Immunogenicity and protective effects of recombinant bivalent COVID-19 vaccine in mice and rhesus macaques.

Coronavirus disease (COVID-19) is still spreading rapidly worldwide, and a safe, effective, and cheap vaccine is still required to combat the COVID-19 pandemic. Here, we report a recombinant bivalent COVID-19 vaccine containing the RBD proteins of the prototype strain and beta variant. Immunization studies in mice demonstrated that this bivalent vaccine had far greater immunogenicity than the ZF2001, a marketed monovalent recombinant protein COVID-19 vaccine, and exhibited good immunization effects against the original COVID-19 strain and various variants. Rhesus macaque challenge experiments showed that this bivalent vaccine drastically decreased the lung viral load and reduced lung lesions in SARS-CoV-2 (the causative virus of COVID-19)-infected rhesus macaques. In summary, this bivalent vaccine showed immunogenicity and protective efficacy that was far superior to the monovalent recombinant protein vaccine against the prototype strain and provided an important basis for developing broad-spectrum COVID-19 vaccines.

Fluorescent Sensor Based on Magnetic Separation and Strand Displacement Amplification for the Sensitive Detection of Ochratoxin A.

Ochratoxin A (OTA) is a common mycotoxin, and it is a significant threat to human health throughout the food chain. In this study, a sensitive and specific fluorescent sensor based on magnetic separation technology combined with chain displacement amplification was developed for fast and easy detection of OTA in food. The designed strand displacement amplification can improve the sensitivity for the detection, and the magnetic nanomaterials can provide a large surface area, thus enhancing the capture efficiency of the target from the sample. Based on those designs, the experimental results showed that the proposed method displayed excellent performance. The linearity range was 0.5-128.0 ng/mL. The detection limit was 0.125 ng/mL; the relative standard deviations were 3.92-7.71%. Additionally, the developed method was satisfactorily applied to determine OTA in wheat, corn, and red wine samples at three spiked levels (1.0, 8.0, and 64.0 ng/mL). The recoveries ranged from 85.45 to 107.8% for wheat flour, 101.34 to 108.35% for corn flour, and 91.15 to 93.80% for red wine, respectively. Compared with high-performance liquid chromatography, the proposed method showed a lower limit of detection and equal recovery. Hence, the designed method is a potential and good detecting tool for OTA residue analysis in complex matrix samples.

Chaihu-Shugan-San inhibits neuroinflammation in the treatment of post-stroke depression through the JAK/STAT3-GSK3ß/PTEN/Akt pathway.

Post-stroke depression (PSD) is one of the most common neuropsychiatric consequence of stroke, affecting cognitive function, recovery of somatic function, and patient survival. The aim of this study was to evaluate whether Chaihu-Shugan-San, a traditional Chinese medicine formula used clinically to treat depression, could improve symptoms in a rat model for PSD, to investigate the potential mechanisms, and to validate the findings in an in vitro oxygen and glucose deprivation (OGD) model. Male rats were subjected to middle cerebral artery occlusion (MCAO) and to chronic unpredictable mild stress (CUMS). The rats were then allocated to experimental groups (n = 15) that were treated with Chaihu-Shugan-San, a JAK-STAT3 inhibitor, a GSK3ß overexpressing virus, or an empty virus (control). The subjects allocated to each group, as well as those that received no treatment and rats that did not undergo MCAO/CUMS, were then subjected to forced swimming, tail suspension, and sugar water preference tests, and their neurological deficit score was determined. Inflammatory factor levels and the expression of proteins related to the JAK/STAT3-GSK3ß/PTEN/Akt pathway were measured, and the synaptic ultrastructure was observed using transmission electron microscopy. Flow cytometry showed microglia polarization towards the M1 phenotype in an in vitro PSD model, which was reversed after treatment with a GSK3ß overexpression virus, Chaihu-Shugan-San, or a JAK-STAT3 inhibitor. The results showed that Chaihu-Shugan-San has a therapeutic effect on an in vivo model for PSD and can regulate microglia polarization through the activation of the JAK/STAT3-GSK3ß/PTEN/Akt pathway, suggesting that it exerts its effect via the inhibition of neuroinflammation.

