Enzyme-Instructed Photoactivatable Supramolecular Antigens on Cancer Cell Membranes for Precision-Controlled T-Cell-Based Cancer Immunotherapy.

Cancer immunotherapies based on cytotoxic CD8+ T lymphocytes (CTLs) are highly promising for cancer treatment. The specific interaction between T-cell receptors and peptide-MHC-I complexes (pMHC-I) on cancer cell membranes critically determines their therapeutic outcomes. However, the lack of appropriate endogenous antigens for MHC-I presentation disables tumor recognition by CTLs. By devising three antigen-loaded self-assembling peptides of pY-K(Ag)-ERGD, pY-K(Ag)-E, and Y-K(Ag)-ERGD to noncovalently generate light-activatable supramolecular antigens at tumor sites in different manners, we report pY-K(Ag)-ERGD as a promising candidate to endow tumor cells with pMHC-I targets on demand. Specifically, pY-K(Ag)-ERGD first generates low-antigenic supramolecular antigens on cancer cell membranes, and a successive light pulse allows antigen payloads to efficiently release from the supramolecular scaffold, directly producing antigenic pMHC-I. Intravenous administration of pY-K(Ag)-ERGD enables light-controlled tumor inhibition when combined with adoptively transferred antigen-specific CTLs. Our strategy is feasible for broadening tumor antigen repertoires for T-cell immunotherapies and advancing precision-controlled T-cell immunotherapies.

A novel IQ mismatch compensation method in wideband direct-conversion receivers.

Direct-conversion receivers (DCRs) have been widely used in recent years due to their small size and low power consumption. However, the mismatch between the in-phase (I) and the quadrature (Q) branches will seriously affect the performance of the DCRs. This paper proposes a novel blind compensation method to suppress the interference introduced by IQ mismatch. Based on the Hilbert transform, our proposed method can obtain the orthogonal signal of the I-channel signal by utilizing the Weaver architecture. Compared with traditional compensation methods, the main difference of the proposed method is that it ignores prior information, training sequences, and additional hardware circuits. Furthermore, the complexity of the proposed blind compensation method is low because no iterative operations are involved in the compensation process. The simulation results show that the proposed method has an excellent compensation performance, especially in wideband applications.

TRPS1 expression in primary and metastatic prostatic adenocarcinoma, muscle invasive bladder urothelial carcinoma, and breast carcinoma: Is TRPS1 truly specific and sensitive for a breast primary?

Trichorhinophalangeal syndrome type 1 (TRPS1) has been reported to be a sensitive and specific immunohistochemical (IHC) marker for breast carcinomas, especially when determining primary site of origin. However, there is limited data on TRPS1 expression in prostate and bladder cancers. A two-phase study was performed with 1) an exploratory cohort analyzing TRPS1 gene alterations in prostate, bladder, and breast carcinoma and TPRS1 mRNA expression data in prostate and bladder carcinoma; and 2) TRPS1 and GATA3 IHC in a confirmatory cohort in prostate, bladder, and breast carcinoma samples. Gene alterations were identified in a subset of breast, bladder, and prostate carcinomas and mRNA was consistently detected. In the IHC cohort, 183/210 (87.1 %) of breast, 22/69 (31.9 %) of prostate, and 20/73 (27.4 %) of urothelial carcinomas showed staining with TRPS1. Intermediate to high expression of TRPS1 was observed in 173/210 (82.8 %) of breast, 17/69 (24.6 %) of prostate, and 15/73 (20.5 %) of urothelial carcinomas. Furthermore, in prostate cancer, 26.9 % of pelvic lymph node metastases and 50 % in sites of distant metastases showed expression. Increased TRPS1 mRNA expression (p = 0.032) and IHC expression (p = 0.040) correlated with worse overall survival in bladder cancer. By comparison, GATA3 IHC stained 136/210 (64.8 %) of breast, 0/69 (0 %) of prostate, and 63/73 (93 %) of bladder carcinomas. Intermediate to high expression of GATA3 was seen in 131/210 (62.4 %) of breast and 63/73 (93 %) of bladder carcinomas. This study shows there is significant staining of TRPS1 in bladder and prostate cancers. As a result, comprehensive studies are needed to establish the true specificity of TRPS1 IHC stain across various tumor types before its widespread clinical adoption.

First-principles studies on the electronic and photocatalytic water splitting properties of surface functionalized Y2C-based MXenes.

