Histologic and Quality Assessment of Genotype-Tissue Expression (GTEx) Research Samples: A Large Postmortem Tissue Collection.

CONTEXT.­: The National Institutes of Health Genotype-Tissue Expression (GTEx) project was developed to elucidate how genetic variation influences gene expression in multiple normal tissues procured from postmortem donors. OBJECTIVE.­: To provide critical insight into a biospecimen's suitability for subsequent analysis, each biospecimen underwent quality assessment measures that included evaluation for underlying disease and potential effects introduced by preanalytic factors. DESIGN.­: Electronic images of each tissue collected from nearly 1000 postmortem donors were evaluated by board-certified pathologists for the extent of autolysis, tissue purity, and the type and abundance of any extraneous tissue. Tissue-specific differences in the severity of autolysis and RNA integrity were evaluated, as were potential relationships between these markers and the duration of postmortem interval and rapidity of death. RESULTS.­: Tissue-specific challenges in the procurement and preservation of the nearly 30 000 tissue specimens collected during the GTEx project are summarized. Differences in the degree of autolysis and RNA integrity number were observed among the 40 tissue types evaluated, and tissue-specific susceptibilities to the duration of postmortem interval and rapidity of death were observed. CONCLUSIONS.­: Ninety-five percent of tissues were of sufficient quality to support RNA sequencing analysis. Biospecimens, annotated whole slide images, de-identified clinical data, and genomic data generated for GTEx represent a high-quality and comprehensive resource for the scientific community that has contributed to its use in approximately 1695 articles. Biospecimens and data collected under the GTEx project are available via the GTEx portal and authorized access to the Database of Genotypes and Phenotypes; procedures and whole slide images are available from the National Cancer Institute.

Notable Histologic Findings in a "Normal" Cohort: The National Institutes of Health Genotype-Tissue Expression (GTEx) Project

CONTEXT.­: The National Institutes of Health (NIH) Genotype-Tissue Expression (GTEx) project was designed to evaluate how genetic variation and epigenetic effects influence gene expression in normal tissue. OBJECTIVE.­: To ensure that the grossly normal-appearing tissues collected were free from disease, each specimen underwent histologic evaluation. DESIGN.­: In total, nearly 30 000 tissue aliquots collected from almost 1000 postmortem donors underwent histologic review by project pathologists, and detailed observations of any abnormalities or lesions present were recorded. RESULTS.­: Despite sampling of normal-appearing tissue, in-depth review revealed incidental findings among GTEx samples that included neoplastic, autoimmune, and genetic conditions; the incidence of some of these conditions among GTEx donors differed from those previously reported for other populations. A number of age-related abnormalities observed during histologic review of tissue specimens are also described. CONCLUSIONS.­: Histologic findings from the GTEx project may serve to improve populational awareness of several conditions and present a unique opportunity for others to explore age- and gender-influenced conditions. Resources from the study, including histologic image and sequencing data, are publicly available for research.

Effect of nurse-physician collaboration on the incidence of complications, negative emotions and quality of life in cervical cancer patients: a randomized controlled study.

The aim of this study was to evaluate the effect of nurse-physician collaboration on the incidence of complications, anxiety and depression, quality of life, and satisfaction with nursing care among cervical cancer patients undergoing three-dimensional intracavitary brachytherapy. In this randomized, single-blinded, placebo-controlled trial, 92 eligible cervical cancer patients were equally divided into two groups upon admission. The control group was given routine nursing, and the intervention group received a nurse-physician collaboration in addition to routine care. Anxiety, depression, and health-related quality of life in both groups were assessed and compared at baseline and discharge. The intervention group had significantly fewer complications and showed marked improvements in mental health and quality of life compared to the control group. Satisfaction with nursing care was substantially greater in the intervention group. These results support the clinical adoption of a nurse-physician collaborative care model in the management of cervical cancer with three-dimensional intracavitary brachytherapy.

