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Background: In India, breast cancer forms the most common malignancy, accounting for 28.2% of all female cancers. Breast cancer consists of phenotypically diverse group of diseases. Due to different relapse abilities, doubling times, and different infiltrative capacities, it is important to identify potential biomarkers that could be used to screen high-risk patient and predict breast cancer prognosis in conjunction with classical pathological parameters. Aims and Objectives: The present study was conducted to evaluate immunohistochemical expression of CD44 in breast carcinoma and to correlate CD44 expression with other clinicopathological parameters and molecular classification of carcinoma breast. Materials and Methods: The present study was a prospective descriptive study conducted on 100 cases of carcinoma breast diagnosed on modified radical mastectomy specimens that were submitted to the Department of Pathology, Pt. B. D. Sharma, PGIMS, Rohtak, Haryana, over the period of 2 years. Results: Out of 100, 64 cases (64%) were CD44 positive. Out of these 64 cases, 9 (9%) cases were 1+, 34 (34%) cases were 2+, and 21 (21%) cases showed 3+ positive expression of CD44 in tumor cells. Loss of CD44 expression was seen in 36 (36%) cases. A statistically significant association of CD44 was seen with multifocality of the tumor, negative estrogen receptor/progesterone receptor (ER/PR) expression, and molecular subtypes. No statistically significant association of CD44 was seen with age, side of tumor, lymph node metastasis, lymphovascular invasion, ductal carcinoma in situ and Ki67, and HER2neu expression. Conclusion: A high CD44 expression in breast carcinoma correlates with aggressive tumor characteristics such as multifocality, negative ER/PR expression, and belonging to the basal subtype which is associated with poor prognosis. Conversely, low CD44 expression is linked to Luminal A and Luminal B subtypes which have good prognosis. These indicate the role of CD44 as a prognostic biomarker in the carcinoma breast.

Purpose: To evaluate the difference in the diagnostic efficacy of 18F-PSMA-1007 PET/CT and pelvic MRI in primary prostate cancer, as well as the correlation between the two methods and histopathological parameters and serum PSA levels. Methods: A total of 41 patients with suspected prostate cancer who underwent 18F-PSMA-1007 PET/CT imaging in our department from 2018 to 2023 were retrospectively collected. All patients underwent 18F-PSMA-1007 PET/CT and MRI scans. The sensitivity, PPV and diagnostic accuracy of MRI and 18F-PSMA-1007 PET/CT in the diagnosis of prostate cancer were calculated after comparing the results of MRI and 18F-PSMA-1007 PET/CT with biopsy. The Spearman test was used to calculate the correlation between 18F-PSMA-1007 PET/CT, MRI parameters, histopathological indicators, and serum PSA levels. Results: Compared with histopathological results, the sensitivity, PPV and diagnostic accuracy of 18F-PSMA-1007 PET/CT in the diagnosis of prostate cancer were 95.1%, 100.0% and 95.1%, respectively. The sensitivity, PPV and diagnostic accuracy of MRI in the diagnosis of prostate cancer were 82.9%, 100.0% and 82.9%, respectively. There was a mild to moderately positive correlation between Gleason (Gs) score, Ki-67 index, serum PSA level and 18F-PSMA-1007 PET/CT parameters (p < 0.05). There was a moderately negative correlation between the expression of AMACR (P504S) and 18F-PSMA-1007 PET/CT parameters (p < 0.05). The serum PSA level and the Gs score were moderately positively correlated with the MRI parameters (p < 0.05). There was no correlation between histopathological parameters and MRI parameters (p > 0.05). Conclusion: Compared with MRI, 18F-PSMA-1007 PET/CT has higher sensitivity and diagnostic accuracy in the detection of malignant prostate tumors. In addition, the Ki-67 index and AMACR (P504S) expression were only correlated with 18F-PSMA-1007 PET/CT parameters. Gs score and serum PSA level were correlated with 18F-PSMA-1007 PET/CT and MRI parameters. 18F-PSMA-1007 PET/CT examination can provide certain reference values for the clinical diagnosis, evaluation, and treatment of malignant prostate tumors. [ABSTRACT FROM AUTHOR]

Background: In India, breast cancer forms the most common malignancy, accounting for 28.2% of all female cancers. Breast cancer consists of phenotypically diverse group of diseases. Due to different relapse abilities, doubling times, and different infiltrative capacities, it is important to identify potential biomarkers that could be used to screen high-risk patient and predict breast cancer prognosis in conjunction with classical pathological parameters. Aims and Objectives: The present study was conducted to evaluate immunohistochemical expression of CD44 in breast carcinoma and to correlate CD44 expression with other clinicopathological parameters and molecular classification of carcinoma breast. Materials and Methods: The present study was a prospective descriptive study conducted on 100 cases of carcinoma breast diagnosed on modified radical mastectomy specimens that were submitted to the Department of Pathology, Pt. B. D. Sharma, PGIMS, Rohtak, Haryana, over the period of 2 years. Results: Out of 100, 64 cases (64%) were CD44 positive. Out of these 64 cases, 9 (9%) cases were 1+, 34 (34%) cases were 2+, and 21 (21%) cases showed 3+ positive expression of CD44 in tumor cells. Loss of CD44 expression was seen in 36 (36%) cases. A statistically significant association of CD44 was seen with multifocality of the tumor, negative estrogen receptor/progesterone receptor (ER/PR) expression, and molecular subtypes. No statistically significant association of CD44 was seen with age, side of tumor, lymph node metastasis, lymphovascular invasion, ductal carcinoma in situ and Ki67, and HER2neu expression. Conclusion: A high CD44 expression in breast carcinoma correlates with aggressive tumor characteristics such as multifocality, negative ER/PR expression, and belonging to the basal subtype which is associated with poor prognosis. Conversely, low CD44 expression is linked to Luminal A and Luminal B subtypes which have good prognosis. These indicate the role of CD44 as a prognostic biomarker in the carcinoma breast. [ABSTRACT FROM AUTHOR]

