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[Display omitted] • The synergistic stress imposed by Cu(II)-Cr(VI) accelerated the deterioration in all systems except for C2-3. • The correlation between Cr(VI) and microbial diversity exhibited a notably higher significance compared to Cu(II), whereas Cu(II) demonstrated greater toxicity relative to Cr(VI). • Cu(II) exhibited a more pronounced influence on denitrification genes, whereas Cr(VI) on aniline-degrading genes. • The Cu(II)-Cr(VI)-aniline systems disrupted the matrix transport chain through its elevated toxicity, consequently impeding the metabolic functionality of the systems. In order to examine the impact of Cu(II)-Cr(VI) co-pollution in printing and dyeing wastewater on the aniline biodegradation system (ABS), loading experiments were conducted on ABS at varying concentrations of Cu(II)-Cr(VI). The synergistic stress imposed by Cu(II)-Cr(VI) accelerated the deterioration of the systems, with only the C2-3 (2 mg/L Cr(VI)-3 mg/L Cu(II)) sustaining stable operation for 42 days. However, its nitrogen removal performance remained significantly impaired, resulting in a total nitrogen (TN) removal rate below 40%. High-throughput sequencing analysis revealed a stronger correlation between Cr(VI) and microbial diversity compared to Cu(II). Metagenomic sequencing results demonstrated that Cu(II) emerged as the dominant factor influencing the distribution of dominant bacteria in C2-3, as well as its contribution to contaminant degradation. The complex co-pollution systems hindered aniline degradation and nitrogen metabolism through the combined bio-toxicity of heavy metals and aniline, thereby disrupting the transport chain within the systems matrix. [ABSTRACT FROM AUTHOR]

In China, males make up the majority of methamphetamine (MA) dependent individuals and the majority of treatment seekers. Childhood trauma (CT) and rumination are associated with an increased risk of MA use. However, the association between CT, rumination, and drug craving remains largely unknown. The present study aims to explore the association between rumination and drug craving in methamphetamine use disorder (MAUD) patients with CT. This study recruited 404 male participants with MAUD from a male drug rehabilitation center in Southwest China. Patients with CT were identified by the short form of Childhood Trauma Questionnaire (CTQ-SF). Rumination and drug craving were assessed by the Ruminative Responses Scale (RRS) and the Obsessive Compulsive Drug Use Scale (OCDUS), respectively. 188 patients (46.5 %) experienced CT. Patients who had experienced CT showed significantly higher RRS symptom rumination score and OCDUS total score than those who had not. In patients with CT, RRS total and all subscale scores were positively associated with OCDUS interference of drug. Furthermore, the RRS brooding (β = 0.34, p < 0.001) and total scores (β = 0.38, p < 0.001) were determined to be separate contributors to the OCDUS total score in patients with CT. Our study suggests that CT is common in male MAUD patients, and those who have suffered CT may exhibit higher levels of rumination and drug craving. Moreover, CT may play an influential role in the association between rumination and drug craving in patients with MAUD. [ABSTRACT FROM AUTHOR]

Corona Virus Disease 2019 (COVID-19) is an acute respiratory infection and a global public health event. The level of aβ 2 GPI is significantly up-regulated in COVID-19 patients. The impact of inactivated vaccination against COVID-19 on aβ 2 GPI and in vitro fertilization and embryo transfer (IVF-ET) remains unknown amidst the universal administration of COVID-19 vaccines. We conducted a retrospective study to assess the impact of COVID-19 inactivated vaccination on aβ 2 GPI levels and its effect on superovulation and pregnancy outcomes. We found aβ 2 GPI level is significantly up-regulated after vaccination. There was no statistical difference in mature egg rate, 2PN fertilization rate, day 3 high-quality embryo rate, blastocyst formation rate, embryo implantation rate and miscarriage rate between the vaccine group and control group. Our findings showed vaccination with COVID-19 inactivated vaccine can elevate the level of aβ 2 GPI in peripheral blood but have no effect on the outcomes of controlled ovarian hyperstimulation and pregnancy in IVF-ET. • This is the first study to explore the correlation between the level of aβ 2 GPI in patients after inactivated COVID-19 vaccination and the outcome of ovulation hyperstimulation and pregnancy in IVF-ET. • The results showed aβ 2 GPI level is significantly up-regulated after inactivated COVID-19 vaccination. • The results showed no statistical difference in mature egg rate, 2PN fertilization rate, day 3 high-quality embryo rate, blastocyst formation rate, embryo implantation rate and miscarriage rate betwee n the vaccine group and control group. [ABSTRACT FROM AUTHOR]

Multi-walled carbon nanotubes (MWCNTs) are one of the ideal reinforcements for metal matrix composites (MMCs), however, it faced a big challenge regarding their mechanical compatibility of MWCNTs reinforced titanium matrix composites (TMCs) due to its strong agglomeration, undesirable interfacial reaction and etc. To overcome this key problem, we employed Cu nanoparticles to decorate MWCNTs (Cu-MWCNTs) and successfully fabricated Cu-MWCNTs reinforced TMCs with the support of hot-pressed sintering (HPS) approach. The addition of Cu nanoparticles not only improved its dispersion, but also effectively reduced the interfacial reaction through the in-situ synthesized interfacial Ti 2 Cu phases and preserving the integrity of MWCNTs. Tensile studies reflected that the addition of 0.5 wt % Cu-MWCNTs was advantageous in improving the tensile properties, breaking through the trade-off between the strength and ductility, which were 15% and 45% higher than the matrix alloy, respectively. The quantitatively analysis of the increased strength proved that the primary strengthening mechanisms included the grain refinement, the solid solution of the carbon atoms from MWCNTs and the efficient load transfer from the multiple interfaces with in-situ synthesized interfacial Ti 2 Cu phases. The improvement in toughness was mainly derived from the high dislocation storage capacity induced by interfacial modification, thus achieving the higher uniform elongation in TMCs. Consequently, this work provided the promising approach to design strong and ductile TMCs. • Fabricated successfully MWCNTs decorated with Cu nanoparticles (Cu-MWCNTs) via a hydrothermal reaction method. • Cu-MWCNTs not only improved the dispersion, but also effectively preserving the integrity of MWCNTs. • Revealed the strengthening-toughening mechanisms induced by the interfacial modification strategy. • Provided a valuable and practical route to design strong and ductile MWCNTs reinforced TMCs. [ABSTRACT FROM AUTHOR]

• TPB-DVA-COF-SPME were fabricated on stainless steel by an in-situ growth strategy. • The COF featured high specific surface area, regular pores, and good hydrophobicity. • The COF possessed high selectivity and enrichment factors for TCAs. • TPB-DVA-COF-SPME-ESI/MS enabled rapid and sensitive analysis of TCAs in biosamples. Tricyclic antidepressants (TCAs) including amitriptyline (AT), doxepin (DOX) and nortriptyline (NT) are the first-line drugs for the clinical treatment of depression; however, monitoring TCA concentrations in biological fluids and tissues is necessary to improve therapeutic effect and determine the cause of death in patients. It is of great significance to develop a rapid and sensitive method for real-time monitoring of TCAs in various biosamples. In this work, we fabricated a novel covalent organic framework (COF) based solid-phase microextraction (SPME) probe by an in-situ step-by-step strategy, which was obtained by sequentially modifying 1,3,5-tri (4-aminophenyl) benzene (TPB) and 2, 5-divinylbenzaldehyde (DVA) on the surface of polydopamine layer. The TPB-DVA-COF-SPME probe possessed high specific surface area (1244 m2· g −1), regular pores (3.23 nm), good hydrophobicity and stability, resulting in efficient enrichment for TCAs. Furthermore, the combination of TPB-DVA-COF-SPME probe and ambient electrospray ionization mass spectrometry system (ESI/MS) was firstly proposed for rapid and sensitive determination of TCAs in biosamples. As a result, the developed method exhibited low limits of detection (LODs) (0.1–0.5 μg∙ L −1), high enrichment factors (39–218), and low relative standard deviations (RSDs) for one probe (1.2–3.8%) and probe-to-probe (2.0–3.7%). Benefiting from these outstanding performance, TPB-DVA-COF-SPME probe was further successfully applied to biosamples (i.e., serum, liver, kidney, and brain) with excellent reusability, indicating the promising applicability of the TPB-DVA-COF-SPME-ESI/MS as a powerful tool for drug monitoring. [ABSTRACT FROM AUTHOR]

