Co-delivery of Siape1 and Melatonin by 125I-loaded PSMA-targeted Nanoparticles for the Treatment of Prostate Cancer.

BACKGROUND: Both apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) inhibition and melatonin suppress prostate cancer (PCa) growth. OBJECTIVE: This study evaluated the therapeutic efficiency of self-assembled and prostate-specific membrane antigen (PSMA)-targeted nanocarrier loading 125I radioactive particles and encapsulating siRNA targeting APE1 (siAPE1) and melatonin for PCa. METHODS: The linear polyarginine R12 polypeptide was prepared using Fmoc-Arg-Pbf-OH. The PSMA-targeted polymer was synthesized by conjugating azide-modified R12 peptide to PSMA monoclonal antibody (mAb). Before experiments, the PSMA-R12 nanocarrier was installed with melatonin and siAPE1, which were subsequently labeled by 125I radioactive particles. In vitro biocompatibility and cytotoxicity of nanocomposites were examined in LNCaP cells and in vivo biodistribution and pharmacokinetics were determined using PCa tumor-bearing mice. RESULTS: PSMA-R12 nanocarrier was ~120 nm in size and was increased to ~150 nm by melatonin encapsulation. PSMA-R12 nanoparticles had efficient loading capacities of siAPE1, melatonin, and 125I particles. The co-delivery of melatonin and siAPE1 by PSMA-R12-125I showed synergistic effects on suppressing LNCaP cell proliferation and Bcl-2 expression and promoting cell apoptosis and caspase-3 expression. Pharmacokinetics analysis showed that Mel@PSMA-R12-125I particles had high uptake activity in the liver, spleen, kidney, intestine, and tumor, and were accumulated in the tumor sites within the first 8 h p.i., but was rapidly cleared from all the tested organs at 24 h p.i. Administration of nanoparticles to PCa tumors in vivo showed that Mel@PSMA-R12- 125I/siAPE1 had high efficiency in suppressing PCa tumor growth. CONCLUSION: The PSMA-targeted nanocarrier encapsulating siAPE1 and melatonin is a promising therapeutic strategy for PCa and can provide a theoretical basis for patent applications.

Action of circulating and infiltrating B cells in the immune microenvironment of colorectal cancer by single-cell sequencing analysis.

BACKGROUND: The complexity of the immune microenvironment has an impact on the treatment of colorectal cancer (CRC), one of the most prevalent malignancies worldwide. In this study, multi-omics and single-cell sequencing techniques were used to investigate the mechanism of action of circulating and infiltrating B cells in CRC. By revealing the heterogeneity and functional differences of B cells in cancer immunity, we aim to deepen our understanding of immune regulation and provide a scientific basis for the development of more effective cancer treatment strategies. AIM: To explore the role of circulating and infiltrating B cell subsets in the immune microenvironment of CRC, explore the potential driving mechanism of B cell development, analyze the interaction between B cells and other immune cells in the immune microenvironment and the functions of communication molecules, and search for possible regulatory pathways to promote the anti-tumor effects of B cells. METHODS: A total of 69 paracancer (normal), tumor and peripheral blood samples were collected from 23 patients with CRC from The Cancer Genome Atlas database (https://portal.gdc.cancer.gov/). After the immune cells were sorted by multicolor flow cytometry, the single cell transcriptome and B cell receptor group library were sequenced using the 10X Genomics platform, and the data were analyzed using bioinformatics tools such as Seurat. The differences in the number and function of B cell infiltration between tumor and normal tissue, the interaction between B cell subsets and T cells and myeloid cell subsets, and the transcription factor regulatory network of B cell subsets were explored and analyzed. RESULTS: Compared with normal tissue, the infiltrating number of CD20+B cell subsets in tumor tissue increased significantly. Among them, germinal center B cells (GCB) played the most prominent role, with positive clone expansion and heavy chain mutation level increasing, and the trend of differentiation into memory B cells increased. However, the number of plasma cells in the tumor microenvironment decreased significantly, and the plasma cells secreting IgA antibodies decreased most obviously. In addition, compared with the immune microenvironment of normal tissues, GCB cells in tumor tissues became more closely connected with other immune cells such as T cells, and communication molecules that positively regulate immune function were significantly enriched. CONCLUSION: The role of GCB in CRC tumor microenvironment is greatly enhanced, and its affinity to tumor antigen is enhanced by its significantly increased heavy chain mutation level. Meanwhile, GCB has enhanced its association with immune cells in the microenvironment, which plays a positive anti-tumor effect.

