Simultaneous carbon, nitrogen and phosphorus removal in sequencing batch membrane aerated biofilm reactor with biofilm thickness control via air scouring aided by computational fluid dynamics.

Membrane aerated biofilm reactor (MABR) is challenged by biofilm thickness control and phosphorus removal. Air scouring aided by computational fluid dynamics (CFD) was employed to detach outer biofilm in sequencing batch MABR treating low C/N wastewater. Biofilm with 177-285 µm thickness in cycle 5-15 achieved over 85 % chemical oxygen demand (COD) and total inorganic nitrogen (TIN) removals at loading rate of 13.2 gCOD/m2/d and 2.64 gNH4+-N/m2/d. Biofilm rheology measurements in cycle 10-25 showed yield stress against detachment of 2.8-7.4 Pa, which were equal to CFD calculated shear stresses under air scouring flowrate of 3-9 L/min. Air scouring reduced effluent NH4+-N by 10 % and biofilm thickness by 78 µm. Intermittent aeration (4h off, 19.5h on) and air scouring (3 L/min, 30 s before settling) in one cycle achieved COD removal over 90 %, TIN and PO43--P removals over 80 %, showing great potential for simultaneous carbon, nitrogen and phosphorus removals.

A Mobile-Based Nutrition Tracker App Enhanced Dietitian-Guided 2:1:1 Diet-Induced Weight Loss: An 8-Week Retrospective Cohort Study in Taiwan.

Effective weight management interventions involve a combination of behavioral strategies focusing on dietary changes. Tracing the change through mobile apps has been proven to be a valuable platform for facilitating weight management in many countries. However, the effectiveness of mobile app-based dietary intervention on weight management in Taiwan remains to be determined. By using the designated mobile app, this study aimed to assess the efficacy of the diet intervention, which is based on a 2:1:1 portion control plate and a flexible low-carbohydrate (FLC) diet. This 8-week retrospective cohort study involved 10,297 participants who were divided into two groups: the intervention group (joined an 8-week diet intervention program with the daily diet record assessed by registered dietitians) and the control group (voluntarily using the app without instructional materials or coaching). After eight weeks of intervention, the intervention group showed a higher weight loss percentage (-4.78% vs. -1.54%), body mass index (BMI) (-1.26 kg/m2 vs. 0.69 kg/m2), and diet record completeness (73.52% vs. 28.91%) compared with the control group. With respect to gender, male participants showed higher baseline weight and higher weight loss (-6.02%) in the intervention group. In the intervention group, 2871 participants (33.4%) lost less than 4% of their weight, 5071 participants (58.9%) lost 4-8% of their body weight, and 662 participants (7.7%) lost >8% of their weight. Compared to the low-effectiveness group (weight lost <4%), the high-effectiveness group (weight lost >8%) had a significantly higher diet record completeness (91.61 ± 15.99 vs. 55.81 ± 32.92), dietary compliance (green light %) (88.93 ± 9.9 vs. 77.75 ±17.5), protein intake % (26.34 ± 2.85 vs. 23.49 ± 3.56), and fat intake % (49.66 ± 6.36 vs. 44.05 ± 7.37). Most importantly, the high-effectiveness group had a lower carbohydrate intake % (24.1 ± 7.86 vs. 32.46 ± 9.61). The results remained significant after being stratified by gender. This study found that the use of online applications plus the intervention of dietitians is beneficial for short-term weight loss. The composition of nutrients and dietary compliance also significantly impacted weight loss.

Identification of Two Linear Epitopes on MGF_110-13L Protein of African Swine Fever Virus with Monoclonal Antibodies.

