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Traditional treatments against advanced non-small cell lung cancer (NSCLC) with high morbidity and mortality continue to be dissatisfactory. Given this situation, there is an urgent requirement for alternative modalities that provide lower invasiveness, superior clinical effectiveness, and minimal adverse effects. The combination of photodynamic therapy (PDT) and immunotherapy gradually become a promising approach for high-grade malignant NSCLC. Nevertheless, owing to the absence of precise drug delivery techniques as well as the hypoxic and immunosuppressive characteristics of the tumor microenvironment (TME), the efficacy of this combination therapy approach is less than ideal. In this study, we construct a novel nanoplatform that indocyanine green (ICG), a photosensitizer, loads into hollow manganese dioxide (MnO2) nanospheres (NPs) (ICG@MnO2), and then encapsulated in PD-L1 monoclonal antibodies (anti-PD-L1) reprogrammed exosomes (named ICG@MnO2@Exo-anti-PD-L1), to effectively modulate the TME to oppose NSCLC by the synergy of PDT and immunotherapy modalities. The ICG@MnO2@Exo-anti-PD-L1 NPs are precisely delivered to the tumor sites by targeting specially PD-L1 highly expressed cancer cells to controllably release anti-PD-L1 in the acidic TME, thereby activating T cell response. Subsequently, upon endocytic uptake by cancer cells, MnO2catalyzes the conversion of H2O2to O2, thereby alleviating tumor hypoxia. Meanwhile, ICG further utilizes O2to produce singlet oxygen (1O2) to kill tumor cells under 808 nm near-infrared (NIR) irradiation. Furthermore, a high level of intratumoral H2O2reduces MnO2to Mn2+, which remodels the immune microenvironment by polarizing macrophages from M2 to M1, further driving T cells. Taken together, the current study suggests that the ICG@MnO2@Exo-anti-PD-L1 NPs could act as a novel drug delivery platform for achieving multimodal therapy in treating NSCLC.

Corticosteroids have beneficial effects in improving outcomes in hospitalized patients with severe COVID-19 by suppressing excessive immune responses. However, the effect of corticosteroids on the humoral and T-cell responses of survivors of COVID-19 1 year after infection remains uncertain, as it relates to the extent of immediate, antigen-specific defense provided by protective memory.

Controlling topological phases of light allows the observation of abundant topological phenomena and the development of robust photonic devices. The prospect of more sophisticated control with topological photonic devices for practical implementations requires high-level programmability. Here we demonstrate a fully programmable topological photonic chip with large-scale integration of silicon photonic nanocircuits and microresonators. Photonic artificial atoms and their interactions in our compound system can be individually addressed and controlled, allowing the arbitrary adjustment of structural parameters and geometrical configurations for the observation of dynamic topological phase transitions and diverse photonic topological insulators. Individual programming of artificial atoms on the generic chip enables the comprehensive statistical characterization of topological robustness against relatively weak disorders, and counterintuitive topological Anderson phase transitions induced by strong disorders. This generic topological photonic chip can be rapidly reprogrammed to implement multifunctionalities, providing a flexible and versatile platform for applications across fundamental science and topological technologies.

A visible-light-induced photocatalyst-free acylative pyridylation of styrenes with 4-acyl-1,4-dihydropyridines (DHPs) and 4-cyanopyridines has been described, featuring mild reaction conditions, a broad substrate scope, and good functional group tolerance. The reaction could also be performed under sunlight irradiation albeit with a slightly lower conversion. 4-Acyl-1,4-DHPs serve a dual role, acting as both a photoreductant to reduce the cyanopyridine to its radical anion intermediate and a radical precursor to produce the acyl radical. The mechanism was especially elucidated through the Hammett analysis, with the quadratic linear regression analysis by using radical dual parameters, σmband σjj·. The findings from Hammett analysis further demonstrate that the rate-limiting step of the process is the single electron transfer between 4-acyl-1,4-DHPs and 4-cyanopyridines.

Synergistic control of the frequency and orbital angular momentum (OAM) of light offers new opportunities for the generation of spatio-temporal optical waveforms and optical metrology. However, their physical realizations are typically bulky and complex owing to challenges in creating, manipulating and detecting mutually coherent, high-dimensional OAM states. Here we achieve combined control over the frequency and the OAM of a comb structure on a photonic chip. Dissipative optical solitons are formed in a nonlinear ring microresonator and emitted owing to engraved angular gratings, with each comb line carrying a distinct OAM. The beam of such a vortex soliton microcomb manifests dynamically revolving, double-helical intensity profiles. The one-to-one correspondence between the OAM and frequencies features a high extinction ratio of over 18.5 dB, enabling precision spectroscopy of optical vortices. Our work provides an integrated solution for realizing coherent light sources that are multiplexed in the spatial and frequency domains, with the potential to establish a new approach to the generation of high-dimensional structured light.

