Clinical Influence of Nursing Intervention Under FOCUS-Plan-Do-Check-Act Cycle Management Model on Preventing and Controlling Central Line-associated Bloodstream Infections in Patients in ICU.

Background: Central venous catheterization is an invasive procedure that may lead to central line-associated bloodstream infection, affecting the patient's prognosis and recovery. Thus, it is essential to master the right interventions for the prevention and control of central line-associated bloodstream infections. FOCUS-Plan-Do-Check-Act (PDCA) cycle management model, also known as Deming circle management model, is a programmed and scientific management method. Objective: We attempted to clarify the impact of nursing intervention on preventing and controlling central line-associated bloodstream infection under the FOCUS- PDCA cycle management model, in order to effectively deplete central line-associated bloodstream infection in each intensive care unit, facilitate early recovery of patients. Design: Our study retrospectively analyzed the clinical data of intensive care unit patients before and after implementation of nursing intervention under the FOCUS-PDCA cycle management model. This study was a retrospective study. Setting: This study was performed in the Department of Infection Management, Taihe County People's Hospital. Participants: A total of 214 intensive care unit patients with indwelling central venous catheters before implementation of nursing intervention under the FOCUS-PDCA cycle management model in our hospital in 2021 were selected as the control group. A total of 220 ICU patients with indwelling CVC after nursing intervention under the FOCUS-PDCA cycle management model in 2022 were included in the experimental group. All patients met the inclusion criteria of patients with CVC puncture catheterization for ≥ 2 days. Interventions: The control group underwent conventional nursing, including (1) nurses observing aseptic technique; (2) nurses regularly inspected and replaced dressings; (3) nurses timely handled abnormal situations at the puncture site; (4) nurses provided relevant education and psychological counseling to patients and their families. The experimental group adopted nursing intervention under the FOCUS-PDCA cycle management model on the basis of that of the control group. Primary Outcome Measures: (1) central venous catheterization puncture status (2) central venous catheterization application status (3) central line-associated bloodstream infection status, and (4) hospitalization status. Results: The one-time success rate of puncture and success rate of puncture in the experimental group exhibited elevation relative to those in the control group (P < .05). The central venous catheterization application rate in the experimental group exhibited depletion relative to that in the control group (P < .05). The daily infection rate of CLABSI in the experimental group exhibited depletion relative to that in the control group, but without statistical significance (P > .05), indicating that nursing intervention under the FOCUS-PDCA cycle management model had no obvious inhibitory effect on the daily infection rate of CLABSI. The time of central line-associated bloodstream infection occurrence in the experimental group was later than that in the control group (P < .05). The hospitalization time and hospitalization expenses in the experimental group exhibited depletion relative to those in the control group (P < .05). Conclusion: Nursing intervention under the FOCUS-PDCA cycle management model can effectively deplete central line-associated bloodstream infection in each intensive care unit, facilitate early recovery of patients, and shorten hospital stay, which is worthy of promotion. Our study provide a clinical nursing reference for the preventing and controlling central line-associated bloodstream infections in patients in each intensive care unit.

UV-assisted synthesis of ultra-small GO-Austar for efficient PTT therapeutic architectonic construction.

Conventional Au nanomaterial synthesis typically necessitates the involvement of extensive surfactants and reducing agents, leading to a certain amount of chemical waste and biological toxicity. In this study, we innovatively employed ultra-small graphene oxide as a reducing agent and surfactant for the in situ generation of small Au nanoparticles under ultraviolet irradiation (UV) at ambient conditions. After ultra-small GO-Au seeds were successfully synthesized, we fabricated small star-like Au nanoparticles on the surface of GO, in which GO effectively prevented Austar from aggregation. To further use GO-Austar for cancer PTT therapy, through the modification of reduced human serum albumin-folic acid conjugate (rHSA-FA) and loading IR780, the final probe GO-Austar@rHSA-FA@IR780 was prepared. The prepared probe showed excellent biocompatibility and superb phototoxicity towards MGC-803 cells in vitro. In vivo, the final probe dramatically increased tumor temperature up to 58.6 °C after 5 minutes of irradiation by an 808 nm laser, significantly inhibiting tumor growth and nearly eradicating subcutaneous tumors in mice. This research provides a novel and simple method for the synthesis of GO-Au nanocomposites, showcasing significant potential in biological applications.

