A Two-Pronged Nanostrategy of Iron Metabolism Disruption to Synergize Tumor Therapy by Triggering the Paraptosis-Apoptosis Hybrid Pathway.

Iron metabolism has emerged as a promising target for cancer therapy; however, the innate metabolic compensatory capacity of cancer cells significantly limits the effectiveness of iron metabolism therapy. Herein, bioactive gallium sulfide nanodots (GaSx), with dual functions of "reprogramming" and "interfering" iron metabolic pathways, were successfully developed for tumor iron metabolism therapy. The constructed GaSx nanodots ingeniously harness hydrogen sulfide (H2S) gas, which is released in response to the tumor microenvironment, to reprogram the inherent transferrin receptor 1 (TfR1)-ferroportin 1 (FPN1) iron metabolism axis in cancer cells. Concurrently, the gallium ions (Ga3+) derived from GaSx act as a biochemical "Trojan horse", mimicking the role of iron and displacing it from essential biomolecular binding sites, thereby influencing the fate of cancer cells. By leveraging the dual mechanisms of Ga3+-mediated iron disruption and H2S-facilitated reprogramming of iron metabolic pathways, GaSx prompted the initiation of a paraptosis-apoptosis hybrid pathway in cancer cells, leading to marked suppression of tumor proliferation. Importantly, the dysregulation of iron metabolism induced by GaSx notably increased tumor cell susceptibility to both chemotherapy and immune checkpoint blockade (ICB) therapy. This study underscores the therapeutic promise of gas-based interventions and metal ion interference strategies for the tumor metabolism treatment.

Advancing the molecular understanding of renal tumorigenesis: Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) as a model system.

In summary, the study's investigation of KMT2C and TSC2 variants in ACD-RCC marks a significant advancement in comprehending this distinct kidney tumor. By illuminating the molecular landscape of ACD-RCC, the research sets the stage for future studies aimed at revealing the complex mechanisms driving tumor development and progression. This understanding could eventually lead to more effective management and treatment strategies for renal cancer patients.

Infectious and Inflammatory Microenvironment Self-Adaptive Artificial Peroxisomes with Synergetic Co-Ru Pair Centers for Programmed Diabetic Ulcer Therapy.

Complex microenvironments with bacterial infection, persistent inflammation, and impaired angiogenesis are the major challenges in chronic refractory diabetic ulcers. To address this challenge, a comprehensive strategy with highly effective and integrated antimicrobial, anti-inflammatory, and accelerated angiogenesis will offer a new pathway to the rapid healing of infected diabetic ulcers. Here, inspired by the tunable reactive oxygen species (ROS) regulation properties of natural peroxisomes, this work reports the design of infectious and inflammatory microenvironments self-adaptive artificial peroxisomes with synergetic Co-Ru pair centers (APCR) for programmed diabetic ulcer therapy. Benefiting from the synergistic Co and Ru atoms, the APCR can simultaneously achieve ROS production and metabolic inhibition for bacterial sterilization in the infectious microenvironment. After disinfection, the APCR can also eliminate ROS to alleviate oxidative stress in the inflammatory microenvironment and promote wound regeneration. The data demonstrate that the APCR combines highly effective antibacterial, anti-inflammatory, and provascular regeneration capabilities, making it an efficient and safe nanomedicine for treating infectious and inflammatory diabetic foot ulcers via a programmed microenvironment self-adaptive treatment pathway. This work expects that synthesizing artificial peroxisomes with microenvironments self-adaptive and bifunctional enzyme-like ROS regulation properties will provide a promising path to construct ROS catalytic materials for treating complex diabetic ulcers, trauma, or other infection-caused diseases.

Associations of dietary pattern, insulin resistance and risk of developing metabolic syndrome among Chinese population.