Mapping global zoonotic niche and interregional transmission risk of monkeypox: a retrospective observational study.

BACKGROUND: Outbreaks of monkeypox have been ongoing in non-endemic countries since May 2022. A thorough assessment of its global zoonotic niche and potential transmission risk is lacking. METHODS: We established an integrated database on global monkeypox virus (MPXV) occurrence during 1958 - 2022. Phylogenetic analysis was performed to examine the evolution of MPXV and effective reproductive number (Rt) was estimated over time to examine the dynamic of MPXV transmissibility. The potential ecological drivers of zoonotic transmission and inter-regional transmission risks of MPXV were examined. RESULTS: As of 24 July 2022, a total of 49 432 human patients with MPXV infections have been reported in 78 countries. Based on 525 whole genome sequences, two main clades of MPXV were formed, of which Congo Basin clade has a higher transmissibility than West African clade before the 2022-monkeypox, estimated by the overall Rt (0.81 vs. 0.56), and the latter significantly increased in the recent decade. Rt of 2022-monkeypox varied from 1.14 to 4.24 among the 15 continuously epidemic countries outside Africa, with the top three as Peru (4.24, 95% CI: 2.89-6.71), Brazil (3.45, 95% CI: 1.62-7.00) and the United States (2.44, 95% CI: 1.62-3.60). The zoonotic niche of MPXV was associated with the distributions of Graphiurus lorraineus and Graphiurus crassicaudatus, the richness of Rodentia, and four ecoclimatic indicators. Besides endemic areas in Africa, more areas of South America, the Caribbean States, and Southeast and South Asia are ecologically suitable for the occurrence of MPXV once the virus has invaded. Most of Western Europe has a high-imported risk of monkeypox from Western Africa, whereas France and the United Kingdom have a potential imported risk of Congo Basin clade MPXV from Central Africa. Eleven of the top 15 countries with a high risk of MPXV importation from the main countries of 2022-monkeypox outbreaks are located at Europe with the highest risk in Italy, Ireland and Poland. CONCLUSIONS: The suitable ecological niche for MPXV is not limited to Africa, and the transmissibility of MPXV was significantly increased during the 2022-monkeypox outbreaks. The imported risk is higher in Europe, both from endemic areas and currently epidemic countries. Future surveillance and targeted intervention programs are needed in its high-risk areas informed by updated prediction.

Conditional editing of the Drosophila melanogaster genome using single transcripts expressing Cas9 and sgRNA.

The CRISPR/Cas9(clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR- associated protein 9) system, a highly efficient, simple, and easy genome editing technology, offers significant potential for genetic engineering and has been commonly applied in gene function studies in Drosophila melanogaster. However, when using CRISPR/Cas9 system to edit Drosophila melanogaster gene, Cas9 and sgRNA expression elements exist in different Drosophila melanogaster individuals, and Cas9 and sgRNA must be integrated into an individual through a complex genetic hybridization process, which has a long and complex operation cycle In this study, on the basis of the CRISPR/Cas9 system, we introduced the tRNA-sgRNA system and triplex elements, used triplex elements to link Cas9 and tRNA-sgRNA genes, stabilized the end of Cas9 mRNA after single transcript cutting, and made the expression of both Cas9 protein and sgRNA with a single transcript a reality. And as we obtained the corresponding phenotypic progeny in one hybridization, genetic manipulation was simplified. We found that conditional knockout of the white(w) gene in the Drosophila melanogaster eye and the broad(br) gene in the adult wing disc resulted in corresponding phenotypes that matched expectations using our new conditional gene editing system. So the significant advances in this new conditional gene editing system over the existing CRISPR/Cas9 system are that it is more efficient, extendable, and easy to use.

Integrative multi-omics analysis depicts the methylome and hydroxymethylome in recurrent bladder cancers and identifies biomarkers for predicting PD-L1 expression.

