Customized Lanthanide Nanobiohybrids for Noninvasive Precise Phototheranostics of Pulmonary Biofilm Infection.

A noninvasive strategy for in situ diagnosis and precise treatment of bacterial biofilm infections is highly anticipated but still a great challenge. Currently, no in vivo biofilm-targeted theranostic agent is available. Herein, we fabricated intelligent theranostic alginate lyase (Aly)-NaNdF4 nanohybrids with a 220 nm sunflower-like structure (NaNdF4@DMS-Aly) through an enrichment-encapsulating strategy, which exhibited excellent photothermal conversion efficiency and the second near-infrared (NIR-II) luminescence. Benefiting from the site-specific targeting and biofilm-responsive Aly release from NaNdF4@DMS-Aly, we not only enabled noninvasive diagnosis but also realized Aly-photothermal synergistic therapy and real-time evaluation of therapeutic effect in mice models with Pseudomonas aeruginosa biofilm-induced pulmonary infection. Furthermore, such nanobiohybrids with a sheddable siliceous shell are capable of delaying the NaNdF4 dissolution and biodegradation upon accomplishing the therapy, which is highly beneficial for the biosafety of theranostic agents.

Effect of Intermittent Low-Pressure Radiofrequency Helium Cold Plasma Treatments on Rice Gelatinization, Fatty Acid, and Hygroscopicity.

To establish the safe and reproducible effects of cold plasma (CP) technology on food products, this study evaluated the gelatinization parameters, fatty acid profile, and hygroscopic properties of rice grains repeatedly treated with low-pressure radiofrequency (RF) helium CP (13.56 MHz, 140 Pa, 120 W-20s, 0-4 times, and 300 g sample). Compared with the untreated (zero times) sample, with an increase in CP treatment times from one to four on rice, the water contact angle and cooking time decreased, while the water absorption rate and freshness index increased, and the pH value remained unchanged. CP repeating treatments essentially had no effect on the gelatinization enthalpy, but significantly increased the peak temperature of gelatinization. From the pasting profile of rice that has been repeatedly CP treated, the peak, breakdown, and setback viscosities in flour paste decreased. CP repeating treatments on rice did not change the short-range molecular order of starch. Compared with the untreated sample, the first helium CP treatment maintained the content of C18:1n9c, C18:2n6c, and C18:3n3, but the second to fourth CP treatment significantly decreased contents of these fatty acids (FAs) as the C18:0 content increased. The first three CP treatments can increase the water and sucrose solvent retention capacity in rice flours. CP repeatedly treated rice first exhibits the similar monolayer water content and solid surface area of water sorption. Principal component analysis shows that contact angle, pasting parameters, and fatty acid profile in milled rice are quite sensitive to CP treatment. Results support that the effect of low-pressure RF 120W helium CP treatment 20 s on rice grains is perdurable, and the improvement of CP intermittent treatments on rice cooking and pasting properties is an added benefit, and the hygroscopic properties of rice was kept.

Palladium(II)-Catalyzed Tandem γ-C(sp2)-H Arylation and Cyclization for the Construction of Natural Product-Like Polycyclic Fused ortho-Quinone Scaffolds.

Here, we report a novel strategy for the direct construction of polycyclic fused ortho-quinone scaffolds through palladium(II)-catalyzed tandem γ-C(sp2)-H arylation and cyclization of arylglyoxals with aryl iodides. This transformation features unique tandem transient directing of γ-C(sp2)-H arylation and cyclization reaction mode, broad substrate scope, especially for the aromatic substrates containing oxygen and sulfur atoms, and avoiding the common issue of aromatization due to the construction of the hexatomic ring.

Association between Urinary Lead and Female Breast Cancer: A Population-Based Cross-Sectional Study.

