Traditional Chinese herbal medicine retention enema combined with perineal massage (THREM): a promising therapeutic strategy for refractory chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a debilitating condition characterized by lower urinary tract symptoms and persistent pelvic pain or discomfort lasting for more than three months. Currently available oral drug therapies exhibit limited efficacy in the treatment of CP/CPPS. Therefore, personalized and combination therapies are recommended by Chinese CP/CPPS guidelines, which primarily include traditional Chinese medicine, radiofrequency therapy, urethral lavage, transrectal prostate massage, extracorporeal shock wave therapy. However, a significant number of patients do not respond well to all types of these therapeutic methods. Among those who have sequentially or simultaneously undergone at least three different treatment modalities, in addition to oral medications, for more than 1 year, they are defined as patients with refractory CP/CPPS. This retrospective study aims to evaluate the clinical effect of traditional Chinese herbal medicine retention enema combined with perineal massage (THREM) in managing refractory CP/CPPS. Methods: A total of 20 patients with refractory CP/CPPS, who did not show significant improvement despite receiving multiple conventional treatments, including oral medications, were included in this study. Following THREM therapy, the International Prostate Symptom Score (IPSS), visual analogue scale (VAS), and National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) quality of life (QoL) score were used to assess treatment efficacy. Results: Six months after THREM therapy, a significant decrease in IPSS, VAS, and QoL scores was observed (P<0.01). Importantly, 85% of the patients experienced a reduction in symptoms of ≥60%, with an average degree of alleviation reaching 70.25%±24.20%. Conclusions: THREM treatment demonstrated excellent efficacy in managing refractory CP/CPPS at least for 6 months. It has promising clinical application prospects. Further research is warranted to validate these results and explore the underlying mechanisms of THREM therapy.

Partial inhibition of class III PI3K VPS-34 ameliorates motor aging and prolongs health span.

Global increase of life expectancy is rarely accompanied by increased health span, calling for a greater understanding of age-associated behavioral decline. Motor independence is strongly associated with the quality of life of elderly people, yet the regulators for motor aging have not been systematically explored. Here, we designed a fast and efficient genome-wide screening assay in Caenorhabditis elegans and identified 34 consistent genes as potential regulators of motor aging. Among the top hits, we found VPS-34, the class III phosphatidylinositol 3-kinase that phosphorylates phosphatidylinositol (PI) to phosphatidylinositol 3-phosphate (PI(3)P), regulates motor function in aged but not young worms. It primarily functions in aged motor neurons by inhibiting PI(3)P-PI-PI(4)P conversion to reduce neurotransmission at the neuromuscular junction (NMJ). Genetic and pharmacological inhibition of VPS-34 improve neurotransmission and muscle integrity, ameliorating motor aging in both worms and mice. Thus, our genome-wide screening revealed an evolutionarily conserved, actionable target to delay motor aging and prolong health span.

Prognostic analysis and nomogram construction for older patients with IDH-wild-type glioblastoma.

As many countries face an ageing population, the number of older patients with glioblastoma (GB) is increasing. Thus, there is an urgent need for prognostic models to aid in treatment decision-making and life planning. A total of 98 patients with isocitrate dehydrogenase (IDH)-wild-type GB aged ≥65 years were analysed from January 2012 to January 2020. Independent prognostic factors were identified by prognostic analysis. Using the independent prognostic factors for overall survival (OS), a nomogram was constructed by R software to predict the prognosis of older patients with IDH-wild-type GB. The concordance index (C-index) and receiver operating characteristic (ROC) curve were used to assess model discrimination, and the calibration curve was used to assess model calibration. Prognostic analysis showed that the extent of resection (EOR), adjusted Charlson comorbidity index (ACCI), O6-methylguanine-DNA methyltransferase (MGMT) methylation status, postoperative radiotherapy, and postoperative temozolomide (TMZ) chemotherapy were independent prognostic factors for OS. MGMT methylation status and subventricular zone (SVZ) involvement were independent prognostic factors for progression-free survival (PFS). A nomogram was constructed based on EOR, ACCI, MGMT methylation status, postoperative radiotherapy and postoperative TMZ chemotherapy to predict the 6-month, 12-month and 18-month OS of older patients with IDH-wild-type GB. The C-index of the nomogram was 0.72, and the ROC curves showed that the areas under the curve (AUCs) at 6, 12 and 18 months were 0.874, 0.739 and 0.779, respectively. The calibration plots showed that the nomogram was in good agreement with the actual observations in predicting the OS of older patients with IDH-wild-type GB. Older patients with IDH-wild-type GB can benefit from gross total resection (GTR), postoperative radiotherapy and postoperative TMZ chemotherapy. A high ACCI score and MGMT nonmethylation are poor prognostic factors. We constructed a nomogram including the ACCI to facilitate clinical decision-making and follow-up interval selection.