Abstract Purpose To evaluate the difference in the diagnostic efficacy of 18F-PSMA-1007 PET/CT and pelvic MRI in primary prostate cancer, as well as the correlation between the two methods and histopathological parameters and serum PSA levels. Methods A total of 41 patients with suspected prostate cancer who underwent 18F-PSMA-1007 PET/CT imaging in our department from 2018 to 2023 were retrospectively collected. All patients underwent 18F-PSMA-1007 PET/CT and MRI scans. The sensitivity, PPV and diagnostic accuracy of MRI and 18F-PSMA-1007 PET/CT in the diagnosis of prostate cancer were calculated after comparing the results of MRI and 18F-PSMA-1007 PET/CT with biopsy. The Spearman test was used to calculate the correlation between 18F-PSMA-1007 PET/CT, MRI parameters, histopathological indicators, and serum PSA levels. Results Compared with histopathological results, the sensitivity, PPV and diagnostic accuracy of 18F-PSMA-1007 PET/CT in the diagnosis of prostate cancer were 95.1%, 100.0% and 95.1%, respectively. The sensitivity, PPV and diagnostic accuracy of MRI in the diagnosis of prostate cancer were 82.9%, 100.0% and 82.9%, respectively. There was a mild to moderately positive correlation between Gleason (Gs) score, Ki-67 index, serum PSA level and 18F-PSMA-1007 PET/CT parameters (p 0.05). Conclusion Compared with MRI, 18F-PSMA-1007 PET/CT has higher sensitivity and diagnostic accuracy in the detection of malignant prostate tumors. In addition, the Ki-67 index and AMACR (P504S) expression were only correlated with 18F-PSMA-1007 PET/CT parameters. Gs score and serum PSA level were correlated with 18F-PSMA-1007 PET/CT and MRI parameters. 18F-PSMA-1007 PET/CT examination can provide certain reference values for the clinical diagnosis, evaluation, and treatment of malignant prostate tumors.

Abstract Wheat is one of the essential crops for the human and animal nutrition, however, contamination with aflatoxigenic fungi, due to the improper storage conditions and high humidity, was the main global threats. So, preventing the growth of aflatoxigenic fungi in stored wheat grains, by using different essential oils was the main objective of this work. Aspergillus flavus EFBL-MU12 PP087400, EFBL-MU23 PP087401 and EFBL-MU36 PP087403 isolates were the most potent aflatoxins producers inhabiting wheat grains. The effect of storage conditions of wheat grains “humidity, temperature, incubation period, and pH” on growth of A. flavus, was assessed by the response surface methodology using Plackett-Burman design and FCCD. The highest yield of aflatoxins EFBL-MU12 B1 and B2 by A. flavus grown on wheat grains were 145.3 and 7.6 μg/kg, respectively, at incubation temperature 35°C, 16% moisture contents, initial pH 5.0, and incubated for 14 days. The tested oils had a powerful antifungal activity for the growth and aflatoxins production by A. flavus in a concentration-dependent manner. Among these oils, cinnamon oil had the highest fungicidal activity for A. flavus at 0.125%, with about 85-90 % reduction to the aflatoxins B1 and B2, conidial pigmentation and chitin contents on wheat grains. From the SEM analysis, cinnamon oils had the most deleterious effect on A. flavus with morphological aberrations to the conidial heads, vegetative mycelia, alteration in conidiophores identity, hyphae shrank, and winding. To emphasize the effect of the essential oils on the aflatoxins producing potency of A. flavus, the molecular expression of the aflatoxins biosynthetic genes was estimated by RT-qPCR. The molecular expression of nor-1, afLR, pKsA and afLJ genes was suppressed by 94-96%, due to cinnamon oil at 0.062% compared to the control. Conclusively, from the results, cinnamon oils followed by the peppermint oils displayed the most fungicidal activity for the growth and aflatoxins production by A. flavus grown on wheat grains.

