ABSTRACT
The hypoxic microenvironment within the tumor microenvironment of breast cancer imposes a challenge in overcoming chemotherapy resistance. In this investigation, we designed a novel strategy utilizing a light-controlled cascade targeting nanomedicine specifically tailored for enhanced immune therapy of breast cancer. Albumin nanoparticle was achieved by crosslinking, followed by loading TPZ and Ce6, and subsequent modification to enable selective binding with CD44 hyaluronic acid to form nanomedicine. Encouragingly, it was demonstrated the remarkable ability of the nanomedicine to effectively internalize into cellular entities, thereby inducing apoptosis in 4T1 cells efficiently in vitro when exposed to light irradiation. In vivo assessments showcased the exceptional aptitude of the nanomedicine not only for preferential accumulation within tumor tissues, but also for substantial suppression of tumor growth. Immune mechanisms have shown that nanomedicine treatment promoted the maturation of DCs in vivo, enhanced the proportion of CD8+ T cells in the spleen and tumor, and simultaneously upregulated the ratio of M1 macrophages favorable for anti-tumor effects. These outcomes collectively advance a fresh perspective for the clinical breast cancer therapy.
ABSTRACT
Antibody-drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2-expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive and HER2-low breast cancer, HER2-positive gastric cancer, and HER2-mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti-HER2 ADC therapy. Studies on anti-HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti-HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti-HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti-HER2 ADC therapy in clinical practice.
Subject(s)
Immunoconjugates , Lung Diseases, Interstitial , Receptor, ErbB-2 , Humans , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/chemically induced , China , Immunoconjugates/therapeutic use , Immunoconjugates/adverse effects , Pneumonia/drug therapy , Female , Consensus , Trastuzumab/therapeutic use , Trastuzumab/adverse effects , Breast Neoplasms/drug therapy , Camptothecin/analogs & derivativesABSTRACT
We present a catalytic strategy for converting lignin into various pharmaceutical intermediates based on a highly selective lignin depolymerization method and a green benzylic oxidation method employing O2. Selective depolymerization of lignin first afforded 4-ethylphenol, which then efficiently generates several pharmaceutical intermediates with a simple 5-step process, resulting in substantial economic benefits. The study provides an innovative solution for the efficient utilization of lignin and the green acquisition of pharmaceutical intermediates.
ABSTRACT
In recent years, the triboelectric-electromagnetic hybrid generator (TEHG) has been widely studied. However, the problems of unsteady output and high starting wind speed of traditional TEHG in the wind energy environment have not been effectively solved. This work introduces an innovative solution in the form of a steady output triboelectric-electromagnetic hybrid generator (SO-TEHG) with variable drag turbine blades. The SO-TEHG integrates the energy management circuit to output steady electric energy under random wind conditions. In addition, the integration of variable drag turbine blades with the triboelectric nanogenerator (TENG) reduces the wind speed threshold required for SO-TEHG activation. In comparison to the traditional turbine blades, which necessitate a minimum wind speed of 3 m/s, the SO-TEHG's innovative design allows it to commence power generation at a lower 2 m/s wind speed, producing an additional output of 50 V. This enhanced starting capability in mild breezes positions the SO-TEHG as an ideal power source for applications. In practical farmland settings, experimental results conclusively demonstrate the SO-TEHG's ability to successfully activate soil hygrothermographs and hydrogen sensors. As a steady power source driven by gentle winds, the SO-TEHG holds tremendous promise for advancing smart agriculture.
