Mindful self-care among oncology nurses in China: a latent profile analysis.

BACKGROUND: Oncology nurses are considered the group with the highest risk for moral distress, compassion fatigue and burnout. Mindful self-care may help oncology nurses improve their well-being and solve psychological problems. However, the investigation and in-depth analysis of mindful self-care among oncology nurses in China is lacking. OBJECTIVES: To identify heterogeneity groups of oncology nurses on mindful self-care ability and examine the sociodemographic correlation to these profiles. DESIGN: Cross-sectional descriptive study. PARTICIPANTS: The study was carried out among oncology nurses in two affiliated comprehensive hospitals and one affiliated oncology hospital. A total of 839 oncology nurses were enrolled in this survey. METHODS: From January to May 2023, a cross-sectional study was carried out among oncology nurses using convenient sampling. The subjects were given the brief Mindful Self-Care Scale (B-MSCS) and the General Demographic Information Questionnaire. Latent profile analysis using the Mplus 7.4 program was used to separate oncology nurses' mindful self-care into a variety of subgroups. The SPSS 25.0 statistical program was used to analyze the data. One-way ANOVA and the chi-square test were performed to compare the score of B-MSCS in each class and the difference in sociodemographic characteristics among the subgroups. Multinomial logistic regression was used to examine the influence of the sociodemographic variables on each class. RESULTS: The total score of the B-MSCS was 76.40 ± 13.19. The support structure dimension had the highest score, with an average mean value of 3.60, and physical care had the lowest score at 2.57. The findings of the latent profile analysis showed that respondents were divided into three classes, moderate mindful self-care(51.2%), low-low mindful relaxation(14.8%), and high-high mindfulness self-awareness(34.0%). Across scale scores and dimensions, three groups demonstrated statistically significant differences (p < 0.05). Univariate analysis revealed significant differences between the three profiles in terms of professional title, position, concern about self-care, interest in mindfulness, and experience with meditation (p < 0.05). Profile membership was predicted by 3 factors, namely, self-care status, interest in mindfulness, and experience with meditation. CONCLUSION: The mindful self-care among oncology nurses can be categorized into three latent profiles: moderate mindful self-care, low-low mindful relaxation, and high-high mindfulness self-awareness. Multinomial logistic regression results indicated that whether oncology nurses concern about self-care, interest in mindfulness and have experience with meditation influenced different latent profiles. Nursing manager should develop targeted intervention based on the typological characteristics of the oncology nurses to improve their mindful self-care ability and mental health.

Short-term changes in chest CT images among individuals at low altitude after entering high-altitude environments.

Objective: To investigate the short-term changes in chest CT images of low-altitude populations after entering a high-altitude environment. Methods: Chest CT images of 3,587 people from low-altitude areas were obtained within one month of entering a high-altitude environment. Abnormal CT features and clinical symptoms were analyzed. Results: Besides acute high-altitude pulmonary edema, the incidence of soft tissue space pneumatosis was significantly higher than that in low-altitude areas. Pneumatosis was observed in the mediastinum, cervical muscle space, abdominal cavity, and spinal cord epidural space, especially the mediastinum. Conclusion: In addition to acute high-altitude pulmonary edema, spontaneous mediastinal emphysema often occurs when individuals in low-altitude areas adapt to the high-altitude environment of cold, low-pressure, and hypoxia. When the gas escapes to the abdominal cavity, it is easy to be misdiagnosed as gastrointestinal perforation. It is also not uncommon for gas accumulation to escape into the epidural space of the spinal cord. The phenomenon of gas diffusion into distant tissue space and the mechanism of gas escape needs to be further studied.

Retrotransposon-mediated disruption of a chitin synthase gene confers insect resistance to Bacillus thuringiensis Vip3Aa toxin.

