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Abstract Background Therapeutic approaches that combine conventional photodynamic therapy (PDT) with gas therapy (GT) to sensitize PDT are an attractive strategy, but the molecular structure design of the complex lacks effective guiding strategies. Results Herein, we have developed a nanoplatforms Cy-NMNO@SiO2 based on mesoporous silica materials loaded NIR-activatable small-molecule fluorescent probe Cy-NMNO for the synergistic treatment of photodynamic therapy/gas therapy (PDT/GT) in antibacterial and skin cancer. The theoretical calculation results showed that the low dissociation of N-NO in Cy-NMNO enabled it to dissociate effectively under NIR light irradiation, which is conducive to produce Cy and NO. Cy showed better 1O2 generation performance than Cy-NMNO. The cytotoxicity of Cy-NMNO obtained via the synergistic effect of GT and PDT synergistically enhances the effect of photodynamic therapy, thus achieving more effective tumor treatment and sterilization than conventional PDT. Moreover, the nanoplatforms Cy-NMNO@SiO2 realized efficient drug loading and drug delivery. Conclusions This work not only offers a promising approach for PDT-GT synergistic drug delivery system, but also provides a valuable reference for the design of its drug molecules. Graphical Abstract

Abstract It remains a challenge to obtain biocompatible afterglow materials with long emission wavelengths, durable lifetimes, and good water solubility. Herein we develop a photooxidation strategy to construct near-infrared afterglow carbon nanodots with an extra-long lifetime of up to 5.9 h, comparable to that of the well-known rare-earth or organic long-persistent luminescent materials. Intriguingly, size-dependent afterglow lifetime evolution from 3.4 to 5.9 h has been observed from the carbon nanodots systems in aqueous solution. With structural/ultrafast dynamics analysis and density functional theory simulations, we reveal that the persistent luminescence in carbon nanodots is activated by a photooxidation-induced dioxetane intermediate, which can slowly release and convert energy into luminous emission via the steric hindrance effect of nanoparticles. With the persistent near-infrared luminescence, tissue penetration depth of 20 mm can be achieved. Thanks to the high signal-to-background ratio, biological safety and cancer-specific targeting ability of carbon nanodots, ultralong-afterglow guided surgery has been successfully performed on mice model to remove tumor tissues accurately, demonstrating potential clinical applications. These results may facilitate the development of long-lasting luminescent materials for precision tumor resection.

Abstract Physical unclonable functions (PUFs) have emerged as a promising encryption technology, utilizing intrinsic physical identifiers that offer enhanced security and tamper resistance. Multi‐level PUFs boost system complexity, thereby improving system reliability and fault tolerance. However, crosstalk‐free multi‐level PUFs remain a persistent challenge. In this study, a hierarchical PUF system that harnesses the spontaneous phase separation of silk fibroin /PVA blend and the random distribution of silicon‐vacancy diamonds within the blend is presented. The thermodynamic instability of phase separation and inherent unpredictability of diamond dispersion gives rise to intricate random patterns at two distinct scales, enabling time‐efficient hierarchical authentication for cryptographic keys. These patterns are complementary yet independent, inherently resistant to replication and damage thus affording robust security and reliability to the proposed system. Furthermore, customized authentication algorithms are constructed: visual PUFs authentication utilizes neural network combined structural similarity index measure, while spectral PUFs authentication employs Hamming distance and cross‐correlation bit operation. This hierarchical PUF system attains a high recognition rate without interscale crosstalk. Additionally, the coding capacity is exponentially enhanced using M‐ary encoding to reinforce multi‐level encryption. Hierarchical PUFs hold significant potential for immediate application, offering unprecedented data protection and cryptographic key authentication capabilities.

