Photodynamic anticancer activity evaluation of novel 5-aminolevulinic acid and 3-hydroxypyridinone conjugates.

5-Aminolevulinic acid (ALA) and its derivatives, serving as the endogenous precursor of the photosensitizer (PS) protoporphyrin IX (PpIX), successfully applied in tumor imaging and photodynamic therapy (PDT). ALA and its derivatives have been used to treat actinic keratosis (AK), basal cell carcinoma (BCC), and improve the detection of superficial bladder cancer. However, the high hydrophilicity of ALA and the conversion of PpIX to heme have limited the accumulation of PpIX, hindering the efficiency and potential application of ALA-PDT. This study aims to evaluate the PDT activity of three rationally designed series of ALA-HPO prodrugs, which were based on enhancing the lipophilicity of the prodrugs and reducing the labile iron pool (LIP) through HPO iron chelators to promote PpIX accumulation. Twenty-four ALA-HPO conjugates, incorporating amide, amino acid, and ester linkages, were synthesized. Most of the conjugates, exhibited no dark-toxicity to cells, according to bioactivity evaluation. Ester conjugates 19a-g showed promoted phototoxicity when tested on tumor cell lines, and this increased phototoxicity was strongly correlated with elevated PpIX levels. Among them, conjugate 19c emerged as the most promising (HeLa, IC50 = 24.25 ± 1.43 µM; MCF-7, IC50 = 43.30 ± 1.76 µM; A375, IC50 = 28.03 ± 1.00 µM), displaying superior photodynamic anticancer activity to ALA (IC50 > 100 µM). At a concentration of 80 µM, the fluorescence intensity of PpIX induced by compound 19c in HeLa, MCF-7, and A375 cells was 18.9, 5.3, and 2.8 times higher, respectively, than that induced by ALA. In conclusion, cellular phototoxicity showed a strong correlation with intracellular PpIX fluorescence levels, indicating the potential application of ALA-HPO conjugates in ALA-PDT.

Evaluation of sustainable development capacity of water sources: a case study of China.

The issue of water scarcity has drawn attention from all over the world. The coordination of the interaction between ecological and environmental development of water sources and socio-economic development is currently an essential issue that needs to be solved in order to safeguard the water resources environment for human survival. In this essay, we suggest a paradigm for assessing the sustainable exploitation of water resources. First, three ecological, economic, and social factors are investigated. Twenty essential evaluation indexes are then constructed using the Delphi approach, along with an index system for assessing the potential of water sources for sustainable development. The weights of each evaluation index were then determined using the combination assignment approach, which was then suggested. The coupled degree evaluation model of the capability for sustainable development of water sources was then developed. In order to confirm the viability and validity of the suggested model, the model was used to assess the Liwu River water source's capacity for sustainable growth in the context of the South-North Water Transfer in Shandong, China. It is believed that the aforementioned study would serve as a helpful resource when evaluating the capacity of water sources for sustainable development.

Ultrauniform, strong, and ductile 3D-printed titanium alloy through bifunctional alloy design.

Coarse columnar grains and heterogeneously distributed phases commonly form in metallic alloys produced by three-dimensional (3D) printing and are often considered undesirable because they can impart nonuniform and inferior mechanical properties. We demonstrate a design strategy to unlock consistent and enhanced properties directly from 3D printing. Using Ti-5Al-5Mo-5V-3Cr as a model alloy, we show that adding molybdenum (Mo) nanoparticles promotes grain refinement during solidification and suppresses the formation of phase heterogeneities during solid-state thermal cycling. The microstructural change because of the bifunctional additive results in uniform mechanical properties and simultaneous enhancement of both strength and ductility. We demonstrate how this alloy can be modified by a single component to address unfavorable microstructures, providing a pathway to achieve desirable mechanical characteristics directly from 3D printing.

Manufacturing of high strength and high conductivity copper with laser powder bed fusion.

