Phytoecdysteroids from Dianthus superbus L.: Structures and anti-neuroinflammatory evaluation.

Six undescribed C27-phytoecdysteroid derivatives, named superecdysones A-F, and ten known analogs were extracted from the whole plant of Dianthus superbus L. Their structures were identified by extensive spectroscopy, mass spectrometric methods, chemical transformations, chiral HPLC analysis, and the single-crystal X-ray diffraction analysis. Superecdysones A and B possess a tetrahydrofuran ring in the side chain and superecdysones C-E are rare phytoecdysones containing a (R)-lactic acid moiety, whereas superecdysone F is an uncommon B-ring-modified ecdysone. Notably, based on the variable temperature (from 333 K to 253 K) NMR experiments of superecdysone C, the missing carbon signals were visible at 253 K and assigned. The neuroinflammatory bioassay of all compounds were evaluated, and 22-acetyl-2-deoxyecdysone, 2-deoxy-20-hydroxyecdysone, 20-hydroxyecdysone, ecdysterone-22-O-benzoate, 20-hydroxyecdysone-20,22-O-R-ethylidene, and acetonide derivative 20-hydroxyecdysterone-20, 22-acetonide significantly suppressed the LPS-induced nitric oxide generation in microglia cells (BV-2), with IC50 values ranging from 6.9 to 23.0 µM. Structure-activity relationships were also discussed. Molecular docking simulations of the active compounds confirmed the possible mechanism of action against neuroinflammations. Furthermore, none compounds showed cytotoxicity against HepG2 and MCF-7. It is the first report about the occurrence and anti-neuroinflammatory activity of the phytoecdysteroids in the genus Dianthus. Our findings demonstrated that ecdysteroids may be used as potential anti-inflammatory drugs.

Light scattering of a uniform uniaxial anisotropic sphere by an on-axis high-order Bessel vortex beam.

Analytical solutions to the scattering of a uniform uniaxial anisotropic sphere illuminated by an on-axis high-order Bessel vortex beam (HOBVB) are investigated. Using the vector wave theory, the expansion coefficients of the incident HOBVB in terms of the spherical vector wave functions (SVWFs) are obtained. According to the orthogonality of the associated Legendre function and exponential function, more concise expressions of the expansion coefficients are derived. It can reinterpret the incident HOBVB faster compared with the expansion coefficients of double integral forms. The internal fields of a uniform uniaxial anisotropic sphere are proposed in the integrating form of the SVWFs by introducing the Fourier transform. The differences of scattering characteristics of a uniaxial anisotropic sphere illuminated by a zero-order Bessel beam, Gaussian beam, and HOBVB are exhibited. Influences of the topological charge, conical angle, and particle size parameters on the angle distributions of the radar cross section are analyzed in detail. The scattering and extinction efficiencies varied with the particle radius, conical angle, permeability, and dielectric anisotropy are also discussed. The results provide insights into the scattering and light-matter interactions and may find important applications in optical propagation and optical micromanipulation of biological and anisotropic complex particles.

A novel CDK4/6 inhibitor combined with irradiation demonstrates potent anti-tumor efficacy in diffuse midline glioma.

OBJECTIVE: Diffuse midline glioma, H3 K27-altered (DMG) is a lethal pediatric brainstem tumor. Despite numerous efforts to improve survival benefits, its prognosis remains poor. This study aimed to design and synthesize a novel CDK4/6 inhibitor YF-PRJ8-1011, which exhibited more potent antitumor activity against a panel of patient-derived DMG tumor cells in vitro and in vivo compared with palbociclib. METHODS: Patient-derived DMG cells were used to assess the antitumor efficacy of YF-PRJ8-1011 in vitro. The liquid chromatography tandem-mass spectrometry method was used to measure the activity of YF-PRJ8-1011 passing through the blood-brain barrier. DMG patient-derived xenograft models were established to detect the antitumor efficacy of YF-PRJ8-1011. RESULTS: The results showed that YF-PRJ8-1011 could inhibit the growth of DMG cells both in vitro and in vivo. YF-PRJ8-1011 could well penetrate the blood-brain barrier. It also significantly inhibited the growth of DMG tumors and prolonged the overall survival of mice compared with vehicle or palbociclib. Most notably, it exerted potent antitumor efficacy in DMG in vitro and in vivo compared with palbociclib. In addition, we also found that YF-PRJ8-1011 combined with radiotherapy also showed more significant inhibition of DMG xenograft tumor growth than radiotherapy alone. CONCLUSION: Collectively, YF-PRJ8-1011 is a novel, safe, and selective CDK4/6 inhibitor for DMG treatment.

