Tumor-Associated Myeloid Cells Selective Delivery of a Therapeutic Tumor Nano-Vaccine for Overcoming Immune Barriers for Effective and Long-Term Cancer Immunotherapy.

Therapeutic cancer vaccines have the potential to induce regression of established tumors, eradicate microscopic residual lesions, and prevent metastasis and recurrence, but their efficacy is limited by the low antigenicity of soluble antigens and the immunosuppressive tumor-associated macrophages (TAMs) that promote tumor growth. In this study, a novel strategy is reported for overcoming these defenses: a dual-targeting nano-vaccine (NV) based on hepatitis B core antigen (HBcAg) derived virus-like particles (VLPs), N-M2T-gp100 HBc NV, equipped with both SIGNR+ dendritic cells (DCs)/TAMs-targeting ability and high-density display of tumor-associated antigen (TAA). N-M2T-gp100 HBc NVs-based immunotherapy has demonstrated an optimal interaction between tumor-associated antigens (TAAs) and the immune composition of the tumor microenvironment. In a melanoma model, N-M2T-gp100 HBc VLPs significantly reducing in situ and abscopal tumor growth, and provide long-term immune protection. This remarkable anti-tumor effect is achieved by efficiently boosting of T cells and repolarizing of M2-like TAMs. This work opens exciting avenues for the development of personalized tumor vaccines targeting not just melanoma but potentially a broad range of cancer types based on functionalized VLPs.

NLRC5 promotes endometrial carcinoma progression by regulating NF-κB pathway-mediated mismatch repair gene deficiency.

The innate immune molecule NLR family CARD domain-containing 5 (NLRC5) plays a significant role in endometrial carcinoma (EC) immunosurveillance. However, NLRC5 also plays a protumor role in EC cells. Mismatch repair gene deficiency (dMMR) can enable tumors to grow faster and also can exhibit high sensitivity to immune checkpoint inhibitors. In this study, we attempted to determine whether NLRC5-mediated protumor role in EC is via the regulation of dMMR. Our findings revealed that NLRC5 promoted the proliferation, migration, and invasion abilities of EC cells and induced the dMMR status of EC in vivo and in vitro. Furthermore, the mechanism underlying NLRC5 regulated dMMR was also verified. We first found NLRC5 could suppress nuclear factor-kappaB (NF-κB) pathway in EC cells. Then we validated that the positive effect of NLRC5 in dMMR was restricted when NF-κB was activated by lipopolysaccharides in NLRC5-overexpression EC cell lines. In conclusion, our present study confirmed the novel NLRC5/NF-κB/MMR regulatory mechanism of the protumor effect of NLRC5 on EC cells, thereby suggesting that the NLRC5-mediated protumor in EC was depend on the function of MMR.

Traditional Chinese medicine for idiopathic membranous nephropathy: A systematic review and meta-analysis.

Background: Idiopathic membranous nephropathy (IMN) is a rare autoimmune disorder that causes nephrotic syndromes in adults. Conventional immunosuppressive therapies often exhibit limited efficacy in achieving remission and may result in notable adverse reactions, warranting the exploration of novel therapeutic approaches for IMN treatment. Traditional Chinese medicine (TCM), which is extensively used for kidney disease management, is a promising alternative. Objective: This study aimed to examine the safety and efficacy of TCM alone or in combination with Western medicine for the management of patients diagnosed with IMN. Methods: This study employed a systematic search of English and Chinese electronic databases to identify randomized controlled trials (RCTs) that examined the application of TCM in the treatment of IMN. RCTs that met the predetermined inclusion and exclusion criteria and assessed the safety and efficacy of TCM alone or in combination with Western medicine in patients with IMN were included in the analysis. The methodological quality of the included studies was evaluated by using a risk-of-bias tool. All statistical analyses were performed using the RevMan software (version 5.4.2). The evidence was evaluated on the https://www.gradepro.org/website. Results: This study included 29 randomized controlled trials (RCTs) involving 1982 patients with moderate methodological quality that met the inclusion criteria. The results showed that, compared to Western medicine alone therapy, the use of TCM alone or in combination with Western medicine significantly improved total remission (TR) rate (risk ratios [RR] 1.38, 95% confidence interval [CI] 1.29-1.46, I2 = 0%, P < 0.00001), complete remission (CR) rate (RR 1.78, 95% CI 1.48-2.15, I2 = 0, P < 0.00001), partial remission (PR) rate (RR 1.27, 95% CI 1.161.40, I2 = 0%, P < 0.00001), and serum albumin (ALB) levels (MD: 4.05, 95% CI: 3.02-5.09, I2 = 91%, P < 0.00001). TCM alone or in combination with Western medicine also reduced proteinuria levels (mean difference [MD]: 1.05, 95% CI: 1.30 to -0.79, I2 = 95%, P < 0.00001), serum creatinine (SCr) levels (MD: 7.47, 95% CI: 13.70 to -1.24, I2 = 97%, P = 0.02), and serum antibodies against M-type phospholipase A2 receptor levels (aPLA2Rab) (MD: 19.24, 95% CI: 33.56 to -4.93, I2 = 87%, P = 0.008). Moreover, the efficacy of combined TCM and Western medicine is superior to that of Western medicine alone in reducing the incidence of infection, hepatotoxicity, and thrombosis. Although the primary and secondary outcomes were consistent, the evidence was generally moderate. Conclusion: The results of this study suggest that TCM alone or in combination with Western medicine may be a feasible alternative therapeutic approach for the treatment of IMN. Nevertheless, additional, rigorously designed, high-quality, and extensive clinical trials are imperative to provide substantial evidence regarding the effectiveness of TCM in managing IMN.

