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After entering host cells by endocytosis, influenza A virus (IAV) is transported along microfilaments and then transported by dynein along microtubules (MTs) to the perinuclear region for genome release. Understanding the mechanisms of dynein-driven transport is significant for a comprehensive understanding of IAV infection. In this work, the roles of dynactin in dynein-driven transport of IAV were quantitatively dissected in situusing quantum dot-based single-virus tracking. It was revealed that dynactin was essential for dynein to transport IAV toward the nucleus. After virus entry, virus-carrying vesicles bound to dynein and dynactin before being delivered to MTs. The attachment of dynein to the vesicles was dependent on dynactin and its subunits, p150Gluedand Arp1. Once viruses reached MTs, dynactin-assisted dynein initiates retrograde transport of IAV. Importantly, the retrograde transport of viruses could be initiated at both plus ends (32%) and other regions on MTs (68%). Subsequently, dynactin accompanied and assisted dynein to persistently transport the virus along MTs in the retrograde direction. This study revealed the dynactin-dependent dynein-driven transport process of IAV, enhancing our understanding of IAV infection and providing important insights into the cell’s endocytic transport mechanism.

Cisplatin is a widely used drug for the clinical treatment of tumors. However, nephrotoxicity limits its widespread use. A series of compounds including eight analogs (G3-G10) and 40 simplifiers (G11-G50) were synthesized based on the total synthesis of Psiguamer A and B, which were novel meroterpenoids with unusual skeletons from the leaves of Psidium guajava. Among these compounds, (d)-G8showed the strongest protective effect on cisplatin-induced acute kidney injury (AKI) in vitroand vivo, and slightly enhanced the antitumor efficacy of cisplatin. A mechanistic study showed that (d)-G8promoted the efflux of cisplatin viaupregulating the copper transporting efflux proteins ATP7A and ATP7B. It enhanced autophagy through the activation of the adenosine monophosphate–activated protein kinase (AMPK) signaling pathway. (d)-G8showed no acute toxicity or apparent pathological damage in the healthy mice at a single dose of 1 g/kg. This study provides a promising lead against cisplatin-induced AKI.

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. Inadequate understanding of the ovulation drivers hinders PCOS intervention. Herein, we report that follicle stimulating hormone (FSH) controls follicular fluid (FF) glutamine levels to determine ovulation. Murine ovulation starts from FF-exposing granulosa cell (GC) apoptosis. FF glutamine, which decreases in pre-ovulation porcine FF, elevates in PCOS patients FF. High-glutamine chow to elevate FF glutamine inhibits mouse GC apoptosis and induces hormonal, metabolic, and morphologic PCOS traits. Mechanistically, follicle-development-driving FSH promotes GC glutamine synthesis to elevate FF glutamine, which maintain follicle wall integrity by inhibiting GC apoptosis through inactivating ASK1-JNK apoptotic pathway. FSH and glutamine inhibit the rapture of cultured murine follicles. Glutamine removal or ASK1-JNK pathway activation with metformin or AT-101 reversed PCOS traits in PCOS models that are induced with either glutamine or EsR1-KO. These suggest that glutamine, FSH, and ASK1-JNK pathway are targetable to alleviate PCOS.

Petroleum-based plastics have been associated with several environmental issues, including land and water pollution, greenhouse gas emissions, and waste accumulation due to their non-biodegradable properties. Bioplastics derived from renewable natural resources have emerged as an eco-friendly substitute for conventional plastics, leading to a reduced carbon footprint and conservation of non-renewable fossil fuels. Seaweed is an attractive material for bioplastic production due to its abundant polysaccharide content, high biomass, rapid growth rate and suitability for consumption. This work aimed to explore the feasibility of producing seaweed bioplastics, specifically starch and carrageenan from Kappaphycus alvarezii, along with chitin extracted from ramshorn snails (Planorbarius corneus). The surface morphology of the bioplastics was assessed through scanning electron microscopy (SEM), and their biodegradability was also examined through a soil burial biodegradation test. Starch-based bioplastics incorporated with carrageenan and chitin exhibited a more substantial network structure, rougher surface texture and smaller void sizes with improved mechanical strength and water barrier properties. The bioplastics underwent decomposition, resulting in fragmentation into small pieces (with more than 76% weight loss) or complete degradation through the enzymatic activity of Acinetobacterspp. and Burkholderia cepacia. Therefore, seaweed-chitin-based bioplastics demonstrate their potential as a sustainable and environmentally friendly alternative to conventional plastics.

