Advances in Portable Heavy Metal Ion Sensors.

Heavy metal ions, one of the major pollutants in the environment, exhibit non-degradable and bio-chain accumulation characteristics, seriously damage the environment, and threaten human health. Traditional heavy metal ion detection methods often require complex and expensive instruments, professional operation, tedious sample preparation, high requirements for laboratory conditions, and operator professionalism, and they cannot be widely used in the field for real-time and rapid detection. Therefore, developing portable, highly sensitive, selective, and economical sensors is necessary for the detection of toxic metal ions in the field. This paper presents portable sensing based on optical and electrochemical methods for the in situ detection of trace heavy metal ions. Progress in research on portable sensor devices based on fluorescence, colorimetric, portable surface Raman enhancement, plasmon resonance, and various electrical parameter analysis principles is highlighted, and the characteristics of the detection limits, linear detection ranges, and stability of the various sensing methods are analyzed. Accordingly, this review provides a reference for the design of portable heavy metal ion sensing.

Multiple amplification-based fluorometric aptasensor for highly sensitive detection of Staphylococcus aureus.

Rapid and accurate detection and identification of Staphylococcus aureus (S. aureus) are of great significance for food safety, environmental monitoring, early clinical diagnosis, and prevention of the spread of drug-resistant bacteria. Herein, we design a fluorometric aptasensor for ultra-sensitive, specific, and rapid detection of S. aureus. The apasensor combines the enrichment and separation of magnetic nanoparticles (MNPs), the biotin-streptavidin conjugation system, and a single S. aureus can release four signaling probes for signal amplification. Aptamer acts as a specific biorecognition element of S. aureus. Four FAM-labeled partially complementary sequences (FAM-pcDNAs) were used as signaling probes. The aptamers were sequential hybridized with the four FAM-pcDNAs to form aptamer&pcDNAs, which were then bound to MNPs via the biotin-streptavidin. When the aptamer specifically recognizes and binds to S. aureus, the FAM-pcDNAs signaling probes are replaced and released into the supernatant. The concentration of S. aureus can be quantified by measuring the fluorescence intensity (λexc/em = 492/520 nm) of the replaced signaling probe FAM-pcDNAs. The results show that the proposed fluorometric aptasensor displays good specificity, ultra-high sensitivity (1.23 cfu/mL), wide linear range (1 ~ 108 cfu/mL), and fast detection speed (~ 1.5 h). The recovery test verifies further that the proposed fluorometric aptasensor can detect S. aureus in spiked blood samples. Since aptamers are easy to customize, we believe that fluorometric aptasensors based on multiple amplification have broad prospects in the construction of practical high-performance biosensors for bacterial detection. KEY POINTS: • Multiple amplification-based fluorometric aptasensor for S. aureus is developed • The aptasensor displays high specificity with a LOD of 1.23 CFU/mL • The aptasensor can directly detect S. aureus in spiked blood samples.

Application strategies of peptide nucleic acids toward electrochemical nucleic acid sensors.

Peptide nucleic acids (PNAs) have attracted tremendous interest in the fabrication of highly sensitive electrochemical nucleic acid biosensors due to their higher stability and increased sensitivity than common DNA probes. The neutral pseudopeptide backbone of PNAs not only makes the PNA/DNA duplexes more stable but also provides many opportunities to construct ultrasensitive nucleic acid sensors. This review presents the details of various protocols for the construction of PNA-based electrochemical nucleic acid sensors. The crucial factors, origin, and development of PNA, immobilization methods of PNA probes and signal generation mechanisms, are discussed. This review aims to provide a reference for ultrasensitive PNA electrochemical biosensor preparation.

Estimation of Winter Wheat Yield in Arid and Semiarid Regions Based on Assimilated Multi-Source Sentinel Data and the CERES-Wheat Model.