BACKGROUND: Previous studies have explored the relationship between serum lead levels and the risk of female breast cancer (FBC). However, it is still uncertain whether urinary lead levels are associated with FBC. This study aimed to investigate the potential association between urinary lead and FBC. METHODS: A cross-sectional case-control study was conducted using the National Health and Nutrition Examination Survey (NHANES), which is a series of cross-sectional, nationally representative surveys of the United States population consisting of 10 survey waves from 1999 to 2018. This study analyzed a total of 2795 female participants (≥20 years), consisting of 210 participants with FBC and 2585 healthy controls. Urinary lead was detected using Inductively Coupled Plasma-Mass Spectrometry, which was divided into four levels by using quartiles-defining cut points. Multivariate logistic regression was used to analyze the association between urinary lead and FBC. RESULTS: Multivariate logistic regression revealed that urinary lead was positively correlated with FBC (Odds ratio [OR], 2.16; 95% confidence interval [CI]: [1.18, 3.95], p < 0.05) in a fully adjusted model. There were significantly increased ORs of FBC in quartile 4 (Q4) and quartile 3 (Q3), compared with the lowest quartile 1 (Q1) (Q4, OR = 1.48, 95% CI [0.89, 2.48]; Q3: OR = 1.01, 95% CI [0.59, 1.73], p for trend = 0.021). No significant interaction effects were observed between urinary lead levels and FBC between the subgroups (age, race, educational status, body mass index (BMI), marital status, family income to poverty ratio, hypertension status, diabetes status, renal function status, smoking history, ever been pregnant, oral contraceptive use, occupation classification, etc.) (All interaction p-value > 0.05). CONCLUSIONS: Urinary lead is likely positively associated with FBC in the US population.

Association between atherosclerosis and primary Sjogren's syndrome: A cross-sectional study.

Background and Aims: Atherosclerosis (AS) risk increases in patients with systemic autoimmune diseases. The association and mechanism between primary Sjogren's syndrome (pSS) and AS haven't been explained for now. We did this cross-sectional study to clarify the prevalence and risk factors of AS in patients with pSS, and to further explore how immune cells and inflammatory cytokines work in the process. Methods: Patients with pSS were enrolled. General information, AS events, immune cells, inflammatory cytokines, and related clinical data were recorded. Prevalence of AS events was calculated. Correlation analysis between immune factors and AS quantitative parameters were conducted by SPSS v20.0. Results: A total of 155 pSS patients were included with a median Framingham 10-year risk of 7%. Sixty-four AS events were recorded, with a prevalence of 41.3%. Carotid intima-media thickness was positively correlated to immunoglobulin (Ig) A (r = 0.245, p = 0.030) and negatively correlated to IgM (r = -0.227, p = 0.045). Left ankle-brachial pulse wave velocity (baPWV) was positively correlated to the course of disease (r = 0.352, p = 0.004), B cells (r = 0.410, p = 0.001), and T helper (Th) cells (r = 0.284, p = 0.029), while negatively correlated to IgM (r = -0.257, p = 0.042). Right baPWV was positively correlated to the course of pSS (r = 0.319, p = 0.010), B cells (r = 0.453, p < 0.001), Th cells (r = 0.302, p = 0.020), and C-reactive protein (CRP) (r = 0.286, p = 0.042). Use of hydroxychloroquine, cyclophosphamide, and glucocorticoids had no impact on AS events. Conclusion: The prevalence of AS in patients with pSS is reported to be 41.3%. Several risk factors have been associated with AS in these patients, including the duration of the disease, levels of Th cells, B lymphocytes, and CRP. Interestingly, IgM appears to have a protective effect against AS. It is worth noting that traditional therapy for pSS does not seem to have any effect in preventing AS events.

Th6-Based Multicomponent Heterometallic Metal-Organic Frameworks Featuring 6,12-Connected Topology for Iodine Adsorption.

Its high coordination number and tendency to cluster make Th4+ suitable for constructing metal-organic frameworks (MOFs) with novel topologies. In this work, two novel thorium-based heterometallic MOF isomers (IHEP-17 and IHEP-18) were assembled from a Th6 cluster, a multifunctional organic ligand [4-(1H-pyrazol-4-yl)benzoic acid (HPyba)], and Cu2+/Ni2+ cations via the one-pot solvothermal synthesis strategy. The framework features a 6,12-connected new topology net and contains two kinds of supramolecular cage structures, Th36M4 and Th24M2, suitable for guest exchange. Both MOF materials can efficiently adsorb I2. X-ray photoelectron spectroscopy, Raman spectroscopy, and single-crystal X-ray diffraction indicate that the adsorbed iodine is uniformly distributed within the Th36M4 cage but not the Th24M2 cage in the form of I3-.

AIEgen-sensitized lanthanide nanocrystals as luminescent probes for intracellular Fe3+ monitoring.

