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Compared with traditional vaccines, nanoparticulate vaccines are especially suitable for delivering antigens of proteins, peptides, and nucleic acids and facilitating lymph node targeting. Moreover, apart from improving pharmacokinetics and safety, nanoparticulate vaccines assist antigens and molecular adjuvants in crossing biological barriers, targeting immune organs and antigen-presenting cells (APC), controlled release, and cross-presentation. However, the process that stimulates and orchestrates the immune response is complicated, involving spatiotemporal interactions of multiple cell types, including APCs, B cells, T cells, and macrophages. The performance of nanoparticulate vaccines also depends on the microenvironments of the target organs or tissues in different populations. Therefore, it is necessary to develop precise nanoparticulate vaccines that accurately regulate vaccine immune response beyond simply improving pharmacokinetics. This Perspective summarizes and highlights the role of nanoparticulate vaccines with precise size, shape, surface charge, and spatial management of antigen or adjuvant for a precision vaccination in regulating the distribution, targeting, and immune response. It also discusses the importance of the rational design of nanoparticulate vaccines based on the anatomical and immunological microstructure of the target tissues. Moreover, the target delivery and controlled release of nanovaccines should be taken into consideration in designing vaccines for achieving precise immune responses. Additionally, it shows that the nanovaccines remodel the suppressed tumor environment and modulate various immune cell responses which are also essential.

Few-shot object detection (FSOD), a formidable task centered around developing inclusive models with annotated constrained samples, has attracted increasing interest in recent years. This discipline addresses unbalanced data distributions, which are particularly relevant to authentic scenarios. Although recent FSOD efforts have achieved considerable success in terms of localization, recognition remains a formidable obstacle. This stems from the fact that typical FSOD models evolve from general object detection frameworks predicated on extensive training data, and they underutilize and mine data information in scenarios with restricted samples, resulting in subpar performance. To address this deficiency, we introduce a groundbreaking methodology that is specifically tailored to overcome the inadequate sample challenge in FSOD tasks. Our approach incorporates a neighborhood information adaption (NIA) module that is designed to dynamically utilize information near the target, assisting in robustly performing object identification within the target domain. In addition, we propose an innovative attention mechanism called all attention, which not only encapsulates the dependencies of each position within a single feature map but also leverages correlations with other feature maps. This methodology culminates in more refined feature representations, which are particularly advantageous in situations with limited data. Comprehensive experiments conducted on the PASCAL VOC and COCO datasets illustrate that our technique achieves a substantial improvement with regard to addressing the FSOD task.

In automated driving, takeover behavior is crucial to safe transition of control. Based on this fact, the goal of the present study is to construct the driver's takeover behavior mode and verify its effectiveness. In the takeover process, we define the takeover behavior mode, which is the inherent mode of completing the takeover task, as the behavioral theoretical framework that drivers should follow when taking over. We conducted a driving simulation experiment to analyze driver takeover behavior in the fog zone, where non-driving-related tasks were external variables. First, we constructed the takeover behavior mode (situation awareness - decision and reaction - takeover performance). Second, we analyzed the characteristics of each stage and the correlation between each stage of the takeover behavior mode accordingly. The result shows that drivers’ performance in each stage differed significantly under different non-driving-related tasks. For example, their saccade and gaze duration were longer on the entertainment task than on the work task, and the driver prioritized the longitudinal stability after taking control of the automated vehicle. Results show that there is a correlation between different stages of takeover behavior mode. In this study, we propose the takeover behavior mode, aiming to help beginners and researchers in this field understand the driver takeover process more intuitively and provide behavioral theoretical support for subsequent studies. In addition, the takeover behavior mode can provide support for training drivers in real-world driving situations.

Exosome metabolite-based noninvasive liquid biopsy is an emerging research hotspot that tends to substitute current means in clinics. Nanostructure-based mass spectrometry enables continuous exosome isolation and metabolic profiling with superior analysis speed and high efficiency. Herein, we construct a heterogeneous MXene hybrid that possesses ternary binding sites for exosome capture and outstanding matrix performance for metabolite analysis. Upon optimizing experimental conditions, the average extraction of exosomes and their metabolic patterns from a 60 mL urine sample is completed within 45 s (40 samples per batch for 30 min). According to the exosomal metabolic patterns and the subsequently established biomarker panel, we distinguish early bladder cancer (BCa) from healthy controls with an area under the curve (AUC) value greater than 0.995 in model training and validation sets. As well, we realize subtype classification of BCa in the blind test on metabolic patterns, with an AUC value of 0.867. We also explore the significant biomarkers that are sensitive to follow-up patients, which indeed present reverse change levels compared with pathological progression. This study has the potential to guide the development of the liquid biopsy approach.