Different types of fruit intake and colorectal cancer risk: A meta-analysis of observational studies.

BACKGROUND: Multiple studies investigating the relationship between intake of different types of fruit and colorectal cancer (CRC) risk have yielded inconsistent results. AIM: To perform a meta-analysis of existing studies to assess the association between the intake of different kinds of fruit and the incidence of CRC. METHODS: We searched online literature databases including PubMed, Embase, WOS, and Cochrane Library for relevant articles available up to August 2022. With data extracted from observational studies, odds ratios (ORs) with 95% confidence intervals (CIs) were assessed using random-effects models. A funnel plot and Egger's test were used to determine publication bias. Furthermore, subgroup analysis and dose-response analysis were performed. All analyses were conducted using R (version 4.1.3). RESULTS: Twenty-four eligible studies involving 1068158 participants were included in this review. The meta-analysis showed that compared to a low intake, a higher intake of citrus, apples, watermelon, and kiwi reduced the risk of CRC by 9% [OR (95%CI) = 0.91 (0.85-0.97)], 25% [OR (95%CI) = 0.75 (0.66-0.85)], 26% [OR (95%CI) = 0.74 (0.58-0.94)], 13% [OR (95%CI) = 0.87 (0.78-0.96)], respectively. No significant association was observed between the intake of other types of fruit and the risk of CRC. In the dose-response analysis, a nonlinear association was found [R (95%CI) = -0.0031 (-0.0047 to -0.0014)] between citrus intake and CRC risk (P < 0.001), with the risk minimized around 120 g/d (OR = 0.85), while no significant dose-response correlation was observed after continued increase in intake. CONCLUSION: We found that a higher intake of citrus, apples, watermelon, and kiwi was negatively associated with the risk of CRC, while the intake of other types of fruits were not significantly associated with CRC. Citrus intake showed a non-linear dose-response relationship with the risk of CRC. This meta-analysis provides further evidence that a higher intake of specific types of fruit is effective in preventing the occurrence of CRC.

Topology of vibrational modes predicts plastic events in glasses.

The plastic deformation of crystalline materials can be understood by considering their structural defects such as disclinations and dislocations. Although also glasses are solids, their structure resembles closely the one of a liquid and hence the concept of structural defects becomes ill-defined. As a consequence it is very challenging to rationalize on a microscopic level the mechanical properties of glasses close to the yielding point and to relate plastic events to structural properties. Here we investigate the topological characteristics of the eigenvector field of the vibrational excitations of a two-dimensional glass model, notably the geometric arrangement of the topological defects as a function of vibrational frequency. We find that if the system is subjected to a quasistatic shear, the location of the resulting plastic events correlate strongly with the topological defects that have a negative charge. Our results provide thus a direct link between the structure of glasses prior their deformation and the plastic events during deformation.

Analysis of the Influencing Factors of Tumor Volume, Body Immunity, and Poor Prognosis after 125I Particle Therapy for Differentiated Thyroid Cancer.