African swine fever caused by African swine fever virus (ASFV) is an acute, highly contagious swine disease with high mortality. To facilitate effective vaccine development and find more serodiagnostic targets, fully exploring the ASFV antigenic proteins is urgently needed. In this study, the MGF_110-13L was identified as an immunodominant antigen among the seven transmembrane proteins. The main outer-membrane domain of MGF_110-13L was expressed and purified. Two monoclonal antibodies (mAbs; 8C3, and 10E4) against MGF_110-13L were generated. The epitopes of two mAbs were preliminary mapped with the peptide fusion proteins after probing with mAbs by enzyme-linked immunosorbent assay (ELISA) and Western blot. And the two target epitopes were fine-mapped using further truncated peptide fusion protein strategy. Finally, the core sequences of mAbs 8C3 and 10E4 were identified as 48WDCQDGICKNKITESRFIDS67, and 122GDHQQLSIKQ131, respectively. The peptides of epitopes were synthesized and probed with ASFV antibody positive pig sera by a dot blot assay, and the results showed that epitope 10E4 was an antigenic epitope. The epitope 10E4 peptide was further evaluated as a potential antigen for detecting ASFV antibodies. To our knowledge, this is the first report of antigenic epitope information on the antigenic MGF_110-13L protein of ASFV.

Enhanced anaerobic digestion performance and sludge filterability by membrane microaeration for anaerobic membrane bioreactor application.

Slow dissolution/hydrolysis of insoluble/macromolecular organics and poor sludge filterability restrict the application potential of anaerobic membrane bioreactor (AnMBR). Bubble-free membrane microaeration was firstly proposed to overcome these obstacles in this study. The batch anaerobic digestion tests feeding insoluble starch and soluble peptone with and without microaeration showed that microaeration led to a 65.7-144.8% increase in methane production and increased critical flux of microfiltration membrane via driving the formation of large sludge flocs and the resultant improvement of sludge settleability. The metagenomic and bioinformatic analyses showed that microaeration significantly enriched the functional genes and bacteria for polysaccharide and protein hydrolysis, microaeration showed little negative effects on the functional genes involved in anaerobic metabolisms, and substrate transfer from starch to peptone significantly affected the functional genes and microbial community. This study demonstrates the dual synergism of microaeration to enhance the dissolution/hydrolysis/acidification of insoluble/macromolecular organics and sludge filterability for AnMBR application.

A qualitative study on experiences of stigma among postoperative oral cancer patients.

AIM: This study aimed to explore the characteristics of stigma in postoperative oral cancer patients to provide a reference for the formulation of targeted intervention measures. METHODS: A qualitative study was conducted on 25 postoperative oral cancer patients in a tertiary A hospital in Hunan, China, from March to July 2021. Semi-structured face-to-face interviews focused on experiences of stigma were performed. The interview data was analyzed using the NVivo V.12 software based on the reflexive intuitive thematic analysis method. The paper complies with the COREQ. RESULTS: The stigma experience of postoperative oral cancer patients can be divided into 3 themes: (1) triggers (impaired appearance and oral function and psycho-social pressure); (2) forms (overall isolation, unpleasant feeling of inferiority, and unpleasant social discrimination); (3) coping strategies (positive psychological adjustment, seeking social support and coming out of the unpleasant shadows). CONCLUSION: Postoperative oral cancer patients clearly articulated that stigma was present in their lives and they experienced multiple forms of stigma. Further work is needed to increase education and awareness about oral cancer to guide them to take positive coping and reduce stigma.

Bacillus coagulans TCI711 Supplementation Improved Nonalcoholic Fatty Liver by Modulating Gut Microbiota: A Randomized, Placebo-Controlled, Clinical Trial.

Background: Nonalcoholic fatty liver disease (NAFLD) has become one of the major problems of chronic liver disease worldwide. It not only causes damage to the liver but also engenders chronic hepatitis and cirrhosis. Recent studies have shown that regulating Bacillus coagulans can improve NAFLD. Objectives: This trial explores whether B. coagulans TCI711 (BCT) could ameliorate NAFLD. Methods: A total of 57 patients with NAFLD were recruited through FibroScan liver fibrosis scanner and divided into placebo (n = 28) and BCT-supplemented groups (n = 29). Specifically, 1 BCT probiotic capsule was supplemented daily for 8 wk. Furthermore, the blood, stool, and fatty liver content were then examined. Results: Parameters evaluated for liver and kidney indicators showed no side effects after supplementing BCT. A significant reduction of 8.7% in the fatty liver was achieved by effectively suppressing the grade of fatty liver as revealed by controlled attenuation parameter. BCT also regulated gut microbiota profiles, with significant increases observed in Bifidobacterium, Eubacterium, Ruminococcaceae, and Sellimonas compared with the baseline. Conclusions: BCT may improve NAFLD by regulating gut microbiota, and parameters evaluated for liver and kidney indicate no side effects.