Comparative nutritional analysis of Porphyra yezoensis strains “Jianghai No. 1” and “Sutong No.1” revealed significant differences in crude protein, crude fat, crude fiber, crude ash, and total sugar. Both strains contained 16 amino acids, with alanine as the highest and histidine the lowest content. Methionine was determined to be the first limiting amino acid for both strains in both amino acid score and chemical score assessment. They also featured 24 fatty acids, differing notably in four saturated fatty acids and five unsaturated fatty acids. All 12 mineral elements were present, notably differing in sodium, magnesium, potassium, calcium, iron, and zinc. The “Jianghai No. 1” strain stands out with its nutrient-rich profile, featuring high protein content, low fat, and abundant minerals, which could potentially command higher market prices and generate greater economic benefits due to its superior nutritional, and set a strong foundation for its future large-scale promotion and cultivation.

BackgroundTuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) and can be difficult to diagnose and treat. We aimed to describe the clinical presentation, diagnosis, disease spectrum, outcome, and prognostic factors of patients treated for TBM in China.MethodsA multicenter retrospective study was conducted from 2009 to 2019 enrolling all presumptive TBM patients referred to Xijing tertiary Hospital from 27 referral centers in and around Shaanxi province, China. Patients with clinical features suggestive of TBM (abnormal CSF parameters) were included in the study if they had adequate baseline information to be classified as “confirmed,” “probable,” or “possible” TBM according to international consensus TBM criteria and remained in follow-up. Patients with a confirmed alternative diagnosis or severe immune compromise were excluded. Clinical presentation, central nervous system imaging, cerebrospinal fluid (CSF) results, TBM score, and outcome—assessed using the modified Barthel disability index—were recorded and compared.FindingsA total of 341 presumptive TBM patients met selection criteria; 63 confirmed TBM (25 culture positive, 42 Xpert-MTB/RIF positive), 66 probable TBM, 163 possible TBM, and 49 “not TBM.” Death was associated with BMRC grade III (OR = 5.172; 95%CI: 2.298–11.641), TBM score ≥ 15 (OR = 3.843; 95%CI: 1.372–10.761), age > 60 years (OR = 3.566; 95%CI: 1.022–12.442), and CSF neutrophil ratio ≥ 25% (OR = 2.298; 95%CI: 1.027–5.139). Among those with confirmed TBM, nearly one-third (17/63, 27.0%) had a TBM score 60 years) have higher TBM scores or CSF neutrophil ratios, have signs of disseminated/miliary TB, and are at greatest risk of death. In general, more effort needs to be done to improve early diagnosis and treatment outcome in TBM patients.

Abstract Background Bicarbonate Ringer’s (BR) solution is a direct liver and kidney metabolism-independent HCO3 − buffering system. We hypothesized that BR solution would be more effective in improving acid-base equilibrium and more conducive to better liver function than Acetate Ringer’s (AR) solution in conventional orthotopic liver transplantation (OLT) patients. Methods Sixty-nine adult patients underwent OLT. Patients in the bicarbonate and acetate groups received BR solution or AR solution as infused crystalloids and graft washing solution, respectively. The primary outcome was the effect on pH and base excess (BE) levels. The secondary outcome measures were the incidence and volume of intraoperative 5% sodium bicarbonate infusion and laboratory indicates of liver and kidney function. Results The pH and absolute BE values changed significantly during the anhepatic phase and immediately after transplanted liver reperfusion in the bicarbonate group compared with the acetate group (all P

Abstract Photochemical glycosylation has attracted considerable attention in carbohydrate chemistry. However, to the best of our knowledge, visible-light-promoted glycosylation via photoactive glycosyl donor has not been reported. In the study, we report a photosensitizer-free visible-light-mediated glycosylation approach using a photoactive 2-glycosyloxy tropone as the donor. This glycosylation reaction proceeds at ambient temperature to give a wide range of O-glycosides or oligosaccharides with yields up to 99%. This method is further applied in the stereoselective preparation of various functional glycosyl phosphates/phosphosaccharides, the construction of N-glycosides/nucleosides, and the late-stage glycosylation of natural products or pharmaceuticals on gram scales, and the iterative synthesis of hexasaccharide. The protocol features uncomplicated conditions, operational simplicity, wide substrate scope (58 examples), excellent compatibility with functional groups, scalability of products (7 examples), and high yields. It provides an efficient glycosylation method for accessing O/N-glycosides and glycans.