LINC00978 regulates metabolic rewiring to promote the malignancy of glioblastoma through AKR1B1.

Glioma is a fatal primary brain tumor. Improved glioma treatment effectiveness depends on a better understanding of its underlying mechanisms. Glioblastoma (GBM), was classified as high-grade glioma with the most lethality and therapeutic resistance. Herein, we reported LINC00978 overexpressed in high-grade gliomas. Down-regulation of LINC00978 in glioblastoma cells inhibited cell proliferation, invasion, migration, and induced apoptosis. In vivo experiments confirmed that the CamK-A siRNA of LINC00978 could effectively inhibit the proliferation of glioblastoma cells. The main pathway and genes regulated by LINC00978 were detected using RNA sequencing to elucidate the molecular mechanism. The results suggest that LINC00978 regulates the expression of genes related to metabolic pathways, including aldo-keto reductase family 1 member B (AKR1B1), which mediates the cytotoxicity of 2-deoxyglucose. LINC00978 positively regulated AKR1B1 expression, and 2-deoxyglucose induced AKR1B1 expression via a LINC00978-dependent mechanism. This research has revealed that LINC00978 promotes the sensitivity of glioblastoma cells to 2DG. LINC00978 is highly expressed in most high-grade glioma patients. Thus, understanding the anticancer mechanism identified in this study may contribute to treating the majority of glioma patients. This study clarified the function and molecular mechanism of LINC00978 in glioblastoma and provided a study basis for LINC00978 to guide the clinical treatment of glioblastoma.

High-efficiency and reliable same-parent thermoelectric modules using Mg3Sb2-based compounds.

Thermoelectric modules can convert waste heat directly into useful electricity, providing a clean and sustainable way to use fossil energy more efficiently. Mg3Sb2-based alloys have recently attracted considerable interest from the thermoelectric community due to their nontoxic nature, abundance of constituent elements and excellent mechanical and thermoelectric properties. However, robust modules based on Mg3Sb2 have progressed less rapidly. Here, we develop multiple-pair thermoelectric modules consisting of both n-type and p-type Mg3Sb2-based alloys. Thermoelectric legs based on the same parent fit into each other in terms of thermomechanical properties, facilitating module fabrication and ensuring low thermal stress. By adopting a suitable diffusion barrier layer and developing a new joining technique, an integrated all-Mg3Sb2-based module demonstrates a high efficiency of 7.5% at a temperature difference of 380 K, exceeding the state-of-the-art same-parent thermoelectric modules. Moreover, the efficiency remains stable during 150 thermal cycling shocks (∼225 h), demonstrating excellent module reliability.

A neurodevelopmental epigenetic programme mediated by SMARCD3-DAB1-Reelin signalling is hijacked to promote medulloblastoma metastasis.

