Plasmodium yoelii surface-related antigen (PySRA) modulates the host pro-inflammatory responses via binding to CD68 on macrophage membrane.

Malaria, one of the major infectious diseases in the world, is caused by the Plasmodium parasite. Plasmodium antigens could modulate the inflammatory response by binding to macrophage membrane receptors. As an export protein on the infected erythrocyte membrane, Plasmodium surface-related antigen (SRA) participates in the erythrocyte invasion and regulates the immune response of the host. This study found that the F2 segment of P. yoelii SRA activated downstream MAPK and NF-κB signaling pathways by binding to CD68 on the surface of the macrophage membrane and regulating the inflammatory response. The anti-PySRA-F2 antibody can protect mice against P. yoelii, and the pro-inflammatory responses such as IL-1ß, TNF-α, and IL-6 after infection with P. yoelii are attenuated. These findings will be helpful for understanding the involvement of the pathogenic mechanism of malaria with the exported protein SRA.

Bibliometric and visualized analysis of applying tumor markers in lung cancer diagnosis from 2000 to 2022.

Background: Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Tumor marker (TM) detection can indicate the existence and growth of a tumor and has therefore been used extensively for diagnosing LC. Here, we conducted a bibliometric analysis to examine TM-related publications for LC diagnosis to illustrate the current state and future trends of this field, as well as to identify additional promising TMs with high sensitivity. Methods: Publications regarding TMs in LC diagnosis were downloaded from the Web of Science Core Collection. CiteSpace was applied to perform a bibliometric analysis of journals, cocitation authors, keywords, and references related to this field. VOSviewer was used to generate concise diagrams about countries, institutions, authors, and keywords. Changes in the TM research frontier were analyzed through citation burst detection. Results: A total of 990 studies were analyzed in this work. The collaboration network analysis revealed that the People's Republic of China, Yonsei University, and Molina R were the most productive country, institution, and scholar, respectively. Additionally, Molina R was the author with the most citations. The National Natural Science Foundation of China was the largest funding source. "Carcinoembryonic antigen (CEA) as tumor marker in lung cancer" was the top reference with the most citations, Lung Cancer was the core journal, and "serum tumor marker" experienced a citation burst over the past 5 years. Conclusion: This bibliometric analysis of TMs in LC diagnosis presents the current trends and frontiers in this field. We summarized the research status of this field and the methods to improve the diagnostic efficacy of traditional serum TMs, as well as provided new directions and ideas for improving the LC clinical detection rate. Priority should be given to the transformation of computer-assisted diagnostic technology for clinical applications. In addition, circulating tumor cells, exosomes, and microRNAs were the current most cutting-edge TMs.

The value of serum TRAP1 in diagnosing small cell lung cancer and tumor immunity.

This study set out to investigate the clinical significance of serum tumor necrosis factor receptor-associated protein 1 (TRAP1) in diagnosing small cell lung cancer (SCLC) with different clinical stages, and to compare the diagnostic efficiency with neuron-specific enolase (NSE), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). Besides, to analyze the role of serum TRAP1 in tumor immunity. A total of 91 patients with SCLC, 99 patients with non-small cell lung cancer (NSCLC), 102 patients with pulmonary nodules (PN), and 75 healthy people were included. The concentrations of serum TRAP1 was detected by enzyme-linked immunosorbent assay (ELISA). NSE, CEA, and CA19-9 were detected by chemiluminescence. The results showed that level of TRAP1 in Group SCLC was lower than other three groups (P < 0.01), whereas NSE in SCLC was significantly higher than the others (P < 0.01), and the levels of CEA and CA19-9 were higher than healthy people and PN patients (P < 0.01). There was a significant difference in TRAP1 levels between patients with limited-stage disease SCLC (LD-SCLC) and extensive-stage disease SCLC (ED-SCLC) (P < 0.0001). The sensitivity and specificity of TRAP1 in diagnosing LD-SCLC were 0.964 and 0.560, respectively, and the area under the curve (AUC) was 0.819. The sensitivity and specificity in diagnosing ED-SCLC were 0.810 and 0.868, respectively, and the AUC was 0.933, which showed high diagnostic value. The AUC of these two groups can be increased to 0.946 and 0.947 in combination of four biomarkers, effectively improving the diagnosis rate of SCLC. Our findings have revealed that serum TRAP1 has high diagnostic value for SCLC and high diagnostic sensitivity for LD-SCLC. It is a potential biomarker for SCLC. Combined detection can effectively improve the diagnosis rate of SCLC. TRAP1 may be secreted into the circulation by mature immune cells and participates in tumor immunity as a carrier of tumor antigens.