Background: Shikonin, a purified naphthoquinone separated from a Traditional Chinese medicinal herb Lithospermum erythrorhixon, which exhibits anticancer properties.Objectives: To clarify the molecular mechanisms of therapeutic effects of shikonin against osteosarcoma.Materials and Methods: Cell Counting Kit-8 (CCK-8) assay was employed to evaluate cell viability. Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) double-staining was conducted to evaluate the apoptotic ratio of the MG-63 cells. The effects of shikonin on the invasiveness of osteosarcoma cells were implemented by a transwell cell migration assay. In the meantime, a western blot assay was employed to detect alterations in the relevant mechanism proteins within osteosarcoma cells. Molecular docking analysis was conducted to anticipate the binding interaction between shikonin and EGFR/protein kinase B (AKT)/mTOR.Results: We observed that shikonin suppressed proliferation and induced apoptosis in the MG-63 cells in a dose-dependent manner. Pursuing these findings, the potential molecular mechanisms were detected. Shikonin intervention blocked epidermal growth factor receptor (EGFR) phosphorylation and decreased epidermal growth factor (EGF)-induced activation of downstream signaling molecules, such as AKT and mammalian target of rapamycin (mTOR) in the MG-63 cells. However, the additional recombinant human epidermal growth factor (rHuEGF) could stimulate the activation of EGFR/AKT/mTOR signaling and reverse cell apoptosis caused by shikonin. Molecular docking analysis showed that shikonin presented the highest bonding ability with EGFR, AKT, and mTOR.Conclusion: Our results show that shikonin inhibits human osteosarcoma development via inactivating EGFR/AKT/mTOR signaling. It demonstrates that shikonin may act as a potential therapeutic agent in osteosarcoma treatment.

Accurate classification of tumor cells is of importance for cancer diagnosis and further therapy. In this study, we develop multimolecular marker-activated transmembrane DNA computing systems (MTD). Employing the cell membrane as a native gate, the MTD system enables direct signal output following simple spatial events of “transmembrane” and “in-cell target encounter”, bypassing the need of multistep signal conversion. The MTD system comprises two intelligent nanorobots capable of independently sensing three molecular markers (MUC1, EpCAM, and miR-21), resulting in comprehensive analysis. Our AND–AND logic-gated system (MTDAND–AND) demonstrates exceptional specificity, allowing targeted release of drug–DNA specifically in MCF-7 cells. Furthermore, the transformed OR–AND logic-gated system (MTDOR–AND) exhibits broader adaptability, facilitating the release of drug–DNA in three positive cancer cell lines (MCF-7, HeLa, and HepG2). Importantly, MTDAND–ANDand MTDOR–AND, while possessing distinct personalized therapeutic potential, share the ability of outputting three imaging signals without any intermediate conversion steps. This feature ensures precise classification cross diverse cells (MCF-7, HeLa, HepG2, and MCF-10A), even in mixed populations. This study provides a straightforward yet effective solution to augment the versatility and precision of DNA computing systems, advancing their potential applications in biomedical diagnostic and therapeutic research.

Single particle collision is an important tool for size analysis at the individual particle level; however, due to complex dynamic behaviors of nanoparticles on the surface of an electrode, the accuracy of size discrimination is limited. A silver (Ag) nanoparticle (NP) was chosen as the research target, and the dynamic behavior of Ag NPs was simplified by enhancing adsorption between Ag NP and Au ultramicroelectrode (UME) in alkaline media. Immediately after, accurate dynamic and thermodynamic information on single Ag NP was accurately extracted from collision events, including current intensity, transferred charge, and duration time. On the basis that there were differences between parameters of different-sized Ag NPs, multiparameter size discrimination was proposed, which improved the accuracy compared to single-parameter discrimination. More intriguingly, multiparameter analysis was combined with artificial intelligence, a tool adept at processing multidimensional data, for the first time. Finally, artificial intelligence-assisted multiparameter size discrimination was successfully used to intelligently distinguish mixed Ag NPs, with an optimal accuracy of more than 95%. To sum up, the artificial intelligence-assisted multiparameter method showed an excellent ability to quickly achieve the most accurate size discrimination of nanoparticles at the level of individual particle and provide an effective guidance for the application of nanoparticles.