Evidence regarding the role of dietary patterns in metabolic syndrome (MetS) is limited. The mechanistic links between dietary patterns, insulin resistance, and MetS are not fully understood. This study aimed to evaluate the associations between dietary patterns and the risk of MetS in a Chinese population using a longitudinal design. Data from the China Health and Nutrition Survey, a nationally representative survey, were analyzed. MetS cases were identified based on biomarker data collected in 2009. Factor analysis was employed to identify dietary patterns, while logistic regression models were utilized to examine the association between dietary patterns and MetS. Mediation models were applied to assess multiple mediation effects. Two dietary patterns were revealed by factor analysis. Participants in the higher quartiles of the traditional Chinese dietary pattern had lower odds of MetS than those in the lowest quartile (Q1) (OR = 0.58, 95%CI: 0.48, 0.69 for Q4; OR = 0.75, 95%CI: 0.63, 0.89 for Q3). Conversely, participants in the higher quartiles of the modern Chinese dietary pattern had higher odds of MetS compared to those in the lowest quartile (Q1) (OR = 1.40, 95%CI: 1.17, 1.68 for Q4; OR = 1.27, 95%CI: 1.06, 1.52 for Q3). Significant associations between dietary patterns and MetS were mediated by insulin resistance. Therefore, dietary patterns in Chinese adults are associated with MetS, and these associations appear to be mediated through insulin resistance. These findings underscore the critical role of dietary patterns in the development of MetS and establish a foundation for culturally tailored dietary interventions aimed at reducing rates the prevalence of MetS among Chinese adults.

PROTAC-Mediated HDAC7 Protein Degradation Unveils Its Deacetylase-Independent Proinflammatory Function in Macrophages.

Class IIa histone deacetylases (Class IIa HDACs) play critical roles in regulating essential cellular metabolism and inflammatory pathways. However, dissecting the specific roles of each class IIa HDAC isoform is hindered by the pan-inhibitory effect of current inhibitors and a lack of tools to probe their functions beyond epigenetic regulation. In this study, a novel PROTAC-based compound B4 is developed, which selectively targets and degrades HDAC7, resulting in the effective attenuation of a specific set of proinflammatory cytokines in both lipopolysaccharide (LPS)-stimulated macrophages and a mouse model. By employing B4 as a molecular probe, evidence is found for a previously explored role of HDAC7 that surpasses its deacetylase function, suggesting broader implications in inflammatory processes. Mechanistic investigations reveal the critical involvement of HDAC7 in the Toll-like receptor 4 (TLR4) signaling pathway by directly interacting with the TNF receptor-associated factor 6 and TGFß-activated kinase 1 (TRAF6-TAK1) complex, thereby initiating the activation of the downstream mitogen-activated protein kinase/nuclear factor-κB (MAPK/NF-κB) signaling cascade and subsequent gene transcription. This study expands the insight into HDAC7's role within intricate inflammatory networks and highlights its therapeutic potential as a novel target for anti-inflammatory treatments.

Effects of platelet-rich plasma combined with isometric quadriceps contraction on cartilage in a rat model of knee osteoarthritis.

Background: Intra-articular injection of platelet-rich plasma (PRP) or isometric contraction of quadriceps (ICQ) has shown positive effects in patients with knee osteoarthritis (KOA). However, the synergistic effect of combining PRP and ICQ intervention (joint intervention) on cartilage repair has not been validated. Thus, this study aimed to explore the reparative effects of joint intervention on cartilage in a KOA rat model. Methods: Fifty-four 2-month-old female Sprague-Dawley rats were randomly divided into the control group (CG, n = 6) and model group (injected with sodium iodoacetate, n = 48). After 1 week, six rats from the model group were randomly selected for validation. The remaining 42 rats were further divided into seven groups: PRP group (PRPG), ICQ group (ICQG), joint intervention group (JIG), normal saline group (NSG), acupuncture group (AG), normal saline and acupuncture group (NSAG) and model blank group (MBG). The intervention lasted for 4 weeks, with PRPG and JIG receiving PRP injections (twice) and ICQG and JIG undergoing ICQ (five times per week, 15 min each session). Results: Histological staining with haematoxylin and eosin as well as transmission electron microscopy revealed severe cartilage damage in MBG, AG, NSAG and NSG, followed by PRPG and ICQG. JIG exhibited a more intact cartilage structure. Compared with JIG, the Mankin scores increased remarkably in PRPG, ICQG, AG, NSAG and NSG (P < 0.01). Relative mRNA expression levels showed the upregulation of IL-1ß in ICQG, NSAG and NSG compared with JIG (P < 0.05) and the upregulation of IL-6, IL-18 and MMP-13 in AG and NSAG (P < 0.05). Compared with PRPG, IL-1ß and IL-6 were upregulated in ICQG, AG, NSAG and NSG (P < 0.05). In addition, IL-18 was upregulated in AG (P < 0.01), and IL-18, MMP-13 and TNF-α were upregulated in NSAG (P < 0.05). Compared with ICQG, IL-1ß, IL-18, MMP-13 and TNF-α were upregulated in NSAG (P < 0.05), and IL-1ß and IL-18 were upregulated in AG (P < 0.05). Conclusion: The combination of PRP and ICQ can alleviate inflammatory responses in cartilage, promote chondrocyte regeneration and facilitate matrix tissue repair. Compared with single interventions, a synergistic effect is observed.