Design, synthesis and biological evaluation of indole-2-carboxylic acid derivatives as novel HIV-1 integrase strand transfer inhibitors.

Integrase plays an important role in the life cycle of HIV-1, and integrase strand transfer inhibitors (INSTIs) can effectively impair the viral replication. However, drug resistance mutations have been confirmed to decrease the efficacy of INSTI during the antiviral therapy. Herein, indole-2-carboxylic acid (1) was found to inhibit the strand transfer of integrase, and the indole nucleus of compound 1 was observed to chelate with two Mg2+ ions within the active site of integrase. Through optimization of compound 1, a series of indole-2-carboxylic acid derivatives were designed and synthesized, and compound 17a was proved to markedly inhibit the effect of integrase, with IC50 value of 3.11 µM. Binding mode analysis of 17a demonstrated that the introduced C6 halogenated benzene ring could effectively bind with the viral DNA (dC20) through π-π stacking interaction. These results indicated that indole-2-carboxylic acid is a promising scaffold for the development of integrase inhibitors.

Spinal Lymphatic Dysfunction Aggravates the Recovery Process After Spinal Cord Injury.

We aimed to evaluate the role of the spinal lymphatic system in spinal cord injury and whether it has an impact on recovery after spinal cord injury. Flow cytometry was used to evaluate the changes in the number of microvesicles after spinal cord injury. Evans blue extravasation was used to evaluate the function of the lymphatic system. Evans blue extravasation and immunofluorescence were used to evaluate the permeability of blood spinal cord barrier. The spinal cord edema was evaluated by dry and wet weight.Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was used to evaluate apoptosis after spinal cord injury. Nuclear factor-kappa B pathway was detected by Western blot. Behavioral tests were used to evaluate limb function. Microvesicles released after spinal cord injury can enter the thoracic duct and then enter the blood through the lymph around the spine. After ligation of the thoracic duct, it can aggravate the neuropathological manifestations and limb function after spinal cord injury. The potential mechanism may involve nuclear factor-kappa B pathway.

Aspartame Intake Delayed Puberty Onset in Female Offspring Rats and Girls.

SCOPE: The disturbance of the hypothalamic-pituitary-gonadal (HPG) axis, gut microbiota (GM) community, and short-chain fatty acids (SCFAs) is a triggering factor for pubertal onset. The study investigates the effects of the long-term intake of aspartame on puberty and GM in animals and humans. METHODS AND RESULTS: Aspartame-fed female offspring rats result in vaginal opening time prolongation, serum estrogen reduction, and serum luteinizing hormone elevation. , 60 mg kg-1 aspartame treatment decreases the mRNA levels of gonadotropin-releasing hormone (GnRH), Kiss1, and G protein-coupled receptor 54 (GPR54), increases the mRNA level of RFamide-related peptide-3 (RFRP-3), and decreases the expression of GnRH neurons in the hypothalamus. Significant differences in relative bacterial abundance at the genus levels and decreased fecal SCFA levels are noted by 60 mg kg-1 aspartame treatment. Among which, Escherichia-Shigella is negatively correlated with several SCFAs. In girls, high-dose aspartame consumption decreases the risk of precocious puberty. CONCLUSIONS: Aspartame reduces the chance of puberty occurring earlier than usual in female offspring and girls. Particularly, 60 mg kg-1 aspartame-fed female offspring delays pubertal onset through the dysregulation of HPG axis and GM composition by inhibiting the Kiss1/GPR54 system and inducing the RFRP-3. An acceptable dose of aspartame should be recommended during childhood.

