Dynamic YAP expression in the non-parenchymal liver cell compartment controls heterologous cell communication.

INTRODUCTION: The Hippo pathway and its transcriptional effectors yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are targets for cancer therapy. It is important to determine if the activation of one factor compensates for the inhibition of the other. Moreover, it is unknown if YAP/TAZ-directed perturbation affects cell-cell communication of non-malignant liver cells. MATERIALS AND METHODS: To investigate liver-specific phenotypes caused by YAP and TAZ inactivation, we generated mice with hepatocyte (HC) and biliary epithelial cell (BEC)-specific deletions for both factors (YAPKO, TAZKO and double knock-out (DKO)). Immunohistochemistry, single-cell sequencing, and proteomics were used to analyze liver tissues and serum. RESULTS: The loss of BECs, liver fibrosis, and necrosis characterized livers from YAPKO and DKO mice. This phenotype was weakened in DKO tissues compared to specimens from YAPKO animals. After depletion of YAP in HCs and BECs, YAP expression was induced in non-parenchymal cells (NPCs) in a cholestasis-independent manner. YAP positivity was detected in subgroups of Kupffer cells (KCs) and endothelial cells (ECs). The secretion of pro-inflammatory chemokines and cytokines such as C-X-C motif chemokine ligand 11 (CXCL11), fms-related receptor tyrosine kinase 3 ligand (FLT3L), and soluble intercellular adhesion molecule-1 (ICAM1) was increased in the serum of YAPKO animals. YAP activation in NPCs could contribute to inflammation via TEA domain transcription factor (TEAD)-dependent transcriptional regulation of secreted factors. CONCLUSION: YAP inactivation in HCs and BECs causes liver damage, and concomitant TAZ deletion does not enhance but reduces this phenotype. Additionally, we present a new mechanism by which YAP contributes to cell-cell communication originating from NPCs.

Polarity-Mediated Antisolvent Control Enables Efficient Lanthanide-Based near-Infrared Perovskite LEDs.

Alloying lanthanide ions (Yb3+) into perovskite quantum dots (Yb3+:CsPb(Cl1-xBrx)3) is an effective method to achieve efficient near-infrared (NIR) luminescence (>950 nm). Increasing the Yb3+ alloying ratio in the perovskite matrix enhances the luminescence intensity of Yb3+ emission at 990 nm. However, high Yb3+ alloying (>15%) results in vacancy-induced inferior material stability. In this work, we developed a polarity-mediated antisolvent manipulation strategy to resolve the incompatibility between a high Yb3+ alloying ratio and inferior stability of Yb3+:CsPb(Cl1-xBrx)3. Precise control of solution polarity enables increased uniformity of the perovskite matrix with fewer trap densities. Employing this strategy, we obtain Yb3+:CsPb(Cl1-xBrx)3 with the highest Yb3+ alloying ratio of 30.2% and a 2-fold higher electroluminescence intensity at 990 nm. We lever the engineered Yb3+:CsPb(Cl1-xBrx)3 to fabricate NIR-LEDs, achieving a peak external quantum efficiency (EQE) of 8.5% at 990 nm: this represents the highest among perovskite NIR-LEDs with an emission wavelength above 950 nm.

Mechanical-Force-Induced Non-spontaneous Dehalogenative Deuteration of Aromatic Iodides Enabled by Using Piezoelectric Materials as a Redox Catalyst.

The development of green and efficient deuteration methods is of great significance for various fields such as organic synthesis, analytical chemistry, and medicinal chemistry. Herein, we have developed a dehalogenative deuteration strategy using piezoelectric materials as catalysts in a solid-phase system under ball-milling conditions. This non-spontaneous reaction is induced by mechanical force. D2O can serve as both a deuterium source and an electron donor in the transformation, eliminating the need for additional stoichiometric exogenous reductants. A series of (hetero)aryl iodides can be transformed into deuterated products with high deuterium incorporation. This method not only effectively overcomes existing synthetic challenges but can also be used for deuterium labelling of drug molecules and derivatives. Bioactivity experiments with deuterated drug molecule suggest that the D-ipriflavone enhances the inhibitory effects on osteoclast differentiation of BMDMs in vitro.