The farmland area in arid and semiarid regions accounts for about 40% of the total area of farmland in the world, and it continues to increase. It is critical for global food security to predict the crop yield in arid and semiarid regions. To improve the prediction of crop yields in arid and semiarid regions, we explored data assimilation-crop modeling strategies for estimating the yield of winter wheat under different water stress conditions across different growing areas. We incorporated leaf area index (LAI) and soil moisture derived from multi-source Sentinel data with the CERES-Wheat model using ensemble Kalman filter data assimilation. According to different water stress conditions, different data assimilation strategies were applied to estimate winter wheat yields in arid and semiarid areas. Sentinel data provided LAI and soil moisture data with higher frequency (<14 d) and higher precision, with root mean square errors (RMSE) of 0.9955 m2 m-2 and 0.0305 cm3 cm-3, respectively, for data assimilation-crop modeling. The temporal continuity of the CERES-Wheat model and the spatial continuity of the remote sensing images obtained from the Sentinel data were integrated using the assimilation method. The RMSE of LAI and soil water obtained by the assimilation method were lower than those simulated by the CERES-Wheat model, which were reduced by 0.4458 m2 m-2 and 0.0244 cm3 cm-3, respectively. Assimilation of LAI independently estimated yield with high precision and efficiency in irrigated areas for winter wheat, with RMSE and absolute relative error (ARE) of 427.57 kg ha-1 and 6.07%, respectively. However, in rain-fed areas of winter wheat under water stress, assimilating both LAI and soil moisture achieved the highest accuracy in estimating yield (RMSE = 424.75 kg ha-1, ARE = 9.55%) by modifying the growth and development of the canopy simultaneously and by promoting soil water balance. Sentinel data can provide high temporal and spatial resolution data for deriving LAI and soil moisture in the study area, thereby improving the estimation accuracy of the assimilation model at a regional scale. In the arid and semiarid region of the southeastern Loess Plateau, assimilation of LAI independently can obtain high-precision yield estimation of winter wheat in irrigated area, while it requires assimilating both LAI and soil moisture to achieve high-precision yield estimation in the rain-fed area.

Multiple m6A RNA methylation modulators promote the malignant progression of hepatocellular carcinoma and affect its clinical prognosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. N6-methyladenosine (m6A) RNA methylation is dynamically regulated by m6A RNA methylation modulators ("writer," "eraser," and "reader" proteins), which are associated with cancer occurrence and development. The purpose of this study was to explore the relationships between m6A RNA methylation modulators and HCC. METHODS: First, using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we compared the expression levels of 13 major m6A RNA methylation modulators between HCC and normal tissues. Second, we applied consensus clustering to the expression data on the m6A RNA methylation modulators to divide the HCC tissues into two subgroups (clusters 1 and 2), and we compared the clusters in terms of overall survival (OS), World Health Organization (WHO) stage, and pathological grade. Third, using least absolute shrinkage and selection operator (LASSO) regression, we constructed a risk signature involving the m6A RNA methylation modulators that affected OS in TCGA and ICGC analyses. RESULTS: We found that the expression levels of 12 major m6A RNA methylation modulators were significantly different between HCC and normal tissues. After dividing the HCC tissues into clusters 1 and 2, we found that cluster 2 had poorer OS, higher WHO stage, and higher pathological grade. Four m6A RNA methylation modulators (YTHDF1, YTHDF2, METTL3, and KIAA1429) affecting OS in the TCGA and ICGC analyses were selected to construct a risk signature, which was significantly associated with WHO stage and was also an independent prognostic marker of OS. CONCLUSIONS: In summary, m6A RNA methylation modulators are key participants in the malignant progression of HCC and have potential value in prognostication and treatment decisions.

TomoGAN: low-dose synchrotron x-ray tomography with generative adversarial networks: discussion.

Synchrotron-based x-ray tomography is a noninvasive imaging technique that allows for reconstructing the internal structure of materials at high spatial resolutions from tens of micrometers to a few nanometers. In order to resolve sample features at smaller length scales, however, a higher radiation dose is required. Therefore, the limitation on the achievable resolution is set primarily by noise at these length scales. We present TomoGAN, a denoising technique based on generative adversarial networks, for improving the quality of reconstructed images for low-dose imaging conditions. We evaluate our approach in two photon-budget-limited experimental conditions: (1) sufficient number of low-dose projections (based on Nyquist sampling), and (2) insufficient or limited number of high-dose projections. In both cases, the angular sampling is assumed to be isotropic, and the photon budget throughout the experiment is fixed based on the maximum allowable radiation dose on the sample. Evaluation with both simulated and experimental datasets shows that our approach can significantly reduce noise in reconstructed images, improving the structural similarity score of simulation and experimental data from 0.18 to 0.9 and from 0.18 to 0.41, respectively. Furthermore, the quality of the reconstructed images with filtered back projection followed by our denoising approach exceeds that of reconstructions with the simultaneous iterative reconstruction technique, showing the computational superiority of our approach.

