Smoking-related cancer death among men and women in an ageing society (China 2020-2040): a population-based modelling study.

BACKGROUND: China is experiencing a postpeak smoking epidemic with accelerating population ageing. Understanding the impacts of these factors on the future cancer burden has widespread implications. METHODS: We developed predictive models to estimate smoking-related cancer deaths among men and women aged ≥35 years in China during 2020-2040. Data sources for model parameters included the United Nations World Population Prospects, China Death Surveillance Database, national adult tobacco surveys and the largest national survey of smoking and all causes of death to date. The main assumptions included stable sex-specific and age-specific cancer mortality rates and carcinogenic risks of smoking over time. RESULTS: In a base-case scenario of continuing trends in current smoking prevalence (men: 57.4%-50.5%; women: 2.6%-2.1% during 2002-2018), the smoking-related cancer mortality rate with population ageing during 2020-2040 would rise by 44.0% (from 337.2/100 000 to 485.6/100 000) among men and 52.8% (from 157.3/100 000 to 240.4/100 000) among women; over 20 years, there would be 8.6 million excess deaths (0.5 million more considering former smoking), and a total of 117.3 million smoking-attributable years of life lost (110.3 million (94.0%) in men; 54.1 million (46.1%) in working-age (35-64 years) adults). An inflection point may occur in 2030 if smoking prevalence were reduced to 20% (Healthy China 2030 goal), and 1.4 million deaths would be averted relative to the base-case scenario if the trend were maintained through 2040. CONCLUSIONS: Coordinated efforts are urgently needed to curtail a rising tide of cancer deaths in China, with intensified tobacco control being key.

Macrophage-Membrane-Camouflaged Nonviral Gene Vectors for the Treatment of Multidrug-Resistant Bacterial Sepsis.

Sepsis is a life-threatening disease caused by systemic bacterial infections, with high morbidity and mortality worldwide. As the standard treatment for sepsis, antibiotic therapy faces the challenge of impaired macrophages and drug-resistant bacteria. In this study, we developed a membrane-camouflaged metal-organic framework (MOF) system for plasmid DNA (pDNA) delivery to combat sepsis. The antimicrobial gene LL37 was efficiently encapsulated in the pH-sensitive MOF, and the nanoparticles were decorated with macrophage membranes in a compatible manner. Macrophage membrane coating allows targeted delivery of LL37 to macrophages and creates macrophage factories for the continuous generation of antimicrobial peptides. Compared to naked nanoparticles, primary bone marrow mesenchymal macrophage membrane-modified nanoparticles greatly improved the survival rate of immunodeficient septic mice through the synergistic effect of efficient gene therapy and inflammatory cytokine sequestration. This study demonstrates an effective membrane biomimetic strategy for efficiently delivering pDNA, offering an excellent option for overcoming sepsis.

Nationwide gastric cancer prevention in China, 2021-2035: a decision analysis on effect, affordability and cost-effectiveness optimisation.

OBJECTIVE: To project future trajectories of the gastric cancer (GC) burden in China under different scenarios of GC prevention and identify strategies to improve affordability and cost-effectiveness. DESIGN: Using a cohort of Chinese men and women born during 1951-1980, we assumed that different prevention strategies were conducted, including eradication of Helicobacter pylori (Hp) and endoscopy screening (one-time, annual, biennial, triennial or stratified according to personal risk). We performed a literature search to identify up-to-date data and populate a Markov model to project the number of new GC cases and deaths during 2021-2035, as well as resource requirements and quality-adjusted life-years (QALYs). We examined the impacts of general (among the whole population) and targeted (high-risk population) prevention. RESULTS: During 2021-2035, 10.0 million new GC cases and 5.6 million GC deaths would occur, with 7.6%-35.5% and 6.9%-44.5%, respectively, being avoidable through various prevention strategies. Relative to the status quo, Hp eradication was a cost-saving strategy. General annual screening dominated other screening strategies, but cost more than CNY 70 000 per QALY gained (willingness-to-pay) compared with Hp eradication. Among endoscopy strategies, targeted screening resulted in 44%-49% lower cost per QALY gained over the status quo than general screening. Among high-risk population, tailoring the screening frequency according to personal risk could reduce endoscopy-related resources by 22% compared with biennial screening and by 55% compared with annual screening, CONCLUSION: Our findings provide important input for future decision-making and investment, highlighting the need and feasibility for China to include GC prevention in its national health plans.