Wheat is one of the essential crops for the human and animal nutrition, however, contamination with aflatoxigenic fungi, due to the improper storage conditions and high humidity, was the main global threats. So, preventing the growth of aflatoxigenic fungi in stored wheat grains, by using different essential oils was the main objective of this work. Aspergillus flavus EFBL-MU12 PP087400, EFBL-MU23 PP087401 and EFBL-MU36 PP087403 isolates were the most potent aflatoxins producers inhabiting wheat grains. The effect of storage conditions of wheat grains "humidity, temperature, incubation period, and pH" on growth of A. flavus, was assessed by the response surface methodology using Plackett-Burman design and FCCD. The highest yield of aflatoxins EFBL-MU12 B1 and B2 by A. flavus grown on wheat grains were 145.3 and 7.6 μg/kg, respectively, at incubation temperature 35°C, 16% moisture contents, initial pH 5.0, and incubated for 14 days. The tested oils had a powerful antifungal activity for the growth and aflatoxins production by A. flavus in a concentration-dependent manner. Among these oils, cinnamon oil had the highest fungicidal activity for A. flavus at 0.125%, with about 85-90 % reduction to the aflatoxins B1 and B2, conidial pigmentation and chitin contents on wheat grains. From the SEM analysis, cinnamon oils had the most deleterious effect on A. flavus with morphological aberrations to the conidial heads, vegetative mycelia, alteration in conidiophores identity, hyphae shrank, and winding. To emphasize the effect of the essential oils on the aflatoxins producing potency of A. flavus, the molecular expression of the aflatoxins biosynthetic genes was estimated by RT-qPCR. The molecular expression of nor-1, afLR, pKsA and afLJ genes was suppressed by 94-96%, due to cinnamon oil at 0.062% compared to the control. Conclusively, from the results, cinnamon oils followed by the peppermint oils displayed the most fungicidal activity for the growth and aflatoxins production by A. flavus grown on wheat grains. [ABSTRACT FROM AUTHOR]

Abstract Background We aimed to determine the performance of 18 F-FAPI PET/CT used for preprocedural assessment of glioblastoma before radiotherapy. Methods Twelve glioblastoma patients having undergone incomplete surgical resection or biopsy were examined with 18 F-FAPI PET/CT and MRI scanning before radiotherapy. All patients had confirmed tumor residues according to findings of histopathological and/or long-term clinical and radiological follow-ups. Lesion characterization data, including SUVmax and tumor-to-background ratio (TBR) on PET/CT were attained. PET/CT and MRI findings were compared in terms of number of lesions. The correlation between immunohistochemistry, molecular expression, and PET/CT parameters was also evaluated. Results 18 F-FAPI PET/CT detected 16 FAPI-avid out of 23 lesions in 12 patients described on MRI. MRI was statistically different from 18 F-FAPI PET/CT for lesion detection according to the exact McNemar statistical test (P = 0.0156). The SUVmax and TBR of the glioblastomas was 7.08 ± 3.55 and 19.95 ± 13.22, respectively. The sensitivity and positive predictive value (PPV) of 18 F-FAPI PET were 69.6% and 100%, respectively. Neither the Ki-67 index nor the molecular expression was correlated with the FAPI-PET/CT parameters. Conclusion 18 F-FAPI PET/CT detects glioblastomas at a lower rate than MRI. However, the 100% PPV of the examination may make it useful for differentiating controversial lesions detected on MRI. The 18 F-FAPI-avid lesions are displayed more clearly probably due to a higher TBR. 18 F-FAPI PET/CT imaging might find application in glioblastoma biopsy and radiotherapy planning.

Aim: Ameloblastoma is a benign but locally aggressive epithelial odontogenic tumor. The present review aimed to identify the most commonly expressed signaling molecule in ameloblastoma detected using cDNA microarray. Materials and Methods: It is a systematic review. In this review, articles were searched using databases--PubMed and Google Scholar and were also searched using Hand Search. All the studies which used cDNA microarray to detect the expression of signaling molecules were included. All the variants of ameloblastoma were included for the review. A total of 22 ameloblastoma cases were included in this systematic review. Out of three studies, 67% of the cases demonstrated upregulation of smoothened (SMO) and sonic hedgehog (SHH). Results: Out of three studies, 33% of the cases showed upregulation of toll-like receptor 2 (TLR2), fos proto-oncogene (FOS), Wnt family member 10a (WntlOa), and patched and down-regulation of insulin-like growth factor 2 (IGF2). Of the 67% of the studies which described SMO and SHH, significant expression of SMO (73 times fold change) was noted. SHH expression was noted to have 0.88 times fold change. Of the 33% of the studies included, the highest average fold change was noted to be associated with FOS (14-fold change time) followed by WntlOa (5.1-fold change times) and TLR2 (3.29-fold change times). However, downregulation of IGF2 by 0.09-fold change times was observed in 33% of the studies. Conclusion: The SMO gene from the SHH pathway was the highest expressed signaling molecule in ameloblastoma. [ABSTRACT FROM AUTHOR]