Case report: Kikuchi-Fujimoto disease: unveiling a case of recurrent fever and enlarged cervical lymph nodes in a young female patient with a literature review of the immune mechanism.

The inflammatory response to viral infection is an important component of the antiviral response, a process that involves the activation and proliferation of CD8+ T, CD4+ T, and dendritic cells; thus, viral infection disrupts the immune homeostasis of the organism, leading to an increased release of inflammatory factors. Kikuchi-Fujimoto disease (KFD) is an inflammatory self-limited disorder of unknown etiology, and it is generally believed that the pathogenesis of this disease includes two aspects: viral infection and autoimmune response. Various immune cells, such as CD8+ T lymphocytes, CD4+ T lymphocytes, and CD123+ plasmacytoid dendritic cells, as well as the cytokines they induce and secrete, such as interferons, interleukins, and tumor necrosis factors, play a crucial role in the pathogenesis of KFD. In this article, we present a case study of a young female patient from China who exhibited typical symptoms of lymph node inflammation and fever. The diagnosis of KFD was confirmed through a lymph node biopsy. She presented with elevated ESR, IL-6, and IFN-γ. Viral markers showed elevated IgG and IgM of cytomegalovirus (CMV) and elevated IgG of Epstein-Barr virus (EBV), while changes occurred in the CD4+ T and CD8+ T cell counts. Eventually, the patient achieved disease relief through steroid treatment. Based on these findings, we conducted a comprehensive review of the involvement of viral infection-induced inflammatory response processes and autoimmunity in the pathogenesis of Kikuchi-Fujimoto disease.

Immunogenicity Analysis of the Recombinant Plasmodium falciparum Surface-Related Antigen in Mice.

Plasmodium falciparum, mainly distributed in tropical and subtropical regions of the world, has received widespread attention owing to its severity. As a novel protein, P. falciparum surface-related antigen (PfSRA) has the structural and functional characteristics to be considered as a malaria vaccine candidate; however, limited information is available on its immunogenicity. Here, we expressed three fragments of recombinant PfSRA in an Escherichia coli system and further analyzed its immunogenicity. The results showed that rPfSRA-immunized mice produced specific antibodies with high endpoint titers (1:10,000 to 1:5,120,000) and affinity antibodies (i.e., rPfSRA-F1a (97.70%), rPfSRA-F2a (69.62%), and rPfSRA-F3a (91.87%)). In addition, the sera of immunized mice recognized both the native PfSRA and recombinant PfSRA, the rPfSRA antibodies inhibited the invasion of P. falciparum into the erythrocytes, and they were dose-dependent in vitro. This study confirmed PfSRA could be immunogenic, especially the F1a at the conserved region N-terminal and provided further support for it as a vaccine candidate against P.falciparum.

USP16-mediated histone H2A lysine-119 deubiquitination during oocyte maturation is a prerequisite for zygotic genome activation.

Maternal-to-zygotic transition (MZT) is the first and key step in the control of animal development and intimately related to changes in chromatin structure and histone modifications. H2AK119ub1, an important epigenetic modification in regulating chromatin configuration and function, is primarily catalyzed by PRC1 and contributes to resistance to transcriptional reprogramming in mouse embryos. In this study, the genome-wide dynamic distribution of H2AK119ub1 during MZT in mice was investigated using chromosome immunoprecipitation and sequencing. The results indicated that H2AK119ub1 accumulated in fully grown oocytes and was enriched at the TSSs of maternal genes, but was promptly declined after meiotic resumption at genome-wide including the TSSs of early zygotic genes, by a previously unidentified mechanism. Genetic evidences indicated that ubiquitin-specific peptidase 16 (USP16) is the major deubiquitinase for H2AK119ub1 in mouse oocytes. Conditional knockout of Usp16 in oocytes did not impair their survival, growth, or meiotic maturation. However, oocytes lacking USP16 have defects when undergoing zygotic genome activation or gaining developmental competence after fertilization, potentially associated with high levels of maternal H2AK119ub1 deposition on the zygotic genomes. Taken together, H2AK119ub1 level is declined during oocyte maturation by an USP16-dependent mechanism, which ensures zygotic genome reprogramming and transcriptional activation of essential early zygotic genes.

