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Solid sodium metal batteries (SSMBs) offer an alternative promising power source for electrochemical energy storage due to their high energy density and high safety. However, the inherent sodium dendrite growth and poor mechanical properties of electrolytes seriously limit their application. Herein, a network structure composed of polyethylene oxide-based composite polymer electrolyte (CPE) is designed with liquid metal nanoparticles (LM) for SSMBs, in which LM can move in the solid electrolyte with the electric field driven. This effect can facilitate the inactivated sodium return to the metal sodium anode, and alloy with dendrites at the same time, which is beneficial for inhibiting the growth of dendrites. The symmetric cell with the CPE containing LM achieves good cyclic stability of more than 1800 and 800 h at 0.1 and 0.2 mA cm-2, respectively. The energy density of the pouch battery can reach 230 Wh kg-1. In sum, LM presents great potential to be employed as a performance reinforcement filler for CPEs, which paves the way for achieving high-performance SSMBs.
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The clinical outcome of spinal fusion surgery is closely related to the success of bone fusion. Nowadays, the interbody cage which is used to replace the disc for spinal fusion is expected to have biological activity to improve osseointegration, especially for the aging and osteoporotic patients. Here, through micro-arc oxidation and hydrothermal treatment (MAO + HT), a bioactive CaP coating with micro/nano multilevel morphology was developed on 3D printed Ti6Al4V alloy then verified in vitro and in sheep anterior cervical decompression fusion model systematically. In vitro studies have confirmed the positive effects of characteristic micro/nano morphology and hydrophilicity of the coating formed after surface treatment on the adhesion, proliferation, and osteogenic differentiation of osteoblast precursor cells. Furthermore, the MAO + HT treated interbody cage showed a closer integration with the surrounding bone tissue, improved kinetic stability of the implanted segment, and significantly reduced incidence of fusion failure during the early postoperative period, which indicated that such a surface modification strategy is applicable to the biomechanical and biological microenvironment of the intervertebral space.
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The xenobiotic metabolism driven by the gut microbiota significantly regulates the bioavailability and toxic effects of environmental pollutants such as plasticizers on aquatic organisms. However, it is still unknown whether the gut microbiota can exhibit variable metabolic ability across host species and which functional bacteria and genes are involved in xenobiotic transformation. This study investigated the enriched gut microbiota community composition and diversity of in vitro enrichment cultures from 6 marine species, namely, yellowfin seabream (Acanthopagrus latus), thorn fish (Terapon jarbua), shortnose ponyfish (Leiognathus brevirostris), mussel (Perna viridis), prawn (Parapenaeopsis hungerfordi) and crab (Charybdis riversandersoni). Pseudomonadota, Bacteroidota and Bacillota were the dominant phyla and Enterobacter, Raoultella, Klebsiella, Dysgonomanas and Lactococcus were the dominant genera in the enriched flora according to 16S rRNA sequencing. Furthermore, the metagenomic results revealed that all enriched gut microbiota presented metabolic genes for carbohydrates, amino acids, lipids, and xenobiotics. In particular, the gut microbiota of yellowfin seabream had the highest abundance of glycoside hydrolase family genes and CYP450 enzyme genes. Klebsiella was identified as a common potential degrader of xenobiotic metabolism. In addition, the Biolog plate test system confirmed that the gut microbiota can metabolize various carbon sources and drive the xenobiotic transformation. According to AWCD analysis of community level physiological profiling (CLPP), yellowfin seabream > mussel > prawn > shortnose ponyfish > crab > thorn fish. The gut microbiota of yellowfin seabream presented a stronger metabolic profile of phthalates and bisphenol analogs which reflected by their AWCD results and concentration variations. Overall, our results demonstrated the diverse metabolic abilities of the gut microbiota from six marine organisms and their potential for altering of the fate of xenobiotics in the ecosystem on the basis of combined taxonomic, metagenomic, and in vitro transformation analysis.
