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Abstract Background Due to the abundant usage of chemotherapy in young triple-negative breast cancer (TNBC) patients, the unbiased prognostic value of BRCA1-related biomarkers in this population remains unclear. In addition, whether BRCA1-related biomarkers modify the well-established prognostic value of stromal tumor-infiltrating lymphocytes (sTILs) is unknown. This study aimed to compare the outcomes of young, node-negative, chemotherapy-naïve TNBC patients according to BRCA1 status, taking sTILs into account. Methods We included 485 Dutch women diagnosed with node-negative TNBC under age 40 between 1989 and 2000. During this period, these women were considered low-risk and did not receive chemotherapy. BRCA1 status, including pathogenic germline BRCA1 mutation (gBRCA1m), somatic BRCA1 mutation (sBRCA1m), and tumor BRCA1 promoter methylation (BRCA1-PM), was assessed using DNA from formalin-fixed paraffin-embedded tissue. sTILs were assessed according to the international guideline. Patients’ outcomes were compared using Cox regression and competing risk models. Results Among the 399 patients with BRCA1 status, 26.3% had a gBRCA1m, 5.3% had a sBRCA1m, 36.6% had tumor BRCA1-PM, and 31.8% had BRCA1-non-altered tumors. Compared to BRCA1-non-alteration, gBRCA1m was associated with worse overall survival (OS) from the fourth year after diagnosis (adjusted HR, 2.11; 95% CI, 1.18–3.75), and this association attenuated after adjustment for second primary tumors. Every 10% sTIL increment was associated with 16% higher OS (adjusted HR, 0.84; 95% CI, 0.78–0.90) in gBRCA1m, sBRCA1m, or BRCA1-non-altered patients and 31% higher OS in tumor BRCA1-PM patients. Among the 66 patients with tumor BRCA1-PM and ≥ 50% sTILs, we observed excellent 15-year OS (97.0%; 95% CI, 92.9–100%). Conversely, among the 61 patients with gBRCA1m and

The myofibrillar protein (MP) of duck meat is prone to excessive oxidation during thermal processing, resulting in a decline in its overall quality. In this paper, the effect of shikimic acid on the oxidative structure of duck muscle fibrin was studied. The findings showed that, at a mass ratio of 1:50,000 (g/g) between shikimic acid and MP, the carbonyl content of MP was reduced by 74.20%, while the sulfhydryl content was increased by 73.56%. MP demonstrated the highest denaturation temperature, whereas its thermal absorption was the lowest. The percentage of α-helixes and β-sheets increased by 16.72% and 24.74%, respectively, while the percentage of irregular structures decreased by 56.23%. In addition, the surface hydrophobicity index of MP exhibited a significant decrease (p < 0.05), while there was a significant increase in its free radical-scavenging ability (p < 0.05). Molecular fluorescence spectrum analysis showed that shikimic acid could bind to MP, altering the internal environment of MP and enhancing its thermal stability. FTIR analysis showed that shikimic acid could enhance the distribution of protein particle sizes by reducing irregular structures, the proportion of β-rotation, and the degree of protein aggregation. It is hoped that this research can offer scientific support for improving meat processing technology.

BackgroundCapecitabine has been reported to be associated with severe gastrointestinal (GI) adverse drug reactions (gastrointestinal ulceration, haemorrhage, and obstruction). However, statistical correlations have not been demonstrated, and specific GI adverse drug reactions, such as GI obstruction, are not listed on its label.AimWe aimed to determine the associations between capecitabine and GI ulceration, haemorrhage, or obstruction among patients with breast cancer by examining data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS).MethodsWe performed disproportionality analysis of GI ulceration, haemorrhage, and obstruction by evaluating the reporting odds ratio (ROR) and the information component (IC) with their 95% confidence intervals (CIs).ResultsWe identified 279 patients with capecitabine-associated GI ulceration, haemorrhage, or obstruction reported between 1 January 2004 and 31 December 2020. One-fourth of the cases of GI ulceration, haemorrhage, or obstruction resulted in death. Capecitabine as a drug class had disproportionately high reporting rates for GI ulceration [ROR 1.94 (1.71–2.21); IC 0.80 (0.60–0.99)], haemorrhage [ROR 2.27 (1.86–2.76); IC 0.99 (0.69–1.28)], and obstruction [ROR 2.19 (1.63–2.95); IC 0.96 (0.51–1.40)].ConclusionPharmacovigilance research on the FAERS has revealed a slight increase in reports of GI ulceration, haemorrhage, and obstruction in capecitabine users, which may cause serious or deadly consequences. In addition to the adverse reactions described in the package insert, close attention should be paid to GI obstruction to avoid discontinuation or life-threatening outcomes.

