Fat deposition, fatty acid profiles, antioxidant capacity and differentially expressed genes in subcutaneous fat of Tibetan sheep fed wheat‐based diets with and without xylanase supplementation

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Abstract

Xylanase, an exogenous enzyme that plays an essential role in energy metabolism by hydrolysing xylan into xylose, has been shown to positively influence nutrient digestion and utilisation in ruminants. The objective of this study was to evaluate the effects of xylanase supplementation on the back-fat thickness, fatty acid profiles, antioxidant capacity, and differentially expressed genes (DEGs) in the subcutaneous fat of Tibetan sheep. Sixty three-month-old rams with an average weight of 19.35 ± 2.18 kg were randomly assigned to control (no enzyme added, WH group) and xylanase (0.2% of diet on a dry matter basis, WE group) treatments. The experiment was conducted over 97 d, including 7 d of adaption to the diets. The results showed that xylanase supplementation in the diet increased adipocyte volume of subcutaneous fat (p < 0.05), shown by hematoxylin and eosin (H&E) staining. Gas chromatography showed greater concentrations of C14:0 and C16:0 in the subcutaneous fat of controls compared with the enzyme-treated group (p < 0.05), while opposite trend was seen for the absolute contents of C18:1n9t, C20:1, C18:2n6c, C18:3, and C18:3n3 (p < 0.05). Compared with controls, supplementation with xylanase increased the activity of T-AOC significantly (p < 0.05). Transcriptomic analysis showed the presence of 1630 DEGs between the two groups, of which 1023 were up-regulated and 607 were down-regulated, with enrichment in 4833 Gene Ontology terms, and significant enrichment in 31 terms (p < 0.05). The common DEGs were enriched in 295 pathways and significantly enriched in 26 pathways. Additionally, the expression of lipid-related genes, including fatty acid synthase, superoxide dismutase, fatty acid binding protein 5, carnitine palmytoyltransferase 1 A, and peroxisome proliferator-activated receptor A were verified via quantitative reverse-transcription polymerase chain reaction. In conclusion, dietary xylanase supplementation was found to reduce subcutaneous fat deposition in Tibetan sheep, likely through modulating the expression of lipid-related genes.

Comprehensive analyses of the clinicopathological features and genomic mutations of combined hepatocellular‐cholangiocarcinoma

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Abstract

Aim

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer that has two different tumor phenotypes in a single tumor nodule. The relationship between genetic mutations and clinicopathological features of cHCC-CCA remains to be elucidated.

Methods

Whole-exome sequencing analyses were carried out in 13 primary and 2 recurrent cHCC-CCAs. The whole-exome analyses and clinicopathological information were integrated.

Results

TP53 was the most frequently mutated gene in this cohort, followed by BAP1, IDH1/2, and NFE2L2 mutations in multiple cases. All tumors with diameters <3 cm had TP53 mutations. In contrast, six of seven tumors with diameters ≥3 cm did not have TP53 mutations, but all seven tumors had mutations in genes associated with various pathways, including Wnt, RAS/PI3K, and epigenetic modulators. In the signature analysis, the pattern of mutations shown in the TP53 mutation group tended to be more similar to HCC than the TP53 nonmutation group. Mutations in recurrent cHCC-CCA tumors were frequently identical to those in the primary tumor, suggesting that those tumors originated from identical clones of the primary cHCC-CCA tumors. Recurrent and co-occurrent HCC tumors in the same patients with cHCC-CCA had either common or different mutation patterns from the primary cHCC-CCA tumors in each case.

Conclusions

The study suggested that there were two subtypes of cHCC-CCA, one involving TP53 mutations in the early stage of the carcinogenic process and the other not involving such mutations. The comparison of the variants between primary and recurrent tumors suggested that cHCC-CCA was derived from an identical clone.

Protein profiles reveal MSH6/MSH2 as a potential biomarker for hepatocellular carcinoma with microvascular invasion MSH6/MSH2 is an biomarker for HCC with HCC

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Abstract

Aim

Microvascular invasion (MVI) is an independent risk factor for postoperative recurrence and metastasis in hepatocellular carcinoma (HCC). However, the specific protein expression profiles that differentiate HCC with MVI from those without MVI remain unclear.

Methods

The profiles of proteins in early-stage HCC tissues and normal liver tissues were characterized by quantitative proteomics techniques. Immunohistochemical (IHC) staining was performed on tissue microarrays from 80 HCC patients to assess the expression of MSH2 and MSH6. Cell counting and colony formation, migration and invasion assays were performed in vitro.