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The most general cancer in men is prostate cancer (PCa), with its risk increasing due to age and obesity. Visfatin, a member of adipokines, is related to cancer progression and metastasis, but its relationship in PCa remains undetermined. In addition, no knowledge is available regarding relations between visfatin polymorphisms and clinicopathological characteristics in PCa. We sought to investigate the functions of four visfatin gene polymorphisms and clinicopathological characteristics on the hazard of developing PCa in 695 Taiwanese males with PCa. Carriers of the GA+AA heterozygote of SNP rs61330082 were at a markedly higher risk of biochemical recurrence than those with the GG genotype. Visfatin rs61330082 and rs11977021 were related with a high risk of perineural invasion, lymphovascular invasion, and biochemical recurrence in prostate-specific antigen (PSA) > 10 PCa patients. The Cancer Genome Atlas database noted that visfatin mRNA level did not prominently differ with pathological T/N stage and overall survival. This finding is the first to document a connection between visfatin polymorphisms and clinicopathological characteristics of PCa in Taiwanese males.
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Nicotinamida Fosforribosiltransferasa , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata , Humanos , Masculino , Nicotinamida Fosforribosiltransferasa/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Taiwán/epidemiología , Anciano , Persona de Mediana Edad , Predisposición Genética a la Enfermedad , Genotipo , Estudios de Asociación Genética , Citocinas/genética , Antígeno Prostático Específico/sangreRESUMEN
Immune checkpoint inhibitors augment the antitumor activity of T cells by inhibiting the negative regulatory pathway of T cells, leading to notable efficacy in patients with non-small cell lung cancer, melanoma, and other malignancies through immunotherapy utilization. However, secondary malignant liver tumors not only lower the liver's sensitivity to immunotherapy but also trigger systemic immune suppression, resulting in reduced overall effectiveness of immune therapy. Patients receiving immunotherapy for non-small cell lung cancer and melanoma experience reduced response rates, progression-free survival, and overall survival when secondary malignant tumors develop in the liver. Through Liu's retrospective analysis, valuable insights are provided for the future clinical management of these patients. Therefore, in patients with gastric cancer (GC), the occurrence of liver metastasis might be indicative of reduced efficacy of immunotherapy. Overcoming liver immune tolerance mechanisms and their negative impacts allows for the potential benefits of immunotherapy in patients with GC and liver metastasis.
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Antibiotics in animal manure pose significant risks to the environment and health. While anaerobic digestion (AD) is commonly used for pig manure treatment, its efficiency in antibiotic removal has been considerably limited. This study investigated the impact of hydrothermal pretreatment (HTP) on sulfadiazine (SDZ) removal in a two-stage AD system. Results indicated that the HTP process reduced SDZ concentration by 40.61%. Furthermore, the SDZ removal efficiency of the AD system coupling HTP increased from 50.90% to 65.04% compared to the untreated system. Biogas yield was also improved by 26.17% while maintaining system stability. Changes induced by HTP in the microbial communities revealed that Firmicutes, Bacteroidetes, Caldatribacteriota, and Proteobacteria emerged as the primary bacterial phyla. Following HTP, the relative abundance of Prevotella, which exhibited a strong negative correlation with SDZ concentration, increased significantly by 25-fold in the acidogenic stage. Proteiniphilum, Syntrophomonas and Sedimentibacter showed notable increases in the methanogenic stage after HTP. The N-heterocyclic metabolism carried out by Prevotella might have been the predominant SDZ degradation pathway in the acidogenic stage, while the benzene ring metabolism and hydroxylation by the Proteiniphilum emerged as the primary degradation pathways in the methanogenic stages. Furthermore, biodegradation intermediates were proven to be less toxic than SDZ itself, indicating that the HTP-enhanced two-stage AD process could be a viable way to lower the environmental risks associated with SDZ. The findings from this study provide valuable insights for removing SDZ from the environment via two-stage AD.