Cognitive dysfunction and posttraumatic stress disorder (PTSD) are common in methamphetamine patients. However, few studies have investigated the cognitive performance of methamphetamine patients with PTSD. The purpose of this study was to investigate the impact of comorbid PTSD on cognitive function in Chinese male methamphetamine patients. We analyzed 464 methamphetamine patients and 156 healthy volunteers. The PTSD Screening Scale (PCL-5) was used to assess PTSD and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function. Compared with healthy controls, methamphetamine patients had more cognitive dysfunction in immediate memory, visuospatial/constructional, language, attention and delayed memory. Moreover, methamphetamine patients with PTSD had less cognitive dysfunction in immediate memory, attention, and delayed memory than methamphetamine patients without PTSD. Further stepwise regression analysis showed that PTSD alterations in arousal and reactivity cluster were risk predictors for language, and PTSD negative alteration in cognition and mood cluster were risk predictors for delayed memory. Our results indicate that methamphetamine patients without PTSD have poorer cognitive dysfunction than those with PTSD. Some demographic and PTSD symptom clusters are protective or risk factors for cognitive dysfunction in methamphetamine patients. • Methamphetamine patients had more cognitive dysfunction than healthy individuals. • Methamphetamine patients without PTSD had worse cognition than those with PTSD. • Different PTSD symptom clusters may have distinct patterns of cognitive deficits. [ABSTRACT FROM AUTHOR]

To date, the pattern of heroin- and methamphetamine-induced cognitive impairment is unclear, especially in the Chinese population. The aim of this study was to compare the similarity and heterogeneity of cognitive impairment between heroin and methamphetamine-dependent patients and to link cognitive impairment to drug-related variables. 567 pure methamphetamine patients, 78 pure heroin patients and 201 healthy volunteers participated in this study. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function including immediate memory, visuospatial/constructional index, language, attention, delayed memory, and total scores. Methamphetamine-dependent and heroin-dependent patients performed significantly worse on all RBANS subtest and total scores (all p < 0.05). Moreover, methamphetamine-dependent patients had more delayed memory impairment than heroin-dependent patients (p = 0.02). In addition, some drug-related variables, such as duration of abstinence, age at first drug use, and duration of drug use, were independently associated with memory and visuospatial/constructional index in methamphetamine patients (all p < 0.05). In contrast, none of the drug-related variables were associated with cognitive performance in heroin patients (all p > 0.05). Chronic heroin and methamphetamine patients may exhibit different patterns of cognitive deficits. • Methamphetamine and heroin patients overlapped in some cognitive impairments. • Methamphetamine patients performed worse on delayed memory. • Methamphetamine and heroin patients may have different patterns of cognitive deficits. [ABSTRACT FROM AUTHOR]

Carbamazepine (CBZ) and its metabolite carbamazepine-10,11-epoxide (CBZEP) play vital role in the treatment of epilepsy. It is of great importance to develop a method for rapid and sensitive monitoring of CBZ and CBZEP due to their narrow therapeutic index. Herein, an imine-linked-based covalent organic framework was synthesized by using 1,3,5-tris (4-aminophenyl) benzene (TPB) and 1,3,5-triformylbenzene (TFB) (denoted as TPB-TFB-COF)，and applied as a solid-phase microextraction (SPME) probe for extracting CBZ and CBZEP. The TPB-TFB-COF showed large surface areas (371 m2 g−1), high regular porosity (1.23 nm) and extraordinary stability, which rendered it an ideal adsorbent for highly efficient enrichment of CBZ and CBZEP. Accordingly, an attractive strategy of the combination of the TPB-TFB–COF–based SPME probe and electrospray ionization mass spectrometry system (ESI/MS) was proposed for rapid screening and sensitive monitoring of CBZ and CBZEP. Under the optimized parameters, the developed method exhibited good linearity for CBZ and CBZEP in the range of 4–1000 μg L−1 with correlation coefficient (r) no less than 0.9953, and the corresponding limits of detection (LODs) were 0.4 and 2.5 μg L−1, respectively. Moreover, high enrichment factors (EFs, 202–351 folds) and satisfactory relative standard deviations (RSDs) of one probe (3.3–5.1%) and probe-to-probe (4.8–5.6%) were obtained. By using the proposed method, sensitive screening and quantitative evaluation of CBZ and CBZEP in mice whole blood and tissue homogenates were successfully achieved, indicating the promising applicability of the TPB-TFB–COF–SPME-AMIS as a powerful tool for drug monitoring. An attractive strategy of the combination of covalent organic framework-based solid phase microextraction probe and electrospray ionization mass spectrometry system was developed for rapid screening and sensitive monitoring of carbamazepine and its metabolite in mice. [Display omitted] • TPB-TFB-COF was synthesized at room temperature and used as SPME adsorbent. • The SPME probe exhibited high adsorption performance towards CBZ and CBZEP. • The TPB-TFB-COF combined with ESI/MS method was simple, fast and highly efficient. • The method can be applied to sensitive determination of CBZ and CBZEP in mice. [ABSTRACT FROM AUTHOR]

Arginine methylation plays vital roles in the cellular functions of the protozoan Trypanosoma brucei. The T. brucei arginine methyltransferase 6 (TbPRMT6) is a type I arginine methyltransferase homologous to human PRMT6. In this study, we report the crystal structures of apo-TbPRMT6 and its complex with the reaction product S-adenosyl-homocysteine (SAH). The structure of apo-TbPRMT6 displays several features that are different from those of type I PRMTs that were structurally characterized previously, including four stretches of insertion, the absence of strand β15, and a distinct dimerization arm. The comparison of the apo-TbPRMT6 and SAH-TbPRMT6 structures revealed the fine rearrangements in the active site upon SAH binding. The isothermal titration calorimetry results demonstrated that SAH binding greatly increases the affinity of TbPRMT6 to a substrate peptide derived from bovine histone H4. The western blotting and mass spectrometry results revealed that TbPRMT6 methylates bovine histone H4 tail at arginine 3 but cannot methylate several T. brucei histone tails. In summary, our results highlight the structural differences between TbPRMT6 and other type I PRMTs and reveal that the active site rearrangement upon SAH binding is important for the substrate binding of TbPRMT6. [ABSTRACT FROM AUTHOR]