SUMO Modification of Histone Demethylase KDM4A in Kaposi's Sarcoma-Associated Herpesvirus-Induced Primary Effusion Lymphoma.

Primary effusion lymphoma (PEL) is a fatal B-cell lymphoma caused by Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Inducing KSHV lytic replication that causes the death of host cells is an attractive treatment approach for PE; however, combination therapy inhibiting viral production is frequently needed to improve its outcomes. We have previously shown that the KSHV lytic protein K-bZIP can SUMOylate histone lysine demethylase 4A (KDM4A) at lysine 471 (K471) and this SUMOylation is required for virus production upon KSHV reactivation. Here, we demonstrate that SUMOylation of KDM4A orchestrates PEL cell survival, a major challenge for the success of PEL treatment; and cell movement and angiogenesis, the cell functions contributing to PEL cell extravasation and dissemination. Furthermore, integrated ChIP-seq and RNA-seq analyses identified interleukin-10 (IL-10), an immunosuppressive cytokine, as a novel downstream target of KDM4A. We demonstrate that PEL-induced angiogenesis is dependent on IL-10. More importantly, single-cell RNA sequencing (scRNA-seq) analysis demonstrated that, at the late stage of KSHV reactivation, KDM4A determines the fates of PEL cells, as evidenced by two distinct cell populations; one with less apoptotic signaling expresses high levels of viral genes and the other is exactly opposite, while KDM4A-K417R-expressing cells contain only the apoptotic population with less viral gene expression. Consistently, KDM4A knockout significantly reduced cell viability and virus production in KSHV-reactivated PEL cells. Since inhibiting PEL extravasation and eradicating KSHV-infected PEL cells without increasing viral load provide a strong rationale for treating PEL, this study indicates targeting KDM4A as a promising therapeutic option for treating PEL. IMPORTANCE PEL is an aggressive and untreatable B-cell lymphoma caused by KSHV infection. Therefore, new therapeutic approaches for PEL need to be investigated. Since simultaneous induction of KSHV reactivation and apoptosis can directly kill PEL cells, they have been applied in the treatment of this hematologic malignancy and have made progress. Epigenetic therapy with histone deacetylase (HDAC) inhibitors has been proved to treat PEL. However, the antitumor efficacies of HDAC inhibitors are modest and new approaches are needed. Following our previous report showing that the histone lysine demethylase KDM4A and its SUMOylation are required for lytic reactivation of KSHV in PEL cells, we further investigated its cellular function. Here, we found that SUMOylation of KDM4A is required for the survival, movement, and angiogenesis of lytic KSHV-infected PEL cells. Together with our previous finding showing the importance of KDM4A SUMOylation in viral production, KDM4A can be a potential therapeutic target for PEL.

A Shift in Molecular Drivers of Papillary Thyroid Carcinoma Following the 2017 World Health Organization Classification: Characterization of 554 Consecutive Tumors With Emphasis on BRAF-Negative Cases.