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Full-reference point cloud quality assessment (FR-PCQA) aims to infer the quality of distorted point clouds with available references. Most of the existing FR-PCQA metrics ignore the fact that the human visual system (HVS) dynamically tackles visual information according to different distortion levels (i.e., distortion detection for high-quality samples and appearance perception for low-quality samples) and measure point cloud quality using unified features. To bridge the gap, in this paper, we propose a perception-guided hybrid metric (PHM) that adaptively leverages two visual strategies with respect to distortion degree to predict point cloud quality: to measure visible difference in high-quality samples, PHM takes into account the masking effect and employs texture complexity as an effective compensatory factor for absolute difference; on the other hand, PHM leverages spectral graph theory to evaluate appearance degradation in low-quality samples. Variations in geometric signals on graphs and changes in the spectral graph wavelet coefficients are utilized to characterize geometry and texture appearance degradation, respectively. Finally, the results obtained from the two components are combined in a non-linear method to produce an overall quality score of the tested point cloud. The results of the experiment on five independent databases show that PHM achieves state-of-the-art (SOTA) performance and offers significant performance improvement in multiple distortion environments. The code is publicly available at https://github.com/zhangyujie-1998/PHM.
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Numerous tire additives are high-production volume chemicals that are used extensively worldwide. However, their presence and partitioning behavior remain largely unknown, particularly in marine environments. This study is the first to reveal the spatiotemporal distribution, multimedia partitioning, and transport processing of 22 tire additives and their transformation products (TATPs) in a highly urbanized estuary (n = 166). Nineteen, 18, and 20 TATPs were detectable in water, suspended particulate matter (SPM), and sediments, respectively, with total levels of 59.7-2021 ng/L, 164-6935 ng/g, and 4.66-58.4 ng/g, respectively. The multimedia partitioning mechanisms of TATPs are governed by their molecular weight, hydrophobicity, and biodegradation rate. Mass inventories coupled with model simulations have revealed that substantial quantities of TATPs accumulate within estuarine environments, and these compounds can be continuously transported into the ocean, particularly during the wet season. According to the multi-criteria evaluation approach, four and three TATPs were identified as high-priority pollutants during the dry and wet seasons, respectively. Unexpectedly, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone was only listed as a medium-priority pollutant. This study underscores the importance of marine surveillance and advocates for particular attention to these ubiquitous but underexplored TATPs in future studies.
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Microorganisms constitute an essential component of the indoor ecosystem and may pose potential health risks after inhalation. However, evidence regarding the impact of indoor airborne microbiome on general respiratory health is scarce. Additionally, while air purification has been shown to be an effective strategy for controlling culturable bioaerosols, its impact on indoor airborne microbiome remains unclear. To determine the impact of indoor airborne microbial exposure on lung function, and whether and how air purification can modify indoor airborne microbiome, we conducted a randomized, double-blind, crossover study employing air purification intervention among 68 healthy young adults in Beijing, China. Indoor airborne bacteria and fungi were characterized using amplicon sequencing technology and quantified by qPCR. Our results indicated positive associations between indoor airborne microbial α-diversity and lung function indices; however, adverse effects from total microbial load were observed. Males were more susceptible to microbial exposure than females. Beneficial effects from richness in Actinobacteria, Bacteroidia, Oxyphotobacteria, Bacilli, Clostridia, Alphaproteobacteria, Gammaproteobacteria, Dothideomycetes, and Sordariomycetes, and detrimental effects from five Proteobacteria genera, including Dechloromonas, Hydrogenophaga, Klebsiella, Pseudomonas, and Tolumonas, were also identified. Air purification contributed to decreased fungal diversity and total fungal load, but not the overall microbial community structure. Our study demonstrates the significant role of indoor airborne microbiome in regulating human respiratory health and provides inspiration for improving health through manipulation of indoor microbiome. Meanwhile, our study also underscores the importance of balancing the potential benefits from decreased microbial load and the underlying risks from reduced microbial diversity while applying environmental microbial interventions.
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Analysis of impurities in illicit drugs provides key information on the manufacture and distribution of methamphetamine (MA). An analysis of 22 specific target compounds in unlawful MA products was conducted using ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). The peak area of the alkaloids was utilized as an important calculation data variable to determine the synthesis method. The results demonstrated that the application of target screening techniques for trace impurity components in samples can aid in determining the synthesis process routes for toxin production in 169 samples. These samples were initially categorized based on their synthesis modes, specifically synthesis routes N, E, and R. The correlation analysis of MA samples with known synthetic routes was carried out using principal coordinate analysis (PCoA) and the Pearson correlation coefficient method. Among the N and R synthesis routes, 15 and 7 groups with strong correlation were screened, respectively. Consistent with the observed scenario, the samples from the synthetic route E showed limited correlation with each other. The experiment provides a focused framework for the management of synthetic raw materials used for the production of drugs and the investigation of drug-related cases. This facilitates a holistic strategy to combat drug-related crimes, from manufacturing laboratory to end-user.