Malic enzyme 2 promotes the progression of hepatocellular carcinoma via increasing triglyceride production.

The incidence and mortality of hepatocellular carcinoma (HCC) are gradually increasing during the past years. Recently, some studies have reported that malic enzyme (ME) plays an important role in cancer development, while the involvement of ME2 in HCC remains still undetermined. Here, we demonstrated that ME2 played an oncogenic role in HCC. ME2 was overexpressed in HCC tissues. TCGA database showed that the ME2 transcript level was inversely associated with the survival of HCC patients. Loss-of-function and gain-of-function assays showed that ME2 promoted HCC cell growth and migration. Furthermore, the xenografted tumorigenesis of MHCC97H cells was retarded by ME2 knockdown. ME2 silencing also suppressed the cell cycle process and induced apoptosis. Mechanistically, ME2 potentiated triglyceride synthesis, inhibition of which suppressed the proliferation and migration. We propose that ME2 promotes HCC progression by increasing triglyceride production.

Role of CxxC-finger protein 1 in establishing mouse oocyte epigenetic landscapes.

During oogenesis, oocytes gain competence and subsequently undergo meiotic maturation and prepare for embryonic development; trimethylated histone H3 on lysine-4 (H3K4me3) mediates a wide range of nuclear events during these processes. Oocyte-specific knockout of CxxC-finger protein 1 (CXXC1, also known as CFP1) impairs H3K4me3 accumulation and causes changes in chromatin configurations. This study investigated the changes in genomic H3K4me3 landscapes in oocytes with Cxxc1 knockout and the effects on other epigenetic factors such as the DNA methylation, H3K27me3, H2AK119ub1 and H3K36me3. H3K4me3 is overall decreased after knocking out Cxxc1, including both the promoter region and the gene body. CXXC1 and MLL2, which is another histone H3 methyltransferase, have nonoverlapping roles in mediating H3K4 trimethylation during oogenesis. Cxxc1 deletion caused a decrease in DNA methylation levels and affected H3K27me3 and H2AK119ub1 distributions, particularly at regions with high DNA methylation levels. The changes in epigenetic networks implicated by Cxxc1 deletion were correlated with the transcriptional changes in genes in the corresponding genomic regions. This study elucidates the epigenetic changes underlying the phenotypes and molecular defects in oocytes with deleted Cxxc1 and highlights the role of CXXC1 in orchestrating multiple factors that are involved in establishing the appropriate epigenetic states of maternal genome.

State transformation-based adaptive tracking control for a class of nonlinear systems with time-varying state constraints.

It is meaningful to study the control problems of nonlinear systems with uncertain parameters and external disturbances, especially for those subject to state constraints. In this paper, a state transformation approach is proposed to address time-varying asymmetric state constraints. By this state transformation, the state constrained problem is transformed into the boundedness problem of the transformed function. When the initial states are in the constrained region, the state constraints can be guaranteed as long as the boundedness of the transformed functions are guaranteed. Compared with the barrier Lyapunov function (BLF) approach, it successfully removes the feasibility test from virtual controllers, and thus broadens its application scope. In addition, for the parametric uncertainties and external disturbances exist in the system simultaneously, the tuning function and the adaptive laws for the upper bounds of disturbances are designed to help realize the control performance of the system. Consequently, a novel tuning function based adaptive backstepping control scheme is given. The designed controller ensures the error signals converge to a small neighbourhood of zero and the asymmetric time-varying constraints on system states are maintained for all the time. Finally, simulation results are given to illustrate the efficacy of the presented control scheme.