The vegetative insecticidal protein Vip3Aa from Bacillus thuringiensis (Bt) has been produced by transgenic crops to counter pest resistance to the widely used crystalline (Cry) insecticidal proteins from Bt. To proactively manage pest resistance, there is an urgent need to better understand the genetic basis of resistance to Vip3Aa, which has been largely unknown. We discovered that retrotransposon-mediated alternative splicing of a midgut-specific chitin synthase gene was associated with 5,560-fold resistance to Vip3Aa in a laboratory-selected strain of the fall armyworm, a globally important crop pest. The same mutation in this gene was also detected in a field population. Knockout of this gene via CRISPR/Cas9 caused high levels of resistance to Vip3Aa in fall armyworm and 2 other lepidopteran pests. The insights provided by these results could help to advance monitoring and management of pest resistance to Vip3Aa.

Clinicopathologic and Molecular Characterization of Inflammatory Bowel Disease-Associated Neuroendocrine Carcinomas and Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms.

The pathogenesis of neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) in the gastrointestinal tract remains poorly understood. This study seeks to characterize the clinicopathologic and molecular features of NEC/MiNEN in patients with inflammatory bowel disease (IBD). Eighteen surgically resected IBD-associated intestinal carcinomas with a minimum of 30% neuroendocrine component were collected from 6 academic centers and compared to a control group of 12 IBD-associated carcinomas lacking neuroendocrine differentiation. Both groups exhibited a male predominance and similar age distribution. The NEC/MiNEN group was more likely to have a higher percentage of Crohn's disease (9/18 vs. 1/12, P=0.024), occur in the rectum (9/18 vs. 3/12) and small intestine (4/18 vs. 0/12) (P<0.01), be diagnosed on resection without a preceding biopsy (6/18 vs. 0/12, P=0.057), and have unidentifiable precursor lesions (10/18 vs. 1/12, P=0.018) than the control group. Synchronous carcinoma, advanced tumor stage (pT3 and pT4), and lymph node metastasis occurred at similar rates; however, the NEC/MiNEN group had a higher incidence of angiovascular invasion (14/18 vs. 4/12, P=0.024), distant metastasis (8/18 vs. 1/12, P=0.049), mortality (8/18 vs. 2/12, P=0.058), and worse survival (Kaplan-Meier, P=0.023) than the control group. All tested cases were mismatch repair proficient. A Ki-67 proliferation index ranged from 25% to 100%. Next-generation sequencing in 11 NEC/MiNEN cases revealed low tumor mutational burdens but complex genetic abnormalities commonly involving TP53 (9/11, 82%), FBXW7 (4/11, 36%), and APC (3/11, 27%), with the other genetic alterations randomly occurring in one or two cases. The neuroendocrine component, which shared similar molecular alterations as the non-neuroendocrine component, was subcategorized into intermediate (G3a)- and high-grade (G3b); the higher-grade correlated with more genetic alterations. In conclusion, IBD-associated NEC/MiNEN shows diverse histologic features, variable precursor lesions, intricate genetic abnormalities, and aggressive biologic behavior. The classification and grading of GI-NEC/MiNEN may be refined for better clinical management.

Comparative Analysis and Regeneration Strategies for Three Types of Cartilage.

Cartilage tissue, encompassing hyaline cartilage, fibrocartilage, and elastic cartilage, plays a pivotal role in the human body due to its unique composition, structure, and biomechanical properties. However, the inherent avascularity and limited regenerative capacity of cartilage present significant challenges to its healing following injury. This review provides a comprehensive analysis of the current state of cartilage tissue engineering, focusing on the critical components of cell sources, scaffolds, and growth factors tailored to the regeneration of each cartilage type.We explore the similarities and differences in the composition, structure, and biomechanical properties of the three cartilage types and their implications for tissue engineering. A significant emphasis is placed on innovative strategies for cartilage regeneration, including the potential for in situ transformation of cartilage types through microenvironmental manipulation, which may offer novel avenues for repair and rehabilitation.The review underscores the necessity of a nuanced approach to cartilage tissue engineering, recognizing the distinct requirements of each cartilage type while exploring the potential of transforming one cartilage type into another as a flexible and adaptive repair strategy. Through this detailed examination, we aim to broaden the understanding of cartilage tissue engineering and inspire further research and development in this promising field.

