Near-infrared imaging for visualizing the synergistic relationship between autophagy and NFS1 protein during multidrug resistance using an ICT-TICT integrated platform.

Drug resistance is a major challenge for cancer treatment, and its identification is crucial for medical research. However, since drug resistance is a multi-faceted phenomenon, it is important to simultaneously evaluate multiple target fluctuations. Recently developed fluorescence-based probes that can simultaneously respond to multiple targets offer many advantages for real-time and in situ monitoring of cellular metabolism, including ease of operation, rapid reporting, and their non-invasive nature. As such we developed a dual-response platform (Vis-H2S) with integrated ICT-TICT to image H2S and viscosity in mitochondria, which could simultaneously track fluctuations in cysteine desulfurase (NFS1 protein and H2S inducer) and autophagy during chemotherapy-induced multidrug resistance. This platform could monitor multiple endogenous metabolites and the synergistic relationship between autophagy and NFS1 protein during multidrug resistance induced by chemotherapy. The results indicated that chemotherapeutic drugs simultaneously up-regulate the levels of NFS1 protein and autophagy. It was also found that the NFS1 protein was linked with autophagy, which eventually led to multidrug resistance. As such, this platform could serve as an effective tool for the in-depth exploration of drug resistance mechanisms.

Polycarboxyl ionic liquid functionalized Yb-MOFs nanoballs based dual-wavelength responsive photoelectrochemical aptasensor for the simultaneous determination of AFB1 and OTA.

Developing an accurate and precise approach for the simultaneous detection of ochratoxin A (OTA) and aflatoxin B1 (AFB1) is significant for food safety surveillance. Herein, a photoelectrochemical sensing platform was constructed based on polycarboxylic ionic liquid functionalized metal-organic framework integrated with gold nanoparticles (Yb-MOFs@AuNPs). Sulfhydryl functionalized hairpin DNA (hDNA) was immobilized on a Yb-MOFs@AuNPs modified glassy carbon electrode (GCE) surface through Au-S bond. After blocking residual active binding sites with BSA, gold nanoparticles-labeled AFB1 aptamer (AuNPs-Apt 1) and gold nanorods-labeled OTA aptamer (AuNRs-Apt 2) were introduced to construct a photoelectrochemical aptasensor for the simultaneous determination of AFB1 and OTA. Due to the surface plasmon resonance effect and the nanometer size effect of gold nanomaterials, the photoelectrochemical aptasensor can output photocurrent responses as being excited with different wavelengths at 520 nm and 808 nm, respectively. When the AFB1 and OTA concentration in the range of 0.001-50.0 ng mL-1, a good linear relationship between the photocurrent difference (ΔI) before and after recognizing targets and the logarithm of AFB1 or OTA concentration was obtained. The detection limits for AFB1 and OTA were 0.40 pg mL-1 and 0.19 pg mL-1, respectively. AFB1 and OTA in corn samples were detected simultaneously by the photoelectrochemical aptasensor.

Integrating Recombinase Polymerase Amplification and Photosensitization Colorimetric Detection in One Tube for Fast Screening of C. sakazakii in Formula Milk Powder.

Cronobacter sakazakii (C. sakazakii) is a widely existing opportunistic pathogen and thus threatens people with low immunity, especially infants. To prevent the outbreak, a rapid and accurate on-site testing method is required. The current standard culture-based method is time-consuming (3-4 days), while the nucleic acid amplification (PCR)-based detection is mostly carried out in central laboratories. Herein, isothermal recombinase polymerase amplification (RPA) coupled with a photosensitization colorimetric assay (PCA) was adopted for the on-site detection of C. sakazakii in powdered infant formulas (PIFs). The lowest visual detection concentration of C. sakazakii is 800 cfu/mL and 2 cfu/g after 8 h bacteria pre-enrichment. Furthermore, to avoid typical cap opening-resulted aerosol pollution, the PCA reagents were lyophilized onto the cap of the RPA tube (containing lyophilized RPA reagents). After amplification, the tube was subjected to simple shaking to mix the PCA reagents with the amplification products for light-driven color development. Such a one-tube assay offered a lowest concentration of 1000 copies of genomic DNA of C. sakazakii within 1 h. After 8 h of bacterial enrichment, the lowest detecting concentration could be pushed down to 5 cfu/g bacteria in PIF. To facilitate on-site monitoring, a portable, battery-powered PCA device was designed to mount the typical RPA 8-tube strip, and a color analysis cellphone APP was further employed for facile readout.