Most studies for comprehensive molecular profiling of papillary thyroid carcinoma (PTC) have been performed before the 2017 World Health Organization (WHO) classification, in which the diagnostic criteria of follicular variants of PTC have been modified and noninvasive follicular thyroid neoplasm with papillary-like nuclear features has been introduced. This study aims to investigate the shift in the incidence of BRAF V600E mutations in PTCs following the 2017 WHO classification and to further characterize the histologic subtypes and molecular drivers in BRAF-negative cases. The study cohort consisted of 554 consecutive PTCs larger than 0.5 cm between January 2019 and May 2022. Immunohistochemistry for BRAF VE1 was performed for all cases. Compared with a historical cohort of 509 PTCs from November 2013 to April 2018, the incidence of BRAF V600E mutations was significantly higher in the study cohort (86.8% vs 78.8%, P = .0006). Targeted RNA-based next-generation sequencing using a FusionPlex Pan Solid Tumor v2 panel (ArcherDX) was performed for BRAF-negative PTCs from the study cohort. Eight cribriform-morular thyroid carcinomas and 3 cases with suboptimal RNA quality were excluded from next-generation sequencing. A total of 62 BRAF-negative PTCs were successfully sequenced, including 19 classic follicular predominant PTCs, 16 classic PTCs, 14 infiltrative follicular PTCs, 7 encapsulated follicular PTCs, 3 diffuse sclerosing PTCs, 1 tall cell PTC, 1 solid PTC, and 1 diffuse follicular PTC. Among them, RET fusions were identified in 25 cases, NTRK3 fusions in 13 cases, BRAF fusions in 5 cases including a novel TNS1::BRAF fusion, NRAS Q61R mutations in 3 cases, KRAS Q61K mutations in 2 cases, NTRK1 fusions in 2 cases, an ALK fusion in 1 case, an FGFR1 fusion in 1 case, and an HRAS Q61R mutation in 1 case. No genetic variants, from our commercially employed assay, were detected in the remaining 9 cases. In summary, the incidence of BRAF V600E mutations in PTCs significantly increased from 78.8% to 86.8% in our post-2017 WHO classification cohort. RAS mutations accounted for only 1.1% of the cases. Driver gene fusions were identified in 8.5% of PTCs and were clinically relevant given the emerging targeted kinase inhibitor therapy. Of the 1.6% of cases for which no driver alteration was detected, the specificity of drivers tested and tumor classification require further investigation.

Extraskeletal Myxoid Chondrosarcomas: The Uncommon Clinicopathologic Manifestations and Significance of TAF15::NR4A3 Fusion.

Extraskeletal myxoid chondrosarcoma (EMC) is an ultrarare sarcoma typically exhibiting myxoid/reticular histology and NR4A3 translocation. However, morphologic variants and the relevance of non-EWSR1::NR4A3 fusions remain underexplored. Three challenging pan-Trk-expressing cases, featuring cellular to solid histology, were subjected to RNA exome sequencing (RES), unveiling different NR4A3-associated fusions. Alongside RES-analyzed cases, fluorescence in situ hybridization was performed to confirm 58 EMCs, with 48 available for pan-Trk immunostaining and KIT sequencing. Except for 1 (2%) NR4A3-rearranged EMC without identifiable partners, 46 (79%), 9 (16%), and 2 (3%) cases harbored EWSR1::NR4A3, TAF15::NR4A3, and TCF12::NR4A3 fusions, respectively. Five EWSR1::NR4A3-positive EMCs occurred in the subcutis (3) and bone (2). Besides 43 classical cases, there were 8 cellular, 4 rhabdoid/anaplastic, 2 solid, and 1 mixed tumor-like variants. Tumor cells were oval/spindle to pleomorphic and formed loose myxoid/reticular to compact sheet-like or fascicular patterns, imparting broad diagnostic considerations. RES showed upregulation of NTRK2/3, KIT, and INSM1. Moderate-to-strong immunoreactivities of pan-Trk, CD117, and INSM1 were present in 35.4%, 52.6%, and 54.6% of EMCs, respectively. KIT p. E554K mutation was detected in 2/48 cases. TAF15::NR4A3 was significantly associated with size >10 cm (78%, P = .025). Size >10 cm, moderate-to-severe nuclear pleomorphism, metastasis at presentation, TAF15::NR4A3 fusion, and the administration of chemotherapy portended shorter univariate disease-specific survival, whereas only size >10 cm (P = .004) and metastasis at presentation (P = .032) remained prognostically independent. Conclusively, EMC may manifest superficial or osseous lesions harboring EWSR1::NR4A3, underrecognized solid or anaplastic histology, and pan-Trk expression, posing tremendous challenges. Most TAF15::NR4A3-positive cases were >10 cm in size, ie, a crucial independent prognosticator, whereas pathogenic KIT mutation rarely occurred.

Long non-coding RNA KIKAT/LINC01061 as a novel epigenetic regulator that relocates KDM4A on chromatin and modulates viral reactivation.