To improve the insufficient performance of anion on cationic surfactants and to further study the influence of anion on the surface properties, a cationic surfactant (cetyltrimethylammonium p-toluenesulfonate, CTATS) was prepared, and the relevant surface properties, including surface tension, critical micelle concentration, foaming ability and stability, corrosion inhibition and oil displacement efficiency were studied. Compared to cetyltrimethylammonium chloride (CTAC), CTATS exhibited higher surface activity, lower foaming volume, higher foam stability, higher corrosion inhibition performance and oil displacement efficiency. The results indicate that the CTATS has better performances as a surfactant type in oil and gas fields.

Combination therapy with the synergistic effect is an effective way in cancer chemotherapy. Herein, an antiangiogenic sorafenib (SOR) and hypoxia-activated prodrug tirapazamine (TPZ)-coencapsulated liposome (LipTPZ/SOR) is prepared for chemotherapy of hepatocellular carcinoma (HCC). SOR is a multi-target tyrosine kinase inhibitor that can inhibit tumor cell proliferation and angiogenesis. The antiangiogenesis effect of SOR can reduce oxygen supply and aggravate tumor hypoxia, which is able to activate hypoxia-sensitive prodrug TPZ, exhibiting the synergistic antitumor effect. LipTPZ/SORat different molar ratios of TPZ and SOR can significantly inhibit the proliferation of hepatocellular carcinoma cells. The mole ratio of TPZ and SOR was optimized to 2:1, which exhibited the best synergetic antitumor effect. The synergistic antitumor mechanism of SOR and TPZ was also investigated in vivo. After treated with SOR, the number of vessels was decreased, and the degree of hypoxia was aggravated in tumor tissues. What is more, in the presence of SOR, TPZ could be activated to inhibit tumor growth. The combination of TPZ and SOR exhibited an excellent synergistic antitumor effect. This research not only provides an innovative strategy to aggravate tumor hypoxia to promote TPZ activation but also paints a blueprint about a new nanochemotherapy regimen for the synergistic chemotherapy of HCC, which has excellent biosafety and bright clinical application prospects.

The practice of oil and gas exploration has confirmed the existence of recoverable shale oil resources in the Permian Lucaogou Formation on the northern edge of the Bogda Mountains. However, previous research on the development characteristics and main controlling factors of shale oil resources in this area is relatively limited. In order to elucidate the development characteristics and principal controlling factors of the shale deposit in the Lucaogou Formation, the characteristics, physical properties, diagenesis, and influencing factors of the shale ore were investigated utilising data derived from outcrop, drilling, seismic, and geochemical analysis. The findings indicate that the shale of the Lucaogou Formation is prevalent and extensive. The deposit’s lithology is predominantly composed of dark grey and grey-black mud shale, interspersed with thin layers of dark grey and grey-black sandy mud shale and dolomite mud shale. The most prevalent minerals are carbonate minerals, followed by feldspar and quartz, with a notable proportion of brittle minerals. The deposit is primarily composed of dissolution pores, bedding fractures, and structural fractures, with a porosity of 1.23–3.26% and permeability of 0.012–0.076 mD, which are characteristic of ultra-low porosity and ultra-low permeability deposits. Among the three deposit types, the sandstone type exhibits the most favourable physical properties, followed by the dolomite type and the shale type, which displays the least favourable properties. The shale of the Lucaogou Formation is currently in the middle diagenetic phase, which is characterised by compaction, cementation (carbonate cementation, mudstone cementation, pebble cementation), and dissolution. The destructive effect of compaction and cementation on the physical properties is counterbalanced by the constructive effect of dissolution. The diagenetic environment has gradually changed from an alkaline environment to a slightly alkaline, slightly acidic stage.