Prediction of biomarkers associated with membranous nephropathy: Bioinformatic analysis and experimental validation.

Membranous nephropathy (MN), the most prevalent form of nephrotic syndrome in non-diabetic adults globally, is currently the second most prevalent and fastest-increasing primary glomerular disease in China. Numerous renal disorders are developed partly due to ferroptosis. However, its relationship to the pathogenesis of MN has rarely been investigated in previous studies; actually, ferroptosis is closely linked to the immune microenvironment and inflammatory response, which might affect the entire process of MN development. In this study, we aimed to identify ferroptosis-related genes that are potentially related to immune cell infiltration, which can further contribute to MN pathogenesis. The microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Ferroptosis-related differentially expressed genes (FDEGs) were identified, which were further used for functional enrichment analysis. The common genes identified using the Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression algorithm and the support vector machine recursive feature elimination (SVM-RFE) algorithm were used to identify the characteristic genes related to ferroptosis. The feasibility of the 7 genes as a distinguishing factor was assessed using the receiver operating characteristic (ROC) curve, with the area under the curve (AUC) score serving as the evaluation metric. Gene set enrichment analysis (GSEA) and correlation analysis of these genes were further performed. The correlation between the expression of these genes and immune cell infiltration inferred by single sample gene set enrichment analysis (ssGSEA) algorithm was explored. As a result, 7 genes, including NR1D1, YTHDC2, EGR1, ZFP36, RRM2, RELA and PDK4, which were most relevant to immune cell infiltration, were identified to be potential diagnostic genes in MN patients. Next, the signature genes were validated with other GEO datasets. In the subsequent steps, we conducted quantitative real-time fluorescence PCR (qRT-PCR) analysis and immunohistochemistry (IHC) method on the cationic bovine serum albumin (C-BSA) induced membranous nephropathy (MN) rat model and the passive Heymann nephritis (pHN) rat model to examine characteristic genes. Finally, we analysed the mRNA expression patterns of hub genes in MN patients and normal controls using the Nephroseq V5 online platform. In concise terms, our study successfully identified biomarkers specific to MN patients and delved into the potential interplay between these markers and immune cell infiltration. This knowledge bears significance for the diagnosis and prospective treatment strategies for individuals affected by MN.

Efficient fluorescence coupling microlens integrated fiber magnetometer probe based on nitrogen vacancy centers.

The nitrogen vacancy (NV) centers in diamonds have gathered increasing interest as an emerging quantum sensing platform with high sensitivity and spatial resolution. Integration of micro-sized diamond and fiber is an essential method to build an NV center endoscope probe and enable NV center sensors for practical application. However, the low fluorescence collection efficiency of fibers due to their small numerical aperture (NA) has limited the sensitivity of the sensors. In this paper, a cone-shape microlens was fabricated using the photopolymerization process at the end of a multimode fiber to boost the laser excitation and fluorescence collection efficiency of NV centers. Experiments demonstrated that over 21 times fluorescence intensity enhancement and 12 times sensitivity improvement were achieved. This fiber-microlens magnetometer probe exhibited a 2.1-nT/Hz1/2 sensitivity over a bandwidth of 100 Hz with ∼80-µm diameter diamond. This research presented a robust and large NA diamond integrated fiber-microlens magnetometer probe, which can also be expanded to magnetic field scan and real-time monitoring.

