Unveiling a rare BRAF mutation in minimally invasive follicular thyroid carcinoma: A case report.

RATIONALE: Molecular testing is becoming more widely used; however, the accuracy of diagnostic testing remains a primary consideration, especially for molecular testing that detects specific mutations associated with cancers. PATIENT CONCERNS: A 45-year-old female without documented comorbidities presented a thyroid nodule during a routine health examination. Initial evaluation revealed a 3.8-cm nodule in the left lobe of thyroid, classified as Bethesda System category III on fine needle aspiration cytology. Genetic molecular testing detected the BRAF V600E mutation via quantitative polymerase chain reaction assay, raising concern for papillary thyroid cancer (PTC). DIAGNOSES: The preoperative impression was PTC based on the detection of BRAF V600E mutation. INTERVENTIONS: The patient underwent thyroidectomy as well as lymph node dissection with the expectation to treat PTC. OUTCOMES: The final pathology unexpectedly revealed minimally invasive follicular carcinoma. Confirmatory Sanger sequencing unveiled a novel sequence variation involving nucleotide duplication within the range of 1794 to 1802, a non-V600E BRAF mutation not previously reported in follicular thyroid carcinoma. LESSONS: This case study demonstrates the clinical relevance of exercising caution in molecular testing and its interpretation of results. For genetic testing used for diagnostic purposes, rigorous validation or cross-checking using different methods should always be considered to ensure appropriate interpretation of molecular results.

In Situ, Fusion-Free, Multiplexed Detection of Small Extracellular Vesicle miRNAs for Cancer Diagnostics.

Tumor-derived small extracellular vesicle (sEV) microRNAs (miRNAs) are emerging biomarkers for cancer diagnostics. Conventional sEV miRNA detection methods necessitate the lysis of sEVs, rendering them laborious and time-consuming and potentially leading to damage or loss of miRNAs. Membrane fusion-based in situ detection of sEV miRNAs involves the preparation of probe-loaded vesicles (e.g., liposomes or cellular vesicles), which are typically sophisticated and require specialist equipment. Membrane perforation methods employ chemical treatments that can induce severe miRNA degradation or leaks. Inspired by previous studies that loaded nucleic acids into EVs or cells using hydrophobic tethers for therapeutic applications, herein, we repurposed this strategy by conjugating a hydrophobic tether onto molecular beacons to aid their transportation into sEVs, allowing for in situ detection of miRNAs in a fusion-free and multiplexing manner. This method enables simultaneous detection of multiple miRNA species within serum-derived sEVs for the diagnosis of prostate cancer, breast cancer, and gastric cancer with an accuracy of 83.3%, 81.8%, and 100%, respectively, in a cohort of 66 individuals, indicating that it holds a high application potential in clinical diagnostics.

Effects of long-term exposure to air pollutant mixture on blood pressure in typical areas of North China.

BACKGROUND: Studies about the combined effects of gaseous air pollutants and particulate matters are still rare. OBJECTIVES: This study was performed based on baseline survey of the Diverse Life-Course Cohort in the Beijing-Tianjin-Hebei (BTH) Region of North China to evaluate the association of long-term air pollutants with blood pressure and the combined effect of the air pollutants mixture among 32821 natural han population aged 20 years or above. METHODS: Three-year average exposure to air pollutants (PM10, PM2.5, PM1, O3, SO2, NO2, and CO) and PM2.5 components [black carbon (BC), ammonium (NH4+), nitrate (NO3-), sulfate (SO42-), and organic matter (OM)] of residential areas were calculated based on well-validated models. Generalized linear mixed models (GLMMs) were used to estimate the associations of air pollutants exposure with the systolic blood pressure (SBP), diastolic blood pressure (DBP), Mean arterial pressure (MAP), pulse pressure (PP) and prevalent hypertension. Quantile g-Computation and Bayesian Kernel Machine Regression (BKMR) were employed to assess the combined effect of the air pollutant mixture. RESULTS: We found that long-term exposures of O3, PM2.5, and PM2.5 components were stably and strongly associated with elevated SBP, DBP, and MAP and prevalent hypertension. O3 increased SBP, DBP, and MAP at a similar extent, but with greater effects; while, PM2.5 and PM2.5 components had a greater impact on SBP than DBP, which increased PP simultaneously. In multi-pollutant models, the combined effects of the air pollutant mixture on blood pressure and prevalent hypertension was predominantly influenced by O3, PM2.5, and O3, OM in different models, respectively. For example, O3, PM2.5 contributed 57.25 %, 39.22 % of the positive combined effect of the air pollutant mixture on SBP; and O3, OM positively contributed 70.00 %, 30.00 % on prevalent hypertension, respectively. There were interactions between O3, CO, SO2 and PM2.5 components on hbp, SBP and PP. CONCLUSIONS: The results showed positive associations of air pollutant mixtures with blood pressure, where O3 and PM2.5 (especially OM) might be primary contributors. There were interactions between gaseous air pollutants and PM2.5 components on blood pressure and prevalent hypertension.