Metal–organic framework-based metal ion therapy has attracted increasing attention to promote the cascade wound-healing process. However, multimetal ion synergistic administration and accurately controlled ion release are still the challenges. Herein, an aptamer-functionalized silver@cupriferous Prussian blue (ACPA) is established as a metal-based theranostic nanoagent for a chronic nonhealing diabetic wound treatment. Prussian blue offers a programmable nanoplatform to formulate metal ion prescriptions, achieving cooperative wound healing. Silver, copper, and iron ions are released from ACPA controlled by the near-infrared-triggered mild hyperthermia and then synergistically participate in antipathogen, cell migration, and revascularization. ACPA also demonstrates a unique core–satellite nanostructure which enables it with improved surface-enhanced Raman scattering (SERS) capability as potent bacteria-targeted Raman-silent nanoprobe to monitor the residual bacteria during wound healing with nearly zero background. The theranostic feature of ACPA allows high-performance SERS imaging-guided chronic wound healing in infectious diabetic skin and keratitis.

Beauveria bassianaacts as an endophytic fungus that controls herbivorous pests by stimulating plant defenses and inducing systemic resistance. Through multiomics analysis, 325 differential metabolites and 1739 differential expressed genes were observed in tomatoes treated with B. bassianaby root irrigation; meanwhile, 152 differential metabolites and 1002 differential genes were observed in tomatoes treated by local leaf spraying. Among the upregulated metabolites were α-solanine, 5-O-caffeoylshikimic acid, clerodendrin A, and peucedanin, which demonstrated anti-insect activity. These differential metabolites were primarily associated with alkaloid biosynthesis, flavonoid biosynthesis, and tryptophan metabolism pathways. Furthermore, the gene silencing of UDP-glucose:sterol glucosyltransferase, a gene involved in α-solanine synthesis, indicated that B. bassianacould inhibit the reproduction of whiteflies by regulating α-solanine. This study highlighted the ability of B. bassianato modulate plant secondary metabolites and emphasized the significance of understanding and harnessing multitrophic interactions of endophytic B. bassianafor sustainable agriculture.

Tertiary lymphoid structures (TLSs) are formed in inflamed tissues, and recent studies demonstrated that the appearance of TLSs in tumor sites is associated with a good prognosis for tumor patients. However, the process of natural TLSs’ formation was slow and uncontrollable. Herein, we developed a nanovaccine consisting of Epstein–Barr virus nuclear antigen 1 (EBNA1) and a bi-adjuvant of Mn2+and cytosine-phosphate-guanine (CpG) formulated with tannic acid that significantly inhibited the development of mimicry nasopharyngeal carcinoma by fostering TLS formation. The nanovaccine activated LT-α and LT-β pathways, subsequently enhancing the expression of downstream chemokines, CCL19/CCL21, CXCL10 and CXCL13, in the tumor microenvironment. In turn, normalized blood and lymph vessels were detected in the tumor tissues of the nanovaccine group, correlated with increased infiltration of lymphocytes. Especially, the proportion of the B220+CD8+T, which was produced via trogocytosis between T and B cells during activation of T cells, was increased in tumors of the nanovaccine group. Furthermore, the intratumoral effector memory T cells (Tem), CD45+, CD3+, CD8+, CD44+, and CD62L–, did not decrease after blocking the egress of T cells from tumor-draining lymph nodes by FTY-720. These results demonstrated that the nanovaccine can foster TLS formation, which thus enhances local immune responses significantly, delays tumor outgrowth, and prolongs the median survival time of murine models of mimicry nasopharyngeal carcinoma, demonstrating a promising strategy for nanovaccine development.

Molecular diagnosing, typing, and staging have been considered to be the ideal alternatives of imaging-based detection methods in clinics. Designer matrix-based analytical tools, with high speed, throughout, efficiency and low/noninvasiveness, have attracted much attention recently for in vitro metabolite detection. Herein, we develop an advanced metabolic analysis tool based on highly porous metal oxides derived from available metal–organic frameworks (MOFs), which elaborately inherit the morphology and porosity of MOFs and newly incorporate laser adsorption capacity of metal oxides. Through optimized conditions, direct high-quality fingerprinting spectra in 0.5 μL of urine are acquired. Using these fingerprinting spectra, we can discriminate the renal cell carcinoma (RCC) from healthy controls with higher than 0.99 of area under the curve (AUC) values (R2Y(cum) = 0.744, Q2(cum) = 0.880), as well, from patients with other tumors (R2Y(cum) = 0.748, Q2(cum) = 0.871). We also realize the typing of three RCC subtypes, including clear cell RCC, chromophobe RCC (R2Y(cum) = 0.620, Q2(cum) = 0.656), and the staging of RCC (R2Y(cum) = 0.755, Q2(cum) = 0.857). Moreover, the tumor sizes (threshold value is 3 cm) can be remarkably recognized by this advanced metabolic analysis tool (R2Y(cum) = 0.710, Q2(cum) = 0.787). Our work brings a bright prospect for designer matrix-based analytical tools in disease diagnosis, typing and staging.