Temperature Thresholds of Pyrogenic Dissolved Organic Matter in Heating Experiments Simulating Forest Fires.

Heating temperature (HT) during forest fires is a critical factor in regulating the quantity and quality of pyrogenic dissolved organic matter (DOM). However, the temperature thresholds at which maximum amounts of DOM are produced (TTmax) and at which the DOC gain turns into net DOC loss (TT0) remain unidentified on a component-specific basis. Here, based on solid-state 13C nuclear magnetic resonance, absorbance and fluorescence spectroscopies, and Fourier transform ion cyclotron resonance mass spectrometry, we analyzed variations in DOM composition in detritus and soil with HT (150-500 °C) and identified temperature thresholds for components on structural, fluorophoric, and molecular formula levels. TTmax was similar for detritus and soil and ranged between 225 and 250 °C for bulk dissolved organic carbon (DOC) and most DOM components. TT0 was consistently lower in detritus than in soil. Moreover, temperature thresholds differed across the DOM components. As the HT increased, net loss was observed initially in molecular formulas tentatively associated with carbohydrates and aliphatics, then proteins, peptides, and polyphenolics, and ultimately condensed aromatics. Notably, at temperatures lower than TT0, particularly at TTmax, burning increased the DOC quantity and thus might increase labile substrates to fuel soil microbial community. These composition-specific variations of DOM with temperature imply nonlinear and multiple temperature-dependent wildfire impacts on soil organic matter properties.

Inhibition Effect and Molecular Mechanisms of Quercetin on the Aß42 Dimer: A Molecular Dynamics Simulation Study.

Amyloid-ß (Aß) dimer as the smallest oligomer has recently been drawing attention due to its neurotoxicity, transient nature, and heterogeneity. The inhibition of Aß dimer's aggregation is the key to primary intervention of Alzheimer's disease. Previous experimental studies have reported that quercetin, the widespread polyphenolic constituent of multiple fruits and vegetables, can hamper the formation of Aß protofibrils and disaggregate Aß fibrils. However, the molecular mechanisms of quercetin in the suppression of the Aß(1-42) dimer's conformational changes still remain elusive. In this work, to investigate the inhibitory mechanisms of quercetin molecules on the Aß(1-42) dimer, an Aß(1-42) dimer based on monomeric the Aß(1-42) peptide with enriched coil structures is constructed. The early molecular mechanisms of quercetin molecules on inhibiting the Aß(1-42) dimer at two different Aß42-to-quercetin molar ratios (1:5 and 1:10) are explored via all-atom molecular dynamics simulations. The results indicate that quercetin molecules can impede the configurational change of the Aß(1-42) dimer. The interactions and the binding affinity between the Aß(1-42) dimer and quercetin molecules in the Aß42 dimer + 20 quercetin system are stronger in comparison with that in the Aß42 dimer + 10 quercetin system. Our work may be helpful in developing new drug candidates for preventing the conformational transition and further aggregation of the Aß dimer.

Metal-rich cascade nanosystem for dual-pathway ferroptosis resistance regulation and photothermal effect for efficient tumor combination therapy.

Despite the therapeutic response of ferroptosis in various tumors, ferroptosis resistance has been found in numerous studies, significantly hindering the progress of ferroptosis anti-tumor therapy. Herein, we propose a metal-rich cascade nanosystem (Simvastatin-HMPB-Mn@GOx) combined with the dual-pathway regulation of ferroptosis resistance and photothermal therapy for efficient tumor combination therapy. The manganese-bonded hollow mesoporous Prussian blue (HMPB-Mn) serves as the photothermal agent and metal donor, and dissociates multivalent metal ions Mn2+, Fe3+ and Fe2+ to consume glutathione and amplify the Fenton reaction. Glucose oxidase (GOx) absorbed serves as the converter to provide hydrogen peroxide (H2O2) for the cascade Fenton reaction, causing a high burst of hydroxyl radicals (˙OH) and lipid peroxidation. Simvastatin innovatively acts as a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) inhibitor to decrease the expression of coenzyme Q10 (CoQ10) and glutathione peroxidase 4 (GPX4), eventually defeating ferroptosis resistance. The nanosystem acted in both classical and non-classical ferroptosis pathways and showed significant ferroptosis- and hyperthermia-induced anti-tumor efficacy both in vitro and in vivo. Thus, this study offers a promising way for ferroptosis and phototherapy to achieve complete tumor regression.