Abstract Prescribing appropriate exercise is an important means to improve the safety and efficacy of cardiac rehabilitation. Improper exercise may induce an increased cardiovascular risk in older persons with coronary heart disease. Cardiopulmonary exercise testing (CPET)-guided cardiac rehabilitation could be helpful for providing clinical evidence for cardiac rehabilitation therapy in older persons after percutaneous coronary intervention (PCI). We retrospectively included older persons who underwent PCI and cardiac rehabilitation based on CPET at the Cardiac Rehabilitation Center of Peking University Third Hospital from January 2014 to December 2019. Patients’ baseline and follow-up clinical data were collected. A total of 403 older persons after PCI were included in the study. The mean age was 80.5 ± 4.3. The mean follow-up time was 12 ± 2 months. During the follow-up period, no significant exercise-related adverse events occurred, and the peak oxygen uptake (VO2peak) increased compared with baseline (15.5 ± 3.8 ml/min/kg vs. 17.3 ± 4.1 ml/min/kg). Among the 90 patients (22.2%) without exercise habits at baseline who started regular exercise during follow-up, the improvement in VO2peak was most significant, at 3.2 ± 0.4 ml/min/kg. Cardiac rehabilitation based on CPET improved exercise habits and exercise tolerance in older persons with coronary heart disease after PCI.

This research project envisions using a lunar observation platform to measure the full-wave (0.2~100 μm) and shortwave (0.2~4.3 μm) radiation of the Earth, achieving an accurate estimation of the overall radiation budget of the Earth. Based on the lunar platform, the system analyzes Earth’s radiation characteristics and geometric attributes, as well as the sampling properties of observation times. Informed by these analyses, an Earth-facing optical radiation measurement system tailored to these specifications is designed. The optical system adopts an off-axis three-mirror configuration with a secondary image plane, incorporating a field stop at the primary image plane to effectively suppress solar stray light, scattered lunar surface light, and background radiation from the instrument itself, ensuring the satisfactory signal-to-noise ratio, detection sensitivity, and observation duration of the instrument. At the same time, stringent requirements are imposed for the surface treatments of instrument components and temperature control accuracy to further ensure accuracy. Simulation analyses confirm that the design satisfies requirements, achieving a measurement accuracy of better than 1% across the entire optical system. This Moon-based Earth-radiation measurement system, with capabilities for Earth-pointing tracking, radiation energy detection, and stray-light suppression, furnishes a more comprehensive dataset, helping to advance our understanding of the mechanisms driving global climate change

Hyperspectral detection of the change rate of organic matter content in agricultural remote sensing requires a high signal-to-noise ratio (SNR). However, due to the large number and efficiency limitation of the components, it is difficult to improve the SNR. This study uses high-efficiency convex grating with a diffraction efficiency exceeding 50% across the 360–850 nm range, a back-illuminated Complementary Metal Oxide Semiconductor (CMOS) detector with a 95% efficiency in peak wavelength, and silver-coated mirrors to develop an imaging spectrometer for detecting soil organic matter (SOM). The designed system meets the spectral resolution of 10 nm in the 360–850 nm range and achieves a swath of 100 km and a spatial resolution of 100 m at an orbital height of 648.2 km. This study also uses the basic structure of Offner with fewer components in the design and sets the mirrors of the Offner structure to have the same sphere, which can achieve the rapid adjustment of the co-standard. This study performs a theoretical analysis of the developed Offner imaging spectrometer based on the classical Rowland circular structure, with a 21.8 mm slit length; simulates its capacity for suppressing the +2nd-order diffraction stray light with the filter; and analyzes the imaging quality after meeting the tolerance requirements, which is combined with the surface shape characteristics of the high-efficiency grating. After this test, the grating has a diffraction efficiency above 50%, and the silver-coated mirrors have a reflection value above 95% on average. Finally, the laboratory tests show that the SNR over the waveband exceeds 300 and reaches 800 at 550 nm, which is higher than some current instruments in orbit for soil observation. The proposed imaging spectrometer has a spectral resolution of 10 nm, and its modulation transfer function (MTF) is greater than 0.23 at the Nyquist frequency, making it suitable for remote sensing observation of SOM change rate. The manufacture of such a high-efficiency broadband grating and the development of the proposed instrument with high energy transmission efficiency can provide a feasible technical solution for observing faint targets with a high SNR.