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T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological tumor that requires novel treatment strategies, especially for relapsed/refractory cases. Dihydroorotate dehydrogenase (DHODH), a key enzyme in the de novo pyrimidine synthesis pathway, has been identified as a potential target for tumors. Besides, Teriflunomide (TRF) is a DHODH inhibitor with anticancer effects; however, its role in T-ALL remains poorly understood. Here, we investigated the potential anticancer effects of TRF on T-ALL cells, and the results showed that TRF inhibited cell proliferation, caused S-phase cell cycle arrest, and promoted apoptosis of T-ALL (MOLT4 and JURKAT) cell lines. In addition, TRF reduced the infiltration capacity of T-ALL cells in T-ALL xenograft mice while up-regulating the expression of P53 and BTG2. The BTG2 knockdown significantly attenuated the inhibitory effect of TRF on cellular growth and suppressed the TRF-mediated elevated expression of P53 in T-ALL cells. Moreover, combined treatment with TRF and daunorubicin (DNR) significantly reduced cell viability and promoted apoptosis in DNR-resistant T-ALL cells. Our study provides valuable insights into the critical role of TRF in treating T-ALL while increasing the sensitivity of DNR-resistant T-ALL cells to DNR.
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Single-crystalline covalent organic frameworks (COFs) are highly desirable toward understanding their pore chemistry and functions. Herein, two 50-100 µm single-crystalline three-dimensional (3D) COFs, TAM-TFPB-COF and TAPB-TFS-COF, were prepared from the condensation of 4,4',4â³,4â´-methanetetrayltetraaniline (TAM) with 3,3',5,5'-tetrakis(4-formylphenyl)bimesityl (TFPB) and 3,3',5,5'-tetrakis(4-aminophenyl)bimesityl (TAPB) with 4,4',4â³,4â´-silanetetrayltetrabenzaldehyde (TFS), respectively, in 1,4-dioxane under the catalysis of acetic acid. Single-crystal 3D electron diffraction reveals the triply interpenetrated dia-b networks of TAM-TFPB-COF with atom resolution, while the isostructure of TAPB-TFS-COF was disclosed by synchrotron single-crystal X-ray diffraction and synchrotron powder X-ray diffraction with Le Bail refinements. The nitrogen sorption measurements at 77 K disclose the microporosity nature of both activated COFs with their exceptionally high Brunauer-Emmett-Teller surface areas of 3533 and 4107 m2 g-1, representing the thus far record high specific surface area among imine-bonded COFs. This enables the activated COFs to exhibit also the record high methane uptake capacities up to 28.9 wt % (570 cm3 g-1) at 25 °C and 200 bar among all COFs reported thus far. This work not only presents the structures of two single-crystalline COFs with exceptional microporosity but also provides an example of atom engineering to adjust permanent microporous structures for methane storage.
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Aquatic organisms in the environment are frequently exposed to a variety of organic chemicals, while these biological species may show different sensitivities to different chemical groups present in the environment. This study evaluated species sensitivity, hazards, and risks of six classes of organic chemicals in the aquatic environment. None of the taxonomic groups were the most sensitive or tolerant to all chemicals, as one group sensitive to one class of chemicals might possess adaptations to other chemical groups. Polychlorinated biphenyls were generally the most toxic chemical group, followed by polybrominated diphenyl ethers, polycyclic aromatic hydrocarbons, and pharmaceuticals and personal care products, while per- and polyfluoroalkyl substances and phthalate esters were the less toxic chemical groups. The hazard of organic chemicals was closely related to their physicochemical properties, including hydrophobicity and molecular weight. It was shown that 20% of the evaluated chemicals exhibited medium or high ecological risks with the worst-case scenario in the Pearl River Estuary. This novel work represented a comprehensive comparison of chemical hazards and species sensitivity among different classes of organic chemicals, and the reported results herein have provided scientific evidence for ecological risk assessment and water quality management to protect aquatic ecosystems against organic chemicals.
