When synchronous mucinous metaplasia and neoplasia of the female genital tract and peutz-jeghers syndrome meet: a case report and literature reviews.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is characterized by the presence of hamartomatous polyps in the gastrointestinal tract and mucocutaneous pigmentation on the lips, oral mucosa, nose, fingers, and toes. Synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) refers to the occurrence of multifocal mucinous lesions in at least two sites, including the cervix, uterus, fallopian tubes, and ovaries, in the female genital tract. SMMN-FGT and PJS are rare diseases with a very low incidence, especially when occurring simultaneously. CASE PRESENTATION: We report a case in which a woman with a large mass on the left ovary underwent a gynecological surgery and was diagnosed with cervical gastric-type adenocarcinoma and mucinous lesions in the endometrium, bilateral fallopian tubes, and ovary, i.e., SMMN-FGT, by postoperative paraffin pathology. The patient sought medical attention for abdominal distension and enlargement. A gynecological ultrasound revealed a multilocular cystic mass in the pelvis, while serum tumor markers were within normal limits, with mildly elevated carbohydrate antigen 199 and carbohydrate antigen 125 levels. Cervical thin-prep cytology test result was negative. The patient had a family history of PJS with black spots on her skin and mucous membranes since the age of 8 years. She underwent multiple partial small bowel resections and gastrointestinal polypectomy owing to intestinal obstruction and intussusception. She underwent left adnexectomy, hysterectomy, right salpingectomy, greater omental resection, appendectomy and right ovary biopsy, and received six courses of adjuvant chemotherapy with Lopressor plus Carboplatin. Genetic testing revealed a heterozygous serine threonine kinase 11 germline mutation and there were no signs of recurrence during the 18-month follow-up period after treatment. CONCLUSIONS: This is a rare case in which PJS was complicated by SMMN-FGT. Owing to its extreme rarity, there are no guidelines, but reported cases appear to indicate a poor prognosis. We retrospectively reviewed all cases of collisions between PJS and SMMN-FGT and explored the clinical features, pathological characteristics, diagnosis, treatment methods, and prognosis when the two diseases coexisted. The aim is to deepen the clinicians' understanding of this disease for early detection, diagnosis and treatment.

Case report: Bilateral facial palsy with paresthesias and positive anti-GT1a antibodies.

Bilateral facial palsy with paresthesia (FDP) is a rare variant of GBS, characterized by simultaneous bilateral facial palsy and paresthesia of the distal limbs. Mounting evidence indicates that the presence of anti-GT1a IgG has a pathogenic role as an effector molecule in the development of cranial nerve palsies in certain patients with GBS, whereas anti-GT1a antibody is rarely presented positive in FDP. Here, we report the case of a 33-year-old male diagnosed with FDP presented with acute onset of bilateral facial palsy and slight paresthesias at the feet as the only neurological manifestation. An antecedent infection with no identifiable reason for the fever or skin eruptions was noted in the patient. He also exhibited cerebrospinal fluid albuminocytologic dissociation and abnormal nerve conduction studies. Notably, the testing of specific serum anti-gangliosides showed positive anti-GT1a IgG/IgM Ab. The patient responded well to intravenous immunoglobulin therapy. This case brings awareness to a rare variant of GBS, and provides the first indication that anti-GT1a antibodies play a causative role in the development of FDP. The case also suggests that prompt management with IVIG should be implemented if FDP is diagnosed.

Tannic acid protects against colitis by regulating the IL17 - NFκB and microbiota - methylation pathways.