• Eleven PMFs in 116 citrus accessions were determined by UPLC–ESI-QTOF-MS/MS and HPLC–DAD. • The spatiotemporal and species-specific distribution of PMFs in citrus was revealed. • The clustering of eleven PMFs by HCA agreed with classic citrus taxonomy. • Wild or semi-wild mandarins contained large amounts of total or specific PMFs. • PMF accumulation may be a phenotype inherited from mandarin ancestors. Citrus fruits are the main dietary source of polymethoxylated flavones (PMFs) with significant effects on consumer health. In this study, eleven main PMFs were evaluated in the fruit flavedo or leaves of 116 citrus accessions via UPLC–DAD–ESI-QTOF-MS/MS combined with HPLC–DAD analysis, which revealed significant species-specific and spatiotemporal characteristics. All Citrus reticulata and their natural or artificial hybrids were found to have detectable PMFs, especially in the fruit flavedo of the wild or early-cultivated mandarins at early fruit development stages. However, PMFs were not detected in citrons, pummelos, kumquats, trifoliata oranges, papedas, Chinese box oranges and 'Mangshanyegan'. The results enlightened that PMF accumulation only in mandarins and mandarin hybrids is a phenotype inherited from mandarin ancestors. This study provides a comprehensive PMF profile in various citrus germplasms and will benefit future functional citrus breeding practices aimed at designing plants rich in total or specific PMFs for health benefits. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) is an aggressive and immunogenic subtype of breast cancer. The absence of biomarker has given immune checkpoint inhibitors (ICIs) a broad prospect in this type of breast cancer. The infiltration of regulatory T cells (Tregs) expressing transcription factor forkhead box P3 (Foxp3) in the tumor microenvironment (TME) is the key factor leading to ICIs resistance. Therefore, elimination of tumor antigen-specific Tregs may be an important aspect of improving ICIs efficacy. In this study, it based on the Gene Expression Omnibus and The Cancer Genome Atlas database, along with in vivo and in vitro experimental models, to verified that the high expression of integrin-linked kinase (ILK) in TNBC is the key differential factor leading to the high infiltration of Foxp3 + -Tregs in the TME. Then, we selected ILK-specific inhibitor, OSU-T315, to intervene in vitro and vivo. Importantly, we found that OSU-T315 blocked the secretion of CCL17/CCL22 in tumor cells by inhibiting the ILK/NF-κB pathway, resulting in the apoptosis of Foxp3 + -Tregs and decreased programmed cell death-1 (PD-1) expression. Therefore, our findings indicate a novel mechanism of OSU-T315 with potential therapeutic application in TNBC., 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 B.V. All rights reserved.)

Objective: This study aimed to investigate the correlation between computed tomography (CT) derived body composition and 30-day mortality in patients with pulmonary infections caused by carbapenem-resistant Klebsiella pneumoniae ( K. pneumoniae )., Methods: A total of 89 eligible participants from a tertiary teaching hospital, enrolled between January 1, 2016, and December 31, 2020, were included in the study. We analyzed the relationship between visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), total adipose tissue (TAT), and skeletal muscle (SM) and 30-day mortality in patients infected with carbapenem-resistant K. pneumoniae (CRKP) in the pulmonary region. Furthermore, we established Cox regression models and a personalized nomogram model to predict the probability of 30-day mortality in these infected patients., Results: Individuals with high VAT exhibited a higher likelihood of 30-day all-cause mortality (P<0.01) and 30-day mortality due to CRKP infection (P<0.01) compared to those with low VAT. Similar results were observed for TAT. After adjusting for significant comorbidities and other clinical characteristics, Cox regression analysis revealed that male gender (adjusted HR = 4.37; 95% CI = 0.96-19.92, P=0.06), vasopressor use (adjusted HR = 3.65; 95% CI = 1.04-12.85, P=0.04), and VAT (adjusted HR = 1.16; 95% CI = 1.01-1.34, P=0.03) were independent risk factors for 30-day all-cause mortality among these infectious patients., Conclusion: The study results highlight the significant prognostic value of CT-quantified visceral adipose tissue in patients with CRKP pulmonary infection. Individuals with high VAT are more prone to mortality within 30 days compared to those with low VAT., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Ying et al.)

Groundwater contamination by nitrate and sulfate in mining areas is a significant challenge. Consequently, the inputs sources of these contaminants and their evolution have received considerable attention, with the knowledge gained critical for improved management of water quality. This study integrated data on multiple stable isotopes and water chemistry data and a Bayesian isotope mixing model to investigate the relative contributions of inputs sources of sulfate and nitrate sources to bodies of water in a karst mining area in southwest China. The outcomes indicated that hydrochemical component in the water bodies of the study area is mainly derived from the dissolution of silicate rocks, carbonate rocks and sulfate minerals as well as the oxidation of sulfides. The human and agricultural wastewater, soil nitrogen, and fertilizers were the predominant inputs sources of nitrate to the mine water environment; the predominant inputs sources of sulfide were mineral oxidation, evaporite dissolution, atmospheric deposition, and sewage. Groundwater is mainly recharged from atmospheric precipitation, and surface water is closely hydraulically connected to groundwater. Nitrogen and oxygen isotope composition and water chemistry indicative of nitrification dominate the nitrogen cycle in the study area. The oxidation of pyrite and bacterial sulfate reduction (SRB) had no significant impact on the stable isotopes of groundwater. The results of this study demonstrate the inputs of different sources to nitrate and sulfate in karst mines and associated transformation processes. The results of this study can assist in the conservation of groundwater quality in mining areas and can act as a reference for future related studies., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Accumulation of pathological tau is a hallmark of Alzheimer's disease (AD), which correlates more closely with cognitive impairment than does the amyloid-β (Aβ) burden. Autophagy is a powerful process for the clearance of toxic proteins including aberrant tau. However, compromised autophagy is demonstrated in neurodegeneration including AD, and current autophagy inducers remain enormously challenging due to inability of restoring autophagy pathway and lack of targeting specificity. Here, pathogenic tau-specific autophagy based on customized nanochaperone is developed for AD treatment. In this strategy, the nanochaperone can selectively bind to pathogenic tau and maintain tau homeostasis, thereby ensuring microtubule stability which is important for autophagy pathway. Meanwhile, the bound pathogenic tau can be sequestered in autophagosomes by in situ autophagy activation of nanochaperone. Consequently, autophagosomes wrapping with pathogenic tau are able to be trafficked along the stabilized microtubule to achieve successful fusion with lysosomes, resulting in the enhancement of autophagic flux and pathologic tau clearance. After treatment with this nanochaperone-mediated autophagy strategy, the tau burden, neuron damages, and cognitive deficits of AD mice are significantly alleviated in the brain. Therefore, this work represents a promising candidate for AD-targeted therapy and provides new insights into future design of anti-neurodegeneration drugs., (© 2024 Wiley‐VCH GmbH.)

Background: Lung adenocarcinoma (LUAD), a predominant subtype of non-small cell lung cancers, continues to challenge treatment outcomes due to its heterogeneity and complex tumor microenvironment (TME). Dysregulation in nucleotide metabolism has been identified as a significant factor in tumorigenesis, suggesting its potential as a therapeutic target., Methods: This study analyzed LUAD samples from The Cancer Genome Atlas (TCGA) using Non-negative Matrix Factorization (NMF) clustering, Weighted Correlation Network Analysis (WGCNA), and various machine learning techniques. We investigated the role of nucleotide metabolism in relation to clinical features and immune microenvironment through large-scale data analysis and single-cell sequencing. Using in vivo and in vitro experiments such as RT-qPCR, Western Blot, immunohistochemistry, and subcutaneous tumor formation in mice, we further validated the functions of key nucleotide metabolism genes in cell lines and animals., Results: Nucleotide metabolism genes classified LUAD patients into two distinct subtypes with significant prognostic differences. The 'C1' subtype associated with active nucleotide metabolism pathways showed poorer prognosis and a more aggressive tumor phenotype. Furthermore, a nucleotide metabolism-related score (NMRS) calculated from the expression of 28 key genes effectively differentiated between patient outcomes and predicted associations with oncogenic pathways and immune responses. By integrating various immune infiltration algorithms, we delineated the associations between nucleotide metabolism signature genes and the tumor microenvironment, and characterized their distribution differences at the cellular level by analyzing single-cell sequencing dataset related to immunochemotherapy. Finally, we demonstrated the differential expression of the key nucleotide metabolism gene AUNIP acts as an oncogene to promote LUAD cell proliferation and is associated with tumor immune infiltration., Conclusion: The study underscores the pivotal role of nucleotide metabolism in LUAD progression and prognosis, highlighting the NMRS as a valuable biomarker for clinical outcomes and therapeutic responses. Specifically, AUNIP functions as a critical oncogene, offering a promising target for novel treatment strategies in LUAD., 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, Wang, Zeng, Chen and Wang.)