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Organismos Acuáticos , Compuestos Orgánicos , Contaminantes Químicos del Agua , Animales , Organismos Acuáticos/efectos de los fármacos , Ecosistema , Monitoreo del Ambiente , Éteres Difenilos Halogenados/toxicidad , Compuestos Orgánicos/análisis , Compuestos Orgánicos/toxicidad , Bifenilos Policlorados/toxicidad , Hidrocarburos Policíclicos Aromáticos/toxicidad , Hidrocarburos Policíclicos Aromáticos/análisis , Medición de Riesgo , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidadRESUMEN
In 2013, the second outbreak of peste des petits ruminants occurred in China, leading to a spillover in more than 20 provinces and municipalities over the next few months. Thereafter, the epidemic situation was stable owing to strict prevention and control measures. In February 2024, several bharals and argali with suspected symptoms of PPR were discovered in Rutog country, Tibet Autonomous Region. Samples collected from these animals were delivered to our laboratory for diagnosis; the results of fluorescence quantitative reverse-transcription (RT) PCR indicated that all samples were positive for PPR viral RNA. The N and F gene fragments were amplified successfully via RT-PCR, and these results confirmed that these animals were infected with PPRV. A PPRV strain (subsequently named ChinaTibet2024) was sequenced, and its genome length was 15,954 nucleotides. A phylogenetic tree analysis using N and F genes and viral genomes showed that the ChinaTibet2024 genome was classified into lineage IV of the PRRV genotypes. The genome of the ChinaTibet2024 strain was found to be closely related to PPRVs isolated in China between 2013 and 2014. A base insertion and a base deletion were detected in the M gene 5' untranslated region. Results indicated that the prevalent PPRV strains in China did not show significant changes and that special attention should be paid to the surveillance of wild animals as an important part of PPR prevention and control.
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This study analyzed the effects of Trichoderma harzianum on the growth of continuous cropping Lagenaria siceraria and the physical and chemical properties of rhizosphere soil and microbial community structure, using Illumina Miseq (PE300) high-throughput sequencing technology along with physiological and biochemical detection. The results indicated that after applying T. harzianum, the growth of L. siceraria was significantly promoted, with increases in plant height, fresh weight, and dry weight of 21.42%, 24.5%, and 4.5%, respectively. The pH of the rhizosphere soil decreased from 7.78 to 7.51, while the electrical conductivity, the available phosphorus, the available potassium, and the total nitrogen were markedly higher compared to the control group and increased by 13.95%, 22.54%, 21.37%, and 16.41%, respectively. The activities of catalase and sucrase in the rhizosphere increased by 18.33% and 61.47%, and the content of soil organic carbon (SOC) increased by 27.39%, which indicated that T. harzianum could enhance soil enzyme activity and promotes the transformation of organic matter. The relative abundance of beneficial bacteria such as Pseudomonas increased, while the relative abundance of harmful fungi such as Fusarium and Podosphaera decreased significantly.
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During the summer of 2024, COVID-19 cases surged globally, driven by variants derived from JN.1 subvariants of SARS-CoV-2 that feature new mutations, particularly in the N-terminal domain (NTD) of the spike protein. In this study, we report on the neutralizing antibody (nAb) escape, infectivity, fusion, and stability of these subvariants-LB.1, KP.2.3, KP.3, and KP.3.1.1. Our findings demonstrate that all of these subvariants are highly evasive of nAbs elicited by the bivalent mRNA vaccine, the XBB.1.5 monovalent mumps virus-based vaccine, or from infections during the BA.2.86/JN.1 wave. This reduction in nAb titers is primarily driven by a single serine deletion (DelS31) in the NTD of the spike, leading to a distinct antigenic profile compared to the parental JN.1 and other variants. We also found that the DelS31 mutation decreases pseudovirus infectivity in CaLu-3 cells, which correlates with impaired cell-cell fusion. Additionally, the spike protein of DelS31 variants appears more conformationally stable, as indicated by reduced S1 shedding both with and without stimulation by soluble ACE2, and increased resistance to elevated temperatures. Molecular modeling suggests that the DelS31 mutation induces a conformational change that stabilizes the NTD and strengthens the NTD-Receptor-Binding Domain (RBD) interaction, thus favoring the down conformation of RBD and reducing accessibility to both the ACE2 receptor and certain nAbs. Additionally, the DelS31 mutation introduces an N-linked glycan modification at N30, which shields the underlying NTD region from antibody recognition. Our data highlight the critical role of NTD mutations in the spike protein for nAb evasion, stability, and viral infectivity, and suggest consideration of updating COVID-19 vaccines with antigens containing DelS31.