Tannic acid, a bioactive polyphenol found in various phytogenic foods and medicinal plants, has potential prevention effects on colitis, though more evidence and mechanistic studies are required to substantiate this. In this study, we investigated the effects of different doses from 0 to 3 mg/mL of tannic acid on mice, ultimately selecting a dose of 3 mg/mL for the anti-colitis trial based on growth and intestinal morphology assessments. Using the DSS-induced colitis model, we found that tannic acid may alleviate colitis by inhibiting the IL-17 - NF-κB p65 signaling pathway and modulating epigenetic pathways, particularly methylation modifications. Additionally, tannic acid altered the gut microbiota, increasing the abundances of Prevotella, Eubacterium_siraeum_group, and Enterorhabdus in the colon. Supplementation with Eubacterium siraeum via gavage also inhibited colitis, accompanied by increased folate and methylation regulators in the colon. These findings suggest that tannic acid may inhibit colitis through the suppression of the IL-17 - NF-κB pathway and the enhancement of microbiota-mediated methylation pathways.

SIRT1 as a potential therapeutic target in pelvic organ prolapse due to protective effects against oxidative stress and cellular senescence in human uterosacral ligament fibroblasts.

INTRODUCTION: The pathogenesis of pelvic organ prolapse (POP), an age-related disease, has not been fully elucidated. Therapeutic targets of POP are limited. Silencing information regulator 2 related enzyme 1 (SIRT1), a gene considered capable of regulating oxidative stress and cellular senescence, has been widely demonstrated involved in aging and age-related diseases. The present study aimed to explore the role of SIRT1 in POP in vivo and in vitro. METHODS: Expression levels of SIRT1 in uterosacral ligament (USL) tissues from patients with or without POP were measured using immunohistochemical assays. SRT1720, a SIRT1 agonist, was used to upregulate SIRT1, and hydrogen peroxide (H2O2) was used to establish an oxidative stress model in human uterosacral ligament fibroblasts (hUSLFs). The effects of SIRT1 on cell viability, apoptosis, senescence, and reactive oxygen species (ROS) levels were detected, respectively. Western blot assays were used to examine expression levels of apoptosis- and senescence-associated biomarkers. Unpaired Student's t test, Mann-Whitney U test, χ2 test, and one-way ANOVA were performed for determining statistically significant differences. RESULTS: Compared to the control group, expression levels of SIRT1 were downregulated in USL tissues and hUSLFs from patients with POP, and associated with stage (p < 0.05). hUSLFs of patients with POP had lower growth rates (p < 0.0001) than those of the control group, which were improved by upregulating SIRT1 (p < 0.05). The senescent proportion was higher in the POP group than the control group (43.63 ± 10.62% vs. 4.84 ± 5.32%, p < 0.0001), which could be reduced by upregulating SIRT1 (p < 0.0001). High ROS levels in the POP group were also alleviated by SRT1720. H2O2 exposure increased ROS levels, inhibited proliferation, and triggered apoptosis and senescence in hUSLFs of patients without POP in a concentration-dependent manner. Further, these damages were alleviated by pretreatment with SRT1720. CONCLUSIONS: SIRT1 is downregulated in patients with POP, and the development of SIRT1 activators or agonists may have applications in the treatment and prevention of POP through antioxidative stress and antisenescence effects.

Research Progress and Application of Multimodal Flexible Sensors for Electronic Skin.

In recent years, wearable electronic skin has garnered significant attention due to its broad range of applications in various fields, including personal health monitoring, human motion perception, human-computer interaction, and flexible display. The flexible multimodal sensor, as the core component of electronic skin, can mimic the multistimulus sensing ability of human skin, which is highly significant for the development of the next generation of electronic devices. This paper provides a summary of the latest advancements in multimodal sensors that possess two or more response capabilities (such as force, temperature, humidity, etc.) simultaneously. It explores the relationship between materials and multiple sensing capabilities, focusing on both active materials that are the same and different. The paper also discusses the preparation methods, device structures, and sensing properties of these sensors. Furthermore, it introduces the applications of multimodal sensors in human motion and health monitoring, as well as intelligent robots. Finally, the current limitations and future challenges of multimodal sensors will be presented.

Discovery of Novel Aryl Triazolone Dihydropyridines (ATDPs) Targeting Highly Conserved Residue W229 as Promising HIV-1 NNRTIs.