How abnormal neurodevelopment relates to the tumour aggressiveness of medulloblastoma (MB), the most common type of embryonal tumour, remains elusive. Here we uncover a neurodevelopmental epigenomic programme that is hijacked to induce MB metastatic dissemination. Unsupervised analyses of integrated publicly available datasets with our newly generated data reveal that SMARCD3 (also known as BAF60C) regulates Disabled 1 (DAB1)-mediated Reelin signalling in Purkinje cell migration and MB metastasis by orchestrating cis-regulatory elements at the DAB1 locus. We further identify that a core set of transcription factors, enhancer of zeste homologue 2 (EZH2) and nuclear factor I X (NFIX), coordinates with the cis-regulatory elements at the SMARCD3 locus to form a chromatin hub to control SMARCD3 expression in the developing cerebellum and in metastatic MB. Increased SMARCD3 expression activates Reelin-DAB1-mediated Src kinase signalling, which results in a MB response to Src inhibition. These data deepen our understanding of how neurodevelopmental programming influences disease progression and provide a potential therapeutic option for patients with MB.

The migration and loss of water in emulsified surimi gels prepared with different phase states of lipids: Effect of freeze-thawing treatments.

The freeze-thawing (FT) stability generally correlates well with the economic value and acceptability of frozen surimi-based products. However, quality changes of emulsified surimi gels under FT conditions are still unclear. Therefore, the gel properties of samples with different phase states of lipids (lard, lard + soybean oil, and soybean oil) were investigated at FT conditions. Results showed that the soybean oil evidently improved the rheological behaviors of sols/gels compared to the lard group. The moisture content of samples with different lipids decreased by 2.40%-2.71% after 4 FT cycles. With increasing FT cycles, the water-holding capacity decreased accompanied by the increase of cooking loss. Spin-spin relaxation spectra and hydrogen proton density images proved the occurrence of water migration of gels during these processes. Better gel integrity was observed in samples consisting of soybean oil, where the proportion of pores was lower than those with lard regardless of FT treatments. Additionally, the intermolecular forces of gels also changed under FT treatments. There results suggested that the lipids with different phase states affected the migration and loss of water in emulsified surimi gels under FT cycles. PRACTICAL APPLICATION: The quality changes of heating-induced surimi gel products under frozen storage have been ignored, especially the emulsified surimi gels. This study discloses the changes of the gel properties in emulsified gel products with different phase states of lipids after FT treatments, which provides critical insights into the quality improvement of this novel emulsified surimi product during processing, storage, and transportation.

The interfacial and assembly properties of in situ producing silica nanoparticle at oil-water interface.

In multiphase materials, structured fluid-fluid interfaces can provide mechanical resistance against destabilization, applicable for conformance control, Pickering emulsion, liquid 3D printing and molding, etc. Currently all research prepare the particle-ladened fluid-fluid interfaces by dispersing ex situ acquired particles to the immiscible interface, which limits their application in the harsh environment, such as oil reservoir which can impair particle stability and transport ability. Here, we investigated the interfacial and assembly properties of the interface where SiO2 nanoparticles (NPs) were in situ produced. The experimental results show that ammonia as catalyst could accelerate the processes of silica NPs formation as well as the interfacial tension (IFT) evolution. High temperature could not accelerate the reaction processes to achieve the lowest equilibrium IFT, but it induced the sine-wave IFT evolution curves regardless of the presence of ammonia. The equilibrium IFTs corresponded to the saturation states of interfaces trapping with SiO2 NPs, while the sine-wave fluctuating patterns of IFT were attributed to the alternating transition between interfacial jammed and unjammed states changing along with the reaction process. Silica NPs diffusing into aqueous phase with high salinity also showed good stability, due to the abundant surface decoration with in situ anchored organic species.

In Situ Produced Nanoparticles at the Oil-Water Interface for Conformance Control and Enhanced Oil Recovery.