As one of the principal protections of UHVDC transmission lines, pilot protection requires strict synchronization and small data flow by exchanging the current on both terminals under the limitation of DC protection action rapidity. To solve this problem, this paper finds that the DC voltage and current on both terminals of the line have different plane distribution characteristics when faults occur internally and externally in the system area, and then advances a novel pilot protection method for UHVDC transmission lines based on U-I characteristics. By setting up the U-I plane with DC voltage and current as variables, analyzing the dynamic trajectory of the real-time captured U-I plane, constructing protection criteria based on the U-I plane on the rectifier side and inverter side separately, and finally converting the judgment results into state information. Both terminals of the line identify the fault location by exchanging the longitudinal comparison of state information. This protection project only utilizes the instant tracks of voltage and current in the rectifier side and inverter side at the time of fault to judge. The principle is simple and can quickly locate faults. The state messages of the two terminals are not modified by the data asynchrony on both terminals. This protection method is convenient for setting, has high sensitivity, and can quickly identify interior and exterior faults. The results are testified by theoretical analysis and simulation verification.

With the improvement of marine ecological environment, land-based pollution caused by marine outfall has gradually become an important factor restricting the modernization of marine ecological environment governance system and capability.Based on the current situation of China′s sewage outlets into the sea, this paper analyzed the impact of sewage outlets into the sea on the marine ecological environment and the necessity of controlling sewage outlets into the sea. As an effective means and tool of social governance, the law studied the improvement measures of China′s sewage outlets into the sea from a legal perspective. Among the relevant legislation for the control of the discharge outlets into the sea, the Law of the People′s Republic of China on Maritime Environmental Protection is a special law for the reduction of marine pollution and the protection of the marine ecological environment. Based on this law, this paper considered the pollution problem caused by the discharge outlet into the sea from the legal angle, and studied the feasibility and the insufficiency of the operation of the record system in the treatment of the discharge outlet into the sea in China, analyzed the current management situation of the existing total emission control system on the discharge outlets into the sea, and focused on the regulatory limitations of the existing legal system on the discharge of pollutants into the sea caused by the discharge outlets into the sea. This paper put forward the corresponding legal suggestions from these aspects: perfecting the detailed legislation of the management of the discharge outlet into the sea, improving the loopholes of the supervision system, promoting the comprehensiveness of the supervision system, and increasing the participation of the public in the prevention and control of the pollution of the marine environment.

Abstract Gallium-based liquid metal has gained significant attention in conformal flexible electronics due to its high electrical conductivity, intrinsic deformability, and biocompatibility. However, the fabrication of large-area and highly uniform conformal liquid metal films remains challenging. Interfacial self-assembly has emerged as a promising method, but traditional approaches face difficulties in assembling liquid metal particles. Here, we realized the multi-size universal self-assembly (MUS) for liquid metal particles with various diameters (100 cm2) and high floating yield (50–90%). Moreover, the films can be conformally transferred onto complex surfaces such as human skin, allowing for the fabrication of substrate-free flexible devices. This eliminates interference from traditional substrate mechanical responses, making the liquid metal e-tattoo more user-friendly.

This paper presents a novel approach—an efficient closed-form approximation iterative fitting algorithm based on laser absorption spectra. Through this closed-form approximation iterative fitting, key parameters such as peak value, spectral line width, and normalized signal area serve as indicators for iteration completion, improving the speed without compromising accuracy. Furthermore, it employs the spectral signal of n cycles as a window for further processing, minimizing external interference. The results show that the proposed method averages 9.75 iterations, while the Levenberg–Marquardt fitting method averages 60.17 iterations. The average iteration time for the proposed method is 588.83 ms, a substantial 81.7% reduction compared to the 3210.5 ms required by the Levenberg–Marquardt fitting. These results decisively demonstrate the efficacy of the proposed method in reducing iteration time and enhancing measurement precision.