Background: We aimed to determine the performance of 18 F-FAPI PET/CT used for preprocedural assessment of glioblastoma before radiotherapy. Methods: Twelve glioblastoma patients having undergone incomplete surgical resection or biopsy were examined with 18 F-FAPI PET/CT and MRI scanning before radiotherapy. All patients had confirmed tumor residues according to findings of histopathological and/or long-term clinical and radiological follow-ups. Lesion characterization data, including SUVmax and tumor-to-background ratio (TBR) on PET/CT were attained. PET/CT and MRI findings were compared in terms of number of lesions. The correlation between immunohistochemistry, molecular expression, and PET/CT parameters was also evaluated. Results: 18 F-FAPI PET/CT detected 16 FAPI-avid out of 23 lesions in 12 patients described on MRI. MRI was statistically different from 18 F-FAPI PET/CT for lesion detection according to the exact McNemar statistical test (P = 0.0156). The SUVmax and TBR of the glioblastomas was 7.08 ± 3.55 and 19.95 ± 13.22, respectively. The sensitivity and positive predictive value (PPV) of 18 F-FAPI PET were 69.6% and 100%, respectively. Neither the Ki-67 index nor the molecular expression was correlated with the FAPI-PET/CT parameters. Conclusion: 18 F-FAPI PET/CT detects glioblastomas at a lower rate than MRI. However, the 100% PPV of the examination may make it useful for differentiating controversial lesions detected on MRI. The 18 F-FAPI-avid lesions are displayed more clearly probably due to a higher TBR. 18 F-FAPI PET/CT imaging might find application in glioblastoma biopsy and radiotherapy planning. [ABSTRACT FROM AUTHOR]

Endocrine tumors like thyroid carcinoma are becoming more frequent. No clinically informative predictors were found. Thus, effective gene networks and representative biomarkers can illuminate thyroid cancer prevention molecular mechanisms. TBC1D4 is an activating protein molecule that plays an important role in regulating cell metabolism and signal transduction. The aim of this study was to investigate the expression characteristics of TBC1D4 activating protein molecules and identify key module genes that prevent thyroid cancer progression. GSE65144 data were downloaded from GEO. "limma" in R found DEGs with a false discovery rate < 0.05 and a log2 fold change <1. WGCNA builds gene co-expression networks, screens key modules, and filters hub genes. Overlapping genes become hub genes. Hub genes underwent GO and KEGG pathway enrichment analysis. We used Lasso to extract hub gene expression results' distinctive genes. Key genes. GEPIA database determined expression and survival impact. A total of 3220 DEGs. Thyroid cancer was mostly associated with darkred, darkturquoise, and green modules. Venn screened 639 hub genes. Cytokine-cytokine receptor interaction was the primary KEGG enrichment. Hub genes were 14. Finally, ARHGAP6, TBC1D4, and TC2N were important genes. Through gene screening and functional enrichment analysis, we identified a group of genes related to TBC1D4 activating protein and constructed the corresponding protein interaction network. [ABSTRACT FROM AUTHOR]

Carbohydrates remobilization in non-leaf organs has a potential association with the formation of cotton yield. However, our understanding of the physiological and molecular mechanisms regulating carbon remobilization during flowering is still limited. The objectives of the study were to: i) evaluate the potential of carbohydrate remobilization in stems and roots to yield formation; ii) unravel the carbon metabolism and transport associated gene expression patterns regulating carbon remobilization. Two cotton lines 4003-6 and 4003-10 were employed to examine leaf photosynthesis, reproductive biomass accumulation, and carbon dynamics in stems and roots during reproductive growth. The results showed that decreasing leaf photosynthetic capacity combined with rapidly increasing reproductive biomass and leaf area index is accompanied by the initiation of carbohydrate remobilization during first flowering to peak flowering. The proportion of sucrose to total nonstructural carbohydrate was also decreased at that period. The upper and lower of stem recorded higher soluble sugars and starch concentrations, respectively compared to the two others. The gross contribution rate of carbon remobilization to seed cotton yield ranged from 2.83% to 7.12%. Key genes and sugar transporters related to starch and sucrose metabolism in the lower stem exhibited significant up- or down-regulated expressions indicating their important roles in carbon reserves remobilization. Three pivotal sugar transporters SWEET1 , TMT2 , and ERLD5 presented higher transcript levels at peak flowering suggesting more active sugar movement occurring at that stage. The present study provides potential target genes for engineering carbohydrate metabolism and transport to improve the remobilization efficiency of nonstructural carbohydrates. • The lower stem records higher starch concentration compared to the other parts. • The gross contribution rate of carbon remobilization to cotton yield was below 10%. • Starch biosynthesis in stems is decreased at peak flowering relative to peak squaring. • Sucrose metabolism in the stem is more active at peak flowering than peak squaring. • SWEET is up-regulated significantly in stems at peak flowering relative to peak squaring. [ABSTRACT FROM AUTHOR]

Pulsed focused ultrasound (pFUS) utilizes short cycles of sound waves to mechanically shake cells within tissues which, in turn, causes transient local increases in cytokines, growth factors and cell adhesion molecules. Although the effect of pFUS has been investigated in several different organs including the kidney, muscle and heart, its effect on the pancreas has not been investigated. In the present work, we applied pFUS to the rodent pancreas with the following parameters: 1.1-MHz frequency, 5-Hz pulse repetition frequency, 5% duty cycle, 10-ms pulse length, 160-s duration. Low-intensity pFUS had a spatial average temporal average intensity of 11.5 W/cm2 and a negative peak pressure of 3 MPa; high-intensity pFUS had a spatial average temporal average intensity of 18.5 W/cm2 and negative peak pressure of 4 MPa. Here we found that pFUS changed the expression of several cytokines while having no effect on the underlying tissue histology or health of pancreatic cells (as reflected by no significant change in plasma levels of amylase and lipase). Furthermore, we found that this effect on cytokine expression in the pancreas was acoustic intensity dependent; while pFUS at low intensities turned off the expression of several cytokines, at high intensities it had the opposite effect and turned on the expression of these cytokines. The ability to non-invasively manipulate the microenvironment of the pancreas using sound waves could have profound implications for priming and modulating this organ for the application of cellular therapies in the context of both regenerative medicine (i.e., diabetes and pancreatitis) and oncology (i.e., pancreatic cancer). [ABSTRACT FROM AUTHOR]