Autocatalytic bifunctional supramolecular hydrogels for osteoporotic bone repair.

Conventional bone scaffolds, which are mainly ascribed to highly active osteoclasts and an inflammatory microenvironment with high levels of reactive oxygen species and pro-inflammatory factors, barely satisfy osteoporotic defect repair. Herein, multifunctional self-assembled supramolecular fiber hydrogels (Ce-Aln gel) consisting of alendronate (Aln) and cerium (Ce) ions were constructed for osteoporotic bone defect repair. Based on the reversible interaction and polyvalent cerium ions, the Ce-Aln gel, which was mainly composed of ionic coordination and hydrogen bonds, displayed good injectability and autocatalytic amplification of the antioxidant effect. In vitro studies showed that the Ce-Aln gel effectively maintained the biological function of osteoblasts by regulating redox homeostasis and improved the inflammatory microenvironment to enhance the inhibitory effect on osteoclasts. Ribonucleic acid (RNA) sequencing further revealed significant downregulation of various metabolic pathways, including apoptosis signaling, hypoxia metabolism and tumor necrosis factor-alpha (TNF-α) signaling via the nuclear factor kappa-B pathway after treatment with the Ce-Aln gel. In vivo experiments showed that the clinical drug-based Ce-Aln gel effectively promoted the tissue repair of osteoporotic bone defects by improving inflammation and inhibiting osteoclast formation at the defect. Notably, in vivo systemic osteoporosis was significantly ameliorated, highlighting the strong potential of clinical translation for precise therapy of bone defects.

Construction of 2-Substituted-3-aryl Benzofurans and Indoles through an Acid-Catalyzed Cascade Intramolecular Friedel-Crafts Reaction/Rearrangement/Aromatization Process.

We present here a new method for the synthesis of 2-substituted-3-aryl benzoheterocycles through a more challenging constrained [1,5]-type Friedel-Crafts reaction/rearrangement and aromatization process. By using the readily available 2-aryoxy-1,3-indandiones and 2-arylamino-1,3-indandiones, a range of 2-substituted-3-aryl benzofurans and indoles were prepared in good to excellent yields (yields up to 86%) under the catalysis of CF3SO3H or Sm(OTf)3. Compared with previous methods for constructing similar structures, this approach offers several advantages, including the use of easily accessible starting materials, mild reaction conditions, high yield, excellent regio- and diastereoselectivity, and a broad substrate scope.

Correction: Chen et al. Bromelain Ameliorates Atherosclerosis by Activating the TFEB-Mediated Autophagy and Antioxidant Pathways. Antioxidants 2023, 12, 72.

In the original publication [...].

Advances in the investigation of N6-isopentenyl adenosine i6A RNA modification.

Prenylation (isopentenylation), a key post-transcriptional modification with a hydrophobic prenyl group onto the biomacromolecules such as RNA and proteins, influences their localization and function. Prenyltransferases mediate this process, while cytokinin oxidases degrade the prenylated adenosine in plants. This review summarizes current progress in detecting prenylation modifications in RNA across species and their effects on protein synthesis. Advanced methods have been developed to label and study these modifications in vitro and in vivo, despite challenges posed by the inert chemical properties of prenyl groups. Continued advancements in bioorthogonal chemistry promise new tools for understanding the precise biological functions of prenylated RNA modifications and other related proteins.