The size of the reference group is among the most critical determinants of genomic estimated breeding values (GEBVs) accuracy. However, small- and medium-sized pig farms often need help accumulating adequate reference data, posing significant challenges to breeding programs. To solve this problem, exploring the potential benefits of combining reference groups of different sizes is necessary to improve GEBV accuracy. The primary objective of this investigation was to assess a more effective statistical model for combined multi-populations and its potential to enhance the accuracy of GEBVs for small and medium populations. Three populations were simulated using the QMSim software, each consisting of different sizes (300, 600, and 1 500, respectively). To assess the impact of heritability on the accuracy of GEBVs, four different levels of heritability (0.05, 0.15, 0.35, and 0.5) were simulated. Simultaneously, to investigate the impact of kinship on multi-populations, the study created four distinct scenarios for the three sizes of populations. These scenarios included: (1) the three groups are all independent, (2) the large group and the small group with a familial connection (n = 1 800), a middle group (n = 600) acting independently with no kinship, (3) the large group with a familial connection to the middle group (n = 2 100) but no connection to the small group (n = 300), and (4) the small group with a familial connection to the middle group (n = 900), while the large group (n = 1 500) acted independently with no kinship. This study evaluates and compares the accuracy of predicting breeding values using four different methods, including genomic best linear unbiased prediction (GBLUP), single-stepGBLUP (ssGBLUP), and two Bayesian models (Bayes A and Bayes B), with varying sizes of reference groups. In each scenario, three different prediction strategies were compared: (1) Merging all three different sizes of populations for predicting, (2) predicting each independent population separately, and (3) the other two populations predict the population. Our findings reveal that combining populations enhances the Bayesian models, with Bayes B yielding the highest accuracy. In independent populations, the best linear unbiased prediction (BLUP) models demonstrated the highest accuracy. However, in cases where populations were related and the heritability was high, the Bayes B model exhibited the highest overall accuracy (slightly higher than BLUP models) in the independent population. Our results underscore the importance of considering population combinations when using genetic models to predict breeding values, particularly for pig farmers with limited resources.

Background: The choroid is the most vascularized structure in the human eye, associated with numerous retinal and choroidal diseases. However, the vessel distribution of choroidal sublayers has yet to be effectively explored due to the lack of suitable tools for visualization and analysis. Methods: In this paper, we present a novel choroidal angiography strategy to more effectively evaluate vessels within choroidal sublayers in the clinic. Our approach utilizes a segmentation model to extract choroidal vessels from OCT B-scans layer by layer. Furthermore, we ensure that the model, trained on B-scans with high choroidal quality, can proficiently handle the low-quality B-scans commonly collected in clinical practice for reconstruction vessel distributions. By treating this process as a cross-domain segmentation task, we propose an ensemble discriminative mean teacher structure to address the specificities inherent in this cross-domain segmentation process. The proposed structure can select representative samples with minimal label noise for self-training and enhance the adaptation strength of adversarial training. Results: Experiments demonstrate the effectiveness of the proposed structure, achieving a dice score of 77.28 for choroidal vessel segmentation. This validates our strategy to provide satisfactory choroidal angiography noninvasively, supportting the analysis of choroidal vessel distribution for paitients with choroidal diseases. We observed that patients with central serous chorioretinopathy have evidently (P

BackgroundPrevious studies have demonstrated improvements in motor, behavioral, and emotional areas following transcranial direct current stimulation (tDCS), but no published studies have reported the efficacy of tDCS on postoperative recovery quality in patients undergoing lower limb major arthroplasty. We hypothesized that tDCS might improve postoperative recovery quality in elderly patients undergoing lower limb major arthroplasty.MethodsNinety-six patients (≥65 years) undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) were randomized to receive 2 mA tDCS for 20 min active-tDCS or sham-tDCS. The primary outcome was the 15-item quality of recovery (QoR-15) score on postoperative day one (Т2). Secondary outcomes included the QoR-15 scores at the 2nd hour (T1), the 1st month (Т3), and the 3rd month (Т4) postoperatively, numeric rating scale scores, and fatigue severity scale scores.ResultsNinety-six elderly patients (mean age, 71 years; 68.7% woman) were analyzed. Higher QoR-15 scores were found in the active-tDCS group at T2 (123.0 [114.3, 127.0] vs. 109.0 [99.3, 115.3]; median difference, 13.0; 95% CI, 8.0 to 17.0; p