Additive manufacturing (AM), known as 3D printing, enables rapid fabrication of geometrically complex copper (Cu) components for electrical conduction and heat management applications. However, pure Cu or Cu alloys produced by 3D printing often suffer from either low strength or low conductivity at room and elevated temperatures. Here, we demonstrate a design strategy for 3D printing of high strength, high conductivity Cu by uniformly dispersing a minor portion of lanthanum hexaboride (LaB6) nanoparticles in pure Cu through laser powder bed fusion (L-PBF). We show that trace additions of LaB6 to pure Cu results in an improved L-PBF processability, an enhanced strength, an improved thermal stability, all whilst maintaining a high conductivity. The presented strategy could expand the applicability of 3D printed Cu components to more demanding conditions where high strength, high conductivity and thermal stability are required.

Organo-Ptii Complexes for Potent Photodynamic Inactivation of Multi-Drug Resistant Bacteria and the Influence of Configuration.

PtII based organometallic photosensitizers (PSs) have emerged as novel potent photodynamic inactivation (PDI) reagents through their enhanced intersystem crossing (ISC) processes. Currently, few PtII PSs have been investigated as antibacterial materials, with relatively poor performances reported and with structure-activity relationships not well described. Herein, a pair of configurational isomers are reported of Bis-BODIPY (4,4-difluoro-boradizaindacene) embedded PtII PSs. The cis-isomer (cis-BBP) displayed enhanced 1O2 generation and better bacterial membrane anchoring capability as compared to the trans-isomer (trans-BBP). The effective PDI concentrations (efficiency > 99.9%) for cis-BBP in Acinetobacter baumannii (multi-drug resistant (MDR)) and Staphylococcus aureus are 400 nM (12 J cm-2) and 100 nM (18 J cm-2), respectively; corresponding concentrations and light doses for trans-BBP in the two bacteria are 2.50 µM (30 J cm-2) and 1.50 µM (18 J cm-2), respectively. The 50% and 90% minimum inhibitory concentration (MIC50 and MIC90) ratio of trans-BBP to cis-BBP is 22.22 and 24.02 in A. baumannii (MDR); 21.29 and 22.36 in methicillin resistant S. aureus (MRSA), respectively. Furthermore, cis-BBP displays superior in vivo antibacterial performance, with acceptable dark and photoinduced cytotoxicity. These results demonstrate cis-BBP is a robust light-assisted antibacterial reagent at sub-micromolecular concentrations. More importantly, configuration of PtII PSs should be an important issue to be considered in further PDI reagents design.

Lightweight and Real-Time Infrared Image Processor Based on FPGA.

This paper presents an FPGA-based lightweight and real-time infrared image processor based on a series of hardware-oriented lightweight algorithms. The two-point correction algorithm based on blackbody radiation is introduced to calibrate the non-uniformity of the sensor. With precomputed gain and offset matrices, the design can achieve real-time non-uniformity correction with a resolution of 640×480. The blind pixel detection algorithm employs the first-level approximation to simplify multiple iterative computations. The blind pixel compensation algorithm in our design is constructed on the side-window-filtering method. The results of eight convolution kernels for side windows are computed simultaneously to improve the processing speed. Due to the proposed side-window-filtering-based blind pixel compensation algorithm, blind pixels can be effectively compensated while details in the image are preserved. Before image output, we also incorporated lightweight histogram equalization to make the processed image more easily observable to the human eyes. The proposed lightweight infrared image processor is implemented on Xilinx XC7A100T-2. Our proposed lightweight infrared image processor costs 10,894 LUTs, 9367 FFs, 4 BRAMs, and 5 DSP48. Under a 50 MHz clock, the processor achieves a speed of 30 frames per second at the cost of 1800 mW. The maximum operating frequency of our proposed processor can reach 186 MHz. Compared with existing similar works, our proposed infrared image processor incurs minimal resource overhead and has lower power consumption.

Rapid and effective removal of copper, nitrate and trichloromethane from aqueous media by aluminium alloys.

