Evolution and Antigenic Differentiation of Avian Influenza A(H7N9) Virus, China.

We characterized the evolution and molecular characteristics of avian influenza A(H7N9) viruses isolated in China during 2021-2023. We systematically analyzed the 10-year evolution of the hemagglutinin gene to determine the evolutionary branch. Our results showed recent antigenic drift, providing crucial clues for updating the H7N9 vaccine and disease prevention and control.

Interleukin-17A educated hepatic stellate cells promote hepatocellular carcinoma occurrence through fibroblast activation protein expression.

BACKGROUND: Liver cancer is typified by a complex inflammatory tumor microenvironment, where an array of cytokines and stromal cells orchestrate a milieu that significantly influences tumorigenesis. Interleukin-17A (IL-17A), a pivotal pro-inflammatory cytokine predominantly secreted by Th17 cells, is known to play a substantial role in the etiology and progression of liver cancer. However, the precise mechanism by which IL-17A engages with hepatic stellate cells (HSCs) to facilitate the development of hepatocellular carcinoma (HCC) remains to be fully elucidated. This investigation seeks to unravel the interplay between IL-17A and HSCs in the context of HCC. METHODS: An HCC model was established in male Sprague-Dawley rats using diethylnitrosamine to explore the roles of IL-17A and HSCs in HCC pathogenesis. In vivo overexpression of Il17a was achieved using adeno-associated virus. A suite of molecular techniques, including RT-qPCR, enzyme-linked immunosorbent assays, Western blotting, cell counting kit-8 assays and colony formation assays, was employed for in vitro analyses. RESULTS: The study findings indicate that IL-17A is a key mediator in HCC promotion, primarily through the activation of hepatic progenitor cells (HPCs). This pro-tumorigenic influence appears to be mediated by HSCs, rather than through a direct effect on HPCs. Notably, IL-17A-induced expression of fibroblast activation protein (FAP) in HSCs emerged as a critical factor in HCC progression. Silencing Fap in IL-17A-stimulated HSCs was observed to reverse the HCC-promoting effects of HSCs. CONCLUSIONS: The collective evidence from this study implicates the IL-17A/FAP signaling axis within HSCs as a contributor to HCC development by enhancing HPC activation. These findings bolster the potential of IL-17A as a diagnostic and preventative target for HCC, offering new avenues for therapeutic intervention.

Early vs late anticoagulation in acute ischemic stroke with indications outside atrial fibrillation.

BACKGROUND: Current literature lacks guidance on the safety of administering anticoagulation in acute ischemic stroke with emergent indications that require anticoagulation other than atrial fibrillation. Therefore, we tend to rely on studies investigating acute ischemic stroke in atrial fibrillation for anticoagulation recommendations. METHODS: We retrospectively reviewed data for patients with acute ischemic stroke who had a non-atrial fibrillation emergent indication for anticoagulation (e.g., intra-arterial thrombus, intracardiac thrombus, acute coronary syndrome, acute limb ischemia, deep vein thrombosis and pulmonary embolism) diagnosed within 3 days of acute ischemic stroke. Patients who received anticoagulation ≤ 3 days of stroke onset (Group A) were compared to those who either received it afterwards or did not receive it at all (Group B). RESULTS: Out of the 558 patients, only 88 patients met our inclusion criteria. Of the total cohort, 55.7 % patients were males, and basic demographics were similar in both groups except for milder strokes in Group A (national institute of health stroke scale 6 vs. 12.5, p = 0.03). Only 2 patients in Group A and 1 patient in Group B developed intracranial hemorrhage, which was not statistically significant. Group A patients had a lower incidence of both new diagnosis (2 % vs. 34.2 % %, p < 0.001) and propagation of an established venous thromboembolism. They also had a lower rate of any thromboembolic complication (2 % vs. 42 %, p < 0.001). CONCLUSION: Early anticoagulation (i.e., ≤ 3 days) in non-atrial fibrillation ischemic stroke patients with an emergent indication may be safe and carry a lower risk of thromboembolic complications than later anticoagulation.

Effect of Metal Elements on Microstructure and Mechanical Properties of Ultrafine Cemented Carbide Prepared by SPS.