Formalin Fixation, Delay to Fixation, and Time in Fixative Adversely Impact Copy Number Variation Analysis by aCGH.

Although molecular profiling of DNA isolated from formalin-fixed, paraffin-embedded (FFPE) tumor specimens has become more common in recent years, it remains unclear how discrete FFPE processing variables may affect detection of copy number variation (CNV). To better understand such effects, array comparative genomic hybridization (aCGH) profiles of FFPE renal cell carcinoma specimens that experienced different delays to fixation (DTFs; 1, 2, 3, and 12 hours) and times in fixative (TIFs; 6, 12, 23, and 72 hours) were compared to snap-frozen tumor and blood specimens from the same patients. A greater number of regions containing CNVs relative to commercial reference DNA were detected in DNA from FFPE tumor specimens than snap-frozen tumor specimens even though they originated from the same tumor blocks. Extended DTF and TIF affected the number of DNA segments with a copy number status that differed between FFPE and frozen tumor specimens; a DTF ≥3 hours led to more segments, while a TIF of 72 hours led to fewer segments. Importantly, effects were not random as a higher guanine-cytosine (GC) content and/or a higher percentage of repeats were observed among stable regions. While limiting aCGH analysis to FFPE specimens with a DTF <3 hours and a TIF <72 hours may circumvent some effects, results from FFPE specimens should be validated against fresh or frozen specimens whenever possible.

Successful inguinal interstitial brachytherapy in metastatic cervical carcinoma: a case report.

Background: Treatment of metastatic cervical cancer is a tricky issue. Currently, the National Comprehensive Cancer Network (NCCN) guideline recommends chemotherapy combined with bevacizumab for recurrent or metastatic cervical cancer. Still, the recurrence rate is high and the survival rate is low after standard treatment. We urgently need to achieve a multimodal therapy approach for recurrent or metastatic cervical cancer. Case description: We report the case of a patient with stage IB2 cervical squamous carcinoma who developed multiple metastases within a short term after receiving first-line standard treatment, and she underwent interstitial brachytherapy after systemic therapy with an encouraging outcome. The patient developed suspected inguinal lymph node metastases after 9 months at the end of first-line therapy and multiple metastases in the inguinal lymph nodes, anterior abdominal wall, and right lung after 17 months. As the patient had residual inguinal lymph nodes after systemic therapy, she received 3D-printed template-guided interstitial brachytherapy to the inguinal lymph nodes and maintenance therapy. By Sep 2023, she had achieved a good treatment outcome with a progression-free survival (PFS) of 36 months. Conclusion: Based on our patient response, when multiple metastases develop in the short term in early-stage cervical squamous carcinoma after first-line therapy, we may consider implementing local therapy combined with systemic therapy.

Case report: Interstitial implantation radiotherapy combined with immunotherapy and GM-CSF in oligometastatic platinum-resistant ovarian cancer.

Background: Treatment for platinum-resistant ovarian cancer is challenging. Currently, platinum-resistant ovarian cancer is typically treated with non-platinum single-agent chemotherapy ± bevacizumab, but the prognosis is often extremely poor. In the treatment of platinum-resistant ovarian cancer patients, reports of triple therapy with interstitial implantation radiotherapy combined with immunotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF) (PRaG for short) are relatively rare. Case description: Here, we report a patient with oligometastatic platinum-resistant ovarian cancer. The patient achieved partial response (PR) of the lesion and sustained benefit for more than six months after receiving interstitial implantation radiotherapy combined with immunotherapy along with GM-CSF. Conclusion: This triple therapy may provide additional options for these patients.

