Deciphering the effect of phytosterols on Alzheimer's disease and Parkinson's disease: the mediating role of lipid profiles.

BACKGROUND: Studies have suggested that blood circulating phytosterols, plant-derived sterols analogous to cholesterol, were associated with blood lipid levels and the risk of Alzheimer's disease (AD) and Parkinson's disease (PD). This Mendelian randomization (MR) study is performed to determine the causal effect of circulating phytosterols on AD and PD and evaluate the mediation effect of blood lipids. METHODS: Leveraging genome-wide association studies summary-level data for phytosterols, blood lipids, AD, and PD, univariable and multivariable MR (MVMR) analyses were conducted. Four types of phytosterols (brassicasterol, campesterol, sitosterol, and stigmasterol), three blood lipids parameters (high-density lipoprotein cholesterol [HDL-C], non-HDL-C, and triglyceride), two datasets for AD and PD were used. Inverse-variance weighted method was applied as the primary analysis, and false discovery rate method was used for adjustment of multiple comparisons. RESULTS: Using the largest AD dataset, genetically proxied higher levels of stigmasterol (OR = 0.593, 95%CI = 0.431-0.817, P = 0.004) and sitosterol (OR = 0.864, 95%CI = 0.791-0.943, P = 0.004) significantly correlated with a lower risk of AD. No significant associations were observed between all four types of phytosterols levels and PD. MVMR estimates showed that the above causal associations were missing after integrating the blood lipids as exposures. Sensitivity analyses confirmed the robustness of these associations, with no evidence of pleiotropy and heterogeneity. CONCLUSION: The study supports a potential beneficial role of blood stigmasterol and sitosterol in reducing the risk of AD, but not PD, which is dependent on modulating blood lipids. These insights highlight circulating stigmasterol and sitosterol as possible biomarkers and therapeutic targets for AD.

Global trends in colorectal cancer and metabolic syndrome research: a bibliometric and visualization analysis.

Numerous studies have demonstrated a robust correlation between metabolic syndrome (MetS) and colorectal cancer (CRC). Nonetheless, no systematic analysis or visualization of relevant publications has been conducted via bibliometrics. This research, centred on 616 publications obtainable through the Web of Science Core Collection (WoSCC), employed CiteSpace software and VOSviewer software for correlation analyses of authors, journals, institutions, countries, keywords, and citations. The findings indicate that the Public Library of Science had the highest number of publications, while the United States, China, and South Korea were the most contributory nations. Recent years have seen the mechanisms linking Metabolic Syndrome with Colorectal Cancer, including diet, obesity, insulin resistance, and intestinal flora, remain a burgeoning research area. Furthermore, bariatric surgery appears to be a promising new area of study. This paper presents the initial bibliometric and visualization analysis of research literature concerning CRC and MetS which examines research trends and hotspots.

Lanthanide-Polyoxometalate-Based Film with Reversible Photochromism and Luminescent Switching Properties for Erasable Inkless Security Printing.

Security printing is of the utmost importance in the information era. However, the excessive use of inks and paper still faces many economic and environmental issues. Thus, developing erasable inkless security printing materials is a remarkable strategy to save resources, protect the environment, and improve information security. To this endeavor, a photoresponsive lanthanide-polyoxometalate-doped gelatin film with high transparency was developed through the solution casting method. Attenuated total reflection Fourier-transform infrared spectroscopy confirmed the electrostatic and hydrogen bond interactions between gelatin and lanthanide-polyoxometalate. Absorption spectra, luminescent spectra, and digital images indicated that the film displayed reversible photochromism behavior and was accompanied by luminescent switching property upon exposure to UV irradiation and oxygen (in the dark) alternately, which allowed its potential application as a reprintable medium for inkless security printing. The printed information can be erased upon exposure to oxygen in the dark, and the film can be reused for printing again. The film exhibited excellent erasability, reprintability, renewability, and low toxicity. In addition, multiple encryption strategies were designed to improve information security. This work offers an attractive alternative strategy for constructing a reprintable film for inkless security printing in terms of simplifying the preparation process, saving resources, and protecting the environment.