The abnormal Fe3+ level is known to cause various diseases, such as heart failure, liver damage and neurodegeneration. In situ probing Fe3+ in living cells or organisms is highly desired for both biological research and medical diagnostics. Herein, hybrid nanocomposites NaEuF4@TCPP were constructed by the assembly of an aggregation-induced emission luminogen (AIEgen) TCPP and NaEuF4 nanocrystals (NCs). The anchored TCPP on the surface of NaEuF4 NCs can reduce rotational relaxation of the excited state and efficiently transfer the energy to the Eu3+ ions with minimized nonradiative energy loss. Consequently, the prepared NaEuF4@TCPP nanoparticles (NPs) exhibited an intense red emission with a 103-fold enhancement relative to that in NaEuF4 NCs under 365 nm excitation. A selectively quenching response to Fe3+ ions for the NaEuF4@TCPP NPs makes them luminescent probes for sensitive detection of Fe3+ ions with a low detection limit of 340 nM. Moreover, the luminescence of NaEuF4@TCPP NPs could be recovered by the addition of iron chelators. Benefiting from their good biocompatibility and stability in living cells, together with the characteristic of the reversible luminescence response, the lipo-coated NaEuF4@TCPP probes were successfully applied for real-time monitoring of Fe3+ ions in living HeLa cells. These results are expected to motivate the exploration of AIE-based lanthanide probes for sensing and biomedical applications.

Revealing and modeling of fire products in gas-phase for epoxy/black phosphorus-based nanocomposites.

This work aims at revealing and optimizing the mechanism, to promote the design of phosphorus-based flame retardants (PFRs) for controlling the spread of fire risk caused by the continuous spread of polymers. Herein, we synthesized about 10 nm TiO2 grown in situ on the surface of BP through a simple hydrothermal procedure to introduce it into epoxy (EP/BP-TiO2). In the first place, EP/BP-TiO22.0 nanocomposite achieves a reduction of 58.96% and 50.35% in PHRR and THR, respectively. Secondly, the pyrolysis of BP from Pn to P4, P3 and P2 is revealed. As a guide, P4 is established as a characteristic product of the analytical model for evaluating the effects in the gas phase for BP-based hybrids. Finally, this work clarifies the enhancement path for BP-TiO2 is optimized for the capturing of OH· and H· radicals by P4(POx). Crucially, this study reveals and controls the mechanism of the BP-based hybrids at the molecular level, which is expected to provide a promising analytical model for broad market PFRs design to address the risks and challenges of casualties and ecology caused by composites fire.

Menopause-Related Symptoms and Influencing Factors in Mosuo, Yi, and Han Middle-Aged Women in China.

Although previous studies showed that women's menopause-related symptoms varied in different ethnic groups and countries, and were affected by specific social and cultural factors, few studies have been conducted to explore menopause-related symptoms and its influencing factors in middle-aged women among ethnic groups in China. This study aimed to explore the characteristics of menopause-related symptoms and its influencing factors among Mosuo, Yi, and Han women in Yongning area of Yunnan province, China. A cross-cultural design by snowball sampling method was used to recruit 208 women aged 40-60 from Yongning Township, Ninglang County, Yunnan province, China. The 11-item Menopause Rating Scale (MRS) was used to assess menopause-related symptoms. Compared with Yi and Han women, Mosuo women were accorded the highest family status. Multiple linear regression analyses showed that ethnicity, age, family support, and family decision-making patterns were associated with the severity of menopause-related symptoms. Yi and Han women had more severe menopause-related symptoms than Mosuo women. Among the three groups, women living in "female-dominated" and "co-deliberated" households had significantly lower scores of menopause-related symptoms than those in "male-dominated" households. This study indicates that menopause-related symptoms vary among middle-aged women in different ethnic groups. A higher level of female status in the family and family support may be protective factors of menopause-related symptoms in middle-aged women.

Identification and evaluation of a lipid-lowering small compound in preclinical models and in a Phase I trial.