Recently, MXenes, an emerging family of two-dimensional (2D) materials, have attracted increasing interest for photocatalytic water splitting due to their various excellent physical and chemical properties, such as large specific surface area, good hydrophilicity, and remarkable light absorption ability. However, the photocatalysts of MXenes with symmetric structures are limited by rapid recombination of photo-generated carriers and the prerequisite of a large band gap no less than 1.23 eV. Differently, Janus MXenes with different surface functional groups facilitate the separation of photo-generated electrons and holes with the help of the intrinsic electric field. And, at the same time, there is no prerequisite for the band gap of Janus MXene photocatalysts as long as they possess appropriate band edge positions. Here, we explored the structural, electronic and photocatalytic water splitting properties of symmetric Y2CT2 and Janus Y2CTT' MXenes (T, T' = H, F, Cl, OH) using the density functional theory (DFT) method. Our calculations show that all the investigated Y2CT2 are not suitable photocatalysts for photocatalytic water splitting at all pH values (pH = 0, 7, and 14). In contrast, all the investigated Janus Y2CTT' MXenes are good water splitting photocatalysts with high optical absorption coefficients and remarkable solar-to-hydrogen (STH) efficiencies larger than 18% at pH = 14. Moreover, the STH efficiencies are larger than 18% even at all investigated pH values for Y2CHCl (18.5-22.6%), Y2 CFCl (∼18.7%), and Y2 C(OH)Cl (∼19.4%). Based on the first-principles calculations, we here for the first time propose an easy strategy to design Janus MXene photocatalyst candidates with possible high STH efficiency according to the electronic properties of their symmetric counterparts. Our study is helpful for the future design of Janus MXenes and more generally Janus 2D photocatalysts for water splitting with high STH efficiency.

A hub gene signature as a therapeutic target and biomarker for sepsis and geriatric sepsis-induced ARDS concomitant with COVID-19 infection.

Background: COVID-19 and sepsis represent formidable public health challenges, characterized by incompletely elucidated molecular mechanisms. Elucidating the interplay between COVID-19 and sepsis, particularly in geriatric patients suffering from sepsis-induced acute respiratory distress syndrome (ARDS), is of paramount importance for identifying potential therapeutic interventions to mitigate hospitalization and mortality risks. Methods: We employed bioinformatics and systems biology approaches to identify hub genes, shared pathways, molecular biomarkers, and candidate therapeutics for managing sepsis and sepsis-induced ARDS in the context of COVID-19 infection, as well as co-existing or sequentially occurring infections. We corroborated these hub genes utilizing murine sepsis-ARDS models and blood samples derived from geriatric patients afflicted by sepsis-induced ARDS. Results: Our investigation revealed 189 differentially expressed genes (DEGs) shared among COVID-19 and sepsis datasets. We constructed a protein-protein interaction network, unearthing pivotal hub genes and modules. Notably, nine hub genes displayed significant alterations and correlations with critical inflammatory mediators of pulmonary injury in murine septic lungs. Simultaneously, 12 displayed significant changes and correlations with a neutrophil-recruiting chemokine in geriatric patients with sepsis-induced ARDS. Of these, six hub genes (CD247, CD2, CD40LG, KLRB1, LCN2, RETN) showed significant alterations across COVID-19, sepsis, and geriatric sepsis-induced ARDS. Our single-cell RNA sequencing analysis of hub genes across diverse immune cell types furnished insights into disease pathogenesis. Functional analysis underscored the interconnection between sepsis/sepsis-ARDS and COVID-19, enabling us to pinpoint potential therapeutic targets, transcription factor-gene interactions, DEG-microRNA co-regulatory networks, and prospective drug and chemical compound interactions involving hub genes. Conclusion: Our investigation offers potential therapeutic targets/biomarkers, sheds light on the immune response in geriatric patients with sepsis-induced ARDS, emphasizes the association between sepsis/sepsis-ARDS and COVID-19, and proposes prospective alternative pathways for targeted therapeutic interventions.

A SARS-CoV-2 related signature that explores the tumor microenvironment and predicts immunotherapy response in esophageal squamous cell cancer.