The Combination of Bioactive Herbal Compounds with Biomaterials for Regenerative Medicine.

Regenerative medicine aims to restore the function of diseased or damaged tissues and organs by cell therapy, gene therapy, and tissue engineering, along with the adjunctive application of bioactive molecules. Traditional bioactive molecules, such as growth factors and cytokines, have shown great potential in the regulation of cellular and tissue behavior, but have the disadvantages of limited source, high cost, short half-life, and side effects. In recent years, herbal compounds extracted from natural plants/herbs have gained increasing attention. This is not only because herbal compounds are easily obtained, inexpensive, mostly safe, and reliable, but also owing to their excellent effects, including anti-inflammatory, antibacterial, antioxidative, proangiogenic behavior and ability to promote stem cell differentiation. Such effects also play important roles in the processes related to tissue regeneration. Furthermore, the moieties of the herbal compounds can form physical or chemical bonds with the scaffolds, which contributes to improved mechanical strength and stability of the scaffolds. Thus, the incorporation of herbal compounds as bioactive molecules in biomaterials is a promising direction for future regenerative medicine applications. Herein, an overview on the use of bioactive herbal compounds combined with different biomaterial scaffolds for regenerative medicine application is presented. We first introduce the classification, structures, and properties of different herbal bioactive components and then provide a comprehensive survey on the use of bioactive herbal compounds to engineer scaffolds for tissue repair/regeneration of skin, cartilage, bone, neural, and heart tissues. Finally, we highlight the challenges and prospects for the future development of herbal scaffolds toward clinical translation. Overall, it is believed that the combination of bioactive herbal compounds with biomaterials could be a promising perspective for the next generation of regenerative medicine.

Nanozyme-induced deep learning-assisted smartphone integrated colorimetric and fluorometric dual-mode for detection of tetracycline analogs.

In this work, a colorimetric and fluorescent dual-mode probe controlled by NH2-MIL-88 B (Fe, Ni) nanozymes was developed to visually detect tetracycline antibiotics (TCs) residues quantitatively, as well as accurately distinguish the four most widely used tetracycline analogs (tetracycline (TC), chrycline (CTC), oxytetracycline (OTC), and doxycycline (DC)). Colorless substrate 3,3',5,5'-tetramethylbenzidine (TMB) may be oxidized to blue oxidized TMB by the Fe Fenton reaction, which was catalyzed by the NH2-MIL-88 B (Fe, Ni) nanozyme with POD-like activity. The colorimetric detection system allows TCs to interact with NH2-MIL-88 B (Fe, Ni). This inhibits the production of ·OH, weakens the oxidation process of TMB, and ultimately lightens the blue color in the system by blocking the electron transfer between NH2-MIL-88 B (Fe, Ni) and H2O2. Furthermore, TCs can interact with NH2-MIL-88 B (Fe, Ni) as a result of the internal filtering effect, which causes the fluorescence intensity to decrease as TCs concentration increases. Additionally, a portable instrument that combines a smartphone sensing platform with colorimetric and fluorescent signals was created for the quick, visual quantitative detection of TCs. The colorimetric and fluorescent dual-mode nano platform enables color change, with detection limits (LODs) of 0.182 µM and 0.0668 µM for the spectrometer and smartphone sensor, respectively, based on the inhibition of fluorescence and enzyme-like activities by TCs. Overall, the colorimetric and fluorescence dual-mode sensor has good stability, high specificity, and an efficient way to eliminate false-positive issues associated with a single detection mode.