Developing non-statin-based small compounds to battle the global epidemic of hyperlipidemia remains challenging. Here, we report the discovery of DC371739, an indole-containing tetrahydroisoquinoline compound with promising lipid-lowering effects, both in vitro and in vivo, and with good tolerability in a Phase I clinical trial (NCT04927221). DC371739 significantly reduced the plasma levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides simultaneously in several animal models and showed preliminary positive results in the Phase I trial. Mechanistically, DC371739 acts in a distinct manner from other known lipid-lowering reagents. We show that it physically binds HNF-1α, impeding the transcription of both PCSK9 and ANGPTL3, two genes that are known to contribute to hypercholesterolemia and dyslipidemia. Moreover, the distinct mechanism of action of DC371739 allows its combination with atorvastatin treatment to additively improve dyslipidemia, while providing a potential alternative therapeutic strategy for individuals with statin intolerance.

Construction of bismaleimide resin with enhanced flame retardancy and mechanical properties based on a novel DOPO-derived bismaleimide monomer.

It's known that the application of bismaleimide resins (BMI) is limited due to its brittleness and poor flame retardancy. A novel type of BMI monomer (MADQ) based on the typical phosphorus series flame retardant DOPO is designed to improve the fire safety of BMI. Besides, aliphatic long chain structure is introduced in MADQ, which is supposed to be conducive to reducing the rigidity of the BMI cross-linked network and thus to improve the toughness of BMI. It's seen that with the incorporation of 5.24 wt% MADQ, the peak of heat release rate (PHRR) and total heat release (THR) of resultant BMI/MADQ-5 is reduced by 37.7% and 33.9%, respectively. Meanwhile, with modification of 1.07 wt% MADQ, BMI/MADQ-1 possesses UL-94V-0 rating. The relevant mechanism analysis reveals that the phosphaphenanthrene group in MADQ can exert flame retardancy effect both in condensed and gas phase. Besides, the impact strength of the BMI/MADQ is maximally increased by nearly 90.1%. Furthermore, the BMI/MADQ still maintains high tensile strength and thermal stability, which indicates the modification of MADQ did not deteriorate other properties of BMI. An innovative research idea and research basis for the preparation of intrinsic flame-retardant and toughened BMI is provided in this work.

Boosting the Self-Trapped Exciton Emission in Alloyed Cs2 (Ag/Na)InCl6 Double Perovskite via Cu+ Doping.

Fundamental understanding of the effect of doping on the optical properties of 3D double perovskites (DPs) especially the dynamics of self-trapped excitons (STEs) is of vital importance for their optoelectronic applications. Herein, a unique strategy via Cu+ doping to achieve efficient STE emission in the alloyed lead-free Cs2 (Ag/Na)InCl6 DPs is reported. A small amount (1.0 mol%) of Cu+ doping results in boosted STE emission in the crystals, with photoluminescence (PL) quantum yield increasing from 19.0% to 62.6% and excitation band shifting from 310 to 365 nm. Temperature-dependent PL and femtosecond transient absorption spectroscopies reveal that the remarkable PL enhancement originates from the increased radiative recombination rate and density of STEs, as a result of symmetry breakdown of the STE wavefunction at the octahedral Ag+ site. These findings provide deep insights into the STE dynamics in Cu+ -doped Cs2 (Ag/Na)InCl6 , thereby laying a foundation for the future design of new lead-free DPs with efficient STE emission.

Hierarchical core-shell SiO2@COFs@metallic oxide architecture: An efficient flame retardant and toxic smoke suppression for polystyrene.

SiO2@3COFs@CuO and SiO2@3COFs@Fe2O3 are prepared in this study. Then SiO2 and its hybrids are incorporated into PS through solution blending method. The thermal stability, mechanical performance, combustion performance and smoke density of PS and its nanocomposite are investigated. The temperature at 5 wt% weight loss and the maximum weight loss rate of PS/SiO2@3COFs@ Fe2O3 (PS 4) under air are 15 and 14 °C higher than that of neat one, respectively. The glass-transition temperature of PS/SiO2@3COFs (PS 2) is 1.5 °C lower than that of PS, which can conclude that SiO2@3COFs contributes to impact strength of PS 0. The peak heat release rate (20.8%) and total heat release (14.0%) of PS 2 decreases further compared with that of PS 0. The smoke density of PS 4 is 23.1% lower than that of neat PS. The influence of SiO2 and its nano-hybrids on the pyrolysis and combustion of PS is investigated. Incorporation of SiO2 and its nano-hybrids shows little effect on pyrolysis process of PS. However, heat resistance of PS is enhanced obviously and thermal degradation rate of PS is also decreased through incorporation of SiO2 and its nano-hybrids. The gaseous pyrolysis products (aromatic compounds and alkenyl compounds) of PS and its nanocomposite also decrease.

