RAAS in diabetic retinopathy: mechanisms and therapies.

Diabetic retinopathy (DR) is a complication of diabetes with a complex pathophysiology and multiple factors involved. Recently, it has been found that the upregulation of the renin-angiotensin-aldosterone system (RAAS) leads to overexpression of angiotensin II (Ang II), which induces oxidative stress, inflammation, and angiogenesis in the retina. Therefore, RAAS may be a promising therapeutic target in DR. Notably, RAAS inhibitors are often used in the treatment of hypertension. Still, the potential role and mechanism of DR must be further studied. In this review, we discuss and summarize the pathology and potential therapeutic goals of RAAS in DR.

Identification and quantification of N6-methyladenosine by chemical derivatization coupled with 19F NMR spectroscopy.

N 6-Methyladenosine (6mA) is a well-known prokaryotic DNA modification that has been shown to play epigenetic roles in eukaryotic DNA. Accurate detection and quantification of 6mA are prerequisites for molecular understanding of the impact of 6mA modification on DNA. However, the existing methods have several problems, such as high false-positive rate, time-consuming and complex operating procedures. Chemical sensors for the selective detection of 6mA modification are rarely reported in the literature. Fluorinated phenylboronic acid combined with 19F NMR analysis is an effective method for determining DNA or RNA modification. In this study, we presented a simple and fast chemical method for labelling the 6th imino group of 6mA using a boric-acid-derived probe. Besides, the trifluoromethyl group of trifluoromethyl phenylboronic acid (2a) could detect 6mA modification through 19F NMR. Combined with this sensor system, 6mA modification could be detected well and quickly in 6 types of deoxynucleoside mixtures and DNA samples. Taken together, the method developed in the current study has potential for specific detection of 6mA in biological samples.

Activation of persulfate by g-C3N4/nZVI@SBC for degradation of total petroleum hydrocarbon in groundwater.

In this study, we synthesized a high removal efficiency catalyst using biochar-supported nanoscale zero-valent iron and g-C3N4, denoted as g-C3N4/nZVI@SBC, to activate persulfate (PS) for the degradation of total petroleum hydrocarbon (TPH) in groundwater. We characterized the morphology and physiochemical properties of g-C3N4/nZVI@SBC with scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR), BET surface area analysis, and X-ray photoelectron spectroscopy (XPS). To assess the performance of the g-C3N4/nZVI@SBC catalyst, we investigated various reaction parameters, such as the mass ratio of g-C3N4 to nZVI@SBC, PS concentration, initial pH, initial TPH concentration, and the presence of coexisting ions in the system. The results from batch experiments and repeated use trials indicate that g-C3N4/nZVI@SBC exhibited both excellent catalytic activation capability and impressive durability, making it a promising choice for TPH degradation. Specifically, when the PS concentration reached 1 mM, the catalyst dosage was 0.3 g/L, and the g-C3N4 to nZVI@SBC mass ratio was 2, we achieved a remarkable TPH removal efficiency of 93.8%. Through electron paramagnetic resonance (EPR) testing and quenching experiments, we identified sulfate radicals, hydroxyl radicals, and superoxide radicals as the primary active substance involved in the TPH degradation process. Moreover, the g-C3N4/nZVI@SBC composite proved highly effective for in-situ TPH removal from groundwater and displayed an 86% removal rate, making it a valuable candidate for applications in permeable reactive barriers (PRB) aimed at enhancing environmental remediation. In summary, by skillfully utilizing g-C3N4/nZVI@SBC, this study has made notable advancements in synthesis and characterization, presenting a feasible and innovative approach to addressing TPH pollution in groundwater.

Targeted immunotherapy to cancer stem cells: A novel strategy of anticancer immunotherapy.

Cancer is a major disease that endangers human health. Cancer drug resistance and relapse are the two main causes contributing to cancer treatment failure. Cancer stem cells (CSCs) are a small fraction of tumor cells that are responsible for tumorigenesis, metastasis, relapse, and resistance to conventional anticancer therapies. Therefore, CSCs are considered to be the root of cancer recurrence, metastasis, and drug resistance. Novel anticancer strategies need to face this new challenge and explore their efficacy against CSCs. Recently, immunotherapy has made rapid advances in cancer treatment, and its potential against CSCs is also an interesting area of research. Meanwhile, immunotherapy strategies are novel therapeutic modalities with promising results in targeting CSCs. In this review, we summarize the targeting of CSCs by various immunotherapy strategies such as monoclonal antibodies(mAb), tumor vaccines, immune checkpoint inhibitors, and chimeric antigen receptor-T cells(CAR-T) in pre-clinical and clinical studies. This review provides new insights into the application of these immunotherapeutic approaches to potential anti-tumor therapies in the future.

