Case report: Whole exome sequencing identified a novel mutation (p.Y301H) of MAF in a Chinese family with congenital cataracts.

Background: Congenital cataracts stand as the primary cause of childhood blindness globally, characterized by clouding of the eye's lens at birth or shortly thereafter. Previous investigations have unveiled that a variant in the V-MAF avian musculoaponeurotic-fibrosarcoma oncogene homolog (MAF) gene can result in Ayme-Gripp syndrome and solitary cataract. Notably, MAF mutations have been infrequently reported in recent years. Methods: In this investigation, we recruited a Chinese family with non-syndromic cataracts. Whole exome sequencing and Sanger sequencing were applied to scrutinize the genetic anomaly within the family. Results: Through whole exome sequencing and subsequent data filtration, a new mutation (NM_005360, c.901T>C/p.Y301H) in the MAF gene was detected. Sanger sequencing validated the presence of this mutation in another affected individual. The p.Y301H mutation, situated in an evolutionarily preserved locus, was not detected in our 200 local control cohorts and various public databases. Additionally, multiple bioinformatic programs predicted that the mutation was deleterious and disrupted the bindings between MAF and its targets. Conclusion: Hence, we have documented a new MAF mutation within a Chinese family exhibiting isolated congenital cataracts. Our study has the potential to broaden the spectrum of MAF mutations, offering insights into the mechanisms underlying cataract formation and facilitating genetic counseling and early diagnosis for congenital cataract patients.

Preparation, Characterization, and Antioxidant Activities of Extracts from Amygdalus persica L. Flowers.

A novel water-soluble Amygdalus persica L. flowers polysaccharide (APL) was successfully isolated and purified from Amygdalus persica L. flowers by hot water extraction. Its chemical components and structure were analyzed by IR, GC-MS, and HPLC. APL consisted of rhamnose, arabinose, mannose and glucose in a molar ratio of 0.17:0.034:1.0:0.17 with an average molecular weight of approximately 208.53 kDa and 15.19 kDa. The antioxidant activity of APL was evaluated through radical scavenging assays using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 3-ethylbenzthiazoline-6-sulfonic acid (ABTS), Hydroxyl radical scavenging, Superoxide radical scavenging, and the reducing power activity was also determined in vitro. Besides, in vivo antioxidant experiment, zebrafish (Danio rerio) embryos were treated with different concentrations of APL and then exposed to LPS to induce oxidative stress. Treatment with APL at 50 or 100 µg/mL significantly reduced LPS-induced oxidative stress in the zebrafish, demonstrating the strong antioxidant activity of APL. Moreover, the effect of APL on zebrafish depigmentation was tested by analyzing the tyrosinase activity and melanin content of zebrafish embryos. APL showed a potential reduction in the total melanin content and tyrosinase activity after treatment. This work provided important information for developing a potential natural antioxidant in the field of cosmetics and food.

Bioactive secondary metabolites isolated from the soft coral derived Penicillium sp. SCSIO 41038.

Chemical investigation of the Penicillium sp. SCSIO 41038 led to the isolation and characterization of one new cyclopiazonic acid-type alkaloid, speradine I (1), and one new phloroglucinol derivative, speradine J (8), along with 13 known compounds. Their structures were determined on the basis of extensive spectroscopic analysis, and by a comparison with data from the literature. All the compounds were evaluated for their antitumor (22Rv1 and PC-3) and enzyme inhibitory activity against acetylcholinesterase (AChE) in vitro.

Case report: Identification of novel fibrillin-2 variants impacting disulfide bond and causing congenital contractural arachnodactyly.

Background: Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue disorder with clinical features of arthrogryposis, arachnodactyly, crumpled ears, scoliosis, and muscular hypoplasia. The heterozygous pathogenic variants in FBN2 have been shown to cause CCA. Fibrillin-2 is related to the elasticity of the tissue and has been demonstrated to play an important role in the constitution of extracellular microfibrils in elastic fibers, providing strength and flexibility to the connective tissue that sustains the body's joints and organs. Methods: We recruited two Chinese families with arachnodactyly and bilateral arthrogryposis of the fingers. Whole-exome sequencing (WES) and co-segregation analysis were employed to identify their genetic etiologies. Three-dimensional protein models were used to analyze the pathogenic mechanism of the identified variants. Results: We have reported two CCA families and identified two novel missense variants in FBN2 (NM_001999.3: c.4093T>C, p.C1365R and c.2384G>T, p.C795F). The structural models of the mutant FBN2 protein in rats exhibited that both the variants could break disulfide bonds. Conclusion: We detected two FBN2 variants in two families with CCA. Our description expands the genetic profile of CCA and emphasizes the pathogenicity of disulfide bond disruption in FBN2.