Design and Simulation of a Passive Micromixer with Gourd-Shaped Channel.

A gourd-shaped contraction-expansion design is proposed for a passive planar micromixer in this study. The mixing performance of the micromixer is analyzed numerically and compared with a T-shaped planar micromixer. The gourd-shaped contraction-expansion structure can enhance the vortex-formation and mixing abilities of the micromixer. The numerical simulation reveals that the gourd-shaped structure can improved vortex generation and mixing efficiency within a high Reynolds number range. The micromixer with an optimized waist width of 50 µm reaches a mixing efficiency of approximately 83.25% and maintains a moderate pressure drop of 4860 Pa at Re = 100. This study can shed light on the design of new 2D micromixers from the point view of bionics.

Diketopyrrolopyrrole Amphiphile-Based Micelle-Like Fluorescent Nanoparticles for Selective and Sensitive Detection of Mercury(II) Ions in Water.

A technique for encapsulating fluorescent organic probes in a micelle system offers an important alternative method to manufacture water-soluble organic nanoparticles (ONPs) for use in sensing Hg2+. This article reports on a study of a surfactant-free micelle-like ONPs based on a 3,6-di(2-thienyl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione (TDPP) amphiphile, (2-(2-(2-methoxyethoxy)ethyl)-3,6-di(2-thiophyl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione (NDPP) fabricated to monitor Hg2+ in water. NDPP was synthesized through a simple one-step modification of a commercially available dye TDPP with a flexible and hydrophilic alkoxy. This study reports, for the first time, that TDPP dyes can respond reversibly, sensitively, and selectively to Hg2+ through TDPP-Hg-TDPP complexation, similar to the well-known thymine(T)-Hg-thymine(T) model and the accompanying molecular aggregation. Interestingly, transmission electron microscopy (TEM) and dynamic light scattering (DLS) confirmed that, in water, NDPP forms loose micelle-like fluorescent ONPs with a hydrohobic TDPP portion encapsulated inside. These micelle-like nanoparticles offer an ideal location for TDPP-Hg complexation with a modest molecular aggregation, thereby providing both clear visual and spectroscopic signals for Hg2+ sensing. An estimated detection limit of 11 nM for Hg2+ sensing with this NDPP nanoparticle was obtained. In addition, NDPP ONPs show good water solubility and high selectivity to Hg2+ in neutral or alkalescent water. It was superior to most micelle-based nanosensors, which require a complicated process in the selection or synthesis of suitable surfactants. The determinations in real samples (river water) were made and satisfactory results were achieved. This study provides a low-cost strategy for fabricating small molecule-based fluorescent nanomaterials for use in sensing Hg2+. Moreover, the NDPP nanoparticles show potential ability in Hg2+ ion adsorption and recognization of cysteine using NDPP-Hg composite particle.

[Recognition study of double strand DNA with hairpin oligopolyamide].

Selective recognition of double strands DNA(ds DNA) has been a research hot spot in molecular biology and biomedicine for a couple decades. Based on the selective interaction between natural nucleic acid/synthetic molecular ligands and ds DNA, gene diagnosis, gene therapy and gene editing would be realized. Hairpin oligopolyamide is a molecular ligand with excellent cellular permeability and nucleases-resistance which can target ds DNA sequence with high affinity and specificity at minor groove. This paper reviews the binding properties and biomedical applications of hairpin oligopolyamide targeting ds DNA, which provide references for further design and application of hairpin oligopolyamide.

Electrochemical Probing through a Redox Capacitor To Acquire Chemical Information on Biothiols.