Recent investigations have shown that the necroptosis of tissue cells in joints is important in the development of osteoarthritis (OA). This study aimed to investigate the potential effects of exogenous skeletal stem cells (SSCs) on the necroptosis of subchondral osteoblasts in OA. Human SSCs and subchondral osteoblasts isolated from human tibia plateaus were used for Western blotting, real-time PCR, RNA sequencing, gene editing, and necroptosis detection assays. In addition, the rat anterior cruciate ligament transection OA model was used to evaluate the effects of SSCs on osteoblast necroptosis in vivo. The micro-CT and pathological data showed that intra-articular injections of SSCs significantly improved the microarchitecture of subchondral trabecular bones in OA rats. Additionally, SSCs inhibited the necroptosis of subchondral osteoblasts in OA rats and necroptotic cell models. The results of bulk RNA sequencing of SSCs stimulated or not by tumor necrosis factor α suggested a correlation of SSCs-derived tumor necrosis factor α-induced protein 3 (TNFAIP3) and cell necroptosis. Furthermore, TNFAIP3-derived from SSCs contributed to the inhibition of the subchondral osteoblast necroptosis in vivo and in vitro. Moreover, the intra-articular injections of TNFAIP3-overexpressing SSCs further improved the subchondral trabecular bone remodeling of OA rats. Thus, we report that TNFAIP3 from SSCs contributed to the suppression of the subchondral osteoblast necroptosis, which suggests that necroptotic subchondral osteoblasts in joints may be possible targets to treat OA by stem cell therapy.Graphical Abstract

Skeletal stem cells (SSC) have gained attentions as candidates for the treatment of osteoarthritis due to their osteochondrogenic capacity. However, the immunomodulatory properties of SSC, especially under delivery operations, have been largely ignored. In the study, we found that Pdpn+and Grem1+SSC subpopulations owned immunoregulatory potential, and the single-cell RNA sequencing (scRNA-seq) data suggested that the mechanical activation of microgel carriers on SSC induced the generation of Pdpn+Grem1+Ptgs2+SSC subpopulation, which was potent at suppressing macrophage inflammation. The microgel carriers promoted the YAP nuclear translocation, and the activated YAP protein was necessary for the increased expression of Ptgs2 and PGE2in microgels-delivered SSC, which further suppressed the expression of TNF-ɑ, IL-1β and promoted the expression of IL-10 in macrophages. SSC delivered with microgels yielded better preventive effects on articular lesions and macrophage activation in osteoarthritic rats than SSC without microgels. Chemically blocking the YAP and Ptgs2 in microgels-delivered SSC partially abolished the enhanced protection on articular tissues and suppression on osteoarthritic macrophages. Moreover, microgel carriers significantly prolonged SSC retention time in vivowithout increasing SSC implanting into osteoarthritic joints. Together, our study demonstrated that microgel carriers enhanced SSC reprogramming towards immunomodulatory phenotype to regulate macrophage phenotype transformation for effectively osteoarthritic therapy by promoting YAP protein translocation into nucleus. The study not only complement and perfect the immunological mechanisms of SSC-based therapy at the single-cell level, but also provide new insight for microgel carriers in stem cell-based therapy.

Liquid biopsy is of great significance in tumor early diagnosis and treatment stratification. PD-L1-positive small extracellular vesicles (PD-L1+sEVs) are closely related to tumor growth and immunotherapy response, which are considered valuable liquid biopsy biomarkers. In contrast to conventional in vitrodetection, in vivodetection has the ability to improve the detection efficiency and enable continuous or real-time dynamic monitoring. However, in vivodetection of PD-L1+sEVs has multiple difficulties, such as high cell background, complex blood environments, and lack of a specific and stable detection method. Herein, the in vivodetection of PD-L1+sEVs method was constructed, which efficiently separated sEVs based on the microfluidic device and quantitatively analyzed PD-L1+sEVs by aptamer recognition and hybridization chain reaction. The concentration of PD-L1+sEVs was continuously monitored, and significant differences at different stages of tumor as well as a correlation with tumor volume were found. Diseased and healthy individuals could also be effectively distinguished based on the concentration of PD-L1+sEVs. The method with good stability, biocompatibility, and detection performance provided a powerful means for in vivodetection of PD-L1+sEVs, contributing to the clinical diagnosis and treatment of tumor.