A new quinolone and acetylcholinesterase inhibitors from a sponge-associated fungus Penicillium sp. SCSIO41033.

The chemical investigation of the EtOAc extract from the solid rice medium cultured with a sponge-associated fungus Penicillium sp. SCSIO41033 led to the isolation of two quinolones including a new one, penicinolone (1), three xanthone derivatives (3-5), and four anthraquinones (6-9). Their structures were determined by comprehensive analysis of 1H and 13C NMR, COSY, HSQC, and HMBC spectroscopic, and HRESIMS mass spectrometric data. The bioactive assays revealed that compounds 1 and 2 showed no antimicrobial activities against five bacteria and eight fungi, and compounds 5, 8 and 9 exhibited inhibition against AChE with IC50 values of 45.9, 42.5 and 40.5 µg/mL. Molecular docking analysis was performed to explore the interactions between active molecules and AChE protein, which indicated that xanthone and anthraquinone derivatives had the potential for developing AChE inhibitors.

Dietary fish and omega-3 polyunsaturated fatty acids intake and cancer survival: A systematic review and meta-analysis.

Fish and omega-3 polyunsaturated fatty acids (PUFA) have been suggested to play a role in improving cancer prognosis. However, results from epidemiological studies remain inconsistent. Here we assess the association between dietary fish and/or omega-3 PUFAs intake and cancer prognosis with meta-analysis of observational studies. A systematic search of related publications was performed using PubMed and Web of Science databases. Hazard ratios (HR) and 95% confidence intervals (CI) were extracted and then pooled using a random-effect model. Potential linear and non-linear dose-response relationships were explored using generalized least squares estimation and restricted cubic splines. As a result, 21 cohort studies were included in our analysis. Compared to the lowest category, the highest category of fish intake was associated with a significant lower mortality in patients with ovarian cancer (n = 1, HR = 0.74, 95% CI: 0.57-0.95) and overall cancer (n = 12, HR = 0.87, 95% CI: 0.81-0.94). Marine omega-3 PUFAs intake rather than total omega-3 PUFAs intake showed significant protective effects on survival of overall cancer (n = 8, HR = 0.81, 95% CI: 0.71-0.94), in particular prostate cancer (n = 2, HR = 0.62, 95% CI: 0.46-0.82). Dose-response meta-analysis indicated a nonlinear and a linear relationship between fish intake, as well as marine omega-3 PUFAs intake, and overall cancer survival, respectively. In conclusion, our analysis demonstrated a protective effect of dietary fish and marine omega-3 PUFAs consumption on cancer survival.

Changes in serum amino acid levels in non-small cell lung cancer: a case-control study in Chinese population.