Portable, intelligent MIECL sensing platform for ciprofloxacin detection using a fast convolutional neural networks-assisted Tb@Lu2O3 nanoemitter.

Environmental pollution caused by ciprofloxacin is a major problem of global public health. A machine learning-assisted portable smartphone-based visualized molecularly imprinted electrochemiluminescence (MIECL) sensor was developed for the highly selective and sensitive detection of ciprofloxacin (CFX) in food. To boost the efficiency of electrochemiluminescence (ECL), oxygen vacancies (OVs) enrichment was introduced into the flower-like Tb@Lu2O3 nanoemitter. With the specific recognition reaction between MIP as capture probes and CFX as detection target, the ECL signal significantly decreased. According to, CFX analysis was determined by traditional ECL analyzer detector in the concentration range from 5 × 10-4 to 5 × 102 µmol L-1 with the detection limit (LOD) of 0.095 nmol L-1 (S/N = 3). Analysis of luminescence images using fast electrochemiluminescence judgment network (FEJ-Net) models, achieving portable and intelligent quick analysis of CFX. The proposed MIECL sensor was used for CFX analysis in real meat samples and satisfactory results, as well as efficient selectivity and good stability.

A smart cysteine-activated and heavy-atom-free nano-photosensitizer for photodynamic therapy to treat cancers.

A smart and heavy-atom-free photoinactive nano-photosensitizer capable of being activated by cysteine at the tumor site to generate highly photoactive nano-photosensitizers that show strong NIR absorption and fluorescence with a good singlet oxygen quantum yield (16.8%) for photodynamic therapy is reported.

Cascade Co8FeS8@Co1-xS nano-enzymes trigger efficiently apoptosis-ferroptosis combination tumor therapy.

This study involved the preparation of Metal Organic Frameworks (MOF)-derived Co8FeS8@Co1-xS nanoenzymes with strong interfacial interactions. The nanoenzymes presented the peroxidase (POD)-like activity and the oxidation activity of reduced glutathione (GSH). Accordingly, the dual activities of Co8FeS8@Co1-xS provided a self-cascading platform for producing significant amounts of hydroxyl radical (•OH) and depleting reduced glutathione, thereby inducing tumor cell apoptosis and ferroptosis. More importantly, the Co8FeS8@Co1-xS inhibited the anti-apoptosis protein B-cell lymphoma-2 (Bcl-2) and activated caspase family proteins, which caused tumor cell apoptosis. Simultaneously, Co8FeS8@Co1-xS affected the iron metabolism-related genes such as Heme oxygenase-1 (Hmox-1), amplifying the Fenton response and promoting apoptosis and ferroptosis. Therefore, the nanoenzyme synergistically killed anti-apoptotic tumor cells carrying Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. Furthermore, Co8FeS8@Co1-xS demonstrated good biocompatibility, which paved the way for constructing a synergistic catalytic nanoplatform for an efficient tumor treatment.

Exosomes-Mediated Signaling Pathway: A New Direction for Treatment of Organ Ischemia-Reperfusion Injury.

Ischemia reperfusion (I/R) is a common pathological process which occurs mostly in organs like the heart, brain, kidney, and lung. The injury caused by I/R gradually becomes one of the main causes of fatal diseases, which is an urgent clinical problem to be solved. Although great progress has been made in therapeutic methods, including surgical, drug, gene therapy, and transplant therapy for I/R injury, the development of effective methods to cure the injury remains a worldwide challenge. In recent years, exosomes have attracted much attention for their important roles in immune response, antigen presentation, cell migration, cell differentiation, and tumor invasion. Meanwhile, exosomes have been shown to have great potential in the treatment of I/R injury in organs. The study of the exosome-mediated signaling pathway can not only help to reveal the mechanism behind exosomes promoting reperfusion injury recovery, but also provide a theoretical basis for the clinical application of exosomes. Here, we review the research progress in utilizing various exosomes from different cell types to promote the healing of I/R injury, focusing on the classical signaling pathways such as PI3K/Akt, NF-κB, Nrf2, PTEN, Wnt, MAPK, toll-like receptor, and AMPK. The results suggest that exosomes regulate these signaling pathways to reduce oxidative stress, regulate immune responses, decrease the expression of inflammatory cytokines, and promote tissue repair, making exosomes a competitive emerging vector for treating I/R damage in organs.