Endothelial-to-mesenchymal transition (EndMT) is a key driver of atherosclerosis. Aerobic glycolysis is increased in the endothelium of atheroprone areas, accompanied by elevated lactate levels. Histone lactylation, mediated by lactate, can regulate gene expression and participate in disease regulation. However, whether histone lactylation is involved in atherosclerosis remains unknown. Here, we report that lipid peroxidation could lead to EndMT-induced atherosclerosis by increasing lactate-dependent histone H3 lysine 18 lactylation (H3K18la) in vitro and in vivo , as well as in atherosclerotic patients' arteries. Mechanistically, the histone chaperone ASF1A was first identified as a cofactor of P300, which precisely regulated the enrichment of H3K18la at the promoter of SNAI1 , thereby activating SNAI1 transcription and promoting EndMT. We found that deletion of ASF1A inhibited EndMT and improved endothelial dysfunction. Functional analysis based on Apoe KO Asf1a ECKO mice in the atherosclerosis model confirmed the involvement of H3K18la in atherosclerosis and found that endothelium-specific ASF1A deficiency inhibited EndMT and alleviated atherosclerosis development. Inhibition of glycolysis by pharmacologic inhibition and advanced PROTAC attenuated H3K18la, SNAI1 transcription, and EndMT-induced atherosclerosis. This study illustrates precise crosstalk between metabolism and epigenetics via H3K18la by the P300/ASF1A molecular complex during EndMT-induced atherogenesis, which provides emerging therapies for atherosclerosis., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors.)

The exploration of the next-generation small diameter vascular grafts (SDVGs) will never stop until they possess high biocompatibility and patency comparable to autologous native blood vessels. Integrating biocompatible electrospinning (ES) matrices with highly bioactive stem cells (SCs) provides a rational and promising solution. ES is a simple, fast, flexible and universal technology to prepare extracellular matrix-like fibrous scaffolds in large scale, while SCs are valuable, multifunctional and favorable seed cells with special characteristics for the emerging field of cell therapy and regenerative medicine. Both ES matrices and SCs are advanced resources with medical application prospects, and the combination may share their advantages to drive the overcoming of the long-lasting hurdles in SDVG field. In this review, the advances on SDVGs based on ES matrices and SCs (including pluripotent SCs, multipotent SCs, and unipotent SCs) are sorted out, and current challenges and future prospects are discussed., 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 Wang, Chen, Hu, He, Shen, Yang, Wang, Weng and He.)

Cytokines are powerful in cancer immunotherapy, however, their therapeutic potential is limited by the severe systemic toxicity. Here a potent strategy to reduce the toxicity of systemic cytokine therapy by delivering its denatured form using a finely designed nanochaperone, is described. It is demonstrated that even if the denatured protein cargos are occasionally released under normal physiological conditions they are still misfolded, while can effectively refold into native states and release to function in tumor microenvironment. Consequently, the systemic toxicity of cytokines is nearly completely overcome. Moreover, an immunogenic cell death (ICD)-inducing chemotherapeutic is further loaded and delivered to tumor using this nanochaperone to trigger the release of tumor-associated antigens (TAAs) that are subsequently captured in situ by nanochaperone and then reflows into lymph nodes (LNs) to promote antigen cross-presentation. This optimized personalized nanochaperone-vaccine demonstrates unprecedented suppressive effects against large, advanced tumors, and in combination with immune checkpoint blockade (ICB) therapy results in a significant abscopal effect and inhibition of postoperative tumor recurrence and metastasis. Hence, this approach provides a simple and universal delivery strategy to reduce the systemic toxicities of cytokines, as well as provides a robust personalized cancer vaccination platform, which may find wide applications in cancer immunotherapy., (© 2024 Wiley‐VCH GmbH.)

Citrus fruits have abundant flavonoid glycosides (FGs), an important class of natural functional and flavor components. However, there have been few reports about the modification of UDP-glycosyltransferases (UGTs) on flavonoids in citrus. Notably, in flavonoid biosynthesis, 7- O -glucosylation is the initial and essential step of glycosylation prior to the synthesis of flavanone disaccharides, the most abundant and iconic FGs in citrus fruits. Here, based on the accumulation of FGs observed at the very early fruit development stage of two pummelo varieties, we screened six novel flavonoid 7- O -glucosyltransferase genes ( 7GlcTs ) via transcriptomic analysis and then characterized them in vitro . The results revealed that four Cg7GlcTs possess wide catalytic activities towards various flavonoid substrates, with CgUGT89AK1 exhibiting the highest catalytic efficiency. Transient overexpression of CgUGT90A31 and CgUGT89AK1 led to increases in FG synthesis in pummelo leaves. Interestingly, these two genes had conserved sequences and consistent functions across different germplasms. Moreover, CitUGT89AK1 was found to play a role in the response of citrus to Huanglongbing infection by promoting FG production. The findings improve our understanding of flavonoid 7- O -glucosylation by identifying the key genes, and may help improve the benefits of flavonoid biosynthesis for plants and humans in the future., Competing Interests: The authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Polymethoxyflavones (PMFs) are a class of abundant specialized metabolites with remarkable anticancer properties in citrus. Multiple methoxy groups in PMFs are derived from methylation modification catalyzed by a series of hydroxylases and O -methyltransferases (OMTs). However, the specific OMTs that catalyze the systematic O -methylation of hydroxyflavones remain largely unknown. Here, we report that PMFs are highly accumulated in wild mandarins and mandarin-derived accessions, while undetectable in early-diverging citrus species and related species. Our results demonstrated that three homologous genes, CreOMT3 , CreOMT4 , and CreOMT5 , are crucial for PMF biosynthesis in citrus, and their encoded methyltransferases exhibit multisite O -methylation activities for hydroxyflavones, producing seven PMFs in vitro and in vivo. Comparative genomic and syntenic analyses indicated that the tandem CreOMT3 , CreOMT4 , and CreOMT5 may be duplicated from CreOMT6 and contributes to the genetic basis of PMF biosynthesis in the mandarin group through neofunctionalization. We also demonstrated that N17 in CreOMT4 is an essential amino acid residue for C3-, C5-, C6-, and C3'- O -methylation activity and provided a rationale for the functional deficiency of OMT6 to produce PMFs in early-diverging citrus and some domesticated citrus species. A 1,041-bp deletion in the CreOMT4 promoter, which is found in most modern cultivated mandarins, has reduced the PMF content relative to that in wild and early-admixture mandarins. This study provides a framework for reconstructing PMF biosynthetic pathways, which may facilitate the breeding of citrus fruits with enhanced health benefits., Competing Interests: Competing interests statement:The authors declare no competing interest.

