Gaucher Disease Coexisting with Cytomegalovirus Infection: A Rare Presentation in an Infant.

BACKGROUND Gaucher disease is a rare autosomal recessive disorder characterized by mutations in the glucocerebrosidase gene, resulting in deficient enzyme activity and accumulation of glucocerebroside in macrophages, which leads to pathological changes in affected organs. The atypical clinical manifestations of Gaucher disease often contribute to delays in diagnosis and treatment. CASE REPORT We present the case of a 4-month-old female infant admitted to the Department of Pediatrics with progressive hepatosplenomegaly since birth. Concurrently, she had cytomegalovirus infection and sensory neurological hearing loss. Gaucher disease diagnosis was confirmed through whole-exome sequencing and validated by a glucocerebrosidase activity test, revealing the mutation site as c.1448T>C. This report outlines the differential diagnosis process for Gaucher disease in this infant before confirmation, contributing valuable insights for early diagnosis. CONCLUSIONS Our case underscores the challenge of diagnosing Gaucher disease due to its atypical presentation. The coexistence of cytomegalovirus infection complicates the clinical picture, emphasizing the need for careful differential diagnosis. Unfortunately, delayed diagnosis is all too common in rare diseases like Gaucher disease, even when the clinical presentation is seemingly typical. This highlights the need for increased awareness and education within the medical community to facilitate early recognition, which is essential for prompt intervention and improved outcomes. This report contributes valuable clinical and genetic information, aiming to enhance awareness and deepen the understanding of Gaucher disease in infants, particularly those with concurrent infections.

New Phenol Derivatives from the Haima Cold Seep-Derived Fungus Aspergillus subversicolor CYH-17.

Seven new phenol derivatives, subversins A-E (1-5), subversic acid A (6) and epi-wortmannine G (7); one new natural product, 4-hydroxy-7-methoxyphthalide (8); and five known compounds (9-13) were isolated from the fungus Aspergillus subversicolor CYH-17 collected from the Haima cold seep. The structures and absolute configurations of these compounds were determined via NMR, MS, optical rotation, electronic circular dichroism (ECD) calculation, X-ray diffraction analysis and comparison with the literature. Compounds 2 and 5 were two pairs of enantiomers. All compounds were tested for their α-glucosidase and acetylcholinesterase (AChE) inhibitory activity, antioxidant activity and antibacterial activity, but no obvious activity was observed among these studied compounds.

Glycolysis related lncRNA SNHG3 / miR-139-5p / PKM2 axis promotes castration-resistant prostate cancer (CRPC) development and enzalutamide resistance.

Although androgen deprivation therapy (ADT) by the anti-androgen drug enzalutamide (Enz) may improve the survival level of patients with castration-resistant prostate cancer (CRPC), most patients may eventually fail due to the acquired resistance. The reprogramming of glucose metabolism is one type of the paramount hallmarks of cancers. PKM2 (Pyruvate kinase isozyme typeM2) is a speed-limiting enzyme in the glycolytic mechanism, and has high expression in a variety of cancers. Emerging evidence has unveiled that microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have impact on tumor development and therapeutic efficacy by regulating PKM2 expression. Herein, we found that lncRNA SNHG3, a highly expressed lncRNA in CRPC via bioinformatics analysis, promoted the invasive ability and the Enz resistance of the PCa cells. KEGG pathway enrichment analysis indicated that glucose metabolic process was tightly correlated with lncRNA SNHG3 level, suggesting lncRNA SNHG3 may affect glucose metabolism. Indeed, glucose uptake and lactate content determinations confirmed that lncRNA SNHG3 promoted the process of glycolysis. Mechanistic dissection demonstrated that lncRNA SNHG3 facilitated the advance of CRPC by adjusting the expression of PKM2. Further explorations unraveled the role of lncRNA SNHG3 as a 'sponge' of miR-139-5p and released its binding with PKM2 mRNA, leading to PKM2 up-regulation. Together, Our studies suggest that lncRNA SNHG3 / miR-139-5p / PKM2 pathway promotes the development of CRPC via regulating glycolysis process and provides valuable insight into a novel therapeutic approach for the disordered disease.

