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Graphite carbon nitride (g‐C3N4) has garnered considerable attention due to its excellent photocatalytic properties for the degradation of organic matter in wastewater treatment. Herein, sulfur‐doped g‐C3N4 nanosheets (CN−S‐X) were successfully synthesized via physical steam activation using thiourea and urea as precursors. Comprehensive characterizations demonstrate that the enhanced photocatalysis is attributed to the ultrathin structure, highly active site, vacancy defects, and high specific surface area due to the synergy of S doping and steam activation. The as‐prepared CN−S‐25 photocatalyst exhibits a desirable degradation efficiency of 95.4 % for methylene blue dye with a high degradation rate of 2.65×10−2 min−1 under visible‐light irradiation, which are 2.1 and 5.52 times those for bulk g‐C3N4, respectively as well as good reusability and stability. This study provides a simple and promising strategy to regulate the nanostructure of g‐C3N4 for highly efficient photocatalytic degradation of organic pollutants. [ABSTRACT FROM AUTHOR]

Objectives: Elevated thioredoxin‐interacting protein (TXNIP)‐induced pyroptosis contributes to the pathology of diabetic kidney disease (DKD). However, the molecular mechanisms in dysregulated TXNIP in DKD remain largely unclear. Materials and methods: Transcriptomic analysis identified a novel long noncoding RNA—Prader Willi/Angelman region RNA, SNRPN neighbour (PWARSN)—which was highly expressed in a proximal tubular epithelial cell (PTEC) under high glucose conditions. We focused on revealing the functions of PWARSN in regulating TXNIP‐mediated pyroptosis in PTECs by targeting PWARSN expression via lentivirus‐mediated overexpression and CRISPR‐Cas9‐based knockout in vitro and overexpressing PWARSN in the renal cortex by AAV‐9 targeted injection in vivo. A number of molecular techniques disclosed the mechanisms of PWARSN in regulating TXNIP induced‐pyroptosis in DKD. Results: TXNIP‐NOD‐like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and PTEC pyroptosis were activated in the renal tubules of patients with DKD and in diabetic mice. Then we explored that PWARSN enhanced TXNIP‐driven PTECs pyroptosis in vitro and in vivo. Mechanistically, cytoplasmic PWARSN sponged miR‐372‐3p to promote TXNIP expression. Moreover, nuclear PWARSN interacted and facilitated RNA binding motif protein X‐linked (RBMX) degradation through ubiquitination, resulting in the initiation of TXNIP transcription by reducing H3K9me3‐enrichment at the TXNIP promoter. Further analysis indicated that PWARSN might be a potential biomarker for DKD. Conclusions: These findings illustrate distinct dual molecular mechanisms for PWARSN‐modulated TXNIP and PTECs pyroptosis in DKD, presenting PWARSN as a promising therapeutic target for DKD. [ABSTRACT FROM AUTHOR]

Benzo[a]pyrene (B[a]P) and polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants. The effects in organisms of exposures to binary mixtures of such contaminants remain obscure. Attenuated total reflection Fourier‐transform infrared (ATR‐FTIR) spectroscopy is a label‐free, non‐destructive analytical technique allowing spectrochemical analysis of macromolecular components, and alterations thereof, within tissue samples. Herein, we employed ATR‐FTIR spectroscopy to identify biomolecular changes in rat liver post‐exposure to B[a]P and BDE‐47 (2,2′,4,4′‐tetrabromodiphenyl ether) congener mixtures. Our results demonstrate that significant separation occurs between spectra of tissue samples derived from control versus exposure categories (accuracy = 87%; sensitivity = 95%; specificity = 79%). Additionally, there is significant spectral separation between exposed categories (accuracy = 91%; sensitivity = 98%; specificity = 90%). Segregation between control and all exposure categories were primarily associated with wavenumbers ranging from 1600 to 1700 cm−1. B[a]P and BDE‐47 alone, or in combination, induces liver damage in female rats. However, it is suggested that binary exposure apparently attenuates the toxic effects in rat liver of the individual contaminants. This is supported by morphological observations of liver tissue architecture on hematoxylin and eosin (H&E)‐stained liver sections. Such observations highlight the difficulties in predicting the endpoint effects in target tissues of exposures to mixtures of environmental contaminants. B[a]P or BDE‐47 alone or in combination can cause damage to the liver of female rats. We suggest that BDE‐47 and B[a]P have similar mechanisms of action in inducing liver damage in rats. It is speculated that binary exposure to these agents can result in attenuated toxic effects in rat liver compared with the effects induced following exposure to individual contaminants. [ABSTRACT FROM AUTHOR]