NNRTI is an important component of the highly active antiretroviral therapy (HAART), but the rapid emergence of drug resistance and poor pharmacokinetics limited their clinical application. Herein, a series of novel aryl triazolone dihydropyridines (ATDPs) were designed by structure-guided design with the aim of improving drug resistance profiles and pharmacokinetic profiles. Compound 10n (EC50 = 0.009-17.7 µM) exhibited the most active potency, being superior to or comparable to that of doravirine (DOR) against the whole tested viral panel. Molecular docking was performed to clarify the reason for its higher resistance profiles. Moreover, 10n demonstrated excellent pharmacokinetic profile (T1/2 = 5.09 h, F = 108.96%) compared that of DOR (T1/2 = 4.4 h, F = 57%). Additionally, 10n was also verified to have no in vivo acute or subacute toxicity (LD50 > 2000 mg/kg), suggesting that 10n is worth further investigation as a novel oral NNRTIs for HIV-1 therapy.

Integrating portable NIR spectrometry with deep learning for accurate Estimation of crude protein in corn feed.

This study investigates the challenges encountered in utilizing portable near-infrared (NIR) spectrometers in agriculture, specifically in developing predictive models with high accuracy and robust generalization abilities despite limited spectral resolution and small sample sizes. The research concentrates on the near-infrared spectra of corn feed, utilizing spectral processing techniques and CNNs to precisely estimate crude protein content. Five preprocessing methods were implemented alongside two-dimensional (2D) correlation spectroscopy, resulting in the development of both one-dimensional (1D) and 2D regression models. A comparative analysis of these models in predicting crude protein content demonstrated that 1D-CNNs exhibited superior predictive performance within the 1D category. For the 2D models, CropNet and CropResNet were utilized, with CropResNet demonstrating more accurate and superior predictive capabilities. Overall, the integration of 2D correlation spectroscopy with suitable preprocessing techniques in deep learning models, particularly the 2D CropResNet, proved to be more precise in predicting the crude protein content in corn feed. This finding emphasis the potential of this approach in the portable spectrometer market.

Precision in wheat flour classification: Harnessing the power of deep learning and two-dimensional correlation spectrum (2DCOS).

Wheat flour is a ubiquitous food ingredient, yet discerning its various types can prove challenging. A practical approach for identifying wheat flour types involves analyzing one-dimensional near-infrared spectroscopy (NIRS) data. This paper introduces an innovative method for wheat flour recognition, combining deep learning (DL) with Two-dimensional correlation spectrum (2DCOS). In this investigation, 316 samples from four distinct types of wheat flour were collected using a near-infrared (NIR) spectrometer, and the raw spectra of each sample underwent preprocessing employing diverse methods. The discrete generalized 2DCOS algorithm was applied to generate 3792 2DCOS images from the preprocessed spectral data. We trained a deep learning model tailored for flour 2DCOS images - EfficientNet. Ultimately, this DL model achieved 100% accuracy in identifying wheat flour within the test set. The findings demonstrate the viability of directly transforming spectra into two-dimensional images for species recognition using 2DCOS and DL. Compared to the traditional stoichiometric method Partial Least Squares Discriminant Analysis (PLS_DA), machine learning methods Support Vector Machines (SVM) and K-Nearest Neighbors (KNN), and deep learning methods one-dimensional convolutional neural network (1DCNN) and residual neural network (ResNet), the model proposed in this paper is better suited for wheat flour identification, boasting the highest accuracy. This study offers a fresh perspective on wheat flour type identification and successfully integrates the latest advancements in deep learning with 2DCOS for spectral type identification. Furthermore, this approach can be extended to the spectral identification of other products, presenting a novel avenue for future research in the field.

Advancements in Brain Research: The In Vivo/In Vitro Electrochemical Detection of Neurochemicals.