Genetic variations in DNA excision repair pathway contribute to the chemosensitivity and prognosis of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a hematologic malignancy with a high recurrence rate and poor long-term prognosis. DNA excision repair systems, such as base excision repair (BER) and nucleotide excision repair (NER), play a major role in maintaining genomic stability and integrity. Further intensive investigations are necessary to uncover additional AML prognosis loci. In this study, we analyzed 16 candidate SNPs within NER and BER pathways in AML patients. Our results showed the GT/GG genotype of the XPC rs2228001 polymorphism was significantly associated with WBC count in dominant models (OR = 0.41, 95 % CI = 0.18-0.96, p = 0.039). Additionally, the rs25487 and rs3213245 SNPs in the XRCC1 gene, in both co-dominant and dominant models, were significantly associated with PLT count in AML (p < 0.05). The GG genotype of rs1130409 in APEX1 was more prone to adverse cytogenetics in both the codominant and recessive models (p < 0.05). Furthermore, the GA genotypes of ERCC8 rs158572 in codominant model was significantly correlated with refractory group (p < 0.05). ERCC8 rs158572 and XRCC1 rs3213245 in both codominant and dominant models were significantly correlated with the MRD positivity (p < 0.05). Kaplan-Meier analysis revealed an link between overall survival (OS) and the co-dominant, dominant, and recessive models of rs2228001 in XPC. Additionally, patients with the GG and GT/GG genotype in the co-dominant, dominant model and recessive model in XPC rs2228001 exhibited significantly longer survival (p < 0.05). Multivariate Cox analyses indicated that rs2228001 in both co-dominant and dominant models were independent favorable factors impacting patient OS (OR < 1). Our findings suggest that genetic polymorphisms in DNA excision repair pathway genetic polymorphisms contribute to the chemosensitivity and prognosis of acute myeloid leukemia.

An ingestible near-infrared fluorescence capsule endoscopy for specific gastrointestinal diagnoses.

Early diagnosis of gastrointestinal (GI) diseases is important to effectively prevent carcinogenesis. Capsule endoscopy (CE) can address the pain caused by wired endoscopy in GI diagnosis. However, existing CE approaches have difficulty effectively diagnosing lesions that do not exhibit obvious morphological changes. In addition, the current CE cannot achieve wireless energy supply and attitude control at the same time. Here, we successfully developed a novel near-infrared fluorescence capsule endoscopy (NIFCE) that can stimulate and capture near-infrared (NIR) fluorescence images to specifically identify subtle mucosal microlesions and submucosal lesions while capturing conventional white light (WL) images to detect lesions with significant morphological changes. Furthermore, we constructed the first synergetic system that simultaneously enables multi-attitude control in NIFCE and supplies long-term power, thus addressing the issue of excessive power consumption caused by the NIFCE emitting near-infrared light (NIRL). We performed in vivo experiments to verify that the NIFCE can specifically "light up" tumors while sparing normal tissues by synergizing with probes actively aggregated in tumors, thus realizing specific detection and penetration. The prototype NIFCE system represents a significant step forward in the field of CE and shows great potential in efficiently achieving early targeted diagnosis of various GI diseases.

Expression of a SAG protein with a CAP domain from Eimeria necatrix and its role in invasion and immunoprotection.