Biodegradable Ferroelectric Molecular Plastic Crystal HOCH2(CF2)7CH2OH Structurally Inspired by Polyvinylidene Fluoride.

Ferroelectric materials, traditionally comprising inorganic ceramics and polymers, are commonly used in medical implantable devices. However, their nondegradable nature often necessitates secondary surgeries for removal. In contrast, ferroelectric molecular crystals have the advantages of easy solution processing, lightweight, and good biocompatibility, which are promising candidates for transient (short-term) implantable devices. Despite these benefits, the discovered biodegradable ferroelectric materials remain limited due to the absence of efficient design strategies. Here, inspired by the polar structure of polyvinylidene fluoride (PVDF), a ferroelectric molecular crystal 1H,1H,9H,9H-perfluoro-1,9-nonanediol (PFND), which undergoes a cubic-to-monoclinic ferroelectric plastic phase transition at 339 K, is discovered. This transition is facilitated by a 2D hydrogen bond network formed through O-H···O interactions among the oriented PFND molecules, which is crucial for the manifestation of ferroelectric properties. In this sense, by reducing the number of -CF2- groups from ≈5 000 in PVDF to seven in PFND, it is demonstrated that this ferroelectric compound only needs simple solution processing while maintaining excellent biosafety, biocompatibility, and biodegradability. This work illuminates the path toward the development of new biodegradable ferroelectric molecular crystals, offering promising avenues for biomedical applications.

PFKL promotes cell viability and glycolysis and inhibits cisplatin chemosensitivity of laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) with a high incidence and mortality rate, has a serious impact worldwide. Phosphofructokinase-1 liver type (PFKL) is a major enzyme in glycolysis progress, but its role in modulating tumorigenesis and cisplatin (DDP) chemosensitivity of LSCC was still unclear. The mRNA and protein levels of PFKL were detected by qRT-PCR and immunohistochemical assay. Cell Counting Kit-8 assay and flow cytometry were carried out to observe cell viability, as well as apoptosis and mitochondrial reactive oxygen species (mito-ROS). Extracellular acidification rate and lactate content were measured using extracellular flux analysis and lactate assay kit. Immunofluorescent staining was used to evaluate the expression of γ-H2AX foci. DNA damage was detected via single-cell gel electrophoresis. Western blotting was introduced to evaluate the protein level of PFKL, LDHA, γ-H2AX, cleaved PARP, H3K27ac, and H3K9ac. Mice xenograft model of LSCC was built for in vivo validation. The PFKL expression was significantly increased in LSCC and associated with poor survival of LSCC patients. Knockdown of PFKL in LSCC cells significantly inhibited cell viability, ECAR, lactate content, and LDHA expression, but promoted mito-ROS level. Furthermore, knockdown of PFKL enhanced response of LSCC cells to DDP by increasing DDP-induced apoptosis, promoting DDP-induced mito-ROS level, γ-H2AX foci, tail DNA, and the expression of γ-H2AX and cleaved PARP. However, the overexpression of PFKL in LSCC cells had opposite experimental results. Nude mice tumor formation experiment proved that downregulation of PFKL significantly enhanced response of cells to DDP, demonstrated by reduced tumor volume, weight and increased TUNEL-positive cells. Suppression of CBP/EP300-mediated PFKL transcription inhibited cell viability and glycolysis and promoted mito-ROS in LSCC. PFKL promotes cell viability and DNA damage repair in DDP-treated LSCC through regulation of glycolysis pathway.

Identifying Associations between Small Nucleolar RNAs and Diseases via Graph Convolutional Network and Attention Mechanism.