KDM4A is a histone lysine demethylase that has been described as an oncogene in various types of cancer. The importance of KDM4A-mediated epigenetic regulation in tumorigenesis is just emerging. Here, by using Kaposi's sarcoma associated herpesvirus (KSHV) as a screening model, we identified 6 oncogenic virus-induced long non-coding RNAs (lncRNAs) with the potential to open chromatin. RNA immunoprecipitation revealed KSHV-induced KDM4A-associated transcript (KIKAT)/LINC01061 as a binding partner of KDM4A. Integrated ChIP-seq and RNA-seq analysis showed that the KIKAT/LINC01061 interaction may mediate relocalization of KDM4A from the transcription start site (TSS) of the AMOT promoter region and transactivation of AMOT, an angiostatin binding protein that regulates endothelial cell migration. Knockdown of AMOT diminished the migration ability of uninfected SLK and iSLK-BAC16 cells in response to KIKAT/LINC01061 overexpression. Thus, we conclude that KIKAT/LINC01061 triggered shifting of KDM4A as a potential epigenetic mechanism regulating gene transactivation. Dysregulation of KIKAT/LINC01061 expression may represent a novel pathological mechanism contributing to KDM4A oncogenicity.

SFTSV Gn-Head mRNA vaccine confers efficient protection against lethal viral challenge.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus, causing thrombocytopenia and hemorrhagic fever, with a fatality rate ranging from 12% to 30%. SFTSV possesses Gn and Gc glycoproteins, which are responsible for host cell receptor attachment and membrane fusion, respectively, to infect host cells. We have previously reported a protein subunit vaccine candidate (sGn-H-FT) of the SFTSV soluble Gn head region (sGn-H) fused with self-assembling ferritin (FT) nanoparticles, displaying strong protective immunogenicity. In this study, we present messenger RNA (mRNA) vaccine candidates encoding sGn-H or sGn-H-FT, both of which exhibit potent in vivo immunogenicity and protection capacity. Mice immunized with either sGn-H or sGn-H-FT mRNA lipid nanoparticle (LNP) vaccine produced strong total antibodies and neutralizing antibodies (NAbs) against sGn-H. Importantly, NAb titers remained high for an extended period. Finally, mice immunized with sGn-H or sGn-H-FT mRNA LNP vaccine were fully protected from a lethal dose of SFTSV challenge, showing no fatality. These findings underscore the promise of sGn-H and sGn-H-FT as vaccine antigen candidates capable of providing protective immunity against SFTSV infection.

LncRNA landscape and associated ceRNA network in placental villus of unexplained recurrent spontaneous abortion.

BACKGROUND: Unexplained recurrent spontaneous abortion (URSA) is one of the most challenging conditions frustrates women of childbearing age profoundly. The gene expression patterns and biological characteristics of placental villus in patients with URSA remain largely unknown. The aim of our study was to identify potential lncRNAs as well as their action mechanisms in URSA. METHOD: The ceRNA microarray was used to identify the mRNA and lncRNA expression profiles of URSA patients and normal pregnancy. Functional enrichment analyses for differentially expressed mRNAs in URSA were performed. Protein-protein interaction analysis of differentially expressed mRNAs was performed to identify hub genes and key modules. Subsequently, the co-dysregulated ceRNA network of URSA was established, and the enrichment analyses for the mRNAs in the ceRNA network was implemented. qRT-PCR was performed to validated the expression of key ENST00000429019 and mRNAs in URSA. RESULTS: We found that URSA placental villus have distinct mRNA and lncRNA expression profiles through ceRNA microarray, with a total of 347 mRNAs and 361 lncRNAs differentially expressed compared with controls. The functional enrichment analysis revealed that ncRNA processing, DNA replication, cell cycle, apoptosis, cytokine-mediated signaling pathway, ECM-receptor interaction were the potentially disrupted pathways in URSA patients. Then we constructed a co-dysregulated ceRNA network and found differentially expressed mRNAs were regulated by a small fraction of hub lncRNAs. Finally, we found a key network of ENST00000429019 and three cell proliferation or apoptosis related key mRNAs (CDCA3, KIFC1, NCAPH), and validated their expression and regulation in tissue and cellular levels. CONCLUSIONS: This study identified a key ceRNA network, which might take part in URSA and correlate with cell proliferation and apoptosis. Optimistically, this study may deepen our apprehensions about the underlying molecular and biological causes of URSA and provide an important theoretical basis for future therapeutic strategies for patients with URSA.

