 3.8%, 13.0%) in AC outpatient visits. Similar positive associations were observed when adjusting for other pollutants (PM 2.5 , CO, SO 2 and NO 2 ) in two-pollutant and multi-pollutant models. Furthermore, the positive association remained consistent when using mixed-effects regression models or further adjusting for meteorological conditions. In addition, no effect modification of the AC-ozone association by sex, age and season was apparent. This study provides evidence supporting a positive association between short-term ozone exposure and AC risk in China. This highlights the potential value of mitigating ozone pollution to reduce the risk of ocular surface disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Planting density is an effective strategy for regulating both oat lodging and forage quality. To delve into the regulatory mechanisms of planting density on lodging and oat forage quality, lodging-resistant variety LENA and lodging-sensitive variety QY2 were grown in 2018 and 2019 growing seasons, and four planting densities were implemented: 2.25 × 10 6 plants/ha (D1), 4.5 × 10 6 plants/ha (D2), 6.75 × 10 6 plants/ha (D3), and 9 × 10 6 plants/ha (D4). At the milk stage, we measured the contents of potassium, calcium, magnesium, silicon, lignin, crude fiber, starch, soluble sugar, and soluble protein in the second and third stem internodes of the plants. The results revealed the lodging-resistant variety LENA demonstrated significantly higher contents of calcium, potassium, silicon, crude fiber, lignin, and lower contents of starch, soluble sugar, and soluble protein ( p < 0.01). Similar trends in the physicochemical properties of stem internodes for both oat varieties with increasing planting density. Crude fiber, soluble sugar, magnesium, starch, potassium, and lignin were the key characteristics affecting the lodging coefficient, and variety and planting density affected the lodging coefficient mainly by regulating the synthesis of starch, soluble sugar, and crude fiber. At planting density D3, stem internodes exhibited higher physicochemical properties and a lower lodging coefficient, favoring oat forage production. The results offer a valuable theoretical foundation and practical reference for oat lodging-resistant cultivation.

With the continuous advancement of nanotechnology, the application of gold nanorods (AuNRs) functionalized with polysaccharides in the realm of cancer photothermal therapy is garnering increasing attention. To harness photothermal therapy for cancer treatment, FLP-MPBA-AuNRs were successfully synthesized in this study for the first time, utilizing Poria cocos polysaccharides (FLP), mercaptophenylboronic acid (MPBA), and gold nanorods (AuNRs). FLP-MPBA-AuNRs are a nanomaterial characterized by a unique rod-shaped structure, featuring a long diameter of 29.3 nm and a short diameter of 6.5 nm, which conferred exceptional photothermal stability and remarkable photothermal conversion efficiency. Under near-infrared light irradiation, FLP-MPBA-AuNRs elicited significant photothermal effects, effectively curtailing the proliferation of various cancer cells. Additionally, FLP-MPBA-AuNRs impeded cancer progression by inducing cell apoptosis and releasing reactive oxygen species (ROS). Furthermore, FLP-MPBA-AuNRs suppressed the metastasis and growth of cancer cells in zebrafish models. In summary, FLP-MPBA-AuNRs showcased immense potential in cancer therapy by inhibiting tumor cell growth through photothermal and photodynamic mechanisms., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Research on the mechanism and application of checkpoint inhibitory receptors in hematologic diseases has progressed rapidly. However, in the treatment of relapserefractory (R/R) hematologic malignancies and anti-programmed cell death protein 1 (PD-1), patients who are resistant to anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) are in urgent need of alternative therapeutic targets. T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) has a broad prospect as an inhibitory receptor like PD-1, but its more specific mechanism of action and application in hematologic diseases still need to be further studied. In this review, we discuss the mechanism of TIGIT pathway, combined effects with other immune checkpoints, immune-related therapy, the impact of TIGIT on hematopoietic stem cell transplantation (HSCT) and the tumor microenvironment (TME) provides a potential therapeutic target for hematologic malignancies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: Cardiac glycosides (CGs), traditionally used for heart failure, have shown potential as anti-cancer agents. This study aims to explore their multifaceted mechanisms in cancer cell biology using proteome integral solubility alteration (PISA), focusing on the interaction with key proteins implicated in cellular metabolism and mitochondrial function., Methods: We conducted lysate-based and intact-cell PISA assays on cancer cells treated with CGs (Digoxin, Digitoxin, Ouabain) to analyze protein solubility changes. This was followed by mass spectrometric analysis and bioinformatics to identify differentially soluble proteins (DSPs). Molecular docking simulations were performed to predict protein-CG interactions. Public data including gene expression changes upon CG treatment were re-analyzed for validation., Results: The PISA assays revealed CGs' broad-spectrum interactions, particularly affecting proteins like PKM2, ANXA2, SLC16A1, GOT2 and GLUD1. Molecular docking confirmed stable interactions between CGs and these DSPs. Re-analysis of public data supported the impact of CGs on cancer metabolism and cell signaling pathways., Conclusion: Our findings suggest that CGs could be repurposed for cancer therapy by modulating cellular processes. The PISA data provide insights into the polypharmacological effects of CGs, warranting further exploration of their mechanisms and clinical potential., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: This study was designed to investigate the biological role and the reaction mechanism of Tweety family member 3 (TTYH3) in oral squamous cell carcinoma (OSCC)., Design: The mRNA and protein expressions of TTYH3 were assessed with RT-qPCR and western blot. After silencing TTYH3 expression, the proliferation of OSCC cells were detected using cell counting kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) staining and colony formation assay. Cell migration and invasion were detected using wound healing and transwell. Gelatin zymography protease assay was used to detect matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-2 (MMP9) activity and western blot was used to detect the expressions of proteins associated with proliferation and epithelial-mesenchymal transition (EMT). The mRNA expression of TTYH3 in THP-1-derived macrophage was detected using real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). The number of CD86-positive cells and CD206-positive cells was detected using immunofluorescence assay. RT-qPCR was used to detect the expressions of M2 markers arginase 1 (ARG1), chitinase-like 3 (YM1) and mannose receptor C-type 1 (MRC1)., Results: In this study, it was found that TTYH3 expression was upregulated in OSCC cell lines and TTYH3 knockdown could inhibit the proliferation, migration, invasion and EMT process in OSCC via suppressing M2 polarization of tumor-associated macrophages., Conclusions: Collectively, TTYH3 facilitated the progression of OSCC through the regulation of tumor-associated macrophages polarization., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Non-alcoholic fatty liver disease (NAFLD) poses a significant global public health concern. Liupao tea (LPT) is a Chinese national geographical indication product renowned for its lipid-lowering properties. However, the precise mechanisms and active constituents contributing to the efficacy of LPT against NAFLD remain unclear., Purpose: This study aims to comprehensively explore the therapeutic potential of Liupao tea extract (LPTE) in alleviating NAFLD through an integrated strategy., Methods: Initially, network pharmacology analysis was conducted based on LPTE chemical ingredient analysis, identifying core targets and key components. Potential active ingredients were validated through chemical standards based on LC-MS/MS. To confirm the pharmacological efficacy of LPTE in NAFLD, NAFLD mice models were employed. Alterations in hepatic lipid metabolism were comprehensively elucidated through integration of metabolomics, lipidomics, network pharmacology analysis, and real-time PCR analysis. To further explore the binding interactions between key components and core targets, molecular docking and microscale thermophoresis (MST) analysis were employed. Furthermore, to investigate LPTE administration effectiveness on gut microbiota in NAFLD mice, a comprehensive approach was employed. This included Metorigin analysis, 16S rRNA sequencing, molecular docking, and fecal microbiome transplantation (FMT)., Results: Study identified naringenin, quercetin, luteolin, and kaempferol as the potential active ingredients of LPTE. These compounds exhibited therapeutic potential for NAFLD by targeting key proteins such as PTGS2, CYP3A4, and ACHE, which are involved in the metabolic pathways of hepatic linoleic acid (LA) and glycerophospholipid (GP) metabolism. The therapeutic effectiveness of LPTE was observed to be comparable to that of simvastatin. Furthermore, LPTE exhibited notable efficacy in alleviating NAFLD by influencing alterations in gut microbiota composition (Proteobacteria phylum, Lactobacillus and Dubosiella genus) that perhaps impact LA and GP metabolic pathways., Conclusion: LPTE could be effective in preventing high-fat diet (HFD)-induced NAFLD by modulating hepatic lipid metabolism and gut microbiota. This study firstly integrated bioinformatics and multi-omics technologies to identify the potential active components and key microbiota associated with LPTE's effects, while also primally elucidating the action mechanisms of LPTE in alleviating NAFLD. The findings offer a conceptual basis for LPTE's potential transformation into an innovative pharmaceutical agent for NAFLD prevention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

