Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

Rubisco small subunit (RbCS) is co-opted by potyvirids as the scaffold protein in assembling a complex for viral intercellular movement.

Plant viruses must move through plasmodesmata (PD) to complete their life cycles. For viruses in the Potyviridae family (potyvirids), three viral factors (P3N-PIPO, CI, and CP) and few host proteins are known to participate in this event. Nevertheless, not all the proteins engaging in the cell-to-cell movement of potyvirids have been discovered. Here, we found that HCPro2 encoded by areca palm necrotic ring spot virus (ANRSV) assists viral intercellular movement, which could be functionally complemented by its counterpart HCPro from a potyvirus. Affinity purification and mass spectrometry identified several viral factors (including CI and CP) and host proteins that are physically associated with HCPro2. We demonstrated that HCPro2 interacts with both CI and CP in planta in forming PD-localized complexes during viral infection. Further, we screened HCPro2-associating host proteins, and identified a common host protein in Nicotiana benthamiana-Rubisco small subunit (NbRbCS) that mediates the interactions of HCPro2 with CI or CP, and CI with CP. Knockdown of NbRbCS impairs these interactions, and significantly attenuates the intercellular and systemic movement of ANRSV and three other potyvirids (turnip mosaic virus, pepper veinal mottle virus, and telosma mosaic virus). This study indicates that a nucleus-encoded chloroplast-targeted protein is hijacked by potyvirids as the scaffold protein to assemble a complex to facilitate viral movement across cells.

Impaired intestinal FXR signaling is involved in aberrant stem cell function leading to intestinal failure-associated liver disease in pediatric patients with short bowel syndrome.

Intestinal failure-associated liver disease (IFALD) is a serious complication of long-term parenteral nutrition in patients with short bowel syndrome (SBS), and is the main cause of death in SBS patients. Prevention of IFALD is one of the major challenges in the treatment of SBS. Impairment of intestinal barrier function is a key factor in triggering IFALD, therefore promoting intestinal repair is particularly important. Intestinal repair mainly relies on the function of intestinal stem cells (ISC), which require robust mitochondrial fatty acid oxidation (FAO) for self-renewal. Herein, we report that aberrant LGR5+ ISC function in IFALD may be attributed to impaired farnesoid X receptor (FXR) signaling, a transcriptional factor activated by steroids and bile acids. In both surgical biopsies and patient-derived organoids (PDOs), SBS patients with IFALD represented lower population of LGR5+ cells and decreased FXR expression. Moreover, treatment with T-ßMCA in PDOs (an antagonist for FXR) dose-dependently reduced the population of LGR5+ cells and the proliferation rate of enterocytes, concomitant with decreased key genes involved in FAO including CPT1a. Interestingly, however, treatment with Tropifexor in PDOs (an agonist for FXR) only enhanced FAO capacity, without improvement in ISC function and enterocyte proliferation. In conclusion, these findings suggested that impaired FXR may accelerate the depletion of LGR5 + ISC population through disrupted FAO processes, which may serve as a new potential target of preventive interventions against IFALD for SBS patients.

A distinct subset of urothelial cells with enhanced EMT features promotes chemotherapy resistance and cancer recurrence by increasing COL4A1-ITGB1 mediated angiogenesis.

Drug resistance and tumor recurrence remain clinical challenges in the treatment of urothelial carcinoma (UC). However, the underlying mechanism is not fully understood. Here, we performed single-cell RNA sequencing and identified a subset of urothelial cells with epithelial-mesenchymal transition (EMT) features (EMT-UC), which is significantly correlated with chemotherapy resistance and cancer recurrence. To validate the clinical significance of EMT-UC, we constructed EMT-UC like cells by introducing overexpression of two markers, Zinc Finger E-Box Binding Homeobox 1 (ZEB1) and Desmin (DES), and examined their histological distribution characteristics and malignant phenotypes. EMT-UC like cells were mainly enriched in UC tissues from patients with adverse prognosis and exhibited significantly elevated EMT, migration and gemcitabine tolerance in vitro. However, EMT-UC was not specifically identified from tumorous tissues, certain proportion of them were also identified in adjacent normal tissues. Tumorous EMT-UC highly expressed genes involved in malignant behaviors and exhibited adverse prognosis. Additionally, tumorous EMT-UC was associated with remodeled tumor microenvironment (TME), which exhibited high angiogenic and immunosuppressive potentials compared with the normal counterparts. Furthermore, a specific interaction of COL4A1 and ITGB1 was identified to be highly enriched in tumorous EMT-UC, and in the endothelial component. Targeting the interaction of COL4A1 and ITGB1 with specific antibodies significantly suppressed tumorous angiogenesis and alleviated gemcitabine resistance of UC. Overall, our findings demonstrated that the driven force of chemotherapy resistance and recurrence of UC was EMT-UC mediated COL4A1-ITGB1 interaction, providing a potential target for future UC treatment.

