The Anthocyanin Accumulation Related ZmBZ1, Facilitates Seedling Salinity Stress Tolerance via ROS Scavenging.

Anthocyanins are a class of antioxidants that scavenge free radicals in cells and play an important role in promoting human health and preventing many diseases. Here, we characterized a maize Bronze gene (BZ1) from the purple colored W22 introgression line, which encodes an anthocyanin 3-O-glucosyltransferase, a key enzyme in the anthocyanin synthesis pathway. Mutation of ZmBZ1 showed bronze-colored seeds and reduced anthocyanins in seeds aleurone layer, seedlings coleoptile, and stem of mature plants by comparison with purple colored W22 (WT). Furthermore, we proved that maize BZ1 is an aleurone layer-specific expressed protein and sub-located in cell nucleus. Real-time tracing of the anthocyanins in developing seeds demonstrated that the pigment was visible from 16 DAP (day after pollination) in field condition, and first deposited in the crown part then spread all over the seed. Additionally, it was transferred along with the embryo cell activity during seed germination, from aleurone layer to cotyledon and coleoptile, as confirmed by microscopy and real-time qRT-PCR. Finally, we demonstrated that the ZmBZ1 contributes to stress tolerance, especially salinity. Further study proved that ZmBZ1 participates in reactive oxygen scavenging (ROS) by accumulating anthocyanins, thereby enhancing the tolerance to abiotic stress.

Electrochemical strategies for the detection of cTnI.

Acute myocardial infarction (AMI) is the main cause of death from cardiovascular diseases. Thus, early diagnosis of AMI is essential for the treatment of irreversible damage from myocardial infarction. Traditional electrocardiograms (ECG) cannot meet the specific detection of AMI. Cardiac troponin I (cTnI) is the main biomarker for the diagnosis of myocardial infarction, and the detection of cTnI content has become particularly important. In this review, we introduced and compared the advantages and disadvantages of various cTnI detection methods. We focused on the analysis and comparison of the main indicators and limitations of various cTnI biosensors, including the detection range, detection limit, specificity, repeatability, and stability. In particular, we pay more attention to the application and development of electrochemical biosensors in the diagnosis of cardiovascular diseases based on different biological components. The application of electrochemical microfluidic chips for cTnI was also briefly introduced in this review. Finally, this review also briefly discusses the unresolved challenges of electrochemical detection and the expectations for improvement in the detection of cTnI biosensing in the future.

The effect of China's new cooperative medical scheme on health expenditures among the rural elderly.

BACKGROUND: The alarming progression of an increasingly aging population in China has attracted much attention within the country and abroad. In 2003, the Chinese central government launched the New Cooperative Medical Scheme (NCMS) to resolve problems of healthcare inequity in regions with inadequate infrastructure and relative poverty. The purpose of this study was to investigate the effect of NCMS on health expenditures by the Chinese rural elderly population. METHODS: The data were obtained from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), which was conducted in 2005, 2008, 2011 and 2014. Elderly people living in rural areas and 60 years old or above were screened for the investigation. The sample size was 7472 in 2005, 11,705 in 2008, 9239 in 2011, and 6059 in 2014. The OOP% and reimbursement ratio were the medical expenses paid by individuals accounting for their per capita annual income and the medical expenses paid by medical insurance accounting for their total medical expenses, respectively. By controlling for individuals' sociodemographic characteristics, pensions, demands and utilization of health services, we estimated the effect of the NCMS on the OOP% and reimbursement ratio for the rural elderly using seemingly unrelated regression (SUR). RESULTS: The NCMS coverage ranged from 11.63% in 2005 to 80.34% in 2014. The medical expenses of the elderly also increased from an average of $204.77 in 2005 to $696.23 in 2014, which was more than three times as much as in 2005. From 2005 to 2014, the reimbursement ratio for medical expenses of rural elderly people with NCMS increased significantly from 30.6% in 2005 to 56.1% in 2014. The proportion of reimbursement ratio for rural seniors with NCMS increased by 6.4% across each survey cycle (every 3 years). However, the NCMS resulted in an insignificant decrease in OOP% by 1.4% across each survey cycle (every 3 years). Among other medical insurances, public insurance and private elder insurance had significant positive impacts on reimbursement ratio but did not influence OOP%. CONCLUSIONS: NCMS remarkably increased the rural elderly's reimbursement ratio but insignificantly decreased the rural elderly's OOP%. In addition, the proportion of reimbursement ratio for NCMS participants increased by 6.4% every 3 years. Lower outpatient reimbursement, migration, limited reimbursement scope, an increasing demand for medical services and the rapid growth of medical expenses may be reasons for the gaps between the nominal reimbursement ratio and the actual reimbursement ratio and OOP%. Policymakers should further modify NCMS policies in rural China.