BACKGROUND: Urinary bladder cancer (UBC) is a common malignancy of the urinary tract; however, the mechanism underlying its high recurrence and responses to immunotherapy remains unclear, making clinical outcome predictions difficult. Epigenetic alterations, especially DNA methylation, play important roles in bladder cancer development and are increasingly being investigated as biomarkers for diagnostic or prognostic predictions. However, little is known about hydroxymethylation since previous studies based on bisulfite-sequencing approaches could not differentiate between 5mC and 5hmC signals, resulting in entangled methylation results. METHODS: Tissue samples of bladder cancer patients who underwent laparoscopic radical cystectomy (LRC), partial cystectomy (PC), or transurethral resection of bladder tumor (TURBT) were collected. We utilized a multi-omics approach to analyze both primary and recurrent bladder cancer samples. By integrating various techniques including RNA sequencing, oxidative reduced-representation bisulfite sequencing (oxRRBS), reduced-representation bisulfite sequencing (RRBS), and whole exome sequencing, a comprehensive analysis of the genome, transcriptome, methylome, and hydroxymethylome landscape of these cancers was possible. RESULTS: By whole exome sequencing, we identified driver mutations involved in the development of UBC, including those in FGFR3, KDMTA, and KDMT2C. However, few of these driver mutations were associated with the down-regulation of programmed death-ligand 1 (PD-L1) or recurrence in UBC. By integrating RRBS and oxRRBS data, we identified fatty acid oxidation-related genes significantly enriched in 5hmC-associated transcription alterations in recurrent bladder cancers. We also observed a series of 5mC hypo differentially methylated regions (DMRs) in the gene body of NFATC1, which is highly involved in T-cell immune responses in bladder cancer samples with high expression of PD-L1. Since 5mC and 5hmC alternations are globally anti-correlated, RRBS-seq-based markers that combine the 5mC and 5hmC signals, attenuate cancer-related signals, and therefore, are not optimal as clinical biomarkers. CONCLUSIONS: By multi-omics profiling of UBC samples, we showed that epigenetic alternations are more involved compared to genetic mutations in the PD-L1 regulation and recurrence of UBC. As proof of principle, we demonstrated that the combined measurement of 5mC and 5hmC levels by the bisulfite-based method compromises the prediction accuracy of epigenetic biomarkers.

Identification and functional analysis of Dmrt1 gene and the SoxE gene in the sexual development of sea cucumber, Apostichopus japonicus.

Members of the Doublesex and Mab-3-related transcription factor (Dmrt) gene family handle various vital functions in several biological processes, including sex determination/differentiation and gonad development. Dmrt1 and Sox9 (SoxE in invertebrates) exhibit a very conserved interaction function during testis formation in vertebrates. However, the dynamic expression pattern and functional roles of the Dmrt gene family and SoxE have not yet been identified in any echinoderm species. Herein, five members of the Dmrt gene family (Dmrt1, 2, 3a, 3b and 5) and the ancestor SoxE gene were identified from the genome of Apostichopus japonicus. Expression studies of Dmrt family genes and SoxE in different tissues of adult males and females revealed different expression patterns of each gene. Transcription of Dmrt2, Dmrt3a and Dmrt3b was higher expressed in the tube feet and coelomocytes instead of in gonadal tissues. The expression of Dmrt1 was found to be sustained throughout spermatogenesis. Knocking-down of Dmrt1 by means of RNA interference (RNAi) led to the downregulation of SoxE and upregulation of the ovarian regulator foxl2 in the testes. This indicates that Dmrt1 may be a positive regulator of SoxE and may play a role in the development of the testes in the sea cucumber. The expression level of SoxE was higher in the ovaries than in the testes, and knocking down of SoxE by RNAi reduced SoxE and Dmrt1 expression but conversely increased the expression of foxl2 in the testes. In summary, this study indicates that Dmrt1 and SoxE are indispensable for testicular differentiation, and SoxE might play a functional role during ovary differentiation in the sea cucumber.

Evaluation of Myocardial Perfusion Classification for Interventional Treatment of Chronic Total Occlusion of Coronary Artery / 中山大学学报(医学科学版)