ABSTRACT
Background: Breast cancer is the most common malignant tumor in women globally. Despite advances in primary treatment, the role of adjuvant therapy in reducing recurrence and improving survival is critical; however, there is a notable lack of tailored prognostic models for patients receiving adjuvant therapy. This study used the Surveillance, Epidemiology, and End Results (SEER) database to develop a prognostic nomogram for breast cancer patients receiving adjuvant therapy. Methods: The data of breast cancer patients who received adjuvant therapy after surgery in 2014-2015 were extracted from the SEER database. Univariate Cox regression identified significant prognostic variables that were further refined by least absolute shrinkage and selection operator (LASSO) regression and cross-validation analyses. These variables were incorporated into a multivariate Cox regression analysis to establish the predictive model. This model was visualized and validated using various statistical measures. Results: A total of 54,960 patients were included in the study, with 38,472 in the training set and 16,488 in the validation set. Age, sex, race, marital status, grade, tumor (T) stage, lymph node (N) stage, subtype, and radiotherapy were found to be significant independent risk factors of 1-, 3-, and 5-year overall survival (OS). The receiver operating characteristic curve area for 1-, 3-, and 5-year OS was >0.76 in both sets. The consistency index values were 0.768 and 0.763 for the training and validation sets, respectively. The calibration curves showed good fit, and the nomogram exhibited substantial clinical utility. Conclusions: Incorporating various significant factors, the constructed nomogram was able to effectively predict the prognosis of breast cancer patients who received adjuvant therapy. This nomogram extends understandings of complex prognosis scenarios. In addition, it could enhance personalized treatment plans and assist in patient counseling.
ABSTRACT
INTRODUCTION: Qi-Fu-Yin has been used to treat Alzheimer's disease (AD) in China. Oxidative stress has been recognized as a factor in AD progress. To date, there is no quality control method to ensure batch-to-batch consistency of Qi-Fu-Yin, and the potential antioxidant compounds in Qi-Fu-Yin remain uncertain. OBJECTIVES: The aim of this study is to identify the potential antioxidant compounds of Qi-Fu-Yin and establish quality control standards for Qi-Fu-Yin. METHODS: High-performance liquid chromatography was used to establish and quantify the fingerprints of Qi-Fu-Yin from various batches. Ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS) was used to identify the common peaks. Bivariate correlation analysis, partial least squares regression analysis, and gray correlation analysis were used to establish the spectrum-effect relationship. RESULTS: Forty-nine common peaks were determined through the establishment of fingerprints. Among them, 35 common peaks were preliminarily characterized. The multiple statistical correlation analysis methods identified six compounds as potential antioxidant constituents of Qi-Fu-Yin, and their antioxidant activities were validated in vitro. All six antioxidant compounds derived from two herbs. Therefore, three chemical index compounds derived from other three herbs were added to the quantitative analysis, while for two herbs, no peaks could be included. Eventually, six antioxidant constituents and three index compounds were quantitatively determined to provide a relatively comprehensive quality control for Qi-Fu-Yin. CONCLUSIONS: The study elucidated the antioxidant substance basis of Qi-Fu-Yin and provided a relatively comprehensive approach for the assay of Qi-Fu-Yin, which is a promising advance in the quality control of Qi-Fu-Yin.
ABSTRACT
It is of great significance to establish a low-cost, high-efficiency, self-powered micrometeorological monitoring system for agriculture, animal husbandry, and transportation. However, each additional detection element in the meteorological monitoring system increases the power consumption of the whole system by about 0.7 W. As a renewable energy technology, a triboelectric nanogenerator has the advantages of low price and self-powered sensing. To reduce the power consumption of the micrometeorological monitoring system, this work introduces an innovative solution: the wind-gathering enhanced triboelectric-electromagnetic hybrid generator (WGE-TEHG). Coupling the thin-film vibrating triboelectric nanogenerator (TENG) and electromagnetic generator (EMG), the TENG is used to monitor wind direction and the EMG is used to monitor wind speed and provide energy needed by the system. In particular, the TENG can be used as a self-powered sensor to reduce the power consumption of the sensing system. Besides, the TENG is used to produce slit effect to enhance the output performance of EMG. The experimental results show that the WGE-TEHG can build a self-powered natural environment micrometeorological sensing system. It can monitor the wind direction, wind speed, temperature, and relative humidity. This research has great application value for the self-powered sensing implementation of a hybrid TENG and EMG.