In general, Cu(II) is the critical factor in catalyzing reactive oxygen species (ROS) production and accelerating amyloid-β (Aβ) oligomer formation in Alzheimer's disease (AD). Natural chelating agents with good biocompatibility and appropriate binding affinity with Cu(II) have emerged as potential candidates for AD therapy. Herein, we tested the capability of guluronic acid disaccharide (Di-GA), a natural chelating agent with the moderate association affinity to Cu(II), in inhibiting ROS production and Aβ oligomer formation. The results showed that Di-GA was capable of chelating with Cu(II) and reducing ROS production, even in solutions containing Fe(II), Zn(II), and Aβ. In addition, Di-GA can also capture Cu(II) from Cu-Aβ complexes and decrease Aβ oligomer formation. The cellular results confirmed that Di-GA prevented SH-SY5Y cells from ROS and Aβ oligomer damage by reducing the injury of ROS and Aβ oligomers on cell membrane and decreasing their intracellular damage on mitochondria. Notably, the slightly higher efficiency of Di-GA in chelating with Cu(I) than Cu(II) can be benefit for its in vivo applications, as Cu(I) is not only the most active but also the special intermediate specie during ROS production process. All of these results proved that Di-GA could be a promising marine drug candidate in reducing copper-related ROS damage and Aβ oligomer toxicity associated with AD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Intervention mapping (IM) is a planning approach that reflects the intricate decision-making process involved in the design of behavior interventions. The development and implementation of IM is complex in preventing HIV/AIDS transmission. Therefore, it is significant to conduct a perfect preliminary work to successfully implement HIV/AIDS prevention. The objectives of this review were to collect and evaluate the data of the first three steps using IM to prevent HIV/AIDS transmission, and summarize the key points in the preliminary steps of IM. A total of 18 studies were identified, and six studies completely described the tasks in the first three steps of IM. Three studies described the logic model of the problem ( n  = 3). Six studies reported the matrix of behavior changes ( n  = 6), including personal and environmental determinants. Among the selected determinants, most studies reported the personal level determinants (self-efficacy and skills, knowledge, attitudes, and norms). The most used practical applications in reducing HIV/AIDS risk behaviors were video roles ( n  = 8) and role-model stories ( n  = 5). The review may be helpful for healthcare professionals to carefully design and implement the key procedures of the first three steps of the IM programs for people with HIV/AIDS in preventing HIV/AIDS transmission.

Infectious spleen and kidney necrosis virus (ISKNV), a member of the genus Megalocytivirus in the family Iridoviridae , can infect over 50 fish species and cause significant economic losses in Asia. Our previous study showed that hypoxia triggers the hypoxia-inducible factor pathway (HIF-pathway), leading to increased replication of ISKNV through promoting the upregulation of viral hypoxic response genes like orf077r . This study delved into the molecular mechanism of how ISKNV manipulates the HIF-pathway to enhance its replication. In vitro and in vivo experiments confirmed that ISKNV infection activated the HIF-pathway, which in turn promoted ISKNV replication. These findings suggest that ISKNV actively manipulates the HIF-pathway. Co-immunoprecipitation experiments revealed that the ISKNV-encoded protein VP077R interacts with the Von Hippel-Lindau (VHL) protein at the HIF-binding region, competitively inhibiting the interaction of HIF-1α with VHL. This prevents HIF degradation and activates the HIF-pathway. Furthermore, VP077R interacts with factor-inhibiting HIF (FIH), recruiting FIH and S-phase kinase-associated protein 1 (Skp1) to form an FIH - VP077R - Skp1 complex. This complex promotes FIH protein degradation via ubiquitination, further activating the HIF-pathway. These findings indicated that ISKNV takes over the HIF-pathway by releasing two "brakes" on this pathway (VHL and FIH) via VP077R, facilitating virus replication. We speculate that hypoxia initiates a positive feedback loop between ISKNV VP077R and the HIF pathway, leading to the outbreak of ISKNV disease. This work offers valuable insights into the complex interactions between the environment, host, and virus.

Objective: This study aims to examine the possible relationship between body composition parameters, sarcopenia, and clinical outcomes in hepatocellular carcinoma (HCC) patients who received immune checkpoint inhibitor (ICI) treatment., Methods: Three online databases, including Embase, PubMed, and the Cochrane Library, were thoroughly searched for literature describing the relationship between body composition parameters, sarcopenia, and outcomes of ICI-treated HCC patients from the start of each database to 21 January 2024. The Newcastle-Ottawa Scale was used to rate the quality of the studies. The assessed outcomes included hazard ratio (HR) for OS and PFS, as well as odds ratio (OR) for ORR and DCR., Results: This analysis included a total of 15 articles with a combined patient cohort of 1543 individuals. The results demonstrated that HCC patients with low skeletal muscle index (SMI) had significantly inferior OS (HR: 1.68, p  < 0.001), PFS (HR: 1.45, p  < 0.001), ORR (OR: 0.64, p  = 0.044), and DCR (OR: 0.58, p  = 0.009) compared to those with high SMI. The presence of sarcopenia in HCC patients was significantly related to poorer OS (HR: 1.63, p  < 0.001) and PFS (HR: 1.48, p  < 0.001), as well as a lower ORR (OR: 0.64, p  = 0.020) and DCR (OR: 0.58, p  = 0.007) in comparison to those without sarcopenia. Subgroup analysis demonstrated that these findings were consistent with the multivariate analysis. Moreover, high subcutaneous adipose index (SAI) levels were associated with better OS (HR: 0.46, p  = 0.001) and PFS (HR: 0.68, p  = 0.021) than those with low SAI levels., Conclusion: The presence of sarcopenia and low SMI in HCC patients undergoing treatment with ICIs was found to be related to inferior treatment response and reduced long-term effectiveness.