GDF11 mitigates high glucose-induced cardiomyocytes apoptosis by inhibiting the ALKBH5-FOXO3-CDR1as/Hippo signaling pathway.

Diabetic cardiomyopathy remains a formidable health challenge with a high mortality rate and no targeted treatments. Growth differentiation factor 11 (GDF11) has shown promising effects on cardiovascular diseases; however, its role and the underlying mechanism in regulating diabetic cardiomyopathy remain unclear. In this study, we developed mouse models of diabetic cardiomyopathy using leptin receptor-deficient (db/db) mice and streptozocin-induced C57BL/6 mice. The diabetic cardiomyopathy model mice exhibited apparent structural damage in cardiac tissues and a significant increase in the expression of apoptosis-related proteins. Notably, we observed a significant decreased expression of GDF11 in the myocardium of mice with diabetic cardiomyopathy. Moreover, GDF11 cardiac-specific knock-in mice (transgenic mice) exhibited improved cardiac function and reduced apoptosis. Moreover, exogenous administration of GDF11 mitigated high glucose-induced cardiomyocyte apoptosis. Mechanistically, we demonstrated that GDF11 alleviated high glucose-induced cardiomyocytes apoptosis by inhibiting the activation of the alkylation repair homolog 5 (ALKBH5)-forkhead box group O3a (FOXO3)-cerebellar degeneration-related protein 1 transcript (CDR1as)/Hippo signaling pathway. Consequently, this novel mechanism effectively counteracted myocardial cell apoptosis, providing valuable insights into potential therapeutic strategies for clinical diabetic cardiomyopathy.

Health benefits from the rapid reduction in ambient exposure to air pollutants after China's clean air actions: progress in efficacy and geographic equality.

Clean air actions (CAAs) in China have been linked to considerable benefits in public health. However, whether the beneficial effects of CAAs are equally distributed geographically is unknown. Using high-resolution maps of the distributions of major air pollutants (fine particulate matter [PM2.5] and ozone [O3]) and population, we aimed to track spatiotemporal changes in health impacts from, and geographic inequality embedded in, the reduced exposures to PM2.5 and O3 from 2013 to 2020. We used a method established by the Global Burden of Diseases Study. By analyzing the changes in loss of life expectancy (LLE) attributable to PM2.5 and O3, we calculated the gain of life expectancy (GLE) to quantify the health benefits of the air-quality improvement. Finally, we assessed the geographic inequality embedded in the GLE using the Gini index (GI). Based on risk assessments of PM2.5 and O3, during the first stage of CAAs (2013 to 2017), the mean GLE was 1.87 months. Half of the sum of the GLE was disproportionally distributed in about one quarter of the population exposed (GI 0.44). During the second stage of CAAs (2017 to 2020), the mean GLE increased to 3.94 months and geographic inequality decreased (GI 0.18). According to our assessments, CAAs were enhanced, from the first to second stages, in terms of not only preventing premature mortality but also ameliorating health inequalities. The enhancements were related to increased sensitivity to the health effects of air pollution and synergic control of PM2.5 and O3 levels. Our findings will contribute to optimizing future CAAs.

Hollow CoZnSe@CN nanocage with enzymatic activity for determination of tetracycline using smartphone platforms and virtual reality revealing.

Antibiotic residues in the environment pose a serious threat to ecosystems and human health. Therefore, it is important to develop sensitive and rapid in situ detection methods. In this work, the designed nanozymes, with excellent four enzyme activities, were proved to be constituted of unique hollow nanocage structures (CoZnSe@CN HCs). Based on the peroxidase-like enzymes, a portable colorimetric sensor was constructed for the on-site determination of tetracycline (TC) in real samples. The linear range of TC detection was 0.1-100 µM, and the detection limit was 0.02 µM. At the same time, colorimetric detection and smartphones have also been combined for on-site colorimetric detection of TC. In-depth exploration of the detection mechanism showed that TC could be bound with the material, inhibiting the production of oxidized 3,3',5,5'-tetramethylbenzidine. The sensor was also used for the detection of TC in environmental soil and water samples. This study can provide an intelligent detection method for environmental monitoring.

