Discovery of anticancer function of Febrifugine: Inhibition of cell proliferation, induction of apoptosis and suppression steroid synthesis in bladder cancer cells.

Bladder cancer is a prevalent malignancy affecting the urinary system, which presents a significant global health concern. Although there are many treatments for bladder cancer, identifying more effective drugs and methods remains an urgent problem. As a pivotal component of contemporary medical practice, traditional Chinese medicine (TCM) assumes a crucial role in the realm of anti-tumor therapy, especially with the identification of active ingredients and successful exploration of pharmacological effects. Febrifugine, identified as a quinazoline-type alkaloid compound extracted from the Cytidiaceae family plant Huangchangshan, exhibits heightened sensitivity to bladder cancer cells in comparison to control cells (non-cancer cells) group. The proliferation growth of bladder cancer cells T24 and SW780 was effectively inhibited by Febrifugine, and the IC50 was 0.02 and 0.018 µM respectively. Febrifugine inhibits cell proliferation by suppressing DNA synthesis and induces cell death by reducing steroidogenesis and promoting apoptosis. Combined with transcriptome analysis, Febrifugine was found to downregulate low density lipoprotein receptor-associated protein, lanosterol synthase, cholesterol biosynthesis second rate-limiting enzyme, 7-dehydrocholesterol reductase, flavin adenine dinucleotide dependent oxidoreductase and other factors to inhibit the production of intracellular steroids in bladder cancer T24 cells. The results of animal experiments showed that Febrifugine could inhibit tumor growth. In summary, the effect of Febrifugine on bladder cancer is mainly through reducing steroid production and apoptosis. Therefore, this study contributes to the elucidation of Febrifugine's potential as an inhibitor of bladder cancer and establishes a solid foundation for the future development of novel therapeutic agents targeting bladder cancer.

Protein Post-Translational Modifications Based on Proteomics: A Potential Regulatory Role in Animal Science.

Genomic studies in animal breeding have provided a wide range of references; however, it is important to note that genes and mRNA alone do not fully capture the complexity of living organisms. Protein post-translational modification, which involves covalent modifications regulated by genetic and environmental factors, serves as a fundamental epigenetic mechanism that modulates protein structure, activity, and function. In this review, we comprehensively summarize various phosphorylation and acylation modifications on metabolic enzymes relevant to energy metabolism in animals, including acetylation, succinylation, crotonylation, ß-hydroxybutylation, acetoacetylation, and lactylation. It is worth noting that research on animal energy metabolism and modification regulation lags behind the demands for growth and development in animal breeding compared to human studies. Therefore, this review provides a novel research perspective by exploring unreported types of modifications in livestock based on relevant findings from human or animal models.

Miniature Magnetic Resonance Imaging System for in Situ Monitoring of Bacterial Growth and Biofilm Formation.

In situ monitoring of bacterial growth can greatly benefit human healthcare, biomedical research, and hygiene management. Magnetic resonance imaging (MRI) offers two key advantages in tracking bacterial growth: non-invasive monitoring through opaque sample containers and no need for sample pretreatment such as labeling. However, the large size and high cost of conventional MRI systems are the roadblocks for in situ monitoring. Here, we proposed a small, portable MRI system by combining a small permanent magnet and an integrated radio-frequency (RF) electronic chip that excites and reads out nuclear spin motions in a sample, and utilize this small MRI platform for in situ imaging of bacterial growth and biofilm formation. We demonstrate that MRI images taken by the miniature--and thus broadly deployable for in situ work--MRI system provide information on the spatial distribution of bacterial density, and a sequential set of MRI images taken at different times inform the temporal change of the spatial map of bacterial density, showing bacterial growth.

Proteomics, Transcriptomics, and Phosphoproteomics Reveal the Mechanism of Talaroconvolutin-A Suppressing Bladder Cancer via Blocking Cell Cycle and Triggering Ferroptosis.