Structure of Self-assembled Peptide Determines the Activity of Aggregation-Induced Emission Luminogen-Peptide Conjugate for Detecting Alkaline Phosphatase.

The unique property of turning on their fluorescence after aggregation or assembly makes aggregation-induced emission luminogens (AIEgens) ideal luminescent molecules for the construction of self-assembled peptide-based nanoprobes. However, the characteristic highly twisted or propeller-shaped molecular conformation of AIEgens tends to prevent the assembly of AIEgen-peptides. Here, we show that (i) the distance between tetraphenylethene (TPE) and assembled peptides should not be too far (less than five glycines), otherwise the self-assembly of peptides cannot limit the intramolecular rotation of conjugated TPE and the luminous efficiency of TPE-peptide to alkaline phosphatase (ALP) will decrease; (ii) properly increasing the number of amino acids with self-assembly ability (three phenylalanines) can improve their ALP-responsive self-assembly and luminescence ability; (iii) the strategy of co-assembly with a non-AIEgen-capped self-assembled peptide is a simple and effective way to realize the efficient assembly and luminescence of AIEgen-peptides; and (iv) the hydrophilic and hydrophobic balance of the probe should always be considered in the construction of an efficient AIEgen-peptide probe. In addition, AIEgen-peptide probes show good selectivity and sensitivity for ALP detection both in vitro and in live bacteria. These insights illustrated here are crucial for guiding the design of AIEgen-conjugated supramolecular materials, especially for the construction of AIEgen-peptides, for enzymes detection, biomarker imaging, diseases therapy, and other biomedical fields.

Tunable type-II lateral MoSi2N4/WSi2N4 heterostructures for photocatalytic applications.

Combining various two-dimensional crystals has emerged as an exciting way to tailor the properties of lateral heterostructures for new-generation optoelectronic devices. Herein, a seamless lateral heterostructure based on MoSi2N4 and MoSi2N4 monolayers along armchair interfaces is predicted, and its electronic and optical properties are investigated by using first principles calculations. Our calculations indicate that the MoSi2N4/WSi2N4 lateral heterostructures (HSs) possess excellent stability due to the very small lattice mismatch. In contrast to their parent monolayers with wide indirect band gaps, all (MoSi2N4)m(WSi2N4)n lateral HSs are direct gap semiconductors, and their direct gap nature is independent of compositions and strains. The band alignment of (MoSi2N4)m(WSi2N4)16-m lateral HSs undergoes a quasi-type-I to type-II to quasi-type-II to quasi-type-I band transition with an increase in m. (MoSi2N4)8(WSi2N4)8 is a type-II semiconductor, and the band arrangement changes from type-II to quasi-type-I upon applying tensile strain. Compared with pristine materials, the band edges of MoSi2N4/WSi2N4 lateral HSs are more favorable for photocatalytic water splitting. Furthermore, MoSi2N4/WSi2N4 lateral HSs exhibit higher visible light absorption. These results greatly expand the optoelectronic applications of Mxenes in the 2D realm.

Hypertoxic self-assembled peptide with dual functions of glutathione depletion and biosynthesis inhibition for selective tumor ferroptosis and pyroptosis.

Abundant glutathione (GSH) is a biological characteristic of lots of tumor cells. A growing number of studies are utilizing GSH depletion as an effective adjuvant therapy for tumor. However, due to the compensatory effect of intracellular GSH biosynthesis, GSH is hard to be completely exhausted and the strategy of GSH depletion remains challenging. Herein, we report an L-buthionine-sulfoximine (BSO)-based hypertoxic self-assembled peptide derivative (NSBSO) with dual functions of GSH depletion and biosynthesis inhibition for selective tumor ferroptosis and pyroptosis. The NSBSO consists of a hydrophobic self-assembled peptide motif and a hydrophilic peptide derivative containing BSO that inhibits the synthesis of GSH. NSBSO was cleaved by GSH and thus experienced a morphological transformation from nanoparticles to nanofibers. NSBSO showed GSH-dependent cytotoxicity and depletion of intracellular GSH. In 4T1 cells with medium GSH level, it depleted intracellular GSH and inactivated GSH peroxidase 4 (GPX4) and thus induced efficient ferroptosis. While in B16 cells with high GSH level, it exhausted GSH and triggered indirect increase of intracellular ROS and activation of Caspase 3 and gasdermin E, resulting in severe pyroptosis. These findings demonstrate that GSH depletion- and biosynthesis inhibition-induced ferroptosis and pyroptosis strategy would provide insights in designing GSH-exhausted medicines.