Functionalized Thienopyrazines on NiOx Film as Self-Assembled Monolayer for Efficient Tin-Perovskite Solar Cells Using a Two-Step Method.

Three functionalized thienopyrazines (TPs), TP-MN (1), TP-CA (2), and TPT-MN (3) were designed and synthesized as self-assembled monolayers (SAMs) deposited on the NiOx film for tin-perovskite solar cells (TPSCs). Thermal, optical, electrochemical, morphological, crystallinity, hole mobility, and charge recombination properties, as well as DFT-derived energy levels with electrostatic surface potential mapping of these SAMs, have been thoroughly investigated and discussed. The structure of the TP-MN (1) single crystal was successfully grown and analyzed to support the uniform SAM produced on the ITO/NiOx substrate. When we used NiOx as HTM in TPSC, the device showed poor performance. To improve the efficiency of TPSC, we utilized a combination of new organic SAMs with NiOx HTM, the TPSC device exhibited the highest PCE of 7.7% for TP-MN (1). Hence, the designed NiOx/TP-MN (1) acts as a new model system for the development of efficient SAM-based TPSC. To the best of our knowledge, the combination of organic SAMs with anchoring CN/CN or CN/COOH groups, and NiOx HTM for TPSC has never been reported elsewhere. The TPSC device based on the NiOx/TP-MN bilayer exhibits great enduring stability for performance, retaining ~80% of its original value for shelf storage over 4000 h.

Chiral Herbicide Fluorochloridone: Absolute Configuration, Stereoselective Bioactivity, Toxicity, and Degradation in the Potatoes.

Fluorochloridone (FLC) is a chiral herbicide that has four stereoisomers. This study systematically assessed the stereoselectivity of FLC to reveal the selective environmental behavior of its four isomers. Absolute configuration confirmation, evaluation of stereoselective bioactivity toward monocotyledonous and dicotyledonous weeds, toxicity to Danio rerio, and the stereoselective degradation in the potato system under field conditions of FLC were conducted. The four FLC stereoisomers were effectively separated on a superchiral S-AD column. The absolute configurations of the four stereoisomers of FLC were confirmed as (-)-(3S, 4S), (+)-(3S, 4R), (-)-(3R, 4S), and (+)-(3R, 4R)-FLC using single-crystal X-ray diffraction. The activities of the four stereoisomers were in the order of (-)-(3S, 4S)-FLC > (+)-(3R, 4R)-FLC > (+)-(3S, 4R)-FLC > (-)-(3R, 4S)-FLC, and the rate of selective degradation were in the order of (-)-(3R, 4S)-FLC > (+)-(3R, 4R)-FLC > (-)-(3S, 4R)-FLC > (+)-(3S, 4S)-FLC. The toxicity of the isomers were in the order of (-)-(3R, 4S)-FLC > (+)-(3R, 4R)-FLC > (-)-(3S, 4S)-FLC > (+)-(3S, 4R). Based on the results of bioactivity, toxicity, and degradation behavior assessments, the stereoisomer mixture containing (3R,4R)-FLC and (3S,4S)-FLC was concluded to be a better option than racemic FLC for increasing bioactivity and reducing usage.

Tumor-intrinsic IFNα and CXCL10 are critical for immunotherapeutic efficacy by recruiting and activating T lymphocytes in tumor microenvironment.