ABSTRACT
Background/purpose: Producing tooth crowns through dental technology is a basic function of dentistry. The morphology of tooth crowns is the most important parameter for evaluating its acceptability. The procedures were divided into four steps: tooth collection, scanning skills, use of mathematical methods and software, and machine learning calculation. Materials and methods: Dental plaster rods were prepared. The effective data collected were to classify 121 teeth (15th tooth position), 342 teeth (16th tooth position), 69 teeth (21st tooth position), and 89 teeth (43rd tooth position), for a total of 621 teeth. The procedures are divided into four steps: tooth collection, scanning skills, use of mathematical methods and software, and machine learning calculation. Results: The area under the curve (AUC) value was 0, 0.5, and 0.72 in this study. The precision rate and recall rate of micro-averaging/macro-averaging were 0.75/0.73 and 0.75/0.72. If we took a newly carved tooth picture into the program, the current effectiveness of machine learning was about 70%-75% to evaluate the quality of tooth morphology. Through the calculation and analysis of the two different concepts of micro-average/macro-average and AUC, similar values could be obtained. Conclusion: This study established a set of procedures that can judge the quality of hand-carved plaster sticks and teeth, and the accuracy rate is about 70%-75%. It is expected that this process can be used to assist dental technicians in judging the pros and cons of hand-carved plaster sticks and teeth, so as to help dental technicians to learn the tooth morphology more effectively.
ABSTRACT
Molecular understanding of the solid-liquid interface is challenging but essential to elucidate the role of the environment on the kinetics of electrochemical reactions. Alkali metal cations (M+), as a vital component at the interface, are found to be necessary for the initiation of carbon dioxide reduction reaction (CO2RR) on coinage metals, and the activity and selectivity of CO2RR could be further enhanced with the cation changing from Li+ to Cs+, while the underlying mechanisms are not well understood. Herein, using ab initio molecular dynamics simulations with explicit solvation and enhanced sampling methods, we systematically investigate the role of M+ in CO2RR on Cu surface. A monotonically decreasing CO2 activation barrier is obtained from Li+ to Cs+, which is attributed to the different coordination abilities of M+ with *CO2. Furthermore, we show that the competing hydrogen evolution reaction must be considered simultaneously to understand the crucial role of alkali metal cations in CO2RR on Cu surfaces, where H+ is repelled from the interface and constrained by M+. Our results provide significant insights into the design of electrochemical environments and highlight the importance of explicitly including the solvation and competing reactions in theoretical simulations of CO2RR.
ABSTRACT
BACKGROUND: Immunohistochemistry (IHC) is an essential technique in surgical and clinical pathology for detecting diagnostic, prognostic, and predictive biomarkers for personalized cancer therapy. However, the lack of standardization and reference controls results in poor reproducibility, and a reliable tool for IHC quantification is urgently required. The objective of this study was to describe a novel approach in which H3F3B (histone H3, family 3B) can be used as an internal reference standard to quantify protein expression levels using IHC. METHODS: The authors enrolled 89 patients who had human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). They used a novel IHC-based assay to measure protein expression using H3F3B as the internal reference standard. H3F3B was uniformly expressed at the protein level in all tumor regions in cancer tissues. HER2 expression levels were measured with the H-score using HALO software. RESULTS: Kaplan-Meier analysis indicated that, among patients who had HER2-positive BC in The Cancer Genome Atlas data set and the authors' data set, the subgroup with low HER2 expression had a significantly better prognosis than the subgroup with high HER2 expression. Furthermore, the authors observed that HER2 expression levels were precisely evaluated using the proposed method, which can classify patients who are at higher risk of HER2-positive BC to receive trastuzumab-based adjuvant therapy. Dual-color IHC with H3F3B is an excellent tool for internal and external quality control of HER2 expression assays. CONCLUSIONS: The proposed IHC-based quantification method accurately assesses HER2 expression levels and provides insights for predicting clinical prognosis in patients with HER2-positive BC who receive trastuzumab-based adjuvant therapy.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Histones , Immunohistochemistry , Reproducibility of Results , Receptor, ErbB-2/genetics , Trastuzumab/therapeutic use , Reference Standards , Biomarkers, Tumor/metabolismABSTRACT
The water flow energy of rivers is an important renewable and clean energy that plays a vital role in human life but is challenging to harvest at low flow velocity. This work proposes a bionic fish-shaped triboelectric-electromagnetic hybrid generator (BF-TEHG) via a two-stage swing mechanism for harvesting water flow energy. It is designed to simulate the shape of fish, effectively improving its ability to utilize low-velocity water flow energy and enabling it to operate at a minimum flow rate of 0.24 m/s. Furthermore, the impact of motion parameters on electrical performance is studied. The triboelectric and electromagnetic power-generation units can generate peak powers of 0.55 and 0.34 mW in the simulated river environments with a flow velocity of 0.98 m/s. In applications, after being immersed in water for 40 days, the BF-TEHG maintains its electrical performance without reduction, indicating excellent water immersion durability. Therefore, this work proposes an efficient strategy to harvest low-velocity water flow energy and provides an acceptable candidate for monitoring water flow conditions.
