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1.
Front Pharmacol ; 15: 1349105, 2024.
Article in English | MEDLINE | ID: mdl-38962301

ABSTRACT

Emergence delirium is a common postoperative complication in patients undergoing general anesthesia, especially in children. In severe cases, it can cause unnecessary self-harm, affect postoperative recovery, lead to parental dissatisfaction, and increase medical costs. With the widespread use of inhalation anesthetic drugs (such as sevoflurane and desflurane), the incidence of emergence delirium in children is gradually increasing; however, its pathogenesis in children is complex and unclear. Several studies have shown that age, pain, and anesthetic drugs are strongly associated with the occurrence of emergence delirium. Alterations in central neurophysiology are essential intermediate processes in the development of emergence delirium. Compared to adults, the pediatric nervous system is not fully developed; therefore, the pediatric electroencephalogram may vary slightly by age. Moreover, pain and anesthetic drugs can cause changes in the excitability of the central nervous system, resulting in electroencephalographic changes. In this paper, we review the pathogenesis of and prevention strategies for emergence delirium in children from the perspective of brain electrophysiology-especially for commonly used pharmacological treatments-to provide the basis for understanding the development of emergence delirium as well as its prevention and treatment, and to suggest future research direction.

2.
Small ; : e2403300, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38966902

ABSTRACT

Pore size sieving, Donnan exclusion, and their combined effects seriously affect ion separation of membrane processes. However, traditional polymer-based membranes face some challenges in precisely controlling both charge distribution and pore size on the membrane surface, which hinders the ion separation performance, such as heavy metal ion removal. Herein, the heterocharged covalent organic framework (COF) membrane is reported by assembling two kinds of ionic COF nanosheets with opposite charges and different pore sizes. By manipulating the stacking quantity and sequence of two kinds of nanosheets, the impact of membrane surface charge and pore size on the separation performance of monovalent and multivalent ions is investigated. For the separation of anions, the effect of pore size sieving is dominant, while for the separation of cations, the effect of Donnan exclusion is dominant. The heterocharged TpEBr/TpPa-SO3H membrane with a positively charged upper layer and a negatively charged bottom layer exhibits excellent rejection of multivalent anions and cations (Ni2+, Cd2+, Cr2+, CrO4 2-, SeO3 2-, etc). The strategy provides not only high-performance COF membranes for ion separation but also an inspiration for the engineering of heterocharged membranes.

3.
Vaccine ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38960787

ABSTRACT

OBJECTIVES: Leukemia cell-derived exosomes (LEXs), carrying leukemia cell-specific antigens, can serve as a source of antigen for dendritic cell (DC) vaccine loading. However, LEX-targeted DC-based vaccines have demonstrated limited antitumor immune effects in clinical trials, attributed to the low immunogenicity of LEXs and the scant levels of costimulatory molecules on DCs. The costimulatory molecules CD80 and CD86, which are crucial to DC function, play a significant role in enhancing immune efficacy. In this study, we explored the anti-leukemia immune response of costimulatory molecule gene-modified LEX-targeted DCs (LEX-8086) in vitro and in animal models. METHODS: DCs were incubated with LEX-8086 to produce LEX-8086-targeted DCs (DCsLEX-8086). ELISA, cytotoxicity assays and flow cytometry utilized to assess the antitumor efficacy of DCsLEX8086 in vitro. Flow cytometry was used to evaluate the immunomodulatory function of DCsLEX8086 in animal models. RESULTS: Our findings indicated that LEX-8086 enhanced the maturation and antigen-presenting ability of DCs. Immunization with DCsLEX8086 significantly activated CD8+ T cells and boosted the CTL response in vitro. More importantly, DCsLEX-8086 effectively suppressed tumor growth and exerted anti-leukemia effects in both prophylactic and therapeutic animal models. Furthermore, DCsLEX-8086 promoted the proportion of CD4+ T cells, CD8+ T cells and M1 macrophages in the tumor environments both prophylactically and therapeutically. Treatment with DCsLEX-8086 showed no significant difference in the levels of M2 macrophages but decreased the proportion of Tregs within the tumor bed during therapeutic experiments. CONCLUSION: The results suggested that DCsLEX-8086 induces a more effective anti-leukemia immunity compared to DCsLEX-null in vivo and in vitro. DCsLEX-8086 might achieve antitumor effects by elevating the numbers of CD4+ T cells, CD8+ T cells, and M1 macrophages in tumors. Our findings indicate that DCsLEX-8086 could be leveraged to develop a new, highly effective vaccine for anti-leukemia immunity.