Nanoparticle-assisted enhanced oil recovery (Nano-EOR) has attracted intensive interest in the laboratory as a promising oil recovery technology. However, the nanoparticles' stability and long-distance delivery of nanoparticles (NPs) in large-scale reservoirs are two main challenges. In this work, we developed a novel concept of in situ synthesizing NPs at the oil-water interface inside the reservoir for EOR instead of injecting presynthesized NPs from outside. The pore-scale flooding experiments show that EOR efficiencies for tertiary flooding were 6.3% without reaction (Case 3), 14.6% for slow reaction (Case 1), and 25.4% for relatively quick reaction (Case 4). Examination of the EOR mechanism shows that in situ produced SiO2 NPs in microchannels could alter the substrate wettability toward neutral wetting. Moreover, the produced NPs tended to assemble on the immiscible oil-water interface, forming a barrier toward interface deformation. As the reaction continued, excessive surface-modified NPs could also diffuse into aqueous brine and accumulate as a soft gel in the flowing path swept by brine. Collectively, these processes induced a "shut-off" effect and diverted displacing fluids to unswept areas, which consequently increased the sweep efficiency and improved the oil recovery efficiency. Auxiliary bulk-scale experiments also showed that the reaction-induced nanoparticle synthesis and assembly at an immiscible interface reduced the interfacial tension and generated an elastic oil-water interface.

Gene expression and methylation profiles show the involvement of POMC in primary hyperparathyroidsm.

Primary hyperparathyroidism (PHPT) is mainly caused by parathyroid adenoma, which produces excess parathyroid hormones. Its pathogenic mechanisms have not yet been fully understood. To investigate the mechanism in the pathogenesis of PHPT, the transcriptome and genome-wide DNA methylation profiles of parathyroid adenoma were analyzed. The candidate genes that may be involved in the PHPT were verified via qRT-PCR, immunohistochemistry, western blot, and methylation-specific PCR. A total of 1650 differentially expressed genes and 2373 differentially methylated regions were identified. After the integration of its transcriptome and DNA methylation data, IL6, SYP, GNA01, and pro-opiomelanocortin (POMC) were the candidate genes that demonstrated a similar pattern between their mRNA expression and DNA methylation status. Of the 4 candidate genes, POMC, a pro-peptide which is processed to a range of bioactive peptide products like ACTH, was further confirmed to be expressed at low levels at both the mRNA and protein levels, which may be due to POMC promoter hypermethylation. Hypermethylation of the POMC promoter may contribute to its low expression, which may be involved in the pathogenesis of PHPT.

CS-CO: A Hybrid Self-Supervised Visual Representation Learning Method for H&E-stained Histopathological Images.

Visual representation extraction is a fundamental problem in the field of computational histopathology. Considering the powerful representation capacity of deep learning and the scarcity of annotations, self-supervised learning has emerged as a promising approach to extract effective visual representations from unlabeled histopathological images. Although a few self-supervised learning methods have been specifically proposed for histopathological images, most of them suffer from certain defects that may hurt the versatility or representation capacity. In this work, we propose CS-CO, a hybrid self-supervised visual representation learning method tailored for H&E-stained histopathological images, which integrates advantages of both generative and discriminative approaches. The proposed method consists of two self-supervised learning stages: cross-stain prediction (CS) and contrastive learning (CO). In addition, a novel data augmentation approach named stain vector perturbation is specifically proposed to facilitate contrastive learning. Our CS-CO makes good use of domain-specific knowledge and requires no side information, which means good rationality and versatility. We evaluate and analyze the proposed CS-CO on three H&E-stained histopathological image datasets with downstream tasks of patch-level tissue classification and slide-level cancer prognosis and subtyping. Experimental results demonstrate the effectiveness and robustness of the proposed CS-CO on common computational histopathology tasks. Furthermore, we also conduct ablation studies and prove that cross-staining prediction and contrastive learning in our CS-CO can complement and enhance each other. Our code is made available at https://github.com/easonyang1996/CS-CO.

NKX6-1 Is a Less Sensitive But Specific Biomarker of Chromophobe Renal Cell Carcinoma.