Theranostic carbon dots (CDs) have attracted widespread attention recently due to their tunable optical properties and diverse bioactivities. Beyond fluorescent imaging application, the photothermal property endows CDs with the potential for microbial inactivation. However, realization of the effective conversion between fluorescence and heat in one CD system has rarely been reported. Herein, we provide a simple strategy for targeted microbial theranostics based on 4-carboxyphenylboronic acid-derived CDs (PCBA-CDs) which possess concentration-dependent photoluminescence/photothermal features. At lower concentrations, PCBA-CDs show bright and stable fluorescent signals ranging from blue to green. The fluorescence intensity gradually decreases with increasing concentration, while on the contrary, the photothermal effect of PCBA-CDs ascends progressively due to the rearrangement of electronic transitions in aggregated CDs. PCBA-CDs also demonstrate high affinity to the polysaccharide structures on the surface of microbe which allows rapid microbial fluorescence imaging as well as specific photothermal ablation of pathogens in skin wounds using PCBA-CDs at lower and higher concentrations, respectively. This study supplies a facile nanotheranostic strategy for just-in-time microbial management using bioactive CDs.

Gastric cancer (GC) presents high mortality worldwide because of delayed diagnosis. Currently, exosome-based liquid biopsy has been applied in diagnosis and monitoring of diseases including cancers, whereas disease detection based on exosomes at the metabolic level is rarely reported. Herein, the specific aptamer-coupled Au-decorated polymorphic carbon (CoMPC@Au-Apt) is constructed for the capture of urinary exosomes from early GC patients and healthy controls (HCs) and the subsequent exosome metabolic pattern profiling without extra elution process. Combining with machine learning algorithm on all exosome metabolic patterns, the early GC patients are excellently discriminated from HCs, with an accuracy of 100% for both the discovery set and blind test. Ulteriorly, three key metabolic features with clear identities are determined as a biomarker panel, obtaining a more than 90% diagnostic accuracy for early GC in the discovery set and validation set. Moreover, the change law of the key metabolic features along with GC development is revealed through making a comparison among HCs and GC at early stage and advanced stage, manifesting their monitoring ability toward GC. This work illustrates the high specificity of exosomes and the great prospective of exosome metabolic analysis in disease diagnosis and monitoring, which will promote exosome-driven precision medicine toward practical clinical application.

Fluorescence microscopy based on fluorochrome has been rapidly developed as the candidate for morphological identification of pathogenic fungi over recent years, offering superior rapidity and efficacy over traditional culture methods. However, the intrinsic quenching properties of fluorescein limit the clinical application of fluorescence imaging. Herein, we report a nano-strategy by converting a commercial fluorescein dye, fluorescent brightener-33 (FB-33), into carbon dots (FB-CDs) through a one-pot hydrothermal method. FB-CDs exhibit a chitin-targeting capacity allowing the selective recognition and ultrafast imaging of fungi within 30 s. The fluorescence quantum yield of FB-CDs is 51.6% which is 8.6-fold higher than that of commercial dye, FB-33. Moreover, FB-CDs also display superstable fluorescence signals under continuous intense light irradiation for 2 h and long-term storage for more than 2 months. The significantly improved photobleaching resistance meets the prolonged fluorescence observation and quantitative analysis of microbial samples. This work offers a novel nanoconversion strategy of commercial dyes for point-of-care testing of pathogenic organisms.

Photothermal therapy (PTT) in the second near-infrared (NIR-II) window has emerged as a better candidate for deep-tissue tumor elimination. More interestingly, the photothermal ablated tumor cells also manifest somewhat immunostimulation potency to elicit antitumor immunity, although most dying cells are undergoing apoptosis that is commonly considered as immunologically silent. Here, a NIR-II responsive nanosystem is established for tumor photoimmunotherapy using molybdenum dioxide (MoO2) nanodumbbells as the nanoconverter. Meanwhile, an apoptosis-blocking strategy is proposed to regulate the cell death pattern under NIR-II laser irradiation in order to improve the immunogenic cell death. The nanoformulation can efficiently block caspase 8-dependent apoptotic pathway in photothermal ablated tumor cells and transform into more immunogenic death patterns, thereby activating systemic immunity to inhibit tumor growth and metastasis. In addition, this strategy also helps enhance the body’s responses to α-PD-1 immune checkpoint inhibitor, which implies a potential optimal combination for cancer immunotherapy.