Prime editing-mediated correction of the CFTR W1282X mutation in iPSCs and derived airway epithelial cells.

A major unmet need in the cystic fibrosis (CF) therapeutic landscape is the lack of effective treatments for nonsense CFTR mutations, which affect approximately 10% of CF patients. Correction of nonsense CFTR mutations via genomic editing represents a promising therapeutic approach. In this study, we tested whether prime editing, a novel CRISPR-based genomic editing method, can be a potential therapeutic modality to correct nonsense CFTR mutations. We generated iPSCs from a CF patient homozygous for the CFTR W1282X mutation. We demonstrated that prime editing corrected one mutant allele in iPSCs, which effectively restored CFTR function in iPSC-derived airway epithelial cells and organoids. We further demonstrated that prime editing may directly repair mutations in iPSC-derived airway epithelial cells when the prime editing machinery is efficiently delivered by helper-dependent adenovirus (HDAd). Together, our data demonstrated that prime editing may potentially be applied to correct CFTR mutations such as W1282X.

The Value of Targeting CXCR4 With 68Ga-Pentixafor PET/CT for Subtyping Primary Aldosteronism.

CONTEXT: Primary aldosteronism (PA) is one of the leading causes of secondary hypertension, and its diagnostic subtyping consistently presents a clinical challenge. OBJECTIVE: This study aimed to investigate the potential of 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT) in PA classification and its applicability in guiding the development of clinical treatment plans by increasing the sample size. METHODS: We prospectively enrolled 120 patients with either PA or nonfunctional adenoma (NFA) for analysis. All patients underwent 68Ga-Pentixafor PET/CT. Of these, 11 patients underwent adrenal venous sampling (AVS), 77 underwent adrenalectomy, 76 received pathological diagnoses, and 71 underwent immunohistochemical detection of aldosterone synthase (CYP11B2). Immunohistochemistry for C-X-C chemokine receptor 4 (CXCR4) was performed in 62 cases. Follow-up was conducted for all patients. RESULTS: Among the 120 patients, 66 were diagnosed with aldosterone-producing adenoma (APA), 33 with idiopathic hyperaldosteronism (IHA), and 21 with NFA. For APA patients, the sensitivity, specificity, and accuracy of visual analysis using 68Ga-Pentixafor PET/CT were 92.40%, 94.40%, and 93.33%, respectively. Furthermore, for APA patients with a nodule greater than 1 cm in diameter, when the maximum standard uptake value was 7.3 or greater, the specificity was 100%; and for APA patients with a nodule less than 1 cm in diameter, 68Ga-Pentixafor PET/CT also exhibited high sensitivity. AVS was successfully performed in 5 patients. Among the 5 patients, the concordance rate between the AVS and 68Ga-Pentixafor PET/CT for PA subtyping was 60%. In the 77 patients who underwent adrenalectomy, 61 PET/CT scans displayed positive lesions, all of which benefited from the surgery. Additionally, the concordance rate between 68Ga-Pentixafor PET/CT imaging and CYP11B2 was 81.69%. CONCLUSION: 68Ga-Pentixafor PET/CT is a reliable and noninvasive functional imaging technique that demonstrates high accuracy in classifying PA and provides valuable guidance for clinical treatment decision-making.

The emerging role of N6-methyladenine RNA methylation in metal ion metabolism and metal-induced carcinogenesis.

N6-methyladenine (m6A) is the most common and abundant internal modification in eukaryotic mRNAs, which can regulate gene expression and perform important biological tasks. Metal ions participate in nucleotide biosynthesis and repair, signal transduction, energy generation, immune defense, and other important metabolic processes. However, long-term environmental and occupational exposure to metals through food, air, soil, water, and industry can result in toxicity, serious health problems, and cancer. Recent evidence indicates dynamic and reversible m6A modification modulates various metal ion metabolism, such as iron absorption, calcium uptake and transport. In turn, environmental heavy metal can alter m6A modification by directly affecting catalytic activity and expression level of methyltransferases and demethylases, or through reactive oxygen species, eventually disrupting normal biological function and leading to diseases. Therefore, m6A RNA methylation may play a bridging role in heavy metal pollution-induced carcinogenesis. This review discusses interaction among heavy metal, m6A, and metal ions metabolism, and their regulatory mechanism, focuses on the role of m6A methylation and heavy metal pollution in cancer. Finally, the role of nutritional therapy that targeting m6A methylation to prevent metal ion metabolism disorder-induced cancer is summarized.