8R-methoxy-9R-hydroxyl-fumitremorgin C, a new diketopiperazine alkaloid from Haima cold seep-derived fungus Aspergillus fumigatus CYH-5.

One novel diketopiperazine derivative 8R-methoxy-9R-hydroxyl-fumitremorgin C (1), together with twelve known compounds, was separated from the fungus Aspergillus fumigatus CYH-5 collected from Haima cold seep. The structures of the compounds were identified by NMR, MS, optical rotation, hydrolysis reaction and comparing with literatures. Among them, compounds 10 and 11 exhibited inhibitory effect against bacteria. Compound 11 showed inhibitory activity on α-glucosidase and compound 8 displayed acetylcholinesterase (AchE) inhibitory activity.

A bibliometric analysis on discovering anti-quorum sensing agents against clinically relevant pathogens: current status, development, and future directions.

Background: Quorum sensing is bacteria's ability to communicate and regulate their behavior based on population density. Anti-quorum sensing agents (anti-QSA) is promising strategy to treat resistant infections, as well as reduce selective pressure that leads to antibiotic resistance of clinically relevant pathogens. This study analyzes the output, hotspots, and trends of research in the field of anti-QSA against clinically relevant pathogens. Methods: The literature on anti-QSA from the Web of Science Core Collection database was retrieved and analyzed. Tools such as CiteSpace and Alluvial Generator were used to visualize and interpret the data. Results: From 1998 to 2023, the number of publications related to anti-QAS research increased rapidly, with a total of 1,743 articles and reviews published in 558 journals. The United States was the largest contributor and the most influential country, with an H-index of 88, higher than other countries. Williams was the most productive author, and Hoiby N was the most cited author. Frontiers in Microbiology was the most prolific and the most cited journal. Burst detection indicated that the main frontier disciplines shifted from MICROBIOLOGY, CLINICAL, MOLECULAR BIOLOGY, and other biomedicine-related fields to FOOD, MATERIALS, NATURAL PRODUCTS, and MULTIDISCIPLINARY. In the whole research history, the strongest burst keyword was cystic-fibrosis patients, and the strongest burst reference was Lee and Zhang (2015). In the latest period (burst until 2023), the strongest burst keyword was silver nanoparticle, and the strongest burst reference was Whiteley et al. (2017). The co-citation network revealed that the most important interest and research direction was anti-biofilm/anti-virulence drug development, and timeline analysis suggested that this direction is also the most active. The key concepts alluvial flow visualization revealed seven terms with the longest time span and lasting until now, namely Escherichia coli, virulence, Pseudomonas aeruginosa, virulence factor, bacterial biofilm, gene expression, quorum sensing. Comprehensive analysis shows that nanomaterials, marine natural products, and artificial intelligence (AI) may become hotspots in the future. Conclusion: This bibliometric study reveals the current status and trends of anti-QSA research and may assist researchers in identifying hot topics and exploring new research directions.

[Clinical and genetic analysis of a case of Turner syndrome with rapidly progressive puberty and a literature review].