[Cloning and functional analysis of flavanone synthase â ¡ from Dendrobium huoshanense].

Flavonoid C-glycosides are a class of natural products that are widely involved in plant defense responses and have diverse pharmacological activities. They are also important active ingredients of Dendrobium huoshanense. Flavanone synthase Ⅱ has been proven to be a key enzyme in the synthesis pathway of flavonoid C-glycosides in plants, and their catalytic product 2-hydroxyflavanone is the precursor compound for the synthesis of various reported flavonoid C-glycosides. In this study, based on the reported amino acid sequence of flavanone synthase Ⅱ, a flavanone synthase Ⅱ gene(DhuFNSⅡ) was screened and verified from the constructed D. huoshanense genome localization database. Functional validation of the enzyme showed that it could in vitro catalyze naringenin and pinocembrin to produce apigenin and chrysin, respectively. The open reading frame(ORF) of DhuFNSⅡ was 1 644 bp in length, encoding 547 amino acids. Subcellular localization showed that the protein was localized on the endoplasmic reticulum. RT-qPCR results showed that DhuFNSⅡ had the highest expression in stems, followed by leaves and roots. The expression levels of DhuFNSⅡ and other target genes in various tissues of D. huoshanense were significantly up-regulated after four kinds of abiotic stresses commonly encountered in the growth process, but the extent of up-regulation varied among treatment groups, with drought and cold stress having more significant effects on gene expression levels. Through the identification and functional analysis of DhuFNSⅡ, this study is expected to contribute to the elucidation of the molecular mechanism of the formation of quality metabolites of D. huoshanense, flavonoid C-glycosides, and provide a reference for its quality formation and scientific cultivation.

Association between Charlson comorbidity index and survival outcomes in patients with prostate cancer: A meta-analysis.

Objective: This meta-analysis aimed to assess the influence of comorbidity, as assessed by the Charlson comorbidity index (CCI), on survival outcomes in patients with prostate cancer (PCa). Methods: We conducted a comprehensive search of the PubMed, Web of Science, and Embase databases to identify studies that examined the association between CCI-defined comorbidity and survival outcomes in PCa patients. We employed a random effect model to merge adjusted hazard ratios (HR) with 95 % confidence intervals (CI) for survival outcomes. Results: Sixteen studies reporting on 17 articles, which collectively included 457,256 patients. For the presence (CCI score ≥1) versus absence (CCI score of 0) of comorbidity, the pooled HR was 1.59 (95 % CI 1.43-1.77) for all-cause mortality, 0.98 (95 % CI 0.90-1.08) for PCa-specific mortality, and 1.88 (95 % CI 1.61-2.21) for other-cause mortality. When compared to a CCI score of 0, the pooled HR of all-cause mortality was 1.30 (95 % CI 1.18-1.44) for a CCI score of 1, 1.65 (95 % CI 1.37-2.00) for a CCI score ≥2, and 1.75 (95 % CI 1.57-1.95) for a CCI score ≥3. Additionally, the pooled HR of other cause mortality was 1.53 (95 % CI 1.41-1.67) for a CCI score of 1, 1.93 (95 % CI 1.74-2.75) for a CCI score ≥2, and 3.95 (95 % CI 2.13-7.34) for a CCI score ≥3. Conclusions: Increased comorbidity, as assessed by the CCI, significantly predicts all-cause and other-cause mortality in patients with PCa, but not PCa-specific mortality. The risk of all-cause and other-cause mortality increases with the burden of comorbidity.

Decreased retinal vascular density is associated with cognitive impairment in CADASIL: an optical coherence tomography angiography study.