Optimizing the timing of diagnostic testing after positive findings in lung cancer screening: a proof of concept radiomics study.

BACKGROUND: The timeliness of diagnostic testing after positive screening remains suboptimal because of limited evidence and methodology, leading to delayed diagnosis of lung cancer and over-examination. We propose a radiomics approach to assist with planning of the diagnostic testing interval in lung cancer screening. METHODS: From an institute-based lung cancer screening cohort, we retrospectively selected 92 patients with pulmonary nodules with diameters ≥ 3 mm at baseline (61 confirmed as lung cancer by histopathology; 31 confirmed cancer-free). Four groups of region-of-interest-based radiomic features (n = 310) were extracted for quantitative characterization of the nodules, and eight features were proven to be predictive of cancer diagnosis, noise-robust, phenotype-related, and non-redundant. A radiomics biomarker was then built with the random survival forest method. The patients with nodules were divided into low-, middle- and high-risk subgroups by two biomarker cutoffs that optimized time-dependent sensitivity and specificity for decisions about diagnostic workup within 3 months and about repeat screening after 12 months, respectively. A radiomics-based follow-up schedule was then proposed. Its performance was visually assessed with a time-to-diagnosis plot and benchmarked against lung RADS and four other guideline protocols. RESULTS: The radiomics biomarker had a high time-dependent area under the curve value (95% CI) for predicting lung cancer diagnosis within 12 months; training: 0.928 (0.844, 0.972), test: 0.888 (0.766, 0.975); the performance was robust in extensive cross-validations. The time-to-diagnosis distributions differed significantly between the three patient subgroups, p < 0.001: 96.2% of high-risk patients (n = 26) were diagnosed within 10 months after baseline screen, whereas 95.8% of low-risk patients (n = 24) remained cancer-free by the end of the study. Compared with the five existing protocols, the proposed follow-up schedule performed best at securing timely lung cancer diagnosis (delayed diagnosis rate: < 5%) and at sparing patients with cancer-free nodules from unnecessary repeat screenings and examinations (false recommendation rate: 0%). CONCLUSIONS: Timely management of screening-detected pulmonary nodules can be substantially improved with a radiomics approach. This proof-of-concept study's results should be further validated in large programs.

Detection of Bacterial Alkaline Phosphatase Activity by Enzymatic In Situ Self-Assembly of the AIEgen-Peptide Conjugate.

Abnormal levels of alkaline phosphatase (ALP) activity are associated with various diseases, and many ALP probes have been developed to date. However, the development of ALP-sensitive probes for living cells, especially for the detection of bacterial ALP, remains challenging because of the complex and dynamic context. In this study, we constructed the first fluorescent probe (TPEPy-pY) for sensing bacterial ALP activity. TPEPy-pY is an AIEgen-peptide conjugate with property of aggregation-induced emission (AIE) and could turn on its fluorescence by ALP-catalyzed in situ self-assembly of the probe. The probe shows excellent selectivity and sensitivity for ALP activity, with a detection limit of 6.6 × 10-3 U mL-1. TPEPy-pY performs well in detection and in situ imaging of bacterial ALP activity against E. coli. Also, the detection does not require tedious washing steps and takes approximately 1 h, which is advantageous over commercial ALP kits. Therefore, the proposed strategy paved a new avenue for bacterial ALP detection, and we envision that more self-assembling fluorescent probes will be designed with higher sensitivity in the near future.

Population-based projections of blood supply and demand, China, 2017-2036.