Background: Previous studies have shown the alteration of amino acid (AA) profile in patients with non-small cell lung cancer (NSCLC). However, there is little data regarding AA profile in NSCLC in Chinese population. The aim of this study was to evaluate AA profile in Chinese NSCLC patients, explore its utility in sample classification and further discuss its related metabolic pathways. Methods: The concentrations of 22 AAs in serum samples from 200 patients with NSCLC and 202 healthy controls were determined by liquid chromatography-tandem mass spectrometer (LC-MS/MS). AA levels in different tumor stages and histological types were also discussed. The performance of AA panel in classifying the cases and controls was evaluated in the training data set and validation data set based on the receiver operating characteristic (ROC) curve, and the important metabolic pathways were identified. Results: The concentrations of tryptophan (Trp), phenylalanine (Phe), isoleucine (Ile), glycine (Gly), serine (Ser), aspartic acid (Asp), asparagine (Asn), cystein (Cys), glutamic acid (Glu), ornithine (Orn) and citrulline (Cit) were significantly altered in NSCLC patients compared with controls (all P-FDR < 0.05). Among these, four AAs including Asp, Cys, Glu and Orn were substantially up-regulated in NSCLC patients (FC ≥ 1.2). AA levels were significantly altered in patients with late-stage NSCLC, but not in those with early-stage when comparing with healthy controls. In terms of histological type, these AAs were altered in both adenocarcinoma and squamous cell carcinoma. For discrimination of NSCLC from controls, the area under the ROC curve (AUC) was 0.80 (95% CI [0.74-0.85]) in the training data set and 0.79 (95%CI [0.71-0.87]) in the validation data set. The AUCs for early-stage and late-stage NSCLC were 0.75 (95% CI [0.68-0.81]) and 0.86 (95% CI [0.82-0.91]), respectively. Moreover, the model showed a better performance in the classification of squamous cell carcinoma (AUC = 0.90, 95% CI [0.85-0.95]) than adenocarcinoma (AUC = 0.77, 95% CI [0.71-0.82]) from controls. Three important metabolic pathways were involved in the alteration of AA profile, including Gly, Ser and Thr metabolism; Ala, Asp and Glu metabolism; and Arg biosynthesis. Conclusions: The levels of several AAs in serum were altered in Chinese NSCLC patients. These altered AAs may be utilized to classify the cases from the controls. Gly, Ser and Thr metabolism; Ala, Asp and Glu metabolism and Arg biosynthesis pathways may play roles in metabolism of the NSCLC patient.

Asperbenzophenone A and Versicolamide C, New Fungal Metabolites from the Soft Coral Derived Aspergillus sp. SCSIO 41036.

Two new compounds, asperbenzophenone A (1) and versicolamide C (5), together with fifteen known compounds were isolated from a soft coral derived fungus Aspergillus sp. SCSIO 41036. Their structures were elucidated by spectroscopic methods, ECD analysis, and by a comparison with data from the literature. In bioassay, compound 8 showed significant inhibitory activity against lipopolysaccharide-inducted nitric oxide (NO) in RAW264.7 cells at the concentration of 10 µM. Additionally, the anti-acetylcholinesterase activity assay showed that 14 exhibited weak inhibition with an IC50 value of 157.8 µM.

Dietary glycemic index, glycemic load and cancer risk: a meta-analysis of prospective cohort studies.

PURPOSE: There is considerable inconsistency in results regarding the association of dietary glycemic index (GI) and glycemic load (GL) with cancer risk. We therefore conducted this systematic review and dose-response meta-analysis of prospective cohort studies to evaluate the relationship between dietary GI/GL and cancer risk. METHODS: We searched PubMed and Web of Science for prospective cohort studies of dietary GI/GL in relation to risks of all types of cancer up to 31 March 2021. We used a random-effect model to calculate summary relative risks (RR) and 95% confidence intervals (CI). The certainty of evidence was assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. This study was registered at PROSPERO (CRD42020215338). RESULTS: Overall, 55 cohorts were included in the meta-analysis. We assessed the relationship between dietary GI or GL and risks of 23 cancer types, including hormone-related cancers, cancers from digestive system, respiratory system, urinary system and other cancer sites. High GI diet increased overall risk of cancer with low certainty of evidence (highest vs lowest categories, n = 3, RR 1.04, 95% CI 1.01-1.07). For site-specific cancers, high GI diet increased risks of lung cancer (highest vs lowest categories, n = 5, RR 1.08, 95% CI 1.01-1.18) and breast cancer (highest vs lowest categories, n = 14, RR 1.05, 95% CI 1.01-1.09), especially for postmenopausal breast cancer (highest vs lowest categories, n = 10, RR 1.06, 95% CI 1.00-1.13), all with low certainty of evidence. Additionally, dietary GI was positively related to risk of bladder cancer with low certainty of evidence (highest vs lowest categories, n = 3, RR 1.23, 95% CI 1.09-1.40), as well as negatively related to ovarian cancer risk with very low certainty of evidence (highest vs lowest categories, n = 4, RR 0.83, 95% CI 0.69-1.00) and lymphoma risk with low certainty of evidence (highest vs lowest categories, n = 2, RR 0.84, 95% CI 0.72-0.98). Besides, we found an inverse association of dietary GL with lung cancer risk with low certainty of evidence (highest vs lowest categories, n = 5, RR 0.87, 95% CI 0.80-0.94). CONCLUSION: High dietary GI increased overall cancer risk with low certainty of evidence. For site-specific cancers, high GI diet increased the risks of breast cancer with low certainty of evidence and lung cancer with low certainty of evidence. Dietary GL was inversely associated with lung cancer risk with low certainty of evidence.