BACKGROUND: The existing therapeutic approaches for combating tumors are insufficient in completely eradicating malignancy, as cancer facilitates tumor relapse and develops resistance to treatment interventions. The potential mechanistic connection between SARS-CoV-2 and ESCC has received limited attention. Therefore, our objective was to investigate the characteristics of SARS-CoV-2-related-genes (SCRGs) in esophageal squamous cancer (ESCC). METHODS: Raw data were obtained from the TCGA and GEO databases. Clustering of SCRGs from the scRNA-seq data was conducted using the Seurat R package. A risk signature was then generated using Lasso regression, incorporating prognostic genes related to SCRGs. Subsequently, a nomogram model was developed based on the clinicopathological characteristics and the risk signature. RESULTS: Eight clusters of SCRGs were identified in ESCC utilizing scRNA-seq data, of which three exhibited prognostic implications. A risk signature was then made up with bulk RNA-seq, which displayed substantial correlations with immune infiltration. The novel signature was verified to have excellent prognostic efficacy. CONCLUSION: The utilization of risk signatures based on SCRGs can efficiently forecast the prognosis of ESCC. A thorough characterization of the SCRGs signature in ESCC could facilitate the interpretation of ESCC's response to immunotherapy and offer innovative approaches to cancer therapy.

Brain glucose metabolism on [18F]-FDG PET/CT: a dynamic biomarker predicting depression and anxiety in cancer patients.

Objectives: To explore the correlation between the incidence rates of depression and anxiety and cerebral glucose metabolism in cancer patients. Methods: The experiment subjects consisted of patients with lung cancer, head and neck tumor, stomach cancer, intestinal cancer, breast cancer and healthy individuals. A total of 240 tumor patients and 39 healthy individuals were included. All subjects were evaluated by the Hamilton depression scale (HAMD) and Manifest anxiety scale (MAS), and were examined by whole body Positron Emission Tomography/Computed Tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG). Demographic, baseline clinical characteristics, brain glucose metabolic changes, emotional disorder scores and their relations were statistically analyzed. Results: The incidence rates of depression and anxiety in patients with lung cancer were higher than those in patients with other tumors, and Standard uptake values (SUVs) and metabolic volume in bilateral frontal lobe, bilateral temporal lobe, bilateral caudate nucleus, bilateral hippocampus, left cingulate gyrus were lower than those in patients with other tumors. We also found that poor pathological differentiation, and advanced TNM stage independently associated with depression and anxiety risk. SUVs in the bilateral frontal lobe, bilateral temporal lobe, bilateral caudate nucleus, bilateral hippocampus, left cingulate gyrus were negatively correlated with HAMD and MAS scores. Conclusion: This study revealed the correlation between brain glucose metabolism and emotional disorders in cancer patients. The changes in brain glucose metabolism were expected to play a major role in emotional disorders in cancer patients as psychobiological markers. These findings indicated that functional imaging can be applied for psychological assessment of cancer patients as an innovative method.

Metagenomic insight of fluorene-boosted sludge acidogenic fermentation: Metabolic transformation of amino acids and monosaccharides.

Fluorene (Flu) occurs widely in various environments and its toxicity to organisms is well-known. However, the impact of Flu on complicated biochemical processes involving functional microbial community has been reported rarely. In this study, the facilitation of Flu on the volatile fatty acids (VFAs) generation executed by acidogenic microbial population during sludge acidogenic fermentation (37 °C, SRT = 8 d, pH = 10.0) was investigated. The accumulation of VFAs (particularly acetic acid) increased initially and then declined with the increasing of Flu concentration (0-500 mg/kg dry sludge), which reached a maximum (3211.1 mg COD/L) as Flu content was 200 mg/kg dry sludge. The Flu-enhanced VFAs production was primarily attributed to the shift of hydrolysis/acidification, as well as the corresponding functional microbial community and the activity of enzymes. Based on the metagenomics analysis, the conversion of organic substrates, i.e. amino acid and monosaccharide, into VFAs embraced in hydrolysis/acidification shaped by Flu was constructed at the genetic level. The relative abundances of genes included in aminotransfer and deamination process of amino acid and glycolysis of monosaccharide into VFA-precursors (pyruvate, acetyl-CoA and propionyl-CoA), and the further formation of VFAs were improved due to the Flu presence. This study shed light on the Flu-affected microbial processes at the molecular biology level during acidogenic fermentation and was of great significance in resource recovery of sludge containing persistent organic pollutants.

Identification of the Benzoimidazole Compound as a Selective FLT3 Inhibitor by Cell-Based High-Throughput Screening of a Diversity Library.