Background: Efforts to identify accurate blood biomarkers for neurodegenerative disease hallmarks have been hampered by the lack of a proteomic tool that has the required sensitivity to detect very low concentrations of brain‐derived proteins in plasma or serum and the ability to multiplex many analytes in a single assay. Here we evaluated NULISA™, a recently developed novel immunoassay with attomolar level sensitivity and high multiplex capability1, for its ability to detect serum biomarkers associated with Alzheimer's disease. Method: Serum samples from 31 Alzheimer's disease (AD) patients and 31 non‐AD controls were analyzed using NULISA with a 200plex inflammation panel targeting a broad spectrum of inflammation‐related cytokines, chemokines and other proteins. Five samples failed quality control and were excluded from further analysis, resulting in 28 AD and 29 control samples in the final dataset. Linear model analysis, including age and sex as covariates, was performed for each target for differential expression between AD patients and controls. Result: Two significant proteins were identified. The level of glial fibrillary acidic protein (GFAP) was 1.84‐fold higher in AD patients (adjusted p‐value = 0.00014), whereas the level of S100 calcium‐binding protein A12 (S100A12) was 2‐fold higher in non‐AD controls (adjusted p‐value = 0.031). GFAP serum levels correlated strongly with total tau (Spearman rho = 0.69, p = 1.7e‐09), p‐tau181 (rho = 0.69, p = 1.7e‐09) and amyloid beta 42 (rho = ‐0.71, p = 4.7e‐10) levels in cerebrospinal fluid (CSF). S100A12 levels also correlated significantly with total tau (rho = ‐0.39, p = 0.0031), p‐tau181 (rho = ‐0.36, p = 0.0053) and amyloid beta 42 (rho = 0.38, p = 0.0067) CSF levels. Receiver operating characteristic analysis demonstrated that GFAP strongly discriminated AD from controls with an area under the curve (AUC) of 0.93 (95% CI 0.87‐1.0), and S100A12 also exhibited good discrimination with an AUC of 0.72 (95% CI 0.59‐0.86). Conclusion: This exploratory study identified serum GFAP levels as a strong discriminatory biomarker for AD, consistent with previous studies. S100A12 also demonstrated significant associations with AD and CSF biomarkers and thus warrants further study. NULISA holds great promise for the discovery and validation of blood‐based biomarkers for the early detection and monitoring of neurodegenerative diseases. 1. Feng, W. et al. bioRxiv 2023.04.09.536130 (2023) https://doi.org/10.1101/2023.04.09.536130. [ABSTRACT FROM AUTHOR]