OBJECTIVE: To investigate the clinical features and genetic etiology of a case of Turner syndrome (TS) with rapidly progressive puberty. METHODS: A child who had presented at the Pediatric Endocrinology Clinic of the Shenzhen People's Hospital on January 19, 2022 was selected as the study subject. Clinical data of the child were collected. Peripheral blood sample of the child was subjected to chromosomal microarray analysis (CMA) and multiple ligation-dependent probe amplification (MLPA). Previous studies related to TS with rapidly progressive puberty were retrieved from the CNKI, Wanfang Data Knowledge Service Platform, Boku, CBMdisc and PubMed databases with Turner syndrome and rapidly progressive puberty as the keywords. The duration for literature retrieval was set from November 9, 2021 to May 31, 2022. The clinical characteristics and karyotypes of the children were summarized. RESULTS: The child was a 13-year-and-2-month-old female. She was found to have breast development at 9, short stature at 10, and menarche at 11. At 13, she was found to have a 46,X,i(X)(q10) karyotype. At the time of admission, she had a height of 143.5 cm (< P3), with 6 ~ 8 nevi over her face and right clavicle. She also had bilateral simian creases but no saddle nasal bridge, neck webbing, cubitus valgus, shield chest or widened breast distance. She had menstruated for over 2 years, and her bone age has reached 15.6 years. CMA revealed that she had a 58.06 Mb deletion in the Xp22.33p11.1 region and a 94.49 Mb duplication in the Xp11.1q28 region. MLPA has confirmed monosomy Xp and trisomy Xq. A total of 13 reports were retrieved from the CNKI, Wanfang Data Knowledge Service Platform, Boku, CBMdisc and PubMed databases, which had included 14 similar cases. Analysis of the 15 children suggested that their main clinical manifestations have included short stature and growth retardation, and their chromosomal karyotypes were mainly mosaicisms. CONCLUSION: The main clinical manifestations of TS with rapidly progressive puberty are short stature and growth retardation. Deletion in the Xp22.33p11.1 and duplication in the Xp11.1q28 probably underlay the TS with rapid progression in this child, which has provided a reference for clinical diagnosis and genetic counselling for her.

Identification of a novel amphioxus leucine-rich repeat receptor involved in phagocytosis reveals a role for Slit2-N-type LRR in bacterial elimination.

The basal chordate amphioxus is a model for tracing the origin and evolution of vertebrate immunity. To explore the evolution of immunoreceptor signaling pathways, we searched the associated receptors of the amphioxus Branchiostoma belcheri (Bb) homolog of immunoreceptor signaling adaptor protein Grb2. Mass-spectrum analysis of BbGrb2 immunoprecipitates from B. belcheri intestine lysates revealed a folate receptor (FR) domain- and leucine-rich repeat (LRR)-containing protein (FrLRR). Sequence and structural analysis showed that FrLRR is a membrane protein with a predicted curved solenoid structure. The N-terminal Fr domain contains very few folate-binding sites; the following LRR region is a Slit2-type LRR, and a GPI-anchored site was predicted at the C-terminus. RT-PCR analysis showed FrLRR is a transcription-mediated fusion gene of BbFR-like and BbSlit2-N-like genes. Genomic DNA structure analysis implied the B. belcheri FrLRR gene locus and the corresponding locus in Branchiostoma floridae might be generated by exon shuffling of a Slit2-N-like gene into an FR gene. RT-qPCR, immunostaining, and immunoblot results showed that FrLRR was primarily distributed in B. belcheri intestinal tissue. We further demonstrated that FrLRR localized to the cell membrane and lysosomes. Functionally, FrLRR mediated and promoted bacteria-binding and phagocytosis, and FrLRR antibody blocking or Grb2 knockdown inhibited FrLRR-mediated phagocytosis. Interestingly, we found that human Slit2-N (hSlit2-N) also mediated direct bacteria-binding and phagocytosis which was inhibited by Slit2-N antibody blocking or Grb2 knockdown. Together, these results indicate FrLRR and hSlit2-N may function as phagocytotic-receptors to promote phagocytosis through Grb2, implying the Slit2-N-type-LRR-containing proteins play a role in bacterial binding and elimination.

Investigation on Metabolites in Structure and Biosynthesis from the Deep-Sea Sediment-Derived Actinomycete Janibacter sp. SCSIO 52865.