Individuals with a history of childhood abuse (CA, including neglect and abuse by caregivers before the age of 18 years) have more severe substance dependence problems than those without a history of childhood abuse. However, whether a history of CA exacerbates craving and the mechanism of this effect remain largely unknown. The aim of this study was to explore the role of alexithymia in the effects of CA on craving in a large sample of methamphetamine-dependent individuals based on latent vulnerability theory. A total of 324 methamphetamine-dependent individuals who met DSM-5 criteria for substance use disorder were recruited. CA, alexithymia, and craving data were collected from the Childhood Trauma Questionnaire, the Toronto Alexithymia Scale-20, and the Obsessive Compulsive Drug Use Scale, respectively. t tests and ANCOVA were conducted to compare variables between the CA and non-CA groups, while partial correlation and mediation analyses were conducted to examine the potential mediating role of alexithymia in the relationship between CA and craving. Abused methamphetamine-dependent individuals reported higher levels of craving and higher levels of alexithymia than those of non-abused methamphetamine-dependent individuals. Alexithymia partially mediated the link between CA and craving, especially the effect of CA on craving frequency was fully mediated by alexithymia. Our findings reveal that a history of childhood abuse has a lasting effect on craving in stimulant-dependent individuals, and alexithymia contributes to some extent to the severity of substance abuse problems in abused methamphetamine-dependent individuals., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: With long-term research on the reproductive ability of Qianbei Ma goat, we found that the puberty of the male goats comes at the age of 3 months and reaches sexual maturity at 4 months,the male goats are identified as physically mature at 9 months and able to mate. Compared with other kinds of breeds of goats, Qianbei Ma goat is featured with more faster growth and earlier sexual maturity.Therefore, in order to explore the laws of growth of Qianbei Ma goat before sexual maturity(3-month-old)and after sexual maturity (9-month-old). The testicular tissue was collected to explore their changes in morphology through HE staining, the serum was collected to detect the hormone content, and the mRNA expression profile of the testis was analyzed by transcriptomics. In this way, the effect of testicular development on the reproduction of Qianbei ma goats was further analyzed., Results: The results showed that the area and diameter of spermatogenic tubules were larger at 9 months than 3 months, and the number of spermatocytes, interstitial cells, spermatogonia and secondary spermatocytes in the lumen of the tubules showed a similar trend. The appearance of spermatozoa at age 3 months indicated that puberty had begun in Qianbei Ma goats. The Elasa test for testosterone, luteinizing hormone, follicle stimulating hormone and anti-Müllerian hormone showed that the levels of these hormones in the serum at age 9 months were all highly significantly different than those at age 3 months (P < 0.01). There were 490 differentially expressed genes (DEGs) between the (|log2(fold change)| > 1 and p value < 0.05) 3-month-old and 9-month-old groups, of which 233 genes were upregulated and 257 genes were downregulated (3 months of age was used as the control group and 9 months of age was used as the experimental group). According to the GO and KEGG enrichment analyses of DEGs, PRSS58, ECM1, WFDC8 and LHCGR are involved in testicular development and androgen secretion, which contribute to the sexual maturation of Qianbei Ma goats., Conclusions: Potential biomarker genes and relevant pathways involved in the regulation of testicular development and spermatogenesis in Qianbei Ma goats were identified, providing a theoretical basis and data support for later studies on the influence of testicular development and spermatogenesis before and after sexual maturity in Qianbei Ma goats., (© 2024. The Author(s).)

Volatile terpenoids accumulate in citrus and play important roles in plant defense against various stressors. However, the broad-spectrum response of terpenoid biosynthesis to ubiquitous stressors in citrus has not been comparatively investigated. In this study, volatile terpenoids were profiled under six stressors: high temperature, citrus miner, citrus red mite, citrus canker, Alternaria brown spot, and huanglongbing (HLB). Significant content changes in 15 terpenoids, including β-ocimene, were observed in more than four of the six stressors, implying their possibly universal stress-response effects. Notably, the emission of terpenoids, including β-caryophyllene, β-ocimene, and nerolidol glucoside, was significantly increased by HLB in HLB-tolerant "Shatian" pomelo leaves. The upregulation of CgTPS1 and CgTPS2 and their characterization in vivo identified them as mono- or sesquiterpenoid biosynthetic genes. This study provides a foundation for determining stress resistance mechanisms in citrus and biopesticide designations for future industrial applications.

Background: Senescence is a series of degenerative changes in the structure and physiological function of an organism. Whether JPX (just proximal to XIST)-a newly identified age-related noncoding RNA by us-is associated with atherosclerosis is still unknown. Our study was to investigate the role of JPX and provide insights into potential therapies targeting atherosclerosis., Methods: We analyzed clinical data from multiple tissues including meniscus tissue, leukemia cells, and peripheral blood monocytes to identify age-related noncoding RNAs in senescent vascular smooth muscle cells (VSMCs). The molecular mechanism of JPX was investigated by capture hybridization analysis of RNA targets and chromatin immunoprecipitation. IGVTools and real-time quantitative polymerase chain reaction were used to evaluate the JPX expression during phenotype regulation in age-related disease models. The therapeutic potential of JPX was evaluated after establishing an atherosclerosis model in smooth muscle-specific Jpx knockout mice., Results: JPX expression was upregulated in activated ras allele (H- ras V12)-induced senescent VSMCs and atherosclerotic arteries. JPX knockdown substantially reduced the elevation of senescence-associated secretory phenotype (SASP) genes in senescent VSMCs. Cytoplasmic DNA leaked from mitochondria via mitochondrial permeability transition pore formed by VDAC1 (voltage-dependent anion channel 1) oligomer activates the STING (stimulator of interferon gene) pathway. JPX could act as an enhancer for the SASP genes and functions as a scaffold molecule through interacting with phosphorylated p65/RelA and BRD4 (bromodomain-containing protein 4) in chromatin remodeling complex, promoting the transcription of SASP genes via epigenetic regulation. Smooth muscle knockout of Jpx in Apoe KO mice resulted in a decrease in plaque area, a reduction in SASP gene expression, and a decrease in senescence compared with controls., Conclusions: As an enhancer RNA, JPX can integrate p65 and BRD4 to form a chromatin remodeling complex, activating SASP gene transcription and promoting cellular senescence. These findings suggest that JPX is a potential therapeutic target for the treatment of age-related atherosclerosis., Competing Interests: Disclosures None.

Background: Excessive free radicals are implicated in the pathophysiology of tardive dyskinesia (TD), and Ginkgo biloba extract (EGb761) scavenges free radicals, thereby enhancing antioxidant enzymes such as mitochondrial manganese superoxide dismutase (MnSOD). This study examined whether EGb761 treatment would improve TD symptoms and increase MnSOD activity, particularly in TD patients with specific MnSOD Val-9Ala genotype., Methods: An EGb761 (240 mg/day) 12-week double-blind clinical trial with 157 TD patients was randomized. The severity of TD was measured by the Abnormal Involuntary Movement Scale (AIMS) and plasma MnSOD activity was assayed before and after 12 weeks of treatment. Further, in an expanded sample, we compared MnSOD activity in 159 TD, 227 non-TD and 280 healthy controls, as well as the allele frequencies and genotypes for the MnSOD Ala-9Val polymorphism in 352 TD, 486 non-TD and 1150 healthy controls., Results: EGb761 significantly reduced TD symptoms and increased MnSOD activity in TD patients compared to placebo (both p < 0.01). Moreover, we found an interaction between genotype and treatment response (p < 0.001). Furthermore, in the EGb761 group, patients carrying the Ala allele displayed a significantly lower AIMS total score than patients with the Val/Val genotype. In addition, MnSOD activity was significantly lower at baseline in TD patients compared with healthy controls or non-TD patients., Conclusion: EGb761 treatment enhanced low MnSOD activity in TD patients and produced greater improvement in TD symptoms in patients with the Ala allele of the MnSOD Ala-9Val polymorphism.