PURPOSE: This study aimed to assess alterations in retinal vascular density in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients using optical coherence tomography angiography (OCTA) and investigate their association with MRI and cognitive features. METHODS: Twenty-five patients with CADASIL and forty healthy controls were evaluated by Cirrus HD-OCT 5000 with AngioPlex OCTA to determine changes in macular retinal vasculature. Retinal vasculature parameters between two groups were compared. The MRI lesion burden and neuropsychological scales were also examined in patients. The association between OCTA parameters and MRI/cognitive features was evaluated using partial Spearman rank correlation. RESULTS: The vessel density and perfusion density of whole image in macular region (vessel density: t = - 2.834, p = 0.005; perfusion density: t = - 2.691, p = 0.007) were significantly decreased in patients with CADASIL. Moreover, vessel density of whole image in macular region was negatively associated with Fazekas scores (ρ = - 0.457; p = 0.025) and the number of lacunar infractions (ρ = - 0.425, p = 0.038) after adjustment for age. Decreased macular vessel density and perfusion density of whole image were also associated with MoCA scores (vessel density: ρ = 0.542, p = 0.006; perfusion density: ρ = 0.478, p = 0.018) and other domain-specific neuropsychological tests (p < 0.05) after adjustment for age. CONCLUSION: Decreased retinal vascular density was associated with increased MRI lesion burden and cognitive impairment in patients with CADASIL. Our findings suggest that the degree of retinal vascular involvement, as demonstrated by OCTA, may be consistent with the severity of MRI lesions and the degree of cognitive impairment in patients.

Villosol reverses 5-FU resistance in colorectal cancer by inhibiting the CDKN2A gene regulated TP53-PI3K/Akt signaling axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Patrinia villosa (Juss.) (PV) is the drug of choice in traditional Chinese medicine for the treatment of colorectal cancer (CRC) and has achieved reliable efficacy in clinic. Villosol is the active ingredient in PV. However, the molecular mechanism by which Villosol reverses chemoresistance in CRC remains unclear. AIM OF THE STUDY: Analysis of the molecular mechanism by which Villosol, the active ingredient of PV, reverses CRC/5-FU resistance through modulation of the CDKN2A gene was validated by network pharmacology techniques and experiments. MATERIALS AND METHODS: We identified CDKN2A as a gene associated with 5-FU resistance through gene chip analysis. Next, we conducted a series of functional analyses in cell lines, animal samples, and xenograft models to investigate the role, clinical significance, and abnormal regulatory mechanisms of CDKN2A in 5-FU resistance in CRC. In addition, we screened and obtained a raw ingredient called Villosol, which targets CDKN2A, and investigated its pharmacological effects. RESULTS: Analysis of CRC cells and animal samples showed that the upregulation of CDKN2A expression was strongly associated with 5-FU resistance. CRC cells overexpressing CDKN2A showed reduced sensitivity to 5-FU and enhanced tumor biology in vitro. Inhibition of aberrant activation of CDKN2A enhances the expression of TP53. Mechanistically, overexpression of CDKN2A activates the PI3K/Akt pathway and induces resistance to 5-FU. Villosol inhibited CDKN2A, and CRC/5-FU cells regained sensitivity to 5-FU. Villosol effectively reverses 5-FU resistance through the CDKN2A-TP53-PI3K/Akt axis. CONCLUSION: Changes in CDKN2A gene expression can be used to predict the response of CRC patients to 5-FU therapy. Additionally, inhibiting CDKN2A activation with Villosol may present a new approach to overcoming 5-FU resistance in clinical settings.

A SEER-Medicare Based Quality Score for Patients With Metastatic Upper Tract Urothelial Carcinoma.

BACKGROUND: Population-based studies evaluating outcomes for metastatic upper tract urothelial carcinoma (mUTUC) are sparse and rarely capture both patients with de novo (synchronous) metastases and those who progress to metastatic disease (metachronous). Herein we evaluated the outcomes and costs associated with synchronous and metachronous mUTUC, utilizing a novel Methodology. Additionally, we created a guideline-based quality score to improve care in this space. PATIENTS AND METHODS: We identified all patients with mUTUC aged 66 years and older included in the SEER-Medicare linked database between 2004 and 2012. Achievement of 3 quality criteria was assessed: (1) cancer-specific survival (CSS)>12 months; (2) receipt of systemic therapy; (3) receipt of hospice/palliative care. Total healthcare and out-of-pocket costs were evaluated. Regression analyses were performed to assess characteristics associated with quality criteria and total healthcare costs. RESULTS: Of the 1223 patients identified, at least one quality criterion was met in just 40.2% and only 54 patients (4.4%) received palliative care. In multivariable analysis, patients with synchronous mUTUC (OR:0.55, 95%CI:0.41-0.72), and at least 3 comorbidities (OR:0.68, 95%CI:0.47-0.98) were less likely to achieve at least 1 quality criterion. Meeting at least 1 quality criterion was associated with increased costs ($94,677, 95%CI:87,702-101,652 versus $63,575, 95%CI:59,598-67,552). CONCLUSIONS: Less than half of patients with mUTUC met at least 1 quality criterion. Quality score achievement was associated with a modest increase in total healthcare spending. These findings not only provide guidance for future study of rare diseases using secondary data, but also highlight inadequacies in the current management of mUTUC.