The rising prevalence of obesity has resulted in an increased demand for innovative and effective treatment strategies. Houttuynia cordata Thunb. (H. cordata) has demonstrated promising potential in preventing obesity. However, the mechanism underlying the anti-obesity effects of H. cordata and its bioactive component, sodium houttuybonate (SH), remains unclear. Our study reveals that SH treatment promotes the browning of inguinal white adipose tissue (iWAT) and prevents the obesity induced by a high-fat diet. SH significantly mitigates ferroptosis by upregulating glutathione peroxidase 4 ( Gpx4 ) and decreasing malondialdehyde (MDA) levels, while also enhancing superoxide dismutase (SOD) levels. Furthermore, SH promotes the phosphorylation of AMP-activated protein kinase (AMPK), which subsequently increases the expression of nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1) in the iWAT. However, the effects of SH were attenuated by ML385, an Nrf2 inhibitor. Collectively, our findings suggest that SH induces iWAT browning and prevents diet-induced obesity primarily through the AMPK/NRF2/HO-1 pathway by inhibiting ferroptosis.

DNA methylation is an important epigenetic regulatory mechanism which plays a crucial role in cell differentiation and development. Its function is closely related to DNA methyltransferase 3 alpha (DNMT3A), which can affect gene expression and stem cell differentiation. The mutation rate of the DNMT3A gene is relatively high in Acute myeloid leukemia (AML), but its type and pathogenic mechanism are not yet clear. Further research on DNMT3A may help to identify its pathogenic targets and provide a basis for precise treatment of AML. This article has provided a review for the research progress on the expression of the DNMT3A gene in AML.

Objective: Polyfluoroalkyl substances (PFAS) are known endocrine disruptors, that have been the subject of limited research regarding their impact on human lean body mass. The aim of this study was to investigate the effects of PFAS exposure on lean body mass., Methods: We performed a cross-sectional data analysis involving 1022 adolescents and 3274 adults from the National Health and Nutrition Examination Survey (NHANES) 2011-2018, whose lean body mass was measured by dual-energy X-ray absorptiometry. The lean mass index (LMI) was calculated as lean body mass dividing by the square of height. The association between PFAS and LMI was examined through a multivariate-adjusted weighted generalized linear model. Moreover, weighted quantile sum (WQS) regression models were employed to futher examine the relationship between the mixture of PFAS and LMI., Results: Regression analyses revealed an inverse correlation between PFAS exposure and LMI after adjusting for potential covariates. Adults with higher serum PFAS concentrations manifested a reduction in whole LMI ( β  = -0.193, 95 % confidence interval (CI): -0.325 to -0.06). Notably, this correlation was particularly significant in adult females and individuals with obesity, and it was observed across diverse anatomical regions, including lower limbs, right arm, trunk, and whole lean body mass. In adult females, the association between PFAS and whole LMI was statistically significant ( β  = -0.294, 95 % CI: -0.495 to -0.094), and a similar trend was found in obese individuals ( β  = -0.512, 95 % CI: -0.762 to -0.261). WQS regression analyses supported the results obtained from weighted linear regression analyses., Conclusions: Our study suggests that exposure to PFAS, whether individually or in combination, is associated with decreased lean body mass in specific body areas, with sex and obesity serving as major influencing factors., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Min Zhao reports financial support was provided by 10.13039/501100001809National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Resistivity data has important applications in geophysical exploration, but the impact of electrode offsets on resistivity response characteristics remains unclear. This study aims to explore the influence of horizontal electrode offset angles and vertical offsets caused by topographical variations on the forward modeling of resistivity data. By analyzing experimental models with different measurement arrays, the paper revealed their influence laws on the buried depth of the target body and resistivity resolution. Utilizing tools like ZondRes3D, we conducted 3D resistivity forward modeling and analyzed the results in detail. It is found that horizontal electrode offsets lead to pseudo-anomalies in the apparent resistivity response, which is related to the offset angles and the number of electrodes. Under different conditions, the horizontal electrode offsets exhibit a "gradient variation" pattern. In addition, topographical variations can also cause distortions and offsets in the apparent resistivity curves and the locations of the anomaly response. Specifically, the measuring lines near the edge of the target bodies are more susceptible to these effects. Based on the comprehensive experimental results, we have drawn several conclusions regarding the impact of electrode offsets and topographical variations, including the effects of offset angles on the pseudo-anomalies, the anomalous response laws under different topographic conditions, as well as anomalous situations under specific angles. These findings provide crucial insights for interpreting resistivity data in geophysical exploration and addressing practical engineering problems, and offer guidance for optimizing measuring line layouts and post-processing terrain correction algorithms., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction Background: Disulfidptosis is a prevalent apoptotic mechanism, intrinsically linked to cancer prognosis. However, the specific involvement of disulfidptosis-related long non-coding RNA (DRLncRNAs) in Kidney renal clear cell carcinoma (KIRC) remains incompletely understood. This study aims to elucidate the potential prognostic significance of disulfidptosis-related LncRNAs in KIRC., Materials and Methods: Expression profiles and clinical data of KIRC patients were retrieved from the TCGA database to discern differentially expressed DRLncRNAs correlated with overall survival. Cox univariate analysis, Lasso Regression, and Cox multivariate analysis were used to construct a clinical prediction model., Results: Six signatures, namely FAM83C.AS1, AC136475.2, AC121338.2, AC026401.3, AC254562.3, and AC000050.2, were established to evaluate overall survival (OS) in the context of Kidney renal clear cell carcinoma (KIRC) in this study. Survival analysis and ROC curves demonstrated the strong predictive performance of the associated signature. The nomogram exhibited accurate prognostic predictions for overall patient survival, offering substantial clinical utility. Gene set enrichment analysis revealed that risk signals were enriched in various immune-related pathways. Furthermore, the risk features exhibited significant correlations with immune cells, immune function, immune cell infiltration, and immune checkpoints., Conclusion: This study has unveiled, for the first time, six disulfdptosis-related LncRNA signatures, laying a solid foundation for enhanced and precise prognostic predictions in KIRC., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Malignant cerebral edema (MCE) is associated with both net water uptake (NWU) and infarct volume. We hypothesized that NWU weighted by the affected Alberta Stroke Program Early Computed Tomography Score (ASPECTS) regions could serve as a quantitative imaging biomarker of aggravated edema development in acute ischemic stroke with large vessel occlusion (LVO). The aim of this study was to evaluate the performance of weighted NWU (wNWU) to predict MCE in patients with mechanical thrombectomy (MT)., Methods: We retrospectively analyzed consecutive patients who underwent MT due to LVO. NWU was computed from nonenhanced computed tomography scans upon admission using automated ASPECTS software. wNWU was derived by multiplying NWU with the number of affected ASPECTS regions in the ischemic hemisphere. Predictors of MCE were assessed through multivariate logistic regression analysis and receiver operating characteristic curves., Results: NWU and wNWU were significantly higher in MCE patients than in non-MCE patients. Vessel recanalization status influenced the performance of wNWU in predicting MCE. In patients with successful recanalization, wNWU was an independent predictor of MCE (adjusted odds ratio 1.61; 95% confidence interval [CI] 1.24-2.09; P < 0.001). The model integrating wNWU, National Institutes of Health Stroke Scale, and collateral score exhibited an excellent performance in predicting MCE (area under the curve 0.80; 95% CI 0.75-0.84). Among patients with unsuccessful recanalization, wNWU did not influence the development of MCE (adjusted odds ratio 0.99; 95% CI 0.60-1.62; P = 0.953)., Conclusions: This study revealed that wNWU at admission can serve as a quantitative predictor of MCE in LVO with successful recanalization after MT and may contribute to the decision for early intervention., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Artificial grasslands of F . kryloviana in the region surrounding Qinghai Lake have been observed to a decline in productivity following three years of establishment. Traditional fertilization practices, aimed at maintaining ecological balance, have predominantly focused on the application of phosphorus. However, it remains unclear whether phosphorus fertilizers offer a superior advantage over nitrogen fertilizers in sustaining productivity. Consequently, from 2017 to 2019, we conducted an experimental to assess the impact of nitrogen and phosphorus fertilization on forage yield and quality. We designed with four levels of phosphorus and two levels of nitrogen, resulting in eight distinct fertilizer combinations. Our experimental findings indicate that the degradation of artificial grasslands leads to a shift in the allocation pattern of aboveground biomass. There was a respective decrease of 68.2 % and 62.5 % in the biomass proportions of stems and ears, contrasted by a greater than 200 % increase in the biomass proportion of leaves. The application of nitrogen not only elevated the total aboveground biomass but also promoted a preferential allocation of biomass to stems and leaves, consequently enhancing the forage's crude protein content. Nitrogen fertilization significantly increased aboveground biomass, and crude protein content by 63.21 %, and 6 %, respectively. Phosphorus fertilization's impact varied annually but favored the distribution of biomass to stems and ears. The net photosynthetic rate improved by over 53.12 % with fertilizer application, although the differences among treatments were not statistically significant. The balanced application of nitrogen and phosphorus fertilizers significantly bolstered the aboveground biomass, ear biomass, stem biomass, leaf biomass, and crude protein content in varying years by 17.25 %-209.83 %, 34.7 %-438.9 %, 25.5 %-250.2 %, 18.4 %-133.3 %, and 10.21 %-25.62 %, respectively. Our analysis revealed that nitrogen-only fertilization exhibited the most optimal fertilizer use efficiency and economic returns. In conclusion, nitrogen fertilization is crucial for sustaining the productivity and quality of F. kryloviana artificial grasslands. The local practice of 75 kg ha -1 phosphorus fertilizer is detrimental to the maintenance of productivity in F. kryloviana artificial grasslands. This study offers valuable insights into the optimization of fertilization strategies for sustainable forage production within alpine regions., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wenhui Liu reports financial support was provided by Qinghai innovation platform construction project. Wenhui Liu reports financial support was provided by China Agriculture Research System. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Festuca kryloviana is a significant native grass species in the Qinghai Lake region, and its low emergence rate is a primary factor limiting the successful establishment of cultivated grasslands. The region's arid and low-rainfall climate characteristics result in reduced soil moisture content at the surface. Despite the recognized impact of water availability on plant growth, the specific role of moisture in seedling development remains not fully elucidated. This study aims to investigate the germination rate and seedling growth velocity of F. kryloviana seeds under varying moisture conditions, and to integrate physiological and transcriptomic analyses of seedlings under these conditions to reveal the mechanisms by which water influences seedling development., Results: The emergence rate of F. kryloviana seedlings exhibited an initial increase followed by a decrease with increasing moisture content. The highest emergence rate, reaching 75%, was observed under 20% soil moisture conditions. By the eighth day of the experiment, the lengths of the plumules and radicles under the optimal emergence rate (full water, FW) were 21.82% and 10.87% longer, respectively, than those under closely matching the soil moisture content during the background survey (stress water, SW). The differential development of seedlings under varying moisture regimes is attributed to sugar metabolism within the seeds and the accumulation of abscisic acid (ABA). At FW conditions, enhanced sugar metabolism, which generates more energy for seedling development, is facilitated by higher activities of α-amylase, sucrose synthase, and trehalose-6-phosphate synthase compared to SW conditions. This is reflected at the transcriptomic level with upregulated expression of the α-amylase (AMY2) gene and trehalose-6-phosphate synthase (TPS6), while genes associated with ABA signaling and transduction are downregulated. Additionally, under FW conditions, the expression of genes related to the chloroplast thylakoid photosystems, such as photosystem II (PSII) and photosystem I (PSI), is upregulated, enhancing the seedlings' light-capturing ability and photosynthetic efficiency, thereby improving their autotrophic capacity. Furthermore, FW treatment enhances the expression of the non-enzymatic antioxidant system, promoting metabolism within the seeds. In contrast, SW treatment increases the activity of the enzymatic antioxidant system, including peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT), to cope with water stress., Conclusions: Our experiment systematically evaluated the impact of moisture conditions on the growth and development of F. kryloviana seedlings. Physiological and transcriptomic data collectively indicate that adequate water (20%) supply enhances seedling growth and development by reducing ABA levels and increasing α-amylase activity within seeds, thereby boosting sugar metabolism and promoting the growth of seedling, which in turn leads to an improved emergence rate. Considering water management in future cultivation practices may be a crucial strategy for enhancing the successful establishment of F. kryloviana in grassland ecosystems., (© 2024. The Author(s).)