Anti-Oxidative and Anti-Aging Effects of Probiotic Fermented Ginseng by Modulating Gut Microbiota and Metabolites in Caenorhabditis elegans.

Antioxidative and antiaging abilities of probiotic fermented ginseng (PG) were evaluated in Caenorhabditis elegans (C. elegans). Lifespan and effect on heat stress and acute oxidative stress in C. elegans were significantly enhanced by PG. Antioxidative enzymes such as T-SOD, GSH-PX, CAT were significantly up-regulated, and MDA, ROS and apoptosis levels were significantly down-regulated. At the same time, PG exerted antioxidant and anti-aging activities by reducing the expression of DAF-2 mRNA and increasing the expression of SKN-1 and SOD-3 mRNA in C. elegans. In addition, the mechanism of antioxidative and antiaging activities of PG was explored through gut microbiota sequencing and untargeted metabolomics. The results of gut microbiota indicated that PG could significantly improve the composition and structure of microbes in the gut of C. elegans, and the relative abundance of beneficial bacteria was up-regulated. Untargeted metabolomic results elucidated that PG modulated antioxidant and antiaging activities through neuroactive ligand-receptor interaction, Citrate cycle (TCA cycle), pyruvate metabolism, ascorbate and aldarate metabolism and D-Arginine and D-ornithine metabolism of C. elegans. These results indicated that PG had excellent antioxidant and anti-aging activities, providing research value for the development of functional foods and improvement of aging-related diseases.

Squamous-columnar junction of Von Ebner's glands may be a significant origin of squamous cell carcinomas in the base of the tongue.

Objectives: The histological origin of base of the tongue (BOT) carcinomas is still elusive, and most studies have been focusing on the lingual tonsil. In this study, we sought to identify the existence of the squamous-columnar junction (SCJ) in the human Von Ebner's glandular duct and explored the potential of that in forming squamous cell carcinomas in BOT. Materials and methods: The specific genomes of BOT carcinoma were acquired and screened out by The Cancer Genome Atlas (TCGA) database analysis. The 4-nitroquinoline-1-oxide (4-NQO)-treated mouse model was used to explore the transformation of SCJ during cancerization. We used immunohistochemistry to confirm the characteristics of SCJ in human Von Ebner's gland, which were further compared with those in the anus and cervix. Results: The SCJ in the human Von Ebner's glandular duct was found to be similar to that of the cervix and anus. The transformation zone in the 4-NQO-treated mouse model had a multilayered epithelium structure similar to that of HPV16-transgenic mice. In human, the transformation zone of Von Ebner's gland is also similar to that of the cervix and anus. Conclusion: It is the first time that the existence of SCJ in the opening of the human Von Ebner's glandular duct was confirmed. The SCJ of Von Ebner's glands may be a significant origin of squamous cell carcinomas in BOT.

Discovery and therapeutic implications of bioactive dihydroxylated phenolic acids in patients with severe heart disease and conditions associated with inflammation and hypoxia.