Objective: To analyze the influencing factors of tumor volume, body immunity, and poor prognosis after 125I particle therapy for differentiated thyroid cancer. Methods: A total of 104 patients with differentiated TC who were treated with 125I particles during January 2020 to January 2021 was picked. These subjects were graded as low-dose group (80Gy-110Gy) and high-dose group (110Gy-140Gy) according to the minimum dose received by 90% of the target volume (D90) after surgery. The tumor volume before and after treatment was compared, and fasting venous blood was collected before and after treatment. The content of thyroglobulin (Tg) was detected by electrochemiluminescence immunoassay. The levels of absolute lymphocyte count (ALC), lymphocytes, neutrophils, and monocytes were detected on automatic blood cell analyzer. The lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ration (PLR) were calculated. The changes in the condition of patients were closely observed, and the occurrence of adverse reactions in the two groups were compared. The risk factors influencing the efficacy of 125I particle therapy for differentiated TC were analyzed through multivariate logistic regression analysis. Results: The total effective rate of patients in the low- and high-dose groups was 78.85% and 82.69%, respectively (P > 0.05). Compared with the pretreatment period, the tumor volume and Tg level in both groups were much lower (P < 0.05), and the differences in tumor volume and Tg level had no statistically significant difference between the two groups before and after treatment (P > 0.05). At 1 week of the treatment, the total incidence of adverse reactions such as nausea, radiation gastritis, radiation parotitis, and neck discomfort was obviously higher in the high-dose group than in the low-dose group (P < 0.05). At 1 month of treatment, the incidence of adverse reactions such as nausea was markedly higher in the high-dose group than in the low-dose group (P < 0.05). After treatment, serum NLR and PLR contents were memorably elevated and LMR level was sharply decreased in both groups, and serum NLR and PLR contents were higher and LMR content was lower in the high-dose group than in the low-dose group (P < 0.05). Multivariate logistic regression analysis showed that the pathological type of follicular adenocarcinoma, tumor size ≥ 2 cm, clinical stage of III~IV, distant metastasis, and high TSH level before 125I particle treatment were all risk factors related to the efficacy of 125I particle treatment of TC (P < 0.05). Conclusion: The efficacy of low-dose and high-dose 125I particles in the treatment of differentiated thyroid cancer is comparable, among which low-dose 125I particles have fewer adverse effects and have less impact on the immunity of the body, which is well tolerated by patients and can be widely used in clinical practice. In addition, the pathological type of follicular adenocarcinoma, tumor size ≥ 2 cm, clinical stage III~IV, distant metastasis, and high TSH level before 125I particle treatment are all risk factors that affect the poor effect of 125I particles on thyroid cancer treatment, and early monitoring of the above index changes can help evaluate the prognosis.

Role of neuronavigation in the surgical management of brainstem gliomas.

Objective: NeuroNavigation (NN) is a widely used intraoperative imaging guidance technique in neurosurgical operations; however, its value in brainstem glioma (BSG) surgery is inadequately reported and lacks objective proof. This study aims to investigate the applicational value of NN in BSG surgery. Method: A retrospective analysis was performed on 155 patients with brainstem gliomas who received craniotomy from May 2019 to January 2022 at Beijing Tiantan Hospital. Eighty-four (54.2%) patients received surgery with NN. Preoperative and postoperative cranial nerve dysfunctions, muscle strength, and Karnofsky (KPS) were evaluated. Patients' radiological features, tumor volume, and extent of resection (EOR) were obtained from conventional MRI data. Patients' follow-up data were also collected. Comparative analyses on these variables were made between the NN group and the non-NN group. Result: The usage of NN is independently related to a higher EOR in diffuse intrinsic pontine glioma (DIPG) (p=0.005) and non-DIPG group (p<0.001). It was observed that fewer patients in the NN group suffered from deterioration of KPS (p=0.032) and cranial nerve function (p=0.017) in non-DIPG group, and deterioration of muscle strength (p=0.040) and cranial nerve function (p=0.038) in DIPG group. Moreover, the usage of NN is an independent protective factor for the deterioration of KPS (p=0.04) and cranial nerve function (p=0.026) in non-DIPG patients and the deterioration of muscle strength (p=0.009) in DIPG patients. Furthermore, higher EOR subgroups were found to be independently related to better prognoses in DIPG patients (p=0.008). Conclusion: NN has significant value in BSG surgery. With the assistance of NN, BSG surgery achieved higher EOR without deteriorating patients' functions. In addition, DIPG patients may benefit from the appropriate increase of EOR.

Defect-engineered Sulfur Vacancy Modified NiCo2 S4-x Nanosheet Anchoring Polysulfide for Improved Lithium Sulfur Batteries.