Cyclic Peptides from the Soft Coral-Derived Fungus Aspergillus sclerotiorum SCSIO 41031.

Three novel cyclic hexapeptides, sclerotides C-E (1-3), and a new lipodepsipeptide, scopularide I (4), together with a known cyclic hexapeptide sclerotide A (5), were isolated from fermented rice cultures of a soft coral-derived fungus: Aspergillus sclerotiorum SCSIO 41031. The structures of the new peptides were determined by 1D and 2D NMR spectroscopic analysis, Marfey's method, ESIMS/MS analysis, and single crystal X-ray diffraction analysis. Scopularide I (4) exhibited acetylcholinesterase inhibitory activity with an IC50 value of 15.6 µM, and weak cytotoxicity against the human nasopharyngeal carcinoma cell line HONE-EBV with IC50 value of 10.1 µM.

A Functional Polymorphism in Accessible Chromatin Region Confers Risk of Non-Small Cell Lung Cancer in Chinese Population.

BACKGROUND: The disease-associated non-coding variants identified by genome-wide association studies (GWASs) were enriched in open chromatin regions (OCRs) and implicated in gene regulation. Genetic variants in OCRs thus may exert regulatory functions and contribute to non-small cell lung cancer (NSCLC) susceptibility. OBJECTIVE: To fine map potential functional variants in GWAS loci that contribute to NSCLC predisposition using chromatin accessibility and histone modification data and explore their functions by population study and biochemical experimental analyses. METHODS: We mapped the chromatin accessible regions of lung tissues using data of assay for transposase-accessible chromatin using sequencing (ATAC-seq) in The Cancer Genome Atlas (TCGA) and prioritized potential regulatory variants within lung cancer GWAS loci by aligning with histone signatures using data of chromatin immunoprecipitation assays followed by sequencing (ChIP-seq) in the Encyclopedia of DNA Elements (ENCODE). A two-stage case-control study with 1,830 cases and 2,001 controls was conducted to explore the associations between candidate variants and NSCLC risk in Chinese population. Bioinformatic annotations and biochemical experiments were performed to further reveal the potential functions of significant variants. RESULTS: Sixteen potential functional single-nucleotide polymorphisms (SNPs) were selected as candidates from bioinformatics analyses. Three variants out of the 16 candidate SNPs survived after genotyping in stage 1 case-control study, and only the results of SNP rs13064999 were successfully validated in the analyses of stage 2 case-control study. In combined analyses, rs13064999 was significantly associated with NSCLC risk [additive model; odds ratio (OR) = 1.17; 95%CI, 1.07-1.29; p = 0.001]. Functional annotations indicated its potential enhancer bioactivity, and dual-luciferase reporter assays revealed a significant increase in luciferase activity for the reconstructed plasmid with rs13064999 A allele, when compared to the one with wild-type G allele (pA549  < 0.001, pSK-MES-1 = 0.004). Further electrophoretic mobility shift assays (EMSA) and super-shift assays confirmed a stronger affinity of HP1γ for the binding motif containing SNP rs13064999 A allele. CONCLUSION: These findings suggested that the functional variant rs13064999, identified by the integration of ATAC-seq and ChIP-seq data, contributes to the susceptibility of NSCLC by affecting HP1γ binding, while the exact biological mechanism awaits further exploration.

Cytotoxicity of polyketides and steroids isolated from the sponge-associated fungus Penicillium citrinum SCSIO 41017.