Research has shown that small nucleolar RNAs (snoRNAs) play crucial roles in various biological processes, and understanding disease pathogenesis by studying their relationship with diseases is beneficial. Currently, known associations are insufficient, and conventional biological experiments are costly and time-consuming. Therefore, developing efficient computational methods is crucial for identifying potential snoRNA-disease associations. In this paper, a method to identify snoRNA-disease associations based on graph convolutional network and multi-view graph attention mechanism (GCASDA) is proposed. Firstly, the similarity matrices of snoRNAs and diseases are calculated based on biological entity-related information, and the weights of the edges between the snoRNA nodes and the disease nodes are supplemented by random forest. Then two homogeneous graphs and one heterogeneous graph are constructed. Subsequently, different types of embedded features are extracted from the graphs using specific graph convolutional network structure and integrated through a multi-view graph attention mechanism to obtain node embedded feature representations. Finally, for each pair of nodes, in addition to their global features, node interaction features are passed together to a multilayer perceptron neural network (MLP) to identify snoRNA-disease associations. Experimental results show that GCASDA achieves 0.9356 and 0.9294 in AUC and AUPR, respectively, and significantly outperformed other state-of-the-art methods on the basis of different evaluation metrics. Furthermore, the case study could further demonstrate the realistic feasibility of GCASDA.

Advances of long non-coding RNAs in osteoclast differentiation and osteoporosis.

INTRODUCTION: Osteoclasts, which are responsible for bone resorption, are specialized multinucleated cells generated from monocyte/macrophage progenitor cells or hematopoietic stem cells (HSCs). Physiological bone remodeling can become pathological, such as osteoporosis, when osteoclastogenesis is out of balance. Thousands of long noncoding RNAs (lncRNAs) influence important molecular and biological processes. Recent research has revealed gene expression regulation function that numerous lncRNAs regulate nuclear domain organization, genome stability. Furthermore, the research of lncRNAs has substantial clinical implications for the treatment of existing and new diseases. AREAS COVERED: In this review, we gather the most recent research on lncRNAs and their potential for basic research and clinical applications in osteoclast and osteoporosis. We also discuss the findings here in order to fully understand the role of lncRNAs in osteoclast differentiation and osteoporosis, as well as to provide a solid basis for future research exploring associated mechanisms and treatments. EXPERT OPINION: LncRNA has been considered as an important role in the regulation of osteoclast differentiation and osteoporosis. It is exciting to investigate pathophysiological processes in osteoporosis and the therapeutic potential of lncRNAs. We hope that this review will offer promising prospects for the development of precision and individualized approaches to treatment.

Evidence for archaeal metabolism of D-amino acids in the deep marine sediments.

The deep marine sediments represent a major repository of organic matter whilst hosting a great number of uncultivated microbes. Microbial metabolism plays a key role in the recycling of organic matter in the deep marine sediments. D-amino acids (DAAs) and DAA-containing muropeptides, an important group of organic matter in the deep marine sediments, are primarily derived from bacterial peptidoglycan decomposition. Archaea are abundant in the deep ocean microbiome, yet their role in DAA metabolism remains poorly studied. Here, we report bioinformatic investigation and enzymatic characterization of deep marine sedimentary archaea involved in DAA metabolism. Our analyses suggest that a variety of archaea, particularly the Candidatus Bathyarchaeota and the Candidatus Lokiarchaeaota, can metabolize DAAs. DAAs are converted into L-amino acids via amino acid racemases (Ala racemase, Asp racemase and broad substrate specificity amino acid racemase), and converted into α-keto acid via d-serine ammonia-lyase, whereas DAA-containing di-/tri-muropeptides can be hydrolyzed by peptidases (dipeptidase and D-aminopeptidase). Overall, this study reveals the identity and activity of deep marine sedimentary archaea involved in DAA metabolism, shedding light on the mineralization and biogeochemical cycling of DAAs in the deep marine sediments.

The mechanism of interaction between tri-para-cresyl phosphate and human serum protein: a multispectroscopic and in-silico study.