The low conductivity of sulfur and the shuttle effect of lithium polysulfides (LiPSs) are the two intrinsic obstacles that limit the application of lithium-sulfur batteries (LSBs). Herein, a sulfur vacancy introduced NiCo2 S4 nanosheet array grown on carbon nanofiber (CNF) membrane (NiCo2 S4-x /CNF) is proposed to serve as a self-supporting and binder-free interlayer in LSBs. The conductive CNF skeleton with a non-woven structure can effectively reduce the resistance of the cathode and accommodate volume expansion during charge-discharge process. The bonding between CNF matrix and NiCo2 S4 nanosheet is enhanced by in situ growth, ensuring fast electron transfer. Besides, the sulfur vacancies in NiCo2 S4 enhance the chemisorption of LiPSs, and the highly active sites at vacancies can accelerate the LiPSs conversion kinetics. LSB paired with NiCo2 S4-x /CNF interlayer achieved improved stability in 500 cycles at 0.2 C and long life of 3000 cycles at 3 C. More importantly, a high areal capacity of 9.69 mAh cm-2 is achieved with a sulfur loading of 10.8 mg cm-2 and a low electrolyte to sulfur (E/S) ratio of 4.8. This work provides insight into the sulfur vacancy in catalysis design for LiPSs conversion and demonstrates a promising direction for electronic defect engineering in material design for LSBs.

Characterization of ZmPMP3g function in drought tolerance of maize.

The genes enconding proteins containing plasma membrane proteolipid 3 (PMP3) domain are responsive to abiotic stresses, but their functions in maize drought tolerance remain largely unknown. In this study, the transgenic maize lines overexpressing maize ZmPMP3g gene were featured by enhanced drought tolerance; increases in total root length, activities of superoxide dismutase and catalase, and leaf water content; and decreases in leaf water potential, levels of O2-·and H2O2, and malondialdehyde content under drought. Under treatments with foliar spraying with abscisic acid (ABA), drought tolerance of both transgenic line Y7-1 overexpressing ZmPMP3g and wild type Ye478 was enhanced, of which Y7-1 showed an increased endogenous ABA and decreased endogenous gibberellin (GA) 1 (significantly) and GA3 (very slightly but not significantly) and Ye478 had a relatively lower ABA and no changes in GA1 and GA3. ZmPMP3g overexpression in Y7-1 affected the expression of multiple key transcription factor genes in ABA-dependent and -independent drought signaling pathways. These results indicate that ZmPMP3g overexpression plays a role in maize drought tolerance by harmonizing ABA-GA1-GA3 homeostasis/balance, improving root growth, enhancing antioxidant capacity, maintaining membrane lipid integrity, and regulating intracellular osmotic pressure. A working model on ABA-GA-ZmPMP3g was proposed and discussed.

Identification of ferroptosis-related genes in male mice with sepsis-induced acute lung injury based on transcriptome sequencing.

BACKGROUND: Sepsis can result in acute lung injury (ALI). Studies have shown that pharmacological inhibition of ferroptosis can treat ALI. However, the regulatory mechanisms of ferroptosis in sepsis-induced ALI remain unclear. METHODS: Transcriptome sequencing was performed on lung tissue samples from 10 sepsis-induced mouse models of ALI and 10 control mice. After quality control measures, clean data were used to screen for differentially expressed genes (DEGs) between the groups. The DEGs were then overlapped with ferroptosis-related genes (FRGs) to obtain ferroptosis-related DEGs (FR-DEGs). Subsequently, least absolute shrinkage and selection operator (Lasso) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) were used to obtain key genes. In addition, Ingenuity Pathway Analysis (IPA) was employed to explore the disease, function, and canonical pathways related to the key genes. Gene set enrichment analysis (GSEA) was used to investigate the functions of the key genes, and regulatory miRNAs of key genes were predicted using the NetworkAnalyst and StarBase databases. Finally, the expression of key genes was validated with the GSE165226 and GSE168796 datasets sourced from the Gene Expression Omnibus (GEO) database and using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Thirty-three FR-DEGs were identified between 1843 DEGs and 259 FRGs. Three key genes, Ncf2, Steap3, and Gclc, were identified based on diagnostic models established by the two machine learning methods. They are mainly involved in infection, immunity, and apoptosis, including lymphatic system cell migration and lymphocyte and T cell responses. Additionally, the GSEA suggested that Ncf2 and Steap3 were similarly enriched in mRNA processing, response to peptides, and leukocyte differentiation. Furthermore, a key gene-miRNA network including 2 key genes (Steap3 and Gclc) and 122 miRNAs, and a gene-miRNA network with 1 key gene (Steap3) and 3 miRNAs were constructed using NetworkAnalyst and StarBase, respectively. Both databases predicted that mmu-miR-15a-5p was the target miRNA of Steap3. Finally, Ncf2 expression was validated using both datasets and qRT-PCR, and Steap3 was validated using GSE165226 and qRT-PCR. CONCLUSIONS: This study identified two FR-DEGs (Ncf2 and Steap3) associated with sepsis-induced ALI via transcriptome analyses, as well as their functional and metabolic pathways.