To satisfy the needs of precision machining, ultrafine tungsten carbide (WC)-based cemented carbide with fine grain size and excellent mechanical properties was prepared. Ultrafine cemented carbide was prepared by spark plasma sintering (SPS) using WC, Co as raw materials and metal elements V, and Cr as additives, and the effects of metal elements on the microstructure and mechanical properties of cemented carbide were investigated. The results show that the specimen (91.6WC-1.2V-1.2Cr-6Co) prepared at 1350 °C, 6 min, 25 MPa has the best mechanical properties (HV 2322.9, KIC 8.7 MPa·m1/2) and homogeneous microstructure. The metal elements could react with WC to form a (W, V, Cr) Cx segregation layer, which effectively inhibits the growth of WC grains (300 nm). The combination of SPS and metal element additives provides a new approach for the preparation of ultrafine cemented carbides with excellent properties.

Electrochemical detection of SARS-CoV-2 based on copper nanoflower-triggered in situ growth of electroactive polymers.

SARS-CoV-2, the pathogen of COVID-19, has introduced massive confirmed cases and millions of deaths worldwide, which poses a serious public health threat. For the early diagnosis of COVID-19, we have constructed an electrochemical biosensor-combined magnetic separation system with copper nanoflower-triggered cascade signal amplification strategy. In the proposed system, magnetic beads were utilized to fabricate the recognition element for capturing the conserved sequence of SARS-CoV-2. As the copper ions source, oligonucleotides modified copper nanoflowers with special layered structure provide numerous catalysts for click chemistry reaction. When target sequence RdRP_SARSr-P2 appears, copper nanoflowers will be bound with magnetic beads, thus prompting the Cu(I)-catalyzed azide-alkyne cycloaddition reaction through the connection of the SARS-CoV-2 conserved sequence. Then, a large number of signal molecules FMMA can be grafted onto the modified electrode surface by electrochemically mediated atom-transfer radical polymerization to amplify the signal for the quantitative analysis of SARS-CoV-2. Under optimal conditions, a linear range from 0.1 to 103 nM with a detection limit of 33.83 pM is obtained. It provides a powerful tool for the diagnosis of COVID-19, which further benefits the early monitoring of other explosive infectious diseases effectively, thus guaranteeing public health safety.

Stable and efficient luminescence of Cs4PbBr6-xIx PQDs glass: a potential material for wide color gamut display.

Zero-dimensional Cs4PbBr6-xIx perovskite quantum dots (PQDs) glass is successfully prepared via a melt quenching method, which provides infinite possibilities for achieving the whole family of zero-dimensional PQDs glass. The test results demonstrate excellent thermal stability and high photoluminescence quantum yields (PLQYs) of Cs4PbBr6-xIx PQDs glass (up to 50%). Finally, the combination of Cs4PbBr6-xIx PQDs glass with an InGaN blue chip is used to fabricate white light-emitting diodes (WLED), which show good color stability at a large operating current, and the color gamut area reaches 137% of NTSC. The above results indicate that zero-dimensional Cs4PbBr6-xIx PQDs glass materials have a broad application prospect in the display lighting field.

NQO1 promotes an aggressive phenotype in hepatocellular carcinoma via amplifying ERK-NRF2 signaling.

Patients with hepatocellular carcinoma (HCC) are usually diagnosed at the later stages and have poor survival outcomes. New molecules are urgently needed for the prognostic predication and individual treatment. Our study showed that high levels of NQO1 expression frequently exist in HCC with an obvious cancer-specific pattern. Patients with NQO1-high tumors are significantly associated with poor survival outcomes and serve as independent predictors. Functional experiments showed that NQO1 promotes the growth and aggressiveness of HCC in both in vitro and in vivo models, and the underlying mechanism involved NQO1-derived amplification of ERK/p38-NRF2 signaling. Combined block of ERK and NRF2 signaling generated stronger growth inhibition compared with any single block, especially for HCC with high-NQO1. Therefore, NQO1 is a potential biomarker for HCC early diagnosis and prognosis prediction, and also attractive for cancer-specific targets for HCC treatment.

miR169c-NFYA-C-ENOD40 modulates nitrogen inhibitory effects in soybean nodulation.