Internal tandem duplication in the FLT3 receptor tyrosine kinase (FLT3/ITD mutation) occurs in approximately 25% of acute myeloid leukemia (AML) patients. To specifically target this driver mutation in AML, we assessed and compared the cell-based cytotoxicity of a diversity library (10,000 compounds) against the normal cell line BaF3 and the isogenic leukemic cell line BaF3/ITD. A benzoimidazole scaffold-based compound (HP1142) was identified as the most selective compound against a series of murine and human leukemia cells with FLT3/ITD. Novel benzoimidazole compounds were further designed to improve the aqueous solubility of HP1142. The most potent compound, HP1328, demonstrated desirable pharmaceutical and pharmacokinetic properties. Treatment with HP1328 significantly reduced the leukemia burden and prolonged the survival of mice with FLT3/ITD leukemia. Our findings establish the specific activity of the benzoimidazole compound against FLT3/ITD leukemia and warrant further investigation in this subset of leukemia patients with poor prognosis.

Mg/ZrO2 Metal Matrix Nanocomposites Fabricated by Friction Stir Processing: Microstructure, Mechanical Properties, and Corrosion Behavior.

Magnesium (Mg) and its alloys have attached more and more attention because of their potential as a new type of biodegradable metal materials. In this work, AZ31/ZrO2 nanocomposites with good uniformity were prepared successfully by friction stir processing (FSP). The scanning electron microscope (SEM) and transmission electron microscope (TEM) were used to characterize the microstructure of the composites. The mechanical properties, electrochemical corrosion properties and biological properties were evaluated. In addition, the effect of reinforced particles (ZrO2) on the microstructure and properties of the composite was studied comparing with FSP AZ31 Mg alloy. The results show that compared with the base metal (BM), the AZ31/ZrO2 composite material achieves homogenization, densification, and grain refinement after FSP. The combination of dynamic recrystallization and ZrO2 particles leads to grain refinement of Mg alloy, and the average grain size of AZ31/ZrO2 composites is 3.2 µm. After FSP, the c-axis of grain is deflected under the compression stress of shoulder and the shear stress of pin. The ultimate tensile strength (UTS) and yield strength (YS) of BM were 283 and 137 MPa, respectively, the UTS and YS of AZ31/ZrO2 composites were 427 and 217 MPa, respectively. The grain refinement and Orowan strengthening are the major strengthening mechanisms. Moreover, the corrosion resistance in simulated body fluid of Mg alloy is improved by grain refinement and the barrier effect of ZrO2.

Domino Carbopalladation/C-H Activation as a Quick Access to Polycyclic Frameworks.

A new type of domino reaction for synthesis of heterocycles fusing the important bioactive cores, such as oxindole, indoline, and isoquinoline, is presented. Upon exposure to the very common palladium catalyst, the conceptually designed N-alkenyl iodobiaryls undergo a sequential carbopalladation/C-H activation to build polycyclic frameworks. These novel unique frameworks may provide structure sources in fragment-based drug discovery.

Elimination of stem-like cancer cell side-population by auranofin through modulation of ROS and glycolysis.

Cancer side-population (SP) represents a sub-population of stem-like cancer cells that have an important role in drug resistance due to their high expression of the ATP-binding cassette transporter ABCG2 involved in drug export. Auranofin (AF), a clinical drug of gold complex that is used in treatment of rheumatoid arthritis, has been reported inducing tumor antiproliferation. However, whether AF can impact SP cells remains unclear. Our study showed that AF caused a depletion of SP cells and a downregulation of stem cell markers, and impaired their ability to form tumor colonies in vitro and incidence to develop tumors in vivo of lung cancer cells. Reactive oxygen species (ROS) had an important role in mediating AF-induced depletion of SP cells, which could be reversed by antioxidant NAC. Further study revealed that AF could also cause ATP depletion by inhibition of glycolysis. The depletion of cellular ATP might impair the function of ABCG2 pump, leading to increased drug accumulation within the cells and thus enhancing anticancer activity of chemotherapeutic agents such as adriamycin. Synergistic effect of AF and adriamycin was demonstrated both in vitro and in vivo. Simultaneous increase of ROS and inhibition of glycolysis is a novel strategy to eliminate stem-like cancer cells. Combination of AF with adriamycin seems to be promising to enhance therapeutic effectiveness.

Coordination coupling enhanced two-photon absorption of a ZnS-based microhybrid for two-photon microscopy imaging in HepG2.