Endocrine-disrupting chemicals encompass a variety of chemicals that may interfere with the endocrine system and produce negative effects on organisms. Among them, bisphenol A is considered a major pollutant in numerous countries. The harmful effects of BPA on environmental and human health are intensely studied. However, the effects of BPA on terrestrial insects are still poorly investigated, despite that several plants can accumulate BPA in their tissues, leading to potential contamination of herbivorous insects. Here, we used the leafworm Spodoptera littoralis, a polyphagous species, to study BPA effects on post-embryonic development. We studied the effects of BPA ingestion at environmental doses (e.g., 0.01, 0.1, and 1 μg/g of BPA) and high doses (e.g., 25 μg/g) on larval weight and stage duration, pupal length and sex ratio. BPA effects were investigated in more detail during the last larval instar, a crucial period for preparing pupation and metamorphosis, which are under endocrine control. We monitored the haemolymph concentration of ecdysteroids, hormones controlling moult and metamorphosis, as well as the expression levels of several nuclear receptors involved in the ecdysteroid signalling pathway. Our integrative study showed that, upon exposure doses, BPA can induce various effects on the viability, developmental time, growth and sex ratio. These effects were correlated with a delay of the ecdysteroid peak during the last larval instar and a modification of expression of EcR, USP, E75AB, E75D and Br-c. We provide new evidence about the events that occur after BPA exposure in insect contaminated by food ingestion. • Ingestion of BPA induced effects on mortality, development and growth. • Ingestion of BPA disrupted the ecdysteroid peak in last larval stage. • BPA disrupted the expression of nuclear receptor in last larval stage. [ABSTRACT FROM AUTHOR]

Purpose: Fertility-preserving treatment (FPT) has been widely used for young patients with early stage endometrial cancer (EC). However, the literature on the effectiveness and safety of FPT remains controversial. The aim of this study was to investigate malignant transformation in EC after FPT by immunohistochemistry (IHC).Methods: A retrospective analysis of pre- and post-treatment biopsy specimens from 24 patients with grade 1 endometrioid adenocarcinoma (EAC) or complex atypical hyperplasia (CAH) was performed. The expression levels of ARID1A, PTEN, and β-catenin were assessed by IHC.Results: The protein expression levels of ARID1A, PTEN, and β-catenin were not significantly different between pre- and post-treatment specimens. However, there was a significant difference between pre-treatment and normal specimens as well as between post-treatment and normal specimens. The protein expression of β-catenin was significantly increased in patients with progression compared with those without progression after FPT.Conclusion: The morphologic normalization of patients with EC after FPT may not be accompanied by the absence of tumor malignancy, and β-catenin may serve as a biomarker for the response to FPT. These results may contribute to a better understanding of the malignant transformation of EC after FPT and the optimization of treatment strategies for young patients with birth plans. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • The yield of Taxol by A. flavipes was increased by 5 folds with addition of fluconazole. • The expression of ts, dbat, bapt and pbcR genes were increased by 10 folds upon addition of fluconazole. • The molecular expression of HSP70 was induced by 13 folds upon addition of fluconazole. Abstract Taxol is a blockbuster anticancer drug that commercially synthesized from 10-decaetylbaccatin III intermediate of Taxus baccata , however, this technology has been challenged by reproducibility and association of unwanted compounds. Recently, endophytic fungi with fast growing and feasibility of molecular engineering raise the hope for sustainable production of Taxol, unfortunately the loss of their productivity with multiple subculturing is the main challenge to authenticate this approach industrially. Thus, searching for novel fungal isolates with molecular and metabolic functional stability for Taxol production was the objective of this work. Among the experimented fungal isolates, Aspergillus flavipes, a soil-dwelling saprophyte, gave the highest Taxol yield (185 μg/l). Metabolically, A. flavipes had a strong stability for Taxol production till the 10th subcultures (185-160 μg/l) on the same cultural conditions. The yield of Taxol by A. flavipes was increased by 5 folds (850 μg/ L) with fluconazole (1.0 μg/ml) addition to 5 days old culture. The expression of Taxol biosynthetic genes ts, dbat , bapt and transcriptional factor pbcR was significantly increased by 8–10 folds upon fluconazole addition that correlates with Taxol yield. HSP70 was induced by 13 folds with addition of fluconazole to cultures of A. flavipes. Thus, Taxol biosynthesis could be transcriptionally regulated by pbcR and post-translationally modified by HSP70 chaperones. To the best of knowledge, this is the first report exploring the potency of saprophytic A. flavipes for Taxol production with metabolic stability with multiple subculturing. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to develop a Vision Transformer model with multitask classification framework that is appropriate for predicting four molecular expressions of glioma simultaneously based on MR imaging.Materials and Methods: A total of 188 glioma (grades II-IV) patients with an immunohistochemical diagnosis of IDH, MGMT, Ki67 and P53 expression were enrolled in our study. A Vision Transformer (ViT) model, including three independent networks based on T2WI, T1CWI and T2 + T1CWI (T2-net, T1C-net and TU-net), was developed for the prediction of four glioma molecular expressions simultaneously. To evaluate the model performance, the accuracy rate, recall, precision, F1-score, and area under the receiver operating characteristic curve (AUC) were calculated.Results: The proposed ViT model achieved high accuracy in predicting IDH, MGMT, Ki67 and P53 expression in gliomas. Among the three networks using the ViT model, TU-net achieved the best results with the highest values of accuracy (range, 0.937-0.969), precision (range, 0.949-0.972), recall (range, 0.873-0.991), F1-score (range, 0.910-0.981) and AUC (range, 0.976-0.984). Comparisons were also made between our ViT model and convolutional neural network (CNN)-based models, and the proposed ViT model outperformed the existing CNN-based models.Conclusion: Vision Transformer is a reliable approach for the prediction of glioma molecular biomarkers and can be a viable alternative to CNNs. [ABSTRACT FROM AUTHOR]