Vaccines can improve the quality of human life by preventing the burden of infectious diseases. Also, vaccination is becoming a powerful medication for preventing and treating tumors. Various vaccines have been developed based on the origin of the antigens. Herein, we focus on the subunit vaccines whose antigens are proteins or peptides. The advantage of subunit vaccines is safety for recipients; however, the immunogenicity of subunit antigens is relatively low. Nanoparticular delivery systems have been applied to improve the immunocompetence of subunit vaccines by targeting lymph nodes, and effectively present antigens to immune cells. Moreover, adding appropriate molecular adjuvants may strengthen the antigens to elicit immune response. In this perspective article, we first elucidate the characteristics of immunity induced by subunit nanovaccines and then summarize the strategies to fabricate subunit nanovaccines with delivering materials. Herein we highlight non-covalent interaction to fabricate nanoparticular subunit vaccines.

Human health is always under global spotlight, but now it suffers from severe environmental issue and various diseases. Developing highly selective and effective extraction technique for environmental pollutant removal and target protein/peptide molecules conduces to the solution of environmental contamination and early disease detection, which will promise human health to a great degree. Metal-organic frameworks (MOFs) are typical porous nanomaterials featuring rigid structure, large specific surface area, thermal and chemical stability, numerous active sites and easy functionalization. Moreover, multitudinous combination of metal centers and organic ligands often endows MOFs with structure and function diversity. Owing to such splendid merits, MOFs are able to act as advanced adsorbents for sample-pretreatment in proteomics and environmental field, which indicates great efficiency, reproducibility, convenience and cost-effectiveness. In this review, the novel design of MOFs and their applications in proteomics and environmental research are roughly summarized. We first introduce the representative researches of functional MOFs in protein post-translational modifications including glycosylation and phosphorylation, mainly focusing on hydrophilic interaction liquid chromatography (HILIC) or metal-oxide affinity chromatography (MOAC). The important role of MOFs in enzyme immobilization is also covered. Then MOF-based adsorptive removal of diverse environmental contaminants embracing plasticizers, pesticides and varied water pollutants (pharmaceutical and personal care products, organic dyes and heavy metals), in which multiple chemical and non-chemical interactions play a vital role, is emphatically discussed. Finally, we analyze the existing problems and challenges in the way of wider practical applications and put forward prospective anticipation.

Inhibition or knockout of Sirt1 or Nrf2 resulted in increased ROS and reduced cell testosterone production, and their activation protected or enhanced steroidogenic function, suggesting that Sirt1 and Nrf2 are involved in maintaining the Leydig cell oxidant/antioxidant environment and steroid production.Previous studies reported that, with aging, Leydig cell intracellular antioxidants are reduced in concentration and intracellular ROS levels increase, suggesting that oxidant/antioxidant imbalance may contribute to the reduced testosterone production that characterizes the aging cells. As yet, little is known about how the Leydig cell oxidant/antioxidant environment is regulated. Sirt1, an enzyme that deacetylates transcription factors, and the transcription factor Nrf2, have been shown to be associated with cellular response to oxidative stress. We hypothesized that Sirt1 and/or Nrf2 might be involved in regulating the oxidant/antioxidant environment of Leydig cells, and therefore, the testosterone production. We found that Sirt1 and Nrf2 are present in the Leydig cells of Brown Norway rats, though reduced in aged cells. In MA-10 cells in which Sirt1 or Nrf2 were suppressed by nicotinamide (NAM) or ML385, respectively, or in which siRNAs were used for knockdown of Sirt1or Nrf2, increased ROS levels and decreased progesterone production occurred. In rat Leydig cells, inhibition of Sirt1 by culturing the cells with NAM resulted in increased ROS and reduced testosterone production, and subsequent removal of NAM from the culture medium resulted in increased testosterone production. Activation of rat Leydig cells Sirt1 with honokiol or of Nrf2 with sulforaphane resulted in the maintenance of testosterone production despite the exposure of the cells to oxidizing agent. These results, taken together, suggest that Sirt1 and Nrf2 are involved in maintaining the Leydig cell oxidant/antioxidant environment, and thus in maintaining steroid production.

Effective cancer treatment puts high demands for cancer theranostics. For cancer diagnostics, optical coherence tomography (OCT) technology (including photothermal optical coherence tomography (PT-OCT)) has been widely investigated since it induces changes in optical phase transitions in tissue through environmental changes (such as temperature change for PT-OCT). In this report, redox responsive nanoparticle encapsulating black phosphorus quantum dots was developed as a robust PT-OCT agent. Briefly, black phosphorus quantum dots (BPQDs) are incorporated into cysteine-based poly-(disulfide amide) (Cys-PDSA) to form stable and biodegradable nanoagent. The excellent photothermal feature allows BPQD/Cys-PDSA nanoparticles (NPs) as a novel contrast agent for high-resolution PT-OCT bioimaging. The Cys-PDSA can rapidly respond to glutathione and effectively release BPQDs and drugs in vitroand in vivo. And the obtained NPs exhibit excellent near-infrared (NIR) photothermal transduction efficiency and drug delivery capacity that can serve as novel therapeutic platform, with very low chemo drug dosage and side effects. Both of the polymer and BPQD are degradable, indicating this platform is a rare PT-OCT agent that is completely biodegradable. Overall, our research highlights a biodegradable and biocompatible black phosphorus-based nanoagent for both cancer diagnosis and therapy.