This study examines the association between listening to music at home and subjective well-being, using data from 14,162 respondents in the China General Social Surveys conducted in 2015, 2017, and 2021. Among the respondents, the average happiness score was 3.958. Regression analyzes indicate that frequent music listening is significantly associated with higher happiness levels, with coefficients of 0.384 in the baseline model and 0.570 in the model with control variables. Robustness checks performed across different models support these findings. Instrumental variable analysis, using Mandarin proficiency, yielded a coefficient of 0.212, indicating a robust association despite a slight reduction in magnitude. Heterogeneity analyzes showed consistent associations across genders, religious beliefs, and regions, with slightly stronger associations observed for females and non-religious individuals. Mediation analysis identified mental health and class identity as significant mediators, contributing to a total association of 0.146. These results highlight the positive correlation between music listening and well-being, suggesting the potential value of integrating music resources into well-being strategies.

Abstract Advanced antibacterial technologies are needed to counter the rapid emergence of drug-resistant bacteria. Image-guided therapy is one of the most promising strategies for efficiently and accurately curing bacterial infections. Herein, a chemiluminescence (CL)-dynamic/guided antibacteria (CDGA) with multiple reactive oxygen species (ROS) generation capacity and chemiexcited near-infrared emission has been designed for the precise theranostics of bacterial infection by employing near-infrared emissive carbon nanodots (CDs) and peroxalate as CL fuels. Mechanistically, hydrogen peroxide generated in the bacterial microenvironment can trigger the chemically initiated electron exchange between CDs and energy-riched intermediate originated from the oxidized peroxalate, enabling bacterial induced inflammation imaging. Meanwhile, type I/II photochemical ROS production and type III ultrafast charge transfer from CDs under the self-illumination can inhibit the bacteria proliferation efficiently. The potential clinical utility of CDGA is further demonstrated in bacteria infected mice trauma model. The self-illuminating CDGA exhibits an excellent in vivo imaging quality in early detecting wound infections and internal inflammation caused by bacteria, and further are proven as efficient broad-spectrum antibacterial nanomedicines without drug-resistance, whose sterilizing rate is up to 99.99%.

Nitrous oxide (N2O) emission during the sewage treatment process is a serious environmental issue that requires attention. However, the N2O emission in constructed wetlands (CWs) as affected by different nitrogen forms in influents remain largely unknown. This study investigated the N2O emission profiles driven by microorganisms in CWs when exposed to two typical nitrogen sources (NH4+-N or NO3–-N) along with different carbon source supply (COD/N ratios: 3, 6, and 9). The results showed that CWs receiving NO3–-N caused a slight increase in total nitrogen removal (by up to 11.8 %). This increase was accomplished by an enrichment of key bacteria groups, including denitrifiers, dissimilatory nitrate reducers, and assimilatory nitrate reducers, which enhanced the stability of microbial interaction. Additionally, it led to a greater abundance of denitrification genes (e.g., nirK, norB, norC, and nosZ) as inferred from the database. Consequently, this led to a gradual increase in N2O emission from 66.51 to 486.77 ug-N/(m2·h) as the COD/N ratio increased in CWs. Conversely, in CWs receiving NH4+-N, an increasing influent COD/N ratio had a negative impact on nitrogen biotransformation. This resulted in fluctuating trend of N2O emissions, which decreased initially, followed by an increase at later stage (with values of 122.87, 44.00, and 148.59 ug-N/(m2·h)). Furthermore, NH4+-N in the aquatic improved the nitrogen uptake by plants and promoted the production of more root exudates. As a result, it adjusted the nitrogen-transforming function, ultimately reducing N2O emissions in CWs. This study highlights the divergence in microbiota succession and nitrogen transformation in CWs induced by nitrogen form and COD/N ratio, contributing to a better understanding of the microbial mechanisms of N2O emission in CWs with NH4+-N or NO3–-N at different COD/N ratios.