Tubeimosides are pan-coronavirus and filovirus inhibitors that can block their fusion protein binding to Niemann-Pick C1.

SARS-CoV-2 and filovirus enter cells via the cell surface angiotensin-converting enzyme 2 (ACE2) or the late-endosome Niemann-Pick C1 (NPC1) as a receptor. Here, we screened 974 natural compounds and identified Tubeimosides I, II, and III as pan-coronavirus and filovirus entry inhibitors that target NPC1. Using in-silico, biochemical, and genomic approaches, we provide evidence that NPC1 also binds SARS-CoV-2 spike (S) protein on the receptor-binding domain (RBD), which is blocked by Tubeimosides. Importantly, NPC1 strongly promotes productive SARS-CoV-2 entry, which we propose is due to its influence on fusion in late endosomes. The Tubeimosides' antiviral activity and NPC1 function are further confirmed by infection with SARS-CoV-2 variants of concern (VOC), SARS-CoV, and MERS-CoV. Thus, NPC1 is a critical entry co-factor for highly pathogenic human coronaviruses (HCoVs) in the late endosomes, and Tubeimosides hold promise as a new countermeasure for these HCoVs and filoviruses.

Value of nomogram based on dual-layer detector spectral CT quantitative parameters and conventional CT features for evaluating high-grade pattern of pulmonary invasive non-mucinous adenocarcinoma / 中华放射学杂志

Objective:To explore the value of nomogram based on dual-layer detector spectral CT quantitative parameters and conventional CT feature in evaluating high-grade pattern (HGP) of pulmonary invasive non-mucinous adenocarcinoma.Methods:This study was a case-control study. A total of 71 patients with pathologically confirmed pulmonary invasive non-mucinous adenocarcinoma in the First Affiliated Hospital of Soochow University from February 2022 to May 2023 were retrospectively enrolled, which were divided into HGP and non-HGP groups according to pathological results. Conventional CT features were analyzed, including size, shape, density, internal signs, margins, and pleural retraction. The iodine concentration (IC), electron density (ED), and normalized iodine concentration (NIC) of the lesions in both the arterial phase (AP) and venous phase (VP) were measured. Differences between the two groups were analyzed using independent sample t-test, Mann-Whitney U test, or χ2 test. Multivariate logistic regression analysis was used to select the independent influencing factors of HGP in pulmonary invasive non-mucinous adenocarcinoma, and the conventional CT feature model, the spectral CT quantitative parameter model, and the combined model were constructed and expressed in a nomogram. The area under the curve (AUC) of receiver operating characteristic curve was used to assess the performance of each model, and was compared by DeLong test. Decision curves (DCA) was used to assess the clinical net benefit of the models. Results:There were significant differences between HGP group and non-HGP group in terms of density, lobulation, spiculation, IC AP, IC VP, NIC AP, ED AP and ED VP (all P<0.05). The multivariate logistic regression analysis showed that the solid nodule ( OR=15.452, 95% CI 4.246-56.235, P<0.001), lobulation ( OR=7.069, 95% CI 1.618-30.883, P=0.009), ED AP( OR=1.183, 95% CI 1.064-1.315, P=0.002) and IC VP ( OR=0.231, 95% CI 0.072-0.744, P=0.014) were independent influencing factors for predicting HGP in pulmonary invasive non-mucinous adenocarcinoma. The AUC of the conventional CT feature model, spectral CT quantitative parameter model, and the combined model were 0.835, 0.890, and 0.915, respectively. The AUC of the combined model was better than that of the conventional CT feature model ( Z=2.67, P=0.008). The DCA analysis demonstrated that the nomogram had higher clinical net benefit than the conventional CT feature model. Conclusions:The nomogram based on the quantitative parameters of dual-layer detector spectral CT and conventional CT features have favorable diagnostic efficacy in predicting HGP in pulmonary invasive non-mucinous adenocarcinoma, and can be used as a reliable tool for non-invasive diagnosis of HGP before surgery.