Correction to "Fluorescent Sensor Based on Magnetic Separation and Strand Displacement Amplification for the Sensitive Detection of Ochratoxin A".

[This corrects the article DOI: 10.1021/acsomega.3c01408.].

Identification of potential key genes and functional role of CENPF in osteosarcoma using bioinformatics and experimental analysis.

Osteosarcoma, which arises from bone tissue, is considered to be one of the most common types of cancer in children and teenagers. As the etiology of osteosarcoma has not been fully elucidated, the overall prognosis for patients is generally poor. In recent years, the development of bioinformatical technology has allowed researchers to identify numerous molecular biological characteristics associated with the prognosis of osteosarcoma using online databases. In the present study, Gene Expression Omnibus (GEO) database was used and three microarray datasets were obtained. The GEO2R web tool was utilized and differentially expressed genes (DEGs) in osteosarcoma tissue were identified. Venn analysis was performed to determine the intersection of the DEG profiles. DEGs were analyzed by Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Protein-protein interactions (PPIs) between these DEGs were analyzed using the Search Tool for the Retrieval of Interacting Genes database, and the PPI network was then visualized using Cytoscape software. The top ten genes were identified based on measurement of degree, density of maximum neighborhood component, maximal clique centrality and mononuclear cell counts in the PPI network, and five overlapping genes [origin recognition complex subunit 6 (ORC6), IGF-binding protein 5 (IGFBP5), minichromosome maintenance 10 replication initiation factor (MCM10), MET proto-oncogene, receptor tyrosine kinase (MET) and centromere protein F (CENPF)] were identified. Additionally, three module networks were analyzed by Molecular Complex Detection (MCODE), and six key genes [ORC6, MCM10, DEP domain containing 1 (DEPDC1), CENPF, TIMELESS interacting protein (TIPIN) and shugoshin 1 (SGOL1)] were screened. Combined with the results from Cytoscape and MCODE, eight hub genes (ORC6, MCM10, DEPDC1, CENPF, TIPIN, SGOL1, MET and IGFBP5) were obtained. Furthermore, Kaplan-Meier plotter survival analysis was used to evaluate the prognostic value of these eight hub genes in patients with osteosarcoma. Oncomine and GEPIA databases were applied to further confirm the expression levels of hub genes in tissue. Finally, the functional roles of the core gene CENPF were investigated using Cell Counting Kit-8, wound healing and Transwell assays, which indicated that CENPF knockdown inhibited the proliferation, migration and invasion of osteosarcoma cells. These results provided potential prognostic markers, as well as a basis for further investigation of the mechanism underlying osteosarcoma.

The association between soy-based food and soy isoflavone intake and the risk of gastric cancer: a systematic review and meta-analysis.

Soy contains many bioactive phytochemicals, such as isoflavones, which have the effect of preventing many cancers. Some studies have shown the beneficial effect of soy-based food and isoflavone intake on gastric cancer (GC), while others claimed no effect. Therefore, whether the beneficial effect of soy-based food is related to its fermentation or whether its protective effect comes from isoflavones still remains inconclusive. Our aim was to investigate the relationship between total soybean, fermented soybean, non-fermented soybean and isoflavone intake, and the risk of GC. Ten cohort studies and 21 case-control studies involving 916 354 participants were included. The association between soy-based food and isoflavone intake and the risk of GC was calculated with the pooled relative risks (RRs) for the highest versus lowest intake categories. The results showed that isoflavone intake might be a protective factor to GC, but the result was not statistically significant (RR = 0.92; 95% CI: 0.79-1.07). However, total soybean intake could significantly decrease the risk of GC by 36% (RR = 0.64; 95% CI: 0.51-0.80), which might be credited to non-fermented soybean products (RR = 0.79; 95% CI: 0.71-0.87). In contrast, high intake of fermented soybean products could increase the risk of GC (RR = 1.19; 95% CI: 1.02-1.38). High intake of total soybean and non-fermented soybean products could reduce the risk of GC, and high intake of fermented soybean products could increase the risk, which indicated that the beneficial effect of soy-based food might be related to its non-fermentation. However, high intake of isoflavones may not be associated with the incidence of GC. © 2021 Society of Chemical Industry.