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF- κ B)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF- κ B via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF- κ B and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction., Competing Interests: The authors declare no conflicts of interest., (© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Cathepsin S (CTSS) is a member of the cysteine protease family closely related to reproductive regulation in goats. However, its effect on litter size in goats remains unclear. In this study, the relationship between CTSS gene polymorphisms and litter size was revealed by analyzing the DNA sequence and mRNA expression of CTSS in the gonadal axis of Qianbei Ma goats. In addition, bioinformatics methods were used to evaluate the effect of non-synonymous mutations on CTSS protein structure and function. CTSS was expressed in all parts of the gonadal axis of Qianbei Ma goats, with the highest expression in the uterus in the multi-lamb group and in the fallopian tube in the single-lamb group. The sequencing results showed that four SNPs in CTSS , including g.7413C → T, g.8816A → T, g.9191 T → G and g.10193G → A, were significantly correlated with litter size ( p  < 0.05). All four analyzed mutation sites were in strong linkage disequilibrium ( r 2  > 0.33, D' > 0.70). Additionally, the haplotype Hap1/2 had a significantly higher frequency than the other haplotypes ( p  < 0.05). g.7413C → T and g.8816A → T were non-synonymous mutations. The g.7413C → T mutation resulted in the substitution of serine 161 of the CTSS protein with phenylalanine (p.S161F), and the g.8816A → T mutation resulted in the substitution of aspartate 219 with tyrosine (p.N219Y). p.S161F was highly conserved across 13 species and that p.N219Y was relatively conserved in cloven-hoofed species. Mutations at two sites changed the local conformation of the CTSS protein, reduced its stability, and affected its function and goat breed evolution. These findings confirm that CTSS affects the lambing traits of goats and provide a theoretical basis for the regulatory mechanism of CTSS in affecting litter size., 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 © 2023 Zhang, Chen, Ruan, Guo, Chen, Tang, Ji and Fu.)

Background: The ThermoCool STSF catheter is used for ablation of ischemic ventricular tachycardia (VT) in routine clinical practice, although outcomes have not been studied and the catheter does not have Food and Drug Administration (FDA) approval for this indication. We used real-world health system data to evaluate its safety and effectiveness for this indication., Methods: Among patients undergoing ischemic VT ablation with the ThermoCool STSF catheter pooled across two health systems (Mercy Health and Mayo Clinic), the primary safety composite outcome of death, thromboembolic events, and procedural complications within 7 days was compared to a performance goal of 15%, which is twice the expected proportion of the primary composite safety outcome based on prior studies. The exploratory effectiveness outcome of rehospitalization for VT or heart failure or repeat VT ablation at up to 1 year was averaged across health systems among patients treated with the ThermoCool STSF vs. ST catheters., Results: Seventy total patients received ablation for ischemic VT using the ThermoCool STSF catheter. The primary safety composite outcome occurred in 3/70 (4.3%; 90% CI, 1.2-10.7%) patients, meeting the pre-specified performance goal, p = 0.0045. At 1 year, the effectiveness outcome risk difference (STSF-ST) at Mercy was - 0.4% (90% CI: - 25.2%, 24.3%) and at Mayo Clinic was 12.6% (90% CI: - 13.0%, 38.4%); the average risk difference across both institutions was 5.8% (90% CI: - 12.0, 23.7)., Conclusions: The ThermoCool STSF catheter was safe and appeared effective for ischemic VT ablation, supporting continued use of the catheter and informing possible FDA label expansion. Health system data hold promise for real-world safety and effectiveness evaluation of cardiovascular devices., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Achieving and controlling the desired movements of active machines is generally accomplished through precise control of artificial muscles in a distributed and serialized manner, which is a significant challenge. The emerging motion control strategy based on self-oscillation in active machines has unique advantages, including directly harvesting energy from constant ambient light, and it has no need for complex controllers. Inspired by the roller, we have innovatively developed a self-rolling roller that consists of a roller and a liquid crystal elastomer (LCE) fiber. By utilizing a well-established dynamic LCE model and subjecting it to constant illumination, we have investigated the dynamic behavior of the self-rolling roller. Based on numerical calculations, it has been discovered that the roller, when subjected to steady illumination, exhibits two distinct motion regimes: the static regime and the self-rolling regime. The self-rolling regime, characterized by continuous periodic rolling, is sustained by the interaction between light energy and damping dissipation. The continuous periodic rolling observed in the self-rolling regime is maintained through the interplay between the dissipation of damping and the absorption of light energy. In the static state, the rolling angle of the roller begins to decrease rapidly and then converges to zero. Detailed investigations have been conducted to determine the critical conditions required to initiate self-rolling, as well as the essential system parameters that influence its frequency and amplitude. The proposed self-rolling roller has superiorities in its simple structure, light weight, alternative to manual labor, and speediness. This advancement is expected to inspire greater design diversity in micromachines, soft robotics, energy harvesters, and similar areas.

Analysis of cis -diol compounds is essential, because they play important roles in cosmetics, food, pharmaceuticals, and living organisms. Herein, we describe the development of a matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) method to analyse cis -diol compounds. In this method, a 6-borono-1-methylquinoline-1-ium (BMQI) reactive matrix was designed for in situ derivatisation of cis -diol compounds based on the boronate affinity interaction between boronic acid and cis -diol groups. Compared to traditional commercial matrices and other boronic acid reagents, BMQI can significantly accelerate the desorption/ionisation process, improve reproducibility, exhibit free background interference, and enhance signal intensity in the analysis of various cis -diol compounds even for amounts as low as 1 nmol. The BMQI-assisted laser desorption/ionisation mass spectrometry (LDI-MS) was successfully applied to the rapid screening and identification of sugar alcohols in different sugar-free foods. This work provides an alternative method to the LDI-MS analysis of cis -diol-containing molecules, and the method can be extended to other food samples and biofluids.

To explore the influence mechanism of different concentrations of salinity on the electro-enhanced aniline biodegradation system, a control group and experimental groups (0%-NaCl, 0.5%-NaCl, 1.5%-NaCl, 2.5%-NaCl, 3.5%-NaCl) were established. The experimental results showed that the electric field strengthened the denitrification performance, while salinity had little effect on the degradation efficiency of aniline and chemical oxygen demand (COD). The removal rate of TN reached 79.6% and 74.9% in 0.5%-NaCl and 1.5%-NaCl, respectively, which were superior than 0%-NaCl. As salinity increased, the nitrogen removal effect was negatively affected. Microbial diversity analysis indicated that the microbial community structure was uniform in the control group, 0%-NaCl, and 0.5%-NaCl, with the dominant genus OLB8 ensuring the nitrogen removal performance. In contrast, in the 2.5%-NaCl and 3.5%-NaCl experimental groups, the organic degrading bacteria were still active, while nitrifiers and denitrifiers were severely damaged. In conclusion, this study suggested that low concentrations of salinity can improve the decontamination performance of the electro-enhanced aniline biodegradation system, while high concentrations of salinity could lead to the collapse of the decontamination mechanism., 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 © 2023 Elsevier Ltd. All rights reserved.)

