The prevalence and characteristics of frailty in cirrhosis patients: a meta-analysis and systematic review.

Objectives: This study aimed to assess the prevalence of frailty in cirrhosis patients and the distribution of age, sex, and body mass index (BMI) in cirrhotic patients with frailty. Methods: We performed a thorough literature search using PubMed, Embase, Web of Science, and the Cochrane Library from inception to 29 February 2024. The estimated prevalence with a 95% confidence interval (CI) was calculated with a random effect model. Subgroup analysis and sensitivity analysis were performed to assess the heterogeneity and characterize the distribution of age, sex, and body mass index (BMI) in cirrhotic patients. Publication bias was assessed by the funnel plot, Begg's test, and Egger's test. Results: The 16 included studies, which were all observational, reported a prevalence of frailty in 8,406 cirrhosis patients ranging from 9 to 65%, and the overall estimated prevalence was 27% (95% CI: 21-33%; I2 = 97.7%, P < 0.001). This meta-analysis indicated that the estimated prevalence of frailty in cirrhosis patients was high, and compared to the non-frail cohort, the frail cohort tended to have a higher mean age, with a mean age of 63.3 (95% CI: 59.9, 66.7; Z = 36.48; P < 0.001), and a larger proportion of male patients with worse liver function, with a mean of 73.5% (95% CI: 71.4, 75.5%; Z = 7.65; P < 0.001), ND in the frail cohort, 54.8% (95% CI: 43.1, 66.5%; P < 0.001) and 23.4% (95% CI: 13.2, 33.7%; P < 0.001) were classified into Child-Pugh B and C, respectively. Meanwhile, the patients in the non-frail cohort are more likely to have a higher BMI, with a mean of 28.4 (95% CI: 24.1, 32.7; Z = 13.07; P < 0.001). Conclusion: The current study suggests that cirrhosis patients have a high prevalence of frailty. Compared with the non-frail cohort, the frail patients tend to be male, older, and have a lower BMI with worse liver function.

Methodologies and key considerations for implementing the International Classification of Diseases-11th revision morbidity coding: insights from a national pilot study in China.

OBJECTIVE: The aim of this study was to disseminate insights from a nationwide pilot of the International Classification of Diseases-11th revision (ICD-11). MATERIALS AND METHODS: The strategies and methodologies employed to implement the ICD-11 morbidity coding in 59 hospitals in China are described. The key considerations for the ICD-11 implementation were summarized based on feedback obtained from the pilot hospitals. Coding accuracy and Krippendorff's alpha reliability were computed based on the coding results in the ICD-11 exam. RESULTS: Among the 59 pilot hospitals, 58 integrated ICD-11 Coding Software into their health information management systems and 56 implemented the ICD-11 in morbidity coding, resulting in 3 723 959 diagnoses for 873 425 patients being coded over a 2-month pilot coding phase. The key considerations in the transition to the ICD-11 in morbidity coding encompassed the enrichment of ICD-11 content, refinement of tools, provision of systematic and tailored training, improvement of clinical documentation, promotion of downstream data utilization, and the establishment of a national process and mechanism for implementation. The overall coding accuracy was 82.9% when considering the entire coding field (including postcoordination) and 92.2% when only one stem code was considered. Krippendorff's alpha was 0.792 (95% CI, 0.788-0.796) and 0.799 (95% CI, 0.795-0.803) with and without consideration of the code sequence, respectively. CONCLUSION: This nationwide pilot study has enhanced national technical readiness for the ICD-11 implementation in morbidity, elucidating key factors warranting careful consideration in future endeavors. The good accuracy and intercoder reliability of the ICD-11 coding achieved following a brief training program underscore the potential for the ICD-11 to reduce training costs and provide high-quality health data. Experiences and lessons learned from this study have contributed to WHO's work on the ICD-11 and can inform other countries when formulating their transition plan.