Bioinformatics and experimental validation were combined to explore lactylation-related biomarkers in HBV-associated acute liver failure.

BACKGROUND AND AIM: Currently, hepatitis B virus-related acute liver failure (HBV-ALF) has limited treatment options. Studies have shown that histone lactylation plays a role in the progression of liver-related diseases. Therefore, it is essential to explore lactylation-related gene (LRGs) biomarkers in HBV-ALF to provide new information for the treatment of HBV-ALF. METHODS: Two HBV-ALF-related datasets (GSE38941 and GSE14668) and 65 LRGs were used. First, the differentially expressed genes (DEGs) were derived from differential expression analysis, the key module genes from weighted gene co-expression network analysis; and LRGs were used to intersect to obtain the candidate genes. Subsequently, the feature genes obtained from least absolute shrinkage and selection operator regression analysis and support vector machine analysis were intersected to obtain the candidate key genes. Among them, genes with consistent and significant expression trends in both GSE38941 and GSE14668 were used as biomarkers. Subsequently, biomarkers were analyzed for functional enrichment, immune infiltration, and sensitive drug prediction. RESULTS: In this study, five candidate genes (PIGM, PIGA, EGR1, PIGK, and PIGL) were identified by intersecting 6461 DEGs and 2496 key module genes with 65 LRGs. We then screened four candidate key genes from the machine learning algorithm, among which PIGM and PIGA were considered biomarkers in HBV-ALF. Moreover, the results of enrichment analysis showed that the significant enrichment signaling pathways for biomarkers included allograft rejection and valine, leucine, and isoleucine degradation. Thereafter, 11 immune cells differed significantly between groups, with resting memory CD4+ T cells having the strongest positive correlation with biomarkers. Methylphenidate hydrochloride is a potential therapeutic drug for PIGM. CONCLUSION: Two genes, PIGM and PIGA, were identified as biomarkers related to LRGs in HBV-ALF, providing a basis for understanding HBV-ALF pathogenesis.

Heritability and genetic correlations of obesity indices and cardiometabolic traits in the Northern Chinese families.

OBJECTIVE: This study aimed to investigate the heritability of various obesity indices and their shared genetic factors with cardiometabolic traits in the Chinese nuclear family. METHODS: A total of 1270 individuals from 538 nuclear families were included in this cross-sectional study. Different indices were used to quantify fat mass and distribution, including body index mass (BMI), visceral fat index (VFI), and body fat percent (BFP). Heritability and genetic correlations for all quantitative traits were estimated using variance component models. The susceptibility-threshold model was utilized to estimate the heritability for binary traits. RESULTS: Heritability estimates for obesity indices were highest for BMI (59%), followed by BFP (49%), and VFI (40%). Heritability estimates for continuous cardiometabolic traits varied from 24% to 50%. All obesity measures exhibited consistently significant positive genetic correlations with blood pressure, fasting blood glucose, and uric acid (rG range: 0.26-0.57). However, diverse genetic correlations between various obesity indices and lipid profiles were observed. Significant genetic correlations were limited to specific pairs: BFP and total cholesterol (rG = 0.24), BFP and low-density lipoprotein cholesterol (rG = 0.25), and VFI and triglyceride (rG = 0.33). CONCLUSION: The genetic overlap between various obesity indices and cardiometabolic traits underscores the importance of pleiotropic genes. Further studies are warranted to investigate specific shared genetic and environmental factors between obesity and cardiometabolic diseases.

lncSNHG16 promotes hepatocellular carcinoma development by inhibiting autophagy.