Eimeria necatrix is a high pathogenic pathogen, which seriously endangers the poultry industry. The surface antigens (SAGs) of Apicomplexa are a kind of membrane protein anchored on the surface of the parasites through its carboxyl terminal glycosylphosphatidylinositol (GPI) structure. However, little is known about GPI-linked surface proteins in E. necatrix. In the present work, the E. necatrix sag gene (Ensag-CAP) was amplified and cloned for expression of the recombinant protein (rEnSAG-CAP). The full length Ensag-CAP gene was 813 bp, coding 270 amino acids with a predicated molecular weight of 28.86 kDa and contained a CAP domain with four sequence motifs CAP1, CAP2, CAP3 and CAP4. The rEnSAG-CAP was about 32 kDa and mainly expressed in a soluble form. Western blot analysis indicated that the rEnSAG-CAP could be recognized by anti-rEnSAG-CAP monoclonal antibody (anti-rEnSAG-CAP McAb) and the convalescent serum of chicken infected with E. necatrix. Native protein of EnSAG-CAP was detected in second-generation merozoites (MZ-2) using anti-rEnSAG-CAP polyclonal antibody (anti-rEnSAG-CAP pAb). The findings from the indirect immunofluorescence assay and enzyme digestion utilizing Bacillus cereus phosphoinositide-specific phospholipase C (PI-PLC) revealed that EnSAG-CAP predominantly localized at the surfaces of SZ and MZ-2 via a GPI anchor. It was observed that EnSAG-CAP can be cleaved from MZ-2 by PI-PLC. Real-time quantitative PCR (qPCR) analysis showed that transcript levels of Ensag-CAP in MZ-2 was significantly higher than that in SZ (P < 0.05). The anti-rEnSAG-CAP McAb in vitro could significantly inhibit the sporozoite invasion into MDBK cells (P < 0.01), which suggests that the protein might participate in sporozoite invasion into MDBK cells. rEnSAG-CAP afforded an immune protection against E. necatrix. The ACI value was 164.99 in the chickens immunized with 200 µg rEnSAG-CAP. Chickens immunized with rEnSAG-CAP had a significantly higher antigen-specific serum IgY response (P < 0.0001). The data indicates that EnSAG-CAP could serve as a potential candidate antigen for the development of a recombinant coccidiosis vaccine.

Identification of IL-8 in CSF as a potential biomarker in sepsis-associated encephalopathy.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is frequently present at the acute and chronic phase of sepsis, which is characterized by delirium, coma, and cognitive dysfunction. Despite the increased morbidity and mortality of SAE, the pathogenesis of SAE remains unclear. This study aims to discover the potential biomarkers, so as to clear the pathogenesis potentially contributing to the development of SAE and provide new therapeutic strategies for the treatment of SAE. METHODS: The GSE135838 dataset was obtained from the Gene Expression Omnibus (GEO) database and utilized for analysis the differentially expressed genes (DEGs). The DEGs were analyzed by limma package of R language and the extracellular protein-differentially expressed genes (EP-DEGs) were screened by the Human Protein Atlas (HPA) and UniProt database. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out to analyze the function and pathway of EP-DEGs. STRING, Cytoscape, MCODE and Cytohubba were used to construct a protein-protein interaction (PPI) network and screen key EP-DEGs. Key EP-DEGs levels were detected in the cerebrospinal fluid (CSF) of SAE patients and non-sepsis patients with critical illness. ROC curve was used to evaluate the diagnostic of SAE. RESULTS: We screened 82 EP-DEGs from DEGs. EP-DEGs were enriched in cytokine-cytokine receptor interaction, IL-17 signaling pathway and NOD-like receptor signaling pathway. We identified 2 key extracellular proteins IL-1B and IL-8. We clinically verified that IL-6 and IL-8 levels were increased in CSF of SAE patients and CSF IL-8 (AUC = 0.882, 95 % CI = 0.775-0.988) had a higher accuracy in the diagnosis of SAE than CSF IL-6 (AUC = 0.824, 95 % CI = 0.686-0.961). Furthermore, we found that the IL-8 levels in CSF might not associated with Glasgow Coma Scale (GCS) scores of SAE patients. CONCLUSION: IL-8 may be the key extracellular cytokine in the pathogenesis of SAE. Bioinformatics methods were used to explore the biomarkers of SAE and validated the results in clinical samples. Our findings indicate that the IL-8 in CSF might be the potential diagnostic biomarker and therapeutic target in SAE.

Developing an efficient MGCR microneedle nanovaccine patch for eliciting Th 1 cellular response against the SARS-CoV-2 infection.