Optical pressure sensors have the advantage of being impervious to electromagnetic interference. However, it remains difficult to explore the quantitative relationship between the optical response and the exerted applied pressure. Here, for the first time, the quantitative relationship between the deformation of optical resonator and the applied pressure and the optical response characteristics of the structure are investigated in detail by finite element method, and an ultracompact optical pressure sensor with a high sensitivity ~10.2 nm/MPa is demonstrated. Simulation results show that the maximum deformation of the optical resonator is linearly related to the applied pressure and has a limit value at a fixed input pressure as the range of pressure applied increases. The results also imply that the external force can induce a redshift in the resonance wavelength in addition to generating intriguing phenomena like Fano resonance. These observations contribute to the enhancement and diversification of the optical response within the system. The special features of our suggested structure are applicable in optical property change detection under different pressures, chemical high-pressure experimental measurement, and study of chemical reaction kinetics process.

Tetrabromobisphenol A (TBBPA), a widely used brominated flame retardant in electronics manufacturing, has caused global contamination due to improper e-waste disposal. Its persistence, bioaccumulation, and potential carcinogenicity drive studies of its transformation and underlying (a)biotic interactions. This study achieved an anaerobic enrichment culture capable of reductively dehalogenating TBBPA to the more bioavailable bisphenol A. 16S rRNA gene amplicon sequencing and quantitative PCR confirmed that successive dehalogenation of four bromide ions from TBBPA was coupled with the growth of both Dehalobactersp. and Dehalococcoidessp. with growth yields of 5.0 ± 0.4 × 108and 8.6 ± 4.6 × 108cells per μmol Br–released (N= 3), respectively. TBBPA dehalogenation was facilitated by solid humin and reduced humin, which possessed the highest organic radical signal intensity and reducing groups −NH2, and maintained the highest dehalogenation rate and dehalogenator copies. Genome-centric metatranscriptomic analyses revealed upregulated putative TBBPA-dehalogenating rdhA(reductive dehalogenase) genes with humin amendment, cprA-like Dhb_rdhA1gene in Dehalobacterspecies, and Dhc_rdhA1/Dhc_rdhA2genes in Dehalococcoidesspecies. The upregulated genes of lactate fermentation, de novocorrinoid biosynthesis, and extracellular electron transport in the humin amended treatment also stimulated TBBPA dehalogenation. This study provided a comprehensive understanding of humin-facilitated organohalide respiration.

Metabolic disorders of cancer cells create opportunities for metabolic interventions aimed at selectively eliminating cancer cells. Nevertheless, achieving this goal is challenging due to cellular plasticity and metabolic heterogeneity of cancer cells. This study presents a dual-drug-loaded, macrophage membrane-coated polymeric nanovesicle designed to reprogram cancer metabolism with high specificity through integrated extracellular and intracellular interventions. This nanoformulation can target cancer cells and largely reduce their glucose intake, while the fate of intracellular glucose internalized otherwise is redirected at the specially introduced oxidation reaction instead of inherent cancer glycolysis. Meanwhile, it inhibits cellular citrate intake, further reinforcing metabolic intervention. Furthermore, the nanoformulation causes not only H2O2production, but also NADPH down-regulation, intensifying redox damage to cancer cells. Consequently, this nanoformulation displays highly selective toxicity to cancer cells and minimal harm to normal cells mainly due to metabolic vulnerability of the former. Once administered into tumor-bearing mice, this nanoformulation is found to induce the transformation of pro-tumor tumor associated macrophages into the tumor-suppressive phenotype and completely inhibit tumor growth with favourable biosafety.