NKX6-1 is a transcription factor that plays a key role in the development, differentiation, and identity maintenance of beta cells of pancreatic islets. Although NKX6-1 expression has also been discovered in pancreatic well-differentiated neuroendocrine tumors (WDNETs) and duodenal WDNETs, its expression in chromophobe renal cell carcinoma (chRCC) is unexplored. Analysis of mRNA expression and immunohistochemistry of NKX6-1 was performed using the kidney cancer cohort from The Cancer Genome Atlas (TCGA) and paraffin-embedded whole-tissue slides from our 196 collected cases, including 48 chRCCs (43 classic and 5 eosinophilic subtypes), 24 renal oncocytomas (ROs), 46 clear cell renal cell carcinomas, 41 papillary renal cell carcinomas, 14 renal urothelial carcinomas, 7 low-grade oncocytic renal tumors (LOTs), 8 eosinophilic solid and cystic renal cell carcinomas, 3 succinate dehydrogenase-deficient renal cell carcinomas, and 5 renal oncocytic tumors, not otherwise specified. NKX6-1 expression was almost exclusively upregulated in chRCC at both the mRNA and protein levels compared with other renal tumors. NKX6-1 was immunohistochemically positive in 39 of 48 (81.3%) chRCCs, but negative in 46 clear cell renal cell carcinomas, 24 ROs, 7 low-grade oncocytic renal tumors, 8 eosinophilic solid and cystic renal cell carcinomas, 3 succinate dehydrogenase-deficient renal cell carcinomas, and 5 renal oncocytic tumors, not otherwise specified. Diffuse, moderate, and focal NKX6-1 staining were seen in 21, 4, and 14 of the 39 chRCCs, respectively. In contrast, NKX6-1 was focally positive in only 1 of 41 (2.4%) papillary renal cell carcinomas and 2 of 14 (14.3%) renal urothelial carcinomas. Therefore, the sensitivity and specificity of NKX6-1 staining were 81.3% and 98% for chRCC, respectively. In conclusion, NKX6-1 may be a novel potential marker for differentiating chRCC from other renal neoplasms, especially from RO.

Ni-Fe/Reduced Graphene Oxide Nanocomposites for Hexavalent Chromium Reduction in an Aqueous Environment.

We designed and synthesized a novel high efficiency Cr(VI) removal material using reduced graphene oxide (RGO) as a support with high specific surface area and a mixture of Fe and Ni nanoparticles (NPs) as a catalytic reducing agent. Such a design enables the composite particle to be integrated with three functions of adsorption, catalysis, and reduction, where RGO could enhance Cr(VI) adsorption, while Fe/Ni NPs increase the catalytic reducing efficiency. The application of a microchip mixer guaranteed a better mixing of GO and subsequent decoration of Fe and Ni NPs on RGO. Cr(VI) removal experiments with various materials are performed, and the results demonstrated that the Ni-Fe/RGO achieved an adsorption capacity of 150.45 mg/g at pH = 7 and 197.43 mg/g at pH = 5 for Cr(VI), which is higher than those of other reported materials at a pH of ∼7. To the best of our knowledge, this is the first example of Ni-Fe/RGO for efficient Cr(VI) removal by using the synergistic effects of increased adsorption, catalysis-assisted reduction, and enhanced mixing effect of a microchip mixer. This work also provides us with a simple and low-cost method for the fabrication of an effective Cr(VI) removal material.

Gut microbiota and calcium balance.

Microorganisms living on the surface and inside the human body play an important role in the physiological activities of the human body. The largest microecosystem in the human body is the gut microbiome. Calcium disorders are found in many diseases. For example, patients with chronic renal insufficiency present with secondary hyperparathyroidism, which is caused by a calcium imbalance in the body. In addition, calcium dysregulation may affect lipid metabolism in the liver through the calmodulator pathway, leading to cirrhosis, etc. Currently, a considerable number of probiotics have been proven to enhance the body's absorption of calcium. This paper reviews the effects of intestinal flora and related factors such as short-chain fatty acids, estrogen, immune factors and vitamin D on calcium balance.

Preoperative Magnetic Resonance Imaging Radiomics for Predicting Early Recurrence of Glioblastoma.