Rationale: Novel vaccine R&D is essential to interrupt the COVID-19 pandemic and other epidemics in the future. Subunit vaccines have received tremendous attention for their low cost and safety. To improve the immunogenicity of subunit vaccines, we developed a novel vaccine adjuvant system. Methods: Here we rationally designed a CpG 1018 and graphene oxide-based bi-adjuvant system to deliver the Receptor-Binding Domain (RBD) of the SARS-CoV-2 spike protein and obtained the graphene oxide-based complex adjuvant nanovaccine (GCR). Furthermore, we developed a microneedle patch vaccine (MGCR) based on the GCR vaccine. Results: GCR nanovaccine displayed superb antigen loading and encapsulation efficiency. Two dosages of vaccination of GCR nanovaccine could elicit adequate RBD-specific binding antibody response with 2.14-fold higher IgG titer than Alum adjuvant vaccine. The peptide pools assay demonstrated the robust RBD-specific Type 1 Cellular response induced by the GCR nanovaccine in CD8+ T cells. Furthermore, we prepared an MGCR microneedle patch, which generated a similar RBD-specific binding antibody response to the GCR vaccine, sustained a high antibody level above 16 weeks, and significantly elevated the Tcm proportion in mouse spleen. The MGCR microneedle patch vaccine also could be stably stored at room temperature for several months and administrated without medical staff, which maximizes the vaccine distribution efficiency. Conclusion: The vaccine system could significantly improve the vaccine distribution rate in low-income areas and offer a potential vaccination approach to fight against the SARS-Cov-2 infection and other pandemics occurred in the future.

Confining Prepared Ultrasmall Nanozymes Loading ATO for Lung Cancer Catalytic Therapy/Immunotherapy.

Nanozymes with inherent enzyme-mimicking catalytic properties combat malignant tumor progression via catalytic therapy, while the therapeutic efficacy still needs to be improved. In this work, ultrasmall platinum nanozymes (nPt) in a confined domain of a wormlike pore channel in gold nanobipyramidal-mesoporous silica dioxide nanocomposites, producing nanozyme carriers AP-mSi with photoenhanced peroxidase ability, are innovatively synthesized. Afterward, based on the prepared AP-mSi, a lung-cancer nanozymes probe (AP-HAI) is ingeniously produced by removing the SiO2 template, modifying human serum albumin, and loading atovaquone molecules (ATO) as well as IR780. Under NIR light irradiation, inner AuP and IR780 collaborate for photothermal process, thus facilitating the peroxidase-like catalytic process of H2 O2 . Additionally, loaded ATO, a cell respiration inhibitor, can impair tumor respiration metabolism and cause oxygen retention, hence enhancing IR780's photodynamic therapy (PDT) effectiveness. As a result, IR780's PDT and nPt nanozymes' photoenhanced peroxidase-like ability endow probes a high ROS productivity, eliciting antitumor immune responses to destroy tumor tissue. Systematic studies reveal that the obvious reactive oxygen species (ROS) generation is obtained by the strategy of using nPt nanozymes and reducing oxygen consumption by ATO, which in turn enables lung-cancer synergetic catalytic therapy/immunogenic-cell-death-based immunotherapy. The results of this work would provide theoretical justification for the practical use of photoenhanced nanozyme probes.

Examination of gametocyte protein 22 localization and oocyst wall formation in Eimeria necatrix using laser confocal microscopy and scanning electron microscopy.

