CD11b-NOX2 mutual regulation-mediated microglial exosome release contributes to rotenone-induced inflammation and neurotoxicity in BV2 microglia and primary cultures.

Epidemiological studies have revealed a potent association between chronic exposure to rotenone, a commonly used pesticide, in individuals and the incidence of Parkinson's disease (PD). We previously identified the contribution of the activation of microglial NADPH oxidase (NOX2) in rotenone-induced neurotoxicity. However, the regulation of NOX2 activation remains unexplored. Integrins are known to be bidirectionally regulated in the plasma membrane through the inside-out and outside-in signaling. CD11b is the α-chain of integrin macrophage antigen complex-1. This study aimed to investigate whether CD11b mediates rotenone-induced NOX2 activation. We observed that rotenone exposure increased NOX2 activation in BV2 microglia, which was associated with elevated CD11b expression. Silencing CD11b significantly reduced rotenone-induced ROS production and p47phox phosphorylation, a key step for NOX2 activation. Furthermore, the Src-FAK-PKB and Syk-Vav1-Rac1 signaling pathways downstream of CD11b were found to be essential for CD11b-mediated NOX2 activation in rotenone-intoxicated microglia. Interestingly, we also found that inhibition of NOX2 decreased rotenone-induced CD11b expression, indicating a crosstalk between CD11b and NOX2. Subsequently, the inhibition of the CD11b-NOX2 axis suppressed rotenone-induced microglial activation and exosome release. Furthermore, inhibiting exosome synthesis in microglia blocked rotenone-induced gene expression of proinflammatory factors and related neurotoxicity. Finally, blocking the CD11b-NOX2 axis and exosome synthesis or endocytosis mitigated microglial activation and dopaminergic neurodegeneration in rotenone-intoxicated midbrain primary cultures. Our findings highlight the crucial involvement of the CD11b-NOX2 axis in rotenone-induced inflammation and neurotoxicity, offering fresh perspectives on the underlying mechanisms of pesticide-induced neuronal damage.

Mechanism of norcantharidin intervention in gastric cancer: analysis based on antitumor proprietary Chinese medicine database, network pharmacology, and transcriptomics.

BACKGROUND: Combining antitumor proprietary Chinese medicine (pCm) with radiotherapy and chemotherapy can effectively improve tumor cure rates and enhance patients' quality of life. Gastric cancer (GC) severely endangers public health. Despite satisfactory therapeutic effects achieved by using antitumor pCm to treat GC, its underlying mechanism remains unclear. OBJECTIVE: To integrate existing research data, construct a database of antitumor pCm, and study the intervention mechanisms in GC by focusing on their monomer components. METHODS: We constructed an antitumor pCm database based on China's medical insurance catalog, and employed network pharmacology, molecular docking methods, cell experiments, transcriptomics, and bioinformatics to investigate the intervention mechanisms of effective pCm components for GC. RESULTS: The study built an antitumor pCm database including 55 pCms, 171 Chinese herbal medicines, 1955 chemical components, 2104 targets, and 32 disease information. Network pharmacology and molecular docking technology identified norcantharidin as an effective component of antitumor pCm. In vitro experiments showed that norcantharidin effectively inhibited GC cell proliferation, migration, and invasion; blocked the G2/M cell cycle phase; and induced GC cell apoptosis. Transcriptomic results revealed that norcantharidin affected biological processes, such as cell adhesion, migration, and inflammatory responses by influencing PI3K-AKT, NF-κB, JAK-STAT, TNF-α signaling pathways, and EMT-related pathways. Core molecules of norcantharidin involved in GC intervention include SERPINE1, SHOX2, SOX4, PRDM1, TGFR3, TOX, PAX9, IL2RB, LAG3, and IL15RA. Additionally, the key target SERPINE1 was identified using bioinformatics methods. CONCLUSION: Norcantharidin, as an effective component of anti-tumor pCm, exerts its therapeutic effects on GC by influencing biological processes such as cell adhesion, migration, and inflammation. This study provides a foundation and research strategy for the post-marketing re-evaluation of antitumor pCms.