Background: Tannic acid (TA), a naturally occurring polyphenol, has shown diverse potential in preventing intestinal damage in piglet diarrhea induced by Enterotoxigenic Escherichia coli (ETEC) K88. However, the protective effect of TA on ETEC k88 infection-induced post-weaning diarrhea and its potential mechanism has not been well elucidated. Therefore, an animal trial was carried out to investigate the effects of dietary supplementation with TA on the intestinal diarrhea of weaned piglets challenged with ETEC K88. In addition, porcine intestinal epithelial cells were used as an in vitro model to explore the mechanism through which TA alleviates intestinal oxidative damage and inflammation., Results: The results indicated that TA supplementation (2 and 4 g kg -1 ) reduced diarrhea rate, enzyme activity (diamine oxidase [DAO] and Malondialdehyde [MAD]) and serum inflammatory cytokines concentration (TNF-α and IL-1β) (P < 0.05) compared to the Infection group (IG), group in vivo. In vitro, TA treatment effectively alleviated ETEC-induced cytotoxicity, increased the expression of ZO-1, occludin and claudin-1 at both mRNA and protein levels. Moreover, TA pre-treatment increased the activity of antioxidant enzymes (such as T-SOD) and decreased serum cytokine levels (TNF-α and IL-1β). Furthermore, TA increased cellular antioxidant capacity by activating the Nrf2 signaling pathway and decreased inflammatory response by down-regulating the expression of TLR4, MyD88, NF-kB and NLRP3., Conclusion: The present study showed that TA reduced the diarrhea rate of weaned piglets by restoring the intestinal mucosal mechanical barrier function, alleviating oxidative stress and inflammation. The underlying mechanism was achieved by modulating the p62-keap1-Nrf2 and TLR4-NF-κB-NLRP3 pathway. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