OBJECTIVE: To investigate the expression of long non-coding RNA lncSNHG16 in hepatocellular carcinoma (HCC), associations between its expression and patient survival, and its potential role in regulating autophagy in the disease. METHODS: Expression of lncSNHG16 was measured using quantitative real-time PCR in HCC cells in culture and HCC tissues from patients. Effects of lncSNHG16 overexpression were examined in HCC cultures using assays of cell proliferation, wound healing, and migration or invasion in Transwell dishes. Effects of lncSNHG16 overexpression were also examined in subcutaneous tumor in mice. Relationships of lncSNHG16 expression to autophagy and apoptosis in HCC cultures were explored using western blotting and flow cytometry. RESULTS: Higher lncSNHG16 expression in HCC tissues was associated with significantly worse overall and recurrence-free survival of patients. Overexpressing lncSNHG16 in HCC cell culture promoted cell proliferation, migration, and invasion while suppressing apoptosis. lncSNHG16 was associated with upregulation of STAT3 as well as inhibition of autophagy and associated apoptosis. Overexpressing lncSNHG16 accelerated tumor growth and weight in mice. CONCLUSION: The non-coding RNA lncSNHG16 suppresses autophagy and associated apoptosis in HCC, making it a potential therapeutic target.

Oleanane-type triterpenoids from Sabia limoniacea and their anti-inflammatory activities.

Eighteen new oleanane-type triterpenoids were isolated from the stems of Sabia limoniacea, including sabialimon A (1), a triterpenoid with an unprecedented 6/6/6/7/7 pentacyclic skeleton and seventeen undescribed triterpenoids, sabialimons B-R (2 - 18), along with six previously described analogs (19 - 24). Their structures were fully elucidated via extensive spectroscopic analysis including 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), experimental electronic circular dichroism measurements and X-ray crystallographic studies. Compound 1 is the first triterpenoid that possesses a rare ring system (6/6/6/7/7) with an oxygen-bearing bridge between C-17 and C-18 and a hemiketal form at C-17, which is generated a larger ring by the degradation of C-28 and D/E-ring expansion. Biological evaluation revealed that sabialimon I (9), sabialimon K (11), sabialimon P (16) and 11,13(18)-oleanadien-28-hydroxymethyl 3-one (20) exhibited significantly inhibitory activities against nitric oxide (NO) release with IC50 values of 29.65, 23.41, 18.12 and 26.64 µM, respectively, as compared with the positive control (dexamethasone, IC50 value: 40.35 µM). Furthermore, sabialimon P markedly decreased the secretion of TNF-α, iNOS, IL-6 and NF-κB and inhibited the expression of COX-2 and NF-κB/p65 in LPS-induced RAW264.7 cells in a dose-dependent manner.

Double-network polyphenol chitosan hydrogels with instant aldehyde-ß-cyclodextrin-based structure as potential for treating bacterially infected wounds.

Treatment of multiple bacterial infected wounds by eliminating bacteria and promoting tissue regeneration remains a clinical challenge. Herein, dual-network hydrogels (CS-GA/A-ß-CD) with snap-structure were designed to achieve curcumin immobilization, using gallic acid-grafted chitosan (CS-GA) and aldehyde-ß-cyclodextrin (A-ß-CD) crosslinked. A-ß-CD were able to achieve rapid dissolution (≥222.35 mg/mL H2O), and helped CS-GA/A-ß-CD achieve rapid gelation (≤66.23 s). By adjusting the ratio of aldehyde groups of A-ß-CD, mechanical properties and drug release can be controlled. CS-GA/A-ß-CD/Cur exhibited excellent antimicrobial properties against S. aureus, E. coli, and P. aeruginosa. In vivo experiments demonstrated that CS-GA/A-ß-CD/Cur achieved acute bacterial infection wound healing after 20th days, proving its great potential for wound dressing.