Rural racial disparities and barriers in mammography utilization among Medicare beneficiaries in Texas: A longitudinal study.

This study examined rural racial/ethnic disparities in long-term mammography screening practices among Medicare beneficiaries. A retrospective longitudinal study was conducted using 100% Texas Medicare data for women aged 65-74 who enrolled in Medicare between 2010-2013. Of the 114,939 eligible women, 21.2% of Hispanics, 33.3% of non-Hispanic Blacks (NHB), and 38.4% non-Hispanic Whites (NHW) in rural areas were regular users of mammography, compared to 33.5%, 44.9%, and 45.3% of their counterparts in urban areas, respectively. Stratification analyses showed rural Hispanics and NHB were 33% (95% CI, 25% - 40%) and 22% (95% CI, 6% - 36%) less likely to be regular users of mammography compared to their urban counterparts. Major barriers to routine mammography screening included the lack of a primary care provider, frequent hospitalization, and comorbidity. The findings of this study highlight the importance of addressing rural racial disparities in mammography utilization among older women to ensure equitable screening practices for all populations.

Chinese Ultrasound Doctors Association Guideline on Operational Standards for 2-D Shear Wave Elastography Examination of Musculoskeletal Tissues.

The Ultrasound Physician Branch of the Chinese Medical Doctor Association sought to develop evidence-based recommendations on the operational standards for 2-D shear wave elastography examination of musculoskeletal tissues. A consensus panel of 22 Chinese musculoskeletal ultrasound experts reviewed current scientific evidence and proposed a set of 12 recommendations for 13 key issues, including instruments, operating methods, influencing factors and image interpretation. A final consensus was reached through discussion and voting. On the basis of research evidence and expert opinions, the strength of recommendation for each proposition was assessed using a visual analog scale, while further emphasizing the best available evidence during the question-and-answer session. These expert consensus guidelines encourage facilitation of the standardization of clinical practices for collecting and reporting shear wave elastography data.

Insulin resistance is associated with the presence and severity of retinopathy in patients with type 2 diabetes.

BACKGROUND: To assess the relationship between novel insulin resistance (IR) indices and the presence and severity of diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: This is a cross-sectional study involving 2211 patients. The study outcomes were DR events. The study exposures were IR indices including estimated glucose disposal rate (eGDR), natural logarithm of glucose disposal rate (lnGDR), metabolic insulin resistance score (METS-IR), triglyceride glucose index-body mass index (TyG-BMI), triglyceride glucose index-waist-to-hip ratio (TyG-WHR), and triglyceride/high-density lipoprotein cholesterol(TG/HDL-c ratio). We used binary and multivariate ordered logistic regression models to estimate the association between different IR indices and the presence and severity of DR. Subject work characteristic curves were used to assess the predictive power of different IR indices for DR. RESULTS: DR was present in 25.4% of participants. After adjusting for all covariates, per standard deviation (SD) increases in eGDR (ratio [OR] 0.38 [95% CI 0.32-0.44]), lnGDR (0.34 [0.27-0.42]) were negatively associated with the presence of DR. In contrast, per SD increases in METS-IR (1.97 [1.70-2.28]), TyG-BMI (1.94 [1.68-2.25]), TyG-WHR (2.34 [2.01-2.72]) and TG/HDL-c ratio (1.21 [1.08-1.36]) were positively associated with the presence of DR. eGDR was strongly associated with severity of DR. Of all variables, eGDR had the strongest diagnostic value for DR (AUC = 0.757). CONCLUSIONS: Of the six IR indices, eGDR was significantly associated with the presence and severity of DR in patients with type 2 diabetes. eGDR has a good predictive value for DR. Thus, eGDR maybe a stronger marker of DR.