Genome-Wide Identification and Characterization of Argonaute, Dicer-like and RNA-Dependent RNA Polymerase Gene Families and Their Expression Analyses in Fragaria spp.

In the growth and development of plants, some non-coding small RNAs (sRNAs) not only mediate RNA interference at the post-transcriptional level, but also play an important regulatory role in chromatin modification at the transcriptional level. In these processes, the protein factors Argonaute (AGO), Dicer-like (DCL), and RNA-dependent RNA polymerase (RDR) play very important roles in the synthesis of sRNAs respectively. Though they have been identified in many plants, the information about these gene families in strawberry was poorly understood. In this study, using a genome-wide analysis and a phylogenetic approach, 13 AGO, six DCL, and nine RDR genes were identified in diploid strawberry Fragaria vesca. We also identified 33 AGO, 18 DCL, and 28 RDR genes in octoploid strawberry Fragaria × ananassa, studied the expression patterns of these genes in various tissues and developmental stages of strawberry, and researched the response of these genes to some hormones, finding that almost all genes respond to the five hormone stresses. This study is the first report of a genome-wide analysis of AGO, DCL, and RDR gene families in Fragaria spp., in which we provide basic genomic information and expression patterns for these genes. Additionally, this study provides a basis for further research on the functions of these genes and some evidence for the evolution between diploid and octoploid strawberries.

Targeted sequencing reveals the relationship between mutations and patients' clinical indicators, blood cell counts and early progression in diffuse large-B cell lymphoma.

In the current study, we assessed the relationship between mutations and the blood cell counts and early progression of patients with diffuse large-B cell lymphoma (DLBCL). A total of 109 patients with newly diagnosed DLBCL were included in this study. UBE2A mutation was only found in patients with bone marrow involvement. The mutations of ZNF608, SF3B1, DTX1, and NCOR2 were related to blood cell counts. NCOR2 mutations were only detected in patients of the noncomplete response group (PR + SD + PD). In addition, the mutations of ATM, BTG2, TBL1XR1, and TP53 were linked to lower PFS/OS rate, while SGK1, SCOS1, and NFKBIE were related to higher PFS/OS rate. Importantly, we identified that Ann Arbor stage (III-IV), B symptoms, absolute lymphocyte count (ALC) abnormity, and MTOR mutation were the four independent influencing factors of the 12-month progression of DLBCL patients. Overall, this study revealed that mutations were associated with the early progression of DLBCL.

Identification and characterization of miRNAs and PHAS loci related to the early development of the embryo and endosperm in Fragaria × ananassa.

BACKGROUND: The strawberry fleshy fruit is actually enlarged receptacle tissue, and the successful development of the embryo and endosperm is essential for receptacle fruit set. MicroRNAs (miRNAs) and phased small interfering RNAs (phasiRNAs) play indispensable regulatory roles in plant growth and development. However, miRNAs and phasiRNAs participating in the regulation of strawberry embryo and endosperm development have yet to be explored. RESULTS: Here, we performed genome-wide identification of miRNA and phasiRNA-producing loci (PHAS) in strawberry seeds with a focus on those involved in the development of the early embryo and endosperm. We found that embryos and endosperm have different levels of small RNAs. After bioinformatics analysis, the results showed that a total of 404 miRNAs (352 known and 52 novel) and 156 PHAS genes (81 21-nt and 75 24-nt genes) could be found in strawberry seed-related tissues, of which four and nine conserved miRNA families displayed conserved expression in the endosperm and embryo, respectively. Based on refined putative annotation of PHAS loci, some auxin signal-related genes, such as CM3, TAR2, AFB2, ASA1, NAC and TAS3, were found, which demonstrates that IAA biosynthesis is important for endosperm and embryo development during early fruit growth. Additionally, some auxin signal-related conserved (miR390-TAS3) and novel (miR156-ASA1) trigger-PHAS pairs were identified. CONCLUSIONS: Taken together, these results expand our understanding of sRNAs in strawberry embryo and endosperm development and provide a genomic resource for early-stage fruit development.