Zero-valent iron (ZVI) has been extensively studied for its efficacy in removing heavy metals, nitrate, and chlorinated organic compounds from contaminated water. However, its limited effectiveness due to rapid passivation and poor selectivity is prompting for alternative solutions, such as the use of aluminium alloys. In this study, the efficacy of five distinct aluminium alloys, namely Al-Mg, Al-Fe, Al-Cu, and Al-Ni, each comprising 50 % Al by mass at a concentration of 10 g/L, was assessed using copper, nitrate and trichloromethane (TCM) as model contaminants. Results show that chemical pollutants reacted immediately with Al-Mg. On the contrary, the remaining three alloys exhibited a delay of 24 h before demonstrating significant reactivity. Remarkably, Al-Mg alloy reduced nitrate exclusively to ammonium, indicating minimal preference for nitrate reduction to N2. In contrast, the Al-Cu, Al-Ni, and Al-Fe alloys exhibited N2 selectivity of 3 %, 5 %, and 19 %, respectively. The removal efficiency of copper, nitrate and TCM reached 99 % within 24 h, 95 % within 48h and 48 % within 48h, respectively. Noteworthy findings included the correlation between Fe concentration within the Al-Fe alloy and an increased N2 selectivity from 9.3 % to 24.1 %. This resulted in an increase of Fe concentration from 10 % to 58 % albeit with a concurrent reduction in reactivity. Cu2+ removal by Al-Fe alloy occurred via direct electron transfer, while the removal of nitrate and TCM was facilitated by atomic hydrogen generated by the alloy's hydrolysis. Intriguingly, nitrate and TCM suppressed Cu2+ reduction, whereas Cu2+ improved nitrate reduction and TCM degradation. These findings demonstrate the great potential of Al-Mg and Al-Fe alloys as highly efficient agents for water remediation.

Autoimmune hepatitis with confluent necrosis indicates severe liver injury but responds well to standard immunosuppressive therapy.

We aimed to study the effects of different extensive confluent necrosis on complete biochemical remission, side effects of immunosuppressants, and outcomes in patients with autoimmune hepatitis (AIH). Patients with liver biopsy, receiving standard immunosuppressive therapy (IST), and regular follow-up were retrospectively recruited. Demographic and clinicopathological characteristics between Ishak confluent necrosis scores ≤4 (the non-severe AIH group) and ≥5 (the severe AIH group) were compared. The Kaplan-Meier Survival analysis, Cox regression analysis, and log-rank test were performed. Bilateral p<0.05 was considered statistical significance. One hundred and forty-two patients were enrolled, the median age was 56.0, and 83.8% were female. There were no significant differences in aminotransferases and immunological markers between the two groups. Patients in the severe AIH group had significantly worse liver synthetic function, a higher proportion of cirrhosis, and histologically a higher degree of portal inflammation, interface hepatitis, fibrosis stage, and a higher histological activity index score (all p<0.05). Patients in the severe AIH group had a lower response than the other group after four weeks (57.1% vs. 86.3%, p=0.002). However, differences in complete biochemical remission (CBR) were insignificant. Eight patients experienced end-point events. Kaplan-Meier survival analysis showed no significant difference between the two groups (p=0.343). For adverse effects of IST, patients in the severe group tended toward a higher incidence of corticosteroid adverse effects without statistical significance. Our study indicated that patients with histologically severe confluent necrosis (Ishak score≥5) had significantly worse liver synthetic function and a higher degree of liver fibrosis before IST. Compared with their counterparts, this subgroup of patients showed delayed biochemical response but eventually comparable CBRs, side effects, and long-term outcomes.

A spatial registration method based on 2D-3D registration for an augmented reality spinal surgery navigation system.