Curcumin-loaded protein imprinted mesoporous nanosphere for inhibiting amyloid aggregation.

Some natural variants of human lysozyme are associated with systemic non-neurological amyloidosis that leads to amyloid protein fibril deposition in different tissues. Inhibition of amyloid fibrillation by nanomaterials is considered to be an effective approach to treating amyloidosis. Here, we prepared a targeted, highly loaded curcumin lysozyme-imprinted nanosphere (CUR-MIMS) that could effectively inhibit the aggregation of lysozyme with lysozyme adsorption capacity of 193.57 mg g-1 and the imprinting factor (IF) of 3.72. CUR-MIMS could bind to lysozyme through hydrophobic interactions and effectively reduce the hydrophobicity of the total solvent-exposed surface in lysozyme fibrillation, thus reducing the self-assembly process triggered by hydrophobic interactions. Thioflavin T (ThT) analysis demonstrated that CUR-MIMS inhibited the aggregation of amyloid fibrils in a dose-dependent manner (inhibition efficiency of 56.07 %). Circular dichroism (CD) spectrum further illustrated that CUR-MIMS could significantly inhibit the transition of lysozyme from α-helix structure to ß-sheet. More importantly, biological experiments proved the good biocompatibility of CUR-MIMS, which indicated the potential of our system as a future therapeutic platform for amyloidosis.

Organocatalyst treatment improves variant calling and mutant detection in archival clinical samples.

Formalin fixation of biological specimens damages nucleic acids and limits their use in genomic analyses. Previously, we showed that RNA isolation with an organocatalyst (2-amino-5-methylphenyl phosphonic acid, used to speed up reversal of formalin-induced adducts) and extended heated incubation (ORGΔ) improved RNA-sequencing data from formalin-fixed paraffin-embedded (FFPE) tissue samples. The primary goal of this study was to evaluate whether ORGΔ treatment improves DNA-sequencing data from clinical FFPE samples. We isolated RNA and DNA ± ORGΔ from paired FFPE and frozen human renal and ovarian carcinoma specimens collected as part of the National Cancer Institute Biospecimen Pre-analytical Variables program. Tumor types were microscopically confirmed from adjacent tissue sections. Following extraction, DNA was fragmented and sequenced and differences were compared between frozen and FFPE sample pairs. Treatment with ORGΔ improved concurrent SNP calls in FFPE DNA compared to non-ORGΔ FFPE samples and enhanced confidence in SNP calls for all FFPE DNA samples, beyond that of matched frozen samples. In general, the concordant SNPs identified in paired frozen and FFPE DNA samples agreed for both genotype and homozygosity vs. heterozygosity of calls regardless of ORGΔ treatment. The increased confidence in ORGΔ FFPE DNA variant calls relative to the matched frozen DNA suggests a novel application of this method. With further optimization, this method may improve quality of DNA-sequencing data in FFPE as well as frozen tissue samples.

Self-Organization Formation of Multicellular Spheroids Mediated by Mechanically Tunable Hydrogel Platform: Toward Revealing the Synergy of Chemo- and Noninvasive Photothermal Therapy against Colon Microtumor.

Three-dimensional (3D) tumor cell culture offers a more tissue-recapitulating model in cancer treatment evaluation. However, conventional models based on cell-substrate adhesion deprivation are still of insufficient real tumor mimic. In this work, a novel method is proposed for inducing multicellular spheroids (MCSs) formation based on hydrogel with tunable microenvironmental properties. Colon tumor cells DLD1 cultured on hydrogel substrate with proper physical stimulation form MCSs via self-organization. Chemotherapy based on clinical drug and far-infrared photothermal therapy is evaluated with DLD1 MCSs obtained by this method. The synergism of chemotherapy and noninvasive photothermal therapy based on graphene device is further verified in MCSs model and it is believed this method holds potential in in vitro anti-tumor strategies evaluation for precision medicine.