Background: Although quercetin exhibits promising anti-tumor properties, its clinical application is limited due to inherent defects and a lack of tumor targeting.Objectives: This study aimed to prepare and characterize active targeting folate-chitosan modified quercetin liposomes (FA-CS-QUE-Lip), and its antitumor activity in vitroand in vivowas also studied.Materials and Methods: Box-Behnken Design (BBD) response surface method was used to select the optimal formulation of quercetin liposomes (QUE-LP). On this basis, FA-CS-QUE-LP was obtained by connecting folic acid chitosan complex (FA-CS) and QUE-LP. The release characteristics in vitroof QUE-LP and FA-CS-QUE-LP were studied. Its inhibitory effects on HepG2 cells were studied by the MTT method. The pharmacokinetics and pharmacodynamics in vivo were studied in healthy Wistar mice and S180 tumor-bearing mice, respectively.Results: The average particle size, zeta potential and encapsulation efficiency of FA-CS-QUELP were 261.6 ± 8.5 nm, 22.3 ± 1.7 mV, and 98.63 ± 1.28 %, respectively. FA-CS-QUE-LP had a sustained release effect and conformed to the Maloid-Banakar release model (R2=0.9967). The results showed that FA-CS-QUE-LP had higher inhibition rates on HepG2 cells than QUE-Sol (P < 0.01). There was a significant difference in AUC, t1/2, CL and other pharmacokinetic parameters among QUE-LP, FA-CS-QUE-LP, and QUE-Sol (P < 0.05). In in vivoantitumor activity study, the weight inhibition rate and volume inhibition rate of FA-CS-QUE-LP were 30.26% and 37.35%, respectively.Conclusion: FA-CS-QUE-LP exhibited a significant inhibitory effect on HepG2 cells, influenced the pharmacokinetics of quercetin in mice, and demonstrated a certain inhibitory effect on S180 tumor-bearing mice, thus offering novel avenues for cancer treatment.

In recent years, the cargo profiles of extracellular vesicles (EVs), which were inherited from their parent cells, have emerged as a reliable biomarker for liquid biopsy (LB) in disease diagnosis, prognosis, and treatment monitoring. EVs secreted by different cells exhibit distinct characteristics, particularly in terms of disease diagnosis and prediction. However, currently available techniques for the quantitative analysis of EV cargoes, including enzyme-linked immunosorbent assay (ELISA), cannot specifically identify the cellular origin of EVs, thus seriously affecting the accuracy of EV-based liquid biopsy. In light of this, we here developed ultrabright fluorescent nanosphere (FNs)-based test strips which have the unique capability to specifically assess the levels of PD-L1-positive EVs (PD-L1+EVs) derived from both tumor cells and immune cells in bodily fluids. The levels of PD-L1+EV subpopulations in human saliva were quantified using the ultrabright fluorescent nanosphere-based test strips with more convenience and higher efficiency (detection time <30 min). Results demonstrated that the fluorescence intensity of the test line exhibited a good linear relationship respectively with the PD-L1 levels of tumor cell- (R2= 0.993) and immune cell-derived EVs (R2= 0.982) in human saliva. By assessing the levels of PD-L1+EV subpopulations, our test strips hold immense potential for advancing the application of PD-L1+EV subpopulation-based predictions in tumor diagnosis and prognosis evaluation. In summary, by integrating the benefits of FNs and lateral flow chromatography, we here provide a strategy to accurately measure the cargo levels of EVs originating from diverse cell sources in bodily fluids.

Different volume fractions of nanocrystals were induced in Metglas (FeSiB) of magnetoelectric (ME) antennas by isothermal heat treatment. When the volume fraction is 3.3%, the initial permeability and maximum piezomagnetic coefficient of the Metglas increase by 46% and 68%, respectively, compared with the pristine Metglas. The ME coupling coefficient ( $\alpha _{\text {ME}}$ ) of ME antenna at the resonance frequency and 1 kHz is 19890 and 1455 V/cm $\cdot $ Oe, respectively (216% and 197% higher than that of the pristine antenna). The ME antenna shows both enhanced reception and transmission performance. The direct detection limit is 0.3 pT [one order better than the pristine antenna (3.2 pT)]. The transmitting intensity at 30 cm in the long axis direction is enhanced by 148%. This result shows that the optimal volume fraction of nanocrystals in magnetic layers is essential for the performance of ME antennas and ME devices.