OsNSUN2-Mediated 5-Methylcytosine mRNA Modification Enhances Rice Adaptation to High Temperature.

Extreme weather events can cause heat stress that decreases crop production. Recent studies have demonstrated that protein degradation and rRNA homeostasis as well as transcription factors are involved in the thermoresponse in plants. However, how RNA modifications contribute to temperature stress response in plant remains largely unknown. Herein, we identified OsNSUN2 as an RNA 5-methylcytosine (m5C) methyltransferase in rice. osnsun2 mutant displayed severe temperature- and light-dependent lesion-mimic phenotypes and heat-stress hypersensitivity. Heat stress enhanced the OsNSUN2-dependent m5C modification of mRNAs involved in photosynthesis and detoxification systems, such as ß-OsLCY, OsHO2, OsPAL1, and OsGLYI4, which increased protein synthesis. Furthermore, the photosystem of osnsun2 mutant was vulnerable to high ambient temperature and failed to undergo repair under tolerable heat stress. Thus, OsNSUN2 mutation reduced photosynthesis efficiency and accumulated excessive reactive oxygen species upon heat treatment. Our findings demonstrate an important mechanism of mRNA m5C-dependent heat acclimation in rice.

Asymptotic tracking control for time-delay nonlinear systems with parametric uncertainties and full state constraints.

This article concentrates on an adaptive backstepping control design of time-delay strict-feedback uncertain nonlinear systems subject to full state constraints. The tan-type barrier Lyapunov functions (tBLFs) and Lyapunov-Krasovskii function are united together, which successfully get over the difficulties of system design in which the first function is involved to ensure full state constraints satisfaction and the second is established to eliminate the effect of delayed states. By employing a new control scheme, asymptotic tracking performance is arrived, and all the states remain in the desirable regions for all the system running time. Meanwhile, the boundedness of all signals of the closed-loop system is guaranteed. The performance of the control scheme is illustrated through a class of single degree of freedom (1-DOF) time-delay electrostatic microactuator systems.

Mammalian nucleolar protein DCAF13 is essential for ovarian follicle maintenance and oocyte growth by mediating rRNA processing.

During mammalian oocyte growth, chromatin configuration transition from the nonsurrounded nucleolus (NSN) to surrounded nucleolus (SN) type plays a key role in the regulation of gene expression and acquisition of meiotic and developmental competence by the oocyte. Nonetheless, the mechanism underlying chromatin configuration maturation in oocytes is poorly understood. Here we show that nucleolar protein DCAF13 is an important component of the ribosomal RNA (rRNA)-processing complex and is essential for oocyte NSN-SN transition in mice. A conditional knockout of Dcaf13 in oocytes led to the arrest of oocyte development in the NSN configuration, follicular atresia, premature ovarian failure, and female sterility. The DCAF13 deficiency resulted in pre-rRNA accumulation in oocytes, whereas the total mRNA level was not altered. Further exploration showed that DCAF13 participated in the 18S rRNA processing in growing oocytes. The lack of 18S rRNA because of DCAF13 deletion caused a ribosome assembly disorder and then reduced global protein synthesis. DCAF13 interacted with a protein of the core box C/D ribonucleoprotein, fibrillarin, i.e., a factor of early pre-rRNA processing. When fibrillarin was knocked down in the oocytes from primary follicles, follicle development was inhibited as well, indicating that an rRNA processing defect in the oocyte indeed stunts chromatin configuration transition and follicle development. Taken together, these results elucidated the in vivo function of novel nucleolar protein DCAF13 in maintaining mammalian oogenesis.

CNOT6L couples the selective degradation of maternal transcripts to meiotic cell cycle progression in mouse oocyte.