【Subjects】 To investigate the clinical application value of myocardial contrast echocardiography （MCE） in selecting CTO-PCI patients. MethodsFrom February 2019 to March 2020， a total of 50 patients with chronic coronary artery occlusion were consecutively selected as the research subjects. MCE and two-dimensional speck-tracking echocardiography were completed before and 12 months after interventional therapy. The primary end point was major adverse cardiovascular events. Patients were divided into groups according to the preoperative myocardial perfusion level of MCE. The improvement of left ventricular function was evaluated by two-dimensional echocardiography and left ventricular global longitudinal strain. ResultsCompared with the abnormal perfusion group， the improvement of GLS in the normal perfusion group was greater （P=0.028）. The wall motion score index （WMSI） of the abnormal perfusion group before PCI was higher than that of the normal perfusion group （P=0.002）. WMSI in the abnormal perfusion group was higher than that in the normal perfusion group one year after PCI （P<0.001）. The left ventricular GLS（P=0.008）.WMSI（P=0.016） and left ventricular end-diastolic volume（P=0.032） in the normal perfusion group were improved compared with those before operation； The postoperative perfusion score of patients with abnormal perfusion was significantly improved （ P=0.032）. ConclusionMCE has clinical application value in optimizing the selection of CTO-PCI patients. CTO patients with different myocardial perfusion types have different benefits after PCI.

Role of defensins in diabetic wound healing.

The adverse consequences resulting from diabetes are often presented as severe complications. Diabetic wounds are one of the most commonly occurring complications in diabetes, and the control and treatment of this is costly. Due to a series of pathophysiological mechanisms, diabetic wounds remain in the inflammatory phase for a prolonged period of time, and face difficulty in entering the proliferative phase, thus leading to chronic non-healing wounds. The current consensus on the treatment of diabetic wounds is through multidisciplinary comprehensive management, however, standard wound treatment methods are still limited and therefore, more effective methods are required. In recent years, defensins have been found to play diverse roles in a variety of diseases; however, the molecular mechanisms underlying these activities are still largely unknown. Defensins can be constitutively or inductively produced in the skin, therefore, their local distribution is affected by the microenvironment of these diabetic wounds. Current evidence suggests that defensins are involved in the diabetic wound pathogenesis, and can potentially promote the early completion of each stage, thus making research on defensins a promising area for developing novel treatments for diabetic wounds. In this review, we describe the complex function of human defensins in the development of diabetic wounds, and suggest potential thera-peutic benefits.

Sexually dimorphic expression of foxl2 in the sea urchin (Mesocentrotus nudus).

Sea urchin (Mesocentrotus nudus) is an important economically mariculture species in several Asian countries, and gonads are the sole edible parts for people. In addition to commercial value, it is an excellent model for studying gonadal development, sex determination and sex differentiation. Identify sex-related genes is an effective way to reveal the molecular mechanism of gonadal development. In the present study, the foxl2 homologous gene was identified in M. nudus. Foxl2 is not a maternal factor, and is detected for the first time in two-arm stages. Additionally, the expression of foxl2 in the testis is higher than in the ovaries at the same developmental stages. The foxl2 transcripts were specifically enriched in the cytoplasm of germ cellsboth in the ovary and testis, but their proteins were more concentrated in the area near the oocyte nucleus. Overall, this study contributes to our understanding of the dynamic and sexually dimorphic expression pattern of foxl2 and provide a useful germ cell marker during gametogenesis in sea urchin.

The correlation between miR -34a-3p, miR -31, PLEK2 and the occurrence, development and prognosis of colorectal cancer.

The current study aimed to explore the correlation between Mir-34A-3p, Mir-31, PLEK2 and the occurrence, development and prognosis of colorectal cancer. For this paper, 120 patients with colorectal cancer were selected as the study group, and their adjacent normal tissues were selected as the control group. The quantitative real-time PCR (QRT-PCR) method was used to detect miR-34a-3p and miR-31 in tissues, and the immunohistochemistry EnVision two-step method was used to detect PLEK2 positive expression. The expressions of miR -34a-3p, miR -31, and PLEK2 in colon cancer tissues and normal cancer tissues were compared, and the correlation between miR -34a-3p, miR -31, and PLEK2 and clinic-pathological characteristics of colorectal cancer patients were analyzed. The results showed that expression of miR -34a-3p, miR -31 and positive expression rate of PLEK2 in colorectal cancer tissues were higher than those in normal adjacent tissues (P<0.05). The expression of miR -34a-3p was related to tumor size, degree of tissue differentiation, lymph node metastasis and TNM stage (P < 0.05). The 3-year survival rate of miR -34a-3p with low expression was lower than miR -34a-3p with high expression, which was a protective factor affecting the poor prognosis of colorectal cancer (P < 0.05). The expression of miR -31 was related to tumor size and TNM stage. The 3-year survival rate of the group with high expression of miR -31 was lower than the group with low expression of miR -31, which was a risk factor affecting the poor prognosis of colorectal cancer (P < 0.05). PLEK2 positive expression was associated with lymph node metastasis, and the 3-year survival rate of the PLEK2 positive group was lower than the PLEK2 low expression group, which was a risk factor for poor prognosis of colorectal cancer (P < 0.05). In general, miR -34a-3p, miR -31, and PLEK2 are closely associated with the occurrence and development of colorectal cancer, and they are all influential factors affecting the prognosis of patients with colorectal cancer, which can provide a basis for the evaluation and treatment of patients, and are worthy of widespread clinical application.