This study focuses on the design and optimization of surface acoustic wave (SAW) magnetic field sensors. We designed and fabricated a SAW standing wave magnetic sensor, successfully enhancing its sensitivity by exploiting both the equivalent acoustic velocity variation induced by the $\Delta {G}$ effect of magnetostrictive materials and the concentration effect of acoustic energy. The experimental results reveal a linear enhancement in sensor sensitivity correlated with the increasing input voltage, peaking at 0.67 mV/Oe under a 1 V input. This design breakthrough introduces novel possibilities for magnetic field detection technology, providing fresh insights and design pathways for the advancement of high-sensitivity magnetic field sensors.

To research the dynamics of the cavitation bubble under the interaction of particle clusters, the bubble morphological evolutionary characteristics near three equal-sized spherical particles are theoretically explored in the present study based on the Weiss theorem and the velocity potential superposition theory. The three particles are arranged symmetrically, and the fluid velocity field near the three particles and the cavitation bubble is obtained. Moreover, the effects of the bubble-particle distance and the maximum radius of the cavitation bubble on the fluid velocity are investigated, and the contribution mechanisms of the fluid velocity field constituents are compared. The analysis has found that: (1) The fluid velocity between the bubble and the particle is lower than that at the other locations in both the growth and collapse phases, thus the bubble cannot always maintain a standard spherical shape. (2) The bubble-particle distance and the maximum radius of the cavitation bubble are the key parameters affecting the circumferential inhomogeneity of the radial velocity of the fluid around the bubble. The larger the maximum radius or the smaller the bubble-particle distance is, the more visible the non-circularity of the bubble morphology. (3) The image bubbles and the linear sinks contribute oppositely to the fluid velocity field, and the presence of the image bubble reduces the fluid velocity. In the low velocity region, the image bubble is the main mechanism contributing to the effect of the particle on the fluid velocity.

Preclinical and clinical studies have demonstrated the synergistic effect of microtubule-targeting agents in combination with Janus kinase 2 (JAK2) inhibitors, prompting the development of single agents with enhanced therapeutic efficacy by dually inhibiting tubulin polymerization and JAK2. Herein, we designed and synthesized a series of substituted 2-amino[1,2,4]triazolopyrimidines and related heterocycles as dual inhibitors for tubulin polymerization and JAK2. Most of these compounds exhibited potent antiproliferative activity against the selected cancer cells, with compound 7gbeing the most active. This compound effectively inhibits both tubulin assembly and JAK2 activity. Furthermore, phosphorylated compound 7g(i.e., compound 7g–P) could efficiently convert to compound 7gin vivo. Compound 7g, whether it was administered directly or in the form of a phosphorylated prodrug (i.e., compound 7g–P), significantly inhibited the growth of A549 xenografts in nude mice. The present findings strongly suggest that compound 7grepresents a promising chemotherapeutic agent with high antitumor efficacy.

The building of practical biosensors that have anti-interference abilities against biofouling of nonspecific proteins and biooxidation of reducing agents in actual biological matrixes remains a great challenge. Herein, a robust photoelectrochemical (PEC) biosensor capable of accurate detection in human serum was pioneered through the integration of a new engineered branching peptide (EBP) into a synergetic dual-photoelectrode system. The synergetic dual-photoelectrode system involved the tandem connection of a C3N4/TiO2photoanode and a AuPt/PANI photocathode, while the EBP as a dual-functional antifouling and recognition probe featured an inverted Y-shaped configuration with one recognition backbone and two antifouling branches. Such an EBP enables a simple procedure for electrode modification and an enhanced antifouling nature compared to a regular linear peptide (LP), as theoretically supported by the results from molecular dynamics simulations. The as-developed PEC biosensor had a higher photocurrent response and a good antioxidation property inherited from the photoanode and photocathode, respectively. Targeting the model protein biomarker of cardiac troponin I (cTnI), this biosensor achieved good performances in terms of high sensitivity, specificity, and anti-interference.