BACKGROUND: Eimeria parasite infection occurs via ingestion of oocysts. The robust, bilayer oocyst wall is formed from the contents of wall-forming bodies (WFBs), WFB1 and WFB2, located exclusively in macrogametocytes. Eimeria necatrix gametocyte proteins 22 and 59 (EnGAM22 and EnGAM59) have been found to localize to WFBs and the oocyst wall. However, the exact localization of these two proteins is not clear. METHODS: WFBs of E. necatrix were extracted from purified gametocytes using a cutoff filter and the extracts of purified WFBs and gametocytes were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Then, the localization of EnGAM22 and EnGAM59 proteins was determined using an indirect immunofluorescence assay. Finally, the development of macrogametocytes and the oocyst wall of E. necatrix was analyzed using laser confocal microscopy and scanning electron microscopy. RESULTS: Purified WFBs had the same shape and size as those observed in macrogametocytes. EnGAM22 protein localized to WFB1, whereas EnGAM59 protein localized to WFB2. Both EnGAM22 and EnGAM59 native proteins were detected in the extracts of WFBs and gametocytes. The outer layer of the oocyst wall was formed by the release of the contents of WFB1 at the surface of the macrogametocyte to form an anti-EnGAM22 positive layer. WFB2 then appeared to give rise to the inner layer, which was anti-EnGAM59 positive. CONCLUSIONS: EnGAM22 and EnGAM59 proteins localized to WFB1 and WFB2 and were involved in the formation of the outer and inner layers of the oocyst wall of E. necatrix, respectively. The processes of macrogametogenesis and oocyst wall formation of E. necatrix are similar to other Eimeria parasites. The anti-EnGAM22 antibody could be used as a tool to track the transport and secretion of proteins in WFB1 during oocyst development.

Recent developments of sonodynamic therapy in antibacterial application.

The rapid emergence of pathogenic bacteria poses a serious threat to global health. Notably, traditional antibiotic therapies suffer from the risk of strengthening bacterial drug resistance. Sonodynamic therapy (SDT) combining sonosensitizers and low-intensity ultrasound (US) has broadened the way towards treating drug-resistant bacteria. The allure of this therapy emerges from the capacity to focus the US energy on bacterial infection sites buried deep in tissues, locally activating the sonosensitizers to produce cytotoxic reactive oxygen species (ROS) with the ability to induce bacterial death. The past decade has witnessed the rapid development of antibacterial SDT owing to their excellent penetration, favorable biocompatibility and specific targeting ability. This review summarizes available sonosensitizers for antibacterial SDT, and digs into innovative biotechnologies to improve SDT efficiency, such as enhancing the targeting ability of sonosensitizers, image-guided assisted SDT, improvement of hypoxia and combination of SDT with other therapies. Finally, we conclude with the present challenges and provide insights into the future research of antibacterial SDT.

Electrochemical Cytosensor Based on a Gold Nanostar-Decorated Graphene Oxide Platform for Gastric Cancer Cell Detection.

Effectively capturing and sensitively detecting cancer cells are critical to clinical diagnosis and cancer therapy. In this work, we prepared gold nanostar-decorated graphene oxide (GO-AuNSs) nanocomposites using a ultraviolet (UV)-induced strategy, and then modified them with a layer of bio-complex rBSA-FA (coupled reduced bovine serum albumin with folic acid) to generate GO-AuNSs@rBSA-FA nanocomposites. Herein, the application of GO and AuNSs not only strengthened the conductivity of the sensing platform but also guaranteed nanocomposites with biocompatible performance. Moreover, the adopted rBSA-FA layer could effectively enhance the stability and specificity towards gastric cancer cells (MGC-803). According to a systemic construction procedure, a novel electrochemical cytosensor based on GO-AuNSs@rBSA-FA was fabricated for MGC-803 cell detection. With the assistance of cyclic voltammetry (CV) and differential pulse voltammetry (DPV), the cytosensor reached a detection limit of 100 cell/mL in a wide linear range of 3 × 102~7 × 106 cell/mL towards MGC-803 cells. The good electrochemical characteristics for the cancer cell analysis indicate a promising prospect of this electrochemical cytosensor in clinical cancer diagnosis.

A Review on Metal- and Metal Oxide-Based Nanozymes: Properties, Mechanisms, and Applications.

Since the ferromagnetic (Fe3O4) nanoparticles were firstly reported to exert enzyme-like activity in 2007, extensive research progress in nanozymes has been made with deep investigation of diverse nanozymes and rapid development of related nanotechnologies. As promising alternatives for natural enzymes, nanozymes have broadened the way toward clinical medicine, food safety, environmental monitoring, and chemical production. The past decade has witnessed the rapid development of metal- and metal oxide-based nanozymes owing to their remarkable physicochemical properties in parallel with low cost, high stability, and easy storage. It is widely known that the deep study of catalytic activities and mechanism sheds significant influence on the applications of nanozymes. This review digs into the characteristics and intrinsic properties of metal- and metal oxide-based nanozymes, especially emphasizing their catalytic mechanism and recent applications in biological analysis, relieving inflammation, antibacterial, and cancer therapy. We also conclude the present challenges and provide insights into the future research of nanozymes constituted of metal and metal oxide nanomaterials.