A study on the efficacy and Safety Evaluation of a novel PD-1/CTLA-4 bispecific antibody.

Tumors constitute a significant health concern for humans, and PD-1 and CTLA-4 monoclonal antibodies have been proven effective in cancer treatment. Some researchers have identified that the combination of PD-1 and CTLA-4 dual blockade demonstrates superior therapeutic efficacy. However, the development of PD-1/CTLA-4 bispecific antibodies faces challenges in terms of both safety and efficacy. The present study discloses a novel PD-1/CTLA-4 bispecific antibody, designated as SH010. Experimental validation through surface plasmon resonance (SPR) confirmed that SH010 exhibits favorable binding activity with both PD-1 and CTLA-4. Flow cytometry analysis demonstrated stable binding of SH010 antibody to CHOK1 cells overexpressing human or cynomolgus monkey PD-1 protein and to 293F cells overexpressing human or cynomolgus monkey CTLA-4 protein. Moreover, it exhibited excellent blocking capabilities in protein binding between human PD-1 and PD-L1, as well as human CTLA-4 and CD80/CD86. Simultaneously, in vitro experiments indicate that SH010 exerts a significant activating effect on hPBMCs. In murine transplant models of human prostate cancer (22RV1) and small cell lung cancer (NCI-H69), administration of varying concentrations of the bispecific antibody significantly inhibits tumor growth. MSD analysis revealed that stimulation of hPBMCs from three different donors with SH010 did not induce the production of cytokine release syndrome. Furthermore, Single or repeated intravenous administrations of SH010 in cynomolgus monkeys show favorable systemic exposure without noticeable drug accumulation or apparent toxicity. In conclusion, SH010 represents a novel cancer therapeutic drug poised to enter clinical trials and obtain market approval.

Bioactivity-guided isolation of potential antidiarrheal constituents from Euphorbia hirta L. and molecular docking evaluation.

Background: Euphorbia hirta L., a member of the Euphorbiaceae family, is extensively used as a folk medicine across various regions. In China, its decoction is traditionally consumed to alleviate diarrhea. This study aimed to evaluate the antidiarrheal activities of Euphorbia hirta and to identify its bioactive constituents through a bioactivity-guided isolation technique. Methods: Oral administration of E. hirta extract to mice was conducted to assess its effects on diarrhea. The anti-diarrheal effects were investigated in an aqueous extract and in three fractions of varying polarities derived from the aqueous extract, as well as in different eluates from D-101 macroporous resin, and in the compounds quercitrin and isoquercitrin, using mouse models with castor oil-induced diarrhea. Results: The aqueous extract demonstrated significant anti-diarrheal activities in a dose-dependent manner in the castor oil-induced diarrheal model. Notably, the ethyl acetate (EtOAc) fraction showed prominent effects. Through bioactivity-guided isolation, two major compounds, isoquercitrin and quercitrin from the active fraction were found to possess antidiarrheal effects. Molecular docking studies revealed that the affinity energy of isoquercitrin and quercitrin were -8.5 and -8.2 kcal mol-1, respectively, which were comparable to the reference drug loperamide, with an affinity energy of -9.1 kcal mol-1. Conclusion: This research provides evidence supporting the development of E. hirta as a therapeutic agent for diarrhea, with isoquercitrin and quercitrin emerging as two key constituents that are likely responsible for its antidiarrheal activity. These findings validate the traditional use of E. hirta and highlight its potential as a natural treatment for diarrhea.

Genetic history and biological adaptive landscape of the Tujia people inferred from shared haplotypes and alleles.