Highly Sensitive Fluorescence-Linked Immunosorbent Assay for the Determination of Human IgG in Serum Using Quantum Dot Nanobeads and Magnetic Fe3O4 Nanospheres.

The aim of this study is to establish a new method with high sensitivity, accuracy, and stability for the determination of human IgG and then expand it to analyze severe acute respiratory syndrome corona virus 2 (SARS-CoV-2)-specific IgM and IgG, which is of great significance for the screening and diagnosis of COVID-19. In this study, the magnetic Fe3O4 nanospheres coupled with mouse antihuman IgG (Ab1IgG) were used as an immune capture probe (Fe3O4@Ab1IgG) to capture and separate the target, and rabbit antihuman IgG (Ab2IgG) coupled with highly luminescent quantum dot nanobeads (QBs) as a fluorescence detection probe (QBs@Ab2IgG) was used to realize high sensitivity detection. After the formation of a sandwich immunocomplex, the fluorescence intensity of the precipitate after magnetic separation was measured at the excitation wavelength of 370 nm. Under optimal conditions, a wide linear range varying from 0.005 to 40 ng·mL-1 was obtained for the detection of human IgG with a lower limit of detection at 4 pg·mL-1 (S/N = 3). The recoveries of intra- and interassays were 90.0-101.9 and 96.0-106.6%, respectively, and the relative standard deviations were 6.3-10.2 and 2.6-10.5%, respectively. Furthermore, the proposed method was successfully demonstrated to detect human IgG in serum samples, and the detection results were not statistically different (P > 0.05) from commercial enzyme-linked immunosorbent assay kits. This method is sensitive, fast, and accurate, which could be expanded to detect the specific IgM and IgG antibodies against SARS-CoV-2.

K237-modified thermosensitive liposome enhanced the delivery efficiency and cytotoxicity of paclitaxel in vitro.

This study aimed to develop novel temperature-sensitive liposomes loading paclitaxel (PTX-TSL) and evaluate them in vitro to improve the delivery efficiency and targeting of PTX. K237 peptide was conjugated to the terminal NHS of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[hydroxyl succinimidyl (polyethylene glycol)-(DSPE-PEG-NHS), and K237-modified PTX-TSL (K237-PTX-TSL) was prepared using a film dispersion method. K237-TSL encapsulation with calcein was synthesized and used to determine the cellular uptake of TSL. The morphology of K237-PTX-TSL was observed using a transmission electron microscope. The particle size and potential were measured using a laser particle size analyzer. The phase transition temperature was detected using the differential scanning calorimetry. The Cell Counting Kit-8 assay and flow cytometry were used to evaluate the effects of K237-PTX-TSL on the proliferation and cell cycle of cell lines SKOV-3 and human umbilical vein endothelial cell (HUVEC). The encapsulation efficiency of K237-PTX-TSL was 94.23% ± 0.76%. The particle diameter was 88.3 ± 4.7 nm. K237-PTX-TSL showed a fast release profile at 42 °C, while it was stable at 37 °C. PTX-TSL combined with hyperthermia significantly inhibited the cell proliferation of SKOV-3 cells and HUVECs due to increased cell arrest in the G2/M phase. The half-minimal inhibitory concentration value of K237-PTX-TSL on SKOV-3 cells and HUVECs was 13.61 ± 1.81 and 5.54 ± 0.95 nmol/L, respectively, which were significantly lower than those with PTX-TSL (p < 0.01). K237 modification could increase the targeting efficiency of TSL to cancer cells and vascular endothelial cells, thus resulting in higher cytotoxicities compared with PTX-TSL, which might be a potential formulation for targeting cancer therapy.

Galectin-7 promotes the invasiveness of human oral squamous cell carcinoma cells via activation of ERK and JNK signaling.