Neurochemicals, crucial for nervous system function, influence vital bodily processes and their fluctuations are linked to neurodegenerative diseases and mental health conditions. Monitoring these compounds is pivotal, yet the intricate nature of the central nervous system poses challenges. Researchers have devised methods, notably electrochemical sensing with micro-nanoscale electrodes, offering high-resolution monitoring despite low concentrations and rapid changes. Implantable sensors enable precise detection in brain tissues with minimal damage, while microdialysis-coupled platforms allow in vivo sampling and subsequent in vitro analysis, addressing the selectivity issues seen in other methods. While lacking temporal resolution, techniques like HPLC and CE complement electrochemical sensing's selectivity, particularly for structurally similar neurochemicals. This review covers essential neurochemicals and explores miniaturized electrochemical sensors for brain analysis, emphasizing microdialysis integration. It discusses the pros and cons of these techniques, forecasting electrochemical sensing's future in neuroscience research. Overall, this comprehensive review outlines the evolution, strengths, and potential applications of electrochemical sensing in the study of neurochemicals, offering insights into future advancements in the field.

Redox-responsive polymer micelles co-encapsulating immune checkpoint inhibitors and chemotherapeutic agents for glioblastoma therapy.

Immunotherapy with immune checkpoint blockade (ICB) for glioblastoma (GBM) is promising but its clinical efficacy is seriously challenged by the blood-tumor barrier (BTB) and immunosuppressive tumor microenvironment. Here, anti-programmed death-ligand 1 antibodies (aPD-L1) are loaded into a redox-responsive micelle and the ICB efficacy is further amplified by paclitaxel (PTX)-induced immunogenic cell death (ICD) via a co-encapsulation approach for the reinvigoration of local anti-GBM immune responses. Consequently, the micelles cross the BTB and are retained in the reductive tumor microenvironment without altering the bioactivity of aPD-L1. The ICB efficacy is enhanced by the aPD-L1 and PTX combination with suppression of primary and recurrent GBM, accumulation of cytotoxic T lymphocytes, and induction of long-lasting immunological memory in the orthotopic GBM-bearing mice. The co-encapsulation approach facilitating efficient antibody delivery and combining with chemotherapeutic agent-induced ICD demonstrate that the chemo-immunotherapy might reprogram local immunity to empower immunotherapy against GBM.

Construction of MoS2-ReS2 Hybrid on Ti3C2Tx MXene for Enhanced Microwave Absorption.

Utilizing interface engineering to construct abundant heterogeneous interfaces is an important means to improve the absorbing performance of microwave absorbers. Here, we have prepared the MXene/MoS2-ReS2 (MMR) composite with rich heterogeneous interfaces composed of two-dimensional Ti3C2Tx MXene and two-dimensional transition metal disulfides through a facile hydrothermal process. The surface of MXene is completely covered by nanosheets of MoS2 and ReS2, forming a hybrid structure. MRR exhibits excellent absorption performance, with its strongest reflection loss reaching -51.15 dB at 2.0 mm when the filling ratio is only 10 wt%. Meanwhile, the effective absorption bandwidth covers the range of 5.5-18 GHz. Compared to MXene/MoS2 composites, MRR with a MoS2-ReS2 heterogeneous interface exhibits stronger polarization loss ability and superior absorption efficiency at the same thickness. This study provides a reference for the design of transition metal disulfides-based absorbing materials.

Phosphorylated YBX2 is stabilized to promote glycolysis in brown adipocytes.

Y-box binding protein 2 (YBX2) is an essential modulator of brown adipose tissue activation, yet the regulation on its own expression and the involved mechanism remains largely unknown. Herein, we report the YBX2 protein level, but not mRNA level, is induced in response to acute ß-adrenergic signaling. In this context, YBX2 is a dual substrate for both AMPK and Akt2. The phosphorylation at Thr115 by AMPK or at Ser137 by Akt2 facilitates YBX2 accumulation in brown adipocytes by decreasing ubiquitination-mediated degradation. Beyond stabilizing PGC1α mRNA, increased YBX2 upon thermogenic activation assists the expression of glycolytic enzymes, promotes glucose utilization and lactate production. Mechanistically, YBX2 modulates translation of glycolytic genes via direct binding to 5'-UTRs of these genes. Together these findings suggest YBX2 is responsive to thermogenic stimuli by phosphorylation modification, and stabilized YBX2 helps to boost glycolysis and thermogenesis in brown adipocytes.