BACKGROUND: High-quality genomic datasets from under-representative populations are essential for population genetic analysis and medical relevance. Although the Tujia are the most populous ethnic minority in southwestern China, previous genetic studies have been fragmented and only partially reveal their genetic diversity landscape. The understanding of their fine-scale genetic structure and potentially differentiated biological adaptive features remains nascent. OBJECTIVES: This study aims to explore the demographic history and genetic architecture related to the natural selection of the Tujia people, focusing on a meta-Tujia population from the central regions of the Yangtze River Basin. RESULTS: Population genetic analyses conducted on the meta-Tujia people indicate that they occupy an intermediate position in the East Asian North-South genetic cline. A close genetic affinity was identified between the Tujia people and neighboring Sinitic-speaking populations. Admixture models suggest that the Tujia can be modeled as a mixture of northern and southern ancestries. Estimates of f3/f4 statistics confirmed the presence of ancestral links to ancient Yellow River Basin millet farmers and the BaBanQinCen-related groups. Furthermore, population-specific natural selection signatures were explored, revealing highly differentiated functional variants between the Tujia and southern indigenous populations, including genes associated with hair morphology (e.g., EDAR) and skin pigmentation (e.g., SLC24A5). Additionally, both shared and unique selection signatures were identified among ethnically diverse but geographically adjacent populations, highlighting their extensive admixture and the biological adaptations introduced by this admixture. CONCLUSIONS: The study unveils significant population movements and genetic admixture among the Tujia and other ethno-linguistically diverse East Asian groups, elucidating the differentiated adaptation processes across geographically diverse populations from the current genetic landscape.

Comparison of Different Intraoral Scanners With Prefabricated Aid on Accuracy and Framework Passive Fit of Digital Complete-Arch Implant Impression: An In Vitro Study.

OBJECTIVES: This study aimed to compare the accuracy of digital complete-arch implant impressions with prefabricated aids using three intraoral scanners (IOSs) and explore the correlation between virtual deviation measurement and physical framework misfit. MATERIALS AND METHODS: Four edentulous maxillary master models with four and six parallel and angular implants were fabricated and scanned by a laboratory scanner as reference scans. Ten scans of each master model were acquired using three IOSs (IOS-T, IOS-M, and IOS-A) with and without prefabricated aids. Trueness and precision of root mean square (RMS) errors were measured. Ten aluminum alloy frameworks were fabricated, and the misfit was measured with a micro-computed tomography scan with one screw tightened. RESULTS: Trueness and precision showed significant improvement when prefabricated aids were used for all three IOSs (p < 0.010). Median (interquartile range) RMS errors of trueness reduced from 67.5 (30.4) to 61.8 (30.3) µm, from 100.6 (35.4) to 45.9 (15.1) µm, and from 52.7 (33.2) to 41.1 (22.5) µm for scanner IOS-T, IOS-M, and IOS-A, respectively (p < 0.010). The precision of IOS-A and IOS-M was significantly better than IOS-T when using prefabricated aid (p < 0.001). RMS errors and the maximum marginal misfit of the framework were significantly correlated (p < 0.001, R2 = 0.845). CONCLUSIONS: With the prefabricated aids, the accuracy of IOSs enhanced significantly in digital complete-arch implant impressions. Three IOSs showed different levels of improvement in accuracy. Virtual RMS errors <62.2 µm could be the clinically acceptable threshold (150 µm) for framework passive fit.

Heterochromatin protein 1 alpha (HP1α) undergoes a monomer to dimer transition that opens and compacts live cell genome architecture.