Comparative transcriptomic analysis delineates adaptation strategies of Rana kukunoris toward cold stress on the Qinghai-Tibet Plateau.

BACKGROUND: Cold hardiness is fundamental for amphibians to survive during the extremely cold winter on the Qinghai-Tibet plateau. Exploring the gene regulation mechanism of freezing-tolerant Rana kukunoris could help us to understand how the frogs survive in winter. RESULTS: Transcriptome of liver and muscle of R. kukunoris collected in hibernation and spring were assisted by single molecule real-time (SMRT) sequencing technology. A total of 10,062 unigenes of R. kukunoris were obtained, and 9,924 coding sequences (CDS) were successfully annotated. Our examination of the mRNA response to whole body freezing and recover in the frogs revealed key genes concerning underlying antifreeze proteins and cryoprotectants (glucose and urea). Functional pathway analyses revealed differential regulated pathways of ribosome, energy supply, and protein metabolism which displayed a freeze-induced response and damage recover. Genes related to energy supply in the muscle of winter frogs were up-regulated compared with the muscle of spring frogs. The liver of hibernating frogs maintained modest levels of protein synthesis in the winter. In contrast, the liver underwent intensive high levels of protein synthesis and lipid catabolism to produce substantial quantity of fresh proteins and energy in spring. Differences between hibernation and spring were smaller than that between tissues, yet the physiological traits of hibernation were nevertheless passed down to active state in spring. CONCLUSIONS: Based on our comparative transcriptomic analyses, we revealed the likely adaptive mechanisms of R. kukunoris. Ultimately, our study expands genetic resources for the freezing-tolerant frogs.

Cobalt-Catalyzed Domino Transformations via Enantioselective C-H Activation/Nucleophilic [3 + 2] Annulation toward Chiral Bridged Bicycles.

Selective synthesis of chiral bridged (hetero)bicyclic scaffolds via asymmetric C-H activation constitutes substantial challenges due to the multiple reactivities of strained bicyclic structures. Herein, we develop the domino transformations through an unprecedented cobalt-catalyzed enantioselective C-H activation/nucleophilic [3 + 2] annulation with symmetrical bicyclic alkenes. The methods offer straightforward access to a wide range of chiral molecules bearing [2.2.1]-bridged bicyclic cores with four and five consecutive stereocenters in a single step. Two elaborate salicyloxazoline (Salox) ligands were synthesized based on the rational design and mechanistic understanding. The well-defined chiral pockets generated from asymmetric coordination around the trivalent cobalt catalyst direct the orientation of bicyclic alkenes, leading to excellent enantioselectivity.

Observation on Microenvironment Changes of Dynamic Catalysts in Acidic CO2 Reduction.

Electrochemical CO2 reduction reaction (CO2RR) in acid can solve alkalinity issues while highly corrosive and reductive acidic electrolytes usually cause catalyst degradation. Inhibiting catalyst degradation is crucial for the stability of acidic CO2RR. Here, we reveal the microenvironment changes of dynamic Bi-based catalysts and develop a pulse chronoamperometry (CA) strategy to improve the stability of acidic CO2RR. In situ fluorescence mappings show that the local pH changes from neutral to acid, and the in situ Raman spectra reveal the dynamic evolution of interfacial water structures in the microenvironment. We propose that the surface charge properties of dynamic catalysts affect the competitive adsorption of K+ and protons, thereby causing the differences in local pH and CO2RR intermediate adsorption. We also develop a pulse CA strategy to reactivate catalysts, and the stability of acidic CO2RR is improved by 2 orders of magnitude for 100 h operation, which is higher than most reports on the stability of acidic CO2RR. This work gives insights on how microenvironment changes affecting the stability of acidic CO2RR, and provides guidance for designing stable catalysts in acidic electrolytes.

Peptidase inhibitor 16 promotes proliferation of pancreatic ductal adenocarcinoma cells through OASL signaling.

Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive cancer with a poor prognosis and a 5-year survival rate of less than 11%. As a member of the CAP superfamily of proteins, the role of peptidase inhibitor 16 (Pi16) in tumor progression is still unclear. Immunohistochemistry and quantitative RT-PCR methods were used to detect the expression levels of Pi16 protein and mRNA in PDAC patients. CRISPR/Cas9 technology was used to knock out the expression of Pi16 in PDAC cell lines. In vivo and in vitro experiments were used to verify the effect of Pi16 on PDAC proliferation ability. By RNA sequencing, we found that oligoadenylate synthetase L (OASL) can serve as a potential downstream target of Pi16. The expression of Pi16 was higher in PDAC tissues than in matched adjacent tissues. High expression of Pi16 was associated with PDAC progression and poor prognosis. Overexpression of Pi16 could promote the proliferation of PDAC cells in vitro and in vivo. Bioinformatics analysis and coimmunoprecipitation assays showed that Pi16 could bind to OASL. Moreover, the functional recovery test confirmed that Pi16 could promote the proliferation of PDAC via OASL. Our present study demonstrates that Pi16 might participate in the occurrence and development of PDAC by regulating cell proliferation by binding to OASL, indicating that Pi16 might be a promising novel therapeutic target for PDAC.

Gas-Liquid Interface Route to Hybrid Copper Bromine Perovskite Single-Crystal Membrane with Dielectric Transitions and Ferromagnetic Exchanges.

Single-crystal membranes (SCMs) show great promise in the fields of sensors, light-emitting diodes, and photodetection. However, the growth of a large-area single-crystal membranes is challenging. We report a new organic-inorganic SCMs [HCMA]2CuBr4 (HCMA = cyclohexanemethylamine) crystallized at the gas-liquid interface. It also has low-temperature ferromagnetic order, high-temperature dielectric anomalies, and narrow band gap indirect semiconductor properties. Specifically, the reversible phase transition of the compound occurs at 350/341 K on cooling/heating and exhibits dielectric anomalies and stable switching performance near the phase transition temperature. The ferromagnetic exchange interaction in the inorganic octahedra and the organic layer enables ferromagnetic ordering at low-temperature 10 K. Finally, the single crystal exhibits an indirect semiconducting property with a narrow band gap of 0.99 eV. Such rich multichannel physical properties make it a potential application in photodetection, information storage and sensors.

Three-Dimensional Bimetallic Ammonium K-Eu Nitrate with a Rare (6,6)-Connected Ion Topology Exhibiting Structural Phase Transition and Photoluminescence Properties.

A K-Eu bimetallic ammonium metal-nitrate three-dimensional (3D) framework incorporating R-N-methyl-3-hydroxyquinuclidine, (RM3HQ)2KEu(NO3)6 (RM3HQ = R-N-methyl-3-hydroxyquinuclidine, 1), was characterized and reported. Distinguishing from the former hybrid rare-earth double perovskites, 1 adopts a mixed corner- and face-sharing K+/Eu3+-centered polyhedral connectivity to form a 3D inorganic framework, showing a rare (6, 6)-connected ion topology with a 66 framework. Notably, 1 exhibits clear phase transition, and the switchable thermodynamic behavior is confirmed by variable-temperature dielectric measurements and second-harmonic generation response. Moreover, 1 also shows photoluminescence properties. The activator Eu3+ plays a crucial role in this process, leading to a significant narrow emission at 592 nm with a photoluminescence quantum yield (PLQY) of 20.76%. The fluorescence lifetime (FLT) of 1 is 4.32 ms. This finding enriches the bimetallic hybrid system for potential electronic and/or luminescence applications.

Palladium-catalyzed (Z)-selective allylation of phosphine oxides with vinylethylene carbonates to construct phosphorus allyl alcohols.

Allylphosphine oxide compounds are important building blocks with broad applications in organic synthesis and pharmaceutical science. Herein, we report an unprecedented palladium-catalyzed allylation of phosphine oxides with vinylethylene carbonates, producing various phosphorus allyl alcohols in excellent yields with high Z-selectivity. In addition, gram-scale synthesis and further functional group transformations demonstrate the practical utility of this synthetic method.

Sustainable Blue Foods from Rice-Animal Coculture Systems.