For exploring structurally diverse metabolites and uniquely metabolic mechanisms, we systematically investigated the chemical constituents and putative biosynthesis of Janibacter sp. SCSIO 52865 derived from the deep-sea sediment based on the OSMAC strategy, molecular networking tool, in combination with bioinformatic analysis. As a result, one new diketopiperazine (1), along with seven known cyclodipeptides (2-8), trans-cinnamic acid (9), N-phenethylacetamide (10) and five fatty acids (11-15), was isolated from the ethyl acetate extract of SCSIO 52865. Their structures were elucidated by a combination of comprehensive spectroscopic analyses, Marfey's method and GC-MS analysis. Furthermore, the analysis of molecular networking revealed the presence of cyclodipeptides, and compound 1 was produced only under mBHI fermentation condition. Moreover, bioinformatic analysis suggested that compound 1 was closely related to four genes, namely jatA-D, encoding core non-ribosomal peptide synthetase and acetyltransferase.

Comparative Study on the Structural Properties and Bioactivities of Three Different Molecular Weights of Lycium barbarum Polysaccharides.

The molecular weight, the triple-helix conformation, the monosaccharide content, the manner of glycosidic linkages, and the polysaccharide conjugates of polysaccharides all affect bioactivity. The purpose of this study was to determine how different molecular weights affected the bioactivity of the Lycium barbarum polysaccharides (LBPs). By ethanol-graded precipitation and ultrafiltration membrane separation, one oligosaccharide (LBPs-1, 1.912 kDa) and two polysaccharides (LBPs-2, 7.481 kDa; LBPs-3, 46.239 kDa) were obtained from Lycium barbarum. While the major component of LBPs-1 and LBPs-2 was glucose, the main constituents of LBPs-3 were arabinose, galactose, and glucose. LBPs-2 and LBPs-3 exhibited triple-helix conformations, as evidenced by the Congo red experiment and AFM data. Sugar residues of LBPs-2 and LBPs-3 were elucidated by NMR spectra. The polysaccharides (LBPs-2 and LBPs-3) exhibited much higher antioxidant capacities than oligosaccharide (LBPs-1). LBPs-3 showed higher oxygen radical absorbance capacity (ORAC) and superoxide dismutase (SOD) activity than LBPs-2, but a lower capability for scavenging ABTS+ radicals. In zebrafish, LBPs-2 and LBPs-3 boosted the growth of T-lymphocytes and macrophages, enhanced the immunological response, and mitigated the immune damage generated by VTI. In addition to the molecular weight, the results indicated that the biological activities would be the consequence of various aspects, such as the monosaccharide composition ratio, the chemical composition, and the chemical reaction mechanism.

Investigation on Metabolites in Structural Diversity from the Deep-Sea Sediment-Derived Bacterium Agrococcus sp. SCSIO 52902 and Their Biosynthesis.

Deep-sea sediment-derived bacterium may make full use of self-genes to produce more bioactive metabolites to adapt to extreme environment, resulting in the discovery of novel metabolites with unique structures and metabolic mechanisms. In the paper, we systematically investigated the metabolites in structurally diversity and their biosynthesis from the deep-sea sediment-derived bacterium Agrococcus sp. SCSIO 52902 based on OSMAC strategy, Molecular Networking tool, in combination with bioinformatic analysis. As a result, three new compounds and one new natural product, including 3R-OH-1,6-diene-cyclohexylacetic acid (1), linear tetradepsipeptide (2), N1,N5-di-p-(EE)-coumaroyl-N10-acetylspermidine (3) and furan fatty acid (4), together with nineteen known compounds (5-23) were isolated from the ethyl acetate extract of SCSIO 52902. Their structures were elucidated by comprehensive spectroscopic analysis, single-crystal X-ray diffraction, Marfey's method and chiral-phase HPLC analysis. Bioinformatic analysis revealed that compounds 1, 3, 9 and 13-22 were closely related to the shikimate pathway, and compound 5 was putatively produced by the OSB pathway instead of the PKS pathway. In addition, the result of cytotoxicity assay showed that compound 5 exhibited weak cytotoxic activity against the HL-60 cell line.

Energy-efficient removal of carbamazepine in solution by electrocoagulation-electrofenton using a novel P-rGO cathode.