Objective: To reveal the alterations in quality of life (QOL) in bone metastases patients after magnetic resonance guided focused ultrasound (MRgFUS). Methods: This retrospective study enrolled 26 patients diagnosed with bone metastases. Patients had various primary malignant tumors and tumor lesions in different locations. All patients received MRgFUS for bone metastasis. Each focal spot sonication pulse that was applied to create energy deposition lasted 20 s and was performed at a frequency of 1.05 MHz. The visual analog scale (VAS) was used to measure pain level and the EORTC QLQ‐BM22 was applied to evaluate QOL for 12 months. The lower the QLQ‐BM22 score, the better the QOL of patients. Results: The painful site subscale of the EORTC QLQ‐BM22 was observed without significant change. Significant reductions in the functional subscales were observed after therapy compared with the baseline. The functional interference was reduced significantly during the first 12 months. From the 2‐month time point onwards, the pain characteristics subscale also decreased significantly. VAS scores had decreased by 40.8% 1 month after the operation and had decreased 10.9% compared with VAS scores preoperation. Scores for pain characteristics decreased by 28.8% after the operation and the scores were still down by 10.8% 1 year after the treatment. VAS scores indicated a significant reduction in pain over the course of the research until the 12‐month time point follow‐up compared with the baseline. Conclusion: MRgFUS therapy improved the QOL of patients with bone metastasis by relieving bone pain. [ABSTRACT FROM AUTHOR]

Objective To explore the outcomes of surgical treatment of sacral neurogenic tumors Methods Between 1 January 2003 and 31 December 2012, data on 64 patients with sacral neurogenic tumors treated with surgery were retrospectively analyzed. The mean age of the 64 cases (35 males and 29 females) was 37.2 years (range, 21-69 years); 38 had neurilemmomas and 26 neurofibromas. Thirty-four of the tumors involved S1 and S2, 11 S3 or lower, and 19 were single presacral soft tissue masses. Tumors were removed via anterior, posterior or combined anteroposterior approaches. Patients with unstable sacroiliac joints underwent iliolumbar fixation. Results Depending on the extent of tumor involvement, one of three surgical approaches was used: a single anterior approach (19 patients), single posterior approach (25 patients), or a combined anteroposterior approach (20 patients). The mean operation time was 3 h (range, 2-6 h) and the mean blood loss 878 mL (range, 400-3120 mL). The mean duration of follow-up was 58.2 months (range, 24-93 months). These surgeries had the following complications. Three patients had massive intraoperative hemorrhage and posterior back pain and discomfort postoperatively. One patient had intraoperative ureteral injuries requiring intraoperative ureteral catheterization. In two patients, the tumor involved the S1 nerve roots bilaterally, necessitating their removal, which resulted in obvious lower limb motion and sphincteric dysfunction. In 13 patients with unilateral tumor involvement of the nerve roots of S1 and lower spinal levels, only the contralateral nerve roots of the S1 and lower levels were preserved; eight of these patients had impaired bladder and bowel function. Posterior incisions failed to heal in 10 patients, secondary wound healing occurred in nine of them and one required a gluteus maximus myocutaneous flap. Three patients developed postoperative cerebrospinal fluid leaks that were and alleviated by waist belt compression bandaging and placing them in the Trendelenburg position. Eight patients developed tumor recurrences postoperatively; pathological examination of the tissue excised in the second surgeries revealed malignant changes in the three patients with neurilemmomas. There were no intraoperative deaths. Rod fractures occurred in three of the 18 patients requiring iliolumbar reconstruction. Conclusions The clinical characteristics of sacral neurogenic tumors make them easy to diagnose. The approach to resection should be determined by the location and size of the tumor. Patients with huge tumors may lose considerable blood intraoperatively and a have higher risk rate of postoperative complications. [ABSTRACT FROM AUTHOR]