Upregulation of dihydropyrimidinase-like 3 (DPYSL3) protein predicts poor prognosis in urothelial carcinoma.

BACKGROUND: Dihydropyrimidinase-like 3 (DPYSL3) is a cytosolic phosphoprotein expressed in the nervous system and is crucial for neurogenesis. A previous study showed that increased DPYSL3 expression promotes tumour aggressiveness in pancreatic ductal adenocarcinoma, gastric cancer, and colon cancer. However, the role of DPYSL3 in affecting the biological behaviour of urothelial carcinoma (UC) is not yet understood. METHODS: A UC transcriptomic dataset from the Gene Expression Omnibus and the Urothelial Bladder Cancer (BLCA) dataset from The Cancer Genome Atlas were used for the in silico study. We collected 340 upper urinary tract urothelial carcinoma (UTUC) and 295 urinary bladder urothelial carcinoma (UBUC) samples for the immunohistochemical study. Fresh tumour tissue from 50 patients was used to examine the DPYSL3 mRNA level. In addition, urothelial cell lines with and without DPYSL3 knockdown were used for the functional study. RESULTS: The in silico study revealed that DPYSL3 correlated with advanced tumour stage and metastasis development while functioning primarily in the nucleobase-containing compound metabolic process (GO:0006139). DPYSL3 mRNA expression is significantly upregulated in advanced UC. Furthermore, overexpression of the DPYSL3 protein is significantly associated with the aggressive behaviour of UTUC and UBUC. DPYSL3 expression independently predicts disease-specific survival (DSS) and metastatic-free survival (MFS) in patients with UC. In non-muscle-invasive UBUC, DPYSL3 expression predicts local recurrence-free survival. UC cell lines with DPYSL3 knockdown exhibited decreased proliferation, migration, invasion, and human umbilical vein endothelial cells (HUVECs) tube formation but increased apoptosis and G1 arrest. Gene ontology enrichment analysis revealed that the enriched processes related to DPYSL3 overexpression in UC were tissue morphogenesis, cell mesenchyme migration, smooth muscle regulation, metabolic processes, and RNA processing. In vivo study revealed DPYSL3 knockdown in UC tumours significantly suppressed the growth of tumours and decreased MYC and GLUT1 protein expression. CONCLUSIONS: DPYSL3 promotes the aggressiveness of UC cells by changing their biological behaviours and is likely associated with cytoskeletal and metabolic process modifications. Furthermore, DPYSL3 protein overexpression in UC was associated with aggressive clinicopathological characteristics and independently predicted poor clinical outcomes. Therefore, DPYSL3 can be used as a novel therapeutic target for UC.

Major pathological remissions in a patient with stage IIIA nonsmall cell lung cancer after neoadjuvant tislelizumab combined with chemotherapy: a case report and literature review.

INTRODUCTION: Currently, there are few reports of patients with locally advanced lung cancer achieving a clinical complete response by medical treatment. Preoperative neoadjuvant immunotherapy combined with chemotherapy is an option for patients with unresectable, locally advanced nonsmall cell lung cancer (NSCLC) which is of great potential, and may change traditional treatment paradigms. There are relatively few large-scale, high-quality randomized-controlled trials yet, and limitations such as short postoperative follow-up period and immature disease-free survival and overall survival data still persist. Thus, evidence-based medical evidence is urgently needed. It is worthy to explore the further treatment of patients who achieved complete response after initial treatment, though lacking of evidence by now. CASE PRESENTATION: We report a stage IIIA lung squamous cell carcinoma case who achieved a major pathologic remission after neoadjuvant treatment with tislelizumab and chemotherapy. CONCLUSION: Our case study contributes to the existing evidence on the feasibility, efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC.

Huntingtin-associated protein 1 is a potential tumor suppressor for gastric cancer.