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To accurately assess the bioavailability risk of heavy metals (HMs) in a representative polymetallic mining region, we undertook an exhaustive analysis of Cu, Pb, Ni, Co, Cd, Zn, Mn, and Cr in soils from diverse land-use types, encompassing agricultural, forest, residential, and mining areas. We employed speciation analysis methods and a modified risk assessment approach to ascertain potential ecological threats posed by the HMs. Our findings reveal that both the total potential ecological risk and the modified bioavailability risks are most pronounced in the soil of the mining area. The modified bioavailability threats are primarily caused by Pb, Ni, Cd, and Co. Although the total potential ecological risk of Cu is high in the local soil, the predominance of its stable forms reduces its mobility, thereby mitigating its detrimental impact on the ecosystem. Additionally, medium modified bioavailability risks were identified in the peripheries of agricultural and forest areas, potentially attributable to geological processes and agricultural activities. Within the urban district, medium risks were observed in residential and mining areas, likely resulting from mining, metallurgy, industrial operations, and traffic-related activities. This study provides critical insights that can assist governmental authorities in devising targeted policies to alleviate health hazards associated with soils in polymetallic mining regions.
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Monitoreo del Ambiente , Metales Pesados , Minería , Contaminantes del Suelo , Suelo , Metales Pesados/análisis , Contaminantes del Suelo/análisis , Medición de Riesgo , Suelo/química , Agricultura , Disponibilidad BiológicaRESUMEN
BACKGROUND: The leucine-rich repeat-containing (LRRC) superfamily members are known for their significant roles in tumorigenesis and cellular proliferation. However, the specific regulatory role of LRRC45 in lung cancer remains unexplored. This study investigated the impact and underlying mechanisms of LRRC45 on the proliferative, migratory, and invasive capacities of lung adenocarcinoma (LUAD) cells, potentially identifying new targets for therapeutic intervention. MATERIAL AND METHODS: The importance of LRRC45 in lung cancer was analyzed using the online databases of UCSC Xena, TCGA, TISIDB, and UALCAN, whereas to detect target gene expression, we used the qRT-PCR, Western blot, and immunofluorescence confocal. The cell growth was monitored by colony formation assay and migration was examined by cell migration assay. Finally, a xenograft mouse tumor model using A549 âcells was used to explore the in vivo effect of LRRC45 in lung cancer. RESULTS: Inhibition of LRRC45 expression led to a notable decrease in proliferation, migration, and invasion of A549 and H1299 âcells. LRRC45 silencing significantly reduced the tumor volume and improved the mice's survival. Additionally, inhibition of LRRC45 expression dramatically suppressed c-MYC, Slug, MMP2, and MMP9 expression. Overexpression of c-MYC and/or Slug in the LRRC45-deficient cells can partially or totally restore the LRRC45 deficiency-suppressed growth. Moreover, the overexpression of MMP2 and/or MMP9 could partially or totally restore LRRC45 deficiency-reduced cell metastasis. CONCLUSIONS: LRRC45 could promote the proliferative, migrative, and invasive capacities of lung cancer cells by increasing c-MYC, Slug, MMP2, and MMP9 expression, indicating the therapeutic implications and potential significance of these pathways in lung cancer.