Meiotic resumption-coupled degradation of maternal transcripts occurs during oocyte maturation in the absence of mRNA transcription. The CCR4-NOT complex has been identified as the main eukaryotic mRNA deadenylase. In vivo functional and mechanistic information regarding its multiple subunits remains insufficient. Cnot6l, one of four genes encoding CCR4-NOT catalytic subunits, is preferentially expressed in mouse oocytes. Genetic deletion of Cnot6l impaired deadenylation and degradation of a subset of maternal mRNAs during oocyte maturation. Overtranslation of these undegraded mRNAs caused microtubule-chromosome organization defects, which led to activation of spindle assembly checkpoint and meiotic cell cycle arrest at prometaphase. Consequently, Cnot6l-/- female mice were severely subfertile. The function of CNOT6L in maturing oocytes is mediated by RNA-binding protein ZFP36L2, not maternal-to-zygotic transition licensing factor BTG4, which interacts with catalytic subunits CNOT7 and CNOT8 of CCR4-NOT Thus, recruitment of different adaptors by different catalytic subunits ensures stage-specific degradation of maternal mRNAs by CCR4-NOT This study provides the first direct genetic evidence that CCR4-NOT-dependent and particularly CNOT6L-dependent decay of selective maternal mRNAs is a prerequisite for meiotic maturation of oocytes.

[Analysis on transfer rate change of heavy metal in decoction and precipitation of Curcuma phaeocaulis before and after processing with vinegar based on ICP-MS].

Chinese herbs are mostly used to make decoction, which would form precipitation after standing for cooling and abandoned by patients. Processing with vinegar can change the property of the herbal pieces, such as the transfer rate of heavy metal into decoction. To analyze the transfer rate change of heavy metal in the decoction and precipitation of Curcuma phaeocaulis before and after processing with vinegar, inductively coupled plasma mass spectrometry (ICP-MS) was used to establish the determination method on five heavy metals in C. phaeocaulis, including Copper (Cu), arsenic (As), chromium (Cd), lead (Pb), mercury (Hg), using microwave to digest the samples, indium (In) as the internal standard, and national level standard material tea leaves GBW10016 (GSB-7 tea) as the quality control standard material. Then, the content of five heavy metals in the herbal pieces, decoction and five heavy metals of 6 representative batches of C. phaeocaulis and their vinegar-processing products was determinated. After computation, the transfer rates of heavy metals in the decoction and precipitation of C. phaeocaulis Val. before and after the processing with vinegar were obtained. The results showed that, after the processing with vinegar, total transfer rate of Pb and Hg was decreased significantly; total transfer rate of Cd and Cu was slightly decreased; total transfer rate of As was slightly increased, however heavy metals in all the precipitation were decreased. The results indicated that processing with vinegar had certain influence on heavy metal transfer rate, with certain synergistic and attenuated effect.

[Study on composition of essential oils in three different origins' Curcumae Rhizoma by AMDIS and retention index].

To compare the differences of essential oils extracted from Curcumae Rhizoma with different origins. The TIC of the essential oils of Curcumae Rhizoma from three different origins recorded by CP(2010) , were investigated by GC-MS combined with automated mass spectral deconvolution and identification system(AMDIS),steps as follow： firstly, overlapped peaks were resolved by AMDIS,secondly, NIST11.L standard MS spectral database combined with retention index were used to assist qualitative analysis, thirdly, the peak area of each split peak were determined by choosing the characteristic fragment ion peak, finally, the relative percentage contents of each compounds were determined through peak area normalization method. The results showed that the components of the essential oils of Curcumae Rhizoma from three origins were different from each other at various degree. In conclusion, the types and content of essential oils could be an indicator to evaluate the quality of Curcumae Rhizoma from different origins and its geoherbalism.

Triterpenoids and Flavonoids from the Leaves of Astragalus membranaceus and Their Inhibitory Effects on Nitric Oxide Production.

Four new cycloartane triterpenes, named huangqiyegenins V and VI and huangqiyenins K and L (1-4, resp.), together with nine known triterpenoids, 5-13, and eight flavonoids, 14-21, were isolated from a 70%-EtOH extract of Astragalus membranaceus leaves. The structures of the new compounds were elucidated by detailed spectroscopic analyses, and the compounds were identified as (9ß,11α,16ß,20R,24S)-11,16,25-trihydroxy-20,24-epoxy-9,19-cyclolanostane-3,6-dione (1), (9ß,16ß,24S)-16,24,25-trihydroxy-9,19-cyclolanostane-3,6-dione (2), (3ß,6α,9ß,16ß,20R,24R)-16,25-dihydroxy-3-(ß-D-xylopyranosyloxy)-20,24-epoxy-9,19-cyclolanostan-6-yl acetate (3), and (3ß,6α,9ß,16ß,24E)-26-(ß-D-glucopyranosyloxy)-16-hydroxy-3-(ß-D-xylopyranosyloxy)-9,19-cyclolanost-24-en-6-yl acetate (4). All isolated compounds were evaluated for their inhibitory activities against LPS-induced NO production in RAW264.7 macrophage cells. Compounds 1-3, 14, 15, and 18 exhibited strong inhibition on LPS-induced NO release by macrophages with IC50 values of 14.4-27.1 µM.