Legume crops contribute a great portion of clean nitrogen (N) to agro-ecosystems through symbiotic N2 fixation in the nodule; however, the nodulation is always inhibited by high N availability which is known as the N inhibitory effect through largely unknown mechanisms. We functionally investigated miR169c-GmNFYA-C-GmENOD40 under multiple N conditions in soybean (Glycine max) (ENOD, Early Nodulin; NFYA, Nuclear Factor-Y Subunit A). We elucidated their regulatory roles in soybean nodulation through analyzing expression patterns, micro-messenger RNA (miRNA-mRNA) interactions, phenotypes of transgenic soybean plants and genetic interactions. We found that miR169c expression was induced by high N, whereas its target GmNFYA-C was preferentially expressed in nodules and induced by rhizobium inoculation. Overexpression of miR169c inhibited nodulation through targeting 3'-UTR of GmNFYA-C, whereas knockout miR169c through CRISPR-cas9 promoted nodulation. However, overexpression of GmNFYA-C promoted soybean nodulation through facilitating rhizobium infection and increasing the expression of symbiotic signaling gene GmENOD40. Besides, GmNFYA-C directly induced the expression of GmENOD40. In addition, overexpression of GmNFYA-C without the target site of miR169c partially attenuated the inhibitory effect of high N on soybean nodulation. We discovered a new regulatory pathway involving the miR169c-NFYA-C-ENOD40 module that regulates soybean nodulation in response to N availability. This pathway provides substantial new insights into the mechanisms underlying the N inhibitory effect on nodulation.

Laparoscopic procedure is associated with lower morbidity for simultaneous resection of colorectal cancer and liver metastases: an updated meta-analysis.

BACKGROUND: It has been demonstrated that simultaneous resection of both primary colorectal lesion and metastatic hepatic lesion is a safe approach with low mortality and postoperative complication rates. However, there are some controversies over which kind of surgical approach is better. The aim of study was to compare the efficacy and safety of laparoscopic surgeries and open surgeries for simultaneous resection of colorectal cancer (CRC) and synchronous colorectal liver metastasis (SCRLM). METHODS: A systemic search of online database including PubMed, Web of Science, Cochrane Library, and Embase was performed until June 5, 2019. Intraoperative complications, postoperative complications, and long-term outcomes were synthesized by using STATA, version 15.0. Cumulative and single-arm meta-analyses were also conducted. RESULTS: It contained twelve studies with 616 patients (273 vs 343, laparoscopic surgery group and open surgery group, respectively) and manifested latest surgical results for the treatment of CRC and SCRLM. Among patients who underwent laparoscopic surgeries, they had lower rates of postoperative complications (OR = 0.66, 95% CI: 0.46 to 0.96, P = 0.028), less intraoperative blood loss (weight mean difference (WMD) = - 113.31, 95% CI: - 189.03 to - 37.59, P = 0.003), less time in the hospital and recovering after surgeries (WMD = - 2.70, 95% CI: - 3.99 to - 1.40, P = 0.000; WMD = - 3.20, 95% CI: - 5.06 to - 1.34, P = 0.001), but more operating time (WMD = 36.57, 95% CI: 7.80 to 65.35, P = 0.013). Additionally, there were no statistical significance between two kinds of surgical approaches in disease-free survival and overall survival. Moreover, cumulative meta-analysis indicated statistical difference in favor of laparoscopic surgery in terms of morbidity was firstly detected in the 12th study in 2018 (OR = 0.66, 95% CI: 0.46 to 0.96, P = 0.028) as the 95% CI narrowed. CONCLUSION: Compared with open surgeries, laparoscopic surgeries are safer (postoperative complications and intraoperative blood loss) and more effective (length of hospital stay and postoperative stay), and it can be considered as the first option for management of SCRLM in high-volume laparoscopic centers. TRIAL REGISTRATION: CRD42020151176.

Preoperative hepatitis B virus DNA level is a risk factor for postoperative liver failure in patients who underwent partial hepatectomy for hepatitis B-related hepatocellular carcinoma.