Platinum-based anticancer drugs can inhibit the growth of cancer cells by disrupting DNA replication, which makes them widely applicable in clinics for treating tumors and cancers. However, owing to the intrinsic or acquired drug resistance and severe side effects caused in the treatment, their successful clinical applications have been limited. Various strategies have been used to address these challenges. Nanocarriers have been used for platinum drug delivery because they can be effectively deposited in tumor tissues to reduce the damage to normal organs for an enhanced permeability and retention (EPR) effect. Furthermore, for synergizing the function of platinum-based drugs with different mechanisms to decrease the toxicities, multicomponent chemotherapy has become an imperative strategy in clinical cancer treatments. This review aims to introduce the mechanisms of action and limitations of platinum-based drugs in clinics, followed by providing the current advancement of nanocarriers including lipids, polymers, dendrimers, micelles and albumin for platinum drug delivery in cancer treatments. In addition, multicomponent chemotherapy based on platinum drugs is introduced in detail. Finally, the prospects of multicomponent chemotherapy for cancer treatment are discussed as well.

The Leydig cells of the mammalian testis produce testosterone (T) in response to luteinizing hormone (LH). In rats and men with reduced serum T levels, T replacement therapy (TRT) will raise T levels, but typically with suppressive effects on sperm formation. The rate-determining step in T formation is the translocation of cholesterol to the inner mitochondrial membrane, mediated by protein-protein interactions of cytosolic and outer mitochondrial membrane proteins. Among the involved proteins is cholesterol-binding translocator protein (TSPO) (18 kDa TSPO). We hypothesized that in contrast to TRT, the administration of the TSPO agonist N,N-dihexyl-2-(4-fluorophenyl)indole-3-acetamide (FGIN-1-27), by stimulating the ability of the Leydig cells to produce T, would result in the elevation of serum T levels while maintaining intratesticular T concentration and therefore without suppression of spermatogenesis. Age-related reductions in both serum and intratesticular T levels were seen in old Brown Norway rats. Both exogenous T and FGIN-1-27 increased serum T levels. With exogenous T, serum LH and Leydig cell T formation were suppressed, and intratesticular T was reduced to below the concentration required to maintain spermatogenesis quantitatively. In contrast, FGIN-1-27 stimulated Leydig cell T formation, resulting in increased serum T without reductions in intratesticular T concentrations or in testicular sperm numbers. FGIN-1-27 also significantly increased serum and intratesticular T levels in rats made LH-deficient by treatment with the gonadotropin-releasing hormone antagonist cetrorelix. These results point to a possible approach to increasing serum T without negative effects on spermatogenesis, based upon stimulating T production by the Leydig cells themselves rather than administering T exogenously.

We reported that FGIN-1-27 (N,N-dihexyl-2-(4-fluorophenyl)indole-3-acetamide, FGIN), a synthetic ligand for translocator protein (TSPO, 18 kDa), increased serum testosterone levels in young and aged Brown Norway rats after its administration daily for 10 days. It is not known, however, how soon after treatment with FGIN serum testosterone rises, how long levels remain elevated after cessation of treatment, or whether the drug acts solely through TSPO. Adult Sprague-Dawley male rats received a single ip dose of FGIN (1 mg/kg BW). Serial blood samples were collected, and serum testosterone and luteinizing hormone (LH) were assessed hourly throughout 24 h. Testosterone concentration was maximal by 3 h, remained significantly higher than the controls at 10 h, and returned to the control level by 24 h. Consistent with the in vivo study, culturing isolated Leydig cells with either FGIN (40 μM) or LH (0.1 ng/ml) resulted in significantly increased testosterone production by 30 min, and the stimulatory effects persisted through 48 h. At a very early (15 min) treatment time, however, FGIN significantly increased testosterone production but LH had not yet done so. Surprisingly, in vivo treatment with FGIN not only increased serum testosterone but also serum LH concentration, raising the possibility that FGIN may increase serum testosterone concentration by dual mechanisms.FGIN-1-27, a TSPO drug ligand, can acutely increase serum testosterone concentration by acting directly on the Leydig cells and indirectly through luteinizing hormone.