Our initial studies detected elevated levels of 3,4-dihydroxyphenyllactic acid (DHPLA) in urine samples of patients with severe heart disease when compared with healthy subjects. Given the reported anti-inflammatory properties of DHPLA and related dihydroxylated phenolic acids (DPAs), we embarked on an exploratory multi-centre investigation in patients with no urinary tract infections to establish the possible pathophysiological significance and therapeutic implications of these findings. Chinese and Caucasian patients being treated for severe heart disease or those conditions associated with inflammation (WBC ≥ 10 ×109/L or hsCRP ≥ 3.0 mg/L) and/or hypoxia (PaO2 ≤ 75 mmHg) were enrolled; their urine samples were analyzed by HPLC, HPLC-MS, GC-MS and biotransformation assays. DHPLA was detected in urine samples of patients, but undetectable in healthy volunteers. Dynamic monitoring of inpatients undergoing treatment showed their DHPLA levels declined in proportion to their clinical improvement. In DHPLA-positive patients' fecal samples, Proteus vulgaris and P. mirabilis were more abundant than healthy volunteers. In culture, these gut bacteria were capable of reversible interconversion between DOPA and DHPLA. Furthermore, porcine and rodent organs were able to metabolize DOPA to DHPLA and related phenolic acids. The elevated levels of DHPLA in these patients suggest bioactive DPAs are generated de novo as part of a human's defense mechanism against disease. Because DHPLA isolated from Radix Salvia miltiorrhizae has a multitude of pharmacological activities, these data underpin the scientific basis of this medicinal plant's ethnopharmacological applications as well as highlighting the therapeutic potential of endogenous, natural or synthetic DPAs and their derivatives in humans.

Global trends in research on irritable bowel syndrome and the brain-gut axis: Bibliometrics and visualization analysis.

Irritable bowel syndrome (IBS) is a gastrointestinal disorder with no structural damage, and its pathogenesis remains unclear. Studies have shown that the brain-gut axis is closely related to the occurrence of IBS. However, studies of IBS related to the brain-gut axis have not been systematically analyzed by bibliometrics and visual analysis. This study is based on 631 publications in the Web of Science Core Collection (WoSCC) to analyze hot spots and trends in this field. The collaborations between different authors, institutions, countries, and keywords were bibliometrically analyzed by CiteSpace software. Meanwhile, VOSviewer analyzed the references. The results show that since 2012, the number of publications has been growing rapidly. According to the collaborative network analysis, the United States, the National University of Ireland, Cork, and J.F. Cryan are the countries, institutions, and authors contributing the most, respectively. Through keywords and literature analysis, mechanisms and therapy associated with IBS and the brain-gut axis have still been a research focus in recent years. Furthermore, the physiological and pathological mechanisms of the brain-gut axis influencing IBS (related to gastrointestinal dysfunction, vagus nerve, visceral pain, intestinal flora, serotonin, tryptophan metabolism, stress, brain-derived neurotrophic factor (BDNF), and malonyldialdehyde) are the future research trends, especially the mechanisms related to intestinal flora. This is the first bibliometric and visualization analysis of IBS and brain-gut axis-related literature to explore research hotspots and trends.

Callispheres® drug-eluting beads transarterial chemoembolization might be an efficient and safety down-staging therapy in unresectable liver cancer patients.

PURPOSE: The purpose was to explore the effect of drug-eluting beads transarterial chemoembolization (DEB-TACE) on down-staging in unresectable liver cancer patients. METHODS: A total of 180 patients with PHC treated by TACE were retrospectively analyzed. These included 80 cases in the DEB-TACE group and 100 cases in the cTACE group. Of these, 56 had complete clinical data (DEB-TACE: 24, cTACE: 32), and 23 patients received hepatectomy after TACE as a down-staging therapy (DEB-TACE: 15, cTACE: 8). Data (including clinical characteristics, clinical efficacy, tumor response, tumor diameters, residual liver volume, and liver function indexes before and after TACE, RFS, OS, and complications were collected and compared. Treatment response was evaluated at 1 month after TACE. Tumor diameter was evaluated by abdominal computed tomography scan. The residual liver volume was evaluated by IQQA liver system, and relapse-free survival (RFS) and overall survival (OS) were calculated by Kaplan-Meier curves. RESULTS: The conversion rate in DEB-TACE group was higher than cTACE group (18.8% vs 8%, p = 0.032). In DEB-TACE group, 17 patients achieved objective response rate (ORR) which was higher than cTACE group (70.8% vs 34.4%, p = 0.007). The tumor necrosis rate was higher in DEB-TACE group, but there was no significant difference between the two groups (p = 0.053). Tumor diameter was decreased after TACE compared to before TACE (DEB-TACE: 9.4 ± 3.3 vs. 5.4 ± 3.5 cm, p = 0.003; cTACE: 9.7 ± 2.6 vs. 6.9 ± 2.2, p = 0.036). As to residual liver volume, it was increased after TACE compared to before TACE (1066.2 cm3 vs. 1180.3 cm3, p = 0.007) in DEB-TACE group, while there was no significant difference in cTACE group (1046.4 cm3 vs. 1170 cm3, p = 0.339) compared by paired-sample t-test, but there was no significant difference before and after TACE when compared by unpaired-sample t-test (p > 0.05). After TACE at 1 month, the AFP level in the DEB-TACE group was significantly lower than that in the cTACE group (p = 0.003). For survival, the median RFS was 26.0 months in DEB-TACE group and 15 months in cTACE group; there was significant difference between the two groups (p = 0.0465). As to OS, the median OS in DEB-TACE group was higher than that in cTACE group, but there was no significant difference between the two groups (p = 0.165). For safety profiles, in terms of liver function and adverse events, there was no significant difference between the two groups. CONCLUSION: Compared with cTACE, DEB-TACE might be a more efficient and safety down-staging treatment in unresectable liver cancer patients.