Galectin-7 is a member of the ß-galactoside-binding protein family, and is highly expressed in oral squamous cell carcinoma (OSCC). The aim of the present study was to investigate the effects of manipulating galectin-7 expression on the biological phenotype of human OSCC cells and the associated molecular mechanisms. Knockdown of endogenous galectin-7 via small interfering RNA (siRNA) was performed and cell proliferation, apoptosis, migration, and invasion were subsequently assessed. The data indicated that galectin-7 silencing had no impact on the proliferation or apoptosis of OSCC cells. However, compared with non-transfected cells, percentage wound closure was significantly lower in galectin-7-silenced cells following 24 h incubation, indicating decreased cell migration. Furthermore, Matrigel invasion assays demonstrated that galectin-7 knockdown significantly reduced the number of invaded cells, compared with the number in non-transfected cells. Western blot analysis indicated that galectin-7 overexpression resulted in a significant increase in the expression of the proteins matrix metalloproteinase (MMP)-2 and MMP-9. The invasive abilities of cells overexpressing galectin-7 significantly decreased following co-transfection with MMP-2- or MMP-9-specific siRNA. Increasing galectin-7 expression significantly enhanced the phosphorylation of extracellular signal-related kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) 1/2. Pharmacological inhibition of ERK or JNK activity significantly suppressed the invasiveness of galectin-7-overexpressing cells and abrogated the upregulation of MMP-2 and MMP-9. Taken together, the results of the current study provide novel evidence for the pro-invasive activity of galectin-7 in OSCC cells, which is associated with activation of ERK and JNK signaling and the induction of MMP-2 and MMP-9.

A PLGA-PEG-PLGA Thermosensitive Gel Enabling Sustained Delivery of Ropivacaine Hydrochloride for Postoperative Pain Relief.

Postoperative pain is a complex physiological response to disease and tissue injury. Moderate-to-severe pain typically occurs within 48 h after surgery. Amino amide local anesthetics are widely applied to manage postoperative pain, and they have high efficacy, a low risk for addiction and limited side effects. However, these anesthetics also have short half-lives, often necessitating continuous injection to obtain satisfactory pain relief. In the current work, we used a poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA (PLGA-PEG-PLGA) temperature-sensitive gel to deliver a local anesthetic, ropivacaine hydrochloride (RP), to prolong its analgesic effect. We investigated the influence of polymer and drug concentration on gelation temperature and the in vitro drug release rate from the temperature-sensitive gel. RP-loaded PLGA-PEG-PLGA solution is a liquid at room temperature and forms a gel at temperatures slightly lower than body temperature. With regard to the gel's drug release rate, 37.5, 51.3 and 72.6% of RP was released at 12, 24 and 48 h, respectively. This in vitro drug release profile conformed to the Higuchi equation. To assess pain control efficacy when using the gel, we evaluated the mechanical paw withdrawal reflex threshold, thermal pain threshold and incision cumulative pain scores in a rat incisional model. The results showed that the anti-pain effect of a single injection of RP-loaded gel at the incision site lasted for 48 h, which is significantly longer than the effect produced by injection of RP solution alone. The use of RP-loaded thermosensitive gels could provide a promising method for managing postoperative pain.

[Analysis of effect of military outpatients' psychological feelings on doctor-patient relationship in orthodontic treatment].

PURPOSE: To explore the effect of military outpatients' psychological feelings on doctor-patient relationship in orthodontic treatment. METHODS: A total of 95 clinic patients who were undergoing orthodontic treatment were asked to complete the questionnaire of dental visit satisfaction scale (DVSS) and orthodontist-patient relationship scale (OPRS). The results of different groups according to identity, gender, age and treatment time were compared. The data was analyzed with SPSS 20.0 software package for correlation analysis and stepwise regression. RESULTS: Except 6-18 months group, psychological feelings of patients had significant impact on doctor-patient relationship (P<0.01). The correlation coefficient was 0.610 between patients' satisfaction of outpatient treatment and doctor-patient relationship (P<0.001). Among 9 psychological feelings of orthodontic treatment, five kinds had significant effect on doctor-patient relationship, including three kinds of positive correlation and two kinds of negative correlation. CONCLUSIONS: The patients' psychological feelings are closely related to doctor-patient relationship. Doctors should try to improve medical quality, strengthen service level and pay much attention to the patients' psychological and social needs.