Exosome metabolite-based liquid biopsy is a promising strategy for large-scale application in practical clinics toward precise medicine. Given the current challenges in successive isolation and analysis of exosomes and their metabolites in this field, we established a low-cost, high-throughput, and rapid platform for serological exosome metabolic biopsy of hepatocellular carcinoma (HCC) via designed core–shell nanoparticles. It starts with the efficient extraction of high-quality serum exosomes and exosome metabolic features, based on which significantly obvious sample clusters are observed by unsupervised cluster analysis. The following integration of feature selection and supervised machine learning enables the identification of six key metabolites and achieves high-performance prediction between HCC, liver cirrhosis, and healthy controls. Specifically, both sensitivity and accuracy achieve 100% among any pairwise intergroup discrimination in a blind test. The quality and reliability of six key metabolites are further evaluated and validated by using different machine learning algorithms and pathway exploration. Our platform contributes to the future growth of new liquid biopsy technologies for precision diagnosis and real-time monitoring of HCC, among other conditions.

Crohn's disease (CD) as a big issue to public health needs an accurate diagnosis urgently that is the common challenge among internal diseases. Herein, we design a mesoporous polydopamine with built-in metal-organic frameworks (dubbed MMP-b-MOFs) to combine with high-throughput mass spectrometry to extract serum peptide fingerprints from CD and healthy controls (HC). Benefitting by the size-exclusion and strong hydrophilicity of MMP-b-MOFs, the extracted peptide fingerprints present extremely high quality. CD and HC are explicitly discriminated with orthogonal partial least squares discriminant analysis (OPLS-DA), the corresponding area under the curve (AUC) value is 1.000. Moreover, eight peptides with clear identity are screened out and achieve the accurate diagnosis and subtype classification of CD, with all AUC values up to 1.000. Moreover, the unsupervised model is also established to precisely classify HC and CD based on these eight clearly identified peptides. This work brings great benefits for clinical detection especially internal medicine.

Teeth staining is a common dental health challenge in many parts of the world. Traditional teeth whitening techniques often lead to enamel damage and soft tissue toxicity due to the use of bioincompatible whitening reagents and continuous strong light irradiation. Herein, an “afterglow” photodynamic therapy (aPDT) for teeth whitening is proposed, which is realized by energy transition pathways of intersystem crossing. The covalent and hydrogen bonds formed by carbon dots embedded in silica nanoparticles (CDs@SiO2) facilitate the passage of energy through intersystem crossing (ISC), thereby extending the half-life of reactive oxygen species (ROS). The degradation efficiency of aPDT on dyes was higher than 95% in all cases. It can thoroughly whiten teeth by eliminating stains deep in the enamel without damaging the enamel structure and causing any tissue toxicity. This study illustrates the superiority of aPDT for dental whitening and the approach to exploring carbon-dots-based nanostructures in the treatment of oral diseases.

Object detection has become a crucial technology in intelligent vision systems, enabling automatic detection of target objects. While most detectors perform well on open datasets, they often struggle with small-scale objects. This is due to the traditional top-down feature fusion methods that weaken the semantic and location information of small objects, leading to poor classification performance. To address this issue, we propose a novel feature pyramid network, the adaptive learnable feature pyramid network (ALFPN). Our approach features an adaptive feature inspection that incorporates learnable fusion coefficients in the fusion of different levels of feature layers, aiding the network in learning features with less noise. In addition, we construct a context-aligned supervisor that adjusts the feature maps fused at different levels to avoid scaling-related offset effects. Our experiments demonstrate that our method achieves state-of-the-art results and is highly robust for the small object detection on the TT-100K, PASCAL VOC, and COCO datasets. These findings indicate that a model’s ability to extract discriminant features is positively correlated with its performance in detecting small objects.

Polyaniline, an organic conducting polymer, exhibits strong light absorption in the near-infrared region. Herein, the potential of polyaniline nanoparticles as the contrast agents for optical coherence tomography imaging was investigated. Polyaniline nanoparticles were synthesized by a facile chemical oxidative method. The optical coherence tomography images obtained from ex vivo swine liver tissues showed the concentration-dependent contrast effect of polyaniline nanoparticles. Then the nanoagents were applied to in vivo optical coherence tomography imaging of tumor tissues using a xenograft tumor mouse model. The penetration depth of the optical coherence tomography signals from tumors injected with polyaniline nanoparticles was significantly lower than that from tumors injected with phosphate buffer solution. The remarkable contrast effect of polyaniline nanoparticles was then quantitatively studied by the attenuation coefficients of optical coherence tomography signals. Furthermore, the permeation dynamics of polyaniline nanoparticles in tissue was also studied by Raman spectroscopy.