Abstract Advanced sustainable biomedical materials are urgently needed for clinical applications; however, developing biomedical materials with exceptional mechanical and bactericidal properties as well as removable functionalities to reduce unintended secondary injury remains a challenge. Here, we report a biomass‐derived composite consisting of water‐soluble fish gelatin (FG) and antibacterial ZnO@silk fibroin (ZSF) microspheres for potential application as the wound dressing. The ZSF microspheres are embedded in a FG matrix to realize the stretchable, antibacterial, and removable ZSF/FG composites. By introducing glycerin as the plasticizer, ZSF/FG composites deliver a tensile strength of 4.5 MPa and stretchability of 550%. Acting as both the germicide and hydrophile components, ZSF microspheres endow the composites with excellent antibacterial capacity and water solubility. To prevent secondary injury, the ZSF/FG composites can be easily removed from the wounds by simply exposing them to excess water. Additionally, the ZSF/FG composites exhibit favorable biocompatibility and sustain high cell viability of over 100%. The full‐thickness skin wound model on infected mice demonstrated an efficient rate of wound closure and a reduced inflammatory response. The ZSF/FG composite shows promise to hasten the healing of infected wounds and is expected a promising candidate as wound dressing for clinical therapy.

Ta/MgO/NiFe/MgO/Ta anisotropic magnetoresistive thin film sensors, which can be used for magnetic scales, were prepared. To improve the magnetoresistance ratio of the sensors, these sensors were vacuum-annealed with the magnetic field applied, and then, both the static and dynamic magnetoresistive responses of the sensors were obtained. The experimental results have shown that the instability of magnetic anisotropy occurs in the sensors after vacuum-annealing, leading to the significant hysteresis and abnormal output voltage peaks. To investigate the underlying physics, the distribution of the non-uniform demagnetizing field along the width of an anisotropic magnetoresistive (AMR) strip is considered, and both the static and dynamic responses of the AMR elements have been calculated on the basis of the Stoner–Wohlfarth model. The results have shown that the calculated results are in good agreement with the experimental data. The calculated results have revealed that the angles between the anisotropic field and the external magnetic field are different during the field cyclings of Hmax (maximum magnetic field) to −Hmax and −Hmax to Hmax. The angle difference is up to 6°, leading to different magnetoresistive responses. This paper is helpful for the understanding about the magnetization rotations in magnetic sensors and the manufacturing of sensors.

Replenishing landscape water with reclaimed water has been an effective way to alleviate urban water shortage. In order to investigate the variation of water quality along the pipeline and flow direction in a typical urban landscape river replenished with reclaimed water, relevant water quality indexes were consecutively monitored for 8 months. Concentrations of chemical oxygen demand (COD), total nitrogen (TN), and total phosphorus (TP) all showed a downward trend along the flow direction in reclaimed water effluent pipeline. However, values of turbidity, COD, and chlorophyll a (Chla) were decreased significantly, while concentrations of TN and TP were increased in the mixed area of reclaimed water and river. Furthermore, along Licun River, an upward trend of COD and ammonia-nitrogen (NH4+-N) was observed in summer, while in other seasons, a falling first and then rising trend of COD concentration appeared. The concentration of NH4+-N randomly fluctuated between 0.08 ​mg/L to 2.05 ​mg/L among all seasons, and TN and nitrate-nitrogen (NO3−-N) were below 15 ​mg/L with a downward first and then upward trend in each season. The concentration of TP showed a slightly upward trend (ranging from 0.08 ​mg/L to 0.57 ​mg/L) and Chla was at a relatively low level (0 – 46.32 ​μg/L). The correlation analysis revealed that light intensity, nitrogen and phosphorus were the influential factors of algae growth in river. In addition, the biomass of emergent plants and submerged plants was increased after replenishing with reclaimed water, playing a vital role in the remediation of urban landscape river.