PtAg18 superatoms costabilized by phosphines and halides: synthesis, structure, and catalysis.

Reported herein is the facial synthesis, molecular structure, and catalysis of a Pt/Ag nanocluster costabilized by organic ligands of phosphines and inorganic ligands of chlorides. The nanocluster with molecular formula of [PtAg18(dppp)6Cl8](SbF6)2 has been obtained facilely by the one pot method. The structure of the cluster could be anatomized as the stabilizaiton of PtAg12-centered icosahedral core by the metalloligand of dppp-Ag-Cl, in which Cl- not only caps the surface Ag atoms but also binds the core and surface motifs. Featuring eight free electrons in its structure, the cluster exhibits high stability. More interestingly, the exposure of surface metal sites endows the cluster with counterintutively  high catalytic activity in hydrogenation reactions.

Acid-switchable nanoparticles induce self-adaptive aggregation for enhancing antitumor immunity of natural killer cells.

Deficiency of natural killer (NK) cells shows a significant impact on tumor progression and failure of immunotherapy. It is highly desirable to boost NK cell immunity by upregulating active receptors and relieving the immunosuppressive tumor microenvironment. Unfortunately, mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors, thus declining antitumor efficiency. Herein, we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15 (IL-15). The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction, which provides a new methodology to trigger aggregation. It shows self-adaptive size-enlargement upon acidity, thus improving drug retention in tumor to over 120 h. The diameter of agglomerates is increased and drug release is effectively promoted following reduced pH values. The nanoparticles activate both NK cell and CD8+ T cell immunity in vivo. It significantly suppresses CT26 tumor in immune-deficient BALB/c mice, and the efficiency is further improved in immunocompetent mice, indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity. The approach reported here provides an innovative strategy to improve drug retention in tumors, which will enhance cancer immunotherapy by boosting NK cells.

MATR3-antisense LINE1 RNA meshwork scaffolds higher-order chromatin organization.

Long interspersed nuclear elements (LINEs) play essential roles in shaping chromatin states, while the factors that cooperate with LINEs and their roles in higher-order chromatin organization remain poorly understood. Here, we show that MATR3, a nuclear matrix protein, interplays with antisense LINE1 (AS L1) RNAs to form a meshwork via phase separation, providing a dynamic platform for chromatin spatial organization. MATR3 and AS L1 RNAs affect the nuclear localization of each other. After MATR3 depletion, the chromatin, particularly H3K27me3-modified chromatin, redistributes in the cell nuclei. Topologically associating domains (TADs) that highly transcribe MATR3-associated AS L1 RNAs show decreased intra-TAD interactions in both AML12 and ES cells. MATR3 depletion increases the accessibility of H3K27me3 domains adjacent to MATR3-associated AS L1, without affecting H3K27me3 modifications. Furthermore, amyotrophic lateral sclerosis (ALS)-associated MATR3 mutants alter biophysical features of the MATR3-AS L1 RNA meshwork and cause an abnormal H3K27me3 staining. Collectively, we reveal a role of the meshwork formed by MATR3 and AS L1 RNAs in gathering chromatin in the nucleus.