BACKGROUND Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC) is a unique form of carcinoma that is important to identify for prognosis and treatment. Immunohistochemistry (IHC) for p16 (also known as cyclin-dependent kinase inhibitor 2A, multiple tumor suppressor 1) is used as a surrogate marker for transcriptionally active, high-risk HPV. The primary objective of this study was to correlate p16 IHC of cell blocks from fine-needle aspirations (FNAs) with surgical pathology specimens of HPV-related oropharyngeal SCC. METHODS In total, 48 patients who had a diagnosis of oropharyngeal or nonoropharyngeal SCC and also had an FNA that demonstrated metastatic SCC with available cell block material were identified. IHC for p16 was evaluated on both FNA cell blocks and surgical pathology specimens. In situ hybridization for high-risk HPV messenger RNA was performed on 31 of the FNA cell blocks. RESULTS Although partial p16 staining was observed in the majority of cell blocks, there was concordance in 47 of 48 FNAs (98%) with surgical pathology specimens when strong positive p16 staining of at least 15% of tumor cells in FNA cell block material was present. In addition, high-risk HPV RNA in situ hybridization demonstrated a high correlation with p16 staining in surgical pathology specimens (96%) and FNAs (93%). CONCLUSIONS There was excellent correlation between p16 IHC of FNA cell blocks and surgical pathology specimens using a cutoff of at least 15% positive staining in cell blocks. The recommended threshold (70% positive staining) for surgical pathology specimens may yield a high rate of false-negative results if applied to FNA cell blocks. Cancer (Cancer Cytopathol) 2015;123:723-731. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) was the most common primary liver cancer, and its resistance to anti-tumor drugs often caused the death of patients suffering with HCC. Matrix stiffness was reported to be closely related to tumor chemoresistance; however, the relationship between HCC drug resistance and three-dimensional (3D) matrix stiffness is still unclear at present. In this study, alginate gel (ALG) beads with controllable matrix stiffness were used to mimic tumor tissue rigidity, and the role of 3D matrix stiffness in regulating the chemoresistance of HCC cells was investigated by using these ALG beads. It was found that HCC cells in ALG beads with 105 kPa stiffness had highest resistance to paclitaxel, 5-FU, and cisplatin. Although the mechanism was still uncovered, ABC transporters and endoplasmic reticulum stress-related molecules were highly expressed in ALG bead-encapsulated HCC cells compared with two-dimensional-cultured cells, which suggested a very complex mechanism underlying HCC drug resistance in 3D culture conditions. In addition, to mimic the specific stiffness of HCC tumor tissue, or other tumor tissues in vivo, response surface methodology (RSM) was used to build up a prediction mathematical model so that ALG beads with desired matrix stiffness could be prepared by simply changing three factors: molecular weight, G content, and alginate concentration. [ABSTRACT FROM AUTHOR]

Background Detection of immunoglobulin light-chain restriction is important in the diagnosis of B-cell non-Hodgkin lymphoma ( B-NHL). Flow-cytometry, commonly used to evaluate light-chain restriction, is impractical to be used in cutaneous specimens. Immunohistochemical and conventional chromogenic in situ hybridization ( CISH) methods on formalin-fixed-paraffin-embedded ( FFPE) tissue lack sufficient sensitivity to detect low-level light-chain expression in B- NHL without plasmacytic differentiation. Ultrasensitive bright-field mRNA-ISH ( BRISH) for in situ light-chain detection in cutaneous B- NHL has been assessed. Design Kappa/lambda mRNA was detected using two-color BRISH (RNAscope 2xPlex, Advanced Cell Diagnostics) on 27 FFPE skin biopsies and excisions from patients with available B-cell PCR clonality studies: 16 clonal B-cell lesions (6 follicle center lymphoma, 5 marginal zone lymphoma, 3 large B-cell lymphoma, and 2 other) and 11 non-clonal B-cell proliferations. Results BRISH was successful in 15/16 clonal B-cell lesions and 11/11 non-clonal proliferations. Light-chain restriction was detected in 15/15 clonal lesions and in 1/11 non-clonal proliferations (96.1% overall concordance with clonality PCR). In 4/5 marginal zone lymphomas, light-chain restriction was detected as strong monotypic mRNA expression in a B-cell subset, consistent with plasmacytic differentiation. Conclusion Ultrasensitive BRISH can successfully detect light-chain restriction in B- NHL from FFPE skin specimens and may be a useful adjunct ancillary tool in cases not resolved by CISH or immunohistochemical methods. [ABSTRACT FROM AUTHOR]