Primary care reforms in managing chronic diseases in Xiamen, China: A tentative assessment.

BACKGROUND: The primary care reform developed in Xiamen City stood out among the dozens of pilot reforms conducted in China. The aim of this study was to investigate the effects of the reform. METHODS: The data were collected from the Annual Statistical Report on Xiamen's Hospitals and face-to-face questionnaire interviews among physicians (n = 107) and community members (n = 399). Binary logistic regression was performed to analyze the factors influencing the community members' preference for treatment in community health centers (CHCs). RESULTS: The drug cost declined nearly 3.0% in hospitals, and outpatient visits increased more quickly (27.1%) in CHCs. A total of 86.2% of community members preferred to receive treatment for slight illness or chronic diseases in CHCs, and 77.9% of them were willing to be referred to CHCs during the recovery period. Patients who were managed by the general practice (GP) team showed higher percentages in examining and controlling blood pressure and blood glucose. CONCLUSION: The reform in Xiamen was easily accepted by physicians and community members. The reform had rendered initial achievements in reducing drug income in hospitals, increasing outpatient visits in CHCs, seeking health care in CHCs, and controlling blood pressure and glucose for patients with chronic diseases.

Fabrication and in vitro characterization of gadolinium-based nanoclusters for simultaneous drug delivery and radiation enhancement.

We report the synthesis of a gadolinium hydroxide (Gd(OH)3) nanorod based doxorubicin (Dox) delivery system that can enhance both magnetic resonance imaging contrast and radiation sensitivity. A simple and cost effective wet-chemical method was utilized in the presence of manganese (Mn) ions and Dox to produce the Gd(OH)3:Mn·Dox nanocluster structure. The Gd(OH)3:Mn·Dox nanocluster was composed of Mn-doped Gd(OH)3 nanorods arranged in parallel with Dox as a linker molecule between the adjacent nanorods. No other studies have utilized Dox as both the linker and therapeutic molecule in a nanostructure to date. The Gd(OH)3 nanorod is reported to have no significant cellular or in vivo toxicity, which makes it an ideal base material for this biomedical application. The Gd(OH)3:Mn·Dox nanocluster exhibited paramagnetic behavior and was stable in a colloidal solution. The nanocluster also enabled high Dox loading capacity and specifically released Dox in a sustained and pH-dependent manner. The positively charged Gd(OH)3:Mn·Dox nanoclusters were readily internalized into MDA-MB-231 breast cancer cells via endocytosis, which resulted in intracellular release of Dox. The released Dox in cells was effective in conferring cytotoxicity and inhibiting proliferation of cancer cells. Furthermore, a synergistic anticancer effect could be observed with radiation treatment. Overall, the Gd(OH)3:Mn·Dox nanocluster drug delivery system described herein may have potential utility in clinics as a multifunctional theranostic nanoparticle with combined benefits in both diagnosis and therapy in the management of cancer.

Synthesis and antibacterial activities of Yanglingmycin analogues.

The synthesis of Yanglingmycin and its enantiomer, along with eighteen Yanglingmycin analogues is reported. The structures were confirmed mainly by analyses of NMR spectral data. Antibacterial activity assays showed that Yanglingmycin and some of its analogues exhibited significant antibacterial activities against two important agricultural pathogenic bacteria, Ralstonia solanacearum and Pseudomonas syringae pv. actinidiae, with minimum inhibitory concentration (MIC) values ranging from 3.91 to 15.62 µg/mL. The antibacterial activities exhibited by Yanglingmycin and its analogues are promising, suggesting potential in the development of compounds for novel bactericides.

Synthesis and Antibacterial Activities of Yanglingmycin Analogues.

The synthesis of Yanglingmycin and its enantiomer, along with eighteen Yanglingmycin analogues is reported. The structures were confirmed mainly by analyses of NMR spectral data. Antibacterial activity assays showed that Yanglingmycin and some of its analogues exhibited significant antibacterial activities against two important agricultural pathogenic bacteria, Ralstonia solanacearum and Pseudomonas syringae pv. actinidiae, with MIC values ranging from 3.91 to 15.62 µg/mL. The antibacterial activities exhibited by Yanglingmycin and its analogues are promising, suggesting potential in the development of compounds for novel bactericides.