[Changing rules study of effective components of Glycyrrhizae Radix et Rhizoma before and after compatibilities in Sini decoction].

The change of the effective components (liquiritin, glycyrrhizic acid, liquiritigenin, isoliquiritigenin) contents of Glycyrrhizae Radix et Rhizoma (GRR) before and after compatibilities in Sini decoction was studied in this paper. Taking single GRR decoction, GRR-Aconiti Lateralis Radix Praeparata (ALRP) decoction, GRR-Zingiberis Rhizoma (ZR) decoction and Sini decoction as test samples, the contents changing of the four effective components of GRR were measured by HPLC. The results showed that the contents of the four effective components of GRR in the single GRR decoction was higher than that in other samples, and the sequence was single GRR decoction > GRR-ZR decoction > GRR-ALRP decoction > Sini decoction. The contents of liquiritin were 11.18, 9.89, 9.67, 9.17 mg · g(-1); the contents of glycyrrhizic acid were 20.76, 15.58, 11.30, 8.52 mg · g(-1); the contents of liquiritigenin were 0.66, 0.57, 0.45, 0.24 mg · g(-1); the contents of isoliquiritigenin were 0.14, 0.07, 0.03, 0.01 mg · g(-1). Therefore, the effective components of GRR decreased obviously after GRR compatibility with ZR providing scientific basis for GRR relieving the strong nature of ZR. The effective components of GRR decreased sharply after GRR compatibility with ALRP providing scientific support for the material foundation research of GRR reducing the toxicity of ALRP. The effective components of GRR decreased further in Sini decoction indicating that the three medicines in Sini decoction were interactional, which reflecting the scientific connotation of the mutual-restraint/mutual-detoxication, mutual-promotion/mutual-assistance compatibilities in Sini decoction.

Initial Characterization of Osteoblast Differentiation and Loss of RUNX2 Stability in the Newly Established SK11 Human Embryonic Stem Cell-Derived Cell Line.

We describe a novel model for investigation of genetically normal human osteoblasts in culture. SK11 is a clonal progenitor cell line derived from human embryonic stem cells. Initially selected based on the expression of chondrogenic markers when differentiated in micromass culture, SK11 cells display typical mRNA expression patterns of bone phenotypic genes under osteogenic conditions. These include osterix, α1(I) collagen, alkaline phosphatase, osteonectin, osteopontin, and osteocalcin. Similar to well-characterized murine osteoblast cultures, the osteoblast master regulator RUNX2 was present during the first few days after plating, but the protein disappeared during the first week of culture. Loss of RUNX2 expression is considered an important regulatory feature for osteoblast maturation. Indeed, following ∼2 weeks of differentiation, SK11 cultures exhibited robust calcium deposition, evidenced by alizarin red staining. We also introduced a lentiviral vector encoding doxycycline (dox)-inducible FLAG-tagged RUNX2 into SK11 cells. Dox-mediated enhancement of RUNX2 expression resulted in accelerated mineralization, which was further increased by co-treatment with BMP-2. Like the endogenous RUNX2, expression of the virally coded FLAG-RUNX2 was lost during the first week of culture despite persistent dox treatment. By following RUNX2 decay after dox withdrawal from day-5 versus day-3 cultures, we demonstrated a developmentally regulated decrease in RUNX2 stability. Availability of culture models for molecular investigation of genetically normal human osteoblasts is important because differences between murine and human osteoblasts, demonstrated here by the regulation of matrix Gla Protein, may have significant biomedical implications.