Global interest grows in blue foods as part of sustainable diets, but little is known about the potential and environmental performance of blue foods from rice-animal coculture systems. Here, we compiled a large experimental database and conducted a comprehensive life cycle assessment to estimate the impacts of scaling up rice-fish and rice-crayfish systems in China. We find that a large amount of protein can be produced from the coculture systems, equivalent to ∼20% of freshwater aquaculture and ∼70% of marine wild capture projected in 2030. Because of the ecological benefits created by the symbiotic relationships, cocultured fish and crayfish are estimated to be carbon-negative (-9.8 and -4.7 kg of CO2e per 100 g of protein, respectively). When promoted at scale to displace red meat, they can save up to ∼98 million tons of greenhouse gases and up to ∼13 million hectares of farmland, equivalent to ∼44% of China's total rice acreage. These results suggest that rice-animal coculture systems can be an important source of blue foods and contribute to a sustainable dietary shift, while reducing the environmental footprints of rice production. To harvest these benefits, robust policy supports are required to guide the sustainable development of coculture systems and promote healthy and sustainable dietary change.

Soil's Hidden Power: The Stable Soil Organic Carbon Pool Controls the Burden of Persistent Organic Pollutants in Background Soils.

Persistent organic pollutants (POPs) tend to accumulate in cold regions by cold condensation and global distillation. Soil organic matter is the main storage compartment for POPs in terrestrial ecosystems due to deposition and repeated air-surface exchange processes. Here, physicochemical properties and environmental factors were investigated for their role in influencing POPs accumulation in soils of the Tibetan Plateau and Antarctic and Arctic regions. The results showed that the soil burden of most POPs was closely coupled to stable mineral-associated organic carbon (MAOC). Combining the proportion of MAOC and physicochemical properties can explain much of the soil distribution characteristics of the POPs. The background levels of POPs were estimated in conjunction with the global soil database. It led to the proposition that the stable soil carbon pools are key controlling factors affecting the ultimate global distribution of POPs, so that the dynamic cycling of soil carbon acts to counteract the cold-trapping effects. In the future, soil carbon pool composition should be fully considered in a multimedia environmental model of POPs, and the risk of secondary release of POPs in soils under conditions such as climate change can be further assessed with soil organic carbon models.

Proteomics identifies hypothermia induced adiponectin protects corneal endothelial cells via AMPK mediated autophagy in phacoemulsification.

AIM: To explore the molecular mechanism underlying the protective effect of hypothermic perfusion on the corneal endothelium during phacoemulsification. METHODS: Phacoemulsification was performed on New Zealand white rabbits. Perfusate at different temperatures was used during the operation, and the aqueous humor was collected for proteomic sequencing after the operation. Corneal endothelial cell injury was simulated by a corneal endothelial cell oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro. Flow cytometry and evaluation of fluorescent LC3B puncta were used to detect apoptosis and autophagy, and western blotting was used to detect protein expression. RESULTS: A total of 381 differentially expressed proteins were identified between the two groups. In vitro, 4 ℃ hypothermia significantly reduced apoptosis and promoted autophagy. Apoptosis increased after autophagy was inhibited by 3-Methyladenine (3-MA). Furthermore, adiponectin (ADIPOQ) knockdown inhibited phospho-AMPK and blocked the protective effect of hypothermia on corneal endothelial cells. CONCLUSIONS: We investigated the differential expression of proteins between the hypothermia group and normothermia group by proteomics. Moreover, hypothermia-induced ADIPOQ can reduce apoptosis by promoting AMPK-mediated autophagy.

Morphological and functional characteristics of the meibomian gland in pediatric patients with epiblepharon.

BACKGROUND: To observe morphologic and functional changes in meibomian glands in pediatric patients with and without lower eyelid epiblepharon. METHODS: In this prospective observation study, 55 eyes of 55 patients( 24 males, 31 females; mean age ± SD,9.82 ± 2.59 years; range 6-14 years) and 60 eyes of 60 controls ( 32 males, 28 females; mean age ± SD,10.57 ± 2.75 years; range 6-14 years) were included. The following tests were performed: eyelid margin abnormality by slit-lamp examination, measurement of noninvasive keratographic break-up time (NIKBUT), grading of absence of meibomian gland (meibography score) assessed with noncontact meibography, morphologic changes of meibomian glands (thinning, dilatation and distortion), tear production by the Schirmer 1 test, and grading of meibum quality and meibomian gland expressibility. RESULTS: The morphologic changes in meibomian glands were more common in the epiblepharon group (56.36%) than in the control group (28.33%) (p = 0.002). The meibum quality was worse in the epiblepharon group than in the control group (p = 0.009), and the NIKBUT was significantly shorter in the epiblepharon group than in the control group (p = 0.012). There was no significant difference in the Schirmer 1 test, meibomian gland expressibility, eyelid margin abnormality score or total meibography score between the two groups. Morphologic changes in the meibomian glands in the upper eyelids (38.18%) were more common than those in the lower eyelids (20%) (p = 0.036) in the epiblepharon group, and the meibography score was higher in the upper eyelids than in the lower eyelids (p = 0.001). CONCLUSION: There are morphological and functional changes in meibomian glands in pediatric patients with lower eyelid epiblepharon. Although the inverted eyelashes were located in the lower eyelid, morphological changes in the meibomian glands were more common in the upper eyelid.