OBJECTIVE: Our objective was to explore the short-term effects of preoperative serum hepatitis B virus DNA level (HBV DNA) on postoperative hepatic function in patients who underwent partial hepatectomy for hepatitis B-related hepatocellular carcinoma (HCC). METHODS: The clinical data of 1,602 patients with hepatitis B-related HCC who underwent partial hepatectomy in our department were retrospectively studied. The patients were divided into three groups according to their preoperative HBV DNA levels: group A <200 IU/mL, group B 200-20,000 IU/mL, and group C >20,000 IU/mL. The rates of postoperative complications, especially the rate of postoperative liver failure, were compared. RESULTS: There were significant differences among the three groups in the rates of postoperative liver failure. On multivariate logistic regression analysis, a high preoperative HBV DNA level was an independent risk factor for postoperative liver failure. CONCLUSIONS: Preoperative HBV DNA level was a significant risk factor for postoperative hepatic dysfunction.

Preparation of mesoporous silica/hydroxyapatite loaded quercetin nanoparticles and research on its antibacterial properties.

In this study, amino-functionalized mesoporous silica/hydroxyapatite nanoparticles (MSNS/HAP) with the property of acid dissociation have been prepared as a traditional Chinese medicine monomer carriers to improve the drug loading rate and antibacterial properties of antimicrobial quercetin (QUE) in vitro. The experimental results confirm that the drug loading rate of MSNs/HAP is 28.94 %, which is about 3.6 times higher than that of aminated mesoporous sililca nanoparticles (MSNs). The drug release of QUE on MSNs/HAP is pH-sensitive in phosphate buffered saline (pH=4.0-7.4). The above fabricated traditional Chinese medicine monomer modified nanocomposites (QUE@MSNs/HAP) displays concentration-dependent inhibitory effect, which shows better antibacterial effect than free QUE. The minimum inhibitory concentration for two tested bacteria, Staphylococcus aureus (S.aureus) and Escherichia coli (E.coli), is 256 mg·L -1. In summary, QUE@MSNs/HAP have successfully prepared, which not only improves the bio-availability of QUE, but also has acid-sensitive drug release properties. Compared with free QUE, its antibacterial performance significantly enhances, which provides a theoretical basis for the application of Chinese medicine molecules in bacterial treatment.

Berberine and chlorogenic acid-assembled nanoparticles for highly efficient inhibition of multidrug-resistant Staphylococcus aureus.

Due to the bacteria resistant to various first-line antibiotics, it is urgent to develop efficient antibiotic alternatives and formulate multidimensional strategies. Herein, supramolecular Chinese medicine nanoparticles are synthesized by self-assembly of berberine (BBR) and chlorogenic acid (CGA), which exhibit higher inhibitory effect against Staphylococcus aureus and multidrug-resistant Staphylococcus aureus (MRSA) than ampicillin, oxacillin, BBR, CGA, as well as mixture of BBR and CGA (minimum inhibitory concentration, MIC = 1.5 µM). The inhibition by BBR/CGA nanoparticles (2.5 µM) reaches 99.06 % for MRSA, which is significantly higher than ampicillin (29.03 %). The nanoparticles with 1/2 MIC can also synergistically restore the antimicrobial activity of ampicillin against MRSA. Moreover, in vivo therapeutic outcome in the murine skin wound infection model suggests that the nanoparticles are able to promote wound healing. This study provides new insights in the application of Chinese medicines self-assembly for MRSA inhibition, as well as solutions for potential persistent clinical infections and drug deficiencies.

IL-17a promotes hepatocellular carcinoma by increasing FAP expression in hepatic stellate cells via activation of the STAT3 signaling pathway.

Studies have shown that hepatic stellate cells (HSCs) and interleukin-17a (IL-17a) play important roles in liver tumorigenesis. In addition, fibroblast activation protein-α (FAP) has been shown to be a key regulator of hepatic stellate cell activation. In this study, in vivo and in vitro experiments were performed to verify the promoting effects of IL-17a administration, IL-17a overexpression, and FAP upregulation in HSCs on liver fibrosis and liver tumorigenesis. The cleavage under targets & release using nuclease (CUT&RUN) technique was used to verify the binding status of STAT3 to the FAP promoter. The in vitro studies showed that IL-17a activated HSCs and promoted HCC development and progression. FAP and IL-17a overexpression also activated HSCs, promoted HCC cell proliferation and migration, and inhibited HCC cell apoptosis. The in vivo studies suggested that IL-17a and FAP overexpression in HSCs facilitated liver tumor development and progression. The CUT&RUN results indicated that FAP expression was regulated by STAT3, which could bind to the FAP promoter region and regulate its transcription status. We concluded that IL-17a promoted HCC by increasing FAP expression in HSCs via activation of the STAT3 signaling pathway.