ABSTRACT
Recently, interventional ablation techniques have gained prominence in tumor treatment guidelines and complement traditional approaches, such as surgery, chemotherapy, and radiotherapy. Conventional ablation techniques, such as microwave, radiofrequency, and cryoablation, have been used; however, they have certain limitations, including the risk of damaging surrounding normal tissues and the heat sink effect caused by tumor blood flow.1 Irreversible electroporation (IRE), an ablation technology independent of thermal energy, is a promising alternative.2 Clinical studies have demonstrated IRE's efficacy in treating tumors, such as pancreatic and liver tumors.3 Recent research has shown that IRE can elicit specific anti-tumor immune responses in the body.5 IRE also plays a crucial role in eliminating residual tumor cells postoperatively and preventing tumor recurrence.
ABSTRACT
The present pavement health monitoring is limited by a professional staff patrol. Herein, a vehicle-mounted pavement health monitoring system (VPHMS) based on a spring-guide-assisted triboelectric sensor (S-TES) is proposed, which uses the vibration generated by vehicles passing through uneven pavements to monitor the pavement damage. The VPHMS consists of S-TES, the integration module, and the terminal display module. The designed S-TES has high stability and can achieve a high linear vibration amplitude measurement within 90 mm. Moreover, the integration module is used to process signals and transmit wireless data transmission. The terminal display module is used to receive signals and display the measurement results on the screen. When a vehicle equipped with VPHMS is driven over uneven pavements, the system can accurately monitor the potholes and upheavals on the pavement in real time. This work has significant application value in fields such as pavement health monitoring and intelligent transportation.
ABSTRACT
Hepatic leukemia factor (HLF) is aberrantly expressed in human malignancies. However, the role of HLF in the regulation of ovarian cancer (OC) remains unknown. Herein, we reported that HLF expression was upregulated in OC tissues and ovarian cancer stem cells (CSCs). Functional studies have revealed that HLF regulates OC cell stemness, proliferation, and metastasis. Mechanistically, HLF transcriptionally activated Yes-associated protein 1 (YAP1) expression and subsequently modulated the Hippo signaling pathway. Moreover, we found that miR-520e directly targeted HLF 3'-UTR in OC cells. miR-520e expression was negatively correlated with HLF and YAP1 expression in OC tissues. The combined immunohistochemical (IHC) panels exhibited a better prognostic value for OC patients than any of these components alone. Importantly, the HLF/YAP1 axis determines the response of OC cells to carboplatin treatment and HLF depletion or the YAP1 inhibitor verteporfin abrogated carboplatin resistance. Analysis of patient-derived xenografts (PDXs) further suggested that HLF might predict carboplatin benefits in OC patients. In conclusion, these findings suggest a crucial role of the miR-520e/HLF/YAP1 axis in OC progression and chemoresistance, suggesting potential therapeutic targets for OC.