4.
Nucleic Acids Res ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39011898

ABSTRACT

Horizontal gene transfer has occurred across all domains of life and contributed substantially to the evolution of both prokaryotes and eukaryotes. Previous studies suggest that many horizontally transferred eukaryotic genes conferred selective advantages to bacterial recipients, but how these eukaryotic genes evolved into functional bacterial genes remained unclear, particularly how bacteria overcome the expressional barrier posed by eukaryotic introns. Here, we first confirmed that the presence of intron would inactivate the horizontally transferred gene in Escherichia coli even if this gene could be efficiently transcribed. Subsequent large-scale genetic screens for activation of gene function revealed that activation events could rapidly occur within several days of selective cultivation. Molecular analysis of activation events uncovered two distinct mechanisms how bacteria overcome the intron barrier: (i) intron was partially deleted and the resulting stop codon-removed mutation led to one intact foreign protein or (ii) intron was intactly retained but it mediated the translation initiation and the interaction of two split small proteins (derived from coding sequences up- and downstream of intron, respectively) to restore gene function. Our findings underscore the likelihood that horizontally transferred eukaryotic intron-containing genes could rapidly acquire functionality if they confer a selective advantage to the prokaryotic recipient.

5.
BMC Genomics ; 25(1): 696, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014336

ABSTRACT

BACKGROUND: The marbling trait of cattle muscles, being a key indicator, played an important role in evaluating beef quality. Two breeds of cattle, namely a high-marbling (Angus) and a low-marbling (Nanyang) one, with their cattle muscles selected as our samples for transcriptome sequencing, were aimed to identify differentially expressed long non-coding RNAs (lncRNAs) and their targets associated with the marbling trait. RESULTS: Transcriptome sequencing identified 487 and 283 differentially expressed mRNAs and lncRNAs respectively between the high-marbling (Angus) and low-marbling (Nanyang) cattle muscles. Twenty-seven pairs of differentially expressed lncRNAs-mRNAs, including eighteen lncRNAs and eleven target genes, were found to be involved in fat deposition and lipid metabolism. We established a positive correlation between fourteen up-regulated (NONBTAT000849.2, MSTRG.9591.1, NONBTAT031089.1, MSTRG.3720.1, NONBTAT029718.1, NONBTAT004228.2, NONBTAT007494.2, NONBTAT011094.2, NONBTAT015080.2, NONBTAT030943.1, NONBTAT021005.2, NONBTAT021004.2, NONBTAT025985.2, and NONBTAT023845.2) and four down-regulated (NONBTAT000850.2, MSTRG.22188.3, MSTRG.22188.4, and MSTRG.22188.5) lncRNAs and eleven genes related to adiponectin family protein (ADIPOQ), cytochrome P450 family (CYP4V2), 3-hydroxyacyl-CoA dehydratase family (HACD4), kinesin family (KIF5C), lipin family (LPIN2), perilipin family (PLIN1), prostaglandin family (PTGIS), solute carrier family (SLC16A7, SLC2213, and SLCO4C1), and containing a transmembrane domain protein family (VSTM1). CONCLUSIONS: These candidate genes and lncRNAs can be regarded as being responsible for regulating the marbling trait of cattle. lncRNAs along with the variations in intramuscular fat marbling established a foundation for elucidating the genetic basis of high marbling in cattle.


Subject(s)
RNA, Long Noncoding , RNA, Messenger , Animals , Cattle/genetics , RNA, Long Noncoding/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Gene Expression Profiling , Transcriptome , Muscle, Skeletal/metabolism
6.
Popul Health Metr ; 22(1): 10, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831424