Chicken melanoma differentiation-associated gene 5 (MDA5) is a member of the RLRs family that recognizes the viral RNAs invading cells and activates downstream interferon regulatory pathways, thereby inhibiting viral replication. The caspase activation and recruitment domain (CARD) is the most important region in MDA5 protein. However, the antiviral and immune enhancement of MDA5 with the CARD region remains unclear. In this study, two truncated MDA5 genes with different CARD regions, namely MDA5-1 with CARD1 plus partial CARD2 domain and MDA5-2 with CARD1 plus complete CARD2 domain, were cloned via reverse transcription PCR and ligated into plasmid Flag-N vector to be Flag-MDA5-1 and Flag-MDA5-2 plasmids. DF-1 cells were transfected with two plasmids for 24 h and then inoculated with H9N2 virus (0.1 MOI) for 6 h to detect the levels of IFN-β, PKR, MAVS, and viral HA, NA, and NS proteins expression. The results showed that MDA5-1 and MDA5-2 increased the expression of IFN-β and PKR, activated the downstream molecule MAVS production, and inhibited the expression of HA, NA, and NS proteins. The knockdown of MDA5 genes confirmed that MDA5-2 had a stronger antiviral effect than that of MDA5-1. Furthermore, the recombinant proteins MDA5-1 and MDA5-2 were combined with H9N2 inactivated vaccine to immunize SPF chickens subcutaneously injected in the neck three times. The immune response of the immunized chicken was investigated. It was observed that the antibody titers and expressions of immune-related molecules from the chicken immunized with MDA5-1 and MDA5-2 group were increased, in which the inducing function of MDA5-2 groups was the highest among all immunization groups. These results suggested that the truncated MDA5 recombinant proteins with complete CARD2 region could play vital roles in antiviral and immune enhancement. This study provides important material for the further study of the immunoregulatory function and clinical applications of MDA5 protein., Competing Interests: The authors declare no conflict of interest.

Therapeutic cancer vaccines, which are designed to amplify tumor-specific T cell responses, have been envisioned as one of the most powerful tools for effective cancer immunotherapy. However, increasing the potency, quality and durability of the vaccine response remains a big challenge. In recent years, materials-based delivery systems focusing on the co-delivery of antigens and adjuvants to enhance cancer vaccination therapy have attracted increasing interest. Among various materials, polymeric nanoparticles (NPs) with different physicochemical properties which can incorporate multiple immunological cues are of great interest. In this review, the recent progress in the design and construction of both ex vivo subunit and in situ cancer vaccines using polymeric NPs is summarized. Especially, we will focus on how these NPs improve the adjuvanticity of vaccines. The design principles of polymeric NPs for ex vivo subunit cancer vaccines and in situ cancer vaccination are also discussed. Finally, we want to briefly discuss molecular chaperones in cancer immunity and the applications of our unique self-assembly mixed shell polymeric micelle-based nanochaperones for cancer vaccines.

The objective of this study is to describe application of the Observational Medical Outcomes Partnership (OMOP) common data model (CDM) to support medical device real-world evaluation in a National Evaluation System for health Technology Coordinating Center (NESTcc) Test-Case involving 2 healthcare systems, Mercy Health and Mayo Clinic. CDM implementation was coordinated across 2 healthcare systems with multiple hospitals to aggregate both medical device data from supply chain databases and patient outcomes and covariates from electronic health record data. Several data quality assurance (QA) analyses were implemented on the OMOP CDM to validate the data extraction, transformation, and load (ETL) process. OMOP CDM-based data of relevant patient encounters were successfully established to support studies for FDA regulatory submissions. QA analyses verified that the data transformation was robust between data sources and OMOP CDM. Our efforts provided useful insights in real-world data integration using OMOP CDM for medical device evaluation coordinated across multiple healthcare systems., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

The bursa of Fabricius, the acknowledged humoral immune organ unique to birds, plays a vital role in B cell development. Bursopentin (BP5) derived from the bursa is reported to induce the development and formation of B cells. However, the mechanism of BP5 on B cell differentiation is still unclear. In this paper, total B lymphocytes from mice immunized with H9N2 subtype AIV vaccine were stimulated with BP5. The results show that BP5 at the experimental dosages promoted B cell differentiation, including the total B cells, activated B cells, differentiated B cells, mature B cells and plasma cells. Then, the in vivo immune experiment proved that the percentages of activated and differentiated B cells from mice immunized with AIV vaccine and 0.25 mg/mL BP5 were increased. To investigate the molecular mechanism of BP5 on B cell differentiation, the gene expression profiles of B cells purified from the spleen cells of mice immunized with AIV vaccine and BP5 were detected following RNA sequencing technology. The results show that BP5 at 0.05 and 0.25 mg/mL induced the enrichment of various biological functions, and stimulated five common significant enrichment pathways in B cells from the immunized mice. Additionally, 120 and 59 differentially expressed genes (DEG) represented transcriptional factors in B cells following 0.05 and 0.25 mg/mL BP5 immunization, respectively. In summary, these results suggest that BP5 regulates various gene expression involved in regulation of B cell development, which provides the knowledge required for additional studies on B cell differentiation in response to bursal-derived peptides and also provides an important experimental basis for improving vaccine immunity., (© 2022. The Author(s).)

Previous studies have shown that dependent individuals (DIs) have higher rates of childhood maltreatment and poorer cognitive performance compared with healthy controls. However, little attention has been paid to the cognitive dysfunction of DIs with childhood maltreatment. The purpose of this study was to explore the cognitive deficits of maltreated methamphetamine-dependent individuals (METH-DIs) using a cross-sectional and case-control design. In addition, we aimed to examine the prevalence of childhood maltreatment and the demographic and clinical characteristics of Chinese male METH-DIs. 330 METH-DIs and 143 healthy controls were recruited and completed a detailed questionnaire on demographic and drug-related variables. Childhood abuse data were collected from the Childhood Trauma Questionnaire-Short Form (CTQ-SF). Cognitive function was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The Beck Depression Inventory, Beck Anxiety Inventory, and Visual Analogue Scale (VAS) were used to assess the clinical state of the METH-DIs. 166 of 326 (50.9%) METH-DIs had experienced at least one type of childhood maltreatment. Maltreated METH-DIs were more likely to have a lower level of education (t 324  = 5.81, p < 0.001), a higher level of depression(t 324  = －2.68, p < 0.01), and a younger onset age of drug use (t 324  = 3.58, p < 0.01) than METH-DIs who had no experience of childhood maltreatment. Maltreated METH-DIs also performed worse on the RBANS attention score than METH-DIs who did not experience maltreatment (F 1,324  = 15.41, p < 0.001, partial η 2  = 0.05). Our findings revealed that some demographic and clinical variables were associated with maltreatment among METH-DIs. Moreover, attention dysfunction was found in maltreated METH-DIs, which conforms to the theory of latent vulnerability., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A synthetic protocol based on Cp*Co III -catalyzed C-H amidation/annulation of 2-aryl-1 H -imidazoles with 1,4,2-dioxazol-5-ones was developed to give imidazo[1,2- c ]quinazoline derivatives with broad substrate scope in moderate to good yields. The method has good prospects of application in the synthesis of imidazo[1,2- c ]quinazoline drugs.

Background: Prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection with high mortality has attached physicians' attention. High visceral adipose tissue (VAT) and high subcutaneous adipose tissue (SAT) were confirmed by previous studies that were closely related to increased pneumonia severity, more complications, and higher mortality in COVID-19. Thus, we speculate that CT-quantified body composition may also be connected to all-cause mortality and bacterial clearance in patients with CRKP bloodstream infection (BSI)., Methods: We investigated the associations of CT-quantified body composition with the mortality of CRKP bloodstream infectious patients. All CT images were obtained at the level of the L3/4 spinal level. The prognostic value of the body composition was analyzed using the Cox regression model, and precise clinical nomograms were established., Results: 72 eligible patients both suffered from CRKP bloodstream infection and performed abdominopelvic CT were included. Factors associated with 30-day all-in hospital mortality included total adipose tissue (TAT) [adjusted hazard ratio (HR) = 1.028, 95% confidence interval (CI), 1.003-1.053; P = 0.025], age [HR = 1.030, 95% CI, 1.000-1.061; P = 0.047] and SOFA scores [HR = 1.138, 95% CI 1.049-1.263; P = 0.002]. Compared with low-VAT, patients with high-VAT show a strikingly poor prognosis in both 30-day all-cause mortality (P = 0.0108, Fig. 2A) and 30-day CRKP BSI mortality (P = 0.0049, Fig. 2C). The results of TAT were similar to VAT., Conclusions: Our study suggested that CT-derived body composition could be a credible and effective alternative to assess the prognosis of patients with BSI owing to CRKP. CT-quantified TAT, age, and SOFA scores were independently associated with 30-day all-cause mortality in these severe infectious patients, while skeletal muscle did not have obvious statistical significance., (© 2022. The Author(s).)