The diagnostic and prognostic values of circulating miRNA-1246 in multiple myeloma.

BACKGROUND/OBJECTIVE: Bone marrow biopsy, the gold standard for the diagnosis of multiple myeloma (MM), has main limitation of the invasiveness. Here, we explored the diagnostic and prognostic values of circulating miR-1246 in patients with MM. MATERIAL AND METHODS: Ninety MM patients and 30 healthy donors (control group) were recruited in this study. The expression of miR-1246 in the peripheral blood samples was detected using qPCR. The receiver operating characteristic (ROC) curve was used to assess the diagnostic value of miR-1246 in MM. The Kaplan-Meier survival analyze was performed to evaluate the prognostic value of miR-1246. RESULTS: The expression level of serum miR-1246 from newly diagnosed MM patients was significantly higher than that of the control group. Circulating miR-1246 level was decreased after treatment in remission patients, but remained high levels in relapsed patients (P < 0.05). ROC analysis demonstrated that miR-1246 showed a high diagnostic value in MM with an area under the curve (AUC) of 0.952, the sensitivity of 87%, and the specificity of 95% [95% confidence interval (CI) 0.902-1.007; P < 0.001]. Kaplan-Meier analysis showed that the progression-free survival (PFS) (14.0 months vs. 26.5 months, P = 0.045) and overall survival (OS) (20.5 months vs. 55.5 months, P = 0.014) were significantly shorter in patients with high miR-1246 expression as compared with those in patients with miR-1246 low expression. Multiple Cox regression model analysis showed that circulating miR-1246 was an independent prognostic factor for PFS (HR 2.786, 95% CI: 1.420-5.467, P = 0.003) and OS (HR 2.995, 95% CI: 1.166-7.689, P = 0.023) in MM patients. CONCLUSION: This study demonstrates that circulating miR-1246 level is elevated in MM patients, which shows high values in the diagnosis and prognosis prediction in patients with MM.

The complete mitochondrial genome of the forest crested lizard, Calotes emma (Squamata, Agamidae) in China by the next generation sequencing.

The whole mitogenome can prove useful tools for phylogenetic reconstruction and efficiently recover with reasonable taxon sampling. Calotes emma is widely distributed and arboreal in habits. However, studies of C. emma are still very limited, including population genetics and evolutionary biology. In this study, we reported the complete mitochondrial genome of the C. emma by next-generation sequencing for future more researches on systematics and evolution of C. emma from the perspective of mitochondrial DNA. The length of mitogenome was 17,688 bp, including 13 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, 22 tRNA genes and a control region. The phylogenetic tree recovered the monophyly of the Calotes and revealed that newly sequenced C. emma well supported as the sister taxon to C. mystaceus by very high posterior probabilities (1.0). The complete mitochondrial genome of C.emma in this study will be helpful for understanding the phylogenetic systematics and relationships, and molecular evolution of Calotes in Agamidae.

EHMT2 (G9a) activation in mantle cell lymphoma and its associated DNA methylation and gene expression.