Quantum modeling simulates nutrient effect of bioplastic polyhydroxyalkanoate (PHA) production in Pseudomonas putida.

Polyhydroxyalkanoates (PHAs) could be used to make sustainable, biodegradable plastics. However, the precise and accurate mechanistic modeling of PHA biosynthesis, especially medium-chain-length PHA (mcl-PHA), for yield improvement remains a challenge to biology. PHA biosynthesis is typically triggered by nitrogen limitation and tends to peak at an optimal carbon-to-nitrogen (C/N) ratio. Specifically, simulation of the underlying dynamic regulation mechanisms for PHA bioprocess is a bottleneck owing to surfeit model complexity and current modeling philosophies for uncertainty. To address this issue, we proposed a quantum-like decision-making model to encode gene expression and regulation events as hidden layers by the general transformation of a density matrix, which uses the interference of probability amplitudes to provide an empirical-level description for PHA biosynthesis. We implemented our framework modeling the biosynthesis of mcl-PHA in Pseudomonas putida with respect to external C/N ratios, showing its optimization production at maximum PHA production of 13.81% cell dry mass (CDM) at the C/N ratio of 40:1. The results also suggest the degree of P. putida's preference in channeling carbon towards PHA production as part of the bacterium's adaptative behavior to nutrient stress using quantum formalism. Generic parameters (kD, kN and theta θ) obtained based on such quantum formulation, representing P. putida's PHA biosynthesis with respect to external C/N ratios, was discussed. This work offers a new perspective on the use of quantum theory for PHA production, demonstrating its application potential for other bioprocesses.

The effect of chemical doping on the lithiation processes of the crystalline Si anode ‒ A first-principles study.

We employed first-principles calculations to investigate the effect of chemical doping on the lithiation kinetics and dynamic properties of the c-Si anode. Our ab initio molecular dynamics simulations reveal that phosphorous/arsenic doping can greatly enhance the lithiation kinetics of c-Si, whereas boron doping is unable to produce such an improvement. Our calculations also show that boron doping could enhance Li insertion into c-Si, but phosphorous/arsenic doping tends to increase the insertion energy of Li ions. Although the migration energy barriers of Li ions may slightly increase (decrease) in the boron-(phosphorus-/arsenic-)doped c-Si, these changes were only effective within the range of the nearest-neighbor distance from dopants. Furthermore, it was found that the phosphorus-/arsenic-doped Si can be more ductile and can more easily undergo plastic deformation upon lithiation, while the c-Si matrix becomes more brittle and stiffer when doped with boron. Our simulation results also demonstrate that phosphorous- and arsenic-doping can effectively speed up the Li-induced structural amorphization of c-Si while boron doping appears to severely slow it down. These findings unambiguously indicate that the induced mechanical softening of the c-Si bond network can be the primary factor that leads to the enhanced lithiation kinetics in the n-type doped c-Si anodes.

Gypenoside inhibits gastric cancer proliferation by suppressing glycolysis via the Hippo pathway.

Gastric cancer (GC) remains a global disease with a high mortality rate, the lack of effective treatments and the high toxicity of side effects are primary causes for its poor prognosis. Hence, urgent efforts are needed to find safe and effective therapeutic strategies. Gypenoside (Gyp) is a widely used natural product that regulates blood glucose to improve disease progression with few toxic side effects. Given the crucial role of abnormal glycometabolism in driving tumor malignancy, it is important to explore the association between Gyp and glycometabolism in GC and understand the mechanism of action by which Gyp influences glycometabolism. In this study, we demonstrated that Gyp suppresses GC proliferation and migration both in vitro and in vivo. We identified that Gyp suppresses the malignant progression of GC by inhibiting glycolysis using network pharmacology and metabolomics. Transcriptome analysis revealed that the Hippo pathway is a key regulator of glycolysis by Gyp in GC. Furthermore, Gyp induced upregulation of LATS1/2 proteins, leading to increased YAP phosphorylation and decreased TAZ protein expression. The YAP agonist XMU-MP-1 rescued the inhibitory effect of Gyp on GC proliferation by reversing glycolysis. These findings confirmed that Gyp inhibits GC proliferation by targeting glycolysis through the Hippo pathway. Our study examined the role of Gyp in the malignant progression of GC, explored its therapeutic prospects, elucidated a mechanism by which Gyp suppresses GC proliferation through interference with the glycolytic process, thus providing a potential novel therapeutic strategy for GC patients.