ABSTRACT

BACKGROUND: There are significant geographic inequities in COVID-19 case fatality rates (CFRs), and comprehensive understanding its country-level determinants in a global perspective is necessary. This study aims to quantify the country-specific risk of COVID-19 CFR and propose tailored response strategies, including vaccination strategies, in 156 countries. METHODS: Cross-temporal and cross-country variations in COVID-19 CFR was identified using extreme gradient boosting (XGBoost) including 35 factors from seven dimensions in 156 countries from 28 January, 2020 to 31 January, 2022. SHapley Additive exPlanations (SHAP) was used to further clarify the clustering of countries by the key factors driving CFR and the effect of concurrent risk factors for each country. Increases in vaccination rates was simulated to illustrate the reduction of CFR in different classes of countries. FINDINGS: Overall COVID-19 CFRs varied across countries from 28 Jan 2020 to 31 Jan 31 2022, ranging from 68 to 6373 per 100,000 population. During the COVID-19 pandemic, the determinants of CFRs first changed from health conditions to universal health coverage, and then to a multifactorial mixed effect dominated by vaccination. In the Omicron period, countries were divided into five classes according to risk determinants. Low vaccination-driven class (70 countries) mainly distributed in sub-Saharan Africa and Latin America, and include the majority of low-income countries (95.7%) with many concurrent risk factors. Aging-driven class (26 countries) mainly distributed in high-income European countries. High disease burden-driven class (32 countries) mainly distributed in Asia and North America. Low GDP-driven class (14 countries) are scattered across continents. Simulating a 5% increase in vaccination rate resulted in CFR reductions of 31.2% and 15.0% for the low vaccination-driven class and the high disease burden-driven class, respectively, with greater CFR reductions for countries with high overall risk (SHAP value > 0.1), but only 3.1% for the ageing-driven class. CONCLUSIONS: Evidence from this study suggests that geographic inequities in COVID-19 CFR is jointly determined by key and concurrent risks, and achieving a decreasing COVID-19 CFR requires more than increasing vaccination coverage, but rather targeted intervention strategies based on country-specific risks.


Subject(s)
COVID-19 , Global Health , Machine Learning , SARS-CoV-2 , Humans , COVID-19/mortality , Risk Factors , Pandemics , COVID-19 Vaccines , Vaccination
7.
Front Genet ; 15: 1377770, 2024.
Article in English | MEDLINE | ID: mdl-38846962

ABSTRACT

Background: Several previous animal and human studies have found a strong association between asthma and spermatozoa quality, but whether these associations are causal or due to bias remains to be elucidated. Methods: We performed a two-sample Mendelian randomization (MR) analysis to assess the causal effect of genetically predicted asthma on the risk of abnormal spermatozoa. Asthma, childhood-onset asthma (COA), and adult-onset asthma (AOA) (sample sizes ranging from 327,670 to 408,442) were included as the exposures. Genetic information for abnormal spermatozoa was obtained from a genome-wide association study (GWAS) comprising 209,921 participants. In univariable MR (UVMR) analysis, the inverse variance weighted (IVW) method was conducted as the primary method, with the MR Egger and weighted median used as supplementary methods for causal inference. Sensitivity analyses, including the Cochran Q test, Egger intercept test, MR-PRESSO, and leave-one-out analysis, were performed to verify the robustness of the MR results. Multivariable MR (MVMR) was conducted to evaluate the direct causal effects of asthma on abnormal spermatozoa risk. Results: UVMR detected causal associations between genetically predicted asthma and an increased risk of abnormal spermatozoa (OR: 1.270, 95% CI: 1.045-1.545, p = 0.017). Moreover, we found that AOA (OR: 1.46, 95% CI: 1.051, 2.018, p = 0.024) has positive causal effects on the risk of abnormal spermatozoa rather than COA (p = 0.558). Sensitivity analysis found little evidence of bias in the current study (p > 0.05). MVMR further confirmed that asthma directly affected the risk of abnormal spermatozoa. Conclusion: Our MR study suggested that genetically predicted asthma could be associated with an increased risk of abnormal spermatozoa, and similar results were obtained in AOA. Further studies are warranted to explain the underlying mechanisms of this association and may provide new avenues for prevention and treatment.