Visual Investigation of Tumor-Promoting Fibronectin Potentiated by Obesity in Pancreatic Ductal Adenocarcinoma Using an MR/NIRF Dual-Modality Dendrimer Nanoprobe.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease characterized by dense stroma. Obesity is an important metabolic factor that greatly increases PDAC risk and mortality, worsens progression and leads to poor chemotherapeutic outcomes. With omics analysis, magnetic resonance and near-infrared fluorescence (MR/NIRF) dual-modality imaging and molecular functional verification, obesity as an important risk factor is proved to modulate the extracellular matrix (ECM) components and enhance Fibronectin (FN) infiltration in the PDAC stroma, that promotes tumor progression and worsens response to chemotherapy by reducing drug delivery. In the study, to visually evaluate FN in vivo and guide PDAC therapy, an FN-targeted nanoprobe, NP-CREKA, is synthesized by conjugating gadolinium chelates, NIR797 and fluorescein isothiocyanate to a polyamidoamine dendrimer functionalized with targeting peptides. A dual-modality strategy combining MR and NIRF imaging is applied, allowing effective visualization of FN in orthotopic PDAC with high spatial resolution, ideal sensitivity and excellent penetrability, especially in obese mice. In conclusion, the findings provide new insights into the potential of FN as an ideal target for therapeutic evaluation and improving treatment efficacy in PDAC, hopefully improving the specific management of PDAC in lean and obese hosts.

Recruiting T-Cells toward the Brain for Enhanced Glioblastoma Immunotherapeutic Efficacy by Co-Delivery of Cytokines and Immune Checkpoint Antibodies with Macrophage-Membrane-Camouflaged Nanovesicles.

Immunotherapy with immune checkpoint inhibitors (CPIs) shows promising prospects for glioblastoma multiforme (GBM) but with restricted results, mainly attributed to the immunosuppressive tumor microenvironment (TME) and the limited antibody permeability of the blood-tumor barrier (BTB) in GBM. Here, nanovesicles with a macrophage-mimicking membrane are described, that co-deliver chemotactic CXC chemokine ligand 10 (CXCL10), to pre-activate the immune microenvironment, and anti-programmed death ligand 1 antibody (aPD-L1), to interrupt the immune checkpoint, aiming to enhance the effect of GBM immunotherapy. Consequently, the tumor tropism of the macrophage membrane and the receptor-mediated transcytosis of the angiopep-2 peptide allow the nanovesicle to effectively cross the BTB and target the GBM region, with 19.75-fold higher accumulation of antibodies compared to the free aPD-L1 group. The CPI therapeutic efficacy is greatly enhanced by CXCL10-induced T-cells recruitment with significant expansion of CD8+ T-cells and effector memory T-cells, leading to the elimination of tumor, prolonged survival time, and long-term immune memory in orthotopic GBM mice. The nanovesicles, that relieve the tumor immunosuppressive microenvironment by CXCL10 to enhance aPD-L1 efficacy, may present a promising strategy for brain-tumor immunotherapy.

Spatial-Drug-Laden Protease-Activatable M1 Macrophage System Targets Lung Metastasis and Potentiates Antitumor Immunity.

Lung metastasis is a critical cause of cancer mortality and its therapy is largely challenged by the limited drug delivery efficiency and robust immunosuppression in metastatic tumors. Herein, we designed a spatial-drug-laden M1 macrophage system with liposomal R848 inside and fibroblast activation protein protease (FAP)-sensitive phospholipid-DM4 conjugate on the membrane of M1 macrophage (RDM). RDM could preferentially accumulate at the metastatic lesions in lungs and responsively release the therapeutic agents as free drug molecules or drug-loaded nanovesicles. RDM treatment notably enhanced the infiltration of CD3+CD8+ T cells to lung metastasis and, respectively, caused an 8.54-, 12.87- and 2.85-fold improvement of the granzyme-B-, interferon-γ-, and Ki67-positive subtypes versus negative control. Moreover, RDM treatment produced a 90.99% inhibition of lung metastasis in 4T1 models and significant prolongation of survival in three murine lung metastatic models. Therefore, the drug-laden FAP-sensitive M1 macrophage system represents a feasible strategy to target lung metastasis and boost antitumor immunity for antimetastasis therapy.

Comparative analysis of hepatitis B virus infections in blood donors born before and after the implementation of universal HBV vaccination in southern China.