Talaroconvolutin-A (TalaA) is a compound from the endophytic fungus T. convolutispora of the Chinese herbal medicine Panax notoginseng. Whether TalaA exerts anticancer activity in bladder cancer remains unknown. Using CCK8 assay, EdU staining, crystal violet staining, flow cytometry, living/dead cell staining, and Western blotting, we studied the anticancer activity of TalaA in vitro. Moreover, we performed xenograft tumor implantation. The antitumor effects were evaluated through H&E and immunohistochemistry staining. Proteomics was conducted to detect changes in the protein profile; transcriptomics was performed to detect changes in mRNA abundance; phosphoproteomics was used to detect changes in protein phosphorylation. TalaA inhibited tumor cell proliferation, DNA replication, and colony formation in a dose-dependent manner in bladder cancer cells. The IC50 values of TalaA on SW780 and UM-UC-3 cells were 5.7 and 8.2 µM, respectively. TalaA (6.0 mg/kg) significantly repressed the growth of xenografted tumors and did not affect the body weight nor cause obvious hepatorenal toxicity. TalaA arrested the cell cycle by downregulating cyclinA2, cyclinB1, and AURKB and upregulating p21/CIP. TalaA also elevated intracellular reactive oxygen species and upregulated transferrin and heme oxygenase 1 to induce ferroptosis. Moreover, TalaA was able to bind to MAPKs (MAPK1, MAPK8, and MAPK14) to inhibit the phosphorylation of ∗SP∗ motif of transcription regulators. This study revealed that TalaA inhibited bladder cancer by arresting cell cycle to suppress proliferation and triggering ferroptosis to cause cell death. Conclusively, TalaA would be a potential candidate for treating bladder cancer by targeting MAPKs, suppressing the cell cycle, and inducing ferroptosis.

Macrophage targeted iron oxide nanodecoys augment innate immunological and drug killings for more effective Mycobacterium Tuberculosis clearance.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is still one of the top killers worldwide among infectious diseases. The escape of Mtb from immunological clearance and the low targeting effects of anti-TB drugs remain the substantial challenges for TB control. Iron is particularly required for Mtb growth but also toxic for Mtb in high dosages, which makes iron an ideal toxic decoy for the 'iron-tropic' Mtb. Here, a macrophage-targeted iron oxide nanoparticles (IONPs)-derived IONPs-PAA-PEG-MAN nanodecoy is designed to augment innate immunological and drug killings against intracellular Mtb. IONPs-PAA-PEG-MAN nanodecoy exhibits preferential uptake in macrophages to significantly increase drug uptake with sustained high drug contents in host cells. Moreover, it can serve as a specific nanodecoy for the 'iron-tropic' Mtb to realize the localization of Mtb contained phagosomes surrounding the drug encapsulated nanodecoys and co-localization of Mtb with the drug encapsulated nanodecoys in lysosomes, where the incorporated rifampicin (Rif) can be readily released under acidic lysosomal condition for enhanced Mtb killing. This drug encapsulated nanodecoy can also polarize Mtb infected macrophages into anti-mycobacterial M1 phenotype and enhance M1 macrophage associated pro-inflammatory cytokine (TNF-α) production to trigger innate immunological responses against Mtb. Collectively, Rif@IONPs-PAA-PEG-MAN nanodecoy can synergistically enhance the killing efficiency of intracellular Mtb in in vitro macrophages and ex vivo monocyte-derived macrophages, and also significantly reduce the mycobacterial burdens in the lung of infected mice with alleviated pathology. These results indicate that Rif@IONPs-PAA-PEG-MAN nanodecoy may have a potential for the development of more effective therapeutic strategy against TB by manipulating augmented innate immunity and drug killings.

Research on the impact of the development of green finance in the China region on residents' health.