Our understanding of heterochromatin nanostructure and its capacity to mediate gene silencing in a living cell has been prevented by the diffraction limit of optical microscopy. Thus, here to overcome this technical hurdle, and directly measure the nucleosome arrangement that underpins this dense chromatin state, we coupled fluorescence lifetime imaging microscopy (FLIM) of Förster resonance energy transfer (FRET) between histones core to the nucleosome, with molecular editing of heterochromatin protein 1 alpha (HP1α). Intriguingly, this super-resolved readout of nanoscale chromatin structure, alongside fluorescence fluctuation spectroscopy (FFS) and FLIM-FRET analysis of HP1α protein-protein interaction, revealed nucleosome arrangement to be differentially regulated by HP1α oligomeric state. Specifically, we found HP1α monomers to impart a previously undescribed global nucleosome spacing throughout genome architecture that is mediated by trimethylation on lysine 9 of histone H3 (H3K9me3) and locally reduced upon HP1α dimerisation. Collectively, these results demonstrate HP1α to impart a dual action on chromatin that increases the dynamic range of nucleosome proximity. We anticipate that this finding will have important implications for our understanding of how live cell heterochromatin structure regulates genome function.

The Impact of Cognitive Load on Cooperation and Antisocial Punishment: Insights from a Public Goods Game Experiment.

This paper investigates the impact of cognitive load on the formation and maintenance of cooperation within a public goods game experiment featuring a punishment option. By integrating the experimental designs of prior studies and manipulating cognitive load through the memorization of numbers with varying digits, we reveal that high cognitive load accelerates the breakdown of cooperation, irrespective of the presence of a punishment system. Furthermore, under high cognitive load, participants are more likely to engage in antisocial punishment, while the punishment of free riders remains unaffected. These findings suggest that increased cognitive load depletes the cognitive resources needed for deliberative decision-making, leading to a higher propensity for antisocial punishment. Our study contributes to the literature by demonstrating the significant influence of cognitive load on cooperative behavior and providing new insights into the causes of antisocial punishment.

Diet-related diseases mediate the effect of masticatory function on premature death in older adults.

AIM: Although poor oral health has been a potentially modifiable risk for mortality, the precise association between functional tooth units (FTUs) and premature death as well as the underlying mechanisms remains unclear. METHODS: This study used data from the National Health and Nutrition Examination Survey (NHANES) 2009-2018. Mortality details were obtained from the National Death Index (NDI). The number of FTUs was defined as pairs of opposing natural and artificial teeth in the premolar and molar area. Weighted logistic regression models were employed to assess the relationship between FTU and premature death. Demographic characteristics, lifestyle habits, and disease histories were adjusted as confounding factors. The propensity score matching (PSM) was conducted to further assess the association between FTU and premature death. Mediation analyses were conducted to assess the role of diet-related diseases in the association between FTU and premature death. RESULTS: The analysis included 4169 individuals aged between 60 and 74 years. Participants with 0 ≤ FTUs ≤ 3 had a significantly higher odds of premature death compared to the 10 ≤ FTUs ≤ 12 group (OR = 2.142, 95% CI 1.091-4.208). After missing data imputation, 0 ≤ FTUs ≤ 3 was still significantly associated with increased odds of premature death (OR = 2.115, 95% CI 1.125-3.975). The relationship between 0 ≤ FTUs ≤ 3 and reference group persisted (OR = 2.196, 95% CI 1.296-3.721) after PSM analyses. For mechanism, mediation analysis showed that diet-related diseases, including diabetes and hypertension, partially mediated the association between FTU and premature death with proportions of 5.089% and 8.437%, respectively. CONCLUSION: The findings revealed a link between impairment of masticatory function and a heightened odds of premature death among older adults. Notably, 0 ≤ FTUs ≤ 3 is significantly correlated to premature death among this demographic, with diabetes and hypertension partially mediating the effect of FTU on premature death. Further longitudinal studies are required to validate the findings.

Overlooked pyrite-mediated heterogeneous Fenton processes: Mechanisms of surface hydroxyl radical generation and associated decontamination performance.