BACKGROUND: Gastric cancer is heterogeneous cancer and the causes of this disease are complex. New diagnostic and therapeutic targets are urgently needed to explore. Huntingtin-associated protein 1 (HAP1) is directly related to Huntington's disease (HD). However, patients with Huntington's disease have a lower incidence of cancer. Therefore, we are committed to studying the correlation between HAP1 and gastric carcinogenesis and development. METHODS AND RESULTS: Immunohistochemical staining, western blot analysis, and RT-qPCR were conducted to explore the localization and expression of HAP1 in gastric cancer. To study the biological significance of HAP1, we overexpressed HAP1 in both MKN28 and AGS cell lines by lentivirus infection. To explore the role of HAP1 in cell proliferation, the cells counting assay, EdU incorporation assay, and colony formation assay were carried out. We performed the wound healing assay and transwell assay to study the cell migration and invasion. To further investigate whether HAP1 could regulate gastric cancer cell death during glucose deprivation, Annexin V-FITC/PI staining was performed. In our study, we elucidated that HAP1 was downregulated in gastric cancer. What's more, overexpressing HAP1 inhibited cell proliferation, cell migration and invasion, and triggered apoptosis during glucose deprivation. More importantly, the antitumor properties and mechanisms of HAP1 have been elucidated further in gastric cancer. CONCLUSIONS: Taken together, the available evidence implies that HAP1 may serve as a potential tumor suppressor, making it a significant target in preventing and treating gastric cancer. This research provides a theoretical basis for the early diagnosis, clinical targeted therapy, and prognosis evaluation of gastric cancer.

Melatonin protects against methotrexate hepatotoxicity in young rats: Impact of PI3K/Akt/mTOR signaling.

With the improvement in children's acute lymphoblastic leukemia (ALL) care, the survival rate in children ALL has improved much. Methotrexate (MTX) plays an essential role in the success of children's ALL treatment. Since hepatotoxicity is commonly reported in individuals treated with intravenous or oral MTX, our study further examined the hepatic effect following intrathecal MTX treatment, which is an essential treatment for leukemia patients. Specifically, we examined the pathogenesis of MTX hepatotoxicity in young rats and explored the impact of melatonin treatment in protection against MTX hepatotoxicity. Successfully, we found that melatonin was able to protect against MTX hepatotoxicity.

Low expression of ZSCAN4 predicts unfavorable outcome in urothelial carcinoma of upper urinary tract and urinary bladder.

BACKGROUND: With the advance in genome-wide analyses, genetic alternations have been found to play an important role in carcinogenesis and aggressiveness of UC. Through bioinformatic analysis of gene expression profiles of urinary bladder urothelial carcinoma (UBUC) from publicly available GEO dataset (GSE31684), Zinc finger and SCAN domain containing 4 (ZSCAN4) was identified as a significant downregulated gene in muscle-invasive bladder cancer when compared with non-muscle-invasive bladder cancer. METHODS: The expression of ZSCAN4 was evaluated by immunohistochemistry in 340 upper urinary tract urothelial carcinomas (UTUCs) and 295 UBUCs. The expression profiles of ZSCAN4 and potential signaling pathways were analyzed bioinformatically. RESULTS: In UTUC, low expression of ZSCAN4 was significantly associated with advanced primary pT stage (P = 0.011), increased nodal metastasis (P = 0.002) and increased vascular invasion (P = 0.019). In UBUC, low expression of ZSCAN4 was significantly correlated with advanced primary pT stage (P < 0.001), increased nodal metastasis (P = 0.001), high histological grade (P = 0.003) and increased vascular invasion (P = 0.003). In survival analysis, low expression of ZSCAN4 acted as an independent negative prognostic factor for disease-specific survival and metastasis-free survival both in UTUC and UBUC. Gene ontology analysis showed that ZSCAN4 mRNA and its co-downregulated genes are associated with the mitotic cell cycle. CONCLUSIONS: Low expression of ZSCAN4 predicted worse outcome in urothelial carcinoma and might have potential regulatory role in cell mitosis.

Efficient Near-Infrared Electroluminescence from Lanthanide-Doped Perovskite Quantum Cutters.