Results

We identified 5164 proteins in both HCC tissues and adjacent normal liver tissues. As compared to HCC without MVI, 148 upregulated proteins and 97 downregulated proteins were found in HCC with MVI. Particularly noteworthy was the remarkable upregulation of MSH6/MSH2 among these dysregulated proteins in HCC with MVI. Further validation through bioinformatics prediction and IHC confirmed the elevated expression of MSH6/MSH2, which correlated with aggressive disease characteristics and poor prognosis. Receiver operating characteristic curve analyses demonstrated a substantial area under curve of 0.761 (specificity: 71.79%, sensitivity: 73.17%) for the combined use of MSH6/MSH2. Knockdown of MSH6/MSH2 significantly inhibited HCC cell proliferation and invasion in vitro.

Conclusions

Our study establishes MSH6 or MSH2 as an oncogene that is prominently overexpressed during HCC progression which provides new targets for HCC with MVI.

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The detection of Bursaphelenchus xylophilus via accelerated strand exchange amplification: An ultra‐rapid and accurate method

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The detection of Bursaphelenchus xylophilus via accelerated strand exchange amplification: An ultra-rapid and accurate method

In this work, an approach for the ultra-fast and accurate detection of B. xylophilus in pinewood called accelerated strand exchange amplification (ASEA) was established for the first time, which only needs one Bst DNA polymerase and a set of primers.


Abstract

One of the most damaging pathogens of pinewood is the pinewood nematode, Bursaphelenchus xylophilus, which could cause an adverse effect on the ecosystems of forests and the commerce of timber. Therefore, it is crucial to realize rapid and accurate B. xylophilus detection. In this work, an accelerated strand exchange amplification method (ASEA) was established to detect B. xylophilus for the first time. By integrating with fast nucleic acid extraction, the whole detection procedure could be finished within 30 min, dramatically shortened the detection time. The ASEA method exhibited high specificity towards B. xylophilus and the detection limit for B. xylophilus plasmid DNA was as low as 1.0 × 100 copies/μL. Furthermore, the ASEA approach also exhibited accurate detection for B. xylophilus when applied to actual pinewood samples, meeting the demand of B. xylophilus detection in realistic scenario. We believe the ASEA method has significant potential for B. xylophilus detection, and it will be helpful for controlling forest pest and quarantine regulations.

Characterization the prognosis role and effects of snoRNAs in melanoma patients

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Abstract

Melanoma is a melanocyte-derived malignant cancer and is known for its early metastasis and high mortality rates. It is a highly cutaneous tumour disease that could be related to the abnormal immune microenvironment, and the identification of reliable diagnostic and prognostic markers is crucial for improving patient outcomes. In the search for biomarkers, various types of RNAs have been discovered and recognized as reliable prognostic markers. Among these, small nucleolar RNAs (snoRNAs) have emerged as a promising avenue for studying early diagnosis and prognostic markers in tumours due to their widespread presence in tissues, tumour specificity and stability. In our study, we analysed snoRNAs data from melanoma samples in the TCGA-SKCM cohort and developed a prognostic model comprising 12 snoRNAs (SNORD9, SNORA31, SNORD14E, SNORA14A, SNORA5A, SNORD83A, SNORA75, AL096855, AC007684, SNORD14A, SNORA65 and AC004839). This model exhibited unique prognostic accuracy and demonstrated a significant correlation with the immune infiltration tumour microenvironment. Additionally, analysis of the GSE213145 dataset, which explored the sensitivity and resistance of immune checkpoint inhibitors, further supported the potential of snoRNAs as prognostic markers for immunotherapy. Overall, our study contributes reliable prognostic and immune-related biomarkers for melanoma patients. These findings can offer valuable insights for the future discovery of novel melanoma treatment strategies and hold promise for improving clinical outcomes in melanoma patients.

Weighted thyroid‐stimulating hormone disturbance in prognosis of hepatitis b virus related acute‐on‐chronic liver failure

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Weighted thyroid-stimulating hormone disturbance in prognosis of hepatitis b virus related acute-on-chronic liver failure

Present study firstly identified TSH was a promising predictor for HBV-ACLF outcome, and then developed a novel prognostic score (mCLIF-OFs) by weighting TSH. Thirdly, we estimated and validated the high performance of the novel mCLIF-OFs from aspects of calibration, discrimination, and clinical net benefit. Those findings would facilitate early assessment of prognosis of HBV-ACLF and provide a novel tool to manage the life-threatening disease.


Abstract

Background

To weighted the prognostic value of thyroid hormones in catastrophic ACLF.

Methods

A retrospective cohort (n=635) and two prospective cohorts (n=353, and 198) were enrolled in this study. The performance of novel developed prognostic score was assessed from aspects of reliability, discrimination, and clinical net benefit.