Design a dual-response two-photon fluorescent probe for simultaneous imaging of mitochondrial viscosity and peroxynitrite in a thrombosis model.

BACKGROUND: Venous thromboembolism is a sudden cardiovascular disease that can lead to death, and its pathologic development is closely related to vascular viscosity and inflammation. However, direct evidence from in vivo is really scarce. The key limitation is that the combined probes cannot detect multiple markers simultaneously, which may lead to unreliable results. Therefore, to develop a single probe that can simultaneously monitor the variations of viscosity in the vascular microenvironment as well as inflammation level during venous thrombosis. RESULTS: A dual-responsive two-photon fluorescent probe, Cou-ONOO, was designed and synthesized. Cou-ONOO provides a visualization tool for monitoring the viscosity of the vascular as well as the inflammatory marker ONOO‾ during thromboembolism via dual-channel simultaneous imaging. As a single probe that can recognize dual targets, Cou-ONOO effectively avoids the problems from unreliable results caused by complex synthesis and differences in intracellular localization, diffusion, and metabolism of different dyes as using combinatorial probes. Using Cou-ONOO, simultaneous imaging the variations of viscosity and ONOO‾at the cellular and tissue levels was successfully performed. In addition, Cou-ONOO also successfully visualized and tracked the viscosity of the vascular microenvironment and ONOO‾ during venous embolism in mice. SIGNIFICANCE: Experimental results show that both viscosity and inflammation are abnormally overexpressed in the microenvironment at the thrombus site during venous thrombosis. An intuitive visualization tool to elucidate the variations of viscosity as well as inflammation level in the vascular microenvironment during thrombosis was provided, which will facilitate a better clinical understanding of the pathological process of thrombosis.

Spontaneous Formation of Ultrasmall Noble Metal Nanoparticles on Cobalt-Based Layered Double Hydroxide for Electrochemical and Environmental Catalysis.

Supported noble metal nanoparticles (NMNPs) are appealing for energy and environment catalysis. To facilitate the loading of NMNPs, in situ reduction of Mn+ on the support with extra reductants/surfactants is adopted, but typically results in aggregated NMNPs with uneven size distributions or blocked active sites of the NMNPs. Herein, the use of cobalt layered double hydroxide (Co-LDH) is proposed as both support and reductant for the preparation of supported NMNPs with ultrasmall sizes and even distributions. The resultant Co-LDH-supported NMNPs exhibit excellent catalytic performance and stability. For example, Ir/Co-LDH displays a low overpotential of 188 mV (10 mA cm-2 ) for electrocatalytic oxygen evolution reaction and a long-term stability over 100 h (100 mA cm-2 ) in overall water splitting. Ru/Co-LDH can achieve a 4-nitrophenol reduction with high rate of 0.36 min-1 and S2- detection with low limit of detection (LOD) of 0.34 µm. Overall, this work provides a green and effective strategy to fabricate supported NMNPs with greatly improved catalytic performances.

Real-time intelligent detection of ethephon based on a high-throughput ratiometric fluorescent probe.