ACE2 maybe serve as a prognostic biomarker in breast invasive carcinoma.

BACKGROUND: Breast cancer is a frequently occurring malignant tumor in women. Angiotensin-converting enzyme 2 (ACE2) is widely expressed in most organs; however, the association of ACE2 with prognosis and immune infiltration in breast invasive carcinoma (BRCA) remains elusive. METHODS: We explored the expression level and prognostic value of ACE2 in patients with BRCA using a series of online bioinformatics analysis databases encompassing Oncomine, UALCAN, Kaplan-Meier plotter, TIMER, LinkedOmics, and GEO. qRT-PCR was performed to verify our findings. RESULTS: Angiotensin-converting enzyme 2 mRNA and protein expression levels were decreased in BRCA tissues, and patients with low ACE2 expression levels had a poor prognosis. DNA promoter methylation of ACE2 significantly downregulated ACE2 expression in BRCA, while the expression of this protein was positively linked to immune infiltration of B cells, CD8+ and CD4+ T cells, neutrophils, and dendritic cells in BRCA tissues. The high expression level of ACE2 in enriched basophils, CD8+ T cells, and type-2 helper T cells, which showed decreasing levels, indicated a better prognosis for BRCA. Enrichment analyses revealed that NF-κB, IL-17, and TNF signaling pathways were highly correlated to ACE2 in BRCA. Verification study revealed that downregulation of ACE2 was associated with a better prognosis in BRCA. Univariate and multivariate analysis confirmed ACE2 expression and clinical stage as independent prognostic factors for breast cancer. CONCLUSIONS: Angiotensin-converting enzyme 2 may be a potential prognostic biomarker and target for BRCA. Nevertheless, future investigations are needed for validating our findings and promoting the clinical application of ACE2 in BRCA.

Effect of Lycium barbarum polysaccharides on cell signal transduction pathways.

Lycium barbarum polysaccharide (LBP), is a major active ingredient Lycium barbarum (LB), which exhibits several beneficial effects through NF-κB, PI3K-Akt-mTOR, p38-MAPK, Wnt-ß-catenin, PI3K-Akt-GSK-3ß, and MyD88 signal pathway, including anti-oxidation, and anti-aging, hypolipidemic and hypoglycemic, radiation, anti-tumor, and neuroprotection. Today, many researching papers are published on the LBP in physiology and pathology; however, the review of the LBP taking part in the signal transduction pathway in physiology and pathology is rear searched. Therefore, this research topic is a collection of reviews and original research articles that focus on the methods of the LBP extraction and its effects on the signal transduction pathway. The aim of this study is to provide theoretical evidence for in-depth analysis of the mechanisms of LBP in clinical clinical research studies.

Structural modification of aluminum oxides for removing fluoride in water: crystal forms and metal ion doping.