BACKGROUND: In order to provide accurate and reliable image guidance for augmented reality (AR) spinal surgery navigation, a spatial registration method has been proposed. METHODS: In the AR spinal surgery navigation system, grayscale-based 2D/3D registration technology has been used to register preoperative computed tomography images with intraoperative X-ray images to complete the spatial registration, and then the fusion of virtual image and real spine has been realised. RESULTS: In the image registration experiment, the success rate of spine model registration was 90%. In the spinal model verification experiment, the surface registration error of the spinal model ranged from 0.361 to 0.612 mm, and the total average surface registration error was 0.501 mm. CONCLUSION: The spatial registration method based on 2D/3D registration technology can be used in AR spinal surgery navigation systems and is highly accurate and minimally invasive.

Targeting BRD4 attenuates the stemness and aggressiveness of ameloblastoma.

BACKGROUND: BRD4, belonging to the bromodomain extra-terminal (BET) protein family, plays a unique role in tumor progression. However, the potential impact of BRD4 in ameloblastoma (AM) remains largely unknown. Herein, we aimed to assess the expression and functional role of BRD4 in AM. METHODS: The expression level of BRD4 was assessed by immunohistochemistry. The proliferation, migration, invasion, and tumorigenic abilities of AM cells were assessed by a series of assays. To explore the molecular expression profile of BRD4-depleted AM cells, RNA sequencing (RNA-seq) was performed. Bioinformatic analysis was performed on AM expression matrices obtained from the Gene Expression Omnibus (GEO). The therapeutic efficacy of BET-inhibitors (BETi) was assessed with AM patient-derived organoids. RESULTS: Upregulation of BRD4 was observed in conventional AMs, recurrent AMs, and ameloblastic carcinomas. Depletion of BRD4 inhibited proliferation, invasion, migration, and tumorigenesis in AM. Administration of BETi attenuated the aggressiveness of AM and the growth of AM patient-derived organoids. Bioinformatic analysis indicated that BRD4 may promote AM progression by regulating the Wnt pathway and stemness-associated pathways. CONCLUSION: BRD4 increases the aggressiveness and promotes the recurrence of ameloblastoma by regulating the Wnt pathway and stemness-associated pathways. These findings highlight BRD4 as a promising therapeutic target in AM management.

Nuclear factor kappa B (NF-κB) participates in the aluminum-induced down-regulation of miR29a/b1.

BACKGROUND: Studies have shown that aluminum (Al) is one of the environmental risk factors leading to Alzheimer's disease (AD), and Al exposure can cause elevated levels of BACE1mRNA, ß-secretase (BACE1), and amyloid beta (Aß) in vivo and in vitro. Previous studies by our research group have shown that this is partly caused by the negative regulation of BACE1 by miRNA29a/b1 (miR29a/b1). Despite the observed the role of nuclear factor kappa B (NF-κB) on many miRNAs, the upstream regulation of NF-κB protein on miR29 remains poorly understood. The purpose of this study was to better define the relationship between NF-κB and miR29a/b1 and the potentially relevant signaling pathways. METHODS: On the one hand, we constructed the animal model of Al exposure by the intraperitoneal injection of aluminum-maltolate (Al(mal)3) in rats. Conversely, NF- κB inhibitors were added to adrenal phaeochromocytoma (PC12) cells exposed to Al(mal)3. RESULTS: We verified that NF-κB shows an increasing trend with Al accumulation in the brain of rats, which is accompanied by a downward trend of miR29a/b1. Notably, the suppression of NF-κB significantly increased miR29a/b1 and affected the expression of BACE1mRNA and downstream proteins. CONCLUSION: Al-induced NF-κB can negatively regulate the expression of miR29a/b1, which then significantly enhances the expression of BACE1 and Aß plaques.

Automatic ultrasound diagnosis of thyroid nodules: a combination of deep learning and KWAK TI-RADS.