Coordination coupling induced self-assembly of ZnS microparticles was performed with the help of a π-conjugated sulphur-terminal Zn(ii) complex ZnS2L (L = N-hexyl-3-{2-[4-2,2':6',2''-terpyridin-4'-yl-phenyl]ethenyl}-carbazole). The interactions between ZnS and ZnS2L components at the interface, which were analyzed by far-IR and XPS, resulted in a tunable single-photon excited fluorescence and an enhanced nonlinear optical response, including a two-photon absorption cross section and a two-photon excited fluorescence. Such an enhancement in nonlinear optical properties was triggered by the coordination coupling effect between terminal S atoms of ZnS2L and naked Zn2+ ions at the surface of ZnS particles. Thus, the novel hybrid system displayed a unique two-photon excited fluorescence to facilitate promising two-photon microscopy imaging of HepG2 cells upon NIR light illumination at 840 nm. The hybrid shows a stronger ability to enter the cells than free ZnS2L.

Breaking the sporoderm of Ganoderma lucidum spores by combining chemical reaction with physical actuation.

The hard and indissolvable sporoderm of Ganoderma lucidum spore (GLS) hinders the release of bioactive components that are significant to disease treatment and vitality enhancement. In this paper, a strategy to break sporoderm was proposed, in which the chemical reaction was cooperated with physical actuation (ultrasonication and refrigeration). Dealing with this chemicophysical treatment, the porous sporoderm of GLS was formed, which was confirmed by scanning electron microscope (SEM). The effect factors and mechanism of breaking sporoderm were discussed, and the efficiency of breaking sporoderm was evaluated by detecting the dissolution behaviour of inner triterpenoids in GLS. In addition, aiming to improve the solubility and stability of GLS product, the ß-cyclodextrin was used to seal the holes on sporoderm of GLS product. The results show that the developed method is effective and feasible in producing high-bioactive and stable GLS product.

A series of stilbazolium salts with A-π-A model and their third-order nonlinear optical response in the near-IR region.

A series of water-soluble stilbazolium salts with A-π-A (A: Acceptor) model have been synthesized and fully characterized. The results obtained from absorption spectra and TD-DFT computational studies show that there is a relative strong intramolecular charge transfer (ICT) transition from pyridine unit to pyridine cation of the stilbazolium salts. Furthermore, it is found that the three stilbazolium salts (T1, T2, T3) show the strong two-photon absorption (2PA) response in the near-infrared (IR) region by Z-scan technique using femtosecond laser. And the stilbazolium salt T3 shows the largest two-photon absorption cross-section and third-order nonlinear optical (NLO) coefficient χ(3) at 730nm, indicating the different terminal substituent group of the pyridinium plays a vital role in third-order NLO behavior.

Highly Sensitive Electrochemical Dopamine Sensor from Poly(diallyldimethylammonium chloride)-Functionalized Graphene Nanoribbon/Gold Nanoparticle Nanocomposite.

A novel graphene oxide nanoribbon/poly(diallyldimethylammonium chloride)/gold nanoparticle (GONR/PDDA/AuNP) nanocomposite was synthesized successfully and used for the sensitive detection of dopamine. The GONR/PDDA/AuNP nanocomposite was characterized by transmission and scanning electron microscopy. The electrochemical sensor based on GONR/PDDA/AuNP nanocomposite. was studied by cyclic voltammetry and electrochemical impedance spectroscopy. Experimental parameters such as GONR/PDDA concentration, volume ratio of GONR/PDDA to AuNP, scan rates, and pH were studied to investigate their effect on peak currents. Under optimal conditions, the GONR/PDDA/AuNP-based sensor exhibited excellent electrocatalytic activity for the detection of dopamine with a wide linear range from 9.99 x 10(-8) to 8.69 x 10(-4) M and a low detection limit of 3.33 x 10(-8) M. Moreover, the proposed sensor exhibits high sensitivity, good reproducibility, and stability, and could therefore potentially be applied in other bioanalytical systems.

Porf-2 Inhibits Neural Stem Cell Proliferation Through Wnt/ß-Catenin Pathway by Its GAP Domain.