Subject(s)
MicroRNAs , Ovarian Neoplasms , Female , Humans , Adaptor Proteins, Signal Transducing/genetics , Carboplatin , Drug Resistance, Neoplasm/genetics , Hippo Signaling Pathway , MicroRNAs/genetics , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Transcription Factors/geneticsABSTRACT
Plants face constant threats from insect herbivores, which limit plant distribution and abundance in nature and crop productivity in agricultural ecosystems. In recent decades, the whitefly Bemisia tabaci, a group of phloem-feeding insects, has emerged as pests of global significance. In this article, we summarize current knowledge on plant defenses against whitefly and approaches to engineer plant resistance to whitefly. Physically, plants deploy trichome and acylsugar-based strategies to restrain nutrient extraction by whitefly. Chemically, toxic secondary metabolites such as terpenoids confer resistance against whitefly in plants. Moreover, the jasmonate (JA) signaling pathway seems to be the major regulator of whitefly resistance in many plants. We next review advances in interfering with whitefly-plant interface by engineering of plant resistance using conventional and biotechnology-based breeding. These breeding programs have yielded many plant lines with high resistance against whitefly, which hold promises for whitefly control in the field. Finally, we conclude with an outlook on several issues of particular relevance to the nature and engineering of plant resistance against whitefly.
ABSTRACT
The monitoring of micro-droplets parameters is significant to the development of droplet microfluidics. However, existing monitoring methods have drawbacks such as high cost, interference with droplet movement, and even the potential for cross-contamination. Herein, a micro-droplets monitoring method (MDMM) based on liquid-solid triboelectric nanogenerator (LS-TENG) is proposed, which can realize non-invasive and self-powered monitoring of micro-droplets in a microfluidic chip. The droplet frequency is monitored by voltage pulse frequency and a mathematical model is established to monitor the droplet length and velocity. Furthermore, this work constructs micro-droplets sensor (MDS) based on the MDMM to carry out the experiment. The coefficients of determination (R2 ) of the fitting curves of the micro-droplets frequency, length, and velocity monitoring are 0.998, 0.997, and 0.995, respectively. To prove the universal applicability of the MDMM, the micro-droplets generated by different liquid media and channel structures are monitored. Eventually, a micro-droplet monitoring system is built, which can realize the counting of micro-droplets and the monitoring of droplet frequency and length. This work provides a novel approach for monitoring micro-droplets parameters, which holds the potential to advance developments in the field of microfluidics.
ABSTRACT
Extracellular vesicle (EV) surface proteins, expressed by primary tumours, are important biomarkers for early cancer diagnosis. However, the detection of these EV proteins is complicated by their low abundance and interference from non-EV components in clinical samples. Herein, we present a MEmbrane-Specific Separation and two-step Cascade AmpLificatioN (MESS2CAN) strategy for direct detection of EV surface proteins within 4 h. MESS2CAN utilises novel lipid probes (long chains linked by PEG2K with biotin at one end, and DSPE at the other end) and streptavidin-coated magnetic beads, permitting a 49.6% EV recovery rate within 1 h. A dual amplification strategy with a primer exchange reaction (PER) cascaded by the Cas12a system then allows sensitive detection of the target protein at 10 EV particles per microliter. Using 4 cell lines and 90 clinical test samples, we demonstrate MESS2CAN for analysing HER2, EpCAM and EGFR expression on EVs derived from cells and patient plasma. MESS2CAN reports the desired specificity and sensitivity of EGFR (AUC = 0.98) and of HER2 (AUC = 1) for discriminating between HER2-positive breast cancer, triple-negative breast cancer and healthy donors. MESS2CAN is a pioneering method for highly sensitive in vitro EV diagnostics, applicable to clinical samples with trace amounts of EVs.