Discovery of bipyridine amide derivatives targeting pRXRα-PLK1 interaction for anticancer therapy.

Retinoid X receptor alpha (RXRα) is an important therapeutic target of cancer. Recently, small molecules (e.g.,XS-060 and its derivatives), which can significantly induce RXRα-dependent mitotic arrest by inhibiting pRXRα-PLK1 interaction, have been demonstrated as excellent anticancer agents. To further obtain novel RXR-targeted antimitotic agents with excellent bioactivity and drug-like properties, we herein synthesized two new series of bipyridine amide derivatives with XS-060 as the lead compound. In the reporter gene assay, most synthesized compounds showed antagonistic activity against RXRα. The most active compound, bipyridine amide B9 (BPA-B9), showed better activity than XS-060, with excellent RXRα-binding affinity (KD = 39.29 ± 1.12 nM) and anti-proliferative activity against MDA-MB-231 (IC50 = 16 nM, SI > 3). Besides, a docking study revealed a proper fitting of BPA-B9 into the coactivator binding site of RXRα, rationalizing its potent antagonistic effect on RXRα transactivation. Further, the mechanism studies revealed that the anticancer activity of BPA-B9 was dependent on its cellular RXRα-targeted mechanism, such as inhibiting pRXRα-PLK1 interaction and inducing RXRα-dependent mitotic arrest. Besides, BPA-B9 displayed better pharmacokinetics than the lead XS-060. Further, animal assays indicated BPA-B9 had significant anticancer efficacy in vivo with no considerable side effects. Together, our study reveals a novel RXRα ligand BPA-B9 targeting the pRXRα-PLK1 interaction, with great potential as a promising anticancer drug candidate for further development.

Isolation of biofluids from tissues using a vacuum-assisted filtration biomedical device.

A biopsy is usually used to remove a piece of tissue from a patient for laboratory testing. The interstitial fluid is taken out at the same time as the tissue sample. Since interstitial fluid flows between cells and capillaries in tissues, similar to blood plasma, it is necessary to separate interstitial fluid from tissues in order to study them separately. Vacuum blood sampling has been used to draw blood into vacuum-sealed tubes, while interstitial fluid can be removed directly from the skin using microneedles with standard pumps. However, no methods are available to separate blood or interstitial fluid from the tissue itself for molecular characterization. In this study, we designed a biomedical device that can separate interstitial fluid from tissue using a vacuum-assisted filtration method. The device has a chamber that collects fluid extracted from the tissue that remains on top of the filter. We characterized the weight change and glycan profiles of tissues before and after vacuum-assisted filtration. The results demonstrate that the biomedical device can remove interstitial fluid and facilitate the analysis of tissue-specific molecules while minimizing information from the interstitial fluid.

Carbonic Anhydrase-Embedded Hydrogen-Bonded Organic Frameworks Coating for Facilitated Offshore CO2 Fixation.

Exhausted emission of carbon dioxide (CO2 ) from ships or offshore platforms has become one of the major contributors to global carbon emissions. Enzymes such as carbonic anhydrase (CA) have been widely used for CO2 mineralization because of their high catalytic rate. However, CA in seawater is easy to inactivate and difficult to reuse. Immobilization would be a feasible solution to address the stability issue, which, however, may cause an increase of internal diffusion resistance and reduced catalytic activity. In this regard, design of high-performance biocatalysts for acquiring high catalytic activity and stability of CA is highly desirable. Herein, a monolithic catalyst of Filler-CA@Lys-HOF-1 (FCLH) was prepared by chemical sorption of CA on the surface of the Filler followed by the coating of Lys-HOF-1. The highest catalytic activity of FCLH was obtained by regulating the amount of HOF-1 monomer added. Due to the protection of Lys-HOF-1, the FCLH showed good tolerance against acidity and salinity, which could retain about 80.2 % of the original activity after 9 h incubation in simulated seawater. The catalytic activity of FCLH could retain 85.4 % of the initial activity after 10 cycles. Hopefully, our study can provide a promising biocatalyst for CO2 mineralization, which may drive down carbon emissions when used for CO2 capture and conversion on offshore platforms.