Corrigendum: Characterizing the neutrophilic inflammation in chronic rhinosinusitis with nasal polyps.

[This corrects the article DOI: 10.3389/fcell.2021.793073.].

Characterisation of the novel HLA-A*24:630 allele by sequencing-based typing.

HLA-A*24:630 differs from HLA-A*24:20:01:01 by one nucleotide substitution in codon 131 in exon 3.

Advances in the treatment of diabetic peripheral neuropathy by modulating gut microbiota with traditional Chinese medicine.

Diabetic peripheral neuropathy (DPN) is one of the strongest risk factors for diabetic foot ulcers (neuropathic ulcerations) and the existing ulcers may further deteriorate due to the damage to sensory neurons. Moreover, the resulting numbness in the limbs causes difficulty in discovering these ulcerations in a short time. DPN is associated with gut microbiota dysbiosis. Traditional Chinese medicine (TCM) compounds such as Shenqi Dihuang Decoction, Huangkui Capsules and Qidi Tangshen Granules can reduce the clinical symptoms of diabetic nephropathy by modulating gut microbiota. The current review discusses whether TCM compounds can reduce the risk of DPN by improving gut mic-robiota.

A genome-wide association study identifies novel loci of vertigo in an Asian population-based cohort.

The contributing genetic factors of vertigo remain poorly characterized, particularly in individuals of non-European ancestries. Here we show the genetic landscape of vertigo in an Asian population-based cohort. In a two-stage genome-wide association study (Ncase = 6199; Ncontrol = 54,587), we identify vertigo-associated genomic loci in DROSHA and ZNF91/LINC01224, with the latter replicating the findings in European ancestries. Gene-based association testing corroborates these findings. Interestingly, both genes are enriched in cerebellum, a key structure receiving sensory input from the vestibular system. Subjects carrying risk alleles from lead SNPs of DROSHA and ZNF91 incur a 1.74-fold risk of vertigo than those without. Moreover, composite clinical-polygenic risk scores allow differentiation between patients and controls, yielding an area under receiver operating characteristic curve of 0.69. This study identified novel genomic loci for vertigo in an Asian population-based cohort, which may help identifying high risk subjects and provide mechanistic insight in understanding the pathogenesis of vertigo.

Ommaya Reservoir-Assisted Treatment for Giant Cystic Solid Craniopharyngioma in Children.

OBJECTIVE: In children with giant cystic solid craniopharyngioma (CP), the Ommaya reservoir was implanted in the CP cavity, and the cystic fluid was continuously drained for 5 days before the tumor resection. METHODS: An 11-year-old male patient was admitted to the hospital due to vision loss for 1 year, intermittent headache, vomiting for 6 months, and frequent urination for 2 months. Besides, magnetic resonance imaging of the head showed cystic solid lesions in the sellar region, suprasellar, and bilateral frontal lobes, with a size of 96.0×82.6×76.0 mm. Before the surgical resection, an Ommaya reservoir was implanted within the tumor cavity. The drainage was continued for 5 days and was 39 to 50 mL (43.80 ± 4.67 mL). Following the tumor shrank, a craniotomy was performed. RESULTS: Following surgical treatment, the CP was entirely removed. The child subsequently developed hypothyroidism and hypocortisolism, for which hormone replacement therapy was administered. No tumor recurrence was observed after 3 years of follow-up. CONCLUSION: The treatment of giant cystic solid CP in children is challenging. Preoperative implantation of the Ommaya reservoir, continuous drainage of cystic fluid, shrinkage of the tumor, and reduction of tumor tension are beneficial for tumor resection.