Skeletal stem/progenitor cells (SSPCs) are tissue-specific stem/progenitor cells localized within skeletons and contribute to bone development, homeostasis, and regeneration. However, the heterogeneity of SSPC populations in mouse long bones and their respective regenerative capacity remain to be further clarified. In this study, we perform integrated analysis using single-cell RNA sequencing (scRNA-seq) datasets of mouse hindlimb buds, postnatal long bones, and fractured long bones. Our analyses reveal the heterogeneity of osteochondrogenic lineage cells and recapitulate the developmental trajectories during mouse long bone growth. In addition, we identify a novel Cd168+SSPC population with highly replicating capacity and osteochondrogenic potential in embryonic and postnatal long bones. Moreover, the Cd168+SSPCs can contribute to newly formed skeletal tissues during fracture healing. Furthermore, the results of multicolor immunofluorescence show that Cd168+SSPCs reside in the superficial zone of articular cartilage as well as in growth plates of postnatal mouse long bones. In summary, we identify a novel Cd168+SSPC population with regenerative potential in mouse long bones, which adds to the knowledge of the tissue-specific stem cells in skeletons.

Improved markers for predicting recurrence are needed to stratify patients with localised (stage I–III) renal cell carcinoma after surgery for selection of adjuvant therapy. We developed a novel assay integrating three modalities—clinical, genomic, and histopathological—to improve the predictive accuracy for localised renal cell carcinoma recurrence.

CRISPR/Cas12a has been believed to be powerful in molecular detection and diagnostics due to its amplified trans-cleavage feature. However, the activating specificity and multiple activation mechanisms of the Cas12a system are yet to be elucidated fully. Herein, a “synergistic activator effect” is discovered, which supports an activation mechanism that a synergistic incorporation of two short ssDNA activators can promote the trans-cleavage of CRISPR/Cas12a, while either of them is too short to work independently. As a proof-of-concept example, the synergistic activator-triggered CRISPR/Cas12a system has been successfully harnessed in the AND logic operation and the discrimination of single-nucleotide variants, requiring no signal conversion elements or other amplified enzymes. Moreover, a single-nucleotide specificity has been achieved for the detection of single-nucleotide variants by pre-introducing a synthetic mismatch between crRNA and the “helper” activator. The finding of “synergistic activator effect” not only provides deeper insight into CRISPR/Cas12a but also may facilitate its expanded application and power the exploration of the undiscovered properties of other CRISPR/Cas systems.

Liquid biopsy technology involves taking samples from body fluids in a minimally invasive way and analyzing tumor markers to achieve early diagnosis and efficacy evaluation of tumors. The development of real-time cancer diagnosis and treatment strategies based on liquid biopsy technology is of great significance to cancer management. This paper described an extracorporeal circulation based on a three-dimensional (3D) magnetic chip (3DMC-system) for in vivo detection and real-time monitoring of circulating tumor cells (CTCs). Utilizing biofunctionalized magnetic nanospheres (MNs) with CTC recognition function, this 3DMC-system could effectively achieve the real-time monitoring of CTCs in vivo with good stability and strong anti-interference. Compared with in vitro CTC detection, in vivo detection could not only detect more CTCs but also detect the presence of CTCs in the blood at an early stage of the tumor, when tumor metastasis is not observed in imaging. In addition, due to the flexibility of the chip design, the system can easily add a treatment module to integrate cancer diagnosis and treatment together. With good biocompatibility and high stability, this 3DMC-system is expected to provide a new personalized medical program for cancer patients.

Extracellular vesicles (EVs), acting as important mediators of intercellular communication, play an essential role in physiological processes, which have unique potential in the medical field. However, the heterogeneity of EVs limits their development for disease diagnosis and therapy, making the EV subpopulation analysis extremely valuable. In this article, a simple microfluidic approach was presented for the on-chip specific isolation and detection of two phenotypes of EVs (Annexin V+EGFR+EVs and Annexin V–EGFR+EVs) based on different biomolecule-modified magnetic nanospheres and a fluorescence labeling technique. Combined with the control of the magnetic field in the microzone and fluid flow, it was easy to form two separate functional regions in the chip to capture different EV subpopulations. This method was successfully applied to the tests of clinical saliva samples in 75 oral squamous cell carcinoma (OSCC) patients and 10 healthy people. The results showed that the total level of EGFR+EVs was much higher in OSCC patients that in healthy people. Meantime, the ratio of Annexin V+EGFR+EVs to Annexin V–EGFR+EVs was found to be negatively correlated with tumor T stage of OSCC patients with a statistical difference, which suggested the ratio as a clinical index for monitoring the progression of OSCC in real time based on a noninvasive method. The approach provided a novel idea for evaluating the tumor T stage of OSCC and a powerful tool for clinical application.

