The BET inhibitor GNE-987 effectively induces anti-cancer effects in T-cell acute lymphoblastic leukemia by targeting enhancer regulated genes.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy originating from T progenitor cells. It accounts for 15% of childhood and 25% of adult ALL cases. GNE-987 is a novel chimeric molecule developed using proteolysis-targeting chimeras (PROTAC) technology for targeted therapy. It consists of a potent inhibitor of the bromodomain and extraterminal (BET) protein, as well as the E3 ubiquitin ligase Von Hippel-Lindau (VHL), which enables the effective induction of proteasomal degradation of BRD4. Although GNE-987 has shown persistent inhibition of cell proliferation and apoptosis, its specific antitumor activity in T-ALL remains unclear. In this study, we aimed to investigate the molecular mechanisms underlying the antitumor effect of GNE-987 in T-ALL. To achieve this, we employed technologies including RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq) and CUT&Tag. The degradation of BET proteins, specifically BRD4, by GNE-987 has a profound impact on T-ALL cell. In in vivo experiments, sh-BRD4 lentivirus reduced T-ALL cell proliferation and invasion, extending the survival time of mice. The RNA-seq and CUT&Tag analyses provided further insights into the mechanism of action of GNE-987 in T-ALL. These analyses revealed that GNE-987 possesses the ability to suppress the expression of various genes associated with super-enhancers (SEs), including lymphoblastic leukemia 1 (LCK). By targeting these SE-associated genes, GNE-987 effectively inhibits the progression of T-ALL. Importantly, SE-related oncogenes like LCK were identified as critical targets of GNE-987. Based on these findings, GNE-987 holds promise as a potential novel candidate drug for the treatment of T-ALL.

Machine Learning Driven Atom-Thin Materials for Fragrance Sensing.

Fragrance plays a crucial role in the daily lives. Its importance spans various sectors, from therapeutic purposes to personal care, making the understanding and accurate identification of fragrances essential. To fully harness the potential of fragrances, efficient and precise fragrance sensing and identification are necessary. However, current fragrance sensors face several limitations, particularly in detecting and differentiating complex scent profiles with high accuracy. To address these challenges, the use of atom-thin materials in fragrance sensors has emerged as a groundbreaking approach. These atom-thin sensors, characterized by their enhanced sensitivity and selectivity, offer significant improvements over traditional sensing technology. Moreover, the integration of Machine Learning (ML) into fragrance sensing has opened new opportunities in the field. ML algorithms applied to fragrance sensing facilitate advancements in four key domains: accurate fragrance identification, precise discrimination between different fragrances, improved detection thresholds for subtle scents, and prediction of fragrance properties. This comprehensive review delves into the synergistic use of atom-thin materials and ML in fragrance sensing, providing an in-depth analysis of how these technologies are revolutionizing the field, offering insights into their current applications and future potential in enhancing the understanding and utilization of fragrances.

Urine is a viral antigen reservoir in hepatitis E virus infection.

BACKGROUND AND AIMS: HEV ORF2 antigen (Ag) in serum has become a tool for diagnosing current HEV infection. Particularly, urinary shedding of HEV Ag has been gaining increasing interest. We aim to uncover the origin, antigenicity, diagnostic performance, and diagnostic significance of Ag in urine in HEV infection. APPROACH AND RESULTS: Clinical serum and urine samples from patients with acute and chronic HEV infection were analyzed for their Ag levels. Ag in urine was analyzed by biochemical and proteomic approaches. The origin of urinary Ag and Ag kinetics during HEV infection was investigated in mouse and rabbit models, respectively. We found that both the Ag level and diagnostic sensitivity in urine were higher than in serum. Antigenic protein in urine was an E2s-like dimer spanning amino acids 453-606. pORF2 entered urine from serum in mice i.v. injected with pORF2. Ag in urine originated from the secreted form of pORF2 (ORF2 S ) that abundantly existed in hepatitis E patients' serum. HEV Ag was specifically taken up by renal cells and was disposed into urine, during which the level of Ag was concentrated >10-fold, resulting in the higher diagnosing sensitivity of urine Ag than serum Ag. Moreover, Ag in urine appeared 6 days earlier, lasted longer than viremia and antigenemia, and showed good concordance with fecal RNA in a rabbit model. CONCLUSIONS: Our findings demonstrated the origin and diagnostic value of urine Ag and provided insights into the disposal of exogenous protein of pathogens by the host kidney.