Background: Dorsal root ganglion neuron-derived immortal cell lines including ND7/23 and F-11 cells have been used extensively as in vitro model systems of native peripheral sensory neurons. However, while it is clear that some sensory neuron-specific receptors and ion channels are present in these cell lines, a systematic comparison of the molecular targets expressed by these cell lines with those expressed in intact peripheral neurons is lacking. Results: In this study, we examined the expression of RNA transcripts in the human neuroblastoma-derived cell line, SHSY5Y, and two dorsal root ganglion hybridoma cell lines, F-11 and ND7/23, using Illumina next-generation sequencing, and compared the results with native whole murine dorsal root ganglions. The gene expression profiles of these three cell lines did not resemble any specific defined dorsal root ganglion subclass. The cell lines lacked many markers for nociceptive sensory neurons, such as the Transient receptor potential V1 gene, but expressed markers for both myelinated and unmyelinated neurons. Global gene ontology analysis on whole dorsal root ganglions and cell lines showed similar enrichment of biological process terms across all samples. Conclusions: This paper provides insights into the receptor repertoire expressed in common dorsal root ganglion neuronderived cell lines compared with whole murine dorsal root ganglions, and illustrates the limits and potentials of these cell lines as tools for neuropharmacological exploration. [ABSTRACT FROM AUTHOR]

Highlights: [•] Effects of pH, incubation temperature, nitrogen and carbon sources, inorganic salts on tannase production were detailed described. [•] The properties of tannases were summarized, including molecular weight, effect of temperature and pH, effect of metal ions, effect of organic solvents and surfactants. [•] Tannase protein sequences and molecular architecture were described in detail. [•] Novel developments in the field of tannase including metagenomic approach and directed evolution were discussed to get novel tannases or improve properties of the existing tannase. [ABSTRACT FROM AUTHOR]

A thermophilic lipolytic bacterium identified as Bacillus sp. L2 via 16S rDNA was previously isolated from a hot spring in Perak, Malaysia. Bacillus sp. L2 was confirmed to be in Group 5 of bacterial classification, a phylogenically and phenotypically coherent group of thermophilic bacilli displaying very high similarity among their 16S rRNA sequences (98.5-99.2%). Polymerase chain reaction (PCR) cloning of L2 lipase gene was conducted by using five different primers. Sequence analysis of the L2 lipase gene revealed an open reading frame (ORF) of 1251 bp that codes for 417 amino acids. The signal peptides consist of 28 amino acids. The mature protein is made of 388 amino acid residues. Recombinant lipase was successfully overexpressed with a 178-fold increase in activity compared to crude native L2 lipase. The recombinant L2 lipase (43.2 kDa) was purified to homogeneity in a single chromatography step. The purified lipase was found to be reactive at a temperature range of 55-80 °C and at a pH of 6-10. The L2 lipase had a melting temperature (Tm) of 59.04 °C when analyzed by circular dichroism (CD) spectroscopy studies. The optimum activity was found to be at 70 °C and pH 9. Lipase L2 was strongly inhibited by ethylenediaminetetraacetic acid (EDTA) (100%), whereas phenylmethylsulfonyl fluoride (PMSF), pepstatin-A, 2-mercaptoethanol and dithiothreitol (DTT) inhibited the enzyme by over 40%. The CD spectra of secondary structure analysis showed that the L2 lipase structure contained 38.6% α-helices, 2.2% ß-strands, 23.6% turns and 35.6% random conformations. [ABSTRACT FROM AUTHOR]