Integration of Protein Nanocage with CpG Motifs: A Virus-Mimicked Core-Shell Nanostructure to Ignite Antitumor Immunity.

The tumor microenvironment typically possesses immunosuppressive properties that hinder the effectiveness of antitumor immune responses, even in the context of immunotherapies. However, it is observed that pathogenic microorganisms can trigger strong immune responses during infection, offering a potential means to counteract the immunosuppressive environment of tumors. In this study, a protein nanocage called CpG@HBc nanocages (NCs) is developed, which mimics the structure of the hepatitis B virus and combines with an immunostimulatory component known as cytosine phosphoguanosine oligonucleotide (CpG). By delivering these immunostimulatory agents, CpG@HBc NCs are able to effectively reverse the suppressive tumor microenvironment, resulting in the inhibition of poorly immunogenic tumors in mice. Through high-dimensional mass cytometry (CyTOF) analysis, remarkable alterations in immune responses is observed induced by CpG@HBc. Treatment with immunogenic CpG@HBc NCs, along with co-injection of an OX40 agonist, sensitized colorectal cancer tumors to T cell immune responses, resulting in significant impairment of tumor growth and robust immune activation. Furthermore, CpG@HBc NCs induced long-term antitumor immunological memory, protecting tumor-cured mice from tumor rechallenge. Overall, these findings highlight the potential of a virus-inspired protein nanocage to mimic anti-viral immunity and offer a unique therapeutic approach for cancer immunotherapy.

Sanqi Qushi Granule Alleviates Proteinuria and Podocyte Damage in NS Rat: A Network Pharmacology Study and in vivo Experimental Validation.

Background: Nephrotic syndrome (NS) and its numerous complications remain the leading causes of morbidity and mortality globally. Sanqi Qushi granule (SQG) is clinically effective in NS. However, its potential mechanisms have yet to be elucidated. Methods: A network pharmacology approach was employed in this study. Based on oral bioavailability and drug-likeness, potential active ingredients were picked out. After acquiring overlapping targets for drug genes and disease-related genes, a component-target-disease network and protein-protein interaction analysis (PPI) were constructed using Cytoscape, followed by GO and KEGG enrichment analyses. Adriamycin was injected into adult male Sprague-Dawley (SD) rats via the tail vein to establish NS model. Kidney histology, 24-hr urinary protein level, creatinine (Cr), blood urea nitrogen (BUN), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL-C) level were assessed. Western blotting, immunohistochemistry, and TUNEL staining were applied. Results: In total, 144 latent targets in SQG acting on NS were screened by a network pharmacology study, containing AKT, Bax, and Bcl-2. KEGG enrichment analysis suggested that PI3K/AKT pathway was enriched primarily. In vivo validation results revealed that SQG intervention ameliorated urine protein level and podocyte lesions in the NS model. Moreover, SQG therapy significantly inhibited renal cells apoptosis and decreased the ratio of Bax/Bcl-2 protein expression. Moreover, we found that Caspase-3 regulated the PI3K/AKT pathway in NS rats, which mediated the anti-apoptosis effect. Conclusion: By combining network pharmacology with experimental verification in vivo, this work confirmed the treatment efficacy of SQG for NS. SQG protected podocyte from injury and inhibited kidney apoptosis in NS rats via the PI3K/AKT pathway at least partially.

The efficacy and safety of Sanqi Qushi Granule in patients with idiopathic membranous nephropathy --protocol of a multicenter, randomized control trial (SQ-AUTUMN).