Evolutionary dynamics and comparative pathogenicity of clade 2.3.4.4b H5 subtype avian influenza viruses, China, 2021-2022.

The recent concurrent emergence of H5N1, H5N6, and H5N8 avian influenza viruses (AIVs) has led to significant avian mortality globally. Since 2020, frequent human-animal interactions have been documented. To gain insight into the novel H5 subtype AIVs (i.e., H5N1, H5N6 and H5N8), we collected 6102 samples from various regions of China between January 2021 and September 2022, and identified 41 H5Nx strains. Comparative analyses on the evolution and biological properties of these isolates were conducted. Phylogenetic analysis revealed that the 41 H5Nx strains belonged to clade 2.3.4.4b, with 13 related to H5N1, 19 to H5N6, and 9 to H5N8. Analysis based on global 2.3.4.4b viruses showed that all the viruses described in this study were likely originated from H5N8, exhibiting a heterogeneous evolutionary history between H5N1 and H5N6 during 2015-2022 worldwide. H5N1 showed a higher rate of evolution in 2021-2022 and more sites under positive selection pressure in 2015-2022. The antigenic profiles of the novel H5N1 and H5N6 exhibited notable variations. Further hemagglutination inhibition assay suggested that some A(H5N1) viruses may be antigenically distinct from the circulating H5N6 and H5N8 strains. Mammalian challenge assays demonstrated that the H5N8 virus (21GD001_H5N8) displayed the highest pathogenicity in mice, followed by the H5N1 virus (B1557_H5N1) and then the H5N6 virus (220086_H5N6), suggesting a heterogeneous virulence profile of H5 AIVs in the mammalian hosts. Based on the above results, we speculate that A(H5N1) viruses have a higher risk of emergence in the future. Collectively, these findings unveil a new landscape of different evolutionary history and biological characteristics of novel H5 AIVs in clade 2.3.4.4b, contributing to a better understanding of designing more effective strategies for the prevention and control of novel H5 AIVs.

Impact of greening trends on biogenic volatile organic compound emissions in China from 1985 to 2022: Contributions of afforestation projects.

The rapid expansion of green areas in China has enhanced carbon sinks, but it also presents challenges regarding increased biogenic volatile organic compound (BVOC) emissions. This study examines the impact of greening trends on BVOC emissions in China from 1985 to 2001 and from 2001 to 2022, focusing on evaluating long-term trends in BVOC emissions within eight afforestation project areas during these two periods. Emission factors for 62 dominant tree species and provincial Plant Functional Types were updated. The BVOC emission inventories were developed for China at a spatial resolution of 27 km × 27 km using the Model of Emissions of Gases and Aerosols from Nature. The national BVOC emissions in 2018 were estimated at 54.24 Tg, with isoprene, monoterpenes, sesquiterpenes, and other BVOC contributing 26.94 Tg, 2.29 Tg, 0.44 Tg, and 24.57 Tg, respectively. Over the past 37 years, BVOC emissions experienced a slow growth rate of 1.7 % (0.79 Tg) during 1985-2001, followed by a significant increase of 12 % (6 Tg) from 2001 to 2022. BVOC emissions in the eight afforestation project areas increased by 2 % and 20 % during the two periods. From 2001 to 2022, at the regional scale, the Shelterbelt program for the middle reaches of the Yellow River area exhibited the largest rate of increase (43 %) in BVOC emissions. The Shelterbelt program for the upper and middle reaches of the Yangtze River made the most largest contribution (45 %) to the national increase in BVOC emissions. Afforestation projects have shifted towards planting more broadleaf trees than needleleaf trees from 2001 to 2022, and there also showed a change from herbaceous plants to broadleaf trees. These trends have led to higher average emission factors for vegetation, resulting in increased BVOC emissions. It underscores the importance of considering BVOC emissions when evaluating afforestation initiatives, emphasizing the need to balancing ecological benefits with potential atmospheric consequences.