The incidence and mortality of lung cancer are on the rise worldwide. However, the benefit of clinical treatment in lung cancer is limited. Owning to important sources of drug development, natural products have received constant attention around the world. Main ingredient polysaccharides in natural products have been found to have various activities in pharmacological research. In recent years, more and more scientists are looking for the effects and mechanisms of different natural product polysaccharides on lung cancer. In this review, we focus on the following aspects: First, natural product polysaccharides have been discovered to directly suppress the growth of lung cancer cells, which can be effective in limiting tumor progression. Additionally, polysaccharides have been considered to enhance immune function, which can play a pivotal role in fighting lung cancer. Lastly, polysaccharides can improve the efficacy of drugs in lung cancer treatment by regulating the gut microbiota. Overall, the research of natural product polysaccharides in the treatment of lung cancer is a promising area that has the potential to lead to new clinical treatments. With better understanding, natural product polysaccharides have the potential to become important components of future lung cancer treatments.

It is an important feature of the 6G that how to realize everything interconnection through large-scale complex heterogeneous networks based on native artificial intelligence (AI).Thanks to the distinct machine learning architecture of data processing locally, federated learning (FL) is regarded as one of the promising solutions to incorporate distributed AI in 6G scenarios, and has become a critical research direction of 6G.Therefore, the necessity of introducing distributed AI into the future 6G especially for internet of things (IoT) scenarios was analyzed.And then, the potentials of FL in meeting the 6G requirements were discussed, and the state-of-the-arts of FL related technologies such as architecture design, resource utilization, data transmission, privacy protection, and service provided for 6G were investigated.Finally, several key technical challenges and potential valuable research directions for FL-empowered 6G were put forward.

Aiming at the problem of difficult detection of sedentarius ciliates, unclear pollution sources and difficult identification of species in the cold-water fish farming, the major parasitic species of the parasites and the infective factors were investigated and analyzed. Samples of cold-water fish and water were collected in different seasons in Hebei Province. Firstly, the sedentarius ciliates on the fish body and in the water environment were initially identified by using morphology. Secondly, a PCR method was established for molecular level identification and phylogenetic analysis. Finally, the reasons for cold-water fish infecting the parasite were analyzed. Morphological identification reveals that the mainly parasitic species of sedentarius ciliates were Epistylis sp. and Vorticella sp.; A PCR method to test the parasites is successfully established. The results of sequences alignment and phylogenetic analysis verify the correctness of morphological test. The established PCR method is used to detect the prevalence of sessile ciliates in the water environment, which is as high as 94.38%, and the infection rate of the fish is up to 100% with no seasonal difference. The parasites in water may be one of the reasons for the long-term infection of the fish. The findings provide a scientific basis for predicting, preventing and treating cold-water fish diseases, as well as serving as a reference for disease prevention and control in the sustainable development of the cold-water fish farming industry.

Abstract Bioinspired multi-compartment architectures are desired in synthetic biology and metabolic engineering, as credited by their cell-like structures and intrinsic ability of assembling catalytic species for spatiotemporal control over cascade reactions like in living systems. Herein, we describe a general Pickering double emulsion-directed interfacial synthesis method for the fabrication of multicompartmental MOF microreactors. This approach employs multiple liquid–liquid interfaces as a controllable platform for the self-completing growth of dense MOF layers, enabling the microreactor with tailor-made inner architectures and selective permeability. Importantly, simultaneous encapsulation of incompatible functionalities, including hydrophilic enzyme and hydrophobic molecular catalyst, can be realized in a single MOF microreactor for operating chemo-enzymatic cascade reactions. As exemplified by the Grubb’ catalyst/CALB lipase driven olefin metathesis/ transesterification cascade reaction and glucose oxidase (GOx)/Fe-porphyrin catalyzed oxidation reaction, the multicompartmental microreactor exhibits 2.24–5.81 folds enhancement in cascade reaction efficiency in comparison to the homogeneous counterparts or physical mixture of individual analogues, due to the restrained mutual inactivation and substrate channelling effects. Our study prompts further design of multicompartment systems and the development of artificial cells capable of complex cellular transformations.