BACKGROUND: Adult nephropathy is mainly caused by idiopathic membranous nephropathy (IMN). In cases of proteinuria, Modified Ponticelli Regimens (MPR) are often successful. However, it can cause adverse side effects. Oral Sanqi Qushi Granule (SQG) with MPR is effective in patients with IMN. However, whether it can improve the remission rate of IMN and shorten the remission time is unknown. In this trial, SQG with MPR on IMN will be evaluated clinically for its efficacy and safety. METHODS: We will randomly assign IMN patients who meet the criteria to receives SQG plus cyclical Cyclophosphamide (CTX)/steroids or with placebo plus cyclical CTX/steroids for 6 months. A 12-month follow-up will be conducted on them. Status of remission will be used to assess treatment efficacy. DISCUSSION: This study aims to appraise whether treatment with SQG plus cyclical CTX/steroids is superior to placebo plus cyclical CTX/steroids in the remission rate of patients with adult IMN. Adverse events of SQG plus MPR will be also evaluated for further researches about Chinese Medicine and MPR on whether it can improve the remission rate of IMN in half a year and shorten the remission time and relieve adverse effects will also be clarified. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200061953 . Registered on 13 July 2022.

Tumor-Derived PD-L1+ Exosomes with Natural Inflammation Tropism for Psoriasis-Targeted Treatment.

Psoriasis is a chronic inflammatory disease whose etiology is directly related to the dysregulation of cutaneous immune homeostasis. However, how to finely modulate the skin immune microenvironment to restore homeostasis remains an important challenge. Inspired by the natural attribute of tumor exosomes in the immune escape, the tumor-derived exosomes as an active targeting nanoplatform for the effective treatment of inflammatory skin disorder were first reported. As keratinocytes and immune cells express high PD-1 during the onset of psoriasiform skin inflammation, the PD-L1-positive exosomes derived from melanoma cells carrying pristimerin with extremely anti-inflammatory potential were yielded to treat psoriasis. The PD-L1+ exosomes carrying pristimerin were characterized, and the cellular uptake was performed to evaluate the PD-1 target capability. The anti-inflammatory action of PD-L1+ exosomes carrying pristimerin was observed in both in vitro and in vivo models of psoriasis. Our exosomes substantially increased pristimerin uptake with CD4+ T cells and keratinocytes, significantly inhibited the proliferation of Th17 cells, and promoted Treg differentiation in a psoriasis-like model. Obviously, PD-L1+ exosomes carrying pristimerin significantly and safely reversed imiquimod (IMQ)-induced psoriasis in mice, indicated by reducing epidermal thickness, decreasing plaque formation, and suppressed excessive inflammatory response, due to its dual targeting of both CD4+ T cells and keratinocytes gathering around the lesion. The inflammatory cell infiltration and pro-inflammatory cytokine production in psoriasis were suppressed by our engineered exosomes. Besides, PD-L1+ exosomes carrying pristimerin treatment alleviated ferroptosis-related changes in psoriatic skin, thereby dampening excessive inflammation and, in turn, decreasing the abnormal proliferation of keratinocytes in psoriatic lesions. This study demonstrates that our engineered exosomes can not only act as a treat-to-target strategy for psoriasis treatment but also provide insight in clinical application of inflammatory disorders.

All Fiber Vector Magnetometer Based on Nitrogen-Vacancy Center.

Magnetometers based on nitrogen-vacancy (NV) centers in diamonds have promising applications in fields of living systems biology, condensed matter physics, and industry. This paper proposes a portable and flexible all-fiber NV center vector magnetometer by using fibers to substitute all conventional spatial optical elements, realizing laser excitation and fluorescence collection of micro-diamond with multi-mode fibers simultaneously and efficiently. An optical model is established to investigate multi-mode fiber interrogation of micro-diamond to estimate the optical performance of NV center system. A new analysis method is proposed to extract the magnitude and direction of the magnetic field, combining the morphology of the micro-diamond, thus realizing µm-scale vector magnetic field detection at the tip of the fiber probe. Experimental testing shows our fabricated magnetometer has a sensitivity of 0.73 nT/Hz1/2, demonstrating its feasibility and performance in comparison with conventional confocal NV center magnetometers. This research presents a robust and compact magnetic endoscopy and remote-magnetic measurement approach, which will substantially promote the practical application of magnetometers based on NV centers.

Specific Activation of CB2R Ameliorates Psoriasis-Like Skin Lesions by Inhibiting Inflammation and Oxidative Stress.