Value of nomogram based on quantitative parameters of dual-layer detector spectral CT and conventional CT features in preoperative prediction of tumor deposits in colorectal cancer / 中华放射学杂志

Objective:To investigate the value of the nomogram based on quantitative parameters of dual-layer detector spectral CT and conventional CT features in preoperatively predicting tumor deposits (TDs) in colorectal cancer.Methods:This study was a case-control study. A total of 126 patients with pathologically confirmed colorectal cancer who underwent preoperative spectral CT scan from January 2022 to March 2023 in the First Affiliated Hospital of Soochow University were enrolled retrospectively. Patients were divided into TDs-positive group ( n=38) and TDs-negative group ( n=88) based on pathological results. The following conventional CT features were assessed: cT stage, cN status, uniformity of enhancement in the venous phase, pericolorectal fat invasion (PFI), maximum tumor diameter, and tumor location. The following quantitative parameters were also measured and calculated: the normalized iodine concentration (NIC) of lesions, the normalized effective atomic number (NZ eff), and the slope of the 40-100 keV spectral curve (K) in the arterial and venous phases, and the difference in NIC between the arterial and venous phases. Multivariate logistic regression analysis was used to select independent predictors of TDs and the nomogram based on spectral CT quantitative parameters and conventional CT features was constructed. The receiver operating characteristic curve was performed to evaluate the diagnostic performance of each parameter and model. DeLong test was used to compare the differences of area under the curve (AUC). Results:Statistically significant differences were found between the TDs-positive and TDs-negative groups for the cT stage, cN status, uniformity of enhancement in the venous phase, PFI, NIC, NZ eff, K in the venous phase and the difference in NIC between the arterial and venous phases ( P<0.05). After multivariate logistic regression analysis, the conventional CT feature model incorporated two features: uniformity of enhancement in the venous phase (OR=9.602, 95% CI 3.728-24.734, P=0.001) and PFI ( OR=2.881, 95% CI 1.177-7.049, P=0.020). The combined model of conventional CT features and spectral CT quantitative parameters incorporated three features: the difference in NIC between the arterial and venous phases ( OR=37.599, 95% CI 8.320-169.912, P=0.001), uniformity of enhancement in the venous phase ( OR=14.978, 95% CI 3.848-58.295, P=0.001), and PFI ( OR=4.013, 95% CI 1.320-12.760, P=0.015), and the nomogram was constructed. The AUC, sensitivity, and specificity of the nomogram for predicting TDs were 0.919 (95% CI 0.865-0.973), 84.2%, and 86.5%, respectively. The AUC of the conventional CT feature model was 0.796 (95% CI 0.707-0.885), which was lower than that of the nomogram, and the difference was statistically significant ( Z=3.87, P=0.001). Conclusion:Dual-layer spectral detector CT can be used to predict TDs in colorectal cancer preoperatively, and the nomogram based on quantitative parameters of dual-layer detector spectral CT and conventional CT features shows good diagnostic performance.

The Discovery of Indole-2-carboxylic Acid Derivatives as Novel HIV-1 Integrase Strand Transfer Inhibitors.

As an important antiviral target, HIV-1 integrase plays a key role in the viral life cycle, and five integrase strand transfer inhibitors (INSTIs) have been approved for the treatment of HIV-1 infections so far. However, similar to other clinically used antiviral drugs, resistance-causing mutations have appeared, which have impaired the efficacy of INSTIs. In the current study, to identify novel integrase inhibitors, a set of molecular docking-based virtual screenings were performed, and indole-2-carboxylic acid was developed as a potent INSTI scaffold. Indole-2-carboxylic acid derivative 3 was proved to effectively inhibit the strand transfer of HIV-1 integrase, and binding conformation analysis showed that the indole core and C2 carboxyl group obviously chelated the two Mg2+ ions within the active site of integrase. Further structural optimizations on compound 3 provided the derivative 20a, which markedly increased the integrase inhibitory effect, with an IC50 value of 0.13 µM. Binding mode analysis revealed that the introduction of a long branch on C3 of the indole core improved the interaction with the hydrophobic cavity near the active site of integrase, indicating that indole-2-carboxylic acid is a promising scaffold for the development of integrase inhibitors.