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Pulmonary cryptococcosis is a common complication in immunocompromised patients. In a mouse model of pulmonary cryptococcosis, Cryptococcus neoformans induces a type 2 immune response that is detrimental to host protection. Long non-coding RNAs (lncRNAs) have emerged as key players in the pathogenesis of infectious diseases. However, the roles and mechanisms of lncRNAs in fungal infection are largely elusive. In the present study, we aimed to explore the roles of LincR-PPP2R5C in pulmonary cryptococcosis. We observed an increase in the level of LincR-PPP2R5C in the lung tissues of C57BL/6J mice after tracheal infection with C. neoformans. Subsequently, we intratracheally infected LincR-PPP2R5C knockout (KO) mice and wild-type mice with C. neoformans. LincR-PPP2R5C deficiency mitigates C. neoformans infection, which can be demonstrated by extending survival time and decreasing fungal burden in the lung. In the lung tissues of infected LincR-PPP2R5C KO mice, there was a notable increase in the levels of type 2 cytokines [interleukin (IL)-4 and IL-5] and an increase in the number of neutrophils in both the lung tissue and bronchoalveolar lavage fluid. Mechanistically, the lack of LincR-PPP2R5C results in increased protein phosphatase 2A phosphorylation, thereby enhancing the fungicidal activity of neutrophils against Cryptococcus neoformans, with IL-4 playing a synergistic role in this process. Overall, LincR-PPP2R5C deficiency mitigated pulmonary cryptococcosis by increasing the fungicidal activity of neutrophils, which was associated with increased IL-4 levels. Our study presented specific evidence of the role of host-derived lncRNAs in the regulation of C. neoformans infection. IMPORTANCE: Pulmonary cryptococcosis is a human fungal disease caused by Cryptococcus neoformans, which is common not only in immunocompromised individuals but also in patients with normal immune function. Therefore, studying the control mechanisms of pulmonary cryptococcosis is highly important. Here, we demonstrated that the deletion of LincR-PPP2R5C leads to increased killing of C. neoformans by neutrophils, thereby reducing pulmonary cryptococcal infection. These findings will greatly enhance our understanding of the mechanisms by which lncRNAs regulate the pathogenesis of C. neoformans, facilitating the use of lncRNAs in pulmonary cryptococcosis therapy.
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Criptococosis , Cryptococcus neoformans , Interleucina-4 , Ratones Endogámicos C57BL , Ratones Noqueados , Neutrófilos , Animales , Neutrófilos/inmunología , Criptococosis/inmunología , Criptococosis/microbiología , Cryptococcus neoformans/inmunología , Cryptococcus neoformans/genética , Ratones , Interleucina-4/genética , Interleucina-4/inmunología , Interleucina-4/metabolismo , ARN Largo no Codificante/genética , Regulación hacia Arriba , Enfermedades Pulmonares Fúngicas/inmunología , Enfermedades Pulmonares Fúngicas/microbiología , Enfermedades Pulmonares Fúngicas/genética , Pulmón/inmunología , Pulmón/microbiología , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: The rate of incidence of metabolic dysfunction-related fatty liver disease (MAFLD) has rapidly increased globally in recent years, but early diagnosis is still a challenge. The purpose of this systematic review and meta-analysis is to identify visfatin for early diagnosis of MAFLD. METHODS: We strictly adhered to the relevant requirements of Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The systematic search was conducted in 7 sources (PubMed, Embase, Cochrane Library, CNKI, Wanfang, CBM, and ClinicalTrials.gov) until February 2024. The meta-analysis was performed using Stata 12. Outcomes were expressed in the form of standardized mean difference (SMD) and 95% confidence interval and were analyzed using meta-analysis. RESULTS: The results showed that there was no significant difference in circulating visfatin levels between patients with MAFLD and controls (SMDâ =â 0.13 [-0.34, 0.60]). However, the outcomes indicated that the level of circulating visfatin was significantly higher in MAFLD patients in the Middle Eastern subgroup (SMDâ =â 0.45 [0.05, 0.85]) and in the obese patient subgroup (SMDâ =â 1.05 [0.18, 1.92]). No publication bias was detected, and sensitivity analysis confirmed the stability of the outcomes. CONCLUSION: The serum visfatin levels of MAFLD patients did not differ significantly from those of controls. However, visfatin concentrations in serum were statistically higher within Middle Eastern or obese MAFLD patients compared to controls. There is a need for further research to investigate visfatin's potential as a biomarker for MAFLD.