Root plasticity improves maize nitrogen use when nitrogen is limiting - an analysis using 3D plant modelling.

Plant phenotypic plasticity plays an important role in nitrogen (N) acquisition and use under nitrogen-limited conditions. However, this role has never been quantified as a function of N availability, leaving it unclear whether plastic responses should be considered as potential targets for selection. A combined modelling and experimentation approach was adopted to quantify the role of plasticity on N uptake and plant yield. Based on a greenhouse experiment we considered plasticity in two maize traits: root-to-leaf biomass allocation ratio and emergence rate of axial roots. In a simulation experiment we individually enabled or disabled both plastic responses for maize stands grown across six N levels. Both plastic responses contributed to maintaining a higher N uptake and plant productivity as N-availability declined, compared to stands in which plastic responses were disabled. We conclude that plastic responses quantified in this study may be a potential target trait in breeding programs for greater N uptake across N levels while it may only be important for the internal use of N under N-limited conditions in maize. Given the complexity of breeding for plastic responses, an a priori model analysis is useful to identify which plastic traits to target for enhanced plant performance.

The BET PROTAC inhibitor GNE-987 displays anti-tumor effects by targeting super-enhancers regulated gene in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is one of the most common primary malignant tumors of bone in children, which develops from osteoblasts and typically occurs during the rapid growth phase of the bone. Recently, Super-Enhancers(SEs)have been reported to play a crucial role in osteosarcoma growth and metastasis. Therefore, there is an urgent need to identify specific targeted inhibitors of SEs to assist clinical therapy. This study aimed to elucidate the role of BRD4 inhibitor GNE-987 targeting SEs in OS and preliminarily explore its mechanism. METHODS: We evaluated changes in osteosarcoma cells following treatment with a BRD4 inhibitor GNE-987. We assessed the anti-tumor effect of GNE-987 in vitro and in vivo by Western blot, CCK8, flow cytometry detection, clone formation, xenograft tumor size measurements, and Ki67 immunohistochemical staining, and combined ChIP-seq with RNA-seq techniques to find its anti-tumor mechanism. RESULTS: In this study, we found that extremely low concentrations of GNE-987(2-10 nM) significantly reduced the proliferation and survival of OS cells by degrading BRD4. In addition, we found that GNE-987 markedly induced cell cycle arrest and apoptosis in OS cells. Further study indicated that VHL was critical for GNE-987 to exert its antitumor effect in OS cells. Consistent with in vitro results, GNE-987 administration significantly reduced tumor size in xenograft models with minimal toxicity, and partially degraded the BRD4 protein. KRT80 was identified through analysis of the RNA-seq and ChIP-seq data. U2OS HiC analysis suggested a higher frequency of chromatin interactions near the KRT80 binding site. The enrichment of H3K27ac modification at KRT80 was significantly reduced after GNE-987 treatment. KRT80 was identified as playing an important role in OS occurrence and development. CONCLUSIONS: This research revealed that GNE-987 selectively degraded BRD4 and disrupted the transcriptional regulation of oncogenes in OS. GNE-987 has the potential to affect KRT80 against OS.

Amide Proton Transfer-Weighted Imaging in Assessing the Aggressive and Proliferative Potential of Bladder Cancer.