In this study, carbamazepine (CBZ) decay in solution has been studied by coupling electrocoagulation with electro-Fenton (EC-EF) with a novel P-rGO/carbon felt (CF) cathode, aiming to accelerate the in-situ generation of •OH, instead of adding Fe2+ and H2O2. Firstly, the fabricated P-rGO and its derived cathode were characterized by XRD, SEM, AFM, XPS and electrochemical test (EIS, CV and LSV). Secondly, it was confirmed that the performance in removal efficiency and electric energy consumption (EEC) by EC-EF (kobs=0.124 min-1, EEC=43.98 kWh/kg CBZ) was better than EF (kobs=0.069 min-1, EEC=61.04 kWh/kg CBZ). Then, P-rGO/CF (kobs=0.248 min-1, EEC=29.47 kWh/kg CBZ, CE=61.04%) showed the best performance in EC-EF, among all studied heteroatom-doped graphene/CF. This superior performance may be associated with its largest layer spacing and richest C=C, which can promote the electron transfer rate and conductivity of the cathode. Thus, more H2O2 and •OH could be produced to degrade CBZ, and almost 100% CBZ was removed with kobs being 0.337 min-1 and the EEC was only 24.18 kWh/kg CBZ, under the optimal conditions (P-rGO loading was 6.0 mg/cm2, the current density was 10.0 mA/cm2, the gap between electrode was 2.0 cm). Additionally, no matter the influent is acidic, neutral or alkaline, no additional pH adjustment is required for the effluent of EC-EF. At last, an inconsecutive empirical kinetic model was firstly established to predict the effect of operating parameters on CBZ removal.

Identification and Characterization of the Amphioxus Lck and Its Associated Tyrosine Phosphorylation-Dependent Inhibitory LRR Receptor.

Amphioxus (e.g., Branchiostoma belcheri, Bb) has recently emerged as a new model for studying the origin and evolution of vertebrate immunity. Mammalian lymphocyte-specific tyrosine kinase (Lck) plays crucial roles in T cell activation, differentiation and homeostasis, and is reported to phosphorylate both the ITIM and ITSM of PD-1 to induce the recruitment of phosphatases and thus the inhibitory function of PD-1. Here, we identified and cloned the amphioxus homolog of human Lck. By generating and using an antibody against BbLck, we found that BbLck is expressed in the amphioxus gut and gill. Through overexpression of BbLck in Jurkat T cells, we found that upon TCR stimulation, BbLck was subjected to tyrosine phosphorylation and could partially rescue Lck-dependent tyrosine phosphorylation in Lck-knockdown T cells. Mass spectrometric analysis of BbLck immunoprecipitates from immunostimulants-treated amphioxus, revealed a BbLck-associated membrane-bound receptor LRR (BbLcLRR). By overexpressing BbLcLRR in Jurkat T cells, we demonstrated that BbLcLRR was tyrosine phosphorylated upon TCR stimulation, which was inhibited by Lck knockdown and was rescued by overexpression of BbLck. By mutating single tyrosine to phenylalanine (Y-F), we identified three tyrosine residues (Y539, Y655, and Y690) (3Y) of BbLcLRR as the major Lck phosphorylation sites. Reporter gene assays showed that overexpression of BbLcLRR but not the BbLcLRR-3YF mutant inhibited TCR-induced NF-κB activation. In Lck-knockdown T cells, the decline of TCR-induced IL-2 production was reversed by overexpression of BbLck, and this reversion was inhibited by co-expression of BbLcLRR but not the BbLcLRR-3YF mutant. Sequence analysis showed that the three tyrosine-containing sequences were conserved with the tyrosine-based inhibition motifs (ITIMs) or ITIM-like motifs. And TCR stimulation induced the association of BbLcLRR with tyrosine phosphatases SHIP1 and to a lesser extent with SHP1/2. Moreover, overexpression of wild-type BbLcLRR but not its 3YF mutant inhibited TCR-induced tyrosine phosphorylation of multiple signaling proteins probably via recruiting SHIP1. Thus, we identified a novel immunoreceptor BbLcLRR, which is phosphorylated by Lck and then exerts a phosphorylation-dependent inhibitory role in TCR-mediated T-cell activation, implying a mechanism for the maintenance of self-tolerance and homeostasis of amphioxus immune system and the evolutionary conservatism of Lck-regulated inhibitory receptor pathway.