Perovskite nanocrystals (PeNCs) deliver size- and composition-tunable luminescence of high efficiency and color purity in the visible range. However, attaining efficient electroluminescence (EL) in the near-infrared (NIR) region from PeNCs is challenging, limiting their potential applications. Here we demonstrate a highly efficient NIR light-emitting diode (LED) by doping ytterbium ions into a PeNCs host (Yb3+ : PeNCs), extending the EL wavelengths toward 1000 nm, which is achieved through a direct sensitization of Yb3+ ions by the PeNC host. Efficient quantum-cutting processes enable high photoluminescence quantum yields (PLQYs) of up to 126 % from the Yb3+ : PeNCs. Through halide-composition engineering and surface passivation to improve both PLQY and charge-transport balance, we demonstrate an efficient NIR LED with a peak external quantum efficiency of 7.7 % at a central wavelength of 990 nm, representing the most efficient perovskite-based LEDs with emission wavelengths beyond 850 nm.

Iodotrimethylsilane as a Reactive Ligand for Surface Etching and Passivation of Perovskite Nanocrystals toward Efficient Pure-red to Deep-red LEDs.

Resurfacing perovskite nanocrystals (NCs) with tight-binding and conductive ligands to resolve the dynamic ligands-surface interaction is the fundamental issue for their applications in perovskite light-emitting diodes (PeLEDs). Although various types of surface ligands have been proposed, these ligands either exhibit weak Lewis acid/base interactions or need high polar solvents for dissolution and passivation, resulting in a compromise in the efficiency and stability of PeLEDs. Herein, we report a chemically reactive agent (Iodotrimethylsilane, TMIS) to address the trade-off among conductivity, solubility and passivation using all-inorganic CsPbI3 NCs. The liquid TMIS ensures good solubility in non-polar solvents and reacts with oleate ligands and produces in situ HI for surface etching and passivation, enabling strong-binding ligands on the NCs surface. We report, as a result, red PeLEDs with an external quantum efficiency (EQE) of ≈23 %, which is 11.2-fold higher than the control, and is among the highest CsPbI3 PeLEDs. We further demonstrate the universality of this ligand strategy in the pure bromide system (CsPbBr3 ), and report EQE of ≈20 % at 640, 652, and 664 nm. This represents the first demonstration of a chemically reactive ligand strategy that applies to different systems and works effectively in red PeLEDs spanning emission from pure-red to deep-red.

High MT2A Expression Predicts Worse Prognosis in Patients with Urothelial Carcinoma.

Introduction: Dysregulation of metal ion homeostasis is associated with urothelial carcinogenesis. From a published urinary bladder urothelial carcinoma (UBUC) transcriptome, we identified metallothionein 2A (MT2A) as the most significantly upregulated gene implicated in cancer progression among metal ion binding-related genes. Therefore, we analyzed the association between MT2A expression and clinical significance in our well-characterized cohort of patients with upper tract urothelial carcinoma (UTUC) and UBUC. Methods: We retrospectively reviewed the clinicopathological characteristics of 295 and 340 patients with UBUC and UTUC, respectively. MT2A expression was assessed using real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. We further correlated MT2A expression with clinicopathological factors, disease-specific survival (DSS) and metastasis-free survival (MFS) using the Pearson's χ2 test, Kaplan-Meier analysis, and multivariate Cox proportional hazards model. Results: High MT2A expression was significantly associated with aggressive pathological features including high tumor stage, lymph node metastasis, high tumor grade, vascular invasion, and perineural invasion. In the Kaplan-Meier analysis, high MT2A expression was significantly correlated with poor DSS (p < 0.0001) and MFS (p < 0.0001); in the multivariate analysis, it was an independent predictor of CSS (p < 0.001) and MFS (p = 0.001). Gene coexpression analysis demonstrated that MT2A overexpression promotes UC progression through complement activation. Conclusion: High MT2A expression correlated with aggressive UC features and was an independent predictor of cancer metastasis and patient survival, suggesting its role in risk stratification and decision-making in patients with UTUC and UBUC.

Anion-Afforded Functions of Ionic Metal-Organic Frameworks: Ionochromism, Anion Conduction, and Catalysis.