Wound healing is a complex biological process that involves tissue regeneration. Traditional wound dressings are dry, cannot provide a moist environment for wound healing, and do not have high antibacterial properties. Hydrogels, which are capable of retaining large amounts of water, can create a moist healing environment. Currently, phototherapies have exhibited a high potential for the treatment of bacterial infections. Therefore, combining hydrogels with phototherapy can adequately overcome the shortcomings of traditional wound treatment methods and show great potential for wound healing owing to their high efficiency, low irritation, and good antibacterial performance. In this review, the application of hydrogels combined with phototherapy in wound healing is summarized. First, the basic principles of photodynamic therapy and photothermal therapy are briefly introduced. In addition, the progress of the application of hydrogel combined with phototherapy in wound healing is systematically investigated. Finally, the challenges and prospects of combining hydrogel with phototherapy in wound healing are discussed. Hydrogels are capable of retaining large amounts of water and can create a moist healing environment. Phototherapies have exhibited a high potential for the treatment of bacterial infections and can avoid the multidrug resistance of bacteria caused by the overuse of antibiotics. This review summarizes hydrogel‐based phototherapy to promote wound healing.

Leydigcells are the testosterone-producing cells in the adult male. Adult Leydig cells (ALCs) develop from stem Leydig cells (SLCs) through at least two intermediate cells, progenitor Leydig cells (PLCs) and immature Leydig cells (ILCs). Microarray gene expression was used to identify the transcriptional changes that occur with the differentiation of SLCs to PLCs and, thus, with the entry of SLCs into the Leydig cell lineage; to comprehensively examine differentiation through the development of ALCs; and to relate the pattern of gene expression in SLCs to that in a well-established stem cell, bone marrow stem cells (BSCs). We show that the pattern of gene expression by SLCs was more similar to the expression by BSCs, an established stem cell outside the male reproductive tract, than to any of the cells in the Leydig cell developmental lineage. These results indicated that the SLCs have many of the molecular characteristics of other stem cells. Pathway analysis indicated that development of Leydig cells from SLCs to PLCs was associated with decreased expression of genes related to adhesion and increased expression of genes related to steroidogenesis. Gene expression changes between PLCs and ILCs and between ILCs and ALCs were relatively minimal, suggesting that these cells are highly similar. In contrast, gene expression changes between SLCs and ALCs were quite distinct.

Previous studies in MA-10 tumor Leydig cells demonstrated that disruption of the mitochondrial electron-transport chain (ETC), membrane potential (ΔΨm), or ATP synthesis independently inhibited steroidogenesis. In contrast, studies of primary Leydig cells indicated that the ETC, ΔΨm, and ATP synthesis cooperatively affected steroidogenesis. These results suggest significant differences between the two systems and call into question the extent to which results from tumor Leydig cells relate to primary cells. Thus, to further understand the similarities and differences between the two systems as well as the impact of ATP disruption on steroidogenesis, we performed comparative studies of MA-10 and primary Leydig cells under similar conditions of mitochondrial disruption. We show that mitochondrial ATP synthesis is critical for steroidogenesis in both primary and tumor Leydig cells. However, in striking contrast to primary cells, perturbation of ΔΨmin MA-10 cells did not substantially decrease cellular ATP content, a perplexing finding because ΔΨmpowers the mitochondrial ATP synthase. Further studies revealed that a significant proportion of cellular ATP in MA-10 cells derives from glycolysis. In contrast, primary cells appear to be almost completely dependent on mitochondrial respiration for their energy provision. Inhibitor studies also suggested that the MA-10 ETC is impaired. This work underscores the importance of mitochondrial ATP for hormone-stimulated steroid production in both MA-10 and primary Leydig cells while indicating that caution must be exercised in extrapolating data from tumor cells to primary tissue.

Carbon dots (CDs) are considered as promising candidates with superior biocompatibilities for multimodel cancer theranostics. However, incorporation of exogenous components, such as targeting molecules and chemo/photo therapeutic drugs, is often required to improve the therapeutic efficacy. Herein, an “all‐in‐one” CDs that exhibit intrinsic bioactivities for bioimaging, potent tumor therapy, and postoperative management is proposed. The multifunctional CDs derived from gallic acid and tyrosine (GT‐CDs) consist of a graphitized carbon core and N, O‐rich functional groups, which endow them with a high near‐infrared (NIR) photothermal conversion efficiency of 33.9% and tumor‐specific cytotoxicity, respectively. A new imaging modality, photothermal optical coherence tomography, is introduced using GT‐CDs as the contrast agent, offering the micrometer‐scale resolution 3D tissue morphology of tumor. For cancer therapy, GT‐CDs initiate the intracellular generation of reactive oxygen species in tumor cells but not normal cells, further induce the mitochondrial collapse and subsequent tumor cellular apoptosis. Combined with NIR photothermal treatment, synergistic antitumor therapy is achieved in vitro and in vivo. GT‐CDs also promote the healing process of bacteria‐contaminated skin wound, demonstrating their potential to prevent postoperative infection. The integrated theranostic strategy based on versatile GT‐CDs supplies an alternative easy‐to‐handle pattern for disease management. "All‐in‐one" carbon dots derived from gallic acid and tyrosine (GT‐CDs) are proposed for multimodel nanotheranostics. GT‐CDs exhibit high near‐infrared photothermal conversion efficiency and tumor‐specific cytotoxicity that allow the photothermal optical coherence tomography and high‐performance synergistic tumor therapy. The intrinsic bioactivities of GT‐CDs also endow them with the potential for wound healing of bacteria‐contaminated skin.