It is well known that Rosa roxburghii, as a homology of both medicine and food, is rich in polysaccharides. To discover bioactive macromolecules for combating cancer, the polysaccharides in R. roxburghii were investigated, leading to the purification of a polysaccharide (RRTP80-1). RRTP80-1 was measured to have an average molecular weight of 8.65 × 10 3  g/mol. Monosaccharide composition analysis revealed that RRTP80-1 was formed from three types of monosaccharides including arabinose, glucose, and galactose. Methylation and GC-MS analysis suggested that the backbone of RRTP80-1 consisted of →5)-α-l-Araf-(1→, →6)-α-d-Glcp-(1→, →2,5)-α-l-Araf-(1→, →4,6)-β-d-Galp-(1→, and →3)-α-l-Araf-(1→, with branch chains composed of α-l-Araf-(1→. In vivo studies indicated that RRTP80-1 exhibited inhibitory activity against the growth and proliferation of neoplasms in the zebrafish tumor xenograft model by suppressing angiogenesis. Additionally, RRTP80-1 was found to upregulate reactive oxygen species (ROS) and nitric oxide (NO) production levels in zebrafish models. All these studies suggest that RRTP80-1 activates the immune system to inhibit tumors. The potential role of the newly discovered homogeneous polysaccharide RRTP80-1 in cancer treatment was preliminarily clarified in this study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: According to data from several observational studies, there is a strong association between circulating inflammatory cytokines and postherpetic neuralgia (PHN), but it is not clear whether this association is causal or confounding; therefore, the main aim of the present study was to analyze whether circulating inflammatory proteins have a bidirectional relationship with PHN at the genetic inheritance level using a Mendelian randomization (MR) study., Methods: The Genome-Wide Association Study (GWAS) database was used for our analysis. We gathered data on inflammation-related genetic variation from three GWASs of human cytokines. These proteins included 91 circulating inflammatory proteins, tumor necrosis factor-alpha (TNF-α), macrophage inflammatory protein 1b (MIP-1b), and CXC chemokine 13 (CXCL13). The PHN dataset was obtained from the FinnGen biobank analysis round 5, and consisted of 1,413 cases and 275,212 controls. We conducted a two-sample bidirectional MR study using the TwoSampleMR and MRPRESSO R packages (version R.4.3.1). Our main analytical method was inverse variance weighting (IVW), and we performed sensitivity analyses to assess heterogeneity and pleiotropy, as well as the potential influence of individual SNPs, to validate our findings., Results: According to our forward analysis, five circulating inflammatory proteins were causally associated with the development of PHN: interleukin (IL)-18 was positively associated with PHN, and IL-13, fibroblast growth factor 19 (FGF-19), MIP-1b, and stem cell growth factor (SCF) showed reverse causality with PHN. Conversely, we found that PHN was closely associated with 12 inflammatory cytokines, but no significant correlation was found among the other inflammatory factors. Among them, only IL-18 had a bidirectional causal relationship with PHN., Conclusion: Our research advances the current understanding of the role of certain inflammatory biomarker pathways in the development of PHN. Additional verification is required to evaluate the viability of these proteins as targeted inflammatory factors for PHN-based treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Hu, Li, Li, Mao and Fan.)

Herein, a covalent organic framework (SO 3 -COF) containing sulfonic acid groups has been developed on the surface of alumina by a one-step method, labeled as SO 3 -COF@Al 2 O 3 . The experimental results show that SO 3 -COF@Al 2 O 3 can effectively inhibit the shuttle effect of soluble lithium polysulfide (LiPSs) in LSBs after loading the active material sulfur, and exhibits better cycling behavior than the initial polymer SO 3 -COF. The initial discharge specific capacity of this electrode material at 0.05C is as high as 1141 mA h g -1 , and the capacity can be maintained at 466 mA h g -1 after 500 cycles with a capacity decay rate of 0.08% per cycle.

Background: Cataract contributes to visual impairment worldwide, and diabetes mellitus accelerates the formation and progression of cataract. Here we found that the expression level of miR-204-5p was diminished in the lens epithelium with anterior lens capsule of cataract patients compared to normal donors, and decreased more obviously in those of diabetic cataract (DC) patients. However, the contribution and mechanism of miR-204-5p during DC development remain elusive., Methods and Result: The mitochondrial membrane potential (MMP) was reduced in the lens epithelium with anterior lens capsule of DC patients and the H2O2-induced human lens epithelial cell (HLEC) cataract model, suggesting impaired mitochondrial functional capacity. Consistently, miR-204-5p knockdown by the specific inhibitor also attenuated the MMP in HLECs. Using bioinformatics and a luciferase assay, further by immunofluorescence staining and Western blot, we identified IGFBP5, an insulin-like growth factor binding protein, as a direct target of miR-204-5p in HLECs. IGFBP5 expression was upregulated in the lens epithelium with anterior lens capsule of DC patients and in the HLEC cataract model, and IGFBP5 knockdown could reverse the mitochondrial dysfunction in the HLEC cataract model., Conclusions: Our results demonstrate that miR-204-5p maintains mitochondrial functional integrity through repressing IGFBP5, and reveal IGFBP5 may be a new therapeutic target and prognostic factor for DC., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Biological nitrogen fixation (BNF) plays a crucial role in nitrogen utilization in agroecosystems. Functional characteristics of plants (grasses vs. legumes) affect BNF. However, little is still known about how ecological zones and cropping patterns affect legume nitrogen fixation. This study's objective was to assess the effects of different cropping systems on aboveground dry matter, interspecific relationships, nodulation characteristics, root conformation, soil physicochemistry, BNF, and nitrogen transfer in three ecological zones and determine the main factors affecting nitrogen derived from the atmosphere (Ndfa) and nitrogen transferred (Ntransfer)., Methods: The 15 N labeling method was applied. Oats ( Avena sativa L.), forage peas ( Pisum sativum L.), common vetch ( Vicia sativa L.), and fava beans ( Vicia faba L.) were grown in monocultures and mixtures (YS: oats and forage peas; YJ: oats and common vetch; YC: oats and fava beans) in three ecological regions (HZ: Huangshui Valley; GN: Sanjiangyuan District; MY: Qilian Mountains Basin) in a split-plot design., Results: The results showed that mixing significantly promoted legume nodulation, optimized the configuration of the root system, increased aboveground dry matter, and enhanced nitrogen fixation in different ecological regions. The percentage of nitrogen derived from the atmosphere (%Ndfa) and percentage of nitrogen transferred (%Ntransfer) of legumes grown with different legume types and in different ecological zones were significantly different, but mixed cropping significantly increased the %Ndfa of the legumes. Factors affecting Ndfa included the cropping pattern, the ecological zone (R), the root nodule number, pH, ammonium-nitrogen, nitrate-nitrogen, microbial nitrogen mass (MBN), plant nitrogen content (N%), and aboveground dry biomass. Factors affecting Ntransfer included R, temperature, altitude, root surface area, nitrogen-fixing enzyme activity, organic matter, total soil nitrogen, MBN, and N%., Discussion: We concluded that mixed cropping is beneficial for BNF and that mixed cropping of legumes is a sustainable and effective forage management practice on the Tibetan Plateau., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Luo, Mi and Liu.)