OBJECTIVE: The function of euchromatic histone-lysine N-methyltransferase 2 (EHMT2) has been studied in several cancers; however, little is known about its role in mantle cell lymphoma (MCL). Thus, this study aimed to characterize the significance and function of EHMT2 in MCL. METHODS: EHMT2 expression in MCL and reactive hyperplasia (RH) were investigated by immunohistochemistry. Genome-wide analysis of DNA methylation was performed on EHMT2 + MCL samples. The function of EHMT2 was determined by CCK8, flow cytometry, and western blot assays. Gene expression profile analysis was performed before and after EHMT2 knockdown to search for EHMT2-regulated genes. Co-immunoprecipitation (Co-IP) experiments were conducted to identify the proteins interacting with EHMT2. RESULTS: EHMT2 was expressed in 68.57% (24/35) of MCLs but not in any RHs. Genome-wide analysis of DNA methylation on EHMT2 + MCLs revealed that multiple members of the HOX, FOX, PAX, SOX, and CDX families were hypermethylated or hypomethylated in EHMT2 + MCLs. BIX01294, a EHMT2 inhibitor, inhibited MCL cell growth and stalled cells in the G1 phase. Additionally, BIX01294 downregulated the expressions of cell cycle proteins, cyclin D1, CDK4, and P21, but upregulated the expressions of apoptosis-related proteins, Bax and caspase-3. Co-IP experiments revealed that EHMT2 interacted with UHRF1, HDAC1, and HDAC2 but not with HDCA3. After EHMT2 knockdown, multiple genes were regulated, including CD5 and CCND1, mostly enriched in the Tec kinase signaling pathway. In addition, several genes (e.g., MARCH1, CCDC50, HIP1, and WNT3) were aberrantly methylated in EHMT2 + MCLs. CONCLUSIONS: For the first time, we determined the significance of EHMT2 in MCL and identified potential EHMT2-regulated genes.

Identification of Imprinted Genes Based on Homology: An Example of Fragaria vesca.

Genomic imprinting has drawn increasing attention in plant biology in recent years. At present, hundreds of imprinted genes have been identified in various plants, and some of them have been reported to be evolutionarily conserved in plant species. In this research, 17 candidate genes in Fragaria vesca were obtained based on the homologous imprinted genes in Arabidopsis thaliana and other species. We further constructed reciprocal crosses of diploid strawberry (F. vesca) using the varieties 10-41 and 18-86 as the parents to investigate the conservation of these imprinted genes. Potentially informative single nucleotide polymorphisms (SNPs) were used as molecular markers of two parents obtained from candidate imprinted genes which have been cloned and sequenced. Meanwhile, we analyzed the SNP site variation ratios and parent-of-origin expression patterns of candidate imprinted genes at 10 days after pollination (DAP) endosperm and embryo for the hybrids of reciprocal cross, respectively. A total of five maternally expressed genes (MEGs), i.e., FvARI8, FvKHDP-2, FvDRIP2, FvBRO1, and FvLTP3, were identified in the endosperm, which did not show imprinting in the embryo. Finally, tissues expression analysis indicated that the five imprinted genes excluding FvDRIP2 mainly expressed in the endosperm. This is the first report on imprinted genes of Fragaria, and we provide a simple and rapid method based on homologous conservation to screen imprinted genes. The present study will provide a basis for further study of function and mechanism of genomic imprinting in F. vesca.

PRMT5 promotes progression of endometrioid adenocarcinoma via ERα and cell cycle signaling pathways.

Protein arginine methyltransferase 5 (PRMT5) has previously been reported to be upregulated in many malignant tumors. This study investigated the significance of PRMT5 in endometrial carcinoma (EC) and explored its function in tumorigenesis. Immunohistochemistry was performed to evaluate PRMT5 expression in 62 EC and 66 endometrial hyperplasia samples. The functions of PRMT5 were investigated by cell counting kit-8, plate colony formation, wound healing, and transwell and flow cytometry assays. Quantitative reverse transcription-polymerase chain reaction and western blotting were used to measure the expression of PRMT5, changes in estrogen receptor α (ERα), and related functional proteins. Coimmunoprecipitation was performed to examine the interaction of PRMT5 with ERα and its coactivator steroid receptor coactivator-1 (SRC1). Compared to endometrial hyperplasia tissue, PRMT5 was overexpressed in endometrioid adenocarcinoma (EAC) but not overexpressed in mucinous EC. The main expression pattern of PRMT5 in EAC was cytoplasmic. However, the positive cases of endometrial hyperplasia showed both cytoplasmic and nuclear positivity in the endometrial glands or were mainly positive in stromal cells. Knockdown of PRMT5 significantly inhibited the growth and migration ability of EAC cells and promoted their apoptosis by regulating cyclin D1, c-myc, p53, and Bcl2 proteins. Furthermore, PRMT5 could form a complex with ERα and SRC1 to promote the expression of ERα. In conclusion, PRMT5 plays a significant role in the progression of EAC by interacting with ERα and impacting the cell cycle signaling pathways.