The acquisition of chemical information is a critical need for medical diagnostics, food/environmental monitoring, and national security. Here, we report an electrochemical information processing approach that integrates (i) complex electrical inputs/outputs, (ii) mediators to transduce the electrical I/O into redox signals that can actively probe the chemical environment, and (iii) a redox capacitor that manipulates signals for information extraction. We demonstrate the capabilities of this chemical information processing strategy using biothiols because of the emerging importance of these molecules in medicine and because their distinct chemical properties allow evaluation of hypothesis-driven information probing. We show that input sequences can be tailored to probe for chemical information both qualitatively (step inputs probe for thiol-specific signatures) and quantitatively. Specifically, we observed picomolar limits of detection and linear responses to concentrations over 5 orders of magnitude (1 pM-0.1 µM). This approach allows the capabilities of signal processing to be extended for rapid, robust, and on-site analysis of chemical information.

Fluorescent Pyrene Assisted Photodeprotection of 2-(2-nitrophenyl)Propyloxycarbonyl Groups on Self-Assembled Monolayers.

Accelerating the photodeprotection rate of photolabile protecting group is conducive to a light-directed chemical reaction, especially for the in situ synthesis of a biochip. Herein, a photosensitizer pyrene was applied to the photodeprotection of 2-(2-nitrophenyl)propyloxycarbony (NPPOC) groups on self-assembled monolayers (SAMs). It was found that the addition of pyrene could largely improve photodeprotection rate, and effectively prevent molecule damage that are often encountered by the photosensitizer 2-isopropyl thioxanthone (ITX). The most likely explanation for this result is that the whole photodeprotection process involves three joint actions, including ultraviolet light irradiation, triplet energy transfer by pyrene, and singlet fluorescence irradiation from pyrene. The joint actions enable the transfer of over-absorbed energy from pyrene to protecting groups in terms of fluorescence rather than free radicals produced by ITX that are detrimental to the molecules modified on glass substrates. Pyrene dissolved in an optimized combination of mixed solvent of dimethylacetamide (DMAC), ethanol, and dioxane with a volume ratio of 1:1:1 was tested to produce a complete photodeprotection of NPPOC groups within 6 min under 365 nm ultraviolet with an intensity of 10.8 mW/cm2. Meanwhile, tens to hundreds of cycles of photodeprotection could be conducted at a high efficiency. This research will shed light on the deprotection of photolabile groups with weak ultraviolet using a fluorescent sensitizer.

[Research progress of probe design software of oligonucleotide microarrays].

DNA microarray has become an essential medical genetic diagnostic tool for its high-throughput, miniaturization and automation. The design and selection of oligonucleotide probes are critical for preparing gene chips with high quality. Several sets of probe design software have been developed and are available to perform this work now. Every set of the software aims to different target sequences and shows different advantages and limitations. In this article, the research and development of these sets of software are reviewed in line with three main criteria, including specificity, sensitivity and melting temperature (Tm). In addition, based on the experimental results from literatures, these sets of software are classified according to their applications. This review will be helpful for users to choose an appropriate probe-design software. It will also reduce the costs of microarrays, improve the application efficiency of microarrays, and promote both the research and development (R&D) and commercialization of high-performance probe design software.

Targeted Delivery of Peptide Nucleic Acid by Biomimetic Nanoparticles Based on Extracellular Vesicle-coated Mesoporous Silica Nanoparticles.