Fish have developed color vision that is closely adapted to their photic environments, where both spectral sensitivity and the number of visual opsins are influenced. The mackerel used in this study is one of the most important fishery stocks in Korea. The opsin gene of the mackerel juveniles after 20 days in hatching was isolated and characterized based on the molecular study of visual photoreceptor. The full-length mackerel opsin gene was obtained by PCR amplification of genomic DNA, as well as cDNA synthesis. Sequence analysis of the opsin gene showed that it contained a 1,080 bp open reading frame encoding 360 amino acids. Based on Schiff’s base formation (S114, K119), glycosylation (E3, F37) and palmitoylation (S281, 282), the deduced amino acid sequence had a typical rod opsin. The mackerel and Gempylus serpens showed 73.7% DNA homology on opsin gene, which was higher than any other of investigated species. In the analysis of phylogenetic relationship, the genetic placement of the mackerel is closer to that of Scombroidei than Labroidei, with supporting somewhat strong bootstrap value. In the analysis of Northern and RT-PCR, the probed products were observed only in rapidly growing juveniles. These findings indicate that in mackerel opsin mRNA expression can be detected in day-20 hatching larvae. It may play an important role in stimulating growth hormone. [ABSTRACT FROM AUTHOR]

The problems of identifying environmental factors involved in the etiology of human disease and performing safety and risk assessments of drugs and chemicals have long been formidable issues. Three principal components for predicting potential human health risks are: (1) the diverse structure and properties of thousands of chemicals and other stressors in the environment; (2) the time and dose parameters that define the relationship between exposure and disease; and (3) the genetic diversity of organisms used as surrogates to determine adverse chemical effects. The global techniques evolving from successful genomics efforts are providing new exciting tools with which to address these intractable problems of environmental health and toxicology. In order to exploit the scientific opportunities, the National Institute of Environmental Health Sciences has created the National Center for Toxicogenomics (NCT). The primary mission of the NCT is to use gene expression technology, proteomics and metabolite profiling to create a reference knowledge base that will allow scientists to understand mechanisms of toxicity and to be able to predict the potential toxicity of new chemical entities and drugs. A principal scientific objective underpinning the use of microarray analysis of chemical exposures is to demonstrate the utility of signature profiling of the action of drugs or chemicals and to utilize microarray methodologies to determine biomarkers of exposure and potential adverse effects. The initial approach of the NCT is to utilize proof-of-principle experiments in an effort to “phenotypically anchor” the altered patterns of gene expression to conventional parameters of toxicity and to define dose and time relationships in which the expression of such signature genes may precede the development of overt toxicity. The microarray approach is used in conjunction with proteomic techniques to identify specific proteins that may serve as signature biomarkers. The longer-range goal of these efforts is to develop a reference relational database of chemical effects in biological systems (CEBS) that can be used to define common mechanisms of toxicity, chemical and drug actions, to define cellular pathways of response, injury and, ultimately, disease. In order to implement this strategy, the NCT has created a consortium of research organizations and private sector companies to actively collaborative in populating the database with high quality primary data. The evolution of discrete databases to a knowledge base of toxicogenomics will be accomplished through establishing relational interfaces with other sources of information on the structure and activity of chemicals such as that of the National Toxicology Program (NTP) and with databases annotating gene identity, sequence, and function. [Copyright &y& Elsevier]

Human population studies involve clinical or epidemiological observations that associate environmental exposures with health endpoints and disease. Clearly, these are the most sought after data to support assessments of human health risk from environmental exposures. However, the foundations of many health risk assessments rest on experimental studies in rodents performed at high doses that elicit adverse outcomes, such as organ toxicity or tumors. Using the results of human studies and animal data, risk assessors define the levels of environmental exposures that may lead to disease in a portion of the population. These decisions on potential health risks are frequently based on the use of default assumptions that reflect limitations in our scientific knowledge. An important immediate goal of toxicogenomics, including proteomics and metabonomics, is to offer the possibility of making decisions affecting public health and public based on detailed toxicity, mechanistic, and exposure data in which many of the uncertainties have been eliminated. Ultimately, these global technologies will dramatically impact the practice of public health and risk assessment as applied to environmental health protection. The impact is already being felt in the practice of toxicology where animal experimentation using highly controlled dose–time parameters is possible. It is also being seen in human population studies where understanding human genetic variation and genomic reactions to specific environmental exposures is enhancing our ability to uncover the causes of variations in human response to environmental exposures. These new disciplines hold the promise of reducing the costs and time lines associated with animal and human studies designed to assess both the toxicity of environmental pollutants and efficacy of therapeutic drugs. However, as with any new science, experience must be gained before the promise can be fulfilled. Given the numbers and diversity of drugs, chemicals and environmental agents; the various species in which they are studied and the time and dose factors that are critical to the induction of beneficial and adverse effects, it is only through the development of a profound knowledge base that toxicology and environmental health can rapidly advance. The National Institute of Environmental Health Sciences (NIEHS), National Center for Toxicogenomics and its university-based Toxicogenomics Research Consortium (TRC), and resource contracts, are engaged in the development, application and standardization of the science upon which to the build such a knowledge base on Chemical Effects in Biological Systems (CEBS). In addition, the NIEHS Environmental Genome Project (EGP) is working to systematically identify and characterize common sequence polymorphisms in many genes with suspected roles in determining chemical sensitivity. The rationale of the EGP is that certain genes have a greater than average influence over human susceptibility to environmental agents. If we identify and characterize the polymorphism in those genes, we will increase our understanding of human disease susceptibility. This knowledge can be used to protect susceptible individuals from disease and to reduce adverse exposure and environmentally induced disease. [Copyright &y& Elsevier]