Phenanthrenes from Juncus effusus.

A chemical investigation of the EtOAc-soluble fraction from the ethanol extract of the medullae of Juncus effusus led to the isolation of three new 9,10-dihydrophenanthrenes, juncuenins E-G (1-3); two new phenanthrenes, dehydrojuncuenins D-E (4-5); one new feruloylated glycoside (6); and one known 9,10-dihydrophenanthrene (7). The structures of these compounds were determined by analyzing their spectroscopic data. Metabolites 1-4 and 7 were further evaluated for their in vitro cytotoxic activities against seven human cancer lines (A549, MCF-7, BEL-7402, HeLa, COLO205, BGC-823, and SK-OV-3). Among them, compound 1 exhibited weak cytotoxicity against MCF-7 and HeLa cell lines. Compound 7 showed moderate cytotoxicity against MCF-7 and HeLa cell lines, with IC50 values of 9.17 and 19.6 µM, respectively.

New dimeric phenanthrene and flavone from Spiranthes sinensis.

From the whole plant of Spiranthes sinensis, one novel dimeric phenanthrene, 2,2'-dihydroxy-5,5',7,7'-tetramethoxy-9,9',10,10'-tetrahydro-3,3'-biphenanthrene (1) and flavone 5-hydroxy-3,7-dimethoxy-4'-(1-hydroxy-3-methylbut-3-en-2-yloxy)-flavone (2) were isolated along with three other known flavonoids, which are reported for the first time from this species. Their structures were established after an extensive analysis by 1D and 2D NMR spectroscopy (NOESY, HSQC, and HMBC) as well as HR-TOF-MS.

Metal-organic framework (UiO-66 and UiO-66-NH2)-based adsorbents for bilirubin removal used in hemoperfusion.

Excessive accumulation of bilirubin in patients with hyperbilirubinemia can lead to tissue and organ damage and neurological diseases, and is even life-threatening in severe cases. Hemoperfusion is an effective method for removing bilirubin, but clinically used hemoperfusion adsorbents have unsatisfactory adsorption capacity and kinetics. In order to obtain a safe and efficient bilirubin adsorbent, Zr-based Metal-Organic Framework (MOF) material UiO-66 with high specific surface area and aqueous medium stability was prepared and modified with varying degrees of amination to improve its adsorption capacity. According to adsorption experiments in aqueous solution and simulated plasma, it was confirmed that the unsaturated coordinated zirconium in UiO-66 can effectively induce the aggregation and precipitation of free bilirubin unbound to albumin and the amino group on UiO-66-NH2 has a strong affinity for albumin bound bilirubin. The adsorption effect of UiO-66-NH2 with a high degree of amino modification is significantly stronger than that of UiO-66-NH2 with a low degree of modification. In simulated plasma with a bilirubin concentration of 40 mg dL-1, the adsorption capacities of UiO-66 and UiO-66-NH2-1.9 can reach 69.08 mg g-1 and 81.13 mg g-1. The adsorption isotherm fitting and adsorption kinetics fitting results also show that UiO-66 and UiO-66-NH2 are good adsorbents for bilirubin. In dynamic adsorption, the adsorbents also showed good performance and did not affect the protein in the plasma. The hemolysis test, coagulation time test, and cytotoxicity test confirmed that the bilirubin adsorbents based on UiO-66 and UiO-66-NH2 have good blood compatibility and biocompatibility. This study provides new ideas for the development of a novel bilirubin adsorbent and a theoretical basis for the study of bilirubin adsorption mechanisms.

Highly efficient cell-microbead encapsulation using dielectrophoresis-assisted dual-nanowell array.

Recent advancements in micro/nanofabrication techniques have led to the development of portable devices for high-throughput single-cell analysis through the isolation of individual target cells, which are then paired with functionalized microbeads. Compared with commercially available benchtop instruments, portable microfluidic devices can be more widely and cost-effectively adopted in single-cell transcriptome and proteome analysis. The sample utilization and cell pairing rate (∼33%) of current stochastic-based cell-bead pairing approaches are fundamentally limited by Poisson statistics. Despite versatile technologies having been proposed to reduce randomness during the cell-bead pairing process in order to statistically beat the Poisson limit, improvement of the overall pairing rate of a single cell to a single bead is typically based on increased operational complexity and extra instability. In this article, we present a dielectrophoresis (DEP)-assisted dual-nanowell array (ddNA) device, which employs an innovative microstructure design and operating process that decouples the bead- and cell-loading processes. Our ddNA design contains thousands of subnanoliter microwell pairs specifically tailored to fit both beads and cells. Interdigitated electrodes (IDEs) are placed below the microwell structure to introduce a DEP force on cells, yielding high single-cell capture and pairing rates. Experimental results with human embryonic kidney cells confirmed the suitability and reproducibility of our design. We achieved a single-bead capture rate of >97% and a cell-bead pairing rate of >75%. We anticipate that our device will enhance the application of single-cell analysis in practical clinical use and academic research.