9.
Acta Trop ; 257: 107308, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38945422

ABSTRACT

Dengue fever is a viral illness, mainly transmitted by Aedes aegypti and Aedes albopictus. With climate change and urbanisation, more urbanised areas are becoming suitable for the survival and reproduction of dengue vector, consequently are becoming suitable for dengue transmission in China. Chongqing, a metropolis in southwestern China, has recently been hit by imported and local dengue fever, experiencing its first local outbreak in 2019. However, the genetic evolution dynamics of dengue viruses and the spatiotemporal patterns of imported and local dengue cases have not yet been elucidated. Hence, this study implemented phylogenetic analyses using genomic data of dengue viruses in 2019 and 2023 and a spatiotemporal analysis of dengue cases collected from 2013 to 2022. We sequenced a total of 15 nucleotide sequences of E genes. The dengue viruses formed separate clusters and were genetically related to those from Guangdong Province, China, and countries in Southeast Asia, including Laos, Thailand, Myanmar and Cambodia. Chongqing experienced a dengue outbreak in 2019 when 168 imported and 1,243 local cases were reported, mainly in September and October. Few cases were reported in 2013-2018, and only six were imported from 2020 to 2022 due to the COVID-19 lockdowns. Our findings suggest that dengue prevention in Chongqing should focus on domestic and overseas population mobility, especially in the Yubei and Wanzhou districts, where airports and railway stations are located, and the period between August and October when dengue outbreaks occur in endemic regions. Moreover, continuous vector monitoring should be implemented, especially during August-October, which would be useful for controlling the Aedes mosquitoes. This study is significant for defining Chongqing's appropriate dengue prevention and control strategies.

10.
Sheng Wu Gong Cheng Xue Bao ; 40(6): 1935-1949, 2024 Jun 25.
Article in Chinese | MEDLINE | ID: mdl-38914502

ABSTRACT

Plant synthetic biology has significant theoretical advantages in exploration and production of plant natural products. However, its contribution to the field of biosynthesis is currently limited due to the lack of efficient chassis systems and related enabling technologies. Synthetic biologists often avoid tobacco as a chassis system because of its long operation cycle, difficulties in genetic and metabolic modification, complex metabolism and purification background, nicotine toxicity, and challenges in accurately controlling for agricultural production. Nevertheless, the tobacco suspension cell chassis system offers a viable solution to these challenges. The objective of this research was to develop a tobacco suspension cell chassis with high scientific and industrial potential. This chassis should exhibit rapid growth, high biomass, excellent dispersion, high transformation efficiency, and minimal nicotine content. Nicotiana benthamiana, which has high applicability in molecular technology, was used to induce suspension cells. The induced suspension cells, named NBS-1, exhibited rapid growth, excellent dispersion, and high biomass, reaching a maximum biomass of 476.39 g/L (fresh weight), which was significantly higher than that of BY-2. The transformation efficiency of the widely utilized pEAQ-HT transient expression system in NBS-1 reached 81%, which was substantially elevated compared to BY-2. The metabolic characteristics and bias of BY-2 and NBS-1 were analyzed using transcriptome data. It was found that the gene expression of pathways related to biosynthesis of flavonoids and their derivatives in NBS-1 was significantly higher, while the pathways related to alkaloid biosynthesis were significantly lower compared to BY-2. These findings were further validated by the total content of flavonoid and alkaloid. In summary, our research demonstrates NBS-1 possesses minimal nicotine content and provides valuable guidance for selecting appropriate chassis for specific products. In conclusion, this study developed NBS-1, a tobacco suspension cell chassis with excellent growth and transformation, high flavonoid content and minimal nicotine content, which has important guiding significance for the development of tobacco suspension cell chassis.


Subject(s)
Nicotiana , Nicotiana/metabolism , Nicotiana/genetics , Synthetic Biology , Plants, Genetically Modified/metabolism , Metabolic Engineering/methods , Cell Culture Techniques/methods , Nicotine/metabolism , Nicotine/biosynthesis , Biomass
11.
J Adv Res ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38876191

ABSTRACT

BACKGROUND: As people age, degenerative bone and joint diseases (DBJDs) become more prevalent. When middle-aged and elderly people are diagnosed with one or more disorders such as osteoporosis (OP), osteoarthritis (OA), and intervertebral disc degeneration (IVDD), it often signals the onset of prolonged pain and reduced functionality. Chronic inflammation has been identified as the underlying cause of various degenerative diseases, including DBJDs. Recently, excessive activation of pyroptosis, a form of programed cell death (PCD) mediated by inflammasomes, has emerged as a primary driver of harmful chronic inflammation. Consequently, pyroptosis has become a potential target for preventing and treating DBJDs. AIM OF REVIEW: This review explored the physiological and pathological roles of the pyroptosis pathway in bone and joint development and its relation to DBJDs. Meanwhile, it elaborated the molecular mechanisms of pyroptosis within individual cell types in the bone marrow and joints, as well as the interplay among different cell types in the context of DBJDs. Furthermore, this review presented the latest compelling evidence supporting the idea of regulating the pyroptosis pathway for DBJDs treatment, and discussed the potential, limitations, and challenges of various therapeutic strategies involving pyroptosis regulation. KEY SCIENTIFIC CONCEPTS OF REVIEW: In summary, an interesting identity for the unregulated pyroptosis pathway in the context of DBJDs was proposed in this review, which was undertaken as a spoiler of peaceful coexistence between cells in a degenerative environment. Over the extended course of DBJDs, pyroptosis pathway perpetuated its activity through crosstalk among pyroptosis cascades in different cell types, thus exacerbating the inflammatory environment throughout the entire bone marrow and joint degeneration environment. Correspondingly, pyroptosis regulation therapy emerged as a promising option for clinical treatment of DBJDs.