Ethephon (ETH) is a common pesticide, and its overuse has resulted in a variety of health problems for humans. However, the existing ETH detection methods are tedious and time-consuming, and real-time ETH identification remains a significant difficulty. To mitigate this concern, a dual-emission ratiometric fluorescent probe Ru@ZrMOF was rationally synthesized for the detection of ETH. In the presence of ETH, the emission peak at 435 nm gradually increased, while the peak at 600 nm remained constant, accompanied by the fluorescence color change from red, pink, blue-violet to blue. The fluorescence intensity ratio (F435/F600) demonstrated two linear relations with the ETH concentration ranges at 3 - 50 µM and 50 - 500 µM, with a lowest detection limit at 1 µM. This was attributed to the formation of Zr-O-P bonds which attenuated the ligand-metal charge transfer (LMCT) process, resulting in the recovery of blue fluorescence of the ligand 2-Aminoterephthalic acid (2-APDC). To validate the practical application of the developed platform, a YOLO v5x-based WeChat applet "96 Speckles" was developed, and a 96-well plate and smartphone-embedded 3D-printed portable toolbox was designed for the real-time intelligent detection of ETH. This smart platform allows for real-time and efficient ETH analysis in various real samples including apples, pears and tomatoes.

Multi-Enzyme Activity of MIL-101 (Fe)-Derived Cascade Nano-Enzymes for Antitumor and Antimicrobial Therapy.

The clinical application of oncology therapy is hampered by high glutathione concentrations, hypoxia, and inefficient activation of cell death mechanisms in cancer cells. In this study, Fe and Mo bimetallic sulfide nanomaterial (FeS2@MoS2) based on metal-organic framework structure is rationally prepared with peroxidase (POD)-, catalase (CAT)-, superoxide dismutase (SOD)-like activities and glutathione depletion ability, which can confer versatility for treating tumors and mending wounds. In the lesion area, FeS2@MoS2 with SOD-like activity can facilitate the transformation of superoxide anions (O2 -) to hydrogen peroxide (H2O2), and then the resulting H2O2 serves as a substrate for the Fenton reaction with FMS to produce highly toxic hydroxyl radicals (∙OH). Simultaneously, FeS2@MoS2 has an ability to deplete glutathione (GSH) and catalyze the decomposition of nicotinamide adenine dinucleotide phosphate (NADPH) to curb the regeneration of GSH from the source. Thus it can realize effective tumor elimination through synergistic apoptosis-ferroptosis strategy. Based on the alteration of the H2O2 system, free radical production, glutathione depletion and the alleviation of hypoxia in the tumor microenvironment, FeS2@MoS2 NPS can not only significantly inhibit tumors in vivo and in vitro, but also inhibit multidrug-resistant bacteria and hasten wound healing. It may open the door to the development of cascade nanoplatforms for effective tumor treatment and overcoming wound infection.

Sulfur vacancy defects mediated CdZnTeS@BC heterojunction: Artificial intelligence-assisted self-enhanced electrochemiluminescence molecularly imprinted sensing of CTC.

Environmental pollution caused by tetracycline antibiotics is a major concern of global public health. Here, a novel and portable molecularly imprinted electrochemiluminescence (MIECL) sensor based on smartphones for highly sensitive detection of chlortetracycline (CTC) has been successfully established. The high-performance ECL emitter of biomass carbon (BC) encapsulated CdZnTeS (CdZnTeS@BC) was successfully synthesized by hydrothermal. The enhanced ECL performance was ascribed to the introduction of the BC and increased the overall electrical conductivity of the nanoemitter, as well as increased the number of sulfur vacancies and doping on the surface of the emitter based on density functional theory calculations. An aniline-CTC molecular imprinted polymer was synthesized on the surface of the CdZnTeS@BC modified electrode by in-situ electropolymerization. The decrease in MIECL signal was attributed to the increase in impedance effect. The MIECL nanoplatform enabled a wide linear relationship in the range of 0.05-100 µmol/L with a detection limit of 0.029 µmol/L for spectrometer sensors. Interestingly, the light emitted during the MIECL reaction can be captured by a smartphone. Thus, machine learning was used to screen the photos that were taken, and color analysis was carried out on the screened photos by self-developed software, thus achieving a portable, convenient, and intelligent sensing mode. Finally, the sensor obtains satisfactory results in the detection of actual samples, with no significant differences from those of liquid chromatography.

Dual-wavelength responsive CuS@COF nanosheets for high-performance photothermal/photodynamic combination treatments.