A multifunctional PAN/PVP nanofiber sponge wound dressing loaded with ZIF-8-derived carbon nanoparticles with adjustable wetness for rapid wound disinfection and exudate management.

Rapid and safe disinfection and exudate management are two major challenges in infected wound care. Therefore, in this work, we developed a novel wound dressing via encapsulating ZIF-8-derived carbon nanoparticles in a hydrophilic nanofiber sponge to address severe wound infection and heavy exudate problems. The dressing can effectively kill bacteria through chemo-photothermal synergistic therapy. Meanwhile, the hydrophilic nanofiber sponge can quickly absorb wound exudate around the wound and accelerate the evaporation rate of liquid through the photothermal effect and its own structure; therefore, it is possible to remove excess liquid and regulate its wetness. In this way, it prevents the problem of wound overhydration often caused by hydrophilic dressings. In our experiment, the dressing showed good antibacterial performance and biocompatibility in vitro and could effectively control wound infection, absorb wound exudate and promote skin wound healing in vivo. Its good therapeutic effect is not only due to effective infection control and wound exudate management, but also because the structure of nanofibers similar to an extracellular matrix provides basic physical support and structural  signals conducive to skin tissue regeneration.

Carboxymethyl cellulose/polyvinyl alcohol composite aerogel supported beta molecular sieve for CH4 adsorption and storage.

Biomass aerogel is attractive in various applications due to their renewable, biodegradable and eco-friendly advantages. Herein, a novel beta molecular sieve/carboxymethyl cellulose/polyvinyl alcohol composite aerogel (beta/CP) is prepared by direct mixing and directional freeze-drying as an efficient gas adsorbent with hierarchical porosity. The beta molecular sieve is uniformly dispersed in the three-dimensional skeleton of the aerogel. By adjusting the loading mass of the beta molecular sieve to constitute a reasonable porosity and pore size distribution, the synergistic effect between pore structures of different scales improves the adsorption performance. The experiment results of beta/CP-4 show that the CH4 adsorption capacity can reach 60.33 cm3/g at 298 K and 100 bar, which is almost the same as that of the pure beta molecular sieve (62.09 cm3/g). The strong interaction between the aerogel and it prevents the molecular sieve agglomeration, improves the pore utilization, and also reduces the cost of using molecular sieve adsorbent. The above results indicate that the composite has good potential for application in the field of CH4 storage.

Sodium Alginate-Based Carbon Aerogel-Supported ZIF-8-Derived Porous Carbon as an Effective Adsorbent for Methane Gas.

Adsorption natural gas (ANG) is a technology in which natural gas is stored on the surface of porous materials at relatively low pressures, which are promising candidates for adsorption of natural gas. Adsorbent materials with a large surface area and porous structure plays a significant role in the ANG technology, which holds promise in increasing the storage density for natural gas while decreasing the operating pressure. Here, we demonstrate a facile synthetic method for rational construction of a sodium alginate (SA)/ZIF-8 composite carbon aerogel (AZSCA) by incorporating ZIF-8 particles into SA aerogel through a directional freeze-drying method followed by the carbonization process. The structure characterization shows that AZSCA has a hierarchical porous structure, in which the micropores originated from MOF while the mesopores are derived from the three-dimensional network of the aerogel. The experimental results show that AZSCA achieved high methane adsorption of 181 cm3·g-1 at 65 bar and 298 K, along with higher isosteric heat of adsorption (Qst) throughout the adsorption range. Thus, the combination of MOF powders with aerogel can find potential applications in other gas adsorption.

Transcriptome Analysis Revealed the Potential Molecular Mechanism of Anthocyanidins' Improved Salt Tolerance in Maize Seedlings.