Pyrite-based Fenton-like processes have been extensively studied for wastewater decontamination; however, most relevant studies placed excessive emphasis on the homogeneous Fenton reaction mediated by aqueous Fe2+, resulting in the proposed technologies facing issues such as additional acid requirements for pH adjustment and excessive iron sludge production. Herein, through in situ shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS), custom dual-chamber reactor experiments, and a series of control experiments, significant hydroxyl radical generation was identified during the pyrite/H2O2 process, while the dominant reactive iron species was verified to the structural Fe sites on the pyrite surface, rather than structural Fe(II) in secondary iron minerals and surface adsorbed Fe2+. Consequently, even with significant suppression of the homogeneous Fenton pathway, the pyrite/H2O2 process exhibited significant degradation efficiency for sulfamethoxazole (SMX) at pH 4. Moreover, the pyrite/H2O2 process was found to selectively remove 50 µM of pollutants with high affinity for pyrite (bisphenol A, carbamazepine, nitrobenzene, and SMX), even in the presence of 50-100 mM methanol. Compared to the typical iron-based reductive catalyst (zero-valent iron, ZVI), pyrite mediated a Fenton process with greater potential for practical applications at pH 4, achieving a 43.75-fold reduction in iron sludge production and almost doubling the H2O2 utilization efficiency. Additionally, in contrast to ZVI, minimal iron oxide formed on the pyrite surface during the oxidation process. Thus, after seven cycles of degradation experiments, the decontamination efficiency of the pyrite/H2O2 process remained stable. These findings are crucial for understanding the complex environmental behavior of pyrite in both natural and engineering processes and provide a new perspective for the efficient utilization of pyrite resources as well.

Identifying cell type-specific transcription factor-mediated activity immune modules reveal implications for immunotherapy and molecular classification of pan-cancer.

Systematic investigation of tumor-infiltrating immune (TII) cells is important to the development of immunotherapies, and the clinical response prediction in cancers. There exists complex transcriptional regulation within TII cells, and different immune cell types display specific regulation patterns. To dissect transcriptional regulation in TII cells, we first integrated the gene expression profiles from single-cell datasets, and proposed a computational pipeline to identify TII cell type-specific transcription factor (TF) mediated activity immune modules (TF-AIMs). Our analysis revealed key TFs, such as BACH2 and NFKB1 play important roles in B and NK cells, respectively. We also found some of these TF-AIMs may contribute to tumor pathogenesis. Based on TII cell type-specific TF-AIMs, we identified eight CD8+ T cell subtypes. In particular, we found the PD1 + CD8+ T cell subset and its specific TF-AIMs associated with immunotherapy response. Furthermore, the TII cell type-specific TF-AIMs displayed the potential to be used as predictive markers for immunotherapy response of cancer patients. At the pan-cancer level, we also identified and characterized six molecular subtypes across 9680 samples based on the activation status of TII cell type-specific TF-AIMs. Finally, we constructed a user-friendly web interface CellTF-AIMs (http://bio-bigdata.hrbmu.edu.cn/CellTF-AIMs/) for exploring transcriptional regulatory pattern in various TII cell types. Our study provides valuable implications and a rich resource for understanding the mechanisms involved in cancer microenvironment and immunotherapy.

Contribution of complexed Fe(â ¡) oxygenation to norfloxacin humification and stabilization: Producing and trapping of more humified products.

Organic pollutants polymerization in advanced oxidation processes or environmental matrices has attracted increasing attention, but little is known about stabilization of the polymerization products. The results in this work revealed the contribution of Fe(Ⅱ) oxygenation to stabilization of the products from norfloxacin (NOR) humification. It was found that upon oxygenation of Fe(Ⅱ) complexed by catechol (CT), NOR polymerized into the products with larger molecular weight through nucleophilic addition. Around 83.9-89.7 % organic carbon (OC) can be retained in the reaction solution and the precipitates at different Fe(II)/CT molar ratio. In this system with humification potential, the produced hydroxyl radical (HO•) dominantly modified, instead of decomposed, the structure of transformation products (TPs). TPs with diversified side chains were formed through hydroxylation and ring-opening, leading to the more humified products. In the subsequent Fe(Ⅱ) oxidative precipitation, Fe-TPs composites were formed as spherical particle clusters, which could steadily incorporate OC species with molecular fractionation. Specifically, lignin-like, tannins-like, condensed aromatic and high-molecular-weight TPs were preferentially preserved in the precipitates, while the recalcitrant aliphatic products mainly retained in the solution. These findings shed light on the role of Fe(Ⅱ) oxygenation in stabilizing the products from pollutants humification, which could strengthen both decontamination and organics sequestration.