In the context of implementing the strategy of "double carbon" and "healthy China," this paper firstly measures the level of green finance development and the comprehensive index of health care accessibility in each province by using the entropy weight method based on 30 provincial panel data from 2007 to 2021. A panel fixed effects model was also used to empirically analyze the effect of regional green finance development on the improvement of residents' health. In addition, a panel threshold model was constructed to empirically test the threshold effect of green finance on residents' health under the influence of four external environments: carbon intensity level, healthcare accessibility, residents' living standard and human capital level. The empirical results show that the regional green financial development in China significantly improves the health level of residents. And the impact has significant regional heterogeneity, as shown in the improvement effect is more significant for the provinces in the central and western regions. In addition, the impact of green financial development on the health level of residents in China is non-linearly influenced by external environmental factors. The improvement effect of green finance on residents' health level is more significant in the provinces with higher carbon intensity level, residents' living standard, human capital level and lower accessibility to medical services. In this regard, regional governments should continue to build and optimize a synergistic development ecosystem of green finance and public health, give full play to the advantages of financial leverage, promote green, low-carbon and high-quality economic and social development, and realize the beautiful vision of harmonious coexistence between human beings and nature.

Gold Nanoparticles: Construction for Drug Delivery and Application in Cancer Immunotherapy.

Cancer immunotherapy is an innovative treatment strategy to enhance the ability of the immune system to recognize and eliminate cancer cells. However, dose limitations, low response rates, and adverse immune events pose significant challenges. To address these limitations, gold nanoparticles (AuNPs) have been explored as immunotherapeutic drug carriers owing to their stability, surface versatility, and excellent optical properties. This review provides an overview of the advanced synthesis routes for AuNPs and their utilization as drug carriers to improve precision therapies. The review also emphasises various aspects of AuNP-based immunotherapy, including drug loading, targeting strategies, and drug release mechanisms. The application of AuNPs combined with cancer immunotherapy and their therapeutic efficacy are briefly discussed. Overall, we aimed to provide a recent understanding of the advances, challenges, and prospects of AuNPs for anticancer applications.

Advances of MnO2 nanomaterials as novel agonists for the development of cGAS-STING-mediated therapeutics.

As an essential micronutrient, manganese plays an important role in the physiological process and immune process. In recent decades, cGAS-STING pathway, which can congenitally recognize exogenous and endogenous DNA for activation, has been widely reported to play critical roles in the innate immunity against some important diseases, such as infections and tumor. Manganese ion (Mn2+) has been recently proved to specifically bind with cGAS and activate cGAS-STING pathway as a potential cGAS agonist, however, is significantly restricted by the low stability of Mn2+ for further medical application. As one of the most stable forms of manganese, manganese dioxide (MnO2) nanomaterials have been reported to show multiple promising functions, such as drug delivery, anti-tumor and anti-infection activities. More importantly, MnO2 nanomaterials are also found to be a potential candidate as cGAS agonist by transforming into Mn2+, which indicates their potential for cGAS-STING regulations in different diseased conditions. In this review, we introduced the methods for the preparation of MnO2 nanomaterials as well as their biological activities. Moreover, we emphatically introduced the cGAS-STING pathway and discussed the detailed mechanisms of MnO2 nanomaterials for cGAS activation by converting into Mn2+. And we also discussed the application of MnO2 nanomaterials for disease treatment by regulating cGAS-STING pathway, which might benefit the future development of novel cGAS-STING targeted treatments based on MnO2 nanoplatforms.

Immunomodulatory activity of manganese dioxide nanoparticles: Promising for novel vaccines and immunotherapeutics.

Manganese (Mn), a nutrient inorganic trace element, is necessary for a variety of physiological processes of animal body due to their important roles in oxidative regulation effects and other aspects of activities. Moreover, manganese ion (Mn2+) has widely reported to be crucial for the regulations of different immunological responses, thus showing promising application as potential adjuvants and immunotherapeutics. Taking the advantages of Mn-based biological and immunological activities, Manganese dioxide nanoparticles (MnO2 NPs) are a new type of inorganic nanomaterials with numerous advantages, including simple preparation, low cost, environmental friendliness, low toxicity, biodegradable metabolism and high bioavailability. MnO2 NPs, as a kind of drug carrier, have also shown the ability to catalyze hydrogen peroxide (H2O2) to produce oxygen (O2) under acidic conditions, which can enhance the efficacy of radiotherapy, chemotherapy and other therapeutics for tumor treatment by remodeling the tumor microenvironment. More importantly, MnO2 NPs also play important roles in immune regulations both in innate and adaptive immunity. In this review, we summarize the biological activities of Manganese, followed by the introduction for the biological and medical functions and mechanisms of MnO2 NPs. What's more, we emphatically discussed the immunological regulation effects and mechanisms of MnO2 NPs, as well as their potentials to serve as adjuvants and immunomodulators, which might benefit the development of novel vaccines and immunotherapies for more effective disease control.