Prognostic factors and Doxorubicin involved in malignant progression of meningioma.

Meningioma was the most primary intracranial tumor, but the molecular characteristics and the treatment of malignant meningioma were still unclear. Nine malignant progression-related genes based prognostic signatures were identified by transcriptome analysis between benign meningioma and malignant meningioma. The external dataset GEO136661 and quantitative Real-time Polymerase Chain Reaction were used to verify the prognostic factors. has-miR-3605-5p, hsa-miR-664b-5p, PNRC2, BTBD8, EXTL2, SLFN13, DGKD, NSD2, and BVES were closed with malignant progression. Moreover, Doxorubicin was identified by Connectivity Map website with the differential malignant progression-related genes. CCK-8 assay, Edu assay, wound healing assay, and trans-well experiment were used to reveal that Doxorubicin could inhibit proliferation, migration and invasion of IOMM-Lee Cells.

Unlocking Enhanced Capacitive Deionization of NaTi2(PO4)3/Carbon Materials by the Yolk-Shell Design.

The low salt adsorption capacities (SACs) of benchmark carbon materials (usually below 20 mg g-1) are one of the most challenging issues limiting further commercial development of capacitive deionization (CDI), an energetically favorable method for sustainable water desalination. Sodium superionic conductor (NASICON)-structured NaTi2(PO4)3 (NTP) materials, especially used in combination with carbon to prepare NTP/C materials, provide emerging options for higher CDI performance but face the problems of poor cycling stability and dissolution of active materials. In this study, we report the development of the yolk-shell nanoarchitecture of NASICON-structured NTP/C materials (denoted as ys-NTP@C) using a metal-organic framework@covalent organic polymer (MOF@COP) as a sacrificial template and space-confined nanoreactor. As expected, ys-NTP@C exhibits good CDI performance, including exemplary SACs with a maximum SAC of 124.72 mg g-1 at 1.8 V in the constant-voltage mode and 202.76 mg g-1 at 100 mA g-1 in the constant-current mode, and good cycling stability without obvious performance degradation or energy consumption increase over 100 cycles. Furthermore, X-ray diffraction used to study CDI cycling clearly exhibits the good structural stability of ys-NTP@C during repeated ion intercalation/deintercalation processes, and the finite element simulation shows why yolk-shell nanostructures exhibit better performance than other materials. This study provides a new synthetic paradigm for preparing yolk-shell structured materials from MOF@COP and highlights the potential use of yolk-shell nanoarchitectures for electrochemical desalination.

Effect of lentinan on gelling properties and structural changes of goose myofibrillar protein under oxidative stress.

BACKGROUND: The reduction of protein oxidation is important for maintaining the product quality of reconstituted meat. In this study, the dose-dependent effects of lentinan (LNT) on gelling properties and chemical changes in oxidatively stressed goose myofibrillar protein were investigated. RESULTS: Myofibrillar protein (MP) with 200 µmol g-1 protein LNT increased gel strength by 87.90 ± 9.26% in comparison with LNT-free myofibrillar protein after oxidation. Scanning electron microscopy analysis revealed that the gel network containing LNT was compact, with small pores and uniform distribution. The absolute value of the zeta potential reduced significantly following oxidation of LNT with 200 µmol g-1 protein at 4 °C for 12 h compared with the zeta potential without LNT, according to the laser particle size analyzer. The incorporation of LNT increased protein solubility and -SH content, inhibited carbonyl formation, enhanced α-helix content and tryptophan intrinsic fluorescence intensity, and reduced exposure of hydrophobic groups and protein aggregation. CONCLUSION: The results indicated that adding LNT to myofibrillar protein could improve gel. This is related to its protective effect on conformational changes in the oxidation system. Lentinan is therefore recommended for oxidatively stressed goose meat processing to enhance the MP gelling potential. © 2023 Society of Chemical Industry.