Anthocyanin, a kind of flavonoid, plays a crucial role in plant resistance to abiotic stress. Salt stress is a kind of abiotic stress that can damage the growth and development of plant seedlings. However, limited research has been conducted on the involvement of maize seedlings in salt stress resistance via anthocyanin accumulation, and its potential molecular mechanism is still unclear. Therefore, it is of great significance for the normal growth and development of maize seedlings to explore the potential molecular mechanism of anthocyanin improving salt tolerance of seedlings via transcriptome analysis. In this study, we identified two W22 inbred lines (tolerant line pur-W22 and sensitive line bro-W22) exhibiting differential tolerance to salt stress during seedling growth and development but showing no significant differences in seedling characteristics under non-treatment conditions. In order to identify the specific genes involved in seedlings' salt stress response, we generated two recombinant inbred lines (RILpur-W22 and RILbro-W22) by crossing pur-W22 and bro-W22, and then performed transcriptome analysis on seedlings grown under both non-treatment and salt treatment conditions. A total of 6100 and 5710 differentially expressed genes (DEGs) were identified in RILpur-W22 and RILbro-W22 seedlings, respectively, under salt-stressed conditions when compared to the non-treated groups. Among these DEGs, 3160 were identified as being present in both RILpur-W22 and RILbro-W22, and these served as commonly stressed EDGs that were mainly enriched in the redox process, the monomer metabolic process, catalytic activity, the plasma membrane, and metabolic process regulation. Furthermore, we detected 1728 specific DEGs in the salt-tolerant RILpur-W22 line that were not detected in the salt-sensitive RILbro-W22 line, of which 887 were upregulated and 841 were downregulated. These DEGs are primarily associated with redox processes, biological regulation, and the plasma membrane. Notably, the anthocyanin synthesis related genes in RILpur-W22 were strongly induced under salt treatment conditions, which was consistented with the salt tolerance phenotype of its seedlings. In summary, the results of the transcriptome analysis not only expanded our understanding of the complex molecular mechanism of anthocyanin in improving the salt tolerance of maize seedlings, but also, the DEGs specifically expressed in the salt-tolerant line (RILpur-W22) provided candidate genes for further genetic analysis.

Konjac glucomannan/cellulose nanofibers composite aerogel supported HKUST-1 for CO2 adsorption.

Biomass aerogels are attractive in various applications owing to their inherent advantages of renewability, biodegradability and eco-friendly. Herein, a novel composite aerogel of konjac glucomannan (KGM)/TEMPO-oxidized cellulose nanofibers (TOCNF)@HKUST-1 (KTA@HKUST-1) is prepared through a facile vacuum impregnation method combined with the directional freeze-drying process, which using KGM and TOCNF as raw materials. The structural analyses disclose that the KTA@HKUST-1 has a hierarchical porosity, in which HKUST-1 can provide micropores for adsorption, while the meso-/macropores from KTA act as high-speed channels to improve diffusion and mass transfer rate to transport CO2 components into the micropores of HKUST-1. The experiment results of KTA@HKUST-1-10 (KTA@H10) show that the CO2 adsorption capacity can reach 3.50 mmol·g-1 at 1 bar and 298 K, and the adsorption capacity retention rate as high as 91.43% after 7 cycles. In addition, the CO2/N2 adsorption selectivity of KTA@H10 can reach 18.42, which has an excellent potential for selective CO2 adsorption.

Healthcare-Seeking Behavior among Chinese Older Adults: Patterns and Predictive Factors.

This study aimed to investigate the patterns and predictive factors of healthcare-seeking behavior among older Chinese adults. A sample of 10,914 participants aged ≥60 years from the 2011, 2013 and 2015 China Health and Retirement Longitudinal Study (CHARLS) was included. The bivariate analyses and Heckman selection model was used to identify predictors of healthcare-seeking behavior. Results shows that the utilization rate of outpatient services increased from 21.61% in 2011 to 32.41% in 2015, and that of inpatient services increased from 12.44% to 17.68%. In 2015, 71.93% and 92.18% chose public medical institutions for outpatient and inpatient services, 57.63% and 17.00% chose primary medical institutions. The individuals who were female, were younger, lived in urban, central or western regions, had medical insurance, had poor self-rated health and exhibited activity of daily living (ADL) impairment were more inclined to outpatient and inpatient services. Transportation, medical expenses, the out-of-pocket ratio and the urgency of the disease were associated with provider selection. The universal medical insurance schemes improved health service utilization for the elderly population but had little impact on the choice of medical institutions. The older adults preferred public institutions to private institutions, preferred primary institutions for outpatient care, and higher-level hospitals for hospitalization.