Objective. There has been a considerable amount of computer-aided diagnosis (CAD) methods highlighted in the field of ultrasonic examination (USE) of thyroid nodules. However, few researches focused on the automatic risk classification, which was the basis for determining whether fine needle aspiration (FNA) was needed. The aim of this work was to implement automatic risk level assessment of thyroid nodules.Approach. Firstly, 1862 cases of thyroid nodules with the results of USE and FNA were collected as the dataset. Then, an improved U-Net++ model was utilized for segmenting thyroid nodules in ultrasound images automatically. Finally, the segmentation result was imported into a multi-task convolutional neural network (MT-CNN), the design of which was based on the clinical guideline called KWAK TI-RADS. Apart from the category of benign and malignant, the MT-CNN also exported the classification result of four malignant features, solid component (SC), hypoechogenicity or marked hypoechogenicity (HMH), microlobulated or irregular margin (MIM), microcalcification (MC), which were used for counting the risk level in KWAK TI-RADS.Main results. The performance of the improved U-Net++ was evaluated on our test set, including 302 cases. The Dice coefficient and intersection over union reached 0.899, 0.816, respectively. The classification accuracy rates of SC, HMH, MIM, MC, were 94.5%, 92.8%, 86.1%, 88.9%, while the false positive (FP) rate was 6.0%, 5.6%, 10.6%, 12.9% respectively. As for the category of benign and malignant, the precision and recall rates were 93.7% and 94.4%.Significance. The proposed CAD method showed favourable performance in the diagnosis of thyroid nodules. Compared with other methods, it could provide reports closer to clinical practice for doctors.

Protein-Assisted Molybdenum Disulfide as Biomimetic Nanozyme for Antibacterial Application.

Molybdenum-based nanomaterials with variable oxidation states can be developed as nanozyme catalysts. In this work, we developed a one-pot method for the preparation of molybdenum disulfide assisted by protein. Protamine was used as a cationic template to link molybdate anions and form complexes. During hydrothermal synthesis, protamine can affect the nucleation process of molybdenum disulfide and inhibit their aggregation, which facilitates the fabrication of small-sized molybdenum disulfide nanoparticles. Moreover, the abundant amino/guanidyl groups of protamine could both physically adsorb and chemically bond to molybdenum disulfide and further modulate the crystal structures. The optimized size and crystalline structure enabled a higher exposure of active sites, which enhanced the peroxidase-like activity of molybdenum disulfide/protamine nanocomposites. Meanwhile, the antibacterial activity of protamine was retained in the molybdenum disulfide/protamine nanocomposites, which could synergize with the peroxidase-like activity of molybdenum disulfide to kill bacteria. Therefore, the molybdenum disulfide/protamine nanocomposites are good candidates for antibacterial agents with lower chances of antimicrobial resistance. This study establishes an easy way to design artificial nanozymes by compounding suitable components.

Evolution of degradation mechanism and fixation strength of biodegradable Zn-Cu wire as sternum closure suture: An in vitro study.

This work reports the first in vitro study on the in-situ biodegradation behaviour and the evolution of fixation strength of Zn-Cu alloy wires in a simulated sternum closure environment. Zn-Cu wires were used to reapproximate the partial bisected sternum models, and their fixation effect was compared with traditional surgical grade 316 L stainless steel (SS) wires in terms of fixation rigidity, critical load, first/ultimate failure characteristics. The metal sutures were then immersed in Hank's balanced salt solution for 12 weeks immersion period, and their corrosion behaviours assessed. Zn-Cu wires showed similar fixation rigidity at 70.89 ± 6.97 N/mm as SS, but the critical load, first failure and ultimate failure characteristics were inferior to SS. The key challenges that limited the fixation effect of the Zn-Cu wires were poor mechanical strength, short elastic region, and strain softening behaviours, which resulted in poor load-bearing capabilities and reduced the knot security of the sutures. The in-situ biodegradation of the Zn-Cu suture was accompanied by the early onset of localised corrosion within the twisted knot and the section located next to the incision line. Crevice corrosion and strain-induced corrosion were the dominant mechanisms in the observed localised corrosion. The localised corrosion on the Zn-Cu sutures did not lead to a significant shift in fixation rigidity, critical load and the first failure characteristics. The findings suggest that the Zn-based biodegradable metallic wires could be a promising sternum closure suture material once the limitations in mechanical characteristics are addressed.