Results

Thyroid-stimulating hormone (TSH) was identified as most potential prognostic predictor for HBV-ACLF among thyroid hormones. The novel score (mCLIF-OFs) was developed with weighted TSH and other scored organs in CLIF-OFs using the retrospective cohort (n=635). The predicted risk and observed probabilities of death were comparable across the deciles of mCLIF-OFs (Hosmer-Lemeshow χ2 =4.28, p=0.83; Brier scaled=11.9). The C-index of mCLIF-OFs (0.885 [0.883-0.887]) for 30-day mortality was significantly higher than that of the CLIF-OFs, CLIF-SOFAs, CLIF-C ACLFs, MELD, and Child-Pugh (all p<0.001). The absolute improvements of prediction error rates of the mCLIF-OFs comparing to the above five scores were from 19.0% to 61.1%. After the analysis of probability density function (PDF), the mCLIF-OFs showed the least overlapping coefficients (27.9%) among above prognostic scores. Additionally, the mCLIF-OFs also show greater net benefit than above five prognostic scores over a wide range of risk threshold of death. Similar results were validated in two prospective ACLF cohorts with HBV and non-HBV etiologies.

Conclusions

Weighted TSH portended the outcome of ACLF patients, which may be treated as “damaged organ” of the hypothalamic-pituitary-thyroid axis. The novel mCLIF-OFs is a reliable prognostic score with better discrimination power and clinical net benefit than CLIF-OFs, CLIF-SOFAs, CLIF-C ACLFs, MELD, and Child-Pugh.

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Dermoscopy of atypical pigmented lesions of the face: Variation according to facial areas

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Abstract

Atypical pigmented facial lesions (aPFLs)—including lentigo maligna (LM) and lentigo maligna melanoma (LMM), solar lentigo (SL), pigmented actinic keratosis (PAK), atypical nevi (AN), seborrheic keratosis (SK) and lichen planus-like keratosis (LPLK)—can exhibit clinical and dermoscopic overlapping features. We aimed to investigate if and how 14 dermoscopic features suggestive for the aforementioned aPFLs vary according to six facial sites among 1197 aPFLs cases (excised to rule out malignancy) along with lesion and patients' metadata. According to distribution and association analysis, aPFLs on the forehead of a male patient aged > 69 years displaying the obliterated follicular openings pattern, appear to be more at risk of malignancy. Of converse, aPFLs of the orbital/cheek/nose area with evident and regular follicular openings with diameter < 10 mm in a female aged below 68 are probably benign. The obliterated follicular openings, keratin plugs, evident and regular follicular openings and target-like pattern features differed significantly among six facial areas in all aPFLs cases. Lesion of the nose may show both features suggestive of malignancy and benignity (e.g. many SL and PAK may display target-like pattern and some LM/LMM cases display keratin plugs and evident and follicular openings), making these features less specific.

The anticancer/cytotoxic effect of a novel gallic acid derivative in non‐small cell lung carcinoma A549 cells and peripheral blood mononuclear cells from healthy individuals and lung cancer patients

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The anticancer/cytotoxic effect of a novel gallic acid derivative in non-small cell lung carcinoma A549 cells and peripheral blood mononuclear cells from healthy individuals and lung cancer patients

This article presents a series of novel derivatives from gallic acid with antioxidant / anticancer properties. These compounds were studied on lymphocytes from healthy individuals and lung cancer patients. Also, gallic acid and its derivatives were examined on non-small cell carcinoma cell line. The anticancer effect of these compounds was revealed which should be confirmed with further future investigations.


Abstract

Gallic acid (GA) is a naturally occurring polyphenol with a strong antioxidant capacity. GA stimulates the apoptosis of cancer cells, thereby suppressing cancer cell invasion. However, the low oral permeability of GA limits its therapeutic use. In order to enhance the antioxidant capacity and oral permeability of GA, a series of compounds analogous to GA were synthesized: 4-methoxybenzenesulfonamide (MBS), 3,4-dimethoxybenzenesulfonamide (DMBS) and 3,4,5-trimethoxybenzenesulfonamide (TMBS). In the new compounds, hydroxyl groups were replaced with various numbers of methoxy groups (stronger electron-donating groups), to increase hydrophobicity and oral permeability compared to GA. In addition, the carboxylic group was replaced with a sulfonyl group (a stronger electron-withdrawing group), to increase the molecular polarity and antioxidative activities of the compounds. The cell counting kit-8 (CCK-8) assay was used to detect the effect of GA, MBS, DMBS, and TMBS on cell proliferation and apoptosis in peripheral blood mononuclear cells (PBMCs) from healthy individuals and non-small cell lung carcinoma A549 cells. Additionally, the comet assay was used to assess the genotoxicity of these compounds in PBMCs from healthy individuals, lung cancer patients, and A549 cells. Compared to untreated cells, TMBS reduced DNA damage more effectively than GA in PBMCs from lung cancer patients and healthy donors. Furthermore, in comparison to GA, TMBS was more cytotoxic in A549 cells. Moreover, TMBS was not cytotoxic in healthy PBMCs, suggesting that TMBS demonstrates therapeutic potential in cancer.