Aiming at the problems of poor model performance and low training efficiency in training streaming data of AI models that provide intelligent services, a high-performance federated continual learning algorithm for heterogeneous streaming data (FCL-HSD) was proposed in the distributed terminal system with privacy data.In order to solve the problem of the current model forgetting old data, a model with dynamically extensible structure was introduced in the local training stage, and an extension audit mechanism was designed to ensure the capability of the AI model to recognize old data at the cost of small storage overhead.Considering the heterogeneity of terminal data, a customized global model strategy based on data distribution similarity was designed at the central server side, and an aggregation-by-block manner was implemented for different modules of the model.The feasibility and effectiveness of the proposed algorithm were verified under various data increment scenarios with different data sets.Experimental results show that, compared with existing works, the proposed algorithm can effectively improve the model performance to classify old data on the premise of ensuring the capability to classify new data.

Achieving quantification of biomarkers in body fluids is crucial to the indication of the state of a person’s body and health. Wearable sensors could offer a convenient, fast and painless sensing strategy. In this work, we fabricated a wearable electrochemical patch sensor for simultaneous detection of dopamine and glucose in sweat. The sensor was printed on a flexible PDMS substrate with a simple screen-printed method. This prepared four-electrode sensor integrated two working electrodes for dopamine and glucose electrochemical sensing, one Ag/AgCl reference electrode and one carbon counter electrode, respectively. Cyclic voltammetry, differential pulse voltammetry and chronoamperometry were used for the evaluation of the wearable electrochemical patch sensor. It exhibits good sensitivity, wide linear range, low limit of detection, good anti-interference and reproducibility toward dopamine and glucose sensing in PBS and sweat.

Milk allergy is one of the most common food allergies, affecting 6 % of young children, and β-lactoglobulin (β-LG) is the main milk allergen. Clostridium tyrobutyricum Z816 was selected for the degradation of β-LG, which was successfully reduced by about 90 % using permeabilized bacteria under the optimized conditions. The hydrolyzed peptides were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and analyzed by molecular modeling, which indicated that C. tyrobutyricum Z816 could effectively degrade the antigenic epitopes of β-LG. Finally, the concentration and digestibility of β-LG in actual samples was quantified using enzyme-linked immunosorbent assay (ELISA) and gastrointestinal digestion simulation experiments. The results showed more than 92 % of β-LG in actual samples was hydrolyzed, and the gastric and total digestibility of whey protein isolate (WPI) was improved by 85.96 % and 64.51 %, respectively. Therefore, C. tyrobutyricum Z816 offers an effective method to degrade β-LG and reduce the occurrence of milk allergies, which has great significance for the development of hypoallergenic dairy products.

Traditional event-driven emergency load shedding determines the quantitative strategy by simulation of a specific set of expected faults, which requires high model accuracy and operation mode matching. However, due to the model complexity of renewable power generators and fluctuating power generation, traditional event-driven load shedding strategy faces the risk of mismatching in high renewable energy penetrated power systems. To address these challenges, this paper proposes an emergency load shedding method based on data-driven strategies and deep reinforcement learning (RL). Firstly, the reason for the possible mismatch of the event-driven load shedding strategy in the renewable power system is analyzed, and a typical mismatch scenario is constructed. Then, the emergency load shedding strategy is transformed into a Markov Decision Process (MDP), and the decision process’s action space, state space, and reward function are designed. On this basis, an emergency control strategy platform based on the Gym framework is established for application of deep reinforcement learning in the power system emergency control strategy. In order to enhance the adaptability and efficiency of the RL intelligence agent to multi-fault scenarios, the Proximal Policy Optimization (PPO) is adopted to optimize the constructed MDP. Finally, the proposed reinforcement learning-based emergency load shedding strategy is trained and verified through a modified IEEE 39-bus system. The results show that the proposed strategy can effectively make correct strategies to restore system frequency in the event-driven load shedding mismatch scenario, and have good adaptability for different faults and operation scenarios.