BACKGROUND: Ki-67 and human epidermal growth factor receptor 2 (HER2) are known oncogenes involved in bladder cancer (BCa) patient risk stratification. Preoperative assessment of their expression level can assist in clinical treatment decision-making. Recently, amide proton transfer-weighted (APTw) MRI has shown promising potential in the diagnosis of several malignancies. However, few studies reported the value of APTw imaging in evaluating Ki-67 and HER2 status of BCa. PURPOSE: To investigate the feasibility of APTw MRI in assessing the aggressive and proliferative potential regarding the expression levels of Ki-67 and HER2 in BCa. STUDY TYPE: Retrospective. SUBJECTS: 114 patients (mean age, 64.78 ± 11.93 [SD] years; 97 men) were studied. FIELD STRENGTH/SEQUENCE: APTw MRI acquired by a three-dimensional fast-spin-echo sequence at 3.0 T MRI system. ASSESSMENT: Patient pathologic findings, included histologic grade and the expression status of Ki-67 and HER2, were reviewed by one uropathologist. The APTw values of BCa were independently measured by two radiologists and were compared between high-/low-tumor grade group, high-/low-Ki-67 expression group, and high-/low-HER2 expression group. STATISTICAL TESTS: The interclass correlation coefficient, independent sample t-test, Mann-Whitney U test, Spearman's rank correlation, and receiver operating characteristic curve (ROC) analysis were used. P < 0.05 was considered statistically significant. RESULTS: Significantly higher APTw values were found in high-grade BCa patients (7.72% vs. 4.29%, P < 0.001), high-Ki-67 expression BCa patients (8.40% vs. 3.25%, P < 0.001) and HER2 positive BCa patients (8.24% vs. 5.40%, P = 0.001). APTw values were positively correlated with Ki-67 (r = 0.769) and HER2 (r = 0. 356) expression status. The area under the ROC curve of the APTw values for detecting Ki-67 and HER2 expression status were 0.883 (95% CI: 0.790-0.945) and 0.713 (95% CI: 0.592-0.816), respectively. DATA CONCLUSIONS: APTw MRI is a potential method to assess the biological and proliferation potential of BCa. TECHNICAL EFFICACY: Stage 2.

Identification, expression and molecular polymorphism of T-cell receptors α and ß from the glacial relict Hucho bleekeri.

The T-cell receptor (TCR) is a specific molecule on the surface of all T cells that mediates cellular adaptive immune responses to antigens. Hucho bleekeri is a critically endangered species and is regarded as a glacial relict that has the lowest-latitude distribution compared with any Eurasian salmonid. In the present study, two TCR genes, namely, TCR α and ß, were identified and characterized in H. bleekeri. Both TCR α and TCR ß have typical TCR structures, including the IgV domain, IgC domain, connecting peptide, transmembrane and cytoplasmic domains. The two TCR genes were constitutionally expressed in various tissues, with the highest expression found in the spleen for TCR α and in the trunk kidney for TCR ß. Challenge of H. bleekeri with LPS or poly(I:C) resulted in significant upregulation of both TCR α and ß expression in headkidney and spleen primary cells, indicating their potential roles in the immune response. Molecular polymorphism analysis of the whole ORF regions of TCR α and ß in different individuals revealed high diversity of IgV domains of these two genes, especially in complementarity-determining region (CDR) 3. The ratio of nonsynonymous substitution occurred at a significantly higher frequency than synonymous substitution in the CDR of TCR α and ß, demonstrating the existence of positive selection. The results obtained in the present study enhance our understanding of TCR roles in regulating immune mechanisms and provide new information for the study of TCR lineage diversity in fish.

Impact of COVID-19 on adverse reactions to subcutaneous specific immunotherapy in children:a retrospective cohort study.

BACKGROUND: COVID-19 is a new infectious disease. To investigate whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increases the adverse reactions of subcutaneous specific immunotherapy (SCIT) in children. METHODS: This study was conducted by collecting relevant data from children who underwent house dust mite SCIT from April 3, 2021, to March 18, 2023, including information on the time of COVID-19 infection, symptoms, and adverse reactions after each allergen injection. A mixed effects model was used to analyze the changes in adverse reactions before and after the COVID-19 infection. RESULTS: Among the records of adverse reactions from 2658 injections in 123 children who underwent SCIT, the overall adverse reaction rate before COVID-19 infection was 39.8% and 30.0% after COVID-19 infection. Compared with pre-infection with COVID-19, the risks of overall adverse reactions, local adverse reactions, and systemic adverse reactions of immunotherapy after COVID-19 infection were reduced (odds ratio [OR] = 0.24, 0.31, and 0.28, all P < 0.05). Among the local adverse reactions, the incidence of the unvaccinated group was the highest (15.3% vs. 7.1%). The incidence of overall and local adverse reactions to SCIT decreased in 2-vaccinated COVID-19 recipients (OR = 0.29-0.31, P < 0.05). CONCLUSIONS: In children, SARS-CoV-2 infection does not increase the incidence of adverse reactions to SCIT. This finding can provide a basis for the implementation of allergen-specific immunotherapy (AIT) during the COVID-19 pandemic.