Trends and recent progresses of selenium nanoparticles as novel autophagy regulators for therapeutic development.

Autophagy, one of the major intracellular degradation systems, plays an important role in maintaining normal cellular physiological functions and protecting organisms from different diseases. Selenium (Se), an essential trace element, is involved in many metabolic regulatory signaling events and plays a key role in human health. In recent years, selenium nanoparticles (Se NPs) have attracted increasing attentions in biomedical field due to their low toxicity, high bioavailability and high bioactivity. Taking the advantage of their advanced biological activities, Se NPs can be used alone as potential therapeutic agents, or combine with other agents and served as carriers for the development of novel therapeutics. More interestingly, Se NPs have been widely reported to affect autophagy signaling, which therefor allow Se NPs to be used as potential therapeutic agents against different diseases. Here, this review suggested the relationships between Se and autophagy, followed by the trends and recent progresses of Se NPs for autophagy regulation in different diseased conditions. More importantly, this work discussed the roles and potential mechanisms of Se NPs in autophagy regulating, which might enhance our understanding about how Se NPs regulate autophagy for potential disease treatment. This work is expected to promote the potential application of Se NPs as novel autophagy regulators, which might benefit the development of novel autophagy associated therapeutics.

Copy Number Variation Analysis Revealed the Evolutionary Difference between Chinese Indigenous Pigs and Asian Wild Boars.

Copy number variation (CNV) has been widely used to study the evolution of different species. We first discovered different CNVs in 24 Anqingliubai pigs and 6 Asian wild boars using next-generation sequencing at the whole-genome level with 10× depth to understand the relationship between genetic evolution and production traits in wild boars and domestic pigs. A total of 97,489 CNVs were identified and divided into 10,429 copy number variation regions (CNVRs), occupying 32.06% of the porcine genome. Chromosome 1 had the most CNVRs, and chromosome 18 had the least. Ninety-six CNVRs were selected using VST 1% based on the signatures of all CNVRs, and sixty-five genes were identified in the selected regions. These genes were strongly correlated with traits distinguishing groups by enrichment in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways, such as growth (CD36), reproduction (CIT, RLN), detoxification (CYP3A29), and fatty acid metabolism (ELOVL6). The QTL overlapping regions were associated with meat traits, growth, and immunity, which was consistent with CNV analysis. Our findings increase the understanding of evolved genome structural variations between wild boars and domestic pigs, and provide new molecular biomarkers to guide breeding and the efficient use of available genetic resources.

Advances of Cobalt Nanomaterials as Anti-Infection Agents, Drug Carriers, and Immunomodulators for Potential Infectious Disease Treatment.

Infectious diseases remain the most serious public health issue, which requires the development of more effective strategies for infectious control. As a kind of ultra-trace element, cobalt is essential to the metabolism of different organisms. In recent decades, nanotechnology has attracted increasing attention worldwide due to its wide application in different areas, including medicine. Based on the important biological roles of cobalt, cobalt nanomaterials have recently been widely developed for their attractive biomedical applications. With advantages such as low costs in preparation, hypotoxicity, photothermal conversion abilities, and high drug loading ability, cobalt nanomaterials have been proven to show promising potential in anticancer and anti-infection treatment. In this review, we summarize the characters of cobalt nanomaterials, followed by the advances in their biological functions and mechanisms. More importantly, we emphatically discuss the potential of cobalt nanomaterials as anti-infectious agents, drug carriers, and immunomodulators for anti-infection treatments, which might be helpful to facilitate progress in future research of anti-infection therapy.