Single-nanoparticle collision electrochemistry (SNCE) has gradually become an attractive analytical method due to its advantages in analytical detection, such as a fast response, low cost, low sample consumption, and in situ real-time detection of analytes. However, the biological analyte’s direct detection based on the SNCE blocking mode has the problems of low sensitivity and specificity. In this work, an SNCE biosensor based on SNCE electrocatalytic strategy was used for the detection of H7N9 AIV. Nucleic acid aptamers were introduced to recognize the target virus (H7N9 AIV). After the recognition event, ssDNA1was released and hybridized with another ssDNA2. Owing to the nicking endonuclease Nt.AlwI-mediated target nucleic acid cyclic amplification, one virus particle can indirectly induce the release of 4.2 × 106Au NPs that can be counted by the SNCE electrocatalytic strategy. The high conversion efficiency greatly improved the detection sensitivity, and the detection limit was as low as 24.3 fg/mL. Therefore, the constructed biosensor can achieve a highly sensitive and specific detection of H7N9 AIV and show a great potential in bioanalytical application.

Multiple myeloma (MM) remains incurable due to relapse, although the use of proteasome inhibitors, immunomodulatory drugs, CD38-targeting antibodies, and autologous stem cell transplantation (auto-SCT) significantly improve the clinical outcomes of patients with newly diagnosed MM. In recent years, the introduction of chimeric antigen receptor T-cell (CAR T-cell) therapy has brought hope to patients with refractory and relapsed MM. The graft-versus-myeloma effect of allogeneic SCT provides the possibility for curing a subset of MM patients. In this review, we summarize the recent advances and challenges of cellular immunotherapies for MM, focusing on auto-SCT, allogeneic SCT, and CAR T-cell approaches. We also discuss future directions, and propose a specific algorithm for cellular therapies for MM and probability of minimal residual disease-directed therapy.

Owing to the high spatiotemporal resolution, the second near-infrared (NIR-II) imaging window can provide high imaging contrast with diminished tissue autofluorescence and suppressed photon scattering to pinpoint the locations for tumor surgery. Due to the unique optical properties and excellent fluorescence performance, quantum dots (QDs) are regarded as ideal nanoprobes for fluorescence-guided surgery (FGS). Moreover, QDs can be excited by a variety of light sources owing to the continuous and wide absorption ranges. Herein, light-emitting diode (LED) was used as the excitation source of QDs-based nanoprobes to realize FGS of tumor with high resolution. Since the LED light could irradiate a large region with consistent light intensity, signal distortion at the edge of imaging field was avoided. The signal intensity of the view edges under LED excitation can be improved by about 5 times compared to laser excitation. Therefore, more micro-vessels and smaller tumors (Vtumor< 5 mm2) could be detected, thus providing more precise guidance for tumor resection surgery.

Viral epidemics pose a serious threat to global public health, making it essential to explore virus-host interactions for uncovering the pathogenesis of viral diseases and developing effective antiviral strategies. Traditional in vitrocell infection models struggle to replicate physiological microenvironment, while animal infection models may encounter obstacles such as species gap, high-cost, and ethical issues. Additionally, potential heterogeneous infection outcomes are usually inaccessible by population-based experiments. Microfluidics, as an emerging interdisciplinary platform, has proven to be a powerful tool for inquiring virus-host interactions. In this review, conventional virological methods were introduced first and remarkable advantages of microfluidics in viral cell biology were highlighted. Next, the in-depth applications of microfluidics in analyzing heterogeneity of virus-host interplays, dynamic monitoring of events related to viral life cycle, and modeling of viral infectious diseases were fully elaborated from the perspective of single-cell chip, multi-cell culture chip and organ-on-a-chip (organ chip). Finally, the opportunities and challenges in developing robust microfluidic methods for virology were discussed. Overall, this review aims to provide an overview of microfluidic-based research on virus-host interaction and promote multidisciplinary collaborations for better understanding and responding to viral threats.