SOAT1 in gallbladder cancer: Clinicopathological significance and avasimibe therapeutics.

The aim of this investigation was to evaluate the differential expression of the sterol O-acyltransferase 1 (SOAT1) protein in gallbladder cancer tissues and cells, investigate the impact of Avastin on the proliferation, migration, invasion capabilities of gallbladder cancer cells, and its potential to induce cell apoptosis. Immunohistochemical analysis of samples from 145 gallbladder cancer patients was conducted, along with analysis of SOAT1 protein, mRNA expression levels, and cholesterol content in gallbladder cancer cell lines SGC-996, NOZ, and gallbladder cancer (GBC)-SD using Western blot and q-PCR techniques. Furthermore, the effects of Avastin on the proliferation, migration, and invasion capabilities of these gallbladder cancer cell lines were studied, and its ability to induce cell apoptosis was evaluated using flow cytometry, Western blot, and immunohistochemical methods. Additionally, gene expression and pathway analysis were performed, and the synergistic therapeutic effects of Avastin combined with gemcitabine were tested in a gallbladder cancer xenograft model. The study found that SOAT1 expression was significantly upregulated in GBC tissues and positively correlated with lymph node metastasis and TNM staging. In vitro experiments demonstrated that Avastin significantly inhibited the proliferation, migration, and invasion capabilities of SGC-996 and GBC-SD cell lines and induced apoptosis. RNA sequencing analysis revealed multiple differentially expressed genes in cells treated with Avastin, primarily enriched in biological pathways such as signaling transduction, malignant tumors, and the immune system. In vivo, experiments confirmed that Avastin could effectively suppress tumor growth in a gallbladder cancer xenograft model and enhanced the treatment efficacy when used in combination with gemcitabine. Overall, these findings provide new insights and strategies for targeted therapy in gallbladder cancer.

Li4 Zn(PO4 )2 :Mn2+ thermosensitive phosphor with dual luminescent centres for optical thermometry.

An optical thermometry strategy based on Mn2+ -doped dual-wavelength emission phosphor has been reported. Samples with different doping content were synthesized through a high-temperature solid-phase method under an air atmosphere. The electronic structure of Li4 Zn(PO4 )2 was calculated using density functional theory, revealing it to be a direct band gap material with an energy gap of 4.708 eV. Moreover, the emitting bands of Mn2+ at 530 and 640 nm can be simultaneously observed when using 417 nm as the exciting wavelength. This is due to the occupation of Mn2+ at the Zn2+ site and the interstitial site. Further analysis was conducted on the temperature-dependent emission characteristics of the sample in the range 293-483 K. Mn2+ has different responses to temperature at different doping sites in Li4 Zn(PO4 )2 . Based on the calculations using the fluorescence intensity ratio technique, the maximum relative sensitivity at a temperature of 483 K was determined to be 1.69% K-1 , while the absolute sensitivity was found to be 0.12% K-1 . The results showed that the Li4 Zn(PO4 )2 :Mn2+ phosphor has potential application in optical thermometry.

Discovery of Novel Cholinesterase Inhibitors Easily Crossing the Blood-Brain Barrier via Structure-Property Relationship Investigation: Methylenedioxy-Cinnamicamide Containing Tertiary Amine Side Chain.