Platelet CFTR inhibition enhances arterial thrombosis via increasing intracellular Cl- concentration and activation of SGK1 signaling pathway.

Platelet hyperactivity is essential for thrombus formation in coronary artery diseases (CAD). Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients with cystic fibrosis elevates intracellular Cl- levels ([Cl-]i) and enhanced platelet hyperactivity. In this study, we explored whether alteration of [Cl-]i has a pathological role in regulating platelet hyperactivity and arterial thrombosis formation. CFTR expression was significantly decreased, while [Cl-]i was increased in platelets from CAD patients. In a FeCl3-induced mouse mesenteric arteriole thrombosis model, platelet-specific Cftr-knockout and/or pre-administration of ion channel inhibitor CFTRinh-172 increased platelet [Cl-]i, which accelerated thrombus formation, enhanced platelet aggregation and ATP release, and increased P2Y12 and PAR4 expression in platelets. Conversely, Cftr-overexpressing platelets resulted in subnormal [Cl-]i, thereby decreasing thrombosis formation. Our results showed that clamping [Cl-]i at high levels or Cftr deficiency-induced [Cl-]i increasement dramatically augmented phosphorylation (Ser422) of serum and glucocorticoid-regulated kinase (SGK1), subsequently upregulated P2Y12 and PAR4 expression via NF-κB signaling. Constitutively active mutant S422D SGK1 markedly increased P2Y12 and PAR4 expression. The specific SGK1 inhibitor GSK-650394 decreased platelet aggregation in wildtype and platelet-specific Cftr knockout mice, and platelet SGK1 phosphorylation was observed in line with increased [Cl-]i and decreased CFTR expression in CAD patients. Co-transfection of S422D SGK1 and adenovirus-induced CFTR overexpression in MEG-01 cells restored platelet activation signaling cascade. Our results suggest that [Cl-]i is a novel positive regulator of platelet activation and arterial thrombus formation via the activation of a [Cl-]i-sensitive SGK1 signaling pathway. Therefore, [Cl-]i in platelets is a novel potential biomarker for platelet hyperactivity, and CFTR may be a potential therapeutic target for platelet activation in CAD.

Influence of ultrasonic pretreatments on microwave hot-air flow rolling drying mechanism, thermal characteristics and rehydration dynamics of Pleurotus eryngii.

BACKGROUND: In order to improve the drying efficiency and reduce the drying energy consumption of Pleurotus eryngii, microwave hot-air flow rolling drying (MHARD) coupled with ultrasonic pretreating time (0, 20, 40, and 60 min) was used to investigate the drying profile, thermal characteristics, water migration, microstructure and rehydration dynamics of P. eryngii using differential scanning calorimetry (DSC), low-field nuclear magnetic resonance (LF-NMR) analysis and scanning electron microscopy (SEM). RESULTS: Results showed that the drying time of P. eryngii was 80, 70, 60 and 50 min, accordingly. Energy consumption was significantly reduced by ultrasonic pretreatment, and moisture effective diffusivity (Deff ) was increased with the increase of ultrasonic pretreating time. DSC curves showed that the drying process was accelerated by ultrasonic pretreatment significantly by enhancing the heat transfer. Meanwhile, SEM images showed that the cell was broken and numbers of irregular holes appeared in the ultrasound-pretreated samples. In terms of rehydration dynamics, Page model could well model the rehydration kinetics of dried P. eryngii with R2 > 0.99. CONCLUSION: The findings indicate that ultrasonic pretreatment is a promising method for MHARD of P. eryngii as it can enhance the drying process, and show potential for industrial application. © 2021 Society of Chemical Industry.

Effect of different drying techniques on drying kinetics, nutritional components, antioxidant capacity, physical properties and microstructure of edamame.