The 8-week rearing trial was conducted to estimate the effect of dietary hydroxyproline (Hyp) supplementation on growth performance, amino acid profiles, fatty acid profiles, and collagen concentration in muscle samples, liquid holding capacity (LHC), pH, cooking loss and antioxidant activities in flesh of post-mortem, histomorphology, ultrastructure and molecular expression of muscle samples, and raw- and cooked-fillet texture characteristics of Yellow River carp (Cyprinus carpio haematopterus). Six isoproteic and isolipidic practical diets were formulated to contain graded levels of Hyp (1.36, 3.93, 7.14, 8.86, 11.45 and 13.69 g/kg of dry matter). A total of 840 carps with an average initial weight of 17.90 ± 0.28 g were randomly allocated to 24 polypropylene tanks with funnel-shaped bottom (400 L capacity filled to 300 L and 35 fish per tank). The results showed that no significant differences were found in growth performance and morphology parameter among all treatments (P > 0.05). With the increase of dietary Hyp levels, the glycine (Gly) content, and the proportion of 22:6n-3, n-3 PUFA and collagen concentration in carp fillet showed a significant ascending tendency, while arginine and proline were in downtrend (P < 0.05). Liquid loss, lipid loss and cooking loss were significantly decreased with the increasing dietary Hyp levels (P < 0.05), and the pH values in muscle samples of carp fed with dietary Hyp (> 3.93 g/kg) were significantly higher than that in control group (P < 0.05). Dietary Hyp supplementation improved the antioxidant properties of hepatopancreas and muscle with the increasing dietary Hyp levels (P < 0.05). Overall, we posed that appropriate dietary Hyp supplementation can promote myogenesis and collagen synthesis in muscle of carp, ultimately improved the raw- and cooked-fillet texture characteristics. The current research will be contributed to find an efficient way to ensure predictable and firmer texture of farmed Yellow River carp. • Dietary Hyp promoted the synthesis of glycine and Lc-PUFA in flesh. • Dietary Hyp promoted the antioxidant properties of hepatopancreas and muscle. • Dietary Hyp improved flesh pH, LHC, cooking loss and the collagen content, and fillet texture. [ABSTRACT FROM AUTHOR]

Background: There are few reports on the comparative medical characteristics of type 2 diabetes models in late stage. An analysis of comparative medical characteristics of Zucker diabetic fatty type 2 diabetes mellitus (ZDF-T2DM) rats during the course of development to late stage disease was performed., Methods: In this study, ZDF rats were fed with high-sugar and high-fat diets to raise the fasting blood glucose, and develop of type 2 diabetes. At the late stage of T2DM, the preliminary comparative medical characteristics of the T2DM model were analyzed through the detection of clinical indicators, histopathology, related cytokine levels, and insulin-related signaling molecule expression levels., Results: In the T2DM group, the fasting blood glucose was higher than 6.8 mmol/L, the serum insulin, leptin, and adiponectin levels were significantly decreased, and glucose intolerance and insulin resistance were measured as clinical indicators. Regarding pathological indicators, a large number of pancreatic islet cells showed the reduction of insulin secretion, resulting in damaged glycogen synthesis and liver steatosis. At the molecular level, the insulin signal transduction pathway was inhibited by decreasing the insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), phosphatidylinositol 3 kinase (PI3K), and glycogen synthesis kinase 3β (GSK-3β) expression levels., Conclusion: The results show that the ZDF/T2DM rats have typical clinical, histopathological, and molecular characteristics of human T2DM and thus can be used as an effective model for T2DM drug development and treatment of advanced T2DM., Competing Interests: None.

Identifying new markers of disease flares in lupus nephritis (LN) that facilitate patient stratification and prognosis is important. Therefore, the aim of the present study was to analyze whether urinary SIRT1 expression was altered in LN and whether SIRT1 values in urine could be valuable biomarker of disease activity. In a cohort study, urinary pellets from 40 patients diagnosed with systemic lupus erythematosus (SLE) were analyzed. Clinical measures of lupus activity were assessed. The expression of SIRT1 was quantified by quantitative PCR (qRT-PCR) and immunoblot, then compared between patients with active lupus nephritis, in remission and healthy controls. Association with lupus activity and renal histological features was also analyzed. A significant increase in SIRT1 mRNA levels in patients with active LN was observed compared with those in remission ( P =0.02) or healthy controls ( P =0.009). In addition, SIRT-1 protein levels were also augmented in LN group than remission ( P =0.029) and controls ( P =0.001). A strong association was found between SIRT1 expression with anti-dsDNA in SLE and in patients with LN. In addition, histological features in LN biopsies were related with SIRT1, increasing its expression in proliferative forms. Finally, SIRT1 expression values showed a strong discriminatory power of renal injury in SLE. Our study demonstrated an altered urinary expression of SIRT1 and a strong association with disease activity in LN patients, being a valuable marker of renal injury. These results showed the role of the SIRT1 pathway in the SLE pathogenesis., (© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)