Insights gained into the injury mechanism of drug and herb induced liver injury in the hepatic microenvironment.

Drug-Induced Liver Injury (DILI) and herb Induced Liver Injury (HILI) continues to pose a substantial challenge in both clinical practice and drug development, representing a grave threat to patient well-being. This comprehensive review introduces a novel perspective on DILI and HILI by thoroughly exploring the intricate microenvironment of the liver. The dynamic interplay among hepatocytes, sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, cholangiocytes, and the intricate vascular network assumes a central role in drug metabolism and detoxification. Significantly, this microenvironment is emerging as a critical determinant of susceptibility to DILI and HILI. The review delves into the multifaceted interactions within the liver microenvironment, providing valuable insights into the complex mechanisms that underlie DILI and HILI. Furthermore, we discuss potential strategies for mitigating drug-induced liver injury by targeting these influential factors, emphasizing their clinical relevance. By highlighting recent advances and future prospects, our aim is to shed light on the promising avenue of leveraging the liver microenvironment for the prevention and mitigation of DILI and HILI. This deeper understanding is crucial for advancing clinical practices and ensuring patient safety in the realm of DILI and HILI.

Effectiveness of Bairui granules in the treatment of respiratory tract infections: A systematic review and meta-analysis.

BACKGROUND: Respiratory tract infections (RTIs) are characterized by a high mortality rate and clinical incidence. Bairui granules (BG), which employ a method of heat elimination and detoxification, have demonstrated benefits in the treatment of infectious respiratory diseases. METHODS: A computerized search of 6 databases was conducted to identify randomized controlled trials (RCTs) relevant to the treatment of RTIs with BG up to November 30, 2023. Two researchers independently conducted data extraction, risk of bias assessment, and grading analysis. To evaluate the stability of the results, trial sequential analysis was employed. RESULTS: This meta-analysis included 31 RCTs with a total of 4073 patients and demonstrated that the use of BG in the treatment of RTIs was associated with enhanced treatment efficacy (relative risk = 1.19, 95% credible interval: 1.16-1.22, P < .001). It also indicated a faster resolution of symptoms including pulmonary rales, cough, and fever, as well as a reduction in serological index factors, compared to the use of Western medicine treatment (WT) alone. Additionally, the duration of hospitalization for patients was significantly reduced (relative risk = -1.36, 95% credible interval: -1.55 to -1.17, P < .001). Trial sequential analysis confirmed the stability and conclusive evidence of the study results. The efficacy of treating RTIs with BG, either alone or in combination with WT, was found to be superior to WT alone. However, further high-quality RCTs are necessary to validate these outcomes. CONCLUSION: The effectiveness of treating RTIs using BG alone or in combination with WT was determined to be superior to using WT alone, with no serious adverse effects observed. However, additional RCTs are essential to further confirm the findings of this study.

Corrigendum: Network pharmacology-based exploration identified the antiviral efficacy of Quercetin isolated from mulberry leaves against enterovirus 71 via the NF-κB signaling pathway.

[This corrects the article DOI: 10.3389/fphar.2023.1260288.].

Association between masticatory function and depression in older adults: Results from NHANES 2009 to 2018.