OBJECTIVE: To estimate the long-term effect of the changing demography in China on blood supply and demand. METHODS: We developed a predictive model to estimate blood supply and demand during 2017-2036 in mainland China and in 31 province-level regions. Model parameters were obtained from World Population Prospects, China statistical yearbook 2016, China's report on blood safety and records from a large tertiary hospital. Our main assumptions were stable age-specific per capita blood supply and demand over time. FINDINGS: We estimated that the change in demographic structure between 2016 (baseline year) and 2036 would result in a 16.0% decrease in blood supply (from 43.2 million units of 200 mL to 36.3 million units) and a 33.1% increase in demand (from 43.2 million units to 57.5 million units). In 2036, there would be an estimated shortage of 21.2 million units. An annual increase in supply between 0.9% and 1.8% is required to maintain a balance in blood supply and demand. This increase is not enough for every region as regional differences will increase, e.g. a blood demand/supply ratio ≥ 1.45 by 2036 is predicted in regions with large populations older than 65 years. Sensitivity analyses showed that increasing donations by 4.0% annually by people aged 18-34 years or decreasing the overall blood discard rate from 5.0% to 2.0% would not offset but help reduce the blood shortage. CONCLUSION: Multidimensional strategies and tailored, coordinated actions are needed to deal with growing pressures on blood services because of China's ageing population.

Enhanced radiotherapy using photothermal therapy based on dual-sensitizer of gold nanoparticles with acid-induced aggregation.

The damaged DNA strands caused by radiotherapy (RT) can repair by themselves. A gold nanoparticles (GNPs) system with acid-induced aggregation was developed into a dual sensitizer owing to its high radioactive rays attenuation ability and enhanced photothermal heating efficiency after GNPs aggregation to achieve a combination therapy of RT and photothermal therapy (PTT). In this combination therapy, the formed GNP aggregates firstly showed a higher sensitize enhancement ratio (SER) value (1.52). Importantly, the self-repair of damaged DNA strands was inhibited by mild PTT through down-regulating the expression of DNA repair protein, thus resulting in a much higher SER value (1.68). Anti-tumor studies further demonstrated that this combination therapy exhibited ideal anti-tumor efficacy. Furthermore, the imaging signals of GNPs in computed tomography and photoacoustic were significantly improved following the GNPs aggregation. Therefore, a dual sensitizer with multimodal imaging was successfully developed and can be further applied as a new anti-tumor therapy.

Dielectric-loaded black phosphorus surface plasmon polariton waveguides.

By using the effective-index method (EIM) and the finite element methods (FEM), a surface plasmon polariton (SPP) waveguide structured by a dielectric ridge placed on monolayer black phosphorus is proposed and analyzed in the infrared spectral region. It is found that the strong anisotropic dispersion of the black phosphorus (BP) gives rise to direction-dependent waveguide modes in a dielectric-loaded black phosphorus waveguide (DLBPW). The effective mode index, propagation loss and cutoff wavelength of higher order modes are investigated along the armchair (AC) and the zigzag (ZZ) directions of the black phosphorus. Moreover, the propagation characteristics of single-mode are investigated for different widths of the dielectric ridge and different polarization directions of the black phosphorus. Via tuning the carrier density, the electromagnetic field propagation features can be effectively modified. Also, the coupling effect by adding more dielectric bridges can tune the propagation properties. These results will lead to great applications in black phosphorus-based optical integrated devices.

Dual Fluorescent- and Isotopic-Labelled Self-Assembling Vancomycin for in†vivo Imaging of Bacterial Infections.

The increase of bacterial resistance demands rapid and accurate diagnosis of bacterial infections. Biosurface-induced supramolecular assembly for diagnosis and therapy has received little attention in detecting bacterial infections. Herein we present a dual fluorescent-nuclear probe based on self-assembly of vancomycin (Van) on Gram-positive bacteria for imaging bacterial infection. A Van- and rhodamine-modified peptide derivative (Rho-FF-Van), as the imaging agent, binds to the terminal peptide of the methicillin-resistant staphylococcus aureus (MRSA) and self-assembles to form nanoaggregates on the surface of MRSA. In an in vivo myositis model, Rho-FF-Van results in a significant increased fluorescence signal at the MRSA infected site. Radiolabeled with iodine-125, Rho-FF-Van shows strong radioactive signal in the MRSA-infected lungs in a murine model. This novel dual fluorescent and nuclear probe promises a new way for in vivo imaging of bacterial infections.