Urinary exosomes-based Engineered Nanovectors for Homologously Targeted Chemo-Chemodynamic Prostate Cancer Therapy via abrogating EGFR/AKT/NF-kB/IkB signaling.

Multi-functional nanovectors based on exosomes from cancer cell culture supernatants in vitro has been successfully utilized for tumor-specific targeting and immune escape. However, the labor-intensive purification procedures for rich-dose and high-purity homogeneous exosomes without using targeting ligands are still a challenging task. Herein, we developed a nanovector Exo-PMA/Fe-HSA@DOX through cloaked by urinary exosome membrane as a chemo/chemodynamic theranostic nano-platform for targeted homologous prostate cancer therapy which pertain to the abrogation of Epidermal Growth Factor Receptor (EGFR) and its downstream AKT/NF-kB/IkB signaling instead of ERK signaling cascades. Urinary exosomes-based nanovectors own the same urological cancer cell membrane antigen inclusive of E-cadherin, CD 47 and are free from intracellular substance such as Histone 3 and COX Ⅳ. The targeting properties of the homologous cancer cell are well preserved in Exo-PMA/Fe-HSA@DOX nanovectors in high purity. Meanwhile, the nanovectors based on urinary exosomes from prostate patients deeply penetrated into prostate cancer DU145 3D MCTS, and successfully achieve superior synergistic low-dose chemo/chemodynamic performance in vivo. In addition, the blockage of bypassing EGFR/AKT/NF-kB/IkB signaling pathway is greatly enhanced via elevated intracellular PMA/Fe-HSA@DOX nanoparticles (NPs). It is expected that the rich source and high purity of urinary exosomes offer a reliable solution for mass production of such nanovectors in the future. The targeted homologous cancer therapy based on the urinary exosomes from cancer patients exemplifies a novel targeted anticancer scheme with efficient and facile method.

SR-A-Targeted Nanoplatform for Sequential Photothermal/Photodynamic Ablation of Activated Macrophages to Alleviate Atherosclerosis.

Cardiovascular and cerebrovascular diseases induced by atherosclerosis (AS) have become the dominant cause of disability and mortality throughout the world. The typical early pathological process of AS involves the activation of inflammatory macrophages in the vulnerable plaque. In this work, we first employed chitosan-coated carbon nanocages (CS-CNCs) as nanocarriers to load Chlorin e6 (Ce6) and then linked dextran sulfate (DS) to the outermost layer by electrostatic adsorption to create a multifunctional therapeutic nanoplatform, CS-CNCs@Ce6/DS. The DS of the nanoplatform can recognize and bind to the type A scavenger receptor (SR-A), which is expressed only on the activated macrophages of the arterial plaque, so the proposed nanoplatform selectively targets these macrophages and accumulates there. Furthermore, DS can competitively inhibit cellular endocytosis of oxidized low-density lipoproteins via blocking of SR-A. The rapid photothermal conversion capability of CS-CNCs enables efficient therapeutic delivery during photothermal therapy (PTT). Interestingly, near-infrared-accelerated drug release induced by initial 808-nm laser irradiation was observed, thus enhancing the Ce6 concentration in the atherosclerotic plaque area and the efficiency of photodynamic therapy (PDT). Sequential photothermal/photodynamic ablation of the activated macrophages reduced pro-inflammatory cytokine secretion and alleviated the proliferation and migration of smooth muscle cells. These finally resulted in the stabilization and shrinkage of atherosclerotic plaques, further inhibiting the development and exacerbation of AS. Therefore, this work achieved a "1 + 1 greater than 2" effect by providing a novel approach to the treatment of atherosclerotic plaques, which is promising for the prevention of AS-related diseases.

Breath analysis based early gastric cancer classification from deep stacked sparse autoencoder neural network.