Multifunctional High-Efficiency Additive with Synergistic Anion and Cation Coordination for High-Performance LiNi0.8Co0.1Mn0.1O2 Lithium Metal Batteries.

Safety and high energy density have long restricted the large-scale practical application of lithium metal batteries because of the unbridled growth of lithium dendrites and the rapid deteriorating cycle performance of the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode. Herein, an additive of RbNO3 with multiple functions is proposed for dendrite-free NCM811 lithium metal batteries. Benefiting from the electrostatic shielding effect formed by Rb+ during the Li+ deposition process and the solvation effect of NO3- to regulate lithium deposition, a high Coulombic efficiency of 95.02% (compared with the low Coulombic efficiency of 89.37% in the blank electrolyte) is acquired in Li//Cu cells, and the uniform growth of the lithium metal deposition with a large strawberry-like morphology is achieved. Moreover, when a cathode of NCM811 matches with a lithium metal anode, an extraordinary capacity retention of 93.67% after 200 cycles with a high Coulombic efficiency of 99.7% in the electrolyte with the RbNO3 system (a capacity retention of 80.1% with a Coulombic efficiency of 98.0% for the blank electrolyte) is achieved at 1C. This work provides guidance for the development of high-efficiency additives with dual synergistic regulation effects of anions and cations for lithium metal batteries in the future.

Synergistic Lysozyme-Photodynamic Therapy Against Resistant Bacteria based on an Intelligent Upconversion Nanoplatform.

The rapid emergence of drug-resistant bacteria has raised a great social concern together with the impetus for exploring advanced antibacterial ways. NIR-triggered antimicrobial photodynamic therapy (PDT) by lanthanide-doped upconversion nanoparticles (UCNP) as energy donor exhibits the advantages of high tissue penetration, broad antibacterial spectrum and less acquired resistance, but is still limited by its low efficacy. Now we designed a bio-inorganic nanohybrid and combined lysozyme (LYZ) with UCNP-PDT system to enhance the efficiency against resistant bacteria. Benefiting from the rapid adhesion to bacteria, intelligently bacteria-responsive LYZ release and synergistic LYZ-PDT effect, the nanoplatform achieves an exceptionally strong bactericidal capacity and conspicuous bacteriostasis on methicillin-resistant S. aureus. These findings pave the way for designing efficiently antibacterial nanomaterials and provide a new strategy for combating deep-tissue bacterial infection.

5-Aminonaphthalene derivatives as selective nonnucleoside nuclear receptor binding SET domain-protein 2 (NSD2) inhibitors for the treatment of multiple myeloma.

Approximately 20% of multiple myeloma (MM) are caused by a chromosomal translocation t (4; 14) that leads to the overexpression of the nuclear receptor binding SET domain-protein 2 (NSD2) histone methyltransferase. NSD2 catalyzes the methylation of lysine 36 on histone H3 (H3K36me2) and is associated with transcriptionally active regions. Using high-throughput screening (HTS) with biological analyses, a series of 5-aminonaphthalene derivatives were designed and synthesized as novel NSD2 inhibitors. Among all the prepared compounds, 9c displayed a good NSD2 inhibitory activity (IC50 = 2.7 µM) and selectivity against both SET-domain-containing and non-SET-domain-containing methyltransferases. Preliminary research indicates the inhibition mechanism of compound 9c by significantly suppressed the methylation of H3K36me2. Compound 9c specifically inhibits the proliferation of the human B cell precursor leukemia cell line RS4:11 and the human myeloma cell line KMS11 by inducing cell cycle arrest and apoptosis with little cytotoxicity. It has been reported that the anti-cancer effect of compound 9c is partly achieved by completely suppressing the transcriptional activation of NSD2-targeted genes. When administered intraperitoneally at 25 mg/kg, compound 9c suppressed the tumor growth of RS4:11 xenografts in vivo and no body weight loss was detected in the tested SCID mice.

In situ confined growth of ultrasmall perovskite quantum dots in metal-organic frameworks and their quantum confinement effect.