BACKGROUND: Peptide nucleic acid (PNA) plays an important role in antimicrobial activity, but its cellular permeability is poor. To overcome this limitation, we constructed biomimetic nanoparticles by using extracellular vesicle (EV)-coated mesoporous silicon nanoparticles (MSNs) to deliver PNA to Staphylococcus aureus (S. aureus) and improve its antisense therapeutic effect. METHOD: MSN was prepared by the sol-gel method, and EV was extracted by affinity resin chromatography. EV was coated on MSN by simple sonication (50 W, 3 min) to prepare biomimetic nanoparticles with PNA-loaded MSN as the core and EV isolated from S. aureus as the shell. RESULTS: The MSN prepared by the sol-gel method had a uniform particle size (100 nm) and well-defined pore size for loading PNA with good encapsulation efficiency (62.92%) and drug loading (7.74%). The concentration of EV extracted by affinity resin chromatography was about 1.74 mg/mL. EV could be well coated on MSN through simple ultrasonic treatment (50 W, 3 min), and the stability and blood compatibility of MSN@ EV were good. Internalization experiments showed that EV could selectively enhance the uptake of biomimetic nanoparticles by S. aureus. Preliminary in vitro antibacterial tests revealed that PNA@MSN@EV exhibited enhanced antibacterial activity against S. aureus and had stronger bactericidal activity than free PNA and PNA@MSN at equivalent PNA concentrations (8 µM). CONCLUSION: Biomimetic nanoparticles based on EV-coated MSN offer a new strategy to improve the efficacy of PNA for the treatment of bacterial infections, and the technology holds promise for extension to the delivery of antibiotics that are traditionally minimally effective or prone to resistance.

Intravenous metastasis of unexpected uterine sarcoma in the context of uterine fibroids: case report and literature review.

Objective: Endometrial stromal tumors are rare and complex mesenchymal tumors that often present with clinical symptoms similar to uterine leiomyomas. Due to their atypical nature, they are prone to be misdiagnosed or overlooked by healthcare professionals. This study presents a case report of an incidentally discovered endometrial stromal sarcoma with venous metastasis, which was initially misdiagnosed as a uterine leiomyoma. In addition, this study reviews previously documented cases of similar tumors. Case report: During a routine medical examination in 2016, a 50-year-old woman was diagnosed with uterine fibroids. In June 2020, she began experiencing moderate, irregular vaginal bleeding. Nevertheless, a histopathological examination indicated an endometrial stromal sarcoma with a striking amalgamation of both low-grade and high-grade features. Molecular analysis identified a rare MED12 gene mutation. The patient underwent total hysterectomy, bilateral salpingectomy, and resection of the metastatic lesions. Postoperative management included radiotherapy, chemotherapy, and hormone therapy. After completion of chemotherapy, the patient was followed up for 27 months with no evidence of tumor recurrence. Conclusion: This case report highlights the importance of pathological, immunohistochemical, and molecular aspects of this rare tumor involving the inferior vena cava and showing the presence of atypical gene mutations. The successful treatment outcome further emphasizes the importance of advances in diagnostic modalities for managing rare tumors like this.

Induction Chemotherapy Followed by Radiotherapy vs Chemoradiotherapy in Nasopharyngeal Carcinoma: A Randomized Clinical Trial.

Importance: Induction chemotherapy plus concurrent chemoradiotherapy is recommended for locoregionally advanced nasopharyngeal carcinoma but is associated with higher rates of acute toxic effects and low compliance. Evidence on de-escalating treatment intensity after induction chemotherapy is limited. Objective: To assess if radiotherapy was noninferior to chemoradiotherapy after induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma. Design, Setting, and Participants: From April 2015 to March 2018, a multicenter, open-label, randomized, noninferiority, phase 3 trial was conducted at 5 Chinese hospitals. A total of 383 patients aged 18 to 70 years with an untreated histologically confirmed nonkeratinizing tumor, Karnofsky performance status score not worse than 70, proper organ function, and stage III to IVB nasopharyngeal cancer were enrolled. Data were analyzed from April 2023 to June 2023. Interventions: Patients were assigned randomly. Both groups received 3 cycles of induction chemotherapy consisting of intravenous administration (on day 1) of cisplatin at 60 mg/m2 and docetaxel at 60 mg/m2 and continuous intravenous infusion (from day 1 to day 5) of daily fluorouracil (600 mg/m2), repeated every 21 days. Subsequently, the patients received radiotherapy alone (induction chemotherapy in combination with radiotherapy [IC-RT] group) or concomitant cisplatin (30 mg/m2/week) with radiotherapy for 6 to 7 weeks (induction chemotherapy combined with chemoradiotherapy [IC-CCRT] group). Main Outcomes and Measures: The primary end point was 3-year progression-free survival (time from the initiation of therapy until the first indication of disease progression or death), with a noninferiority margin of 10%. The secondary end points included overall survival, locoregional failure-free survival, distant metastasis-free survival, response rate, and toxic effects. Results: A total of 383 patients (median [range] age, 48 [19-70] years; 100 women [26%]). Median follow-up time was 76 months (IQR, 70-89 months). The 3-year progression-free survival was 76.2% and 76.8% in the IC-RT (n = 193) and IC-CCRT groups (n = 190), respectively, in the intention-to-treat population, showing a difference of 0.6% (95% CI, -7.9% to 9.1%; P = .01 for noninferiority). Identical outcomes were reported in the per-protocol population. The incidence of grade 3 to 4 short-term toxic effects in the IC-RT group was less than the IC-CCRT group. No differences were observed in late toxic effects. Conclusions and Relevance: The results of this randomized clinical trial suggest that after induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma, radiotherapy alone was noninferior to chemoradiotherapy in terms of 3-year progression-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT02434614.