Two new polyketides, xerucitrinin A (1) and coniochaetone M (8), and one new steroid, 16α-methylpregna-17α,19-dihydroxy-(9,11)-epoxy-4-ene-3,18-dione-20-acetoxy (13), together with eleven known analogues were isolated from fungus Penicillium citrinum SCSIO 41017 associated with the sponge Callyspongia sp. Their structures and absolute configurations were elucidated by NMR spectra, MS, CD, optical rotation, X-ray crystallography, and compared with literature data. Biological evaluation results revealed that 5 exhibited significant cytotoxic activity against MCF-7 cell line with IC50 values of 1.3 µM. Compound 13 showed moderate activity against all cell lines with IC50 values of 13.5-18.0 µM, and compounds 9 and 14 showed weak activity with MIC values of ranging from 125 µg/mL to 250 µg/mL respectively.[Formula: see text].

Bioactive secondary metabolites from the deep-sea derived fungus Aspergillus sp. SCSIO 41029.

Two new compounds classified as one new lumazine peptide, penilumamide K (1) and one new sesquiterpene (2), were obtained from the deep-sea derived fungus Aspergillus sp. SCSIO 41029, together with eleven known compounds (3-13). The structures of 1-13 including absolute configurations were determined by detailed NMR spectroscopy, HR-ESI-MS, chemical derivatization, and optical rotation data. Among them, compound 1 represents the first lumazine peptide reported from deep-sea derived fungus. The bioactive assay exhibited that compounds 1, 3, 4, 5, 7 and 10 had significant potency against α-glucosidase with IC50 values ranging from 18.61 to 109.06 µΜ. In addition, compounds 4 and 9 showed strong antibacterial activity against Staphylococcus aureus with MIC values of 0.78 and 6.25 µg ml-1, respectively.

Structurally diverse polyketides and phenylspirodrimanes from the soft coral-associated fungus Stachybotrys chartarum SCSIO41201.

Four undescribed polyketide derivatives, named arthproliferins A-D (1-4), and one undescribed phenylspirodrimane derivative, named arthproliferin E (7), along with 11 known metabolites (5, 6, 8-16) were isolated from the soft coral-associated fungus Stachybotrys chartarum SCSIO41201. Their structures were determined through spectroscopic methods, X-ray crystallography, and ECD analysis. Compounds 1 and 3-15 were evaluated for their cytotoxic, and antibacterial activities. Among them, compounds 1 and 15 displayed moderate inhibitory activity against methicillin-resistant Staphylococcus aureus ATCC 29213 with an MIC value of 78 and 39 µg/mL, respectively. Furthermore, compound 15 displayed strong cytotoxic activities against the tested cell line with IC50 values less than 39 nM.

Four new steroids from the marine soft coral-derived fungus Penicillium sp. SCSIO41201.

Penicildiones A-D (1-4), four new steroids derivatives together with three known compounds including 16α-methylpregna-17α,19-dihydroxy-(9,11)-epoxy-4-ene-3,18-dione-20-acetoxy (5), stachybotrylactone B (6) and stachybotrin (7) were isolated from the soft coral-derived fungus Penicillium sp. SCSIO41201, cultured in the 1% NaCl PDB substrate. Their structures were determined through spectroscopic methods and X-ray crystallography. Biological evaluation results revealed that 6 exhibited significant cytotoxic activity against HL-60, K562, MOLT-4, ACHN, 786-O, and OS-RC-2 cell lines with IC50 values of 5.23, 4.12, 4.31, 23.55, 7.65 and 10.81 µmol·L-1, respectively, while other compounds showed weak or no cytotoxicity at 50 µmol·L-1.

Urinary bisphenol A and its interaction with ESR1 genetic polymorphism associated with non-small cell lung cancer: findings from a case-control study in Chinese population.