Promising Roles of Circular RNAs as Biomarkers and Targets for Potential Diagnosis and Therapy of Tuberculosis.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, remains one of the most threatening infectious diseases worldwide. A series of challenges still exist for TB prevention, diagnosis and treatment, which therefore require more attempts to clarify the pathological and immunological mechanisms in the development and progression of TB. Circular RNAs (circRNAs) are a large class of non-coding RNA, mostly expressed in eukaryotic cells, which are generated by the spliceosome through the back-splicing of linear RNAs. Accumulating studies have identified that circRNAs are widely involved in a variety of physiological and pathological processes, acting as the sponges or decoys for microRNAs and proteins, scaffold platforms for proteins, modulators for transcription and special templates for translation. Due to the stable and widely spread characteristics of circRNAs, they are expected to serve as promising prognostic/diagnostic biomarkers and therapeutic targets for diseases. In this review, we briefly describe the biogenesis, classification, detection technology and functions of circRNAs, and, in particular, outline the dynamic, and sometimes aberrant changes of circRNAs in TB. Moreover, we further summarize the recent progress of research linking circRNAs to TB-related pathogenetic processes, as well as the potential roles of circRNAs as diagnostic biomarkers and miRNAs sponges in the case of Mtb infection, which is expected to enhance our understanding of TB and provide some novel ideas about how to overcome the challenges associated TB in the future.

Ferroptosis: A mixed blessing for infectious diseases.

To date, it has been confirmed that the occurrence and development of infectious diseases are tightly associated with regulatory cell death processes, such as apoptosis, autophagy, and necroptosis. Ferroptosis, as a newly discovered form of regulatory cell death characterized by iron-dependent lipid peroxidation, is not only closely associated with tumor progression, but is also found to be tightly related to the regulation of infectious diseases, such as Tuberculosis, Cryptococcal meningitis, Malaria and COVID-2019. The emerging critical roles of ferroptosis that has been found in infectious disease highlight ferroptosis as a potential therapeutic target in this field, which is therefore widely expected to be developed into new therapy strategy against infectious diseases. Here, we summarized the underlying mechanisms of ferroptosis and highlighted the intersections between host immunity and ferroptosis. Moreover, we illuminated the roles of ferroptosis in the occurrence and progression of different infectious diseases, which might provide some unique inspiration and thought-provoking perspectives for the future research of these infectious diseases, especially for the development of ferroptosis-based therapy strategy against infectious diseases.

Nanoscale Features of Gambogic Acid Induced ROS-Dependent Apoptosis in Esophageal Cancer Cells Imaged by Atomic Force Microscopy.

Gambogic acid (GA), a kind of polyprenylated xanthone derived from Garcinia hanburyi tree, has showed spectrum anticancer effects both in vitro and in vivo with low toxicity. However, up to now, there is little information about the effects of GA on esophageal cancer. In this study, we aim to test the anticancer effects of GA on esophageal cancer EC9706 cells. We established a nanoscale imaging method based on AFM to evaluate the reactive oxygen species- (ROS-) mediated anticancer effects of GA on esophageal cancer regarding the morphological and ultrastructural changes of esophageal cancer cells. The obtained results demonstrated that GA could inhibit cell proliferation, induce apoptosis, induce cell cycle arrest, and induce mitochondria membrane potential disruption in a ROS-dependent way. And using AFM imaging, we also found that GA could induce the damage of cellular morphology and increase of membrane height distribution and membrane roughness in EC9706 cells, which could be reversed by the removal of GA-induced excessive intracellular ROS. Our results not only demonstrated the anticancer effects of GA on EC9706 cells in ROS-dependent mechanism but also strongly suggested AFM as a powerful tool for the detection of ROS-mediated cancer cell apoptosis on the basis of imaging.

Immunomodulatory roles of selenium nanoparticles: Novel arts for potential immunotherapy strategy development.