Psoriasis is a chronic inflammatory skin disease. Inflammation and oxidative stress play crucial roles in the pathogenesis of psoriasis. Cannabinoid receptor type 2 (CB2R) is an attractive target for treating various inflammatory disorders. However, the precise role and mechanism of CB2R activation in psoriasis remain to be further elucidated. In this study, imiquimod (IMQ)-induced experimental psoriasis mice and tumor necrosis factor-α (TNF-α)-activated keratinocytes (HaCaT) were used to examine the effect of CB2R activation on psoriasis-like lesions and the mechanism in vivo and in vitro. Our results demonstrated that activation of CB2R by the specific agonist GW842166X (GW) significantly ameliorated IMQ-induced psoriasiform skin lesions in mice by reducing epidermal thickness and decreasing plaque thickness. On the one hand, GW alleviated inflammation by decreasing inflammatory cytokines and abating inflammatory cell infiltration. On the other hand, this treatment reduced the level of iNOS and downregulated the expression of CB2R in psoriatic skin tissue. Further studies suggested that the Kelch-like ECH-associated protein 1/nuclear factor erythroid-2-related factor (Keap1/Nrf2) signaling pathway might be involved. Our findings reveal that selective activation of CB2R may serve as a new strategy for the treatment of psoriasis.

Sequential administration of virus-like particle-based nanomedicine to elicit enhanced tumor chemotherapy.

Protein cages have played a long-standing role in biomedicine applications, especially in tumor chemotherapy. Among protein cages, virus like particles (VLPs) have received attention for their potential applications in vaccine development and targeted drug delivery. However, most of the existing protein-based platform technologies are plagued with immunological problems that may limit their systemic delivery efficiency as drug carriers. Here, we show that using immune-orthogonal protein cages sequentially and modifying the dominant loop epitope can circumvent adaptive immune responses and enable effective drug delivery using repeated dosing. We genetically modified three different hepadnavirus core protein derived VLPs as delivery vectors for doxorubicin (DOX). These engineered VLPs have similar assembly characteristics, particle sizes, and immunological properties. Our results indicated that there was negligible antibody cross-reactivity in either direction between these three RGD-VLPs in mice that were previously immunized against HBc VLPs. Moreover, the sequential administration of multiple RGD-VLP-based nanomedicine (DOX@RGD-VLPs) could effectively reduce immune clearance and inhibited tumor growth. Hence, this study could provide an attractive protein cage-based platform for therapeutic drug delivery.

US-Net: A lightweight network for simultaneous speckle suppression and texture enhancement in ultrasound images.

BACKGROUND: Numerous traditional filtering approaches and deep learning-based methods have been proposed to improve the quality of ultrasound (US) image data. However, their results tend to suffer from over-smoothing and loss of texture and fine details. Moreover, they perform poorly on images with different degradation levels and mainly focus on speckle reduction, even though texture and fine detail enhancement are of crucial importance in clinical diagnosis. METHODS: We propose an end-to-end framework termed US-Net for simultaneous speckle suppression and texture enhancement in US images. The architecture of US-Net is inspired by U-Net, whereby a feature refinement attention block (FRAB) is introduced to enable an effective learning of multi-level and multi-contextual representative features. Specifically, FRAB aims to emphasize high-frequency image information, which helps boost the restoration and preservation of fine-grained and textural details. Furthermore, our proposed US-Net is trained essentially with real US image data, whereby real US images embedded with simulated multi-level speckle noise are used as an auxiliary training set. RESULTS: Extensive quantitative and qualitative experiments indicate that although trained with only one US image data type, our proposed US-Net is capable of restoring images acquired from different body parts and scanning settings with different degradation levels, while exhibiting favorable performance against state-of-the-art image enhancement approaches. Furthermore, utilizing our proposed US-Net as a pre-processing stage for COVID-19 diagnosis results in a gain of 3.6% in diagnostic accuracy. CONCLUSIONS: The proposed framework can help improve the accuracy of ultrasound diagnosis.

A nanoformulation for immunosuppression reversal and broad-spectrum self-amplifying antitumor ferroptosis-immunotherapy.

The efficacy of immunotherapy combined with other therapeutic modalities in the management of cancer has been extensively studied. However, no effective strategy to improve the antitumor effects of immunotherapy at the tumor site has been developed. In this study, we describe a nanoformulation (CP) that integrates ferroptosis-inducing cannabinoid nanoparticles with immunostimulatory Poly(I:C) to enhance antitumor immune responses by activating ferroptosis-immunotherapy pathways. The results indicated that CP nanoformulation effectively induced ferroptosis, cellular immunogenic death, and anti-tumor immune responses which initiate T cell responses leading to the inhibition of established tumors. In addition, CP nanoformulations reversed the tumor immunosuppressive microenvironment and promoted tumor ferroptosis. These results indicated that the self-amplifying nanoformulation may be an effective strategy for broad-spectrum cancer immunotherapy.