A combination of cytokeratin 5/6, p63, p40 and MUC5AC are useful for distinguishing squamous cell carcinoma from adenocarcinoma of the cervix.

PURPOSE: Squamous cell carcinomas and adenocarcinomas are the most common types of cervical cancer. Compared to squamous cell carcinomas, adenocarcinomas are more common in younger women and have a poorer prognosis. Yet, so far, no useful biomarkers have been developed for these two types of cancer. In the following study, we examined the combination of cytokeratin 5/6, p63, p40 and MUC5AC for distinguishing squamous cell carcinoma (SCC) from adenocarcinoma of the cervix (AEC). MATERIALS AND METHODS: A total of 101 SCC and 108 AEC were collected. Immunohistochemical analyses were conducted to determine the expression of CK5/6, p63, p40, CK7 and MUC5AC. One pathologist who was blinded to the patient's clinical and pathological data interpreted the staining results. RESULTS: MUC5AC and CK7 were detected in 81.48 and 82.41% of AEC cases compared to 9.9 and 49.50% of SCC cases (P < 0.05); the specificity of MUC5AC was higher than that of CK7 in AEC (P < 0.05). The sensitivity of MUC5AC combined with p40 or p63 was similar to that of CK7, but the specificity was slightly higher than that of CK7 in AEC. Moreover, the expression of MUC5AC was correlated with the degree of tumor differentiation in adenocarcinomas (P = 0.036) and was not related to the prognosis of cervical adenocarcinoma and subtypes. CONCLUSIONS: MUC5AC may be useful as a biomarker for differential diagnoses between squamous carcinoma and adenocarcinoma of the cervix.

The Genome-Wide Analysis of RALF-Like Genes in Strawberry (Wild and Cultivated) and Five Other Plant Species (Rosaceae).

The rapid alkalinization factor (RALF) gene family is essential for the plant growth and development. However, there is little known about these genes among Rosaceae species. Here, we identify 124 RALF-like genes from seven Rosaceae species, and 39 genes from Arabidopsis, totally 163 genes, divided into four clades according to the phylogenetic analysis, which includes 45 mature RALF genes from Rosaceae species. The YISY motif and RRXL cleavage site are typical features of true RALF genes, but some variants were detected in our study, such as YISP, YIST, NISY, YINY, YIGY, YVGY, FIGY, YIAY, and RRVM. Motif1 is widely distributed among all the clades. According to screening of cis-regulatory elements, GO annotation, expression sequence tags (EST), RNA-seq, and RT-qPCR, we reported that 24 RALF genes coding mature proteins related to tissue development, fungal infection, and hormone response. Purifying selection may play an important role in the evolutionary process of RALF-like genes among Rosaceae species according to the result from ka/ks. The tandem duplication event just occurs in four gene pairs (Fv-RALF9 and Fv-RALF10, Md-RALF7 and Md-RALF8, Pm-RALF2 and Pm-RALF8, and Pp-RALF11 and Pp-RALF14) from four Rosaceae species. Our research provides a wide overview of RALF-like genes in seven Rosaceae species involved in identification, classification, structure, expression, and evolution analysis.

The clinicopathological and genetic features of ovarian diffuse large B-cell lymphoma.