Current chemotherapy strategies used in clinic appear with lots of disadvantages due to the low targeting effects of drugs and strong side effects, which significantly restricts the drug potency, causes multiple dysfunctions in the body, and even drives the emergence of diseases. Immunotherapy has been proved to boost the body's innate and adaptive defenses for more effective disease control and treatment. As a trace element, selenium plays vital roles in human health by regulating the antioxidant defense, enzyme activity, and immune response through various specific pathways. Profiting from novel nanotechnology, selenium nanoparticles have been widely developed to reveal great potential in anticancer, antibacterial, and anti-inflammation treatments. More interestingly, increasing evidence has also shown that functional selenium nanoparticles can be applied for potential immunotherapy, which would achieve more effective treatment efficiency as adjunctive therapy strategies for the current chemotherapy. By directly interacting with innate immune cells, such as macrophages, dendritic cells, and natural killer cells, selenium nanoparticles can regulate innate immunity to intervene disease developments, which were reported to boost the anticancer, anti-infection, and anti-inflammation treatments. Moreover, selenium nanoparticles can also activate and recover different T cells for adaptive immunity regulations to enhance their cytotoxic to combat cancer cells, indicating the potential of selenium nanoparticles for potential immunotherapy strategy development. Here, aiming to enhance our understanding of the potential immunotherapy strategy development based on Se NPs, this review will summarize the immunological regulation effects of selenium nanoparticles and the application of selenium nanoparticle-based immunotherapy strategies. Furthermore, we will discuss the advancing perspective of selenium nanoparticle-based potential immunotherapy as a kind of novel adjunctive therapy to enhance the efficiency of current chemotherapies and also introduce the current obstacles for the development of selenium nanoparticles for potential immunotherapy strategy development. This work is expected to promote the future research on selenium nanoparticle-assisted immunotherapy and finally benefit the more effective disease treatments against the threatening cancer and infectious and chronic diseases.

Potentiality of Exosomal Proteins as Novel Cancer Biomarkers for Liquid Biopsy.

Liquid biopsy has been rapidly developed in recent years due to its advantages of non-invasiveness and real-time sampling in cancer prognosis and diagnosis. Exosomes are nanosized extracellular vesicles secreted by all types of cells and abundantly distributed in all types of body fluid, carrying diverse cargos including proteins, DNA, and RNA, which transmit regulatory signals to recipient cells. Among the cargos, exosomal proteins have always been used as immunoaffinity binding targets for exosome isolation. Increasing evidence about the function of tumor-derived exosomes and their proteins is found to be massively associated with tumor initiation, progression, and metastasis in recent years. Therefore, exosomal proteins and some nucleic acids, such as miRNA, can be used not only as targets for exosome isolation but also as potential diagnostic markers in cancer research, especially for liquid biopsy. This review will discuss the existing protein-based methods for exosome isolation and characterization that are more appropriate for clinical use based on current knowledge of the exosomal biogenesis and function. Additionally, the recent studies for the use of exosomal proteins as cancer biomarkers are also discussed and summarized, which might contribute to the development of exosomal proteins as novel diagnostic tools for liquid biopsy.

Advances and Potentials of Polydopamine Nanosystem in Photothermal-Based Antibacterial Infection Therapies.

Bacterial infection remains one of the most dangerous threats to human health due to the increasing cases of bacterial resistance, which is caused by the extensive use of current antibiotics. Photothermal therapy (PTT) is similar to photodynamic therapy (PDT), but PTT can generate heat energy under the excitation of light of specific wavelength, resulting in overheating and damage to target cells or sites. Polydopamine (PDA) has been proved to show plenty of advantages, such as simple preparation, good photothermal conversion effects, high biocompatibility, and easy functionalization and adhesion. Taking these advantages, dopamine is widely used to synthesize the PDA nanosystem with excellent photothermal effects, good biocompatibility, and high drug loading ability, which therefore play more and more important roles for anticancer and antibacterial treatment. PDA nanosystem-mediated PTT has been reported to induce significant tumor inhibition, as well as bacterial killings due to PTT-induced hyperthermia. Moreover, combined with other cancer or bacterial inhibition strategies, PDA nanosystem-mediated PTT can achieve more effective tumor and bacterial inhibitions. In this review, we summarized the progress of preparation methods for the PDA nanosystem, followed by advances of their biological functions and mechanisms for PTT uses, especially in the field of antibacterial treatments. We also provided advances on how to combine PDA nanosystem-mediated PTT with other antibacterial methods for synergistic bacterial killings. Moreover, we further provide some prospects of PDA nanosystem-mediated PTT against intracellular bacteria, which might be helpful to facilitate their future research progress for antibacterial therapy.