12.
Langmuir ; 40(20): 10804-10813, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38723143

ABSTRACT

Efficiently regulating the rebound behavior of droplets post-impact is crucial for various fields, mainly including the development of self-cleaning applications, the design of surface functional materials, and the advancement of industrial techniques. By performing molecular dynamics simulations, we investigated the impact and jumping behavior of droplets on heterogeneous substrates with different wetting regions. We found that, during the impacting evolution process, the retracted droplets would move toward regions with stronger wettability due to the unbalanced force caused by the wettability difference, revealing the directional migration ability. The values of the wettability difference strongly affect the degree of oblique rebound and contact time when droplets can jump off the substrate. We then designed the surfaces with a wettability gradient and found that the oblique rebound angle could be well controlled and the contact time further reduced. Our findings may provide valuable insight into the relationship between the wettability gradient and the behavior of liquid droplets on surfaces, with broad implications for various fields such as surface engineering, materials science, microfluidics, etc.

13.
Appl Microbiol Biotechnol ; 108(1): 340, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38777914

ABSTRACT

Horizontal gene transfer occurs frequently in bacteria, but the mechanism driving activation and optimization of the expression of horizontally transferred genes (HTGs) in new recipient strains is not clear. Our previous study found that spontaneous tandem DNA duplication resulted in rapid activation of HTGs. Here, we took advantage of this finding to develop a novel technique for tandem gene duplication, named tandem gene duplication selected by activation of horizontally transferred gene in bacteria (TDAH), in which tandem duplication was selected by the activation of horizontally transferred selectable marker gene. TDAH construction does not contain any reported functional elements based on homologous or site-specific recombination and DNA amplification. TDAH only contains an essential selectable marker for copy number selection and 9-bp-microhomology border sequences for precise illegitimate recombination. One transformation and 3 days were enough to produce a high-copy strain, so its procedure is simple and fast. Without subsequent knockout of the endogenous recombination system, TDAH could also generate the relatively stable high-copy tandem duplication for plasmid-carried and genome-integrated DNA. TDAH also showed an excellent capacity for increase gene expression and worked well in different industrial bacteria. We also applied TDAH to select the optimal high copy number of ribA for vitamin B2 production in E. coli; the yield was improved by 3.5 times and remained stable even after 12 subcultures. TDAH is a useful tool for recombinant protein production and expression optimization of biosynthetic pathways. KEY POINTS: • We develop a novel and efficient technique (TDAH) for tandem gene duplication in bacterium. TDAH is based on the mechanism of HTG rapid activation. TDAH does not contain any reported functional elements based on homologous recombination and DNA amplification. TDAH only contains an essential selectable marker for copy number selection, so its construction and procedure are very simple and fast. • TDAH is the first reported selected and stable tandem-gene-duplication technique in which the selected high-copy plasmid-carried and genome-integrated DNA could remain stable without the subsequent knockout of recombination system. • TDAH showed an excellent capacity for regulating gene expression and worked well in different industrial bacteria, indicating it is a useful tool for recombinant protein production and expression optimization of biosynthetic pathways. • TDAH was applied to select the optimal high copy number of ribA for vitamin B2 production in E. coli; the yield was improved by 3.5-fold and remained stable even after 12 subcultures.