In the present investigation, a series of dimethoxy or methylenedioxy substituted-cinnamamide derivatives containing tertiary amine moiety (N. N-Dimethyl, N, N-diethyl, Pyrrolidine, Piperidine, Morpholine) were synthesized and evaluated for cholinesterase inhibition and blood-brain barrier (BBB) permeability. Although their chemical structures are similar, their biological activities exhibit diversity. The results showed that all compounds except for those containing morpholine group exhibited moderate to potent acetylcholinesterase inhibition. Preliminary screening of BBB permeability shows that methylenedioxy substituted compounds have better brain permeability than the others. Compound 10c, containing methylenedioxy and pyrrolidine side chain, showed a better acetylcholinesterase inhibition (IC50: 1.52±0.19 µmol/L) and good blood-brain barrier permeability. Further pharmacokinetic investigation of compound 10c using ultra high performance liquid chromatography-mass/mass spectrometry (UPLC-MS/MS) in mice showed that compound 10c in brain tissue reached its peak concentration (857.72±93.56 ng/g) after dosing 30 min. Its half-life in the serum is 331 min (5.52 h), and the CBrain/CSerum at various sampling points is ranged from 1.65 to 4.71(Mean: 2.76) within 24 hours. This investigation provides valuable information on the chemistry and pharmacological diversity of cinnamic acid derivatives and may be beneficial for the discovery of central nervous system drugs.

FOXA2 suppresses gallbladder carcinoma cell migration, invasion, and epithelial-mesenchymal transition by targeting SERPINB5.

BACKGROUND: Gallbladder cancer (GBC), a highly malignant gastrointestinal tumor, lacks effective therapies. Foxhead box A2 (FOXA2) is a tumor suppressor that is poorly expressed in various human malignancies. This study aimed to ascertain FOXA2 expression in GBC and its relevance to tumor metastasis, and to elucidate its regulatory mechanism with epithelial-mesenchymal transition (EMT) as an entry point, in the hope of providing a potential therapeutic target for GBC. METHODS: FOXA2 expression in GBC tissues was first detected using immunohistochemistry (IHC), followed by correlation analysis with clinicopathological characteristics and survival prognosis. Subsequently, the effects of FOXA2 on GBC cell migration and invasion, as well as EMT induction, were evaluated by scratch, Transwell, RT-PCR, and Western blot assays, together with animal experimentation. Ultimately, mRNA sequencing was carried out to identify the key downstream target genes of FOXA2 in controlling the EMT process in GBC cells, and dual-luciferase reporter and chromatin immunoprecipitation assays were used to determine its regulatory mechanism. RESULTS: FOXA2 was underexpressed in GBC tissues and inversely correlated with tumor node metastasis stage, lymph node metastasis, and poor patient prognosis. FOXA2 exerts suppressive effects on EMT and metastasis of GBC in vivo and in vitro. FOXA2 can impede GBC cell migratory and invasive functions and EMT by positively mediating serine protein kinase inhibitor B5 (SERPINB5) expression. CONCLUSION: FOXA2 directly binds to the SERPINB5 promoter region to stimulate its transcription, thereby modulating the migration and invasion behaviors of GBC cells as well as the EMT process, which might be an effective therapeutic target against GBC.

Broadening the Voltage Window of 3D-Printed MXene Micro-Supercapacitors with a Hybridized Electrolyte.

The burgeoning demand for miniaturized energy storage devices compatible with the miniaturization trend of electronic technologies necessitates advancements in micro-supercapacitors (MSCs) that promise safety, cost efficiency, and high-speed charging capabilities. However, conventional aqueous MSCs face a significant limitation due to their inherently narrow electrochemical potential window, which restricts their operational voltage and energy density compared to their organic and ionic liquid counterparts. In this study, we introduce an innovative aqueous NaCl/H2O/EG hybrid gel electrolyte (comprising common salt (NaCl), H2O, ethylene glycol (EG), and SiO2) for Ti3C2Tx MXene MSCs that substantially widens the voltage window to 1.6 V, a notable improvement over traditional aqueous system. By integrating the hybrid electrolyte with 3D-printed MXene electrodes, we realized MSCs with remarkable areal capacitance (1.51 F cm-2) and energy density (675 µWh cm-2), significantly surpassing existing benchmarks for aqueous MSCs. The strategic formulation of the hybrid electrolyte-a low-concentration NaCl solution with EG-ensures both economic and environmental viability while enabling enhanced electrochemical performance. Furthermore, the MSCs fabricated via 3D printing technology exhibit exceptional flexibility and are suitable for modular device integration, offering a promising avenue for the development of high-performance, sustainable energy storage devices. This advancement not only provides a tangible solution to the challenge of limited voltage windows in aqueous MXene MSCs but also sets a new precedent for the design of next-generation MSCs that align with the needs of an increasingly microdevice-centric world.