An exhaustive analysis of post-traumatic brain injury dementia using bibliometric methodologies.

Background: It is widely accepted that traumatic brain injury (TBI) increases the risk of developing long-term dementia, although some controversies surrounding this topic exist. Annually, approximately 69 million individuals suffer from TBI all around the world. Such a large population of TBI patients could lead to a future surge in the number of dementia patients. Due to the potentially severe consequences of TBI, various research projects on post-TBI dementia have emerged worldwide. Therefore, it is essential to comprehend the current status and development of post-TBI dementia for future research. Objective: The purpose of the study was to provide an overview of the field and identify hotspots, research frontiers, and future research trends for post-TBI dementia. Methods: Articles related to post-TBI dementia were retrieved from the Web of Science Core Collection for the period between 2007 and 2022, and analyzing them based on factors such as citations, authors, institutions, countries, journals, keywords, and references. Data analysis and visualization were conducted using VOSviewer, CiteSpace, and an online bibliometric platform (https://bibliometric.com). Results: From 2007 to 2022, we obtained a total of 727 articles from 3,780 authors and 1,126 institutions across 52 countries, published in 262 journals. These articles received a total of 29,353 citations, citing 25,713 references from 3,921 journals. Over the last 15 years, there has been a significant upward trend in both publications and citations. The most productive country was the United States, the most productive institution was Boston University, and the most productive author was McKee AC. Journal of Neurotrauma has been identified as the periodical with the greatest number of publications. Three clusters were identified through cluster analysis of keywords. A burst in the use of the term "outcome" in 2019 is indicative of a future research hotspot. The timeline view of references showed 14 clusters, of which the first 4 clusters collected the majority of papers. The first 4 clusters were "chronic traumatic encephalopathy," "age of onset," "tauopathy," and "cognitive decline," respectively, suggesting some areas of interest in the field. Conclusion: The subject of post-TBI dementia has raised much interest from scientists. Notably, America is at the forefront of research in this area. Further collaborative research between different countries is imperative. Two topical issues in this field are "The association between TBI and dementia-related alterations" and "chronic traumatic encephalopathy (CTE)." Studies on clinical manifestation, therapy, pathology, and pathogenic mechanisms are also popular in the field.

Mammalian Cell-Line-Expressed CD2v Protein of African Swine Fever Virus Provides Partial Protection against the HLJ/18 Strain in the Early Infection Stage.

A cell line expressing the CD2v protein of ASFV was generated. The efficient expression of CD2v protein was determined by immunofluorescence and Western blotting. The CD2v protein was Ni-affinity purified from the supernatant of cell cultures. The CD2v-expressing cells showed properties of hemadsorption, and the secreted CD2v protein exhibited hemagglutinating activity. The antigenicity and immunoprotection ability of CD2v were evaluated by immunizing pigs alone, combined with a cell-line-expressed p30 protein or triple combined with p30 and K205R protein. Immunized pigs were challenged with the highly virulent ASFV strain HLJ/18. Virus challenge results showed that CD2v immunization alone could provide partial protection at the early infection stage. Protein p30 did not show synergistic protection effects in immunization combined with CD2v. Interestingly, immunization with the triple combination of CD2V, p30 and K205R reversed the protection effect. The viremia onset time was delayed, and one pig out of three recovered after the challenge. The pig recovered from ASFV clinical symptoms, the rectal temperature returned to normal levels and the viremia was cleared. The mechanism of this protection effect warrants further investigation.

A Novel Conserved Linear Neutralizing Epitope on the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein.