Near-infrared light triggered multi-hit therapeutic nanosystem for tumor specific photothermal effect amplified signal pathway regulation and ferroptosis.

The high therapeutic resistance of tumor is the primary cause behind tumor recurrence and incurability. In recent years, scientists have devoted themselves to find a variety of treatments to solve this problem. Herein, we propose a multi-hit strategy that is based on the biodegradable hollow mesoporous Prussian blue (HMPB)-based nanosystem for tumor-specific therapy that encapsulated the critical heat shock protein 90 (HSP90) inhibitor 17-dimethylamino-ethylamino-17-demethoxydeldanamycin (17-DMAG). The nanosystem was further modified using thermotropic phase transition material star-PEG-PCL (sPP) and hyaluronic acid (HA), which offers near infrared light (NIR) responsive release characteristic, as well as enhanced tumor cell endocytosis. Upon cell internalization of 17-DMAG-HMPB@sPP@HA and under 808 nm laser irradiation, photothermal-conversion effect of HMPB directly kills cells using hyperthermia, which further causes phase transition of sPP to trigger release of 17-DMAG, inhibits HSP90 activity and blocks multiple signaling pathways, including cell cycle, Akt and HIF pathways. Additionally, the down-regulation of GPX4 protein expression by 17-DMAG and the release of ferric and ferrous ions from gradual degradation of HMPB in the endogenous mild acidic microenvironment in tumors promoted the occurrence of ferroptosis. Importantly, the antitumor effect of 17-DMAG and ferroptosis damage were amplified using photothermal effect of HMPB by accelerating release of ferric and ferrous ions, and reducing HSP90 expression in cells, which induced powerful antitumor effect in vitro and in vivo. This multi-hit therapeutic nanosystem helps provide a novel perspective for solving the predicament of cancer treatment, as well as a promising strategy for design of a novel cancer treatment nanoplatform.

Interstitial brachytherapy combined with PARP inhibitors in the treatment of chemoresistant recurrent epithelial ovarian cancer: A case report.

Background: Chemoresistance generally develops in patients with advanced epithelial ovarian cancer, and the prognosis is still very poor, with an expected survival time of less than one year. For this population of individuals, there is currently no standard protocol for clinical benefit. Case presentation: We report a case of an elderly woman diagnosed with stage IIIC high-grade serous ovarian cancer (HGSOC). During a follow-up time of 6 years, the patient initially received multiple sequential courses of chemotherapy with platinum-based regimens and with no maintenance therapy. Similar to most patients with advanced HGSOC, she developed platinum resistance and experienced poor treatment results with a short progression-free survival (PFS). Ultimately, we gave the patient traditional non-platinum-based chemotherapy with bevacizumab and high-dose-rate interstitial brachytherapy followed by olaparib as a maintenance therapy. Up to now, the patient did response well to the treatment, and the PFS had exceeded 12 months. Conclusion: High-dose-rate interstitial brachytherapy combination with PARP inhibitors may be an option for isolated chemoresistant recurrent epithelial ovarian cancer.

Impact of Preanalytical Factors on the Measurement of Tumor Tissue Biomarkers Using Immunohistochemistry.

Analysis of formalin-fixed paraffin-embedded (FFPE) tissue by immunohistochemistry (IHC) is commonplace in clinical and research laboratories. However, reports suggest that IHC results can be compromised by biospecimen preanalytical factors. The National Cancer Institute's Biospecimen Preanalytical Variables Program conducted a systematic study to examine the potential effects of delay to fixation (DTF) and time in fixative (TIF) on IHC using 24 cancer biomarkers. Differences in IHC staining, relative to controls with a DTF of 1 hr, were observed in FFPE kidney tumor specimens after a DTF of ≥2 hr. Reductions in H-score and/or staining intensity were observed for c-MET, p53, PAX2, PAX8, pAKT, and survivin, whereas increases were observed for RCC1, EGFR, and CD10. Prolonged TIF of 72 hr resulted in significantly reduced H-scores of CD44 and c-Met in kidney tumor specimens, compared with controls with 12-hr TIF. An elevated probability of altered staining intensity due to DTF was observed for nine antigens, whereas for prolonged TIF an elevated probability was observed for one antigen. Results reported here and elsewhere across tumor types and antigens support limiting DTF to ≤1 hr when possible and fixing tissues in formalin for 12-24 hr to avoid confounding effects of these preanalytical factors on IHC.