Organophosphate flame retardants (OPFRs) pose the significant risks to the environment and human health and have become a serious public health issue. Tricresyl phosphates (TCPs), a group of aryl OPFRs, exhibit neurotoxicity and endocrine disrupting toxicity. However, the binding mechanisms between TCPs and human serum albumin (HSA) remain unknown. In this study, through fluorescence and ultraviolet-visible (UV-vis) absorption spectroscopy, molecular docking and molecular dynamics (MD), tri-para-cresyl phosphate (TpCP) was selected to explore potential interactions between HSA and TCPs. The results of the fluorescence spectroscopy demonstrated that a decrease the fluorescence intensity of HSA and a blue shift were observed with the increasing concentrations of TpCP. The binding constant (Ka) was 2.575 × 104 L/mol, 4.701 × 104 L/mol, 5.684 × 104 L/mol and 9.482 × 104 L/mol at 293 K, 298 K, 303 K, and 310 K, respectively. The fluorescence process between HSA and TpCP involved a mix of static and dynamic quenching mechanism. The gibbs free energy (ΔG0) of HSA-TpCP system was -24.452, -25.907, 27.363, and 29.401 kJ/mol at 293 K, 298 K, 303 K, and 310 K, respectively, suggesting that the HSA-TpCP reaction was spontaneous. The enthalpy change (ΔH0) and thermodynamic entropy change (ΔS0) of the HSA-TpCP system were 291.08 J/K mol and 60.83 kJ/mol, respectively, indicating that hydrophobic force was the major driving forces in the HSA-TpCP complex. Furthermore, multispectral analysis also revealed that TpCP could alter the microenvironment of tryptophan residue and the secondary structure of HSA and bind with the active site I of HSA. Molecular docking and MD simulations confirmed that TpCP could spontaneously form a stable complex with HSA, which was consistent with the fluorescence experimental results. This study provides novel insights into the mechanisms of underlying the transportation and distribution of OFPRs in humans.

Termite Fungus Comb Polysaccharides Alleviate Hyperglycemia and Hyperlipidemia in Type 2 Diabetic Mice by Regulating Hepatic Glucose/Lipid Metabolism and the Gut Microbiota.

Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by hyperglycemia and dyslipidemia. The termite fungus comb is an integral component of nests of termites, which are a global pest. Termite fungus comb polysaccharides (TFCPs) have been identified to possess antioxidant, anti-aging, and immune-enhancing properties. However, their physicochemical characteristics and their role in fighting diabetes have not been previously reported. In the current study, TFCPs were isolated and structurally characterized. The yield of TFCPs was determined to be 2.76%, and it was found to be composed of a diverse array of polysaccharides with varying molecular weights. The hypoglycemic and hypolipidemic effects of TFCPs, as well as their potential mechanisms of action, were investigated in a T2D mouse model. The results demonstrated that oral administration of TFCPs could alleviate fasting blood glucose levels, insulin resistance, hyperlipidemia, and the dysfunction of pancreatic islets in T2D mice. In terms of mechanisms, the TFCPs enhanced hepatic glycogenesis and glycolysis while inhibiting gluconeogenesis. Additionally, the TFCPs suppressed hepatic de novo lipogenesis and promoted fatty acid oxidation. Furthermore, the TFCPs altered the composition of the gut microbiota in the T2D mice, increasing the abundance of beneficial bacteria such as Allobaculum and Faecalibaculum, while reducing the levels of pathogens like Mailhella and Acetatifactor. Overall, these findings suggest that TFCPs may exert anti-diabetic effects by regulating hepatic glucose and lipid metabolism and the composition of the gut microbiota. These findings suggest that TFCPs can be used as a promising functional ingredient for the prevention and treatment of T2D.

Quantitative Trait Loci Sequencing and Genetic Mapping Reveal Two Main Regulatory Genes for Stem Color in Wax Gourds.