Bisphenol A (BPA), a well-known endocrine disruptor, was reported to promote migration and invasion of lung cancer cells, but findings in human study is absent. A case-control study in Chinese population was conducted to evaluate the association between BPA exposure and non-small cell lung cancer (NSCLC), and explore the interaction between BPA exposure and estrogen-related genetic polymorphism on NSCLC. BPA concentrations were measured in urine samples using an UHPLC-MS method and rs2046210 in estrogen receptor α (ESR1) gene was genotyped by TaqMan genotyping system. Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the association analyses. As a result, 615 NSCLC cases and 615 healthy controls were enrolled from Wuhan, central China. The mean age was 58.0 (SD: 7.9) years old for controls and 59.2 (SD: 8.8) years old for cancer cases. The creatinine-adjusted BPA levels were significantly higher in NSCLC cases than that in healthy controls (median: 0.97 vs 0.73 µg/L, P < 0.001). Exposure to high levels of BPA was significantly associated with NSCLC (adjusted OR = 1.91, 95%CI: 1.39-2.62, P < 0.001 for the highest quartile). We also observed a shallow concave dose-response relationship about the overall association between BPA and NSCLC. Moreover, interaction analyses showed that BPA exposure interacted multiplicatively with rs2046210, with a marginal P value (P = 0.049), to contribute to NSCLC. In conclusion, exposure to high levels BPA may be associated with NSCLC and the relationship may be modified by genetic polymorphism in ESR1.

Nut Consumption and Risk of Cancer: A Meta-analysis of Prospective Studies.

BACKGROUND: Epidemiologic studies have investigated the association between nut intake and risk for multiple cancers. However, current findings are inconsistent and no definite conclusion has been drawn from prospective studies. We therefore conducted this meta-analysis to evaluate the relationship between nut consumption and risk of cancer. METHODS: Prospective studies reporting associations between nut intake and risk for all types of cancer were identified by searching Web of Science and PubMed databases up to June 2019. Risk ratios (RR) and 95% confidence intervals (CI) were extracted and then pooled across the studies using a random-effect model. A dose-response analysis was modeled by performing restricted cubic splines when data were available. RESULTS: Thirty-three studies that included more than 50,000 cancer cases were eligible for the analysis. When comparing the highest with the lowest category of nut intake, high consumption of nuts was significantly associated with decreased risk of overall cancer (RR = 0.90; 95% CI, 0.85-0.95). The protective effect of nut consumption was especially apparent against cancers from the digestive system (RR = 0.83; 95% CI, 0.77-0.89). Among different nut classes, significant association was only obtained for intake of tree nuts. We also observed a linear dose-response relationship between nut consumption and cancer: Per 20 g/day increase in nut consumption was related to a 10% (RR = 0.90; 95% CI, 0.82-0.99) decrease in cancer risk. CONCLUSIONS: Our analysis demonstrated an inverse association of dietary nut consumption with cancer risk, especially for cancers from the digestive system. IMPACT: This study highlights the protective effect of nuts against cancer.

TERT-rs33963617 and CLPTM1L-rs77518573 reduce the risk of non-small cell lung cancer in Chinese population.

BACKGROUND: Genome-wide association studies (GWAS) have identified 5p15.33 as a susceptible locus for lung cancer. However, for non-small cell lung cancer (NSCLC), low-frequency risk variants in this region have not been systematically studied. We intended to explore the associations between low-frequency variants on 5p15.33 and NSCLC using a next-generation sequencing based approach in this study. METHODS: We have acquisited the variation spectrum of 400 NSCLC patients on 5p15.33 by sequencing the targeted region before. Candidate variants were primarily selected by restricting the minor allele frequency (MAF 1-5%) and then by comparing their frequency in 400 NSCLC patients with 1008 East Asians from The genome Aggregation Database (gnomAD). The associations between candidate variants and NSCLC were discovered and replicated in two case-control sets: discovery stage with 960 cases and 916 controls, and replication stage with 1596 cases and 1614 controls in total. RESULTS: Five low-frequency variants were selected as our candidates and subsequent association analyses showed that 2 polymorphisms were significantly associated with risk of NSCLC, including rs33963617 (OR = 0.63, 95% CI: 0.53-0.76, P = 3.80 × 10-7) in TERT and rs77518573 (OR = 0.73, 95% CI: 0.63-0.84, P = 2.00 × 10-5) in upstream of CLPTM1L. When stratified by histologic subtype, a significant association was only investigated in adenocarcinoma for rs77518573. We also observed an obvious cumulative effect of the two significant variants. CONCLUSIONS: We newly identified two NSCLC related variants on chromosome 5p15.33. Both TERT-rs33963617 and CLPTM1L-rs77518573 conferred reduced risk for NSCLC in Chinese Han population.