Iron overload is related to elevated blood glucose levels in obese children and aggravates high glucose-induced endothelial cell dysfunction in vitro.

INTRODUCTION: This study was performed to investigate the role of iron overload in the early stage of hyperglycemia-induced vascular functional impairment. RESEARCH DESIGN AND METHODS: A total of 196 obese children were enrolled, and data regarding ferritin levels, blood glucose levels, intima-media thickness of carotid arteries, liver function and fibrosis index, hemoglobin, blood pressure, blood lipids, and inflammation indicators were collected. Ferritin levels were compared with a control group, which consisted of 148 healthy non-obese children who were age-matched and gender-matched. Endothelial cells were cultured in high glucose medium and supplemented with ferric citrate with or without iron remover (deferoxamine), a reducing agent (N-acetyl-cysteine), or a nuclear factor-κB (NF-κB) inhibitor (BAY 11-7082). Apoptosis, oxidative stress, nitric oxide levels, and endothelin content were evaluated. DNA microarray analysis was performed to analyze the expression of genes in the NF-κB signaling pathway. RESULTS: Obese children have significantly higher ferritin levels compared with the control group. Ferritin level was positively correlated with hemoglobin and was related to metabolic disorders, including impaired glucose tolerance, higher blood pressure, dyslipidemia, and impaired hepatic function. Endothelial cells treated with ferric citrate showed a significantly higher rate of apoptosis, higher levels of oxidative stress, and impaired vasomotor function under high glucose conditions. The above effects were rescued by treatment with an iron remover, reducing agent, or NF-κB inhibitor. Further, detection of phosphorylated-p65 distribution in cells confirmed activation of the NF-κB pathway. DNA microarrays and subsequent gene oncology enrichment analyses revealed the main processes activated in cells. CONCLUSION: Increased ferritin levels are related to impaired glucose tolerance and other metabolic disorders in obese children. At the cellular level, iron overload aggravated the endothelial cell dysfunction caused by high glucose.

Protein-Based Artificial Nanosystems in Cancer Therapy.

Proteins, like actors, play different roles in specific applications. In the past decade, significant achievements have been made in protein-engineered biomedicine for cancer therapy. Certain proteins such as human serum albumin, working as carriers for drug/photosensitizer delivery, have entered clinical use due to their long half-life, biocompatibility, biodegradability, and inherent nonimmunogenicity. Proteins with catalytic abilities are promising as adjuvant agents for other therapeutic modalities or as anticancer drugs themselves. These catalytic proteins are usually defined as enzymes with high biological activity and substrate specificity. However, clinical applications of these kinds of proteins remain rare due to protease-induced denaturation and weak cellular permeability. Based on the characteristics of different proteins, tailor-made protein-based nanosystems could make up for their individual deficiencies. Therefore, elaborately designed protein-based nanosystems, where proteins serve as drug carriers, adjuvant agents, or therapeutic drugs to make full use of their intrinsic advantages in cancer therapy, are reviewed. Up-to-date progress on research in the field of protein-based nanomedicine is provided.

Diagnostic performance of convolutional neural network-based Tanner-Whitehouse 3 bone age assessment system.