Wafer-scale phase-controlled 2D MoTe2 layers was synthesized for in-situ fabrication of room-temperature high-performance broadband infrared photodetector and device array.

Salivary proteins from mosquitoes have received significant attention lately due to their potential to develop therapeutic treatments or vaccines for mosquito-borne diseases. Here, we report the characterization of LTRIN (lymphotoxin beta receptor inhibitor), a salivary protein known to enhance the pathogenicity of ZIKV by interrupting the LTβR-initiated NF-κB signaling pathway and, therefore, diminish the immune responses. We demonstrated that the truncated C-terminal LTRIN (ΔLTRIN) is a dimeric protein with a stable alpha helix-dominant secondary structure, which possibly aids in withstanding the temperature fluctuations during blood-feeding events. ΔLTRIN possesses two Ca2+ binding EF-hand domains, with the second EF-hand motif playing a more significant role in interacting with LTβR. Additionally, we mapped the primary binding regions of ΔLTRIN on LTβR using hydrogen–deuterium exchange mass spectrometry (HDX-MS) and identified that 91QEKAHIAEHMDVPIDTSKMSEQELQFHY118 from the N-terminal of ΔLTRIN is the major interacting region. Together, our studies provide insight into the recognition of LTRIN by LTβR. This finding may aid in a future therapeutic and transmission-blocking vaccine development against ZIKV.

Ultraviolet high-energy photons of phosphorescent carbon dots for antibacterial applications. Herein, the UV phosphorescent CNDs were achieved by decreasing conjugation size and spatial confinement. As a demonstration, the CNDs are used to inactivate gram-negative/positive bacteria.

With the development of renewable energy and the changes in the characteristics of power grid, it is becoming increasingly difficult to balance power supply and demand in space and time. In addition, the requirement for improved dispatching capability of power grid is increasing. Therefore, the potential of flexible load dispatching should be realized, which can promote the large-scale consumption of renewable energy and the construction of new power grid. Based on the analysis of existing load dispatching studies and the differences in the characteristics of domestic and foreign load dispatchings, a technical architecture and several key technologies are proposed for load resources to participate in power grid dispatching under the new situation, i.e., the autonomous collaborative control system of load dispatching. This system implements the multi-layer coordinated control of main, distribution and micro grids (load aggregators). Adjustable load resources are aggregated through an aggregator operation platform and connected with a dispatcher load regulator platform to realize real-time data interaction with dispatching agencies as well as the monitoring, control, and marketing of aggregators. It supports the load resources to participate in network-wide dispatching optimization via continuous power adjustment. Several key technologies such as the control mode, load modeling, dispatching strategy, and safety protection are also elaborated. Through the closed-loop control of orderly charging piles and energy storage clusters in the North China Power Grid, the feasibility of the proposed architecture and key technologies is verified. This route has successively supported multiple adjustable load aggregators to participate in the ancillary services market of North China Power Grid for peak-shaving. Finally, the technical challenges of load resources participating in power grid dispatching under the dual carbon goals are discussed and prospected.

MicroRNA-199a-5p (miR-199a-5p) and -3p are enriched in the myocardium, but it is unknown whether miR-199a-5p and -3p are co-expressed in cardiac remodeling and what roles they have in cardiac hypertrophy and fibrosis. We show that miR-199a-5p and -3p are co-upregulated in the mouse and human myocardium with cardiac remodeling and in Ang-II-treated neonatal mouse ventricular cardiomyocytes (NMVCs) and cardiac fibroblasts (CFs). miR-199a-5p and -3p could aggravate cardiac hypertrophy and fibrosis in vivo and in vitro. PPAR gamma coactivator 1 alpha (Ppargc1a) and sirtuin 1 (Sirt1) were identified as target genes to mediate miR-199a-5p in promoting both cardiac hypertrophy and fibrosis. However, miR-199a-3p aggravated cardiac hypertrophy and fibrosis through targeting RB transcriptional corepressor 1 (Rb1) and Smad1, respectively. Serum response factor and nuclear factor κB p65 participated in the upregulation of miR-199a-5p and -3p in Ang-II-treated NMVCs and mouse CFs, and could be conversely elevated by miR-199a-5p and -3p. Together, Ppargc1a and Sirt1, Rb1 and Smad1 mediated the pathological effect of miR-199a-5p and -3p by promoting cardiac hypertrophy and fibrosis, respectively. This study suggests a possible new strategy for cardiac remodeling therapy by inhibiting miR-199a-5p and -3p.