The exchangeable counterions in ionic metal-organic frameworks (IMOFs) provide facile and versatile handles to manipulate functions associated with the ionic guests themselves and host-guest interactions. However, anion-exchangeable stable IMOFs combining multiple anion-related functions are still undeveloped. In this work, a novel porous IMOF featuring unique self-penetration was constructed from an electron-deficient tris(pyridinium)-tricarboxylate zwitterionic ligand. The water-stable IMOF undergoes reversible and single-crystal-to-single-crystal anion exchange and shows selective and discriminative ionochromic behaviors toward electron-rich anions owing to donor-acceptor interactions. The IMOFs with different anions are good ionic conductors with low activation energy, the highest conductivity being observed with chloride. Furthermore, integrating Lewis acidic sites and nucleophilic guest anions in solid state, the IMOFs act as heterogeneous and recyclable catalysts to efficiently catalyze the cycloaddition of CO2 to epoxides without needing the use of halide cocatalysts. The catalytic activity is strongly dependent upon the guest anions, and the iodide shows the highest activity. The results demonstrate the great potential of developing IMOFs with various functions related to the guest ions included in the porous matrices.

Analysis of 256 pediatric oral and maxillofacial emergency in-patients during the outbreak of COVID-19.

BACKGROUND/AIMS: Pediatric oral and maxillofacial surgeons have faced severe challenges in ward management due to their high risk of exposure during the COVID-19 epidemic. The aim of this study was to analyze and summarize the treatment methods and infection prevention and control measures applied in emergency cases in the Department of Pediatric Oral and Maxillofacial Surgery, Children's Hospital of Chongqing Medical University, during the COVID-19 epidemic. METHODS: In this retrospective study, information was collected from 256 pediatric emergency patients who were treated from January 23, 2020 to August 9, 2021. The patients' data were statistically analyzed according to age, gender, disease and pathogenesis, operation time, and the main treatment applied in pediatric oral and maxillofacial emergency cases during the COVID-19 epidemic. RESULTS: During the epidemic period, 256 pediatric emergency patients were successfully treated. Among them, there were 170 boys and 86 girls. In all, 182 patients were diagnosed with oral or facial lacerations; 43 had jaw fractures; 26 had maxillofacial infections; and five had dento-alveolar fractures. A total of 246 patients underwent surgery under negative pressure with level 3 protection standards. No doctors or patients infected with COVID-19 were found throughout the stury period. CONCLUSIONS: Pediatric oral and maxillofacial emergency in-patients mainly experienced maxillofacial trauma during the COVID-19 epidemic, followed by infection. Effective diagnosis and treatment, and avoidance of COVID-19 infection can be achieved by strictly following epidemic prevention and treatment procedures.

Positive Cooperative Protonation of a Metal-Organic Framework: pH-Responsive Fluorescence and Proton Conduction.

Positive cooperative binding, a phenomenon prevalent in biological processes, holds great appeal for the design of highly sensitive responsive molecules and materials. It has been demonstrated that metal-organic frameworks (MOFs) can show positive cooperative adsorption to the benefit of gas separation, but potential binding cooperativity is largely ignored in the study of sensory MOFs. Here, we report the first demonstration of positive cooperative protonation of a MOF and the relevant pH response in fluorescence and proton conduction. The MOF is built of Zr-O clusters and bipyridyl-based tetracarboxylate linkers and has excellent hydrolytic stability. It shows a unique pH response that features two synchronous abrupt turn-off and turn-on fluorescent transitions. The abrupt transitions, which afford high sensitivity to small pH fluctuations, are due to cooperative protonation of the pyridyl sites with a Hill coefficient of 1.6. The synchronous dual-emission response, which leads to visual color change, is ascribable to proton-triggered switching between (n, π*) and (π, π*) emissions. The latter emission can be quenched by electron donating anion-dependent through photoinduced electron transfer and ground-state charge transfer. Associated with cooperative protonation, the proton conductivity of the MOF is abruptly enhanced at low pH by two orders, but overhigh acid concentration is adverse because excessive anions can interrupt the conducting networks. Our work shows new perspectives of binding cooperativity in MOFs and should shed new light on the development of responsive fluorescent MOFs and proton conductive materials.