Non-alcoholic fatty liver disease is a prevalent chronic metabolic condition, for which no approved medications are available. As a condiment and traditional Chinese medicine, ginger can be useful in reducing the symptoms of non-alcoholic fatty liver disease. Although its active ingredients and mechanisms of action are unknown, there is a lack of research on them. The purpose of this study is to prepare magnetite (Fe3O4)@Stearoyl-CoA desaturase 1 (SCD1) materials and analyze them using ultra-high performance liquid-chromatography-mass spectrometry (UPLC-MS) for rapid screening of potential inhibitors of SCD1 in ginger. Based on this analysis, it has been shown that the primary components in ginger that bind SCD1 directly are gingerols, with 10-gingerol having a greater affinity for binding to SCD1 than 8-gingerol and 6-gingerol. Moreover, further studies indicated that free fatty acids (FFA)-induced lipid accumulation is improved by this class of compounds in normal human hepatocytes (THLE-3), with 10-gingerol being the most effective compound. This study provides a new insight into the mechanism, by which ginger contributes to the improvement of non-alcoholic fatty liver disease (NAFLD) and provide support for the effective use of 10-gingerol for the treatment of NAFLD.

Manipulating topological invariants is possible by modifying the global properties of optical devices to alter their band structures. This could be achieved by statically altering devices or dynamically reconfiguring devices with considerably different geometric parameters, even though it inhibits switching speed. Recently, optical nonlinearity has emerged as a tool for tailoring topological and non-Hermitian (NH) properties, promising fast manipulation of topological phases. In this work, we observe topologically protected NH phase transitions driven by optical nonlinearity in a silicon nanophotonic Floquet topological insulator. The phase transition occurs from forbidden bandgaps to NH conducting edge modes, which emerge at a nonlinearity-induced gain–loss junction along the boundaries of a topological insulator. We find static NH edge modes and dynamic phase transitions involving exceptional points at a speed of hundreds of picoseconds, which inherently retain topological protections against fabrication imperfections. This work shows an interplay between topology and non-Hermiticity by means of nonlinear optics, and it provides a way of manipulating multiple phase transitions at high speeds that is applicable to many other materials with strong nonlinearities, which could promote the development of unconventionally robust light-controlled devices for classical and quantum applications.

In this article, a method to fast classify (intradural hemorrhage, epidural hemorrhage, and cerebral parenchymal hemorrhage) and locate the bleeding points by using the singularity expansion method (SEM) and backpropagation (BP) neural network optimized by genetic algorithm (GA) and sparrow search algorithm (SSA) is proposed. In the simulation model, the bleeding spot with a radius of 3 mm is successfully identified by the approach. The test accuracy in the simulation for both the bleeding’s localization and classification are 98.0% and 97.4%, respectively. Head phantoms that have all been improved over the previous phantom established are used for experiments. A bleeding target with a volume of 3 mL can be identified in the microwave detection system. In the experiment, the accuracy of classification and localization of the bleeding type are 90% and 94.7%, respectively. The final results demonstrate the capability and effectiveness of the method. Faster determination of bleeding point type and orientation means that patients can be provided with different rescue measures accordingly.

Although chemotherapy remains the standard therapy for tumor treatment, serious side effects can occur because of nontargeted distribution and damage to healthy tissues. Hollow mesoporous silica nanoparticles (HMSNs) modified with lipids offer potential as delivery systems to improve therapeutic outcomes and reduce adverse effects. Herein, we synthesized HMSNs with integrated disulfide bonds (HMSN) for loading with the chemotherapeutic agent oxaliplatin (OXP) which were then covered with the synthesized hypoxia-sensitive lipid (Lip) on the surface to prepare the dual-sensitive lipid-composite nanoparticles (HMSN-OXP-Lip). The empty lipid-composite nanoparticles (HMSN-Lip) would consume glutathione (GSH) in cells because of the reduction of disulfide bonds in HMSN and would also inhibit GSH production because of NADPH depletion driven by Lip cleavage. These actions contribute to increased levels of ROS that induce the immunogenic cell death (ICD) effect. Simultaneously, HMSN-Lip would disintegrate in the presence of high concentrations of GSH. The lipid in HMSN-OXP-Lip could evade payload leakage during blood circulation and accelerate the release of the OXP in the tumor region in the hypoxic microenvironment, which could significantly induce the ICD effect to activate an immune response for an enhanced therapeutic effect. The tumor inhibitory rate of HMSN-OXP-Lip was almost twice that of free OXP, and no apparent side effects were observed. This design provides a dual-sensitive and efficient strategy for tumor therapy by using lipid-composite nanoparticles that can undergo sensitive drug release and biodegradation.