T-cell receptor (TCR) signaling promotes the assembly of RanBP2/RanGAP1-SUMO1/Ubc9 nuclear pore subcomplex via PKC-θ-mediated phosphorylation of RanGAP1.

The nuclear pore complex (NPC) is the sole and selective gateway for nuclear transport, and its dysfunction has been associated with many diseases. The metazoan NPC subcomplex RanBP2, which consists of RanBP2 (Nup358), RanGAP1-SUMO1, and Ubc9, regulates the assembly and function of the NPC. The roles of immune signaling in regulation of NPC remain poorly understood. Here, we show that in human and murine T cells, following T-cell receptor (TCR) stimulation, protein kinase C-θ (PKC-θ) directly phosphorylates RanGAP1 to facilitate RanBP2 subcomplex assembly and nuclear import and, thus, the nuclear translocation of AP-1 transcription factor. Mechanistically, TCR stimulation induces the translocation of activated PKC-θ to the NPC, where it interacts with and phosphorylates RanGAP1 on Ser504 and Ser506. RanGAP1 phosphorylation increases its binding affinity for Ubc9, thereby promoting sumoylation of RanGAP1 and, finally, assembly of the RanBP2 subcomplex. Our findings reveal an unexpected role of PKC-θ as a direct regulator of nuclear import and uncover a phosphorylation-dependent sumoylation of RanGAP1, delineating a novel link between TCR signaling and assembly of the RanBP2 NPC subcomplex.

FeS2/carbon felt as an efficient electro-Fenton cathode for carbamazepine degradation and detoxification: In-depth discussion of reaction contribution and empirical kinetic model.

Carbamazepine (CBZ) decay by electro-Fenton (EF) oxidation using a novel FeS2/carbon felt (CF) cathode, instead of a soluble iron salt, was studied with the aim to accelerate the reaction between H2O2 and ferrous ions, which helps to produce more hydroxyl radicals (•OH) and eliminate iron sludge. First, fabricated FeS2 and its derived cathode were characterized by scanning electron microscopy, high-resolution transmission electron microscopy, and X-ray photoelectron spectroscopy. Anodes were then screened, with DSA (Ti/IrO2-RuO2) showing the best performance under EF oxidation regarding CBZ degradation and electrochemical characterization. Several operating parameters of this EF process, such as FeS2 loading, current density, gap between electrodes (GBE), initial [CBZ], and electrolyte type, were also investigated. Accordingly, a nonconsecutive empirical kinetic model was established to predict changes in CBZ concentration under the given operational parameters. The contribution of different oxidation types to the EF process was calculated using kinetic analysis and quenching experiments to verify the role of the FeS2-modified cathode. The reaction contributions of anodic oxidation (AO), H2O2 electrolysis (EP), and EF oxidation to CBZ removal were 12.81%, 7.41%, and 79.77%, respectively. The •OH exposure of EP and EF oxidation was calculated, confirming that •OH exposure was approximately 22.45-fold higher using FeS2-modified CF. Finally, the 19 intermediates formed by CBZ degradation were identified by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. Accordingly, four CBZ degradation pathways were proposed. ECOSAR software was used to assess the ecotoxicity of intermediates toward fish, daphnia, and green algae, showing that this novel EF oxidation process showed good toxicity reduction performance. A prolonged EF retention time was proposed to be necessary to obtain clean and safe water, even if the targeted compound was removed at an earlier time.

Enhanced performance of microbial fuel cells using Ag nanoparticles modified Co, N co-doped carbon nanosheets as bifunctional cathode catalyst.