Posthepatectomy HBV reactivation in hepatitis B-related hepatocellular carcinoma influences postoperative survival in patients with preoperative low HBV-DNA levels.

OBJECTIVE: This study aimed to clarify the incidence of hepatitis B virus (HBV) reactivation and its significance on long-term survival after partial hepatectomy in patients with HBV-related hepatocellular carcinoma (HCC), who had preoperative low HBV-DNA level of less than 2000 IU/mL. BACKGROUND: HBV reactivation is a frequent complication of systemic chemotherapy in hepatitis B surface antigen-positive patients. Surgery and anesthesia result in a generalized state of immunosuppression in the immediate postoperative period. Data on HBV reactivation and its significance after partial hepatectomy are unclear. PATIENTS AND METHODS: Consecutive patients from January 2006 to December 2007 were retrospectively studied. RESULTS: HBV reactivation happened in 19.1% of patients in 1 year. There were 28 patients whose HBV reactivation was detected after the diagnosis of HCC recurrence. On multivariate analysis, hepatitis B e antigen (HBeAg) positivity, preoperative HBV-DNA above the lower limit of quantification (≥200 IU/mL), Ishak inflammation score of greater than 3, preoperative transarterial chemoembolization (TACE), operation time of more than 180 minutes, blood transfusion, and without prophylactic antiviral therapy were significantly associated with an increased risk of HBV reactivation. HBV reactivation negatively influenced postoperative hepatic functions. The posthepatectomy liver failure rate in patients with HBV reactivation was significantly higher than in those without reactivation (11.8% vs 6.4%; P = 0.002). The 3-year disease-free survival (DFS) rate and overall survival (OS) rates after resection in patients with HBV reactivation were significantly lower than those without reactivation (34.1% vs 46.0%; P = 0.009, and 51.6% vs 67.2%; P < 0.001, respectively). HBeAg positivity, detectable preoperative HBV-DNA level, high Ishak inflammation score, preoperative TACE, long operation time, and blood transfusion were independent risk factors for HBV reactivation, whereas prophylactic antiviral therapy was a protective factor. HBV reactivation, HBeAg positivity, HBV-DNA level of 200 IU/mL or more, tumor diameter greater than 5 cm, presence of satellite nodules, presence of portal vein tumor thrombus, blood transfusion, and resection margin less than 1.0 cm were independent risk factors for DFS. A HBV-DNA level of 200 IU/mL or more, an Ishak fibrosis score of 4 or greater, a tumor diameter greater than 5 cm, the presence of satellite nodules, the presence of portal vein tumor thrombus, a resection margin less than 1.0 cm, no prophylactic antiviral therapy, and HBV reactivation were independent risk factors for OS. CONCLUSIONS: HBV reactivation was common after partial hepatectomy for HBV-related HCC with a preoperative low HBV-DNA level of less than 2000 IU/mL. Routine prophylactic antiviral treatment should be given before partial hepatectomy.

Early viral suppression predicts good postoperative survivals in patients with hepatocellular carcinoma with a high baseline HBV-DNA load.

PURPOSE: To correlate early HBV-DNA suppression by antiviral treatment with posthepatectomy long-term survivals in patients with HBV-related hepatocellular carcinoma (HCC). METHODS: A retrospective study was conducted on patients with a baseline HBV-DNA load of >2,000 IU/ml. The cumulative rates of HBV-DNA undetectability at weeks 24 and 48, as well as long-term tumor recurrence and overall survivals were determined. RESULTS: Of 1,040 patients with a high baseline HBV-DNA load, 865 patients received antiviral treatment. At a median follow-up of 42 months, 616 patients (59.2 %) had developed HCC recurrence and 482 patients (46.3 %) had died. The median time to recurrence was 25 months. In patients who received antiviral treatment, the cumulative rates of HBV-DNA undetectability (<200 IU/ml) were 54.3 and 88.1 % at weeks 24 and 48, respectively. There was no significant difference between the two groups of patients who received antiviral treatment or not for disease-free survival. On multivariate analyses, tumor size >5 cm, blood transfusion, surgical margin <1 cm, presence of satellite nodules, presence of portal vein tumor thrombus and high Ishak inflammation score were significant risk factors of HCC recurrence. Also, tumor size >5 cm, surgical margin <1 cm, presence of satellite nodules, presence of portal vein tumor thrombus and high Ishak fibrosis score were significant factors associated with poor postoperative overall survival. On the other hand, an undetectable HBV-DNA level before week 24 was a significant protective factor of disease-free survival and overall survival. CONCLUSIONS: Early HBV-DNA suppression with antiviral treatment improved prognosis of patients with HBV-related HCC.