Microglia activation and temporal changes in rat model of trigeminal neuralgia.

OBJECTIVES: This study aimed to investigate whether the microglia in the spinal trigeminal nucleus caudal part (Sp5C) were activated in a rat model of trigeminal neuralgia and to explore whether the activation level of microglia is consistent with maxillofacial pain level. METHODS: Chronic constriction injury of trigeminal nerve (CCI) was induced by partial ligation of infraorbital nerve (IoN) in rats. The behavioral change of rats observed at D1, D5, D10, D15, and D30 days post-surgery and the change of pain threshold were detected with electronic Von Frey filaments served as an evaluation index of maxillofacial pain. Weight change was measured by weighing. Ionized calcium binding adaptor molecule-1 (Iba-1) expression level of Sp5C at each time point was detected, and three microglia morphological categories were analyzed by immunohistochemical staining. RESULTS: The changes of behavioral and pain threshold suggested the maxillofacial pain level first increased and then decreased post-surgery in the IoN-CCI group. Both the expressions of Iba-1 and proportion of ameboid morphology in ipsilateral Sp5C increased from D1 and reached their peaks in D10 and D5, respectively. Then, they recovered nearly to the same level with contralateral Sp5C on D30. This trend was consistent with the maxillofacial change. CONCLUSIONS: The model of trigeminal neuralgia in rats constructed by partial ligation of infraorbital nerve can induce the activation of microglia in Sp5C, and the activation level is consistent with maxillofacial pain, which reached its peak at around D10 post-surgery.

NGF-Induced Upregulation of CGRP in Orofacial Pain Induced by Tooth Movement Is Dependent on Atp6v0a1 and Vesicle Release.

The nerve growth factor (NGF) and calcitonin gene-related peptide (CGRP) play a crucial role in the regulation of orofacial pain. It has been demonstrated that CGRP increases orofacial pain induced by NGF. V-type proton ATPase subunit an isoform 1 (Atp6v0a1) is involved in the exocytosis pathway, especially in vesicular transport in neurons. The objective was to examine the role of Atp6v0a1 in NGF-induced upregulation of CGRP in orofacial pain induced by experimental tooth movement. Orofacial pain was elicited by ligating closed-coil springs between incisors and molars in Sprague-Dawley rats. Gene and protein expression levels were determined through real-time polymerase chain reaction, immunostaining, and fluorescence in situ hybridization. Lentivirus vectors carrying Atp6v0a1 shRNA were used to knockdown the expression of Atp6v0a1 in TG and SH-SY5Y neurons. The release of vesicles in SH-SY5Y neurons was observed by using fluorescence dye FM1-43, and the release of CGRP was detected by Enzyme-Linked Immunosorbent Assy. Orofacial pain was evaluated through the rat grimace scale. Our results revealed that intraganglionic administration of NGF and Atp6v0a1 shRNA upregulated and downregulated CGRP in trigeminal ganglia (TG) and trigeminal subnucleus caudalis (Vc), respectively, and the orofacial pain was also exacerbated and alleviated, respectively, following administration of NGF and Atp6v0a1 shRNA. Besides, intraganglionic administration of NGF simultaneously caused the downregulation of Atp6v0a1 in TG. Moreover, the release of vesicles and CGRP in SH-SY5Y neurons was interfered by NGF and Atp6v0a1 shRNA. In conclusion, in the orofacial pain induced by experimental tooth movement, NGF induced the upregulation of CGRP in TG and Vc, and this process is dependent on Atp6v0a1 and vesicle release, suggesting that they are involved in the transmission of nociceptive information in orofacial pain.

Cold Atmospheric Plasma Activates Selective Photothermal Therapy of Cancer.