Compact fiber sensor for pH measurement based on the composite effect of hydrogel deformation and LC refractive index variation.

A novel, to the best of our knowledge, type of compact pH fiber sensor combined with a hydrogel based on the whispering gallery mode (WGM) is proposed and integrates a liquid crystal (LC) microdroplet in a capillary in a compact structure as small as 180 µm. In the research, the hydrogel performs both as a supporting frame and a responsive material that causes morphological deformation of the LC microdroplet with pH variation. Moreover, a new phenomenon of pH-induced LC refractive index variation is observed and applied in the pH measurement, so that the acid itself can also lead the LC microdroplet structure transition. Thus, the WGM method is applied to detect the composite effect simultaneously to improve the sensing capability. The sensitivity of the sensor in the pH range from 4.55 to 6.86 reaches 3.19 nm/pH. The response time is short, within 60 s. The simple and compact structure of the sensor reduces the cost and enhances the stability, which is of great potential for biomedical pH measurement.

An Inverse Emulsion Polymer as a Highly Effective Salt- and Calcium-Resistant Fluid Loss Reducer in Water-Based Drilling Fluids.

To control the fluid loss of water-based drilling fluids (WBDFs) in salt-gypsum formations, a nano-SiO2 graft copolymer was prepared by inverse emulsion polymerization. The polymer (EAANS) was prepared with acrylamide, 2-acrylamido-2-methyl-1-propane sulfonic acid, N-vinylpyrrolidone, and KH570-modified nano-silica (M-SiO2) as raw materials. The molecular structure and morphology of EAANS were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance, thermogravimetric analysis, transmission electron microscopy (TEM), and other methods. In the temperature range of 150 °C, 2 wt % EAANS can reduce the API filtration volume of the base slurry to within 20 mL and the HP-HT filtration volume at 150 °C to 21.8 mL. More importantly, 2 wt % EAANS can maintain the API filtration volume less than 10 mL even when the concentration of NaCl or CaCl2 was as high as 36 or 30 wt %, and as the salt/calcium content increased, the amount of filtration continued to decrease. The results of TEM, X-ray diffraction, particle size distribution, and scanning electron microscopy showed that the fluid loss control mechanism of EAANS was that EAANS can form a crosslinked network structure in the solution and adsorb on the clay surface, so as to reduce the particle size of clay particles, increase the proportion of fine particles in drilling fluids, and finally form a dense filter cake to reduce the filtration volume. Because of the excellent filtration performance of EAANS at high Na+/Ca2+ concentration, EAANS can become a promising WBDF fluid loss reducer in salt-gypsum formations.

Ultra-low sample consumption consecutive-detection method for biochemical molecules based on a whispering gallery mode with a liquid crystal microdroplet.

Ultra-low sample consumption detection has many applications in molecular biology, bioanalytical chemistry, and medical science. In this Letter, a novel, to the best of our knowledge, simple type of ultra-low sample consumption detection method based on a whispering gallery mode is proposed as a means to realize consecutive detection with a liquid crystal (LC) microdroplet for biochemical molecule detection, using deoxyribonucleic acid (DNA) as a model biomarker. The sensor consists of a 105-µm-core multimode fiber fused with a hollow capillary tube, with the LC microdroplet suspended stably in the testing solution. Its application to the detection of salmon sperm DNA yielded an adjustable measurement range of 3.75-11.25 µg/ml and a sensitivity of 0.33 nm/µg/ml. The test solution required as little as 3 nl of the sample, and the limit of detection was 1.32 µg/ml, which corresponds to the effective detection of as little as 3.96 pg of DNA. This method has great potential for application in the ultra-low sample consumption detection of biochemical molecules.

Multifaceted roles of a bioengineered nanoreactor in repressing radiation-induced lung injury.