A Randomized, Single-Dose, Parallel-Controlled Phase I Clinical Comparison of an Omalizumab Biosimilar Candidate with Reference Omalizumab in Healthy Chinese Male Volunteers.

This study evaluated the bioequivalence of omalizumab, a humanized monoclonal antibody against immunoglobulin-E (IgE), with one of its biosimilar candidates. The study was designed as a randomized, double-blind, parallel-controlled trial. A total of subjects who met the inclusion criteria and did not meet the exclusion criteria were dynamically randomly assigned to receive the test drug or the reference drug with a single subcutaneous injection of 150 mg by the minimization method. The test group and the reference group had similar demographic characteristics and baseline characteristics of total IgE. The 90% confidence interval of the geometric average ratio of the area under the serum concentration-time curve from the time 0 to the time of last quantifiable concentration, the area under the serum concentration curve from time 0 to infinity, and the maximum observed serum concentration between the 2 groups were within 80%-125%, showing bioequivalence. The changing trend of total and free IgE in the 2 groups was similar after administration, proving the pharmacodynamic similarity. The 2 groups had no significant difference in the positive rate of antidrug antibodies, and the total positive rate of neutralizing antibodies was 0. The incidence of treatment-emergent adverse events and treatment-related adverse events were similar between the 2 groups, with no serious adverse events. This study shows that the test drug had similar pharmacokinetics, immunogenicity, and safety to the reference omalizumab in healthy male subjects.

Molecular Engineering of Sulfone-Xanthone Chromophore for Enhanced Fluorescence Navigation.

Enriching the palette of high-performance fluorescent dyes is vital to support the frontier of biomedical imaging. Although various rhodamine skeletons remain the premier type of small-molecule fluorophores due to the apparent high brightness and flexible modifiability, they still suffer from the inherent defect of small Stokes shift due to the nonideal fluorescence imaging signal-to-background ratio. Especially, the rising class of fluorescent dyes, sulfone-substituted xanthone, exhibits great potential, but low chemical stability is also pointed out as the problem. Molecular engineering of sulfone-xanthone to obtain a large Stokes shift and high stability is highly desired, but it is still scarce. Herein, we present the combination modification method for optimizing the performance of sulfone-xanthone. These redesigned fluorescent skeletons owned greatly improved stability and Stokes shift compared with the parent sulfone-rhodamine. To the proof of bioimaging capacity, annexin protein-targeted peptide LS301 was introduced to the most promising dyes, J-S-ARh, to form the tumor-targeted fluorescent probe, J-S-LS301. The resulting probe, J-S-LS301, can be an outstanding fluorescence tool for the orthotopic transplantation tumor model of hepatocellular carcinoma imaging and on-site pathological analysis. In summary, the combination method could serve as a basis for rational optimization of sulfone-xanthone. Overall, the chemistry reported here broadens the scope of accessible sulfone-xanthone functionality and, in turn, enables to facilitate the translation of biomedical research toward the clinical domain.

[Evaluation of low intensity Nd: YAG laser and traditional drugs in the treatment of myofascial pain].

PURPOSE: To evaluate the efficacy of low intensity Nd: YAG laser and traditional drugs in the treatment of myofascial pain (MP). METHODS: Eighty patients with MP were divided into laser group(n=40) and traditional medicine group(n=40) according to the principle of randomization and double-blindness. The patients in the laser group were treated with low intensity Nd :YAG laser(1 064 nm, 8 J/cm2, 250 mW) , with an interval of 48 h between the two laser treatments. The whole course of treatment was 10 times. Patients in the traditional medicine group uesd celecoxib capsules, 1 capsulet each time(0.2 g), twice a day for 2 weeks. Before and after each treatment, mouth opening, protrusion excursion, lateral movement of the affected side and lateral movement of the contralateral side were measured, and pain visual analogue scores (VAS) were measured and recorded. The data were statistically analyzed with SPSS 22.0 software package. RESULTS: Patients in laser group had significantly improved mandibular function and movement status(P＜0.05) and pain symptoms(P＜0.05); patients in traditional medicine group had the same significant improvement on mandibular functional movement status(P＜0.05) and pain symptoms (P＜0.05). The total effective rate of the two groups had no significant difference(P＞0.05). The VAS score of patients in laser group was lower than that of traditional medicine group, but the difference was not significant(P＞0.05). CONCLUSIONS: Low intensity Nd: YAG laser and traditional medicine can effectively relieve the symptoms of myofascial pain and improve mandibular function and movement. Laser treatment has the advantages of short course of treatment, high efficiency, no pain and fewer side effects, which is worthy of clinical application.