BACKGROUND: Bone age can reflect the true growth and development status of a child; thus, it plays a critical role in evaluating growth and endocrine disorders. This study established and validated an optimized Tanner-Whitehouse 3 artificial intelligence (TW3-AI) bone age assessment (BAA) system based on a convolutional neural network (CNN). METHODS: A data set of 9,059 clinical radiographs of the left hand was obtained from the picture archives and communication systems (PACS) between January 2012 and December 2016. Among these, 8,005/9,059 (88%) samples were treated as the training set for model implementation, 804/9,059 (9%) samples as the validation set for parameters optimization, and the remaining 250/9,059 (3%) samples were used to verify the accuracy and reliability of the model compared to that of 4 experienced endocrinologists and 2 experienced radiologists. The overall variation of TW3-metacarpophalangeal, radius, ulna and short bones (RUS) and TW3-Carpal bone score, as well as each bone (13 RUS + 7 Carpal) between reviewers and the AI, were compared by Bland-Altman (BA) chart and Kappa test, respectively. Furthermore, the time consumption between the model and reviewers was also compared. RESULTS: The performance of TW3-AI model was highly consistent with the reviewers' overall estimation, and the root mean square (RMS) was 0.50 years. The accuracy of the BAA of the TW3-AI model was better than the estimate of the reviewers. Further analysis revealed that human interpretations of the male capitate, hamate, the first distal and fifth middle phalanx and female capitate, the trapezoid, and the third and fifth middle phalanx, were most inconsistent. The average image processing time was 1.5±0.2 s in the TW3-AI model, which was significantly shorter than manual interpretation. CONCLUSIONS: The diagnostic performance of CNN-based TW3 BAA was accurate and timesaving, and possesses better stability compared to diagnostics made by experienced experts.

Drug-based magnetic imprinted nanoparticles: Enhanced lysozyme amyloid fibrils cleansing and anti-amyloid fibrils toxicity.

Lysozyme amyloid fibrils, the misfolding structures generated from natural state of lysozyme, are found to be related with non-neuropathic systemic amyloidosis. Therefore, inhibiting the formation of amyloid and disaggregating amyloid fibers are both effective strategies. Herein, we present a combination of Epigallocatechin-3-gallate (EGCG), imprinting technology and magnetic nanoparticles to obtain a kind of promising nanomaterials (MINs@EGCG) for amyloid inhibition, drug carrier and facile separation triple functions. We declared the efficacy of MINs@EGCG from two perspectives. For inhibition, Circular dichroism (CD) spectrum illustrated that the miss transition from α-helix structure to ß-sheet could be blocked by MINs@EGCG, and the inhibition efficiency was higher than 80%. These results were further verified by Thioflavin T (ThT) analysis. For disaggregation and cleansing, the helical and highly periodic structure of amyloid fibrils could be converted into their counterparts by MINs@EGCG. Furthermore, with the aid of external magnetic field, the cleansing efficiency of counterparts-MINs@EGCG complex was up to 80%. Most importantly, bio-related experiments showed superior biocompatibility and anti-amyloid fibrils toxicity of MINs@EGCG, indicating the great potential of our system to work as an effective amyloidosis therapy platform.

Deleterious effects of formalin-fixation and delays to fixation on RNA and miRNA-Seq profiles.

The National Cancer Institute conducted the Biospecimen Pre-analytical Variables (BPV) study to determine the effects of formalin fixation and delay to fixation (DTF) on the analysis of nucleic acids. By performing whole transcriptome sequencing and small RNA profiling on matched snap-frozen and FFPE specimens exposed to different delays to fixation, this study aimed to determine acceptable delays to fixation and proper workflow for accurate and reliable Next-Generation Sequencing (NGS) analysis of FFPE specimens. In comparison to snap-freezing, formalin fixation changed the relative proportions of intronic/exonic/untranslated RNA captured by RNA-seq for most genes. The effects of DTF on NGS analysis were negligible. In 80% of specimens, a subset of RNAs was found to differ between snap-frozen and FFPE specimens in a consistent manner across tissue groups; this subset was unaffected in the remaining 20% of specimens. In contrast, miRNA expression was generally stable across various formalin fixation protocols, but displayed increased variability following a 12 h delay to fixation.