Road network maintenance scheduling mainly considers budget limits in the previous studies and largely ignores the capital constraints. This study proposes a bi-objective mixed integer programming model, in which the net present value (NPV) is maximized and the increased total system travel time (ITSTT) due to maintenance activities under the capital constraints is minimized. Since the road network flows cannot reach an equilibrium state overnight due to the variation of network capacity, a link-based day-to-day dynamics model is developed to simulate the transient fluctuation in the traffic flows and calculate the total system travel time of each day. The bi-objective model is solved by the nondominated sorting genetic algorithm-II (NSGA-II) that generates a set of optimal Pareto solutions. The TOPSIS method is then adopted to determine the best compromise solution. Finally, a case study is conducted to demonstrate the effects of key parameters on the values of the two objectives.

Single-photon technologies are vital to a broad range of research areas such as nuclear physics, astrophysics, biology and computer vision. Fields such as LiDAR, single-photon imaging, biomedical imaging, quantum communication, optical quantum computing, quantum metrology, remote sensing and non-line-of-sight (NLOS) imaging also benefit from developments in single-photon technologies. This special issue is intended to bring together a broad range of research article with interests in single-photon detectors, single photon avalanche diode (SPAD), single-photon sources, photon entanglement, NLOS imaging, computational imaging algorithms, and their general applications in quantum information science, 2D and 3D imaging, sensing and metrology. This special issue addresses the current progress and latest breakthroughs in single-photon technologies and their emergent applications, particularly covering the following areas:

Uncovering gas adsorption characteristics of coal at the molecular scale is of great theoretical significance for the study of gas occurrence, coalbed methane exploitation, and carbon dioxide sequestration. In this study, based on proximate analysis, ultimate analysis, 13C nuclear magnetic resonance, and Fourier-transform infrared spectroscopy experiments, the existence forms and relative contents of elements of anthracite in the Qinshui Basin were tested and analyzed, and a macromolecular structure model was constructed. Besides, three types of acidic oxygen-containing functional groups, namely, carboxyl groups, phenolic hydroxyl groups, and lactone groups, were added to the molecular model. Furthermore, CH4adsorption simulation was conducted on the original molecular model of anthracite and models with three types of acidic functional groups added. The following research results were obtained. The molecular formula of the constructed macromolecular model of anthracite in the Qinshui Basin is C193H138N2O7. The molecular structure of coal becomes more compact and curved after structural optimization and annealing optimization. For the four models, the CH4adsorption characteristics of coal molecules all conform to the Langmuir equation under the same simulation conditions. Among them, the original model has the largest CH4adsorption capacity, while the addition of oxygen-containing functional groups reduces the CH4adsorption capacity to varying extents. The reduction of CH4adsorption capacity follows the order: adding carboxyl groups > adding phenolic hydroxyl groups > adding lactone groups, which is mainly attributed to the different adsorption heats and adsorptive potential wells triggered by the addition of acidic functional groups in molecules.

Background Eosinophilic chronic rhinosinusitis with nasal polyps (Eos-CRSwNP) remains a recalcitrant disease with a high recurrence rate.Objective This study aimed to identify a predictor of long-term recurrence in patients with Eos-CRSwNP.Methods A total of 39 Eos-CRSwNP patients who had their initial and recurrent nasal polyps surgically removed were retrospectively included in this study, with 49 Eos-CRSwNP patients without recurrence and 32 patients with non-Eos-CRSwNP matched by randomly chosen. Clinical characteristics were compared among or between groups. Spearman correlation analyses and a backward stepwise multivariate logistic regression analysis were performed to find factors associated with the recurrence and recurrence time of Eos-CRSwNP. Furthermore, a receiver operating characteristic (ROC) curve was used to determine the predictor of long-term Eos-CRSwNP recurrence.Results The number and ratio of tissue eosinophils were highest in Eos-CRSwNP with recurrence and lowest in non-Eos-CRSwNP. The ratio of tissue lymphocytes was highest in non-Eos-CRSwNP and lowest in Eos-CRSwNP with recurrence, with the number of tissue lymphocytes higher in Eos-CRSwNP without recurrence than the other two groups. The numbers of tissue lymphocytes in the initial nasal polyps were lower and the numbers of tissue eosinophils were higher in the group of recurrent nasal polyps that recurred at >5 years after surgery than in the nasal polyps that recurred at <5 years after surgery. The tissue lymphocyte-to-eosinophil ratio (LER) showed a significant negative correlation with the recurrence and the recurrence time of Eos-CRSwNP. A ROC curve revealed that a tissue LER value < 0.67 predicted long-term Eos-CRSwNP recurrence with 72.73% sensitivity and 82.35% specificity (area under the curve  =  0.789).Conclusion Tissue LER is strongly associated with Eos-CRSwNP recurrence and may play a key role in predicting long-term Eos-CRSwNP recurrence.