Peptide nucleic acids (PNAs) patterning by an automated microarray synthesis system through photolithography.

Peptide nucleic acids (PNA) microarray assembled with hundreds of unique PNA oligomers has been regarded as a new and mighty competitor of DNA chip in gene analyzing. However, PNA microarray is still a luxury art due to the difficult and laborious chemical synthesis. Herein, we have developed a fully-automated synthesizer for PNA microarray through photolithography. A preactivation mixer was designed and integrated into the synthesizer in order to get rid of the annoying manual process and increase the coupling efficiency of PNA monomers. The PNA patterning model was carried out to check the performance of the automated synthesizer, revealing that an exposure time of 3 min was sufficient for the complete removal of o-nitroveratryloxycarbonyl (NVOC) groups from the synthetic sites with the help of photosensitizer isopropylthioxanthone and the stepwise yield was measured to be about 98.0%, which is comparable with that from conventional fluorenyl-methyloxycarbonyl (FMOC) chemistry. Those results have definitely demonstrated the possibility and capability of this fully-automated synthesizer to fabricate high-quality PNA microarrays.

DPP-Cu2+ Complexes Gated Mesoporous Silica Nanoparticles For pH and Redox Dual Stimuli-Responsive Drug Delivery.

OBJECTIVE: A simple pH and redox dual stimuli-responsive diketopyrrolopyrrole (DPP)-Cu2+ complexes gated mesoporous silica nanoparticles (MSN) were prepared for precise drug delivery and controlled drug release. METHOD: MSN was prepared by sol-gel method and then laminated. Carboxylic acid (CA)-Pyrrolo[3,4-c] pyrrole-1,4-dione, 2,5-dihydro-3,6-di-2-pyridinyl (PyDPP) was grafted onto the surface of amino-functionalized MSN (MSN-NH2) through a simple amide reaction and then complexed with Cu2+ to form gated molecules after doxorubicin (DOX) loading. RESULTS: Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Low-angle X-ray diffraction (XRD) showed that MSN with uniform particle size (100 nm) and porous structure was successfully prepared. The prepared MSN, MSN- NH2, and MSN-DPP were fully characterized by Zeta potential, Fourier transforms infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and nitrogen adsorption- desorption. High DOX-loading capacity (18.22%) and encapsulation efficiency (89.16%) were achieved by optimizing the mass ratio of MSN to DOX. Release studies showed that the gated molecules of our designed DPP-Cu2+ complexes had a good blocking effect under physiological conditions (the cumulative release rate of drugs within 24 hours was only 4.18%) and responded well to the pH and redox glutathione (GSH) dual stimuli. In vitro cytotoxicity assay showed that MSN-DPP-Cu2+ had good biocompatibility in both Hep G2 cells and L02 cells (the relative cell viability of both cells within 48 hours was above 97%), and the MSN-DPP-Cu2+@DOX could be triggered for efficient drug release in Hep G2 cells. CONCLUSION: The MSN-DPP-Cu2+ described in this research may be a good delivery system for the controlled release of antitumor drugs and can provide a potential possibility for clinical application in the future.