Due to the body's systemic distribution of photothermal agents (PTAs), and to the imprecise exposure of lasers, photothermal therapy (PTT) is challenging to use in treating tumor sites selectively. Striving for PTT with high selectivity and precise treatment is nevertheless important, in order to raise the survival rate of cancer patients and lower the likelihood of adverse effects on other body sections. Here, we studied cold atmospheric plasma (CAP) as a supplementary procedure to enhance selectivity of PTT for cancer, using the classical photothermic agent's gold nanostars (AuNSs). In in vitro experiments, CAP decreases the effective power of PTT: the combination of PTT with CAP at lower power has similar cytotoxicity to that using higher power irradiation alone. In in vivo experiments, combination therapy can achieve rapid tumor suppression in the early stages of treatment and reduce side effects to surrounding normal tissues, compared to applying PTT alone. This research provides a strategy for the use of selective PTT for cancer, and promotes the clinical transformation of CAP.

Designing against phase and property heterogeneities in additively manufactured titanium alloys.

Additive manufacturing (AM) creates digitally designed parts by successive addition of material. However, owing to intrinsic thermal cycling, metallic parts produced by AM almost inevitably suffer from spatially dependent heterogeneities in phases and mechanical properties, which may cause unpredictable service failures. Here, we demonstrate a synergistic alloy design approach to overcome this issue in titanium alloys manufactured by laser powder bed fusion. The key to our approach is in-situ alloying of Ti-6Al-4V (in weight per cent) with combined additions of pure titanium powders and iron oxide (Fe2O3) nanoparticles. This not only enables in-situ elimination of phase heterogeneity through diluting V concentration whilst introducing small amounts of Fe, but also compensates for the strength loss via oxygen solute strengthening. Our alloys achieve spatially uniform microstructures and mechanical properties which are superior to those of Ti-6Al-4V. This study may help to guide the design of other alloys, which not only overcomes the challenge inherent to the AM processes, but also takes advantage of the alloy design opportunities offered by AM.

Buffet-style Cu(II) for enhance disulfiram-based cancer therapy.

Studies have shown that disulfiram (DSF) can combine with Cu2+ to form bis(N, N-diethyldithiocarbamate) copper(II) complex (CuET) as antitumor drugs. However, there is insufficient endogenous Cu2+ dose to eradicate cancer cells selectively. Inspired by the buffet, we use Cu2+ doped hollow zeolitic imidazolate framework nanoparticles (HZIFCu) as the carrier and equipped with DSF and indocyanine green (ICG) and targeted by folic acid (FA) (D&I@HZIFCu-FA) to enhance DSF-based cancer therapy. D&I@HZIFCu-FA could effectively supply Cu2+ by a buffet-style, assisting the "DSF-to-CuET" transformation in the tumor. Additionally, self-supply Cu2+ could convert H2O2 into ·OH by triggering a Fenton-like reaction for chemo-dynamic therapy, and ICG achieves photothermal therapy for tumors under laser irradiation. This work provides a buffet-style for Cu2+ to make DSF a strong candidate for cancer treatment by combining chemotherapy, chemo-dynamic therapy, and photothermal therapy and inspires more research about its applications in tumor therapy.

Evaluation and promotion strategy of resilience of urban water supply system under flood and drought disasters.

With global climate change and the rapid urbanization, urban flood and drought disasters are frequent and urban water supply systems are facing a sea of serious challenges. It is crucial to assess the resilience of urban water supply systems and develop corresponding disaster mitigation and improvement strategies. Urban water supply systems include many subsystems, but existing researches generally focus on a single subsystem. Therefore, this paper proposes a correlation analysis method and a factor analysis method for the resilience evaluation index system of urban water supply systems by combining each subsystem and applying grey system theory. The method can reflect the four dimensions of the water supply process (water source, water plant, supply and distribution network and users) and the five dimensions of the urban management system (society, natural environment, economy, physics and organization). Taking Qingdao as an example, a multi-level integrated evaluation model based on a cloud model is applied to simulate and analyze the resilience of Qingdao's water supply system. As a result, decision support is provided for planning and building resilience systems for urban water systems in the short and long term, based on four main factors.