Rechargeable aqueous zinc batteries have attracted much attention due to their high security, plentiful zinc resources, and environmental friendliness. However, it can only offer limited specific capacity and energy density based on ion insertion chemistry cathode. Herein, we design a low-cost and high-energy density aqueous Zn-S battery where the conversion cathode was fabricated by pitch-derived three-dimensional (3D) amorphous carbon encapsulated industrial-grade sulfur powder. The cost of the chemical substances for this aqueous Zn-S battery might be reduced to $9.38 per kW h based on the affordable cost of the raw ingredients. It is found that the PAC/S-60.33% cathode reveals excellent electrochemical performance, including a high reversible capacity (633.5 mAh g−1at 0.5 A g−1), high energy density (297.5 Wh kg−1), an excellent rate capability (204.5 mAh g−1at 5.5 A g−1), as well as good cycling stability (180 mAh g−1after 400 cycles at 5.0 A g−1). Besides, the reaction mechanism of the cathode was investigated using ex-situX-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and transmission electron microscope (TEM). It was demonstrated that the cathode undergoes a conversion reaction between S and ZnS. Furthermore, the discoveries also offer prospective possibilities to fabricate more secure and inexpensive battery systems.

Graphs have provided an expressive mathematical tool to model quantum-mechanical devices and systems. In particular, it has been recently discovered that graph theory can be used to describe and design quantum components, devices, setups and systems, based on the two-dimensional lattice of parametric nonlinear optical crystals and linear optical circuits, different to the standard quantum photonic framework. Realizing such graph-theoretical quantum photonic hardware, however, remains extremely challenging experimentally using conventional technologies. Here we demonstrate a graph-theoretical programmable quantum photonic device in very-large-scale integrated nanophotonic circuits. The device monolithically integrates about 2,500 components, constructing a synthetic lattice of nonlinear photon-pair waveguide sources and linear optical waveguide circuits, and it is fabricated on an eight-inch silicon-on-insulator wafer by complementary metal–oxide–semiconductor processes. We reconfigure the quantum device to realize and process complex-weighted graphs with different topologies and to implement different tasks associated with the perfect matching property of graphs. As two non-trivial examples, we show the generation of genuine multipartite multidimensional quantum entanglement with different entanglement structures, and the measurement of probability distributions proportional to the modulus-squared hafnian (permanent) of the graph’s adjacency matrices. This work realizes a prototype of graph-theoretical quantum photonic devices manufactured by very-large-scale integration technologies, featuring arbitrary programmability, high architectural modularity and massive manufacturing scalability.

Manipulating the defect tolerance is one of the effective ways to maintain the high power conversion efficiency and keep the stability of perovskite semiconductor materials. So, rapid screening for defects and trap states in the perovskite semiconductor candidates is urgently needed. Theoretical investigations of defects based on density functional theory (DFT) are still limited by their extremely high consumption of computational resources and time. We implement an accelerated material discovery approach using artificial intelligence and DFT, which can predict the defect transition levels in the candidate perovskite semiconductor materials. To verify the accuracy of our models, Cs3Sb2Br9and Cs2SnBr6, which are out of the dataset that we used in machine learning (ML) model construction, are taken as examples. The extrapolation of ML prediction models and the results given by DFT calculations are compared for defect transition energy levels. The two methods are consistent with each other with very small errors. Our strategy avoids complex and time-consuming computational work based on DFT and provides quick and efficient screening of physical properties with low cost.

Pancreatic cancer (PC) is the fourth leading cause of cancer death, and the 5 year survival rate is only 4%. Chemotherapy is the treatment option for the majority of PC patients diagnosed at an advanced stage, whereas the desmoplastic stroma of PC could block the perfusion of chemotherapeutic agents to tumor tissues and contribute generally to chemoresistance. Therefore, the clinical status of PC calls for an urgent exploration in the effective treatment strategy. Chemo-phototherapy is an emerging modality against malignant tumors, but owing to the low targeting ability of theranostic agents or unspecific accumulation in the tumor region, majority of chemo-phototherapy techniques have disappointing therapeutic efficiencies. Herein, we have explored CD71-specific targeting aptamers and paclitaxel (PTX)-modified polydopamine (PDA) nanospheres with the conjugation of peptidomimetic AV3 (termed Apt-PDA@PTX/AV3 bioconjugates) to specifically target and combat PC in vivo by synergistic chemo-phototherapy. After the delivery of nanotheranostic agents to the tumor microenvironment (TME) or subsequent endocytic uptake by PC cells, a simultaneous release of AV3 and PTX from Apt-PDA@PTX/AV3 bioconjugates via near-infrared (NIR) irradiation can decrease desmoplastic stroma to enhance tumor perfusion and tumor-killing effects. Meanwhile, PDA cores utilize NIR laser to create unendurable hyperthermia within TME to “cook” tumors. Taken together, the current study finally suggests that our Apt-PDA@PTX/AV3 bioconjugates could act as a novel therapeutic approach by synergistic chemo-phototherapy for the programmable inhibition of PC.