Skin marker combined with surface-guided auto-positioning for breast DIBH radiotherapy daily initial patient setup: An optimal schedule for both accuracy and efficiency.

BACKGROUND AND PURPOSE: By employing three surface-guided radiotherapy (SGRT)-assisted positioning methods, we conducted a prospective study of patients undergoing SGRT-based deep inspiration breath-hold (DIBH) radiotherapy using a Sentine/Catalys system. The aim of this study was to optimize the initial positioning workflow of SGRT-DIBH radiotherapy for breast cancer. MATERIALS AND METHODS: A total of 124 patients were divided into three groups to conduct a prospective comparative study of the setup accuracy and efficiency for the daily initial setup of SGRT-DIBH breast radiotherapy. Group A was subjected to skin marker plus SGRT verification, Group B underwent SGRT optical feedback plus auto-positioning, and Group C was subjected to skin marker plus SGRT auto-positioning. We evaluated setup accuracy and efficiency using cone-beam computed tomography (CBCT) verification data and the total setup time. RESULTS: In groups A, B, and C, the mean and standard deviation of the translational setup-error vectors were small, with the highest values of the three directions observed in group A (2.4 ± 1.6, 2.9 ± 1.8, and 2.8 ± 2.1 mm). The rotational vectors in group B (1.8 ± 0.7°, 2.1 ± 0.8°, and 1.8 ± 0.7°) were significantly larger than those in groups A and C, and the Group C setup required the shortest amount of time, at 1.5 ± 0.3 min, while that of Group B took the longest time, at 2.6 ± 0.9 min. CONCLUSION: SGRT one-key calibration was found to be more suitable when followed by skin marker/tattoo and in-room laser positioning, establishing it as an optimal daily initial set-up protocol for breast DIBH radiotherapy. This modality also proved to be suitable for free-breathing breast cancer radiotherapy, and its widespread clinical use is recommended.

Alkaloid profiling of the new species Corydalis huangshanensis and other 13 medicinal plants in genus Corydalis.

INTRODUCTION: Corydalis DC., the largest genus of Papaveraceae, comprises numerous species known for their abundant alkaloid content and historical use in clinical medicine. Recently, a new species of genus Corydalis named Corydalis huangshanensis Lu Q. Huang & H. S. Peng was discovered in the Huangshan Mountains of Anhui Province, China. OBJECTIVE: To compare the chemical characteristics of C. huangshanensis and other 13 Corydalis species, aiming to elucidate the potential medicinal value of this new species. MATERIALS AND METHODS: The chemical constituents of C. huangshanensis and other 13 medicinal plants of genus Corydalis were analyzed using ultra-high-performance liquid chromatography Q-Exactive Plus hybrid quadrupole-Orbitrap mass spectrometer (Q-Orbitrap) mass technology. The differences in the alkaloids in the 14 species were distinguished by chemometrics. RESULTS: The mass spectrometry fragmentation information and relative content of 72 alkaloids were obtained. Orthogonal partial least squares discriminant analysis (OPLS-DA) and cluster heat mapping analysis showed that these 14 species were divided into two groups. The clustering relationship between C. huangshanensis and C. decumbens (Thunb.) Pers. was similar, exhibiting similar chemical compositions and characteristics. These results indicate the potential pharmacological effects of C. huangshanensis. CONCLUSION: This study enhances our understanding of the chemical classification of Corydalis and provides a basis for speculations on the medicinal value of C. huangshanensis.

Diesel degradation capability and environmental robustness of strain Pseudomonas aeruginosa WS02.