Subject(s)
Breast Neoplasms , Extracellular Vesicles , Humans , Female , Membrane Proteins , Biotin , Breast Neoplasms/diagnosis , ErbB ReceptorsABSTRACT
Proteins are ubiquitously modified with glycans of varied chemical structures through distinct glycosidic linkages, making the landscape of protein glycosylation challenging to map. Profiling of intact glycopeptides with mass spectrometry (MS) has recently emerged as a powerful tool for revealing matched information of the glycosylation sites and attached glycans (i.e., intact glycosites), but is largely limited to individual glycosylation types. Herein, we describe Click-iG, which integrates metabolic labeling of glycans with clickable unnatural sugars, an optimized MS method, and a tailored version of pGlyco3 software to enable simultaneous enrichment and profiling of three types of intact glycopeptides: N-linked, mucin-type O-linked, and O-GlcNAcylated glycopeptides. We demonstrate the utility of Click-iG by the identification of thousands of intact glycosites in cell lines and living mice. From the mouse lung, heart, and spleen, a total of 2053 intact N-glycosites, 262 intact O-GalNAc glycosites, and 1947 O-GlcNAcylation sites were identified. Click-iG-enabled comprehensive coverage of the protein glycosylation landscape lays the foundation for interrogating crosstalk between different glycosylation pathways.
Subject(s)
Glycopeptides , Proteins , Animals , Mice , Glycopeptides/chemistry , Proteins/metabolism , Glycosylation , Mass Spectrometry , PolysaccharidesABSTRACT
Ultrasonic-assisted metal droplet deposition (UAMDD) is currently considered a promising technology in droplet-based 3D printing due to its capability to change the wetting and spreading behaviors at the droplet-substrate interface. However, the involved contact dynamics during impacting droplet deposition, particularly the complex physical interaction and metallurgical reaction of induced wetting-spreading-solidification by the external energy, remain unclear to date, which hinders the quantitative prediction and regulation of the microstructures and bonding property of the UAMDD bumps. Here, the wettability of the impacting metal droplet ejected by a piezoelectric micro-jet device (PMJD) on non-wetting and wetting ultrasonic vibration substrates is studied, and the corresponding spreading diameter, contact angle, and bonding strength are also discussed. For the non-wetting substrate, the wettability of the droplet can be significantly increased due to the extrusion of the vibration substrate and the momentum transfer layer at the droplet-substrate interface. And the wettability of the droplet on a wetting substrate is increased at a lower vibration amplitude, which is driven by the momentum transfer layer and the capillary waves at the liquid-vapor interface. Moreover, the effects of the ultrasonic amplitude on the droplet spreading are studied under the resonant frequency of 18.2-18.4 kHz. Compared to deposit droplets on a static substrate, such UAMDD has 31% and 2.1% increments in the spreading diameters for the non-wetting and wetting systems, and the corresponding adhesion tangential forces are increased by 3.85 and 5.59 times.
ABSTRACT
The begomovirus-betasatellite complex constantly threatens crops in Asia. However, the quantitative relationship between begomoviruses and betasatellites remains largely unknown. The quantities of tobacco curly shoot virus (TbCSV) and its betasatellite (TbCSB) and their ratio varied significantly in initial infection, and thereafter, the ratio tended to become constant. The TbCSB/TbCSV ratio in agrobacteria inoculum significantly affected that in plants in the initial infection but not thereafter. Null-mutation of ßC1 that encodes a multifunctional protein important for pathogenesis in TbCSB significantly reduced the TbCSB/TbCSV ratio in plants. Viral inoculum plants with higher TbCSB/TbCSV ratios promoted whitefly transmission of the virus. The expression of AV1 encoded by TbCSV, ßC1 encoded by TbCSB and the ßC1/AV1 ratio varied significantly in the initial infection and thereafter the ratio tended to become constant. Additionally, the temporal dynamics of the ratio between another begomovirus and its betasatellite was similar to that of TbCSV and was positively regulated by ßC1. These results indicate that the ratio between monopartite begomoviruses and betasatellites tend to become constant as infection progresses, and is modulated by ßC1, but a higher betasatellite/begomovirus ratio in virally inoculated plants promotes virus transmission by whiteflies. Our findings provide novel insights into the association between begomoviruses and betasatellites.