The postnatal development of Leydig cells can be divided into three distinct stages: initially they exist as fibroblast-like progenitor Leydig cells (PLCs) appearing in the testis by Days 14–21; subsequently, by Day 35, they become immature Leydig cells (ILCs) acquiring steroidogenic organelle structure and enzyme activities but metabolizing most of the testosterone they produce; finally, as adult Leydig cells (ALCs) by Day 90, they actively produce testosterone. The factors controlling proliferation and differentiation of Leydig cells remain largely unknown, and the aim of the present study was to identify changes in gene expression during development through cDNA array analysis of PLCs, ILCs, and ALCs. By cluster analysis, it was determined that the transitions from PLC to ILC to ALC were associated with downregulation of mRNAs corresponding to 107 genes. The downregulated genes included cell-cycle regulators, e.g., cyclin D1 (Ccnd1); growth factors, e.g., basic fibroblast growth factor (Fgf2); growth-factor-related receptors, e.g., platelet-derived growth factor α receptor (Pdgfra); oncogenes, e.g., kit oncogene (Kit); and transcription factors, e.g., early growth response 1 (Egr1). Conversely, expression levels of 264 genes were increased by at least twofold. Most of these were related to differentiated function and included steroidogenic enzymes, e.g., 11β-hydroxysteroid dehydrogenase 2 (Hsd11b2); neurotransmitter receptors, e.g., acetylcholine receptor nicotinic α 4 (Chrna4); stress response factors, e.g., glutathione transferase 8 (Gsta4); and protein turnover enzymes, e.g., tissue inhibitor of metalloproteinase 2 (Timp2). The detection of Hsd11b2mRNA in the array was the first indication that this gene is expressed in Leydig cells, and parallel increases in Hsd11b2mRNA and enzyme activity were recorded. Thus, gene profiling demonstrates that postnatal development is associated with changes in the expression levels of several different clusters of genes consistent with the processes of Leydig cell growth and differentiation.

This article summarizes a talk on Leydig cell aging presented at the 1999 Annual Meeting of the Society for the Study of Reproduction. In the Brown Norway rat, serum testosterone levels decrease with aging, accompanied by increases in serum FSH. The capacity of Leydig cells to produce testosterone is higher in young than in old rats. Binding studies with hCG revealed reduced receptor number in old vs. young Leydig cells. In response to incubation with LH, cAMP production was found to be reduced in old vs. young Leydig cells, indicating that signal tranduction mechanisms in the old cells are affected by aging. Steroidogenic acute regulatory protein and mRNA levels are reduced in old Leydig cells, suggesting that there may be deficits in the transport of cholesterol to the inner mitochondrial membrane of aged cells. The activity of P450 side-chain cleavage enzyme is reduced in old vs. young cells, as are the activities of each of 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase/C17–20 lyase, and 17-ketosteroid reductase. Serum LH levels do not differ between young and old rats, and the administration of LH failed to induce old Leydig cells to produce high (young) testosterone levels, suggesting that the cause of age-related reductions in steroidogenesis is not LH deficits. We hypothesized that reactive oxygen, produced as a by-product of steroidogenesis itself, might be responsible for age-related reductions in testosterone production by the Leydig cells. Consistent with this, long-term suppression of steroidogenesis was found to prevent or delay the reduced steroidogenesis that accompanies Leydig cell aging. A possible explanation of this finding is that long-term suppression of steroidogenesis prevents free radical damage to the cells by suppressing the production of the reactive oxygen species that are a by-product of steroidogenesis itself.

Exosome and inclusive cargoes have manifested significant function in different biological events. In particular, glycopeptides in exosome are closely associated with occurrence and development of various diseases. Developing advanced tools is highly desired to enrich glycopeptides from exosomes, and enrich exosomes from complex biological samples as well. In this work, integration of L-cysteine and titania onto the surface of magnetic nanoparticles is designed to realize the coefficient affinity towards exosomes and inclusive glycopeptides. Benefiting from the synergistic affinity, we separate exosomes from human urine concentrate directly, which was proved by the detection of three typical antigen markers of exosomes. Furthermore, hardly any exosomes remained on materials after ultrasonication, which confirmed the good capture performance of Fe3O4@TiO2@L-Cys and high release effect of direct lysis. Moreover, 146 glycopeptides corresponding to 77 glycoproteins were successfully identified from captured exosomes. These satisfactory results will inspire more efforts to be devoted to this field and will be extremely helpful to in-depth information excavation of biological markers, especially disease-related ones, through exosomes and inclusive glycopeptides.