BACKGROUND: In China, the vaccinated blood donors have rapidly increased by recent years, which may impact blood safety. The true prevalence of HBV between vaccinated blood donors and non-vaccinated blood donors should be explored. STUDY DESIGN AND METHODS: The samples of blood donors were collected and detected for serologic markers of HBV in the Shenzhen Blood Centre (SZBC). The discrepant results were tested with commercial electrochemiluminescence immunoassay (ELCI) for HBsAg, anti-HBs, HBeAg, Anti-HBe and Anti-HBc, alternative MPX ID NAT, nested PCR, and a quantitative real-time polymerase chain reaction (qPCR) assay for HBV DNA. The serological and molecular characteristics of HBV infected blood donors were analysed, and the effects on blood safety for donors born before and after the implementation of universal HBV vaccination were compared. RESULTS: Out of 242 presumed HBV infected donors from 26 318 donations, 131 (0.49%, [95% CI, 0.43-0.59]) chronic HBV infections (CHB, HBsAg detected with or without DNA), 58 (0.22%, [95% CI, 0.17-0.28]) occult hepatitis B infections (OBI, HBsAg not detected, assume anti-HBc positive and/or anti-HBs with HBV DNA) and 3 (0.011%, [95% CI, 0.0023-0.033]) window period (WP) infections were confirmed respectively. There were 28 CHBs (0.44%), 7 OBIs (0.11%) and 1 WP (0.016%) from vaccinated blood donor and 103 CHBs (0.52%), 51 OBIs (0.26%) and 2 WPs (0.01%) from non-vaccinated blood donor. The HBV+ (CHBs, OBIs and WPs) rate (0.56%) in vaccinated donors was lower than in non-vaccinated donors (0.78%, p < 0.05). The HBsAg titers of vaccinated infected blood donors (Median: 128.8 IU/ml) were much higher than non-vaccinated infected blood donors (58.4 IU/ml). The OBI yield rates in the vaccinated blood donors was significantly lower than the non-vaccinated blood donors (p < 0.05). There 102/124 (82.3%) samples were genotype B, 22/124 (17.7%) were genotype C respectively. There was no significant difference in the distribution of genotype between non-vaccinated blood donors (B/C, 86/17) and vaccinated blood donors (B/C, 23/6; p > 0.05). High frequency of vaccine escape mutations M133L (32.4%) and E164G in S region of genotype B strains and substitution L175S (40.9%) related to vaccine escape in S region of genotype C strains were identified. CONCLUSION: The universal HBV vaccination program markedly reduces the risk of HBV infection in blood donors, and provides a significant guarantee for the safety of blood transfusion. Several important mutations detected related vaccine escape and notable mutations needed further investigated.

Macrophage Membrane-Coated Nano-Gemcitabine Promotes Lymphocyte Infiltration and Synergizes AntiPD-L1 to Restore the Tumoricidal Function.

The limited lymphocyte infiltration and exhaustion of tumoricidal functions in solid tumors remain a formidable obstacle to cancer immunotherapy. Herein, we designed a macrophage membrane-coated nano-gemcitabine system (MNGs) to promote lymphocyte infiltration and then synergized anti-programmed death ligand 1 (antiPD-L1) to reinvigorate the exhausted lymphocytes. MNGs exhibited effective intratumor-permeating and responsive drug-releasing capacity, produced notable elimination of versatile immunosuppressive cells, and promoted lymphocyte infiltration into cancer cell regions in tumors, but over 50% of these infiltrated lymphocytes were in the exhausted state. Compared with MNG monotherapy, the MNGs+antiPD-L1 combination produced 31.77% and 30.63% reduction of exhausted CD3+CD8+ T cells and natural killer (NK) cells and 2.83- and 3.17-fold increases of interferon-γ (IFN-γ)-positive subtypes, respectively, thereby resulting in considerable therapeutic benefits in several tumor models. Thus, MNGs provide an encouraging strategy to promote lymphocyte infiltration and synergize antiPD-L1 to restore their tumoricidal function for cancer immunotherapy.