Stem color is an important agronomic trait of wax gourds. However, its regulatory genes have not been identified. In this study, 105 inbred lines constructed from two parents (GX-71 and MY-1) were sequenced and quantitative trait loci sequencing was used to mine the genes that regulate stem color in wax gourds. The results identified two quantitative trait loci related to stem color, qSC5 and qSC12, located on Chr05 (11,134,567-16,459,268) and Chr12 (74,618,168-75,712,335), respectively. The qSC5 had a phenotypic variation rate of 36.9% and a maximum limit of detection of 16.9. And the qSC12 had a phenotypic variation rate of 20.9%, and a maximum limit of detection of 11.2. Bch05G003950 (named BchAPRR2) and Bch12G020400 were identified as candidate genes involved in stem color regulation in wax gourds. The chlorophyll content and expression of BchAPRR2 and Bch12G020400 were significantly higher in green-stemmed wax gourds than in white-stemmed ones. Therefore, BchAPRR2 and Bch12G020400 were considered the main and secondary regulatory genes for wax gourd stem color, respectively. Finally, InDel markers closely linked to BchAPRR2 were developed to validate the prediction of wax gourd stem color traits in 55 germplasm lines, with an accuracy of 81.8%. These findings lay the foundation for exploring the genetic regulation of wax gourd stem color and future research on wax gourd breeding.

Abnormalities of brain structure and function in cervical spondylosis: a multi-modal voxel-based meta-analysis.

Background: Previous neuroimaging studies have revealed structural and functional brain abnormalities in patients with cervical spondylosis (CS). However, the results are divergent and inconsistent. Therefore, the present study conducted a multi-modal meta-analysis to investigate the consistent structural and functional brain alterations in CS patients. Methods: A comprehensive literature search was conducted in five databases to retrieve relevant resting-state functional magnetic resonance imaging (rs-fMRI), structural MRI and diffusion tensor imaging (DTI) studies that measured brain functional and structural differences between CS patients and healthy controls (HCs). Separate and multimodal meta-analyses were implemented, respectively, by employing Anisotropic Effect-size Signed Differential Mapping software. Results: 13 rs-fMRI studies that used regional homogeneity, amplitude of low-frequency fluctuations (ALFF) and fractional ALFF, seven voxel-based morphometry (VBM) studies and one DTI study were finally included in the present research. However, no studies on surface-based morphometry (SBM) analysis were included in this research. Due to the insufficient number of SBM and DTI studies, only rs-fMRI and VBM meta-analyses were conducted. The results of rs-fMRI meta-analysis showed that compared to HCs, CS patients demonstrated decreased regional spontaneous brain activities in the right lingual gyrus, right middle temporal gyrus (MTG), left inferior parietal gyrus and right postcentral gyrus (PoCG), while increased activities in the right medial superior frontal gyrus, bilateral middle frontal gyrus and right precuneus. VBM meta-analysis detected increased GMV in the right superior temporal gyrus (STG) and right paracentral lobule (PCL), while decreased GMV in the left supplementary motor area and left MTG in CS patients. The multi-modal meta-analysis revealed increased GMV together with decreased regional spontaneous brain activity in the left PoCG, right STG and PCL among CS patients. Conclusion: This meta-analysis revealed that compared to HCs, CS patients had significant alterations in GMV and regional spontaneous brain activity. The altered brain regions mainly included the primary visual cortex, the default mode network and the sensorimotor area, which may be associated with CS patients' symptoms of sensory deficits, blurred vision, cognitive impairment and motor dysfunction. The findings may contribute to understanding the underlying pathophysiology of brain dysfunction and provide references for early diagnosis and treatment of CS. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, CRD42022370967.

A vulnerability detection method for IoT protocol based on parallel fuzzy algorithm.

The Internet of Things communication protocol is prone to security vulnerabilities when facing increasing types and scales of network attacks, which can affect the communication security of the Internet of Things. It is crucial to effectively detect these vulnerabilities in order to improve the security of IoT communication protocols and promptly fix them. Therefore, this study proposes a distributed IoT communication protocol vulnerability detection method based on an improved parallelized fuzzy testing algorithm. Firstly, based on design principles and by comparing different communication protocols, a communication architecture for the distribution network's Internet of Things was constructed, and the communication protocols were formalized and decomposed. Next, preprocess the vulnerability detection samples, and then use genetic algorithm to improve the parallelized fuzzy testing algorithm to perform vulnerability detection. Through this improved algorithm, the missed detection rate and false detection rate can be effectively reduced, thereby improving the security of IoT communication protocols. The experimental results show that the highest missed detection rate of this method is only 4.0 %, and the false detection rate is low, with high detection efficiency. This indicates that the method has good performance and reliability in detecting vulnerabilities in IoT communication protocols.