The present study aimed to investigate the effect of hot air drying (HD), microwave rolling-bed drying (MRD), hot air microwave rolling-bed drying (HMRD), pulse-spouted microwave vacuum drying (PSMVD) and freeze-drying (FD) on the drying characteristics, quality properties and microstructure of edamame. Six models were fitted the drying curves, and quality attributes were analyzed. Results indicated that Page model was the most suited model for edamame drying. Compared with HD, MRD and HMRD improved the quality of edamame and decreased the drying time by 45.59% and 36.03% respectively. The FD and PSMVD possessed higher rehydration ability, nutrient retention and antioxidant capacity compared with other methods. Moreover, PSMVD products showed a crunchy texture, the less color change and the shortest drying time (70 min). Microscopy images demonstrated a distinct porous structure in PSMVD, which facilitated the moisture transfer. Overall, PSMVD is a promising dehydration method for obtaining high value-added edamame products.

Quercetin protects islet ß-cells from oxidation-induced apoptosis via Sirt3 in T2DM.

OBJECTIVES: Sirt3 may regulate ROS production and might be involved in ß-cell apoptosis, which plays an important role in the progression of type 2 diabetes mellitus (T2DM). Quercetin is a potent anti-oxidative bioflavonoid, but its effects on T2DM remain to be explored. This study aimed to investigate the effects of quercetin on ß-cell apoptosis and explore its mechanisms. MATERIALS AND METHODS: The effects of quercetin were conducted on db/db mice and INS1 cells. Fasting blood glucose was determined by the colorimetric method, serum insulin was measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, Sirt3 in INS1 cells was knocked down by plasmid transfection. The antioxidant proteins (SOD2 and CAT), apoptosis proteins (cleaved Caspase-3, Bax, and BCL-2), and Sirt3 protein in pancreases and INS1 cells were determined by western blotting. RESULTS: When INS1 cells and diabetic mice were treated with quercetin, the levels of SOD2, CAT, and Sirt3 proteins were increased, the levels of cleaved Caspase-3 and the ratio of Bax to BCL-2 were decreased at different degrees, along with reduced blood glucose levels and elevated insulin levels in diabetic mice. When Sirt3 was knocked down in INS1 cells, increase of two antioxidants and decrease of cell apoptosis generated by quercetin could not occur. CONCLUSION: Quercetin protected islet ß-cells from oxidation-induced apoptosis via Sirt3 in T2DM, which would be beneficial to develop new strategies for preventing ß-cell failure in T2DM.

Value-added application of Platycodon grandiflorus (Jacq.) A.DC. roots (PGR) by ultrasound-assisted extraction (UAE) process to improve physicochemical quality, structural characteristics and functional properties.

Platycodon grandiflorus (Jacq.) A.DC. roots (PGR), a Chinese herb with medicinal and edible value, was powdered by freeze drying (FD) and spray drying (SD) after maceration extraction (ME) or ultrasound-assisted extraction (UAE) to develop a new functional food product. Four PGR powders were obtained namely ME-FD, ME-SD, UAE-FD, and UAE-SD and their powder quality, structural properties, and functionalities were evaluated. UAE-FD powder had the highest powder recovery (85.3 ± 5.79%) and also presented better hydration properties due to the larger particle size compared with other three PGR powders. Four PGR powders exhibited similar thermal decomposition process, molecular structure, amorphous characteristics, amino acids composition, and taste profiles. Furthermore, the UAE-FD PGR powders presented the highest Platycodin D (3.68 ± 0.04 mg/g), total phenolic (2.84 ± 0.11 mg GAE/g), and total flavonoids content (2.11 ± 0.14 mg RE/g), resulting in best antioxidant activity (58.67 ± 2.42 µmol Trolox/g). Therefore UAE-FD is an environment-friendly technique for the production of functional PGR powder with improved nutritional and redispersion properties.

Author Correction: Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys.

Following the publication of our paper (Zhang et al., 2020), it has come to our attention that we erroneously listed two funding sources unrelated to this study in the "ACKNOWLEDGEMENTS" section. Hereby, we wish to update the "ACKNOWLEDGEMENTS" section as a correction.