Uric acid index is a risk for mild cognitive impairment in type 2 diabetes.

BACKGROUND: A new uric acid (UA) index has recently been proposed, while serum uric acid (SUA), fasting triglyceride, and fasting blood glucose levels in the index are shown to affect cognitive function. This study aims to investigate the clinical value of the UA index for assessing mild cognitive impairment (MCI) in type 2 diabetes (T2D) patients. METHODS: This was an observational cross-sectional study with 616 participants. A generalized additive model was used to determine a linear or curvilinear relationship between cognitive performance and the UA index. Logistic regression and random forest models were both developed. A receiver operating characteristic curve (ROC) was delineated and the area under the curve (AUC) was calculated. RESULTS: MCI was diagnosed in 313 participants (50.81%). Compared with the T2D-normal cognitive function group, MCI subjects had higher UA indexes, lower cognitive scores, and lower education levels (p < 0.001). Generalized additive models showed the UA index and the Montreal Cognitive Assessment (MoCA) score to be decreased linearly (p < 0.001). The UA index AUC was 0.751 (95% CI = 0.713-0.789, p < 0.001). The optimal cut-off point for the identification of MCI based on the UA index was 11.26 (sensitivity: 62.3%, specificity: 75.9%). Results for females in the cohort yielded an AUC change of + 2.5%, the less-educated population (AUC change of + 4.7%), and the hypertensive population (AUC change of + 1.1%). The AUCs were 0.791 (95% CI = 0.720-0.863) for the random forest model and 0.804 (95% CI = 0.770-0.837) for the logistic regression model, and no statistical significance was found (p = 0.758). CONCLUSION: This study showed that the increased UA index was independently associated with MCI in patients with T2D, especially among female, less-educated, and hypertensive patients. It could be a potential indicator of MCI in T2D patients.

Association Between Aspirin-Exacerbated Respiratory Disease and Atherosclerotic Cardiovascular Disease: A Retrospective Review of US Claims Data.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) consists of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and hypersensitivity to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs). Asthma is associated with increased risk of atherosclerotic cardiovascular diseases (ASCVD). However, there is lack of data on association between AERD and ASCVD. OBJECTIVE: To investigate the relationship between AERD and subsequent risk of ASCVD. METHODS: An algorithm to find patients with AERD was generated and validated through chart review at our home institution. This algorithm was applied to a national insurance claims database to obtain data for a retrospective cohort study. Demographic and comorbidity data were obtained for propensity matching. Several methods of analysis were performed on the data. RESULTS: A total of 571 patients met criteria for AERD; 3909 met criteria for asthma, CRSwNP, and no allergy to aspirin or NSAIDs (group 1); and 75,050 met criteria for asthma, CRS without nasal polyps, and no allergy to aspirin or NSAIDs (group 2). After covariate adjustment, AERD was significantly associated with ASCVD, including severe ASCVD, over groups 1 and 2 regardless of asthma severity. CONCLUSION: Patients with AERD are at higher risk of ASCVD than patients with asthma and CRSwNP or CRS without nasal polyps, underscoring the need for early ASCVD screening and a consideration for aspirin desensitization or use of a nonaspirin antiplatelet agent in the setting of AERD and comorbid ASCVD.

Rational Design of pH-Independent and High-Fidelity Near-Infrared Tunable Fluorescent Probes for Tracking Leucine Aminopeptidase In Vivo.

Accurate detection of target analytes and generation of high-fidelity fluorescence signals are particularly critical in life sciences and clinical diagnostics. However, the majority of current NIR-I fluorescent probes are vulnerable to pH effects resulting in signal distortion. In this work, a series of fluorescence-tunable and pH-independent probes are reported by combining optically tunable groups of unsymmetric Si-rhodamines and introducing the methoxy instead of the spiro ring on the benzene ring at position 9. To validate the concept, the leucine aminopeptidase response site was introduced into Si-2,6OMe-NH2 with the best optical properties to synthesize Si-LAP for monitoring the intrahepatic LAP in vivo. Therefore, the design approach may provide a new and practical strategy for designing innovative functional fluorescent probes and generating high-stability and high-fidelity fluorescent signals.