Highly efficient antifogging and antibacterial food packaging film fabricated by novel quaternary ammonium chitosan composite.

In this work, a multifunctional food packaging composite coating with transparent, biodegradable, antifogging and antibacterial properties was designed and fabricated by quaternary ammonium salt modified chitosan (HACC) and poly (vinyl alcohol) (PVA) via a facile and environment-friendly solution casting method. A simple quaternization modification enabled the coating simultaneously to achieve excellent antifogging and antibacterial functions. The excellent antifogging property of the HACC/PVA composite coating was attributed to the strong water absorbency of quaternary ammonium chitosan and PVA. A nearly 98% transmittance ratio of coated glasses was achieved during antifogging test. In addition, the inhibition rate of the HACC/PVA composite coating kill against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Botrytis cinerea were up to ~99%. The antibacterial effect was demonstrated by each group of strawberries after storage for 1, 3, 5 days. The multifunctional coating has broad prospects in the application of fruit and vegetable packaging.

Cellular Nanofiber Structure with Secretory Activity-Promoting Characteristics for Multicellular Spheroid Formation and Hair Follicle Regeneration.

Multicellular spheroids can mimic the in vivo microenvironment and maintain the unique functions of tissues, which has attracted great attention in tissue engineering. However, the traditional culture microenvironment with structural deficiencies complicates the culture and collection process and tends to lose the function of multicellular spheroids with the increase of cell passage. In order to construct efficient and functional multicellular spheroids, in this study, a chitosan/polyvinyl alcohol nanofiber sponge which has an open-cell cellular structure is obtained. The hair follicle (HF) regeneration model was employed to evaluate HF-inducing ability of dermal papilla (DP) multicellular spheroids which formed on the cellular structure nanofiber sponge. Through structural fine-tuning, the nanofiber sponge has appropriate elasticity for the creation of a three-dimensional dynamic microenvironment to regulate cellular behavior. The cellular structure nanofiber sponge tilts the balance of cell-substratum and cell-cell interactions to a state which is more conducive to the formation of controllable multicellular spheroids in a short time. More importantly, it improves the secretory activity of high-passaged dermal papilla cells and restores their intrinsic properties. Experiments using BALB/c nude mice show that cultured DP multicellular spheroids could effectively enhance HF-inducing ability. This novel system provides a simple and efficient strategy for multicellular spheroid formation and HF regeneration.

Pd@Au Bimetallic Nanoplates Decorated Mesoporous MnO2 for Synergistic Nucleus-Targeted NIR-II Photothermal and Hypoxia-Relieved Photodynamic Therapy.

Bimetallic nanoparticles have received considerable attention owing to synergistic effect and their multifunctionality. Herein, new multifunctional Pd@Au bimetallic nanoplates decorated hollow mesoporous MnO2 nanoplates (H-MnO2 ) are demonstrated for achieving not only nucleus-targeted NIR-II photothermal therapy (PTT), but also tumor microenvironment (TME) hypoxia relief enhanced photodynamic therapy (PDT). The Pd@Au nanoplates present a photothermal conversion efficiency (PTCE) as high as 56.9%, superior to those PTAs activated in the NIR-II region such as Cu9 S5 nanoparticles (37%), Cu3 BiS3 nanorods (40.7%), and Au/Cu2-x S nanocrystals (43.2%). They further functionalize with transactivator of transcription (TAT) moiety for cell nuclear-targeting and biodegradable hollow mesoporous MnO2 (≈100 nm) loaded with photosensitizer Ce6 (TAT-Pd@Au/Ce6/PAH/H-MnO2 ) to construct a hierarchical targeting nanoplatform. The as-made TAT-Pd@Au/Ce6/PAH/H-MnO2 demonstrates good premature renal clearance escape ability and increased tumor tissue accumulation. It can be degraded in acidic TME and generate O2 by reacting to endogenous H2 O2 to relieve the hypoxia for enhanced PDT, while the released small TAT-Pd@Au nanoplates can effectively enter into the nucleus to mediate PTT. As a result, a remarkable therapeutic effect is achieved owing to the synergistic PTT/PDT therapy. This hierarchical targeting, TME-responsive, cytoplasm hypoxia relief PDT, and nuclear NIR-II PTT synergistic therapy can pave a new avenue for nanomaterials-based cancer therapy.