Subject(s)
Escherichia coli , Gene Duplication , Gene Transfer, Horizontal , Plasmids , Escherichia coli/genetics , Escherichia coli/metabolism , Plasmids/genetics , Bacteria/genetics , Bacteria/metabolism , Gene Dosage , Recombination, Genetic
14.
Phytother Res ; 2024 May 05.
Article in English | MEDLINE | ID: mdl-38706097

ABSTRACT

Inflammatory bowel disease (IBD) is an autoimmune disorder primarily characterized by intestinal inflammation and recurrent ulceration, leading to a compromised intestinal barrier and inflammatory infiltration. This disorder's pathogenesis is mainly attributed to extensive damage or death of intestinal epithelial cells, along with abnormal activation or impaired death regulation of immune cells and the release of various inflammatory factors, which contribute to the inflammatory environment in the intestines. Thus, maintaining intestinal homeostasis hinges on balancing the survival and functionality of various cell types. Programmed cell death (PCD) pathways, including apoptosis, pyroptosis, autophagy, ferroptosis, necroptosis, and neutrophil extracellular traps, are integral in the pathogenesis of IBD by mediating the death of intestinal epithelial and immune cells. Natural products derived from plants, fruits, and vegetables have shown potential in regulating PCD, offering preventive and therapeutic avenues for IBD. This article reviews the role of natural products in IBD treatment by focusing on targeting PCD pathways, opening new avenues for clinical IBD management.

15.
Autophagy ; : 1-17, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38762757

ABSTRACT

Bleomycin exhibits effective chemotherapeutic activity against multiple types of tumors, and also induces various side effects, such as pulmonary fibrosis and neuronal defects, which limit the clinical application of this drug. Macroautophagy/autophagy has been recently reported to be involved in the functions of bleomycin, and yet the mechanisms of their crosstalk remain insufficiently understood. Here, we demonstrated that reactive oxygen species (ROS) produced during bleomycin activation hampered autophagy flux by inducing lysosomal membrane permeabilization (LMP) and obstructing lysosomal degradation. Exhaustion of ROS with N-acetylcysteine relieved LMP and autophagy defects. Notably, we observed that LMP and autophagy blockage preceded the emergence of cellular senescence during bleomycin treatment. In addition, promoting or inhibiting autophagy-lysosome degradation alleviated or exacerbated the phenotypes of senescence, respectively. This suggests the alternation of autophagy activity is more a regulatory mechanism than a consequence of bleomycin-induced cellular senescence. Taken together, we reveal a specific role of bleomycin-induced ROS in mediating defects of autophagic degradation and further regulating cellular senescence in vitro and in vivo. Our findings, conversely, indicate the autophagy-lysosome degradation pathway as a target for modulating the functions of bleomycin. These provide a new perspective for optimizing bleomycin as a clinically applicable chemotherapeutics devoid of severe side-effects.Abbreviations: AT2 cells: type II alveolar epithelial cells; ATG7: autophagy related 7; bEnd.3: mouse brain microvascular endothelial cells; BNIP3L: BCL2/adenovirus E1B interacting protein 3-like; CCL2: C-C motif chemokine ligand 2; CDKN1A: cyclin dependent kinase inhibitor 1A; CDKN2A: cyclin dependent kinase inhibitor 2A; FTH1: ferritin heavy polypeptide 1; γ-H2AX: phosphorylated H2A.X variant histone; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HUVEC: human umbilical vein endothelial cells; HT22: hippocampal neuronal cell lines; Il: interleukin; LAMP: lysosomal-associated membrane protein; LMP: lysosome membrane permeabilization; MTORC1: mechanistic target of rapamycin kinase complex 1; NAC: N-acetylcysteine; NCOA4: nuclear receptor coactivator 4; PI3K: phosphoinositide 3-kinase; ROS: reactive oxygen species; RPS6KB/S6K: ribosomal protein S6 kinase; SA-GLB1/ß-gal: senescence-associated galactosidase, beta 1; SAHF: senescence-associated heterochromatic foci; SASP: senescence-associated secretory phenotype; SEC62: SEC62 homolog, preprotein translocation; SEP: superecliptic pHluorin; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB.

16.
Hortic Res ; 11(4): uhae041, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38638682

ABSTRACT

Long non-coding RNAs (lncRNAs) play essential roles in various biological processes, such as chromatin remodeling, post-transcriptional regulation, and epigenetic modifications. Despite their critical functions in regulating plant growth, root development, and seed dormancy, the identification of plant lncRNAs remains a challenge due to the scarcity of specific and extensively tested identification methods. Most mainstream machine learning-based methods used for plant lncRNA identification were initially developed using human or other animal datasets, and their accuracy and effectiveness in predicting plant lncRNAs have not been fully evaluated or exploited. To overcome this limitation, we retrained several models, including CPAT, PLEK, and LncFinder, using plant datasets and compared their performance with mainstream lncRNA prediction tools such as CPC2, CNCI, RNAplonc, and LncADeep. Retraining these models significantly improved their performance, and two of the retrained models, LncFinder-plant and CPAT-plant, alongside their ensemble, emerged as the most suitable tools for plant lncRNA identification. This underscores the importance of model retraining in tackling the challenges associated with plant lncRNA identification. Finally, we developed a pipeline (Plant-LncPipe) that incorporates an ensemble of the two best-performing models and covers the entire data analysis process, including reads mapping, transcript assembly, lncRNA identification, classification, and origin, for the efficient identification of lncRNAs in plants. The pipeline, Plant-LncPipe, is available at: https://github.com/xuechantian/Plant-LncRNA-pipline.