Research progress of mechanism of action of Saccharomyces boulardii and its application in ulcerative colitis / 国际生物医学工程杂志

Saccharomyces boulardii is a subspecies of Saccharomyces cerevisiae and is a fungal probiotic. It can regulate the intestinal flora and enhance the barrier function of the intestinal tract. Compared with bacterial probiotics, Saccharomyces boulardii is more resistant to acid and oxidation, does not transmit genetic material with bacteria, and can be used in combination with antibiotics. Saccharomyces boulardii can function through a variety of mechanisms, and many proteases secreted by it have antitoxin effects; its own bacteria contain more polyamines, which can nourish the intestinal mucosal cells and regulate the body's metabolic balance. Besides, it can regulate multiple signal pathways to enhance intestinal immunity. Saccharomyces boulardii has been used in the treatment of ulcerative colitis (UC). The results of animal experiments and clinical studies have shown that the application of Saccharomyces boulardii can improve intestinal inflammation and enhance the therapeutic effect of mesalazine. Saccharomyces boulardii can be used as an auxiliary drug for the treatment of UC.

Neutrophil-Lymphocyte Ratio in Predicting Infective Endocarditis: A Case-Control Retrospective Study.

BACKGROUND: Infective endocarditis (IE) is a complex infectious disease with high morbidity and mortality. The inflammation mechanism of IE is a complex network including interactions of inflammatory cytokines and other components of host response. As an important inflammation marker, the prediction ability of neutrophil-to-lymphocyte ratio (NLR) in IE deserves further investigation. METHODS: NLR values were measured and compared between IE patients and healthy controls, good and bad clinical outcome groups. The receiver operating characteristic curves (ROCs) of NLR and cut-off values were measured in IE patients, pathogen-subgroups, and different clinical outcome groups. RESULTS: There were 678 IE patients and 2520 healthy controls enrolled in our study. The number of good and bad clinical outcome patients was 537 and 141, respectively. The value of NLR was significantly higher in IE patients than healthy controls (6.29 ± 9.36 vs. 1.87 ± 0.34, p < 0.001), and the area under the ROC (AUC) was 0.817 (95% CI (0.794, 0.839), p < 0.001). The critical value of NLR for diagnosis of IE was 2.68, with a sensitivity of 69%, and a specificity of 88%. The value of NLR was significantly higher in bad clinical outcome patients than in good clinical outcome patients (5.8 ± 6.02 vs. 3.62 ± 2.61, p < 0.001). The critical value of NLR to predict the outcome of IE was 5.557, with a sensitivity of 39.0% and a specificity of 85.3%. CONCLUSIONS: NLR is a predictive marker for IE patients, especially in Gram-negative bacteria and Gram-positive bacteria-infected IE patients. NLR also can predict the outcome of IE. Early detecting NLR upon admission may assist in early diagnosis and risk stratification of patients with IE.

Rapid development of SARS-CoV-2 receptor binding domain-conjugated nanoparticle vaccine candidate

The ongoing of coronavirus disease 2019 (COVID-19) pandemic caused by novel SARS-CoV-2 coronavirus, resulting in economic losses and seriously threating the human health in worldwide, highlighting the urgent need of a stabilized, easily produced and effective preventive vaccine. The SARS-COV-2 spike protein receptor binding region (RBD) plays an important role in the process of viral binding receptor angiotensin-converting enzyme 2 (ACE2) and membrane fusion, making it an ideal target for vaccine development. In this study, we designed three different RBD-conjugated nanoparticles vaccine candidates, RBD-Ferritin (24-mer), RBD-mi3 (60-mer) and RBD-I53-50 (120-mer), with the application of covalent bond linking by SpyTag-SpyCatcher system. It was demonstrated that the neutralizing capability of sera from mice immunized with three RBD-conjugated nanoparticles adjuvanted with AddaVax or Sigma Systerm Adjuvant (SAS) after each immunization was ~8-to 120-fold greater than monomeric RBD group in SARS-CoV-2 pseudovirus and authentic virus neutralization assay. Most importantly, sera from RBD-conjugated NPs groups more efficiently blocked the binding of RBD to ACE2 or neutralizing antibody in vitro, a further proof of promising immunization effect. Besides, high physical stability and flexibility in assembly consolidated the benefit for rapid scale-up production of vaccine. These results supported that our designed SARS-CoV-2 RBD-conjugated nanoparticle was competitive vaccine candidate and the carrier nanoparticles could be adopted as universal platform for future vaccine development.