To achieve reactive voltage control and resolve the problem of photovoltaic in regional grids with high-proportion photovoltaic access, a multi-cycle reactive voltage rolling optimization control method supporting photovoltaic absorption was proposed, and a multi-cycle reactive voltage rolling optimization control framework was constructed based on the sensitivity-based mathematical model of allowed maximum photovoltaic capacity. First, a reactive power optimization model was built day ahead to minimize the actions of the discrete reactive regulating equipment and the resistance of photovoltaic absorption, and the action plan for discrete reactive power regulating equipment was thus determined. After that, with the determined day-ahead control plan for discrete reactive equipment as the constraint, and with the maximization of photovoltaic absorption and improvement of the dynamic reactive reserve margin of the system as the objectives within day, a reactive voltage rolling optimization control model was built for the optimal control plan for the discrete and continuous reactive equipment; the rolling optimization control model performed optimization once every five minutes, with two hours as a cycle. At last, with a regional grid system as a study case, a simulating calculation was carried out and the control effects after optimization by the proposed multi-cycle reactive voltage rolling optimization control method showed that the maximum voltage deviation of two key nodes had been dropped by 34.21% and 45.98%, respectively, the action times of capacitors and the regulation times of main transformers had been reduced by 61.29% and 64%, respectively, the maximum regulation capacity requirement of continuous reactive equipment in photovoltaic stations had been dropped by 62.17%, and the forecast photovoltaic output could be fully absorbed in this system. These findings verified the feasibility and effectiveness of the proposed method in improving voltage control and promoting maximum photovoltaic absorption of regional grid. The case study showed that the day-ahead optimization control method could alleviate the large fluctuations of photovoltaics by arranging a discrete reactive power equipment adjustment plan, and the within-day rolling optimization control could adjust the output of continuous reactive power equipment to alleviate short-term random fluctuations of photovoltaics after simulating calculation.

Abstract Viral infection can lead to serious illness and death around the world, as exemplified by the spread of COVID-19. Using irradiation rays can inactive virions through ionizing and non-ionizing effect. The application of light in viral inactivation and the underlying mechanisms are reviewed by the research group of Dayong Jin from University of Technology Sydney.

Abstract Previous study found that the solvent extraction efficiency of lipid in microalgae could be greatly improved by washing algae cells before the second time extraction. Based on the "organic solvents–water–organic solvents" method, this research further studied the effect of four solvent systems (acetone, chloroform/methanol, chloroform/methanol/water, dichloromethane/methanol), two types of water treatment (vortex and ultrasonic), three water treatment time gradient (0 s, 30 s, 120 s) on the lipid extraction at three different microalgae growth stages (3rd day, 5th day, 9th day). The results show that the combination of water treatment type, treatment time and solvent is very important to the efficiency of lipid extraction. The total lipid extracted was generally increased by 10–30% after water treatment. Especially under the condition of 120 s vortex water treatment with dichloromethane/methanol as extraction solvent, the total lipid extracted increased by 61.14%. In addition, microalgae cells at different culture stages had different sensitivity to water treatment. In this study, under the combination of chloroform/methanol/water as extraction solvent and vortex water treatment for 120 s, the highest lipid yield was obtained on the ninth day of cell culture, which accounts 47.88% of the cell dry weight (478 mg/g cell dry weight). The changes of cell morphology and structure after water treatment were studied by scanning electron microscope, and it was found that water treatment could seriously destroy the cell membrane damaged by solvent, thus promoting the release of lipids. This study further optimizes the "solvent–water–solvent" lipid extraction method, which neither produces impurities nor damages the lipid quality, and can reduce the amount of organic solvent applied in the classical lipid extraction method with the same lipid yield, so it has a broad application prospect.