Endogenous Protease-Activatable Nanosensor Based on PNA-Peptide-DNA Engineering for AND-Gated and Dual-Model Detection of MicroRNA in Single Living Tumor Cells.

The in situ detection of low-content cancer biomarkers by an endogenous activator instead of an exogenous initiator in vitro remains a great challenge, leaving a gap in the development of a tumor-specific nanosensor with an endogenous protease-activatable manner. Herein, we proposed an endogenous protease-activatable nanosensor (PA-NS) guided by peptide nucleic acid-peptide-DNA copolymers to realize AND-gated and dual-model sensing of miRNA-21 (miR-21) by combining electrochemical detection with optical imaging in living tumor cells, without an additional introduction of an exogenous activator or nanomaterials. Moreover, the PA-NS can only be activated by "dual keys" (overexpressed miR-21 and cathepsin B protease in tumor cells) simultaneously, which enables effective improvement of the tumor-to-healthy cells ratio. The fluorescence intensity measured in single tumor cells was ∼3.5-fold higher than that in single healthy cells, and the electrochemical response decreased ∼30% in the presence of target miRNA. Furthermore, studies on regulation of the protease activity and miR-21 fluctuation under external stimulation have contributed to our understanding of the biological processes and drug screenings underlying disease development. This specific endogenous protease-mediated manner for dual-model detection of miRNA guarantees excellent tumor-selective capability, which offers new opportunities to study cell heterogeneity and provides more reliable fundamentals for the diagnosis and treatment of cancer down to the single-cell level.

Enhanced Single-Particle Collision Electrochemistry at Polysulfide-Functionalized Microelectrodes for SARS-CoV-2 Detection.

Single-particle collision electrochemistry (SPCE) has shown great promise in biosensing applications due to its high sensitivity, high flux, and fast response. However, a low effective collision frequency and a large number of interfering substances in complex matrices limit its broad application in clinical samples. Herein, a novel and universal SPCE biosensor was proposed to realize sensitive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on the collision and oxidation of single silver nanoparticles (Ag NPs) on polysulfide-functionalized gold ultramicroelectrodes (Ps-Au UMEs). Taking advantage of the strong interaction of the Ag-S bond, collision and oxidation of Ag NPs on the Ps-Au UME surface could be greatly promoted to generate enhanced Faraday currents. Compared with bare Au UMEs, the collision frequency of Ps-Au UMEs was increased by 15-fold, which vastly improved the detection sensitivity and practicability of SPCE in biosensing. By combining magnetic separation, liposome encapsulation release, and DNAzyme-assisted signal amplification, the SPCE biosensor provided a dynamic range of 5 orders of magnitude for spike proteins with a detection limit of 6.78 fg/mL and a detection limit of 21 TCID50/mL for SARS-CoV-2. Furthermore, SARS-CoV-2 detection in nasopharyngeal swab samples of infected patients was successfully conducted, indicating the potential of the SPCE biosensor for use in clinically relevant diagnosis.

Privacy preserving federated learning for full heterogeneity.

Federated learning is a novel distribute machine learning paradigm to support cooperative model training among multiple participant clients, where each client keeps its private data locally to protect its data privacy. However, in practical application domains, Federated learning still meets several heterogeneous challenges such data heterogeneity, model heterogeneity, and computation heterogeneity, significantly decreasing its global model performance. To the best of our knowledge, existing solutions only focus on one or two challenges in their heterogeneous settings. In this paper, to address the above challenges simultaneously, we present a novel solution called Full Heterogeneous Federated Learning (FHFL). Firstly, we propose a synthetic data generation approach to mitigate the Non-IID data heterogeneity problem. Secondly, we use knowledge distillation to learn from heterogeneous models of participant clients for model aggregation in the central server. Finally, we produce an opportunistic computation schedule strategy to exploit the idle computation resources for fast-computing clients. Experiment results on different datasets show that our FHFL method can achieve an excellent model training performance. We believe it will serve as a pioneer work for distributed model training among heterogeneous clients in Federated learning.