The continuous emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made it challenging to develop broad-spectrum prophylactic vaccines and therapeutic antibodies. Here, we have identified a broad-spectrum neutralizing antibody and its highly conserved epitope in the receptor-binding domain (RBD) of the spike protein (S) S1 subunit of SARS-CoV-2. First, nine monoclonal antibodies (MAbs) against the RBD or S1 were generated; of these, one RBD-specific MAb, 22.9-1, was selected for its broad RBD-binding abilities and neutralizing activities against SARS-CoV-2 variants. An epitope of 22.9-1 was fine-mapped with overlapping and truncated peptide fusion proteins. The core sequence of the epitope, 405D(N)EVR(S)QIAPGQ414, was identified on the internal surface of the up-state RBD. The epitope was conserved in nearly all variants of concern of SARS-CoV-2. MAb 22.9-1 and its novel epitope could be beneficial for research on broad-spectrum prophylactic vaccines and therapeutic antibody drugs. IMPORTANCE The continuous emergence of new variants of SARS-CoV-2 has caused great challenge in vaccine design and therapeutic antibody development. In this study, we selected a broad-spectrum neutralizing mouse monoclonal antibody which recognized a conserved linear B-cell epitope located on the internal surface of RBD. This MAb could neutralize all variants until now. The epitope was conserved in all variants. This work provides new insights in developing broad-spectrum prophylactic vaccines and therapeutic antibodies.

Fluorescence labeling of extracellular vesicles for diverse bio-applications in vitro and in vivo.

Extracellular vesicles (EVs) are nanosized vesicles enclosed in a lipid membrane that are sustainably released by nearly all cell types. EVs have been deemed as valuable biomarkers for diagnostics and effective drug carriers, owing to the physiological function of transporting biomolecules for intercellular communication. To investigate their biological properties, efficient labeling strategies have been constructed for EV research, among which fluorescence labeling exerts a powerful function due to the capability of visualizing the nanovesicles with high sensitivity both in vitro and in vivo. In one aspect, with the help of functional fluorescence tags, EVs could be differentiated and categorized in vitro by various analytical techniques, which exert vital roles in disease diagnosis, prognosis, and treatment monitoring. Additionally, innovative EV reporters have been utilized for visualizing EVs, in combination with powerful microscopy techniques, which provide potential tools for investigating the dynamic events of EV release and intercellular communication in suitable animal models. In this feature article, we survey the latest advances regarding EV fluorescence labeling strategies and their application in biomedical application and in vivo biology investigation, highlighting the progresses in individual EV imaging. Finally, the challenges and future perspectives in unravelling EV physiological properties and further biomedical application are discussed.

A Systematic Review and Meta-Analysis of the Association between Residual Shunts after Patent Foramen Ovale Closure and Long-Term Cerebrovascular Events.

BACKGROUND: The association between a patent foramen ovale (PFO) and cryptogenic stroke (CS) is well established, and the benefits of PFO closure are clearly recognized. This study aimed to investigate the presence of a residual shunt in patients who have experienced cryptogenic cerebrovascular events following a PFO closure. METHODS: Two researchers systematically searched the PubMed and Embase online database for pertinent clinical studies published between January 2000 and July 2021 concerning the recurrence of cerebrovascular events after PFO closures. RESULTS: Upon screening an initial list of 2,342 articles, six studies were identified, involving 2,083 patients. Overall, the analysis indicated a marked difference in the recurrence of cerebrovascular events in 8.89% of residual shunt (RS) cases compared to only 2.90% of non-RS cases. The summary odds ratio was 3.484 (95% confidence interval, 2.169-5.596), which suggested that RS may be a risk factor for recurrent cerebrovascular events in patients that experienced PFO-related cerebrovascular events within 6 months after PFO closure surgery. CONCLUSIONS: The presence of RS significantly increases the risk of recurrent cerebrovascular events in patients with clinical PFO closure.

Comprehensive mapping of antigenic linear B-cell epitopes on K205R protein of African swine fever virus with monoclonal antibodies.