Enzyme-Instructed Intracellular Molecular Self-Assembly to Boost Activity of Cisplatin against Drug-Resistant Ovarian Cancer Cells.

Anticancer drug resistance demands innovative approaches that boost the activity of drugs against drug-resistant cancers without increasing the systemic toxicity. Here we show the use of enzyme-instructed self-assembly (EISA) to generate intracellular supramolecular assemblies that drastically boost the activity of cisplatin against drug-resistant ovarian cancer cells. We design and synthesize small peptide precursors as the substrates of carboxylesterase (CES). CES cleaves the ester bond pre-installed on the precursors to form the peptides that self-assemble in water to form nanofibers. At the optimal concentrations, the precursors themselves are innocuous to cells, but they double or triple the activity of cisplatin against the drug-resistant ovarian cancer cells. This work illustrates a simple, yet fundamental, new way to introduce non-cytotoxic components into combination therapies with cisplatin without increasing the systemic burden or side effects.

Self-regulated multifunctional collaboration of targeted nanocarriers for enhanced tumor therapy.

Exploring ideal nanocarriers for drug delivery systems has encountered unavoidable hurdles, especially the conflict between enhanced cellular uptake and prolonged blood circulation, which have determined the final efficacy of cancer therapy. Here, based on controlled self-assembly, surface structure variation in response to external environment was constructed toward overcoming the conflict. A novel micelle with mixed shell of hydrophilic poly(ethylene glycol) PEG and pH responsive hydrophobic poly(ß-amino ester) (PAE) was designed through the self-assembly of diblock amphiphilic copolymers. To avoid the accelerated clearance from blood circulation caused by the surface exposed targeting group c(RGDfK), here c(RGDfK) was conjugated to the hydrophobic PAE and hidden in the shell of PEG at pH 7.4. At tumor pH, charge conversion occurred, and c(RGDfK) stretched out of the shell, leading to facilitated cellular internalization according to the HepG2 cell uptake experiments. Meanwhile, the heterogeneous surface structure endowed the micelle with prolonged blood circulation. With the self-regulated multifunctional collaborated properties of enhanced cellular uptake and prolonged blood circulation, successful inhibition of tumor growth was achieved from the demonstration in a tumor-bearing mice model. This novel nanocarrier could be a promising candidate in future clinical experiments.

Synthesis, biodistribution, and imaging of PEGylated-acetylated polyamidoamine dendrimers.

Polyamidoamine (PAMAM) dendrimers have been widely used as drug carriers, non-viral gene vectors and imaging agents. However, the use of dendrimers in biological system is constrained because of inherent toxicity and organ accumulation. In this study, the strategy of acetylation and PEGylation-acetylation was used to minimize PAMAM dendrimers toxicities and to improve their biodistribution and pharmacokinetics for medical application. PEGylated-acetylated PAMAM (G4-Ac-PEG) dendrimers were synthesized by PEGylation of acetylated PAMAM dendrimer of generation 4 (G4) with acetic anhydride and polyethylene glycol (PEG) 3.4 k. To investigate the cytotoxicity and in vivo biodistribution of the conjugates, in vitro cell viability analysis, Iodine-125 (125I) imaging, tissue distribution and hematoxylin-eosin (HE) staining were performed. We find that acetylation and PEGylation-acetylation essentially eliminates the inherent dendrimer cytotoxicity in vitro. Planar gamma (gamma) camera imaging revealed that all the conjugates were slowly eliminated from the body, and higher abdominal accumulation of acetylation PAMAM dendrimer was observed. Tissue distribution analysis showed that PEGylated-acetylated dendrimers have longer blood retention and lower accumulation in organs such as the kidney and liver than the non-PEGylated-acetylated dendrimers, but acetylation only can significantly increase the accumulation of G4 in the kidney and decrease the concentration in blood. Histology results reveal that no obvious damage was observed in all groups after high dose administration. This study indicates that PEGylation-acetylation could improve the blood retention, decrease organ accumulation, and improve pharmacokinetic profile, which suggests that PEGylation-acetylation provides an alternative method for PAMAM dendrimers modification.

Terahertz wave radiation simulation in the Fe thin film.