Radiation-induced lung injury (RILI) is a potentially fatal and dose-limiting complication of thoracic cancer radiotherapy. However, effective therapeutic agents for this condition are limited. Here, we describe a novel strategy to exert additive effects of a non-erythropoietic EPO derivative (ARA290), along with a free radical scavenger, superoxide dismutase (SOD), using a bioengineered nanoreactor (SOD@ARA290-HBc). ARA290-chimeric nanoreactor makes SOD present in a confined reaction space by encapsulation into its interior to heighten stability against denaturing stimuli. In a RILI mouse model, intratracheal administration of SOD@ARA290-HBc was shown to significantly ameliorate acute radiation pneumonitis and pulmonary fibrosis. Our investigations revealed that SOD@ARA290-HBc performs its radioprotective effects by protecting against radiation induced alveolar epithelial cell apoptosis and ferroptosis, suppressing oxidative stress, inhibiting inflammation and by modulating the infiltrated macrophage phenotype, or through a combination of these mechanisms. In conclusion, SOD@ARA29-HBc is a potential therapeutic agent for RILI, and given its multifaceted roles, it may be further developed as a translational nanomedicine for other related disorders.

In Situ biomimetic Nanoformulation for metastatic cancer immunotherapy.

Metastasis is the leading cause of death in cancer patients. Eliciting anti-tumor immune responses against lung metastasis is hindered by the immunosuppressive microenvironment. This study explored a biomimetic nanoformulation, comprising a nanovaccine (OP) that delivers tumor antigens and adjuvants spatially and temporally in a virus-like manner, and a pulmonary surfactant-biomimetic liposome with an immunomodulator, JQ1 (PS-JQ1). The findings of this study showed that intratracheal administration of OP+PS-JQ1 activated lung immune cells without concomitant excess inflammation, enhanced tumor antigen cross-presentation, generated a significantly high antigen-specific CD8+ T cell response, and reshaped the immunocellular composition in B16 melanoma tumor-bearing lung. OP+PS-JQ1 nanoformulation exhibited a striking immunotherapeutic efficacy, induced local and systemic tumor suppression, improved survival of mice, initiated immune memory that prevents recurrence of secondary tumors. This stable and nontoxic nanoformulation provides a simple, flexible, and robust strategy for augmenting anti-tumor immunity for metastatic cancer. STATEMENT OF SIGNIFICANCE: Egg glue proteins are produced by female insects, which can make the eggs firmly attached to the oviposition sites, not affected by wind and rain. However, genes encoding insect egg glue proteins have not yet been reported, and the molecular mechanism underpinning their adhesion is still unknown. Our study makes a significant contribution to the literature as it identifies the sequence, structure, adhesive property, and mechanism of silkworm egg glue protein. Furthermore, it outlines key insights into the structure-function relationships associated with egg glue proteins. We believe that this paper will be of interest to the readership of your journal as it identifies the first complete sequence of insect egg glue proteins, thereby highlighting their potentials future applications in both the biomedical and technical fields.

Tubule-specific protein nanocages potentiate targeted renal fibrosis therapy.

BACKGROUND: Despite the dramatic advances in modern medicine, efficient therapeutic measures for renal fibrosis remain limited. Celastrol (CLT) is effective in treating renal fibrosis in rat models, while causing severe systemic toxicity. Thus, we designed a tubule-specific nanocage (K3-HBc NCs) that effectively deliver CLT to tubular epithelial cell in a virus-like manner. The targeting ligand (K3) to tubular epithelial cells was displayed on the surface of Hepatitis B core protein (HBc) NCs by genetic fusion to the major immunodominant loop region. Ultra-small CLT nanodots were subtly encapsulated into the cavity through electrostatic interaction with the disassembly and reassembly of K3-HBc NCs, to yield K3-HBc/CLT complex. The efficacy of K3-HBc/CLT NCs were demonstrated in Unilateral ureteral obstruction (UUO)-induced renal fibrosis. RESULTS: The self-assembled K3-HBc/CLT could specifically target tubular epithelial cells via affinity with K3 ligand binding to the megalin receptor, significantly attenuating renal fibrosis. Remarkably, K3-HBc/CLT NCs significantly increased therapeutic efficacy and reduced the systemic toxicity in comparison with free CLT in UUO-induced mouse renal fibrosis model. Importantly, analysis of RNA sequencing data suggested that the anti-fibrotic effect of K3-HBc/CLT could be attributed to suppression of premature senescence in tubular epithelial cells via p21Cip1 and p16Ink4a pathway. CONCLUSION: The tubule-specific K3-HBc/CLT represented a promising option to realize precise treatment for renal fibrosis.