Role and mechanism of endoplasmic reticulum stress and NLRP3 inflammasome in acute kidney injury. / å† è´¨ç½‘åº”æ¿€å’ŒNLRP3ç‚Žç—‡å°ä½“åœ¨æ€¥æ€§è‚¾æŸä¼¤ä¸­çš„ä½œç”¨åŠå ¶æœºåˆ¶.

Acute kidney injury (AKI) is a common critical condition in clinical practice, characterized by a rapid decline in renal function within a short period. The pathogenesis of AKI is complex and has not been fully elucidated. In recent years, studies have found that the activation of endoplasmic reticulum stress (ERS) and the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome are closely related to the occurrence of AKI. When the kidneys is damaged, the internal environment of the kidney cells is disrupted, leading to the activation of ERS. Excessive ERS can induce apoptosis of renal cells, leading to the occurrence of AKI. Additionally, the NLRP3 inflammasome can mediate the recognition of endogenous and exogenous danger signal molecules by the host, subsequently activating caspase-1, pro-inflammatory cytokines such as IL-1ß and IL-18, inducing inflammatory responses, and promoting apoptosis of renal cells. In animal models of AKI, the upregulation of ERS markers is often accompanied by increased expression levels of NLRP3 inflammasome-related proteins, indicating that ERS can regulate the activation process of the NLRP3 inflammasome. Clarifying the role and mechanism of ERS and NLRP3 inflammasome in AKI is expected to provide new insights for the prevention and treatment of AKI.

Circ_0073228 serves as a competitive endogenous ribonucleic acid to facilitate proliferation and inhibit apoptosis of hepatocellular carcinoma cells by the miR-139-5p/deoxyribonuclease II axis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy and has extremely poor prognosis and outcome. Homo sapiens deoxyribonuclease II (DNASE2) has been reported to participate in HCC progression. Here, the role of DNASE2 in HCC cells and the putative upstream circRNA that mediates DNASE2 expression was investigated. METHODS: The expression of RNAs in liver hepatocellular carcinoma (LIHC) samples was analyzed by bioinformatic analysis. The proliferation, apoptosis, migration, invasion, and gene expression in HCC cells were investigated using a Cell Counting Kit -8, colony formation, flow cytometry analysis, wound healing, transwell, western blotting, and a quantitative reverse transcriptase-PCR. The binding relationship among circ_0073228, miR-139-5p and DNASE2 was measured by RNA pulldown and luciferase reporter assays. RESULTS: DNASE2 knockdown inhibited proliferation and promoted apoptosis of HCC cells, whereas DNASE2 overexpression showed the opposite results. miR-139-5p targeted DNASE2 and suppressed its expression. Overexpression of miR-139-5p inhibited malignant phenotypes of HCC cells. RPS23-derived circ_0073228, which bound to miR-139-5p, was found to be upregulated in HCC cells. Inhibition of miR-139-5p or overexpression of DNASE2 counteracted the inhibitory effects of circ_0073228 knockdown on HCC cell progression. CONCLUSIONS: circ_0073228 serves as an oncogene to facilitate growth and inhibit apoptosis of HCC cells by regulating the miR-139-5p/DNASE2 axis.

The RNA polymerase II subunit B (RPB2) functions as a growth regulator in human glioblastoma.

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with a poor prognosis. The growth of GBM cells depends on the core transcriptional apparatus, thus rendering RNA polymerase (RNA pol) complex as a candidate therapeutic target. The RNA pol II subunit B (POLR2B) gene encodes the second largest subunit of the RNA pol II (RPB2); however, its genomic status and function in GBM remain unclear. Certain GBM data sets in cBioPortal were used for investigating the genomic status and expression of POLR2B in GBM. The function of RPB2 was analyzed following knockdown of POLR2B expression by shRNA in GBM cells. The cell counting kit-8 assay and PI staining were used for cell proliferation and cell cycle analysis. A xenograft mouse model was established to analyze the function of RPB2 in vivo. RNA sequencing was performed to analyze the RPB2-regulated genes. GO and GSEA analyses were applied to investigate the RPB2-regulated gene function and associated pathways. In the present study, the genomic alteration and overexpression of the POLR2B gene was described in glioblastoma. The data indicated that knockdown of POLR2B expression suppressed tumor cell growth of glioblastoma in vitro and in vivo. The analysis further demonstrated the identification of the RPB2-regulated gene sets and highlighted the DNA damage-inducible transcript 4 gene as the downstream target of the POLR2B gene. The present study provides evidence indicating that RPB2 functions as a growth regulator in glioblastoma and could be used as a potential therapeutic target for the treatment of this disease.