Enhancement of the transesterification efficiency of triglyceride has come under heated study in biodiesel-making industry. In this research, the NiMo/La-Al 2 O 3 nanopowders have been prepared for producing biodiesel efficiently. The screening test showed that the NiMo/La-Al 2 O 3 catalyst has the best catalytic activity for triglyceride transesterification. Besides, the process parameters including reaction temperature, time, oil-to-alcohol ratio and catalyst loading etc., also have been investigated for optimization of the transesterification process. The results showed that with 5 wt% of catalyst loading, and oil to methanol molar ratio of 1:9, the conversion yield of triglyceride could be up to 95.2% within 120 min at 160°C. The NiMo/La-Al 2 O 3 catalyst has the outstanding recycle property, which proved that the prepared NiMo/La-Al 2 O 3 powders can be suitable for biodiesels' production.

Background: Carotenoids and flavonoids are important secondary metabolites in plants, which exert multiple bioactivities and benefits to human health. Although the genes that encode carotenogenesis and flavonoid biosynthetic enzymes are well characterized, the transcriptional regulatory mechanisms that are related to the pathway genes remain to be investigated. In this study, 'Cara cara' navel orange (CNO) fruit at four development stages were used to identify the key genes and TFs for carotenoids and flavonoids accumulation., Results: In this study, CNO was used to investigate the profiles of carotenoids and flavonoids by a combination of metabolomic and transcriptomic analyses. The important stage for the accumulation of the major carotenoid, lycopene was found to be at 120 days after florescence (DAF). The transcripts of five carotenogenesis genes were highly correlated with lycopene contents, and 16, 40, 48, 24 and 18 transcription factors (TFs) were predicted to potentially bind 1-deoxy-D-xylulose-5-phosphate synthase (DXS1), deoxyxylulose 5-phosphate reductoisomerase (DXR), geranylgeranyl diphosphate synthase (GGPPS2), phytoene synthase (PSY1) and lycopene β-cyclase (LCYB) promoters, respectively. Narirutin was the most abundant flavonoid in the flesh at the early stages, 60 DAF was the most important stage for the accumulation of flavonoids, and 17, 22, 14, 25, 24 and 16 TFs could potentially bind phenylalanine ammonia-lyase (PAL-1 and PAL-4), 4-Coumarate-CoA ligase (4CL-2 and 4CL-5), chalcone synthase (CHS-1) and chalcone isomerase (CHI) promoters, respectively. Furthermore, both sets of 15 candidate TFs might regulate at least three key genes and contribute to carotenoids/flavonoids accumulation in CNO fruit. Finally, a hierarchical model for the regulatory network among the pathway genes and TFs was proposed., Conclusions: Collectively, our results suggest that DXS1, DXR, GGPPS2, PSY1 and LCYB genes were the most important genes for carotenoids accumulation, while PAL-1, PAL-4, 4CL-2, 4CL-5, CHS-1 and CHI for flavonoids biosynthesis. A total of 24 TFs were postulated as co-regulators in both pathways directly, which might play important roles in carotenoids and flavonoids accumulation in CNO fruit.

Cellular senescence is closely associated with age-related diseases. Ovarian aging, a special type of organ senescence, is the pathophysiological foundation of the diseases of the reproductive system. It is characterized by the loss of integrity of the surface epithelium and a gradual decrease in the number of human ovarian surface epithelial cells (HOSEpiCs). To contribute to the research on delaying ovarian aging, we aimed to investigate the novel epigenetic mechanism of melatonin in protecting HOSEpiCs. We discovered that melatonin has antagonistic effects against the oncogene-induced senescence (OIS) of HOSEpiCs. Mechanistically, the oncogene Ras decreased the expression of YTHDF2, which is the reader of RNA-m 6 A, by stimulating the generation of reactive oxygen species (ROS). Moreover, we found that the suppression of YTHDF2 increased the expression of MAP2K4 and MAP4K4 by enhancing the stability of the transcription of their mRNAs, thereby upregulating the expression of the senescence-associated secretory phenotype (SASP) through the activation of the MAP2K4 and MAP4K4-dependent nuclear factor-κB (NF-κB) signaling pathways. We further determined that melatonin has antagonistic effects against the OIS of HOSEpiCs by inhibiting the ROS-YTHDF2-MAPK-NF-κB pathway. These findings provide key insights into the potential avenues for preventing and treating ovarian aging., (© 2020 Chongqing Medical University. Production and hosting by Elsevier B.V.)

In this Letter, triazoles as carbene reagents were used for sulfonamide-directed C-H insertion carbenoid functionalization to construct benzylpyridine sulfonamide dual-pharmacophore compounds. This method is simple and efficient and can be used for the late-stage modification of sulfonamide drugs.

A rhodium-catalyzed directed C(sp3)-H amidation to afford 1,2-amino alcohol oxime derivatives has been developed with good yields and a broad substrate scope. In previous methods for this type of reaction, 1-arylethan-1-ol oxime analogues were challenging substrates owing to strong competition from C(sp2)-H bond activation. This Rh-catalyzed C-H activation method overcomes the limitation of competitive C(sp2)-H bond activation.

Nuclear magnetic resonance (NMR) is a powerful tool to interrogate protein structure and dynamics residue by residue. However, the prerequisite chemical-shift assignment remains a bottleneck for large proteins due to the fast relaxation and the frequency degeneracy of the (13) Cα nuclei. Herein, we present a covariance NMR strategy to assign the backbone chemical shifts by using only HN(CO)CA and HNCA spectra that has a high sensitivity even for large proteins. By using the peak linear correlation coefficient (LCC), which is a sensitive probe even for tiny chemical-shift displacements, we correctly identify the fidelity of approximately 92 % cross-peaks in the covariance spectrum, which is thus a significant improvement on the approach developed by Snyder and Brüschweiler (66 %) and the use of spectral derivatives (50 %). Thus, we calculate the 4D covariance spectrum from HN(CO)CA and HNCA experiments, in which cross-peaks with LCCs above a universal threshold are considered as true correlations. This 4D covariance spectrum enables the sequential assignment of a 42 kDa maltose binding protein (MBP), in which about 95 % residues are successfully assigned with a high accuracy of 98 %. Our LCC approach, therefore, paves the way for a residue-by-residue study of the backbone structure and dynamics of large proteins., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We proposed a new stitching method based on sift features to obtain an enlarged view of transmission electron microscopic (TEM) images with a high resolution. The sift features were extracted from the images, which were then combined with fitted polynomial correction field to correct the images, followed by image alignment based on the sift features. The image seams at the junction were finally removed by Poisson image editing to achieve seamless stitching, which was validated on 60 local glomerular TEM images with an image alignment error of 62.5 to 187.5 nm. Compared with 3 other stitching methods, the proposed method could effectively reduce image deformation and avoid artifacts to facilitate renal biopsy pathological diagnosis.