Tumor immunotherapies targeting PD-(L)1 exhibit anti-tumor efficacy in only 10-30% of patients with various cancers. Literature has demonstrated that a "hot tumor" which contains high T lymphocytes in the tumor microenvironment exhibits a better response to immunotherapies than a "cold tumor." This study aimed to investigate whether tumor-intrinsic IFNα and CXCL10 determine the recruitment and activation of CD8+ T cells to become "hot tumor." In this study, we found that CXCL10 overexpressed in a variety of tumors including lung, colon, and liver tumors with a correlation with PD-L1. High PD-L1 and CXCL10 are associated with better survival rates in tumor patients receiving immunotherapies. IFNs-downstream transcriptional factor IRF-1 and STAT1 were correlated with PD-L1 and CXCL10 expression. We demonstrated that IRF-1 and STAT1 were both bound with the promoters of PD-L1 and CXCL10, sharing the same signaling pathway and determining IFNs-mediated PD-L1 and CXCL10 expression. In addition, IFNα significantly increased activation marker IFNγ in PBMCs, promoting M1 type monocyte differentiation, CD4+ T, and CD8+ T cell activation. Particularly, we found that CD8+ T lymphocytes abundantly expressed CXCR3, a receptor of CXCL10, by flow cytometry, indicating that tumor-intrinsic CXCL10 potentially recruited CD8+ T in tumor microenvironment. To demonstrate the hypothesis, immunotherapy-sensitive CT26 and immunotherapy-resistant LL/2 were used and we found that CT26 cells exhibited higher IFNα, IFNγ, CXCL10, and PD-L1 levels compared to LL/2, leading to higher IFNγ expression in mouse splenocytes. Moreover, we found that CD8+ T cells were recruited by CXCL10 in vitro, whereas SCH546738, an inhibitor of CXCR3, inhibited T cell migration and splenocytes-mediated anti-tumor effect. We then confirmed that CT26-derived tumor was sensitive to αPD-L1 immunotherapy and LL/2-tumor was resistant, whereas αPD-L1 significantly increased T lymphocyte activation marker CD107a in CT26-derived BALB/c mice. In conclusion, this study revealed that CXCL10 expression is correlated with PD-L1 in tumors, sharing the same signaling pathway and associating with better immunotherapeutic efficacy. Further evidence in the syngeneic tumor models demonstrated that immunotherapy-sensitive CT26 intrinsically exhibited higher IFNα and CXCL10 compared to immunotherapy-resistant LL/2 to recruit and activate CD8+ T cells in the tumor microenvironment, exhibiting "hot tumor" characteristic of sensitizing αPD-L1 immunotherapies.

Fluorinated Titanium Oxide (TiO2-xFx) Nanospindles as Ultrasound-Triggered Pyroptosis Inducers to Boost Sonodynamic Immunotherapy.

Pyroptosis is an inflammatory form of programmed cell death associated with the immune system that can be induced by reactive oxygen species (ROS). As a therapeutic strategy with better penetration depth, sonodynamic therapy (SDT) is expected to induce pyroptosis of cancer cells and boost the immune response. However, it is still a limited problem to precisely adjust the structure of sonosensitizers to exhibit satisfactory sono-catalytic properties. Herein, fluorinated titanium oxide (TiO2-xFx) sonosensitizers were developed to induce pyroptosis under ultrasound (US) to boost antitumor immune responses, enabling highly effective SDT. On the one hand, the introduction of F atoms significantly reduced the adsorption energy of TiO2-xFx for oxygen and water, which is conducive to the occurrence of sono-catalytic reactions. On the other hand, the process of F replacing O increased the oxygen vacancies of the sonosensitizer and shortened the band gap, which enabled powerful ROS generation ability under US stimulation. In this case, large amounts of ROS could effectively kill cancer cells by inducing mitochondrial damage and disrupting oxidative homeostasis, leading to significant cell pyroptosis. Moreover, SDT treatment with TiO2-xFx not only suppressed tumor proliferation but also elicited robust immune memory effects and hindered tumor recurrence. This work highlighted the importance of precisely regulating the structure of sonosensitizers to achieve efficient ROS generation for inducing pyroptosis, which sets the stage for the further development of SDT-immunotherapy.

A fluorescence aptamer sensor utilizing WS2 nanosheets for sensitive detection of patulin: enhanced specificity and wide applicability.

A tungsten disulfide (WS2) nanosheet-based aptamer sensor was developed to detect patulin (PAT). The 5'-end of the PAT aptamer was modified with a cyanine 3 (Cy3) fluorophore, which self-assembled on WS2 nanosheets. The interaction between the Cy3 fluorophore at the 5'-end of the PAT aptamer and the WS2 nanosheets resulted in reduced fluorescence (FL) intensity due to fluorescence resonance energy transfer (FRET). The introduction of PAT into this sensing system led to hybridization with the PAT aptamer, forming a G-quadruplex/PAT complex with low affinity for the WS2 nanosheet surface. This hybridization increased the distance between the Cy3 fluorophore and the WS2 nanosheets, inhibiting FRET and producing a strong FL signal. Under optimal experimental conditions, the FL intensity of the sensing system demonstrated an excellent linear correlation with PAT concentrations ranging from 0.5 to 40.0 ng mL-1, and it achieved a detection limit (S/N = 3) of 0.23 ng mL-1. This sensing system offers enhanced specificity for PAT detection and has the potential for broad application in detecting other toxins by substituting the sequence of the recognition aptamer.