Oropharyngeal squamous cell carcinoma (SCC) is strongly associated with human papillomavirus (HPV) infection, which is distinctively different from most other head and neck cancers. However, a robust quantitative reverse transcription PCR (RT-qPCR) method for comprehensive expression profiling of HPV genes in routinely fixed tissues has not been reported. To address this issue, we have established a new real-time RT-PCR method for the expression profiling of the E6 and E7 oncogenes from 13 high-risk HPV types. This method was validated in cervical cancer and by comparison with another HPV RNA detection method ( in situ hybridization) in oropharyngeal tumors. In addition, the expression profiles of selected HPV-related human genes were also analyzed. HPV E6 and E7 expression profiles were then analyzed in 150 archived oropharyngeal SCC samples and compared with other variables and with patient outcomes. Our study showed that RT-qPCR and RNA in situ hybridization were 100% concordant in determining HPV status. HPV transcriptional activity was found in most oropharyngeal SCC (81.3%), a prevalence that is higher than in previous studies. Besides HPV16, three other HPV types were also detected, including 33, 35 and 18. Furthermore, HPV and p16 had essentially identical expression signatures, and both HPV and p16 were prognostic biomarkers for the prediction of disease outcome. Thus, p16 mRNA or protein expression signature is a sensitive and specific surrogate marker for HPV transcriptional activity (all genotypes combined). [ABSTRACT FROM AUTHOR]

Lewis J S Jr, Ukpo O C, Ma X-J, Flanagan J J, Luo Y, Thorstad W L & Chernock R D (2012) Histopathology 60, 982-991 Transcriptionally-active high-risk human papillomavirus is rare in oral cavity and laryngeal/hypopharyngeal squamous cell carcinomas - a tissue microarray study utilizing E6/E7 mRNA in situ hybridization Aims: Human papillomavirus is well established in oropharyngeal squamous cell carcinoma as both causative and prognostic, but its significance in non-oropharyngeal tumours is unclear. In particular, the significance of finding viral DNA is not known. We sought to evaluate nonoropharyngeal squamous cell carcinomas for transcriptionally-active human papillomavirus and to compare this with the presence of viral DNA. Methods: We evaluated an 87 patient tissue microarray cohort of oral cavity and laryngeal/hypopharyngeal squamous cell carcinomas for high risk human papillomavirus DNA and E6 and E7 mRNA transcripts by in situ hybridization, and for p16 expression by immunohistochemistry. Results: We found only two of the 73 (2.7%) evaluable cases to harbour transcriptionally-active human papillomavirus. Both of these tumours were from the larynx, one was positive for human papillomavirus DNA by in situ hybridization, and both were extensively positive for p16. All oral cavity and hypopharyngeal tumours were negative for human papillomavirus. Conclusions: Transcriptionally-active human papillomavirus appears to be rare in laryngeal, hypopharyngeal, and oral cavity squamous cell carcinomas. As such, it appears unlikely to be a 'driver' or to be clinically significant in most established tumours. [ABSTRACT FROM AUTHOR]

Patients with carcinoma of unknown primary (CUP) present with metastatic disease for which the primary site cannot be found, despite extensive standard investigation. Here, we describe the development and implementation of the first clinically available microarray-based test for this cancer type (CUPPrint), based on 633 individual tumors representing 30 carcinoma and 17 noncarcinoma classes. Tissue of origin prediction for either fresh frozen or paraffin-embedded tumor samples is achieved with the use of a custom 8-pack 1.9k microarray and robust classification algorithm. An expression profile of 495 genes was used to predict tumor origin by applying a k-nearest neighbor algorithm. Internal cross-validation and analysis of an independent, previously published, 229-sample dataset revealed that clinically informative predictions were made for up to 94% of samples analyzed. Analysis of 13 previously published CUP specimens yielded predicted tumor origins that supported the clinical suspicion in 12 cases (92%). Microarray profiling presents a promising tool to assist in the identification of the primary tumor and might direct a more tailored treatment for CUP patients. © 2009 UICC [ABSTRACT FROM AUTHOR]