The metal halide perovskite quantum dots (APbX3 PeQDs; A = Cs or CH3NH3; X = Cl, Br or I) have emerged as a new type of promising optoelectronic material for light-emitting and photovoltaic applications because of their excellent optical properties. However, the precise control over the size and photoluminescence (PL) emission of APbX3 PeQDs remains a great challenge, which has been one of the main obstacles to the applications of PeQDs. Herein, we report a unique strategy for in situ confined growth of MAPbBr3 (MA = CH3NH3) PeQDs by using porous metal-organic framework (MOF) UiO-66 as a matrix. By introducing Pb(Ac)2 and MABr precursors into the pores of UiO-66 via a stepwise approach, ultrasmall MAPbBr3 PeQDs were in situ grown in the matrix with the size tuned from 6.4 to 3.3 nm by changing the concentration of the Pb(Ac)2 precursor. Accordingly, the PL emission wavelength of the resulting MAPbBr3 PeQDs was blue-shifted from 521 to 486 nm with the size reduction, owing to the strong quantum confinement effect of the PeQDs. Due to the surface passivation effect endowed by the UiO-66 matrix, the ultrasmall MAPbBr3 PeQDs also displayed a high PL quantum yield (PLQY) of 43.3% and a long PL lifetime of 100.3 ns. This study proposes a new strategy to prepare ultrasmall PeQDs and effectively control their sizes and PL emissions, which may open up new avenues for the development of high-performance luminescent PeQDs for diverse applications.

Luminescent lanthanide metal-organic framework nanoprobes: from fundamentals to bioapplications.

Metal-organic frameworks (MOFs), a unique type of porous material characterized by high porosity, large internal surface area and remarkable structural tunability, have emerged as very attractive functional materials for a variety of applications. As a promising subclass of MOFs, lanthanide metal-organic frameworks (Ln-MOFs) integrate the unique advantages of MOFs and the intrinsic features of lanthanide ions, such as sharp emission bands, long luminescent lifetimes, large Stokes shifts, high color purity and high resistance to photobleaching. In this minireview, we provide a brief overview of the most recent advances in luminescent Ln-MOF nanoprobes, which covers from their chemical and physical fundamentals to bioapplications, including their synthetic strategies, optical properties and promising bioapplications in biodetection, bioimaging and therapy. Finally, some of the most important emerging trends and future efforts toward this rapidly evolving field are also envisioned.

Ir(iii)-Catalyzed direct C-H functionalization of N-phenylacetamide with α-diazo quinones: a novel strategy for producing 2-hydroxy-2'-amino-1,2'-biaryl scaffolds.

α-Diazo quinones were applied in an Ir(iii)-catalyzed direct C-H functionalization assisted by N-phenylacetamide for the construction of highly functionalized 2-hydroxy-2'-amino-1,1'-biaryl scaffolds in good to excellent yields. This strategy features operational simplicity, atom- and step-economy and high efficiency.

A Strategy of NIR Dual-Excitation Upconversion for Ratiometric Intracellular Detection.

Intracellular detection is highly desirable for biological research and clinical diagnosis, yet its quantitative analysis with noninvasivity, sensitivity, and accuracy remains challenging. Herein, a near-infrared (NIR) dual-excitation strategy is reported for ratiometric intracellular detection through the design of dye-sensitized upconversion probes and employment of a purpose-built NIR dual-laser confocal microscope. NIR dye IR808, a recognizer of intracellular analyte hypochlorite, is introduced as energy donor and Yb,Er-doped NaGdF4 upconversion nanoparticles are adopted as energy acceptor in the as-designed nanoprobes. The efficient analyte-dependent energy transfer and low background luminescence endow the nanoprobes with ultrahigh sensitivity. In addition, with the nonanalyte-dependent upconversion luminescence (UCL) excited by 980 nm as a self-calibrated signal, the interference from environmental fluctuation can be alleviated. Furthermore, the dual 808/980 nm excited ratiometric UCL is demonstrated for the quantification of the level of intracellular hypochlorite. Particularly, the intrinsic hypochlorite with only nanomolar concentration in live MCF-7 cells in the absence of exogenous stimuli is determined. Such an NIR dual-excitation ratiometric strategy based on dye-sensitized UCL probes can be easily extended to detect various intracellular analytes through tailoring the reactive NIR dyes, which provides a promising tool for probing biochemical processes in live cells and diagnosing diseases.