Fabrication of pH-stimuli hydrogel as bioactive materials for wound healing applications.

Hydrogels exhibit exceptional suitability as wound dressing due to their remarkable three-dimensional (3D) characteristics. Here, we have reported the fabrication of hydrogels from biopolymers carboxymethyl cellulose (CMC), polyvinyl alcohol (PVA), and gelatin via a simple blending method to mimic the natural extracellular matrix. Scanning electron microscopy (SEM), water contact meters (WCM), and Fourier-transform infrared spectroscopy (FTIR) were used to evaluate the chemical structural, morphological, and wettability behavior. The wetting and degradation behavior were also found to be different for different formulations (Min. (51.60o) and Max. (113.60o)) and (Min. (38.82 mg) and Max. (3.72 mg)), respectively. Swelling was investigated in different media, including phosphate buffer saline solution (PBS) and aqueous media. It was observed that the hydrogel displayed the highest degree of swelling in an aqueous medium (Min. (597.32-1121.49 %) and Max. (1089.51-2139.73 %)) compared to PBS media (Min. (567.01-1021.85 %) and Max. (899.13-1639.17 %)). The release of Neomycin was studied in a PBS medium via the Franz diffusion method at 37 °C. The maximal release in various media demonstrated pH-responsive behavior. The viability and proliferation of fibroblast (3T3) cell lines were examined in vitro to evaluate cytocompatibility. Human Embryonic Kidney (HEK) 293 cells were used to evaluate the hydrogels' ability to promote vascularization and angiogenesis. Therefore, the data demonstrate that hydrogels that have been manufactured have qualities that make them promising for use as wound dressings in wound healing applications.

A-Site Engineering of the High-Entropy Perovskite Pr0.4La0.4Ba0.4Sr0.4Ca0.4Fe2O5+δ Cathode for Intermediate-Temperature SOFCs.

Mixed-oxygen ionic and electronic conduction is crucial for the cathode materials of solid oxide fuel cells, ensuring high efficiency and low-temperature operation. However, the electronic and oxygen ionic conductivity of traditional Fe-based layered perovskite cathode materials is low, resulting in insufficient oxygen reduction reactivity. Herein, a type of high-entropy perovskite oxide consisting of five equimolar metals, Pr0.4La0.4Ba0.4Sr0.4Ca0.4Fe2O5+δ (PLBSCF), a high-performance cobalt-free cathode derived from the PrBaFe2O5+δ (PBF), is proposed. Such A-site engineering could not only increase the oxygen vacancy concentration of PLBSCF but also give higher conductivity than PBF, thus significantly reducing the polarization impedance of the symmetric cell to only 0.052 Ω·cm2 at 750 °C. The good output performance of a single cell is also realized. The peak power density of the single cell with PLBSCF-Ce0.9Gd0.1O2-δ (GDC) as the cathode at 750 °C was 0.853 W·cm-2. Additionally, the single cell with the PLBSCF cathode exhibits a good durable performance of 100 h at 750 °C. Combining the distribution of relaxation time analysis, it can be seen that the enhancement of the oxygen reduction reaction is due to the reduction of intermediate-frequency and low-frequency resistance, indicating an improvement in the charge transfer process and adsorption/dissociation process of molecular oxygen.

Giant cell carcinoma of the urinary bladder : Clinicopathologic analysis and oncological outcomes.