Deep learning is an emerging tool, which is regularly used for disease diagnosis in the medical field. A new research direction has been developed for the detection of early-stage gastric cancer. The computer-aided diagnosis (CAD) systems reduce the mortality rate due to their effectiveness. In this study, we proposed a new method for feature extraction using a stacked sparse autoencoder to extract the discriminative features from the unlabeled data of breath samples. A Softmax classifier was then integrated to the proposed method of feature extraction, to classify gastric cancer from the breath samples. Precisely, we identified fifty peaks in each spectrum to distinguish the EGC, AGC, and healthy persons. This CAD system reduces the distance between the input and output by learning the features and preserve the structure of the input data set of breath samples. The features were extracted from the unlabeled data of the breath samples. After the completion of unsupervised training, autoencoders with Softmax classifier were cascaded to develop a deep stacked sparse autoencoder neural network. In last, fine-tuning of the developed neural network was carried out with labeled training data to make the model more reliable and repeatable. The proposed deep stacked sparse autoencoder neural network architecture exhibits excellent results, with an overall accuracy of 98.7% for advanced gastric cancer classification and 97.3% for early gastric cancer detection using breath analysis. Moreover, the developed model produces an excellent result for recall, precision, and f score value, making it suitable for clinical application.

Carbon nanocage-based nanozyme as an endogenous H2O2-activated oxygenerator for real-time bimodal imaging and enhanced phototherapy of esophageal cancer.

Intelligent phototherapy by theranostic nanosystems that can be activated by a tumor microenvironment has high sensitivity and specificity. However, hypoxia and low drug accumulation in tumors greatly limit its clinical application. Herein, we have designed a cage-like carbon-manganese nanozyme, which effectively relieves tumor hypoxia and delivers numerous photosensitizers (PSs) to the tumor site, for real-time imaging and enhanced phototherapy of esophageal cancer. Specifically, bovine serum albumin (BSA) was used as a template and reducing agent for preparing a BSA-MnO2 nanozyme; then a BSA-MnO2/IR820@OCNC (BMIOC) nanosystem was successfully synthesized by crosslinking BSA-MnO2 on the surface of IR820-loaded carboxylated carbon nanocages (OCNCs). Abundant PSs were successfully delivered to tumor sites via hollow OCNCs, and the final loading rate of IR820 reached 42.8%. The intratumor BMIOC nanosystem can be initiated by a tumor microenvironment to switch on its magnetic resonance (MR) imaging signal, and photothermal therapy (PTT) and photodynamic therapy (PDT) functions. Notably, the BSA-MnO2 nanozyme, with intrinsic catalase (CAT)-like activity, catalyzed endogenous H2O2 for oxygen generation to overcome tumor hypoxia and enhance PDT, thereby leading to more efficient therapeutic effects in combination with OCNC-elevated PTT. In addition, the H2O2-activated and acid-enhanced properties enable our nanosystem to be specific to tumors, protecting normal tissues from damage. By integrating a high drug loading capacity, a hypoxia regulation function, an enlarged phototherapy effect, and bimodal imaging into a nanozyme-mediated nanoreactor, this work realizes a "one for all" system and represents promising clinical translation for efficient esophageal cancer theranostics.

Genetic polymorphisms and expression of NLRP3 inflammasome-related genes are associated with Philadelphia chromosome-negative myeloproliferative neoplasms.

Inflammation plays a crucial role in the initiation, progression and prognosis of Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), which could be clinically subdivided into polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Nucleotide binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasomes affect inflammatory diseases and carcinomas by excessive production of cytokines. To investigate a possible association of NLRP3 inflammasome signaling with MPN, we investigated the expression of selected inflammasome-related genes from bone marrow cells of 67 MPN patients as well as gene polymorphisms in NLRP3 (rs35829419), NF-κB1 (rs28362491), CARD8 (rs2043211), IL-1ß (rs16944), and IL-18 (rs1946518). It showed that inflammasome-related genes (NLRP3, NF-κB1, CARD8, IL-1ß, and IL-18) were highly expressed in BM cells from MPN patients and the increased expression was associated with JAK2V617F mutation, white blood cell counts and splenomegaly. Analysis of genetic polymorphisms in 269 MPN patients and 291 healthy controls demonstrated that NF-κB1 (rs28362491) was associated with MPN and increased expression of NF-κB1, NLRP3 and IL-1ß. This research provided novel biomarkers and potential targets for MPN.