Infective Endocarditis Caused by Neisseria Sicca Species 10 Years After Mechanical Aortic Valve Implantation.

We report a rare case of mechanical aortic valve infective endocarditis caused by Neisseria sicca. A 44-year-old man, with a history of aortic valve replacement, presented to the hospital with a 10-day history of fever. Investigations revealed that the blood cultures grew Neisseria sicca. Although the transthoracic echocardiogram (TTE) was negative, a transesophageal echocardiogram showed a 0.5 cm × 0.3 cm piece of vegetation attached to the aortic valve. After eight weeks of therapy, according to the antibiotic susceptibility test, the patient's blood cultures were negative, and repeat TTE showed no vegetation. This report can offer valuable insights for clinical diagnosis and treatment of Neisseria sicca endocarditis, particularly when selecting sensitive antibiotics.

Harmine and exendin-4 combination therapy safely expands human ß cell mass in vivo in a mouse xenograft system.

Five hundred thirty-seven million people globally suffer from diabetes. Insulin-producing ß cells are reduced in number in most people with diabetes, but most individuals still have some residual ß cells. However, none of the many diabetes drugs in common use increases human ß cell numbers. Recently, small molecules that inhibit dual tyrosine-regulated kinase 1A (DYRK1A) have been shown to induce immunohistochemical markers of human ß cell replication, and this is enhanced by drugs that stimulate the glucagon-like peptide 1 (GLP1) receptor (GLP1R) on ß cells. However, it remains to be demonstrated whether these immunohistochemical findings translate into an actual increase in human ß cell numbers in vivo. It is also unknown whether DYRK1A inhibitors together with GLP1R agonists (GLP1RAs) affect human ß cell survival. Here, using an optimized immunolabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO+) protocol in mouse kidneys bearing human islet grafts, we demonstrate that combination of a DYRK1A inhibitor with exendin-4 increases actual human ß cell mass in vivo by a mean of four- to sevenfold in diabetic and nondiabetic mice over 3 months and reverses diabetes, without alteration in human α cell mass. The augmentation in human ß cell mass occurred through mechanisms that included enhanced human ß cell proliferation, function, and survival. The increase in human ß cell survival was mediated, in part, by the islet prohormone VGF. Together, these findings demonstrate the therapeutic potential and favorable preclinical safety profile of the DYRK1A inhibitor-GLP1RA combination for diabetes treatment.

A novel AIE fluorescent probe for the detection and imaging of hydrogen peroxide in living tumor cells and in vivo.

Hydrogen peroxide (H2O2), a key reactive oxygen species (ROS), plays crucial roles in redox signaling pathways and immune responses associated with cell proliferation, differentiation, migration, and disease progression. The selective monitoring of overproduced H2O2 is important for understanding the diagnosis and pathogenesis of diseases such as cardiovascular disease, cancers, diabetes, Parkinson's disease, Alzheimer's disease, and inflammation. In this paper, an AIE fluorescent probe BQM-H2O2 was developed by connecting phenyl borate with the fluorophore BQM-PNH for selective detection of H2O2. In the presence of H2O2 at fw = 99% (pH = 7.4, 1% DMSO), the probe BQM-H2O2 could generate strong fluorescent signals due to the oxidation of the borate ester. The probe exhibited high selectivity and a low detection limit toward H2O2 with the calculated LOD of 112.6 nM. Importantly, it was employed in the detection of exogenous and endogenous hydrogen peroxide in 4T1 cells with low cytotoxicity. This probe has also been successfully applied to imaging of H2O2 in Blab/c mice bearing 4T1 graft tumors.