We present the clinicopathological features of 23 cases of the giant cell subtype of urothelial carcinoma, a rare subtype of bladder cancer recognized in the current World Health Organization classification of urological tumors. Histologically, the architectural pattern of the tumor varied from infiltrating to the solid expansile pleomorphic tumor with giant, bizarre, anaplastic cells. Typical or atypical mitotic figures were frequently present in all cases. Between 10 and 30% of the tumor had a giant cell component. All cases were associated with conventional high-grade urothelial carcinoma, with areas of squamous cell divergent differentiation and micropapillary carcinoma present in six and two cases, respectively. In one case each had sarcomatoid, nested, small cell, or glandular divergent differentiation. At diagnosis, 35% of patients had advanced disease and 12% had distant metastases. When comparing giant cell urothelial carcinoma with conventional urothelial carcinoma in a matched analysis, differences in overall and cancer-specific survival were observed, particularly in the T1 stage category. Immunohistochemical staining showed a similar profile of urothelial lineage with frequent positive expression of uroplakin II, GATA3, CK20, CK7, and S100P in both giant cell and conventional urothelial carcinomas. High Ki67 proliferation (range, 60-90%; mean, 71%) and nuclear p53 accumulation (mutant profile; range, 50-90%; mean, 64%) were observed. Using the 22C3 assay, the expression of PD-L1 was found to be variable in two cases, and beta-HCG was negative. In conclusion, giant cell carcinoma is a subtype of urothelial carcinoma associated with advanced clinical stage and a trend to lower survival rates.

Comprehensive Characterization of Intraductal Oncocytic Papillary Neoplasm of the Pancreas: A Systematic and Critical Review.

Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is a recently recognized pancreatic tumor. Here, we aimed to determine its most essential features with the systematic review tool. PubMed, Scopus, and Embase were searched for studies reporting data on pancreatic IOPN. The clinicopathologic, immunohistochemical, and molecular data were extracted and summarized. Then, a comparative analysis of the molecular alterations of IOPN with those of pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasm from reference cohorts (including The Cancer Genome Atlas) was conducted. The key findings from 414 IOPNs were as follows: 1) The male-to-female ratio was 1.5:1. Pancreatic head was the most common site (131/237; 55.3%), but a diffuse tumor extension involving more than one pancreatic segment was described in about 1 out of 5 cases (49/237; 20.6%). The mean size was 45.5 mm. An associated invasive carcinoma was present in 50% of cases (168/336). In those cases, most tumors were pT1 or pT2 and pN0 (>80%), and vascular invasion was uncommon (20.6%). Regarding survival, more than 90% of patients were alive after surgical resection. 2) Immunohistochemical and molecular features were as follows. The most commonly expressed mucins were MUC5AC (110/112; 98.2%) and MUC6 (78/84; 92.8%). Compared with pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasm, the classic pancreatic drivers KRAS, TP53, CDKN2A, SMAD4, and GNAS were less altered in IOPN (P < .01). Moreover, fusions involving PRKACA or PRKACB gene were detected in all of the 68 cases examined, with PRKACB::ATP1B1 being the most common (27/68 cases; 39.7%). These genomic events emerged as an entity-defining molecular alteration of IOPN (P < .01). Thus, such fusions represent a promising biomarker for diagnostic purposes. Recent evidence also suggests their role in influencing the acquisition of oncocytic morphology. IOPN is a distinct pancreatic neoplasm with specific clinicopathologic and molecular features. Considering the clinical or prognostic implications, its recognition is essential for pathologists and, ultimately, patients' management.

Piezoelectricity in wide bandgap semiconductor 2D crystal GaN nanosheets.

Gallium nitride (GaN) exhibits various potential applications in optics and optoelectronics due to its outstanding physical characteristics, including a wide direct bandgap, strong deep-ultraviolet emission, and excellent electron transport properties. However, research on the piezoelectric and related properties of GaN nanosheets are scarce, as previous small-scale GaN investigations have mainly concentrated on nanowires and nanotubes. Here, we report a strategy for growing 2D GaN nanosheets using chemical vapor deposition on Ga/W liquid-phase substrates. Additionally, utilizing scanning probe techniques, it has been observed that 700 nm-thick GaN nanosheets demonstrate a piezoelectric constant of deff33 = 1.53 ± 0.21 pm V-1 and possess the capability to effectively modulate the Schottky barrier. The piezoelectric characteristics of 2D GaN are offering new options for innovative applications in various fields, including energy harvesting, electronics, sensing, and communications.