AIM: Depression is prevalent among older adults. Although the number of missing teeth is considered to be associated with depression, the relationship between masticatory function, which is usually indicated by functional tooth units (FTUs), and depression in older adults remains unclear. MATERIALS AND METHODS: This study used data from the National Health and Nutrition Examination Survey (NHANES) 2009-2018. The number of FTUs was defined as pairs of opposing natural and artificial teeth. Depression was accessed using the Patient Health Questionnaire (PHQ-9), and participants who scored ≥10 on PHQ-9 were diagnosed with depression. Logistic regression analyses, propensity score matching (PSM) analyses and subgroup analyses were conducted to assess the association between FTU and depression. RESULTS: The analysis included 5764 individuals over 60 years. An association between FTU and the risk of depression among older adults was detected (odds ratio [OR] = 0.951, 95% confidence interval [CI] 0.915-0.989), suggesting protective roles of more FTUs. Significant increase in the risk of depression in 0 ≤ FTUs ≤ 3 was observed compared with 10 ≤ FTUs ≤ 12 (OR = 1.819, 95% CI 1.157-2.858). However, no significant increase in the risk of depression in 4 ≤ FTUs ≤ 9 was found. After PSM, significant increase in the risk of depression in 0 ≤ FTUs ≤ 3 was still detected compared with 4 ≤ FTUs ≤ 12 (OR = 1.484, 95% CI 1.030-2.136). Subgroup analyses demonstrated consistent results in all subgroups, except for individuals aged 76-80 and drinking regularly. CONCLUSIONS: The findings suggested the association between impaired masticatory function and the risk of depression among older adults. Longitudinal studies are needed to elucidate the role of masticatory function impairment in the development of depression further.

The reference genome sequence of Artemisia argyi provides insights into secondary metabolism biosynthesis.

Artemisia argyi, a perennial herb of the genus Artemisia in the family Asteraceae, holds significant importance in Chinese traditional medicine, referred to as "Aicao". Here, we report a high-quality reference genome of Artemisia argyi L. cv. beiai, with a genome size up to 4.15 Gb and a contig N50 of 508.96 Kb, produced with third-generation Nanopore sequencing technology. We predicted 147,248 protein-coding genes, with approximately 68.86% of the assembled sequences comprising repetitive elements, primarily long terminal repeat retrotransposons(LTRs). Comparative genomics analysis shows that A. argyi has the highest number of specific gene families with 5121, and much more families with four or more members than the other 6 plant species, which is consistent with its more expanded gene families and fewer contracted gene families. Furthermore, through transcriptome sequencing of A. argyi in response to exogenous MeJA treatment, we have elucidated acquired regulatory insights into MeJA's impact on the phenylpropanoid, flavonoid, and terpenoid biosynthesis pathways of A. argyi. The whole-genome information obtained in this study serves as a valuable resource for delving deeper into the cultivation and molecular breeding of A. argyi. Moreover, it holds promise for enhancing genome assemblies across other members of the Asteraceae family. The identification of key genes establishes a solid groundwork for developing new varieties of Artemisia with elevated concentrations of active compounds.

Populus euphratica CPK21 Interacts with NF-YC3 to Enhance Cadmium Tolerance in Arabidopsis.

The toxic metal cadmium (Cd) poses a serious threat to plant growth and human health. Populus euphratica calcium-dependent protein kinase 21 (CPK21) has previously been shown to attenuate Cd toxicity by reducing Cd accumulation, enhancing antioxidant defense and improving water balance in transgenic Arabidopsis. Here, we confirmed a protein-protein interaction between PeCPK21 and Arabidopsis nuclear transcription factor YC3 (AtNF-YC3) by yeast two-hybrid and bimolecular fluorescence complementation assays. AtNF-YC3 was induced by Cd and strongly expressed in PeCPK21-overexpressed plants. Overexpression of AtNF-YC3 in Arabidopsis reduced the Cd inhibition of root length, fresh weight and membrane stability under Cd stress conditions (100 µM, 7 d), suggesting that AtNF-YC3 appears to contribute to the improvement of Cd stress tolerance. AtNF-YC3 improved Cd tolerance by limiting Cd uptake and accumulation, activating antioxidant enzymes and reducing hydrogen peroxide (H2O2) production under Cd stress. We conclude that PeCPK21 interacts with AtNF-YC3 to limit Cd accumulation and enhance the reactive oxygen species (ROS) scavenging system and thereby positively regulate plant adaptation to Cd environments. This study highlights the interaction between PeCPK21 and AtNF-YC3 under Cd stress conditions, which can be utilized to improve Cd tolerance in higher plants.