Petroleum hydrocarbon (PHC) degrading bacteria have been frequently discovered. However, in practical application, a single species of PHC degrading bacterium with weak competitiveness may face environmental pressure and competitive exclusion due to the interspecific competition between petroleum-degrading bacteria as well as indigenous microbiota in soil, leading to a reduced efficacy or even malfunction. In this study, the diesel degradation ability and environmental robustness of an endophytic strain Pseudomonas aeruginosa WS02, were investigated. The results show that the cell membrane surface of WS02 was highly hydrophobic, and the strain secreted glycolipid surfactants. Genetic analysis results revealed that WS02 contained multiple metabolic systems and PHC degradation-related genes, indicating that this strain theoretically possesses the capability of oxidizing both alkanes and aromatic hydrocarbons. Gene annotation also showed many targets which coded for heavy metal resistant and metal transporter proteins. The gene annotation-based inference was confirmed by the experimental results: GC-MS analysis revealed that short chain PHCs (C10-C14) were completely degraded, and the degradation of PHCs ranging from C15-C22 were above 90% after 14 d in diesel-exposed culture; Heavy metal (Mn2+, Pb2+ and Zn2+) exposure was found to affect the growth of WS02 to some extent, but not its ability to degrade diesel, and the degradation efficiency was still maintained at 39-59%. WS02 also showed a environmental robustness along with PHC-degradation performance in the co-culture system with other bacterial strains as well as in the co-cultured system with the indigenous microbiota in soil fluid extracted from a PHC-contaminated site. It can be concluded that the broad-spectrum diesel degradation efficacy and great environmental robustness give P. aeruginosa WS02 great potential for application in the remediation of PHC-contaminated soil.

A "Pincer" Type of Acridine-Triazole Fluorescent Dye for Iodine Detection by Both 'Naked-Eye' Colorimetric and Fluorometric Modes.

Iodine, primarily in the form of iodide (I-), is the bioavailable form for the thyroid in the human body. Both deficiency and excess intake of iodide can lead to serious health issues, such as thyroid disease. Selecting iodide ions among anions has been a significant challenge for decades due to interference from other anions. In this study, we designed and synthesized a new pincer-type acridine-triazole fluorescent probe (probe 1) with an acridine ring as a spacer and a triazole as a linking arm attached to two naphthol groups. This probe can selectively recognize iodide ions in a mixed solvent of THF/H2O (v/v, 9/1), changing its color from colorless to light yellow, making it suitable for highly sensitive and selective colorimetric and fluorescent detection in water systems. We also synthesized another molecular tweezer-type acridine-triazole fluorescent probe (probe 2) that exhibits uniform detection characteristics for iodide ions in the acetonitrile system. Interestingly, compared to probe 2, probe 1 can be detected by the naked eye due to its circulation effect, providing a simple method for iodine detection. The detection limit of probe 1 is determined to be 10-8 mol·L-1 by spectrometric titration and isothermal titration calorimetry measurements. The binding stoichiometry between probe 1 and iodide ions is calculated to be 1:1 by these methods, and the binding constant is 2 × 105 mol·L-1.

Malignant transformation of white sponge nevus: a case report of a novel keratin 4 mutation.

BACKGROUND: White Sponge Nevus (WSN) is traditionally considered a benign genetic disorder affecting the oral mucosa, primarily caused by pathogenic mutations in keratin 4 (KRT4) or keratin 13 (KRT13). Despite its benign nature, recent evidence has begun to question the malignant potential of WSN. CASE PRESENTATION: We report a case involving a 70-year-old man who presented with a white lesion on the right floor of his mouth. Initial diagnostic evaluations confirmed the lesion as WSN. Over a one-year follow-up, the lesion underwent malignant transformation, evolving into local epithelial moderate-to-severe dysplasia. Exome sequencing identified a novel insertion mutation in exon 1 of the KRT4 gene, resulting in a deletion-insertion amino acid mutation involving glycine. Single-cell RNA sequencing further revealed altered epithelial proliferation and differentiation dynamics within the lesion. CONCLUSIONS: This case not only expands the known genetic spectrum of KRT4 mutations associated with WSN but also provides preliminary evidence suggesting the malignant potential of WSN. The novel pathogenic mutation in KRT4 is postulated to alter epithelial proliferation and differentiation, thereby raising concerns about the malignant transformation of WSN. Further studies are warranted to confirm these findings.