Abstract Carbon nanodots (CDs) have emerged as an alternative option for traditional nanocrystals due to their excellent optical properties and low toxicity. Nevertheless, high emission efficiency is a long‐lasting pursuit for CDs. Herein, CDs with near‐unity emission efficiency are prepared via atomic condensation of doped pyrrolic nitrogen, which can highly localize the excited states thus lead to the formation of bound excitons and the symmetry break of the π–electron conjugation. The short radiative lifetimes (

The performance of Low-Density Parity-Check (LDPC)-coded Orthogonal Frequency Division Multiplexing (OFDM) is investigated over turbulence channels in underwater wireless optical communications (UWOC). The relation between the bit error ratio (BER) and parameters such as the scintillation coefficient, signal-to-noise ratio (SNR), length of LDPC code, and order of OFDM is quantified by simulation. Results show that while the OFDM with subcarrier quadrature amplitude modulation (QAM-OFDM) has slightly better anti-turbulence performance than the OFDM with subcarrier phase shift keying modulation (PSK-OFDM), the LDPC-coded QAM-OFDM has a much better performance than the QAM-OFDM and the LDPC-coded PSK-OFDM, and, at SNR = 12, it decreases the BER by four orders of magnitude compared to the 16QAM-OFDM system when the scintillation coefficient σξ2 = 0.05.

Traditional fault tree analysis is an effective tool used to evaluate system risk if the required data are sufficient. Unfortunately, the operation and maintenance data of some complex systems are difficult to obtain due to economic or technical reasons. The solution is to invite experts to evaluate some critical aspect of the performance of the system. In this study, the belief degrees of the occurrence of basic events evaluated by experts are measured by an uncertain measure. Then, a system risk assessment method based on an uncertain fault tree is proposed, based on which two general optimization models are established. Furthermore, the genetic algorithm (GA) and the nondominated sorting genetic algorithm II (NSGA-II) are applied to solve the two optimization models, separately. In addition, the proposed risk assessment method is applied for the leakage risk evaluation of a subsea production system, and the two general optimization models are used to optimize the leakage risk and maintenance cost of the subsea production system. The optimization results provide a theoretical basis for practitioners to guarantee the safety of subsea production system.

The heterogeneity of macrophages influences the response to immune checkpoint inhibitor (ICI) therapy. However, few studies explore the impact of APOE+ macrophages on ICI therapy using single‐cell RNA sequencing (scRNA‐seq) and machine learning methods. The scRNA‐seq and bulk RNA‐seq data are Integrated to construct an M.Sig model for predicting ICI response based on the distinct molecular signatures of macrophage and machine learning algorithms. Comprehensive single‐cell analysis as well as in vivo and in vitro experiments are applied to explore the potential mechanisms of the APOE+ macrophage in affecting ICI response. The M.Sig model shows clear advantages in predicting the efficacy and prognosis of ICI therapy in pan‐cancer patients. The proportion of APOE+ macrophages is higher in ICI non‐responders of triple‐negative breast cancer compared with responders, and the interaction and longer distance between APOE+ macrophages and CD8+ exhausted T (Tex) cells affecting ICI response is confirmed by multiplex immunohistochemistry. In a 4T1 tumor‐bearing mice model, the APOE inhibitor combined with ICI treatment shows the best efficacy. The M.Sig model using real‐world immunotherapy data accurately predicts the ICI response of pan‐cancer, which may be associated with the interaction between APOE+ macrophages and CD8+ Tex cells. [ABSTRACT FROM AUTHOR]