Bovine-originated xenografts versus synthetic bone grafting materials in lateral maxillary sinus floor augmentation: A systematic review and meta-analysis.

AIMS: This study aimed to systematically compare the patients undergoing lateral MSFA therapies utilizing bovine-originated xenografts versus varied synthetic bone grafting materials. METHODS: Pubmed, Scopus, Embase, and Cochrane Library were searched up to April 2023, compensated by a manual search in selected journals. Studies reporting histological outcomes (residual bone graft, newly formed bone, non-mineralized tissue) and clinical outcomes (implant survival, ISQ value) were included. Several analyses were performed, including meta-analysis, sensitivity study, and Egger's regression tests. RESULTS: Sixteen clinical/randomized control trials were included in this systematic review, among which 12 were enrolled in a meta-analysis. The percentage of newly formed bone within the grafted sinuses by hybrid HA/TCP was significantly higher than those by xenografts (WMD 2.85, 95%CI [0.72; 4.99]), but those grafted by pure HA (WMD -1.72, 95%CI [-3.15; -0.29]) or TCP (WMD -7.10, 95%CI [-13.02; -1.17]) were significantly lower than xenograft counterparts. The residual bone graft and non-mineralized tissue yielded by synthetic HA, TCP, and HA/TCP showed no significant differences with the xenograft group. CONCLUSION: The chemistry of grafted bone substitutes in lateral MSFA influenced the quantity of newly formed bone. Those grafted with hybrid HA/TCP yielded the highest amount of new bone compared to bovine-originated HA. However, this influence was not significant on residual bone graft and non-mineralized tissue.

Final analysis of a phase II trial of neoadjuvant chemoimmunotherapy for locoregionally advanced head and neck squamous cell carcinoma.

OBJECTIVES: Neoadjuvant chemoimmunotherapy has shown promising results for resectable, locoregionally advanced (LA) head and neck squamous cell carcinoma (L/A HNSCC). We published the first phase II trial of neoadjuvant camrelizumab combined with chemotherapy in resectable, L/A HNSCC, demonstrating it was safe and feasible with favorable pathological complete response (pCR). Here, we report the final analysis results for neoadjuvant chemoimmunotherapy in L/A HNSCC (minimum 2.0 years of follow-up). MATERIALS AND METHODS: Three cycles of chemoimmunotherapy were administered before surgery to patients with L/A HNSCC. Two-year disease-free survival (DFS), overall survival (OS) and quality of life (QOL) were reported. RESULTS: The overall two-year DFS and OS rates were 90 % and 100 %, respectively. With a median follow-up of 33.7 months, 9 of 10 (90 %) patients with pCR were alive and disease free. Patients with TNM stage (II/III) or < 20 % of residual viable tumor trended toward improved DFS; hazard ratio (HR), 0.44 [95 % confidence interval (CI), 0.04-5.28] and HR, 0.26 (95 % CI, 0.03-2.36), respectively. All QLQ-C30 functioning and symptom scales other than nausea and vomiting were resolved at 2 years after the completion of radiotherapy. CONCLUSION: Neoadjuvant camrelizumab in combination with chemotherapy provided encouraging clinical outcomes for patients with L/A HNSCC. Further studies with longer follow-up and larger samples are warranted. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR1900025303. Registered Aug 22, 2019. https://www.chictr.org.cn/showproj.html?proj=41380.