The slow kinetics of oxygen reduction reaction (ORR) and the formation of biofilm on cathode severely limited the performance of microbial fuel cells (MFCs). An efficient way to enhance the power-generation capacity and long-term stability of MFCs is to develop bifunctional catalyst by incorporating the efficient ORR catalysts with antibacterial ingredient. In this study, the Ag/Co-N-C nanosheets were designed and synthesized by decorating Ag nanoparticles (NPs) onto Co-N-C nanosheets, which were prepared from Zn/Co bimetallic metal-organic framework (ZIF-67/ZIF-8) precursor. The Zn/Co ratio, Ag doping amount and the calcination temperature of the precursor were systematically investigated. The optimum sample Ag/Co-N-C-30 revealed the excellent ORR performance with a half-wave potential of 0.80 V vs. RHE, which was slightly lower than that of Pt/C (0.82 V vs. RHE). The MFCs equipped with Ag/Co-N-C-30 cathode exhibited maximum power density of 548 ± 12.6 mW m-2 and superior durability even after 1600 h operation. Besides, the selective antimicrobial ability of Ag/Co-N-C-30 was further explored and the aerobic bacteria in cathode biofilm was found to be obviously inhibited by Ag/Co-N-C-30. The results suggested the Ag/Co-N-C nanosheets can serve as a promising cathode catalyst for practical applications of MFCs.

The influence of maternal vitamin D supplementation on infant vitamin D status: A systematic review and meta-analyses.

BACKGROUND: Inconsistencies exist with regard to effect of maternal vitamin D supplementation on infant vitamin D status. The inconsistencies could be attributed to numerous factors, such as duration of intervention and dosage, among others. In this work, we conducted a systematic review and meta-analysis to determine the influence of maternal vitamin D supplementation on infant vitamin D status. METHODS: A comprehensive systematic search was performed in Scopus, EMBASE, Web of Science, and PubMed/MEDLINE, by investigators, from database inception until November 2019, without using any restrictions. Weighted mean difference (WMD) with the 95 % CI was used for assessing the effects of maternal vitamin D supplementation on 25(OH) D levels in infants. RESULTS: Overall results from 14 studies revealed a non-significant effect of maternal vitamin D administration on the level of 25(OH) D in breastfeeding infants (WMD: -0.464 ng/mL, 95 % CI: -6.68 to 5.75, p = 0.884, I2 = 98 %). Subgroup analyses demonstrated that vitamin D supplementation dosage ≥2000 IU/day (WMD: 9 ng/mL, 95 % CI: 8.19, 9.82, I2 = 99 %) and intervention duration ≥20 weeks (WMD: 16.20 ng/mL, 95 % CI: 14.89, 17.50, I2 = 99 %) significantly increased 25(OH) D. CONCLUSIONS: The main results indicate a non-significant increase in infant vitamin D following maternal vitamin D supplementation. Additionally, vitamin D supplementation dosage ≥2000 IU/day and intervention duration ≥20 weeks significantly increased infant 25(OH) D.

Analysis of Interleukin-4-Induced Class Switch Recombination in Mouse Myeloma CH12F3-2 Cells.

Affinity maturation of B lymphocytes is a process that includes somatic hypermutation and class switch recombination. Class switch recombination is a fundamental factor of the human adaptive immunity. The perturbation of this process has an adverse effect on human health, and results in global chromosome rearrangements and cell transformation. Evaluation of the class switch recombination efficiency is an important component of laboratory diagnosis of immunotoxic components. Here we describe a method for testing the efficiency of the class switch recombination. Cultivation of mouse myeloma CH12F3-2 cell line with anti-CD40 antibodies, transforming growth factor beta, and recombinant interleukin-4 (IL-4) triggers a cascade of signal transduction network events that lead to switching the immunoglobulin isotypes from IgM to IgA. This chapter describes the methodology of class switch recombination assay for assessment of the effect of environmental pollutants in toxicological laboratory diagnostics.