Hematopoietic syndrome of acute radiation syndrome (h-ARS) is an acute illness resulted from the damage of bone marrow (BM) microenvironment after exposure to radiation. Currently, the clinical management of h-ARS is limited to medication-assisted treatment, while there is still no specific therapy for the hematopoietic injury from high-dose radiation exposure. Our study aimed to assemble biomimetic three-dimensional (3D) BM microniches by co-culture of hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stem cells (MSCs) in porous, injectable and viscoelastic microscaffolds in vitro. The biodegradable BM microniches were then transplanted in vivointo the BM cavity for the treatment of h-ARS. We demonstrated that the maintenance of HSPCs was prolonged by co-culture with MSCs in the porous 3D microscaffolds with 84 μm in pore diameter and 11.2 kPa in Young's modulus compared with 2D co-culture system. Besides, the minimal effective dose and therapeutic effects of the BM microniches were investigated on a murine model of h-ARS, which showed that the intramedullary cavity-injected BM microniches could adequately promote hematopoietic reconstitution and mitigate death from acute lethal radiation with a dose as low as 1000 HSPCs. Furthermore, the mRNA expression of Notch1and its downstream target gene Hes1of HSPCs were increased when co-cultured with MSCs, while the Jagged1expression of the co-cultured MSCs was upregulated, indicating the significance of Notch signaling pathway in maintenance of HSPCs. Collectively, our findings provide evidence that biomimetic and injectable 3D BM microniches could maintain HSPCs, promote hematopoiesis regeneration and alleviate post-radiation injury, which provides a promising approach to renovate conventional HSPCs transplantation for clinical treatment of blood and immune disorders.

ABSTRACTAcute myeloid leukemia (AML) is a highly cancerous and aggressive hematologic disease with elevated levels of drug resistance and relapse resulting in high mortality. Recently, bromodomains and extra-terminal (BET) protein inhibitors have been extensively researched in hematological tumors as potential anticancer agents. MZ1 is a novel BET inhibitor that mediates selective proteins degradation and suppression of tumor growth through proteolysis-targeting chimeras (PROTAC) technology. Accordingly, this study aimed to investigate the role and therapeutic potential of MZ1 in AML. In this study, we first identified that AML patients with high BRD4 expression had poor overall survival than those with low expression group. MZ1 inhibited AML cell growth and induced apoptosis and cycle arrest in vitro. MZ1 induced degradation of BRD4, BRD3 and BRD2 in AML cell strains. Additionally, MZ1 also initiated the cleavage of poly-ADP-ribose polymerase (PARP), which showed cytotoxic effects on NB4 (PML-RARa), K562 (BCR-ABL), Kasumi-1 (AML1-ETO), and MV4-11 (MLL-AF4) cell lines representing different molecular subtypes of AML. In AML mouse leukemia model, MZ1 significantly decreased leukemia cell growth and increased the mouse survival time. According to the RNA-sequencing analysis, MZ1 led to c-Myc and ANP32B genes significant downregulation in AML cell lines. Knockdown of ANP32B promoted AML cell apoptosis and inhibited cell growth. Overall, our data indicated that MZ1 had broad anti-cancer effects on AML cell lines with different molecular lesions, which might be exploited as a novel therapeutic strategy for AML patients.

Aging is characterized by a progressive deterioration of physiological integrity, leading to impaired functional ability and ultimately increased susceptibility to death. It is a major risk factor for chronic human diseases, including cardiovascular disease, diabetes, neurological degeneration, and cancer. Therefore, the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences. In recent years, there has been unprecedented progress in aging research, particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes. In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases, we review the descriptive, conceptual, and interventive aspects of the landscape of aging composed of a number of layers at the cellular, tissue, organ, organ system, and organismal levels.