Advances in Extracellular Vesicle Nanotechnology for Precision Theranostics.

Extracellular vesicles (EVs) have increasingly been recognized as important cell surrogates influencing many pathophysiological processes, including cellular homeostasis, cancer progression, neurologic disease, and infectious disease. These behaviors enable EVs broad application prospects for clinical application in disease diagnosis and treatment. Many studies suggest that EVs are superior to conventional synthetic carriers in terms of drug delivery and circulating biomarkers for early disease diagnosis, opening up new frontiers for modern theranostics. Despite these clinical potential, EVs containing diverse cellular components, such as nucleic acids, proteins, and metabolites are highly heterogeneous and small size. The limitation of preparatory, engineering and analytical technologies for EVs poses technical barriers to clinical translation. This article aims at present a critical overview of emerging technologies in EVs field for biomedical applications and challenges involved in their clinic translations. The current methods for isolation and identification of EVs are discussed. Additionally, engineering strategies developed to enhance scalable production and improved cargo loading as well as tumor targeting are presented. The superior clinical potential of EVs, particularly in terms of different cell origins and their application in the next generation of diagnostic and treatment platforms, are clarified.

Smartphone-based pH responsive 3-channel colorimetric biosensor for non-enzymatic multi-antibiotic residues.

Antibiotic residues in animal-derived food pose a risk to food safety and human health. Here, a smartphone-based pH-responsive 3-channel colorimetric biosensor is constructed for rapid detection of non-enzymatic multi-antibiotic residues in milk. In this system, a magnetic separation and enrichment approach is designed to specifically capture different antibiotic residues in complex environment. Indicators loaded on polydopamine-silver nanoparticles with excellently pH responsive visualization properties are utilized to ensure the high sensitivity of detection system. Moreover, smartphones are introduced to fulfill the demand for portable and on-site inspection of practical applications. It achieves simultaneous detection of oxytetracycline, kanamycin and streptomycin in the linear range of 1-105 pg/mL with detection limits of 0.085, 0.168, and 0.307 pg/mL, respectively. The practicality of the reported multi-antibiotic residues detection system is successfully demonstrated and evaluated challenging milk samples. Therefore, this system demonstrates the wide applications in multi-antibiotic residue analysis and food safety guarantee.

Paintable Bioactive Extracellular Vesicle Ink for Wound Healing.

The treatment of cutaneous wounds involving complex biological processes has become a significant public health concern worldwide. Here, we developed an efficient extracellular vesicle (EV) ink to regulate the inflammatory microenvironment and promote vascular regeneration for wound healing. The technology, termed portable bioactive ink for tissue healing (PAINT), leverages bioactive M2 macrophage-derived EVs (EVM2) and a sodium alginate precursor, forming a biocompatible EV-Gel within 3 min after mixing, enabling it to be smeared on wounds in situ to meet diverse morphologies. The bioactive EVM2 reprogram macrophage polarization and promote the proliferation and migration of endothelial cells, thereby effectively regulating inflammation and enhancing angiogenesis in wounds. Through integration with a 3D printing pen, the platform enables EV-Gel to be applied to wound sites having arbitrary shapes and sizes with geometric matches for tissue repairment. When evaluated using a mouse wound model, PAINT technology accelerates cutaneous wound healing by promoting the angiogenesis of endothelial cells and the polarization of macrophages to M2 phenotype in vivo, demonstrating the high potential of bioactive EV ink as a portable biomedical platform for healthcare.