Photothermal therapy (PTT) makes it difficult to achieve good performance on tumor treatments due to insufficient photothermal conversion efficiency, etc. Combining PTT with photodynamic therapy (PDT) and other therapeutic tools can significantly enhance the tumor-killing ability and has been widely used in the development of therapeutic platforms. Copper sulfide nanoparticle (CuS NP) photothermal reagents have the advantages of low toxicity and simple synthesis; therefore, combining CuS NPs with PDT photosensitizers is an effective strategy to construct a PTT/PDT combination therapeutic platform. However, PDT photosensitizers and photothermal agents generally assembled through hydrophobic interaction, suffer from low coating efficiency or the risk of drug leakage, thus seriously restricting their applications. To address these challenges, CuS NPs with excellent photothermal conversion performance were selected as the core material to prepare CuS@COF nanosheets through a dual-ligand assistant strategy with 4,7-bis(4-aminophenyl)-2,1,3-benzothiadiazole (BTD) and 2,4,6-trihydroxybenzene-1,3,5-tricarbaldehyde (TP). As a PTT/PDT combination therapeutic platform, CuS@COF nanosheets possess a porous TP-BDT-based COF shell, and it can sufficiently contact oxygen to provide high singlet oxygen (1O2) yield under 505 nm laser irradiation. Upon illumination with a 1064 nm laser, CuS@COF nanosheets can effectively convert the photon energy into thermal energy with a photothermal conversion efficiency of 63.4%. The results of the CCK8 experiment showed that the phototoxicity of the PTT/PDT combination treatment reached 85.1%, which was much higher than the effect of a single treatment. It was also confirmed in vivo that the tumor inhibition effect of the PDT/PTT combination treatment group was much greater than that of the single treatment group.

Long non-coding RNA LHX1-DT regulates cardiomyocyte differentiation through H2A.Z-mediated LHX1 transcriptional activation.

Long non-coding RNAs (lncRNAs) play widespread roles in various processes. However, there is still limited understanding of the precise mechanisms through which they regulate early stage cardiomyocyte differentiation. In this study, we identified a specific lncRNA called LHX1-DT, which is transcribed from a bidirectional promoter of LIM Homeobox 1 (LHX1) gene. Our findings demonstrated that LHX1-DT is nuclear-localized and transiently elevated expression along with LHX1 during early differentiation of cardiomyocytes. The phenotype was rescued by overexpression of LHX1 into the LHX1-DT-/- hESCs, indicating LHX1 is the downstream of LHX1-DT. Mechanistically, we discovered that LHX1-DT physically interacted with RNA/histone-binding protein PHF6 during mesoderm commitment and efficiently replaced conventional histone H2A with a histone variant H2A.Z at the promoter region of LHX1. In summary, our work uncovers a novel lncRNA, LHX1-DT, which plays a vital role in mediating the exchange of histone variants H2A.Z and H2A at the promoter region of LHX1.

Construction of CuO/Fe2O3 Nanozymes for Intelligent Detection of Glufosinate and Chlortetracycline Hydrochloride.

In this work, CuO/Fe2O3 nanozymes with high peroxidase-like activity were synthesized by using hydrothermal and calcination methods. The high-resolution transmission electron microscopy (HRTEM) proved that the heterogeneous interface of CuO/Fe2O3 was the main reason for the high enzyme-like activity. Strong interactions of CuO and Fe2O3 were successfully verified by X-ray absorption near-edge structure (XANES) characterization. Experiments and density functional theory (DFT) calculations were also used to explain the increased enzyme activity. The heterogeneous interface acted as the main active center, facilitating the electron transfer from CuO to Fe2O3. A colorimetric and intelligent sensing system was constructed based on deep learning. Using the peroxidase-like activity of CuO/Fe2O3, a platform for glufosinate pesticides and chlortetracycline hydrochloride (CTC) with the signal "on-off-on" changes were established. The limit of detection (LOD) of glufosinate and CTC was 28 and 0.69 µM, respectively. It was successfully applied in the detection of environmental water and soil. This study can provide an intelligent detection method for environmental monitoring.