17.
Biochem Pharmacol ; 224: 116230, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38643905

ABSTRACT

One of the effective therapeutic strategies to treat rheumatoid arthritis (RA)-related bone resorption is to target excessive activation of osteoclasts. We discovered that 6-O-angeloylplenolin (6-OAP), a pseudoguaianolide from Euphorbia thymifolia Linn widely used for the treatment of RA in traditional Chinese medicine, could inhibit RANKL-induced osteoclastogenesis and bone resorption in both RAW264.7 cells and BMMs from 1 µM and protect a collagen-induced arthritis (CIA) mouse model from bone destruction in vivo. The severity of arthritis and bone erosion observed in paw joints and the femurs of the CIA model were attenuated by 6-OAP administered at both dosages (1 or 5 mg/kg, i.g.). BMD, Tb.N and BV/TV were also improved by 6-OAP treatment. Histological analysis and TRAP staining of femurs further confirmed the protective effects of 6-OAP on bone erosion, which is mainly due to reduced osteoclasts. Molecular docking indicated that c-Src might be a target of 6-OAP and phosphorylation of c-Src was suppressed by 6-OAP treatment. CETSA and SPR assay further confirmed the potential interaction between 6-OAP and c-Src. Three signaling molecules downstream of c-Src that are vital to the differentiation and function of osteoclasts, NF-κB, c-Fos and NFATc1, were also suppressed by 6-OAP in vitro. In summary, the results demonstrated that the function of c-Src was disrupted by 6-OAP, which led to the suppression of downstream signaling vital to osteoclast differentiation and function. In conclusion, 6-OAP has the potential to be further developed for the treatment of RA-related bone erosion.


Subject(s)
Arthritis, Experimental , Bone Resorption , NF-kappa B , NFATC Transcription Factors , Osteoclasts , Osteogenesis , Animals , Mice , NFATC Transcription Factors/metabolism , RAW 264.7 Cells , Bone Resorption/drug therapy , Bone Resorption/metabolism , Bone Resorption/prevention & control , Arthritis, Experimental/drug therapy , Arthritis, Experimental/pathology , Arthritis, Experimental/metabolism , Arthritis, Experimental/chemically induced , Osteogenesis/drug effects , NF-kappa B/metabolism , Osteoclasts/drug effects , Osteoclasts/metabolism , Male , Signal Transduction/drug effects , CSK Tyrosine-Protein Kinase/metabolism , Molecular Docking Simulation , src-Family Kinases/metabolism , src-Family Kinases/antagonists & inhibitors
18.
Sci Bull (Beijing) ; 69(11): 1706-1715, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38616150

ABSTRACT

Traditional dual-ion lithium salts have been widely used in solid polymer lithium-metal batteries (LMBs). Nevertheless, concentration polarization caused by uncontrolled migration of free anions has severely caused the growth of lithium dendrites. Although single-ion conductor polymers (SICP) have been developed to reduce concentration polarization, the poor ionic conductivity caused by low carrier concentration limits their application. Herein, a dual-salt quasi-solid polymer electrolyte (QSPE), containing the SICP network as a salt and traditional dual-ion lithium salt, is designed for retarding the movement of free anions and simultaneously providing sufficient effective carriers to alleviate concentration polarization. The dual salt network of this designed QSPE is prepared through in-situ crosslinking copolymerization of SICP monomer, regular ionic conductor, crosslinker with the presence of the dual-ion lithium salt, delivering a high lithium-ion transference number (0.75) and satisfactory ionic conductivity (1.16 × 10-3 S cm-1 at 30 °C). Comprehensive characterizations combined with theoretical calculation demonstrate that polyanions from SICP exerts a potential repulsive effect on the transport of free anions to reduce concentration polarization inhibiting lithium dendrites. As a consequence, the Li||LiFePO4 cell achieves a long-cycle stability for 2000 cycles and a 90% capacity retention at 30 °C. This work provides a new perspective for reducing concentration polarization and simultaneously enabling enough lithium-ions migration for high-performance polymer LMBs.