Neural stem cell (NSC) proliferation and differentiation play a pivotal role in the development of brain, the plasticity of the brain network, and the repair for brain function in CNS diseases. The mechanisms regulating NSC behavior are not well elucidated. Previous studies showed porf-2 functions as a modulator in central nerve system development. We here show that porf-2, a conserved family of RhoGAPs, is highly and specifically expressed in NSCs. We also demonstrate that porf-2 inhibits the proliferation of NSCs in vivo and in vitro, but has no effect on NSC differentiation. We investigated which domain is required for the role of porf-2 on NSC proliferation. By using neurosphere formation and Edu assay we confirmed the GAP domain is necessary for its function. In addition, we surveyed a few classical pathways on NSC proliferation and found that porf-2 inhibits NSC proliferation by suppressing the ß-catenin nuclear translocation. Taken together, we show for the first time that porf-2 inhibits NSC proliferation through Wnt/ß-catenin pathway by its GAP domain.

Synthesis of TiO2-loaded Co0.85Se thin films with heterostructure and their enhanced catalytic activity for p-nitrophenol reduction and hydrazine hydrate decomposition.

P-nitrophenol (4-NP) and hydrazine hydrate are considered to be highly toxic pollutants in wastewater, and it is of great importance to remove them. Herein, TiO2-loaded Co0.85Se thin films with heterostructure were successfully synthesized by a hydrothermal route. The as-synthesized samples were characterized by x-ray diffraction, x-ray photoelectron spectroscopy, transmission electron microscopy and selective-area electron diffraction. The results demonstrate that TiO2 nanoparticles with a size of about 10 nm are easily loaded on the surface of graphene-like Co0.85Se nanofilms, and the NH3 · H2O plays an important role in the generation and crystallization of TiO2 nanoparticles. Brunauer-Emmett-Teller measurement shows that the obtained nanocomposites have a larger specific surface area (199.3 m(2) g(-1)) than that of Co0.85Se nanofilms (55.17 m(2) g(-1)) and TiO2 nanoparticles (19.49 m(2) g(-1)). The catalytic tests indicate Co0.85Se-TiO2 nanofilms have the highest activity for 4-NP reduction and hydrazine hydrate decomposition within 10 min and 8 min, respectively, compared with the corresponding precursor Co0.85Se nanofilms and TiO2 nanoparticles. The enhanced catalytic performance can be attributed to the larger specific surface area and higher rate of interfacial charge transfer in the heterojunction than that of the single components. In addition, recycling tests show that the as-synthesized sample presents stable conversion efficiency for 4-NP reduction.

Electrochemical biosensor for Ni(2+) detection based on a DNAzyme-CdSe nanocomposite.

The detection and speciation analysis of metal-ion is very important for environmental monitoring. A novel electrochemical biosensor for Nickel(II) detection based on a DNAzyme-CdSe nanocomposite was developed. We firstly hybridized with capture probe (DNA1) and sequentially with DNA (DNA2) on the gold electrode. Then CdSe QDs were incorporated the specific recognition of DNA2 by covalent assembling. Upon addition of nickel ion into the above system, the substrate strand of the immobilized DNAzyme was catalytically cleaved by target Ni(2+), resulting in disassociation of the shorter DNA fragments containing CdSe QDs. The remaining CdSe QDs on the electrode surface detected by differential pulse anodic stripping voltammetry (DPASV). Under optimal conditions, the as-prepared sensor exhibited high sensitivity and fast response to Ni(2+) with the linear range from 20 nM to 0.2mM and a low detection limit of 6.67 nM. The prepared biosensor also shows good stability and good reproducibility and high selectivity toward target Ni(2+) against other metal ions because of highly specific Ni(2+)-dependent DNAzyme. Thus, our strategy has a good potential in the environment surveys.

Targeting mitochondrial DNA with a two-photon active Ru(ii) phenanthroline derivative.

As a semi-autonomous organelle, the eukaryotic mitochondrion possesses an individual DNA and protein synthesizing system. Therefore, the mitochondrial DNA-targeting probes are powerful tools to understand the functions in physiological processes. Herein, we report a novel Ru(ii) complex (HLRu) based on a phenanthroline derivative to target mitochondrial DNA. The nonlinear optical property study revealed a reverse nonlinear optical refraction character from self-focusing to self-defocusing response before and after complexation with Ru(ii). Furthermore, the two-photon absorption and high biocompatibility of complex HLRu highlight its potential applications in biological processes. It was found that complex HLRu specifically binds to mitochondrial DNA in living cells and enables imaging of tissues with minimal auto-fluorescence. As a result, this complex HLRu probe offers a promising platform to directly monitor mitochondrial DNA in living cells.