Introduction: Non-small cell lung cancer (NSCLC) stands as one of the most prevalent malignancies, and chemotherapy remains the primary treatment for advanced stages. However, the high expression of ABC binding cassette transporters, including MRP, P-gp, and LRP, along with multidrug resistance proteins, has been identified as a significant factor contributing to decreased chemotherapy drug sensitivity. This study aims to explore the impact and underlying mechanisms of Curculiginis Rhizoma [Hypoxidaceae; Curculigo orchioides Gaertn.] (CR) in combination with cisplatin on improving chemoresistance mediated by ABC binding cassette transporters and multidrug resistance proteins in NSCLC., Methods and Results: To unravel the relationship between JNK, MRP, P-gp, and LRP in NSCLC and gain insights into the regulatory mechanism of CR, this study employs an integrated approach encompassing bioinformatics, molecular docking, molecular dynamics, animal and cellular experiments. Bioinformatics analysis revealed a significant increase in the expression levels of JNK, MRP, P-gp, and LRP subtypes in multidrug-resistant non-small cell lung cancer. Subsequent animal experiments have shown that the combination of CR with cisplatin can improve the survival rate of lung cancer mice. Molecular docking and molecular dynamics analyses demonstrated favorable binding interactions between curculigoside and the aforementioned subtypes of JNK, MRP, P-gp, and LRP. In cellular experiments, the combination of cisplatin with both curculigoside and CR extract resulted in a notable decrease in cell viability and downregulation of the expression of JNK1, JNK2, MRP1, MRP2, MRP4, P-gp, and LRP1 in A549/cis cells., Conclusion: Remarkably, curculigoside exerted a significant downregulation effect on the expression levels of JNK1, MRP1, MRP2, MRP4, and LRP1. CR, particularly its main effective metabolite, curculigoside, has the potential to enhance the sensitivity of non-small cell lung cancer to cisplatin by regulating levels of JNK/MRP/LRP/P-gp and mitigating multidrug resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest and approved by the Ethics Committee for exemption from ethical review., (© 2024 Huang et al.)

Recent studies are identified the mitochondria as critical targets of 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47) induced neurotoxicity. This study aimed at examining the impact of PBDE-47 exposure on mitochondrial translation, and its subsequent effect on PBDE-47 neurotoxicity. The Sprague-Dawley (SD) rat model and neuroendocrine pheochromocytoma (PC12) cells were adopted for the measurements of mitochondrial ATP levels, mitochondrial translation products, and expressions of important mitochondrial regulators, such as required meiotic nuclear division 1 (RMND1), estrogen-related receptor α (ERRα), and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α). To delve into the role of PGC-1α/ERRα axis in mitochondrial translation, 2-(4-tert-butylphenyl) benzimidazole (ZLN005) was employed. Both cellular and animal model results shown that PBDE-47 impeded PGC-1α/ERRα axis and mitochondrial translation. PBDE-47 suppressed mitochondrial function in rat hippocampus and PC12 cells by decreasing relative mitochondrial DNA (mtDNA) content, mitochondrial translation products, and mitochondrial ATP levels. Particularly, ZLN005 reversed PBDE-47 neurotoxicity by enhancing mitochondrial translation through activation of PGC-1α/ERRα axis, yet suppressing PGC-1α with siRNA attenuates its neuroprotective effect in vitro. In conclusion, this work highlights the importance of mitochondrial translation in PBDE-47 neurotoxicity by presenting results from cellular and animal models and suggests a potential therapeutic approach through activation of PGC-1α/ERRα axis. ENVIRONMENTAL IMPLICATION: PBDEs have attracted extensive attention because of their high lipophilicity, persistence, and detection levels in various environmental media. Increasing evidence has shown that neurodevelopmental disorders in children are associated with PBDE exposure. Several studies have also found that perinatal PBDE exposure can cause long-lasting neurobehavioral abnormalities in experimental animals. Our recent studies have also demonstrated the impact of PBDE-47 exposure on mitochondrial biogenesis and dynamics, leading to memory and neurobehavioral deficits. Therefore, we explore whether the pathological mechanism of PBDE-47-induced neurotoxicity involves the regulation of mitochondrial translation through the PGC-1α/ERRα axis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Extant Old World camels (genus Camelus) contributed to the economic and cultural exchanges between the East and West for thousands of years. 1 , 2 Although many remains have been unearthed, 3 , 4 , 5 we know neither whether the prevalent hybridization observed between extant Camelus species 2 , 6 , 7 also occurred between extinct lineages and the ancestors of extant Camelus species nor why some populations became extinct while others survived. To investigate these questions, we generated paleogenomic and stable isotope data from an extinct two-humped camel species, Camelus knoblochi. We find that in the mitochondrial phylogeny, all C. knoblochi form a paraphyletic group that nests within the diversity of modern, wild two-humped camels (Camelus ferus). In contrast, they are clearly distinguished from both wild and domesticated (Camelus bactrianus) two-humped camels on the nuclear level. Moreover, the divergence pattern of the three camel species approximates a trifurcation, because the most common topology is only slightly more frequent than the two other possible topologies. This mito-nuclear phylogenetic discordance likely arose due to interspecific gene flow between all three species, suggesting that interspecific hybridization is not exclusive to modern camels but a recurrent phenomenon throughout the evolutionary history of the genus Camelus. These results suggest that the genomic complexity of Old World camels' evolutionary history is underestimated when considering data from only modern species. Finally, we find that C. knoblochi populations began declining prior to the last glacial maximum and, by integrating palaeoecological evidence and stable isotope data, suggest that this was likely due to failure to adapt to a changing environment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Some macrofungi have a long history of being used as traditional or folk medicines, making significant contributions to human health. To discover bioactive molecules with potential anticancer properties, a homogeneous heteropolysaccharide (FOBP90-1) was purified from the medicinal macrofungus Fomitopsis officinalis. FOBP90-1 was found to have a molecular weight of 2.87 × 10 4  g/mol and mainly consist of →6)-α-d-Galp-(1→, →2,6)-α-d-Galp-(1→, →3)-α-l-Fucp-(1→, →6)-β-d-Glcp-(1→, α-d-Manp-(1→, and 3-O-Me-α-l-Fucp-(1→ according to UV, FT-IR, methylation analysis, and NMR data. In addition to its structural properties, FOBP90-1 displayed anticancer activity in zebrafish models. The following mechanistic analysis discovered that the in vivo antitumor effect was linked to immune activation and angiogenesis inhibition. These effects were mediated by the interactions of FOBP90-1 with TLR-2, TLR-4, PD-L1, and VEGFR-2, as determined through a series of experiments involving cells, transgenic zebrafish, molecular docking simulations, and surface plasmon resonance (SPR). All the experimental findings have demonstrated that FOBP90-1, a purified fungal polysaccharide, is expected to be utilized as a cancer treatment agent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Alcohol is implicated in epileptogenesis and seizures attack. An increasing number of studies about alcohol and epilepsy have been published. We aimed to assess research trends and hot spots in the field of alcohol and epilepsy., Patients and Methods: Literature concerning alcohol and epilepsy was systemically searched through the Web of Science database. Collaborative maps were quantitatively analyzed by using the VOSviewer and CiteSpace tools., Results: A total of 1578 papers about the field of alcohol and epilepsy were taken into analysis, which was written by 6840 authors from 2153 institutions in 85 countries, published in 676 journals, and cited 79 667 references from 10 750 journals. The United States was the leading country and had close ties with others. The University of Toronto was the most productive institution. Alcoholism-clinical and experimental research was the fastest-growing journal. Richard J. Bodnar was the author contributing the most literature. Analysis of keywords showed epilepsy, alcohol, seizures, alcohol withdrawal, and management were common themes., Conclusion: The presented study conducted the first bibliometric analysis of the field of alcohol and epilepsy, which will provide insights into the latest progress, evolution paths, frontier research hot spots, and future research trends in the field., (© 2024 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Understanding the optimal extraction methods for flavonoids from Abelmoschus manihot flowers (AMF) is crucial for unlocking their potential benefits. This study aimed to optimize the efficiency of flavonoid extraction from AMF. After comparing extraction methods, the ultrasonic cell crusher demonstrated superior performance over conventional techniques. Four key factors-solid-to-liquid ratio (1:10 to 1:50 g·mL -1 ), ethanol concentration (55% to 95%), ultrasonic time (10 to 50 min), and ultrasonic power (5% to 25% of 900 W)-were investigated and normalized using the entropy weight method. This led to a comprehensive evaluation (CE). Optimization of extraction conditions for the ultrasonic cell crusher was achieved through response surface methodology and a deep neural network model, resulting in optimal parameters: ethanol volume fraction of 66%, solid-to-liquid ratio of 1:21 g/mL, extraction efficiency of 9%, and extraction duration of 35 min, yielding a CE value of 23.14 (RSD < 1%). Additionally, the inhibitory effects of the optimized extracts against Streptococcus mutans ( S. mutans ) were assessed. The results revealed that AMF extract (AMFE) exhibits inhibitory effects on S. mutans , with concomitant inhibition of sucrase and lactate dehydrogenase (LDH). The MIC of AMFE against planktonic S . mutans is 3 mg/mL, with an MBC of 6 mg/mL. Within the concentration range of 1/8 MIC to 2 MIC of AMFE, the activities of sucrase and LDH decreased by 318.934 U/mg prot and 61.844 U/mg prot, respectively. The antioxidant activity of AMFE was assessed using the potassium ferricyanide reduction and phosphomolybdenum methods. Additionally, the effect of AMFE on DPPH, ABTS, and ·OH free radical scavenging abilities was determined. The concentrations at which AMFE exhibited over 90% scavenging rate for ABTS and DPPH free radicals were found to be 0.125 mg/mL and 2 mg/mL, respectively.