19.
Int Immunopharmacol ; 130: 111773, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38430808

ABSTRACT

As bacteria synthesize nutrients primarily in the cecum, coprophagy is indispensable for supplying rabbits with essential nutrients. Recent research has demonstrated its pivotal role in maintaining intestinal microbiota homeostasis and immune regulation in rabbits, although the specific mechanism remains unknown. Here, we used coprophagy prevention (CP) to investigate the effects of coprophagy on the cecum homeostasis and microbiota in New Zealand white rabbits. Furthermore, whether supplementation of Clostridium butyricum (C. butyricum) may alleviate the cecum inflammation and apoptosis caused by CP was also explored. Four groups were randomly assigned: control (Con), sham-coprophagy prevention (SCP), coprophagy prevention (CP), and CP and C. butyricum addition (CPCB). Compared to Con and SCP, CP augmented cecum inflammation and apoptosis, as well as bacterial adhesion to the cecal epithelial mucosa, while decreasing the expression of tight junction proteins (ZO-1, occluding, and claudin-1). The relative abundance of short-chain fatty acids (SCFAs)-producing bacteria was significantly decreased in the CP group. Inversely, there was an increase in the Firmicutes/Bacteroidetes ratio and the relative abundance of Christensenellaceae_R-7_group. Additionally, CP increased the levels of Flagellin, IFN-γ, TNF-a, and IL-1ß in cecum contents and promoted the expression of TLR5/MyD88/NF-κB pathway in cecum tissues. However, the CPCB group showed significant improvements in all parameters compared to the CP group. Dietary C. butyricum supplementation significantly increased the production of SCFAs, particularly butyric acid, triggering anti-inflammatory, tissue repairing, and barrier-protective responses. Notably, CPCB effectively mitigated CP-induced apoptosis and inflammation. In summary, CP disrupts the cecum epithelial barrier and induces inflammation in New Zealand white rabbits, but these effects can be alleviated by C. butyricum supplementation. This process appears to be largely associated with the TLR5/MyD88/NF-κB signaling pathway.


Subject(s)
Clostridium butyricum , Probiotics , Rabbits , Animals , Clostridium butyricum/physiology , NF-kappa B/metabolism , Coprophagia , Myeloid Differentiation Factor 88/metabolism , Toll-Like Receptor 5/metabolism , Fatty Acids, Volatile , Inflammation
20.
Insights Imaging ; 15(1): 98, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38536581

ABSTRACT

OBJECTIVE: To systematically analyze the accuracy of ultrasonic techniques in assessing the nature of gastric contents and their volume. METHODS: English-language articles that used ultrasonic techniques to assess the nature of gastric contents and their volume in patients were selected. In eligible studies, data were recalculated and analyzed for forest plots and subject summary curves of operating characteristics (SROC). Study quality was assessed using the diagnostic accuracy study quality assessment tool QUADAS-2. Publication bias was tested using funnel plots. RESULTS: Nine articles with a total of 523 study subjects were identified for this review. All studies were feasibility studies. The sensitivity of ultrasound assessment of gastric contents ranged from 53 to 100% and the specificity from 48 to 99%. The combined analysis yielded an area under the working characteristic curve for subjects of 97% (95% confidence interval (CI), 95-98%), a sensitivity of 95% (95% CI, 84-99%), and a specificity of 88% (95% CI, 72-95%). There was a high degree of heterogeneity among the studies due to inter-operator differences and small sample sizes. CONCLUSION: Ultrasound techniques have high diagnostic accuracy in assessing the nature of gastric contents and their volume in patients. However, most of the studies were feasibility studies with small sample sizes, lacked standardization, and had high risk of bias. More studies are needed in the future to investigate the diagnostic performance of gastric ultrasound assessment techniques. CRITICAL RELEVANCE STATEMENT: Ultrasonography can be used to assess gastric contents, but standardized data integration and reporting are needed to account for the diagnostic capabilities of this technology. KEY POINTS: • Ultrasound is a safe and feasible tool for assessing gastric contents. • Ultrasound has good diagnostic performance for gastric contents. • There is still a certain heterogeneity within our analysis process; more research is needed in the future to improve our results.

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