PURPOSE: Early recurrence of glioblastoma after standard treatment makes patient care challenging. This study aimed to assess preoperative magnetic resonance imaging (MRI) radiomics for predicting early recurrence of glioblastoma. PATIENTS AND METHODS: A total of 122 patients (training cohort: n = 86; validation cohort: n = 36) with pathologically confirmed glioblastoma were included in this retrospective study. Preoperative brain MRI images were analyzed for both radiomics and the Visually Accessible Rembrandt Image (VASARI) features of glioblastoma. Models incorporating MRI radiomics, the VASARI parameters, and clinical variables were developed and presented in a nomogram. Performance was assessed based on calibration, discrimination, and clinical usefulness. RESULTS: The nomogram consisting of the radiomic signatures, the VASARI parameters, and blood urea nitrogen (BUN) values showed good discrimination between the patients with early recurrence and those with later recurrence, with an area under the curve of 0.85 (95% CI, 0.77-0.94) in the training cohort and 0.84 [95% CI, 0.71-0.97] in the validation cohort. Decision curve analysis demonstrated favorable clinical application of the nomogram. CONCLUSION: This study showed the potential usefulness of preoperative brain MRI radiomics in predicting the early recurrence of glioblastoma, which should be helpful in personalized management of glioblastoma.

UAP1L1 plays an oncogene-like role in glioma through promoting proliferation and inhibiting apoptosis.

BACKGROUND: Uridine diphosphate-N-acetylglucosamine pyrophosphorylase-1-like-1 (UAP1L1) is involved in protein glycosylation and promotes proliferation in some tumors. By analyzing the publicly available Gene Expression Omnibus (GEO) database, we found that UAP1L1 displayed a significant change between paired glioma and normal brain tissues. The purpose of this study was to investigate the expression and functional role of UAP1L1 in glioma. METHODS: To determine the expression level of UAP1L1 in glioma, immunohistochemistry (IHC) staining was performed in tissue microarrays of 160 gliomas and 24 normal brain tissues. The correlation between UAP1L1 expression and the outcomes of glioma patients was analyzed. Human glioblastoma cell lines, U251 and U87, were employed in this study. Endogenous UAP1L1 expression in U251 and U87 cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). A lentiviral short hairpin RNA (shRNA) vector (shUAP1L1) was constructed and used to infect U251 and U87 cells to knock down the expression of UAP1L1. We performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, flow cytometry, human apoptosis antibody array, and in vivo subcutaneous xenograft model to investigate the biological functions of UAP1L1. RESULTS: We revealed that UAP1L1 expression was obviously upregulated in the glioma tissues. The increased UAP1L1 expression level was clinically associated with higher tumor grades and poorer patient prognoses. Moreover, we demonstrated that UAP1L1 knockdown suppressed proliferation and increased apoptosis of glioma cells in vitro. In the xenograft mouse model, we further verified that UAP1L1 knockdown could attenuate the growth of glioma cells in vivo. CONCLUSIONS: These results indicated that UAP1L1 may play an oncogene-like role in glioma, especially in high grade glioma, and thus may be of clinical importance as a future therapeutic target.

Knockdown of lncRNA ANRIL suppresses the production of inflammatory cytokines and mucin 5AC in nasal epithelial cells via the miR-15a-5p/JAK2 axis.

The incidence of allergic rhinitis (AR) is increasing worldwide. Human nasal epithelial cells (HNECs) are the key cells in the occurrence of AR. Antisense non-coding RNA in the INK4 locus (ANRIL) was discovered to be involved in the progression of AR. However, the mechanism by which ANRIL mediates the progression of AR remains to be determined. The present study aimed to further explore the mechanism by which ANRIL regulates AR. Thereby, HNECs were treated with IL-13 to mimic AR in vitro. The mRNA expression levels of ANRIL, microRNA (miR)-15a-5p, JAK2, mucin 5AC (MUC5AC), granulocyte-macrophage colony-stimulating factor (GM-CSF) and eotaxin-1, and protein expression levels of JAK2, STAT3 and phosphorylated-STAT3 in HNECs were analyzed using reverse transcription-quantitative PCR and western blotting, respectively. ELISAs were used to detect the secretory levels of inflammatory cytokines and mucin in cell supernatants. In addition, a dual luciferase reporter assay was used to confirm the downstream target of ANRIL and the target gene of miR-15a-5p. The results revealed that the secretory levels of eotaxin-1, GM-CSF and MUC5AC were significantly upregulated by IL-13 in the supernatant of HNECs. The expression levels of ANRIL and JAK2 were also upregulated in IL-13-induced HNECs, while the expression levels of miR-15a-5p were downregulated. In addition, ANRIL was identified to bind to miR-15a-5p. The IL-13-induced upregulation of eotaxin-1, GM-CSF and MUC5AC mRNA expression and secretory levels was significantly inhibited by the genetic knockdown of ANRIL, while the miR-15a-5p inhibitor effectively reversed this effect. JAK2 was also discovered to be directly targeted by miR-15a-5p. The overexpression of JAK2 significantly suppressed the therapeutic effect of miR-15a-5p mimics on IL-13-induced inflammation in vitro. In conclusion, the findings of the present study suggested that the genetic knockdown of ANRIL may suppress the production of inflammatory cytokines and mucin in IL-13-treated HNECs via regulation of the miR-15a-5p/JAK2 axis. Thus, ANRIL may serve as a novel target for AR treatment.