Ovarian lymphoma, whether a primary or secondary condition, is very rare. Little is known about its genetic aberrations. Here, we reviewed the clinical, morphological and immunohistochemical characteristics of nine ovarian diffuse large B-cell lymphoma (DLBCL) cases and performed fluorescence in situ hybridisation (FISH) analysis to detect MYC, BCL2 and BCL6 translocations. We also performed whole exome sequencing analysis to determine their genomic features compared with those of conventional extranodal DLBCL. The results showed that six of nine cases were bilateral and three cases were left-sided. Histologically, the tumour cells were homogeneous and a starry-sky pattern was very common in ovarian DLBCL (Burkitt-like). Immunohistochemically, most of the cases (7/9) were germinal centre B-cell-like (GCB) subtype, and dual expression of MYC and BCL2 was found in three cases of ovarian DLBCL. A double-hit (involving MYC and BCL6) phenotype was found in one case of ovarian DLBCL (GCB subtype). Sequencing analysis revealed that NOTCH4, NCOR2, BCL10 and CARD11 were frequently mutated both in ovarian DLBCL and conventional extranodal DLBCL. COL27A1, PRKCB, HLA-A, NOTCH3 and HDAC4 mutations were found only in ovarian DLBCL but not in conventional DLBCL, and NOTCH3 and HDAC4 mutations were only identified in the GCB subtype. Furthermore, several signalling pathways including the B-cell receptor, Epstein-Barr virus infection, HTLV-1 infection, Notch, PI3K-AKT and mTOR were found to be involved in ovarian DLBCL. Our results broaden the understanding of the clinicopathological and molecular characteristics of ovarian DLBCL and compare their genetic features to those of conventional extranodal DLBCL for the first time.

Cyclin-dependent kinase subunit 2 overexpression promotes tumor progression and predicts poor prognosis in uterine leiomyosarcoma.

Cyclin-dependent kinase subunit (CKS) 2 is a member of the CKS family, which plays an important role in the regulation of meiosis and mitosis. Overexpression of CKS2 has been reported in several types of tumors. However, few studies have investigated its role in uterine leiomyosarcoma (ULMS). In the present study, the expression of CKS2 in 38 cases of ULMS and 38 cases of uterine leiomyoma (ULM) was analyzed by immunohistochemistry. Moreover, the functional analysis of CKS2 was performed in ULMS cell lines. A significantly higher expression of CKS2 was found in ULMS tissues than in ULM tissues (P<0.01) and high CKS2 expression was associated with increased tumor size, low progesterone receptor expression and poor prognosis in patients with ULMS. Multivariate Cox regression analysis revealed that CKS2 expression status was an independent predictor of overall survival for ULMS. Furthermore, silencing of CKS2 in ULMS cells inhibited cell proliferation, colony formation, migration and invasion, and resulted in cell cycle arrest. In conclusion, the present study demonstrated that CKS2 may serve as a marker for the differential diagnosis of ULMS and ULM. In addition, it may act as an independent prognostic factor in patients with ULMS, and serve as a novel target for ULMS therapy.

Epigenomic profiling of DNA methylation for hepatocellular carcinoma diagnosis and prognosis prediction.

BACKGROUND AND AIM: DNA hypermethylation has emerged as a novel molecular biomarker for the diagnosis and prognosis prediction of many cancers. We aimed to identify clinically useful biomarkers regulated by DNA methylation in hepatocellular carcinoma (HCC). METHODS: Genome-wide methylation analysis in HCCs and paired noncancerous tissues was performed using an Illumina Infinium HumanMethylation 450K BeadChip array. Methylation-specific polymerase chain reaction and pyrosequencing were used to validate the methylation status of selected genes in 100 paired HCCs and noncancerous samples. RESULTS: A total of 97 027 (20.0%) out of 485 577 CpG sites significantly were differed between HCC and noncancerous tissues. Among all the significant CpG sites, 48.8% are hypermethylated and 51.2% are hypomethylated in HCCs. Multiple signaling pathways (AMP-activated protein kinase, estrogen, and adipocytokine) involved in gene methylation were identified in HCC. FES was selected for further analysis based on its high level of methylation confirmed by polymerase chain reaction and pyrosequencing. The result showed that FES hypermethylation was correlated with tumor size (0.001), serum alpha fetoprotein (0.023), and tumor differentiation (0.006). FES protein was significantly downregulated in 51/100 (51%) HCCs, and 94.12% (48/51) of them were due to promoter hypermethylation. Both FES hypermethylation and protein downregulation were associated with the progression-free survival and overall survival of HCC patients. Overexpressed and knockdown of FES confirmed its inhibitory effect on the proliferation and migration of HCC cells. CONCLUSIONS: We identified many new differentially methylated CpGs in HCCs and demonstrate that FES functions as a tumor suppressor gene in HCC and its methylation status could be used as an indicator for prognosis of HCC.