Characterisation of amphioxus protein kinase C-δ/θ reveals a unique proto-V3 domain suggesting an evolutionary mechanism for PKC-θ unique V3.

A primitive adaptive immune system has recently been suggested to be present in a basal chordate amphioxus (Branchiostoma belcheri, Bb), making it an ideal model for studying the origin of adaptive immune. The novel protein kinase C isoform PKC-θ, but not its closest isoform PKC-δ, plays a critical role for mammalian T-cell activation via translocation to immunological synapse (IS) mediated by a unique PKC-θ V3 domain containing one PxxP motif. To understand the evolution of this unique PKC-θ V3 domain and the primitive adaptive immune system in amphioxus, we comparatively studied the orthologs of PKC-δ and -θ from amphioxus and other species. Phylogenetic analysis showed BbPKC-δ/θ to be the common ancestor of vertebrate PKC-δ and PKC-θ, with a V3 domain containing two PxxP motifs. One motif is conserved in both zebrafish and mammalian PKC-θ but is absent in PKC-δ V3 domain of these species, and has already emerged in drosophila PKC-δ. The other non-conserved motif emerged in BbPKC-δ/θ, and only retained in Danio rerio PKC-δ (DrPKC-δ) but lost in mammalian PKC-δ and -θ. Comparative analyses of the sequence and function of BbPKC-δ/θ, DrPKC-δ, DrPKC-θ and Homo sapiens PKC-θ (HsPKC-θ) in IS translocation and T-cell receptor (TCR)-induced NF-κB activation revealed that retention of the conserved PxxP motif and loss of the non-conserved PxxP motif in mammalian PKC-θ and loss of both PxxP motifs in mammalian PKC-δ accomplish the unique function of PKC-θ in T cells. Together, this study suggests an evolutionary mechanism for PKC-θ unique V3 and reveals BbPKC-δ/θ is the common ancestor of PKC-δ and -θ with a functional proto-V3 domain, supplying new evidence for the existence of primitive adaptive immune system in amphioxus.

Variecolortins A-C, Three Pairs of Spirocyclic Diketopiperazine Enantiomers from the Marine-Derived Fungus Eurotium sp. SCSIO F452.

Three pairs of spirocyclic diketopiperazine enantiomers, variecolortins A-C (1-3), were isolated from marine-derived fungus Eurotium sp. SCSIO F452. Compound 1 possesses an unprecedented highly functionalized seco-anthronopyranoid carbon skeleton featuring a 2-oxa-7-azabicyclo[3.2.1]octane core. Compounds 2 and 3 represent rare examples of a 6/6/6/6 tetracyclic cyclohexene-anthrone carbon scaffold. Their structures were determined by spectroscopic analyses, X-ray diffraction, and ECD calculations. Their enantiomers exhibited different antioxidative and cytotoxic activities, and their modes of action were investigated.

Eurotiumins A⁻E, Five New Alkaloids from the Marine-Derived Fungus Eurotium sp. SCSIO F452.

Three new prenylated indole 2,5-diketopiperazine alkaloids (1⁻3) with nine known ones (5⁻13), one new indole alkaloid (4), and one new bis-benzyl pyrimidine derivative (14) were isolated and characterized from the marine-derived fungus Eurotium sp. SCSIO F452. 1 and 2, occurring as a pair of diastereomers, both presented a hexahydropyrrolo[2,3-b]indole skeleton. Their chemical structures, including absolute configurations, were elucidated by 1D and 2D NMR, HRESIMS, quantum chemical calculations of electronic circular dichroism, and single crystal X-ray diffraction experiments. Most isolated compounds were screened for antioxidative potency. Compounds 3, 5, 6, 7, 9, 10, and 12 showed significant radical scavenging activities against DPPH with IC50 values of 13, 19, 4, 3, 24, 13, and 18 µM, respectively. Five new compounds were evaluated for cytotoxic activities.