Femtosecond laser (FL) induced terahertz (THz) source is a new type of THz source based on injecting FL beams into ferromagnetic thin films by nonlinear effects to generate THz wave. It has a wider bandwidth compared to the traditional THz source, which provides higher flexibility and tunability in the application. In this paper, the three-temperature model and the stochastic Landau Lifshitz Gilbert equation at the atomic level are applied to simulate THz wave generation in Fe thin film induced by FL. Simulation results show that under a FL irradiance of 2 J m-2, the maximum demagnetization of the Fe thin film reaches 8.7%. The electromagnetic waves generated completely cover the THz band (0.1-10 THz), which fully satisfied the application requirements of the THz technology, verifying the feasibility of FL inducing the Fe thin film as a THz source. However, when the Fe thin film is overheated, it will be difficult for FL to excite valuable THz waves. Therefore, additional cooling devices are needed to keep the THz source in a workable temperature state, or to use ferromagnetic materials with magnetic moments that can quickly recover to saturation.

Glucopeptide Superstructure Hydrogel Promotes Surgical Wound Healing Following Neoadjuvant Radiotherapy by Producing NO and Anticellular Senescence.

Neoadjuvant radiotherapy, a preoperative intervention regimen for reducing the stage of primary tumors and surgical margins, has gained increasing attention in the past decade. However, radiation-induced skin damage during neoadjuvant radiotherapy exacerbates surgical injury, remarkably increasing the risk of refractory wounds and compromising the therapeutic effects. Radiation impedes wound healing by increasing the production of reactive oxygen species and inducing cell apoptosis and senescence. Here, a self-assembling peptide (R-peptide) and hyaluronic-acid (HA)-based and cordycepin-loaded superstructure hydrogel is prepared for surgical incision healing after neoadjuvant radiotherapy. Results show that i) R-peptide coassembles with HA to form biomimetic fiber bundle microstructure, in which R-peptide drives the assembly of single fiber through π-π stacking and other forces and HA, as a single fiber adhesive, facilitates bunching through electrostatic interactions. ii) The biomimetic superstructure contributes to the adhesion and proliferation of cells in the surgical wound. iii) Aldehyde-modified HA provides dynamic covalent binding sites for cordycepin to achieve responsive release, inhibiting radiation-induced cellular senescence. iv) Arginine in the peptides provides antioxidant capacity and a substrate for the endogenous production of nitric oxide to promote wound healing and angiogenesis of surgical wounds after neoadjuvant radiotherapy.

[Advances on the treatment of Fusobacterium nucleatum-promoted colorectal cancers using nanomaterials].

Fusobacterium nucleatum (Fn) is an oral anaerobic bacterium that has recently been found to colonize on the surface of colorectal cancer cells in humans, and its degree of enrichment is highly negatively correlated with the prognosis of tumor treatment. Numerous studies have shown that Fn is involved in the occurrence and development of colorectal cancer (CRC), and Fn interacts with multiple components in the tumor microenvironment to increase tumor resistance. In recent years, researchers have begun using nanomedicine to inhibit Fn's proliferation at the tumor site or directly target Fn to treat CRC. This review summarizes the mechanism of Fn in promoting CRC and the latest research progress on Fn-related CRC therapy using different nanomaterials. Finally, the applications perspective of nanomaterials in Fn-promoted CRC therapy was prospected.

China's domestic industry redistribution facilitates carbon emissions mitigation.

Industry redistribution is a common economic phenomenon that involves a dynamic configuration of the production location across a region, country, or the world. However, measurements of the associated pollutant emission effects have not been well conducted at the domestically regional level. Here, we calculate the CO2 emission changes induced by China's domestic inter-provincial industry redistribution during 2002-2017 using a counterfactual approach in the multi-regional input-output framework. We find that China's domestic industry redistribution decreased CO2 emissions during 2002-2017 and has considerable potential to continuously mitigate CO2 emissions in the future. We emphasize that the pollution haven effect may accompany the process of industry redistribution but can be weakened by effective policies, including stringent access thresholds in the regions undertaking industry relocation and regional industry structural upgrading. This paper provides policy recommendations for strengthening regional coordination to achieve China's transformation to carbon neutrality.