The histologic, immunohistochemical, and genetic features of classical Hodgkin lymphoma and anaplastic large cell lymphoma with aberrant T-cell/B-cell antigen expression.

Classical Hodgkin lymphoma (cHL) and ALK- anaplastic large cell lymphoma (ALCL) share many morphologic and immunohistochemical features, causing difficulties in differential diagnosis. Aberrant T-cell/B-cell antigen (TCA/BCA) expression in cHL/ALCL has previously been reported, but differences in the broader morphologic and genetic features still remain unclear. We first explored the histologic and immunohistochemical characteristics of cHL and ALCL with or without aberrant expression. Of 68 cHL cases, 10 (14.71%) were found to express 1 or more TCAs, and the frequency was as follows: CD4 > CD2 > CD3 > CD5 = CD7. Only 1 (3.33%) of 30 ALCL cases expressed BCA. Histologically, the main subtypes of cHL with aberrant TCA expression were LD and NS2. These aberrant TCA-expressing cHL tumor cells exhibited some ALCL features, and the aberrant BCA-expressing ALCL tumor cells displayed cHL characteristics. We also performed whole-exome sequencing analysis on cHL and ALCL samples with aberrant expression and compared them with those without aberrant expression. The results of this analysis showed that GNE and CACNB2 mutations, involved in the MAPK signaling pathway, may play an important role in cHL. In addition, 135 mutation sites involved in multiple signaling pathways were identified in ALCL. In the aberrant-expression cases, genetic features were similar between cHL and ALCL, consistent with their morphologic features. Our results broaden the understanding of the histologic and immunohistochemical characteristics of cHL and ALCL with aberrant expression and, for the first time, compare genetic features between cHL and ALCL with and without aberrant expression.

A near-infrared fluorescent probe for the selective detection of HNO in living cells and in vivo.

Nitroxyl (HNO), the one-electron reduced and protonated analogue of nitric oxide (NO), demonstrates distinctive bio-pharmacological effects in the treatment of cardiovascular disorders. Herein, we design and synthesize a near-infrared (NIR) metal-free fluorescent probe Cyto-JN for the detection of nitroxyl (HNO) in living cells and in vivo. The metal-free Cyto-JN is composed of two moieties: the Aza-BODIPY fluorophore and the HNO recognition unit, the diphenylphosphinobenzoyl group. Cyto-JN can react with HNO in a 1 : 1 stoichiometry, which may bring great benefit to the detection efficiency of bioassays. Cyto-JN shows high sensitivity toward HNO and exhibits low cytotoxic effect on cells. Moreover, the probe displays good selectivity for the detection of HNO in the presence of various biologically related species. Cyto-JN can be applied successfully to bio-imaging of HNO in living cells and in mice. The results of flow cytometry confirm that the probe Cyto-JN can be used to detect intracellular HNO qualitatively and quantitatively.

Visualization of nitroxyl (HNO) in vivo via a lysosome-targetable near-infrared fluorescent probe.

We have presented a near-infrared fluorescent probe Lyso-JN for the detection of nitroxyl (HNO) in cells and in vivo. Lyso-JN is comprised of three moieties: an Aza-BODIPY fluorophore, a HNO-response modulator, diphenylphosphino-benzoyl, and a lysosomal locator, alkylmorpholine. The detection mechanism is based on aza-ylide intramolecular ester aminolysis reaction with HNO. The probe holds the ability to capture lysosomal HNO in RAW 264.7 cells, and it is also successfully employed to visualize HNO in mice.