African swine fever virus causes an acute, highly contagious swine disease with high mortality, leading to enormous losses in the pig industry. The K205R, a nonstructural protein of African swine fever virus, is abundantly expressed in the cytoplasm of infected cells at the early stage of infection and induces a strong immune response. However, to date, the antigenic epitopes of this immunodeterminant have not been characterized. In the present study, the K205R protein was expressed in a mammalian cell line and purified using Ni-affinity chromatography. Furthermore, three monoclonal antibodies (mAbs; 5D6, 7A8, and 7H10) against K205R were generated. Indirect immunofluorescence assay and western blot results showed that all three mAbs recognized native and denatured K205R in African swine fever virus (ASFV)-infected cells. To identify the epitopes of the mAbs, a series of overlapping short peptides were designed and expressed as fusion proteins with maltose-binding protein. Subsequently, the peptide fusion proteins were probed with monoclonal antibodies using western blot and enzyme-linked immunosorbent assay. The three target epitopes were fine-mapped; the core sequences of recognized by the mAbs 5D6, 7A8, and 7H10 were identified as 157FLTPEIQAILDE168, 154REKFLTP160, and 136PTNAMFFTRSEWA148, respectively. Probing with sera from ASFV-infected pigs in a dot blot assay demonstrated that epitope 7H10 was the immunodominant epitope of K205R. Sequence alignment showed that all epitopes were conserved across ASFV strains and genotypes. To our knowledge, this is the first study to characterize the epitopes of the antigenic K205R protein of ASFV. These findings may serve as a basis for the development of serological diagnostic methods and subunit vaccines.

Evidence synthesis of Chinese medicine for monkeypox: Suggestions from other contagious pox-like viral diseases.

Background: Monkeypox, a zoonotic disease caused by an Orthopoxvirus, presents an etiology similar to smallpox in humans. Currently, there are no licensed treatments for human monkeypox, so clear and urgent research on its prophylaxis and treatment is needed. Objective: The purpose of this study was to explore the evidence of Chinese medicine for contagious pox-like viral diseases and provide suggestions for the multi-country outbreak management of monkeypox. Methods: The review was registered on INPLASY (INPLASY202270013). Ancient classics in China and clinical trials involving randomized controlled trials , non-RCTs, and comparative observational studies of CM on the prevention and treatment of monkeypox, smallpox, measles, varicella, and rubella were retrieved from the Chinese Medical Code (fifth edition), Database of China Ancient Medicine, PubMed, the Cochrane Library, China National Knowledge Infrastructure, Chongqing VIP, Wanfang, Google Scholar, International Clinical Trial Registry Platform, and Chinese Clinical Trial Registry until 6 July 2022. Both quantitative and qualitative methods were applied to present the data collected. Results: The use of CM to control contagious pox-like viral diseases was traced back to ancient Chinese practice cited in Huangdi's Internal Classic, where the pathogen was recorded nearly two thousand years back. There were 85 articles (36 RCTs, eight non-RCTs, one cohort study, and 40 case series) that met the inclusion criteria, of which 39 studies were for measles, 38 for varicella, and eight for rubella. Compared with Western medicine for contagious pox-like viral diseases, CM combined with Western medicine showed significant improvements in fever clearance time (mean difference, -1.42 days; 95% CI, -1.89 to -0.95; 10 RCTs), rash/pox extinction time (MD, -1.71 days; 95% CI, -2.65 to -0.76; six RCTs), and rash/pox scab time (MD, -1.57 days; 95% CI, -1.94 to -1.19; five RCTs). When compared with Western medicine, CM alone could reduce the time of rash/pox extinction and fever clearance. Chinese herbal formulas, including modified Yinqiao powder, modified Xijiao Dihaung decoction, modified Qingjie Toubiao decoction, and modified Shengma Gegen decoction, were frequently applied to treat pox-like viral diseases and also showed significant effects in shortening the time of fever clearance, rash/pox extinction, and rash/pox scabs. Compared with Western medicine (placental globulin) or no intervention, eight non-randomized trials and observational studies on the prevention of contagious pox-like viral diseases showed a significant preventive effect of Leiji powder among high-risk populations. Conclusion: Based on historical records and clinical studies of CM in managing contagious pox-like viral diseases, some botanical drugs could be an alternative approach for treating and preventing human monkeypox. Prospective, rigorous clinical trials are urgently needed to confirm the potential preventive and treatment effect of Chinese herbal formulas. Systematic Review Registration: [https://inplasy.com/], identifier [INPLASY202270013].