Background: Identifying patients who can benefit from immune checkpoint inhibitors (ICIs) is a critical challenge in immunotherapy. This study aimed to investigate the association between fat mass and obesity-associated protein (FTO) polymorphisms and ICIs treatment outcomes., Method: This retrospective study was conducted on 371 patients with malignant tumors who received ICIs treatment and were followed-up for a minimum duration of 12 months. Seven variants in FTO gene were genotyped using the Sequenome MassARRAY platform, and their associations with ICIs treatment outcomes were analyzed., Results: Pharmacogenomic research revealed that individuals carrying the rs11075995AT/TT genotype were more likely to benefit from ICIs treatment compare to TT genotype. Cox regression analysis showed that rs1125338TT carriers exhibited a shorter progression-free survival (PFS, hazard ratio (HR) = 1.72, 95 % confidence interval (CI) = 1.12-2.46), while rs12596638GG carriers experienced extended PFS (HR = 0.71, 95 % CI = 0.50-0.99). Multiple Cox regression analysis indicated that rs12596638GG (HR = 6.81, 95 %CI = 1.20-38.56) and rs1125338CC (HR = 1.78, 95 %CI = 0.07-0.45), rs12600192CC (HR = 0.13, 95 %CI = 0.037-0.44) genotypes were independently associated with overall survival (OS) after adjusting clinical characteristics. Furthermore, patients with rs12600192CC genotype had a lower risk of severe irAEs compared to those with GG/GC genotypes (P < 0.01)., Conclusion: We identified FTO gene polymorphisms associated with treatment outcomes of ICI treatment in patients with multiple solid cancers, which might serve as potential predictive biomarkers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucopyranoside (TSG) as the primary constituent of Polygonum multiflorum Thumb. (PM) possesses anti-oxidative, antihypercholesterolemic, anti-tumor and many more biological activities. The root of PM has been used as a tonic medicine for thousands of years. However, cases of PM-induced liver injury are occasionally reported, and considered to be related to the host immune status., Aim of the Study: The primary toxic elements and specific mechanisms PM causing liver damage are still not thoroughly clear. Our study aimed to investigate the influences of TSG on the immune response in idiosyncratic hepatotoxicity of PM., Materials and Methods: The male C57BL/6 mice were treated with different doses of TSG and the alterations in liver histology, serum liver enzyme levels, proportions of T cells and cytokines secretion were evaluated by hematoxylin and eosin (HE), RNA sequencing, quantitative real time polymerase chain reaction (qRT-PCR), Flow cytometry (FCM), and enzyme-linked immunosorbent assay (ELISA), respectively. Then, primary spleen cells from drug-naive mice were isolated and cultured with TSG in vitro. T cell subsets proliferation and cytokines secretion after treated with TSG were assessed by CCK8, FCM and ELISA. In addition, mice were pre-treated with anti-CD25 for depleting regulatory T cells (Tregs), and then administered with TSG. Liver functions and immunological alterations were analyzed to evaluate liver injury., Results: Data showed that TSG induced liver damage, and immune cells infiltration in the liver tissues. FCM results showed that TSG could activate CD4+T and CD8+T in the liver. Results further confirmed that TSG notably up-regulated the levels of inflammatory cytokines including TNF-α, IFN-γ, IL-18, perforin and granzyme B in the liver tissues. Furthermore, based on transcriptomics profiles, some immune system-related pathways including leukocyte activation involved in inflammatory response, leukocyte cell-cell adhesion, regulation of interleukin-1 beta production, mononuclear cell migration, antigen processing and presentation were altered in TSG treated mice. CD8+T/CD4+T cells were also stimulated by TSG in vitro. Interestingly, increased proportion of Tregs was observed after TSG treatment in vitro and in vivo. Foxp3 and TGF-β1 mRNA expressions were up-regulated in the liver tissues. Depletion of Tregs moderately enhanced TSG induced the secretion of inflammatory cytokines in serum., Conclusions: Our findings showed that TSG could trigger CD4+T and CD8+T cells proliferation, promote cytokines secretion, which revealed that adaptive immune response associated with the mild liver injury cause by TSG administration. Regulatory T cells (Tregs) mainly sustain immunological tolerance, and in this study, the progression of TSG induced liver injury was limited by Tregs. The results of our investigations allow us to preliminarily understand the mechanisms of PM related idiosyncratic hepatotoxicity., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2024. Published by Elsevier B.V.)

Objective: In this study, we aim to provide a comprehensive analysis of the effectiveness of the risk prevention and control mechanism within the grid management model for community risk prevention. We emphasize the importance of thoroughly examining the risk prevention and control mechanism to enhance risk management efforts in urban communities, particularly in response to unforeseen outbreaks such as COVID-19., Methods: Case studies are widely acknowledged as one of the most effective approaches to examine governance in China. In this study, the "Yuelu Model" serves as an illustrative example to demonstrate the application and effectiveness of grid management in community risk governance. To ensure the validity of the case study, it is imperative to adhere to the principle of representativeness. The collection of case data involves a combination of primary and secondary sources, and supplementary information is obtained through follow-up investigations conducted via WeChat, telephone, and other means, thereby enhancing the comprehensiveness and accuracy of the data., Results: Our analysis reveals significant findings regarding the impact of the grid management model, fulfilling a triple role as a "Social Safety Valve" in the management process: (1) Community stress reduction function, (2) Community alarm function, and (3) Community integration function. Furthermore, we explore the adaptability of the grid management mechanism in addressing community risks, highlighting its effectiveness and potential for broader application., Discussion: The findings of this study suggest that: Firstly, it is crucial to establish a shared information repository among different departments on a big data platform. Secondly, a dynamic government public information internal network should be established through collaborative efforts among multiple departments. Thirdly, implementing a regular (or periodic) early warning mechanism is essential. Lastly, the establishment of a high-quality talent team for power grid management is highly recommended. Our research provides valuable insights to enhance community risk governance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gao and Liu.)