A novel integrated system using patient-derived glioma cerebral organoids and xenografts for disease modeling and drug screening.

A physiologically relevant glioma tumor model is important to the study of disease progression and screening drug candidates. However, current preclinical glioma models lack the brain microenvironment, and the established tumor cell lines do not represent glioma biology and cannot be used to evaluate the therapeutic effect. Here, we reported a real-time integrated system by generating 3D ex vivo cerebral organoids and in vivo xenograft tumors based on glioma patient-derived tissues and cells. Our system faithfully recapitulated the histological features, response to chemotherapy drugs, and clinical progression of their corresponding parental tumors. Additionally, our model successfully identified a case from a grade II astrocytoma patient with typical grade IV GBM features in both organoids and xenograft models, which mimicked the disease progression of this patient. Further genomic and transcriptomic characterization was associated with individual clinical features. We have demonstrated the "GBM-&Normal-like" signature to predict prognosis. In conclusion, we developed an integrated system of parallel models from patient-derived glioma cerebral organoids and xenografts for understanding the glioma biology and prediction of response to chemotherapy drugs, which might lead to a new strategy for personalized treatment for this deadly disease.

FOXI1 expression in chromophobe renal cell carcinoma and renal oncocytoma: a study of The Cancer Genome Atlas transcriptome-based outlier mining and immunohistochemistry.

FOXI1 is a forkhead family transcription factor that plays a key role in differentiation and functional maintenance for the renal intercalated cell (IC). The diagnostic utility of FOXI1 is rarely studied thus far. Comparative analyses of FOXI1 mRNA expression in normal kidney tissue and different renal neoplasms including chromophobe renal cell carcinoma (chRCC), renal oncocytoma (RO), and other renal cell carcinomas were conducted using transcriptomic data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, and single-cell RNA-seq datasets, in combination with integrative analyses using mutant data, karyotype data, and digital slides for cases with anomalous FOXI1 expression in TCGA. Formalin-fixed, paraffin-embedded whole-tissue slides of varied primary renal neoplasms (n = 367) were subjected to FOXI1 staining for validating FOXI1 transcription levels. We confirmed that FOXI1 was significantly upregulated at mRNA levels in ICs, chRCCs, and ROs compared with other renal tubule cell and renal cell carcinoma subtypes. Furthermore, most of the cases with FOXI1 expression outliers were misclassified in the TCGA kidney cancer project. An underlying novel entity with frequent mutations involved in the mTOR pathway was also found. FOXI1 immunoreactivity was consistently noted in ICs of the distal nephron. FOXI1 staining was positive in 85 of 93 chRCCs and 13 of 18 ROs, respectively. FOXI1 staining was not seen in renal neoplasms (n = 254) derived from non-ICs. In conclusion, FOXI1 expression in normal kidney tissue is restricted to ICs. This cell type-specific expression is retained during neoplastic transformation from ICs to chRCCs or ROs. FOXI1 is thereby a potential biomarker of IC-related tumors.