In this paper, the effect of different crystal forms of Al2O3 on fluoride removal was studied. All crystal forms of Al2O3 were based on the same boehmite precursor and were obtained using a hydrothermal and calcination method. γ-Al2O3 had higher fluoride removal performance (52.15 mg/g) compared with θ-Al2O3 and α-Al2O3. Density functional theory (DFT) calculations confirmed that fluoride removal was greatest for γ-Al2O3, followed by θ-Al2O3 and α-Al2O3, and γ-Al2O3 possessed the strongest fluoride binding energy (-3.93 eV). The typical adsorption behaviour was consistent with the Langmuir model and pseudo-second-order model, indicating chemical and monolayer adsorption. Different metal ions were used to modify γ-Al2O3, and lanthanum had the best effect. Lanthanum oxide was shown to play an important role in fluoride removal. The best La/Al doping ratio was 20 At%. The adsorption process of the composite was also consistent with chemical and monolayer adsorption. When the La/Al doping rate was 20%, the adsorption capacity reached 94.64 mg/g. Compared with γ-Al2O3 (1.39 × 10-7 m/s), the adsorption rate of 20La-Al2O3 was 3.93 × 10-7 m/s according to the mass transfer model. Furthermore, DFT was used to provide insight into the adsorption mechanism, which was mainly driven by electrostatic attraction and ion exchange.

Ulnar-Mammary syndrome with TBX3 gene mutation in a Chinese family: A case report and literature review. / TBX3åŸºå› çªå˜è‡´Ulnar-Mammary综合征1ä¾‹å®¶ç³»æŠ¥é“å¹¶æ–‡çŒ®å¤ä¹ .

Ulnar-Mammary syndrome (UMS) is a rare monogenic disorder caused by mutations of the TBX3 gene. This paper reported a family of UMS. The proband, a 15-year old man, was presented with mammary gland dysplasia, ulnar limb defect, short stature, and delayed growth. Whole exome sequencing revealed a 1294_1301dup mutation in exon 6 of the TBX3 gene. Sanger sequencing was used to verify other members of the family, which suggested his mother also carried the same mutation, but merely resulting in the dysplasia of her left little finger. Notably, unilateral finger involvement without any systemic organ involvement was unusual in UMS patients. The proband then was treated with recombinant human growth hormone (rhGH) and human chorionic gonadotropin (hCG). After a year and a half, his height and secondary sexual characteristics were significantly improved. The clinical manifestations of the disease are highly heterogeneous, which is easy to be misdiagnosed and missed. When the diagnosis is unclear, genetic testing is helpful for auxiliary diagnosis.

A small molecule that induces translational readthrough of CFTR nonsense mutations by eRF1 depletion.

Premature termination codons (PTCs) prevent translation of a full-length protein and trigger nonsense-mediated mRNA decay (NMD). Nonsense suppression (also termed readthrough) therapy restores protein function by selectively suppressing translation termination at PTCs. Poor efficacy of current readthrough agents prompted us to search for better compounds. An NMD-sensitive NanoLuc readthrough reporter was used to screen 771,345 compounds. Among the 180 compounds identified with readthrough activity, SRI-37240 and its more potent derivative SRI-41315, induce a prolonged pause at stop codons and suppress PTCs associated with cystic fibrosis in immortalized and primary human bronchial epithelial cells, restoring CFTR expression and function. SRI-41315 suppresses PTCs by reducing the abundance of the termination factor eRF1. SRI-41315 also potentiates aminoglycoside-mediated readthrough, leading to synergistic increases in CFTR activity. Combining readthrough agents that target distinct components of the translation machinery is a promising treatment strategy for diseases caused by PTCs.

Novel Correctors and Potentiators Enhance Translational Readthrough in CFTR Nonsense Mutations.