Solid tumors are dense three-dimensional (3D) multicellular structures that enable efficient receptor-ligand trans interactions via close cell-cell contact. Immunoglobulin-like transcript (ILT)2 and ILT4 are related immune-suppressive receptors that play a role in the inhibition of myeloid cells within the tumor microenvironment. The relative contribution of ILT2 and ILT4 to immune inhibition in the context of solid tumor tissue has not been fully explored. We present evidence that both ILT2 and ILT4 contribute to myeloid inhibition. We found that although ILT2 inhibits myeloid cell activation in the context of trans-engagement by MHC-I, ILT4 efficiently inhibits myeloid cells in the presence of either cis- or trans-engagement. In a 3D spheroid tumor model, dual ILT2/ILT4 blockade was required for the optimal activation of myeloid cells, including the secretion of CXCL9 and CCL5, upregulation of CD86 on dendritic cells, and downregulation of CD163 on macrophages. Humanized mouse tumor models showed increased immune activation and cytolytic T-cell activity with combined ILT2 and ILT4 blockade, including evidence of the generation of immune niches, which have been shown to correlate with clinical response to immune-checkpoint blockade. In a human tumor explant histoculture system, dual ILT2/ILT4 blockade increased CXCL9 secretion, downregulated CD163 expression, and increased the expression of M1 macrophage, IFNγ, and cytolytic T-cell gene signatures. Thus, we have revealed distinct contributions of ILT2 and ILT4 to myeloid cell biology and provide proof-of-concept data supporting the combined blockade of ILT2 and ILT4 to therapeutically induce optimal myeloid cell reprogramming in the tumor microenvironment., (©2024 American Association for Cancer Research.)

Tumor treating fields (TTFields) therapy is a novel and effective noninvasive cancer therapy, and it has been approved by FDA in the treatment of recurrent and newly diagnosed glioblastoma, and malignant pleural mesothelioma. Moreover, TTFields therapy has been widely studied in both clinical trials and preclinical studies in recent years. Based on its high efficacy, research on TTFields therapy has been a hot topic. Thus, the authors made this scientometric analysis of TTfields to reveal the scientometric distributions such as annual publications and citations, countries and institutions, authors, journals, references, and more importantly, research status and hot topics of the field. In recent years, publication numbers have been stable at high values, and citation numbers have been increasing greatly. The United States and Israel were the top two countries with the highest publication numbers, followed by Germany and Switzerland. Scientometric analyses of keywords indicated that clinical applications and antitumor mechanisms are probably the two main parts of current research on TTfields. Most clinical trials of TTfields focus on the treatment of glioblastoma. And a variety of other cancers such as lung cancer especially nonsmall cell lung cancer, hepatic cancer, other brain tumors, etc. have also been studied in both clinical trials and preclinical studies., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Macrofungi, a class of unique natural resources, are gaining popularity owing to their potential therapeutic benefits and edibility. From Fomitopsis officinalis, a medicinal macrofungus with anticancer activity, a homogeneous heteropolysaccharide (FOBP50-1) with a molecular weight of 2.21 × 10 4  g/mol has been extracted and purified. FOBP50-1 was found to be composed of 3-O-methylfucose, fucose, mannose, glucose, and galactose with a ratio of 1: 6.5: 4.4: 8.1: 18.2. The sugar fragments and structure of FOBP50-1 were investigated, which included →6)-α-d-Galp-(1→, →2,6)-α-d-Galp-(1→, →3)-α-l-Fucp-(1→, α-d-Glcp-(1→, →3)-β-d-Manp-(1→, →6)-β-d-Manp-(1→, 3-O-Me-α-l-Fucp-(1→, according to the UV, FT-IR, GC-MS, and NMR data. Besides the structure elucidation, FOBP50-1 showed promising antitumor activity in the zebrafish assays. The following mechanism examination discovered that FOBP50-1 interacted with TLR-4, PD-1, and VEGF to activate immunity and inhibit angiogenesis according to a series of cell, transgenic zebrafish, and surface plasmon resonance (SPR) experiments. The K D values indicating the association of FOBP50-1 with TLR-4, PD-1, and VEGF, were 4.69 × 10 -5 , 7.98 × 10 -6 , 3.04 × 10 -6  M, respectively, in the SPR experiments. All investigations have demonstrated that the homogenous fungal polysaccharide FOBP50-1 has the potential to be turned into a tumor immunotherapy agent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Oat is a dual-purpose cereal used for grain and forage. The demand of oat has been increasing as the understanding of the nutritional, ecological, and economic values of oat increased. However, the frequent lodging during the growing period severely affect the high yielding potential and the quality of the grain and forage of oat., Methods: Therefore, we used the lodging-resistant variety LENA and the lodging-sensitive variety QY2 as materials, implementing four different planting densities: 2.25×10 6 plants/ha (D1), 4.5×10 6 plants/ha (D2), 6.75×10 6 plants/ha (D3), and 9×10 6 plants/ha (D4). At the appropriate growth and development stages, we assessed agronomic traits, mechanical characteristics, biochemical compositions, yield and its components. The study investigated the impact of planting density on the growth, lodging, and yield of oat, as well as their interrelationships. Additionally, we identified the optimal planting density to establish a robust crop structure. The research aims to contribute to the high-yield and high-quality cultivation of oat., Results: We observed that with increasing planting density, plant height, grass and grain yields of both varieties first increased and then decreased; root fresh weight, stem diameter, stem wall thickness, stem puncture strength, breaking strength, compressive strength, lignin and crude fiber contents, and yield components decreased; whereas the lodging rate and lodging coefficient increased. Planting density affects lodging by regulating plant height, height of center of gravity, stem wall thickness, internode length, and root fresh weight of oat. Additionally, it can impact stem mechanical strength by modulating the synthesis of lignin and crude fiber, which in turn affecting lodging resistance. Plant height, height of center of gravity, stem wall thickness, internode length, root fresh weight, breaking strength, compressive strength, lignin and crude fiber content, single-plant weight, grain yield and 1,000-grain weight can serve as important indicators for evaluating oat stem lodging resistance. We also noted that planting density affected grain yield both directly and indirectly (by affecting lodging); high density increased lodging rate and decreased grain yield, mainly by reducing 1,000-grain weight. Nonetheless, there was no significant relationship between lodging and grass yield. As appropriate planting density can increase the yield while maintaining good lodging resistance, in this study, 4.5×10 6 plants/ha (D2) was found to be the best planting density for oat in terms of lodging resistance and grass and grain yield. These findings can be used as a reference for oat planting., Competing Interests: The authors declare there are no competing interests., (©2024 Liu et al.)