Passion fruit-like exosome-PMA/Au-BSA@Ce6 nanovehicles for real-time fluorescence imaging and enhanced targeted photodynamic therapy with deep penetration and superior retention behavior in tumor.

Exosomes (Exos) of approximately 30-150 nm in diameters are the promising vehicles for therapeutic drugs. However, several challenges still exist in clinical applications, such as unsatisfied yield of exosomes, complicated labeling procedure and low drug loading efficiency. In this work, the gram-scale amount of high-purity urinary exosomes can be obtained from gastric cancer patients by non-invasive method. Passion fruit-like Exo-PMA/Au-BSA@Ce6 nanovehicles were fabricated by considerable freshly-urinary Exos loaded efficiently with multi-functionalized PMA/Au-BSA@Ce6 nanoparticles via instant electroporation strategy. In this system, prepared Exo-PMA/Au-BSA@Ce6 nanovehicles could be internalized into cancer cells effectively, and could delay the endocytosis of macrophages and prolong blood circulation time owing to its membrane structure and antigens. Under 633 nm laser irradiation and acidic condition, the structures of nanovehicles would be collapsed and tremendous PMA/Au-BSA@Ce6 nanoparticles could be released inside cancer cells, produced considerable singlet oxygen, inhibiting growth of tumor cells. In vivo experiment of MGC-803 tumor-bearing nude mice showed that prepared Exo-PMA/Au-BSA@Ce6 nanovehicles could target tumor cells with deep penetration and superior retention performance in tumors. This work reports a reliable conjugation-free labeling strategy for tracking exosomes harvested from human urine. Moreover, the integration of multifunctional nanoparticles with urinary Exos paves a versatile road for the development of cancer-targeted photodynamic therapy.

The vacuolization of macrophages induced by large amounts of inorganic nanoparticle uptake to enhance the immune response.

Inorganic nanoparticles (NPs), particularly iron oxide (IO) and gold (Au) NPs, are widely used in a variety of biomedical applications, such as diagnosis and cancer therapy. As an important component of host defense in organisms, macrophages play a crucial role in responding to foreign substances, such as nanoparticles. Thus, it is of utmost importance to understand the nanotoxicity effects on the immune system by investigating the influences of such nanoparticles. In this study, we found that macrophages can take up large amounts of amphiphilic polymer (PMA)-modified Au and IO NPs, which will induce macrophage cell vacuolization and enhance macrophage polarization. This mechanism is an essential part of the immune response in vivo. In addition, we report that smaller-sized nanoparticles (ca. 4 nm) show more significant effects on the macrophage polarization and caused lysosomal damage compared to larger nanoparticles (ca. 14 nm). Moreover, the amount of NP uptake in macrophages decreases upon trapping the PMA with PEG, resulting in reduced vacuolization and a reduced immune response. We hypothesize that vacuoles are formed in large amounts during NP uptake by macrophages, which enhances the immune response and induces macrophages toward M1 polarization. These findings are potentially useful for disease treatment and understanding the immune response when NPs are used in vitro and in vivo.

In vivo comparison of the biodistribution and long-term fate of colloids - gold nanoprisms and nanorods - with minimum surface modification.

Aim: To study the difference in biodistribution of gold nanoprisms (NPr) and nanorods (NR), PEGylated to ensure colloidal stability. Materials & methods: Surface changes were studied for nanoparticles in different media, while the biodistribution was quantified and imaged in vivo. Results: Upon interaction with the mouse serum, NR showed more abrupt changes in surface properties than NPr. In the in vivo tests, while NPr accumulated similarly in the spleen and liver, NR showed much higher gold presence in the spleen than in liver; together with some accumulation in kidneys, which was nonexistent in NPr. NPr were cleared from the tissues 2 months after administration, while NR were more persistent. Conclusion: The results suggest that the differential biodistribution is caused by size-/shape-dependent interactions with the serum.