Epidemiology and prediction of multidrug-resistant bacteria based on hospital level.

OBJECTIVES: Multidrug-resistant bacteria (MDRB) result in nosocomial infections and a substantial disease burden for hospitalised patients worldwide. However, strategies to control drug resistance at the hospital level are lacking. In this study, we aimed to find important indicators for risk assessment and predicting MDRB infections in the hospital. METHODS: Using real-world data and machine learning models, we conducted a retrospective study from 2010 to 2020 in a teaching hospital to analyse the trends and characteristics of MDRB infections. Combining 39 hospital indicators, we used a random forest model and cross-correlation analysis to explore the important factors affecting MDRB and their predictive power. We built a decision tree model to predict the number of hospitalised patients with MDRB infection. RESULTS: The number of hospitalised rescues and rate of rational perioperative antibacterial drug use in type I and II incision operations were correlated with the number of patients with MDRB infection after 1-2 months. The number of hospitalised operations and rate of antibiotics use in emergency patients had an effect on current MDRB-susceptible patients. The indicators, including hospital operation volume and antibacterial drug use, had a positive or negative quantitative relationship with the number of patients with MDRB infection, and their thresholds could be fit to the MDRB prediction model. CONCLUSION: Surgical, emergency, and hospitalised rescue patients showed the highest risk of MDRB infection. Standardised indicators such as clinical pathway rate and rational antibiotic use rate could be used to control the development and spread of MDRB infections in the hospital.

Nanocages engineered from Bacillus Calmette-Guerin facilitate protective Vγ2Vδ2 T cell immunity against Mycobacterium tuberculosis infection.

Tuberculosis (TB), induced by Mycobacterium tuberculosis (Mtb) infection, remains a top killer among infectious diseases. While Bacillus Calmette-Guerin (BCG) is the sole TB vaccine, the clumped-clustered features of BCG in intradermal immunization appear to limit both the BCG protection efficacy and the BCG vaccination safety. We hypothesize that engineering of clumped-clustered BCG into nanoscale particles would improve safety and also facilitate the antigen-presenting-cell (APC)'s uptake and the following processing/presentation for better anti-TB protective immunity. Here, we engineered BCG protoplasts into nanoscale membraned BCG particles, termed as "BCG-Nanocage" to enhance the anti-TB vaccination efficiency and safety. BCG-Nanocage could readily be ingested/taken by APC macrophages selectively; BCG-Nanocage-ingested macrophages exhibited better viability and developed similar antimicrobial responses with BCG-infected macrophages. BCG-Nanocage, like live BCG bacilli, exhibited the robust capability to activate and expand innate-like T effector cell populations of Vγ2+ T, CD4+ T and CD8+ T cells of rhesus macaques in the ex vivo PBMC culture. BCG-Nanocage immunization of rhesus macaques elicited similar or stronger memory-like immune responses of Vγ2Vδ2 T cells, as well as Vγ2Vδ2 T and CD4+/CD8+ T effectors compared to live BCG vaccination. BCG-Nanocage- immunized macaques developed rapidly-sustained pulmonary responses of Vγ2Vδ2 T cells upon Mtb challenge. Furthermore, BCG- and BCG-Nanocage- immunized macaques, but not saline controls, exhibited undetectable Mtb infection loads or TB lesions in the Mtb-challenged lung lobe and hilar lymph node at endpoint after challenge. Thus, the current study well justifies a large pre-clinical investigation to assess BCG-Nanocage for safe and efficacious anti-TB vaccination, which is expected to further develop novel vaccines or adjuvants.