Does Using Indocyanine Green Fluorescence Imaging for Tumors Help in Determining the Safe Surgical Margin in Real-Time Navigation of Laparoscopic Hepatectomy? A Retrospective Study.

BACKGROUND: This study aims to investigate whether indocyanine green (ICG) tumor imaging helps determine the safe surgical margin in laparoscopic hepatectomy. PATIENTS AND METHODS: Eighty-six patients with hepatic malignancies [including hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM)] were included in this study. ICG-R15 testing was performed 5-7 days before surgery. Fluorescence staining of the tumor was detected by a fluorescent laparoscope, and the width of fluorescence band surrounding tumor was measured by an electronic vernier caliper. RESULTS: The positive rate of hepatic malignant lesions successfully stained by ICG fluorescence was 96.0% (95/99). HCC with better differentiation demonstrated non-rim fluorescence patterns, while cases with poor differentiation demonstrated rim patterns. CRLM uniformly demonstrated rim pattern. The width of fluorescence surrounding tumors was 0 in HCC with non-rim patterns. The minimum width of fluorescence surrounding tumors in poor differentiated HCC and CRLM were 2.4 ± 1.9 mm and 2.8 ± 2.5 mm, respectively, with no significant difference (P > 0.05). ICG fluorescence imaging revealed eight small lesions, which were not detected preoperatively in seven patients, of which five lesions were confirmed as malignancies by pathology. CONCLUSIONS: Resection along the ICG fluorescence edge can supply a safe surgical margin only for CRLM, but not for HCC. Otherwise, ICG fluorescence tumor imaging can preliminarily determine the pathological type of hepatic malignancies and histological differentiation of HCC and help detect small lesions that cannot be detected preoperatively.

[Zn2+-Ge4+] co-substitutes [Ga3+-Ga3+] to coordinately broaden the near-infrared emission of Cr3+ in Ga2O3 phosphors.

Here, a "chemical unit co-substitution" method is used to improve the near-infrared (NIR) emission of phosphors, using [Zn2+-Ge4+] to co-substitute [Ga3+-Ga3+] sites to reduce crystal field splitting to affect the structure of gallium oxide. A series of broadband NIR phosphors are synthesized by a high-temperature solid-phase method, and their phase structures, crystal structures, morphologies, diffuse reflectance spectra, and luminescence lifetimes are investigated. The Ga1.68(Zn-Ge)0.3O3:0.02Cr3+ (GZGOC) phosphor exhibits NIR wide-band emission, with a peak wavelength of 766 nm and a half-width of 138 nm. Meanwhile, the quantum yield of photoluminescence can reach 81.2%. The phosphor has good thermal stability. When the temperature reaches 373 K, its emission intensity still remains at 73.4% of that at room temperature. A 460 nm LED chip and this phosphor are used to fabricate a phosphor-converted light emitting diode (pc-LED) device which can be used as a NIR light source. All these results show the application potential of the as-prepared phosphor in NIR imaging.

Latent profile analysis and influencing factors of quality of life in pregnant women with gestational diabetes mellitus.