Premature-termination codons (PTCs) in CFTR (cystic fibrosis [CF] transmembrane conductance regulator) result in nonfunctional CFTR protein and are the proximate cause of ∼11% of CF-causing alleles, for which no treatments exist. The CFTR corrector lumacaftor and the potentiator ivacaftor improve CFTR function with terminal PTC mutations and enhance the effect of readthrough agents. Novel correctors GLPG2222 (corrector 1 [C1]), GLPG3221 (corrector 2 [C2]), and potentiator GLPG1837 compare favorably with lumacaftor and ivacaftor in vitro. Here, we evaluated the effect of correctors C1a and C2a (derivatives of C1 and C2) and GLPG1837 alone or in combination with the readthrough compound G418 on CFTR function using heterologous Fischer rat thyroid (FRT) cells, the genetically engineered human bronchial epithelial (HBE) 16HBE14o- cell lines, and primary human cells with PTC mutations. In FRT lines pretreated with G418, GLPG1837 elicited dose-dependent increases in CFTR activity that exceeded those from ivacaftor in FRT-W1282X and FRT-R1162X cells. A three-mechanism strategy consisting of G418, GLPG1837, and two correctors (C1a + C2a) yielded the greatest functional improvements in FRT and 16HBE14o- PTC variants, noting that correction and potentiation without readthrough was sufficient to stimulate CFTR activity for W1282X cells. GLPG1837 + C1a + C2a restored substantial function in G542X/F508del HBE cells and restored even more function for W1282X/F508del cells, largely because of the corrector/potentiator effect, with no additional benefit from G418. In G542X/R553X or R1162X/R1162X organoids, enhanced forskolin-induced swelling was observed with G418 + GLPG1837 + C1a + C2a, although GLPG1837 + C1a + C2a alone was sufficient to improve forskolin-induced swelling in W1282X/W1282X organoids. Combination of CFTR correctors, potentiators, and readthrough compounds augments the functional repair of CFTR nonsense mutations, indicating the potential for novel correctors and potentiators to restore function to truncated W1282X CFTR.

A novel transcription factor negatively regulates antioxidant response, cell wall integrity and virulence in the fungal insect pathogen, Beauveria bassiana.

Genomic data have identified a class of fungal specific transcription factors (FsTFs) that are thought to regulate unique aspects of fungal gene expression, although the functions of many of these proteins remain unknown. Here, a novel FsTF (BbStf1), which features a leucine zipper dimerization domain and a fungal transcription factor regulatory middle homology region, was characterized in Beauveria bassiana, a filamentous insect fungal pathogen. Transcriptional activation and nuclear localization were experimentally confirmed for BbStf1. Disruption of Bbstf1 resulted in increased tolerance to oxidative stress and cell wall perturbation, accompanied by increased peroxidase (POD) and superoxide dismutase (SOD) activities and ratio of reduced/oxidized glutathione (GSH/GSSG), and by thickened cell wall and altered composition. Gene expression profile analysis revealed that transcription patterns of antioxidant enzyme and cell wall integrity-involved genes were altered in the ∆Bbstf1, including some BbStf1-targeted genes clarified with evidence. The ∆Bbstf1 strain displayed greater virulence to Galleria mellonella in the bioassays through both topical infection and intrahaemocoel injection due to more rapid proliferation in the haemocoel as compared to the wild-type strain. Altogether, BbStf1 acts as a negative regulator of antioxidant response, cell wall integrity and virulence in B. bassiana.

Recent progress in understanding the mechanism of heavy metals retention by iron (oxyhydr)oxides.

Heavy metals are widespread toxic environmental pollutants that can generate enormous health and public concern. Iron (oxyhydr)oxides are ubiquitous in both natural and engineered environments and have great retention capacity of heavy metals due to their high surface areas and reactivity. The sequestration of heavy metal by iron (oxyhydr)oxides is one of the most vital geochemical/chemical processes controlling their environmental fate, transport, and bioavailability. In this review, some of the common iron (oxyhydr)oxides are introduced in detail in terms of their formation, occurrence, structure characteristics and interaction with heavy metals. Moreover, the retention mechanisms of metal cations (e.g., Pb, Cu, Cd, Ni, Zn), metal oxyanions (e.g., As, Sb, Cr), and coexisting multiple metals on various iron (oxyhydr)oxides are fully reviewed. Principal mechanisms of surface complexation, surface precipitation and structural incorporation are responsible for heavy metal retention on iron (oxyhydr)oxides, and greatly dependent on mineral species, metal ion species, reacting conditions (i.e., pH, heavy metal concentration, ionic strength, etc.) and chemical process (i.e., adsorption, coprecipitaton and mineral phase transformation process). The retention mechanisms summarized in this review would be helpful for remediating heavy metal contamination and predicting the long-term behavior of heavy metal in natural and engineered environments.