Three-Dimensional Electrochemical Sensors for Food Safety Applications.

Considering the increasing concern for food safety, electrochemical methods for detecting specific ingredients in the food are currently the most efficient method due to their low cost, fast response signal, high sensitivity, and ease of use. The detection efficiency of electrochemical sensors is determined by the electrode materials' electrochemical characteristics. Among them, three-dimensional (3D) electrodes have unique advantages in electronic transfer, adsorption capacity and exposure of active sites for energy storage, novel materials, and electrochemical sensing. Therefore, this review begins by outlining the benefits and drawbacks of 3D electrodes compared to other materials before going into more detail about how 3D materials are synthesized. Next, different types of 3D electrodes are outlined together with common modification techniques for enhancing electrochemical performance. After this, a demonstration of 3D electrochemical sensors for food safety applications, such as detecting components, additives, emerging pollutants, and bacteria in food, was given. Finally, improvement measures and development directions of electrodes with 3D electrochemical sensors are discussed. We think that this review will help with the creation of new 3D electrodes and offer fresh perspectives on how to achieve extremely sensitive electrochemical detection in the area of food safety.

Novel chimeric antigen receptor T cell-based immunotherapy: a perspective for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is highly aggressive and does not express estrogen receptor (ER), progesterone (PR), or human epidermal growth factor receptor 2 (HER2). It has a poor prognosis, and traditional endocrine and anti-HER2 targeted therapies have low efficacy against it. In contrast, surgery, radiotherapy, and/or systemic chemotherapy are relatively effective at controlling TNBC. The resistance of TNBC to currently available clinical therapies has had a significantly negative impact on its treatment outcomes. Hence, new therapeutic options are urgently required. Chimeric antigen receptor T cell (CAR-T) therapy is a type of immunotherapy that integrates the antigen specificity of antibodies and the tumor-killing effect of T cells. CAR-T therapy has demonstrated excellent clinical efficacy against hematological cancers. However, its efficacy against solid tumors such as TNBC is inadequate. The present review aimed to investigate various aspects of CAR-T administration as TNBC therapy. We summarized the potential therapeutic targets of CAR-T that were identified in preclinical studies and clinical trials on TNBC. We addressed the limitations of using CAR-T in the treatment of TNBC in particular and solid tumors in general and explored key strategies to overcome these impediments. Finally, we comprehensively examined the advancement of CAR-T immunotherapy as well as countermeasures that could improve its efficacy as a TNBC treatment and the prognosis of patients with this type of cancer.

Apatinib combined with camrelizumab in the treatment of recurrent/metastatic nasopharyngeal carcinoma: a prospective multicenter phase II study.

Background: Preclinical studies demonstrated that immune checkpoint inhibitors combined with antiangiogenic drugs have a synergistic anti-tumor effect. This present phase II trial aimed to evaluate the efficacy and safety of apatinib combined with camrelizumab in patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). Methods: Patients with RM-NPC were administered with apatinib at 250 mg orally once every day and with camrelizumab at 200 mg via intravenous infusion every 2 weeks until the disease progressed or toxicity became unacceptable. The objective response rate (ORR) was the primary endpoint, assessed using RECIST version 1.1. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety were the key secondary endpoints. This study was registered with ClinicalTrials.gov, NCT04350190. Results: This study enrolled 26 patients with RM-NPC between January 14, 2021 and September 15, 2021. At data cutoff (March 31, 2023), the median duration of follow-up was 16 months (ranging from 1 to 26 months). The ORR was 38.5% (10/26), the disease control rate (DCR) was 61.5% (16/26), and the median PFS was 6 months (IQR 3.0-20.0). The median OS was 14 months (IQR 6.0-21.25). Treatment-related grade 3 or 4 adverse events occurred in seven (26.9%) patients, and comprised anemia (7.7%), stomatitis (3.8%), headache (3.8%), pneumonia (7.7%), and myocarditis (3.8%). There were no serious treatment-related adverse events or treatment-related deaths. Conclusion: In patients with RM-NPC, apatinib plus camrelizumab showed promising antitumor activity and manageable toxicities.