PURPOSE: Gestational diabetes mellitus (GDM) negatively affects the quality of life of pregnant women and is influenced by several factors. Research to date treats pregnant women with gestational diabetes as a homogeneous group based on their quality of life. We attempted to identify subgroups based on self-reported quality of life and explored variables associated with subgroups. METHODS: From September 1, 2020 to November 29, 2020, pregnant women with GDM from two hospitals in Guangdong Province were selected as subjects by convenience sampling method. Medical records provided sociodemographic data, duration of GDM, pregnancy status, and family history of diabetes. Participants completed validated questionnaires for quality of life, anxiety and depression. Latent profile analysis was used to identify profiles of quality of life in pregnant women with GDM, and then a mixed regression method was used to analyze the influencing factors of different profiles. RESULTS: A total of 279 valid questionnaires were collected. The results of the latent profile analysis showed that the quality of life of pregnant women with GDM could be divided into two profiles: C1 "high worry-high support" group (75.6%) and C2 "low worry-low support" group (24.4%). Daily exercise duration and depression degree are negative influencing factors, making it easier to enter the C1 group (p < 0.05). Disease duration and family history of diabetes are positive influencing factors, making it easier to enter the C2 group (p < 0.05). CONCLUSION: The quality of life of pregnant women with GDM had obvious classification characteristics. Pregnant women with exercise habits and depression are more likely to enter the "high worry-high support" group, and health care providers should guide their exercise according to exercise guidelines during pregnancy and strengthen psychological intervention. Pregnant women with a family history of diabetes and a longer duration of the disease are more likely to fall into the "low worry-low support" group. Healthcare providers can strengthen health education for them and improve their disease self-management abilities.

Comparative study of extracellular vesicles derived from mesenchymal stem cells and brain endothelial cells attenuating blood-brain barrier permeability via regulating Caveolin-1-dependent ZO-1 and Claudin-5 endocytosis in acute ischemic stroke.

BACKGROUND: Blood-brain barrier (BBB) disruption is a major adverse event after ischemic stroke (IS). Caveolin-1 (Cav-1), a scaffolding protein, played multiple roles in BBB permeability after IS, while the pros and cons of Cav-1 on BBB permeability remain controversial. Numerous studies revealed that extracellular vesicles (EVs), especially stem cells derived EVs, exerted therapeutic efficacy on IS; however, the mechanisms of BBB permeability needed to be clearly illustrated. Herein, we compared the protective efficacy on BBB integrity between bone marrow mesenchymal stem cells derived extracellular vesicles (BMSC-EVs) and EVs from brain endothelial cells (BEC-EVs) after acute IS and investigated whether the mechanism was associated with EVs antagonizing Cav-1-dependent tight junction proteins endocytosis. METHODS: BMSC-EVs and BEC-EVs were isolated and characterized by nanoparticle tracking analysis, western blotting, and transmission electron microscope. Oxygen and glucose deprivation (OGD) treated b. End3 cells were utilized to evaluate brain endothelial cell leakage. CCK-8 and TRITC-dextran leakage assays were used to measure cell viability and transwell monolayer permeability. Permanent middle cerebral artery occlusion (pMCAo) model was established, and EVs were intravenously administered in rats. Animal neurological function tests were applied, and microvessels were isolated from the ischemic cortex. BBB leakage and tight junction proteins were analyzed by Evans Blue (EB) staining and western blotting, respectively. Co-IP assay and Cav-1 siRNA/pcDNA 3.1 vector transfection were employed to verify the endocytosis efficacy of Cav-1 on tight junction proteins. RESULTS: Both kinds of EVs exerted similar efficacies in reducing the cerebral infarction volume and BBB leakage and enhancing the expressions of ZO-1 and Claudin-5 after 24 h pMCAo in rats. At the same time, BMSC-EVs were outstanding in ameliorating neurological function. Simultaneously, both EVs treatments suppressed the highly expressed Cav-1 in OGD-exposed b. End3 cells and ischemic cerebral microvessels, and this efficacy was more prominent after BMSC-EVs administration. Cav-1 knockdown reduced OGD-treated b. End3 cells monolayer permeability and recovered ZO-1 and Claudin-5 expressions, whereas Cav-1 overexpression aggravated permeability and enhanced the colocalization of Cav-1 with ZO-1 and Claudin-5. Furthermore, Cav-1 overexpression partly reversed the lower cell leakage by BMSC-EVs and BEC-EVs administrations in OGD-treated b. End3 cells. CONCLUSIONS: Our results demonstrated that Cav-1 aggravated BBB permeability in acute ischemic stroke, and BMSC-EVs exerted similar antagonistic efficacy to BEC-EVs on Cav-1-dependent ZO-1 and Claudin-5 endocytosis. BMSC-EVs treatment was superior in Cav-1 suppression and neurological function amelioration.