Intraoral approach for surgical removal of a nail in penetrating maxillofacial injury.

An unusual case of penetrating maxillofacial injury caused by a nail gun is presented. In this case, the foreign body was shot into the left infratemporal fossa and maxillary sinus through the left cheek. We used an intraoral approach that allowed precise localization of the point of the infratemporal surface of the maxilla through which the nail penetrated the maxillary sinus. The nail was successfully removed and the patient was discharged with complete recovery. The details of the surgical approach as well as localization techniques are described. Different approaches to remove the nail as well as the advantages and disadvantages of each approach are discussed.

Gorham-Stout syndrome affecting the left mandible: A case report.

Gorham-Stout syndrome is an extremely rare condition in which spontaneous, progressive resorption of bone occurs. Owing to its low incidence and variable clinical presentation, the diagnosis is often missed or delayed, and at present, there are no specific guidelines for its treatment. We present the case of a 20-year-old male diagnosed with Gorham-Stout syndrome with involvement of the left mandible, and discuss its diagnostic and therapeutic features.

[Application of cone-beam computed tomography in the diagnosis and treatment of external root resorption of adjacent teeth caused by impacted teeth].

OBJECTIVE: This study aims to investigate the diagnosis and treatment of external root resorption of adjacent teeth caused by impacted teeth via cone-beam computed tomography (CBCT). METHODS: A total of 19 teeth from 15 patients with uncertain external root resorption caused by an adjacent impacted tooth were examined from January 2011 to December 2011. All teeth with uncertain external root resorption were scanned by CBCT. Three dimensions reconstruction were the conducted to determine the location and extent of resorption. RESULTS: In all cases, CBCT identified the accurate location and extent of external root resorption caused by adjacent impacted teeth. Furthermore, the technique provided impacted teeth location in three dimensions, including the relation between the impacted teeth and surrounding vital structures. CONCLUSION: CBCT can provide direct and accurate images of the location and extent of external root resorption, as well as the location of the adjacent impacted teeth in three dimensions. Therefore, the proposed technique provides reliable information for clinical diagnosis and treatment.

Prefabrication of axial vascularized tissue engineering coral bone by an arteriovenous loop: a better model.

The most important problem for the survival of thick 3-dimensional tissues is the lack of vascularization in the context of bone tissue engineering. In this study, a modified arteriovenous loop (AVL) was developed to prefabricate an axial vascularized tissue engineering coral bone in rabbit, with comparison of the arteriovenous bundle (AVB) model. An arteriovenous fistula between rabbit femoral artery and vein was anastomosed to form an AVL. It was placed in a circular side groove of the coral block. The complex was wrapped with an expanded-polytetrafluoroethylene membrane and implanted beneath inguinal skin. After 2, 4, 6 and 8 weeks, the degree of vascularization was evaluated by India ink perfusion, histological examination, vascular casts, and scanning electron microscopy images of vascular endangium. Newly formed fibrous tissues and vasculature extended over the surfaces and invaded the interspaces of entire coral block. The new blood vessels robustly sprouted from the AVL. Those invaginated cavities in the vascular endangium from scanning electron microscopy indicated vessel's sprouted pores. Above indexes in AVL model are all superior to that in AVB model, indicating that the modified AVL model could more effectively develop vascularization in larger tissue engineering bone.

[Incomplete palate cleft patient with mirror-image dextrocardia and situs inversus viscerums: report of one case].

Cleft palate is one of the most common congenital defects, occurring alone or in combination with other malformations. Cleft palate with mirror-image dextrocardia and situs inversus viscerums is rare. This paper presented a case of incomplete cleft palate patient with mirror-image dextrocardia and situs inversus viscerums. The patient had a family history of cleft palate and had no family history of congenital heart disease. He was found to have congenital heart disease during preoperative assessment. Without intracardiac malformation, the patient was routinely operated under general anesthesia. The patient had an uneventful postoperative course and was discharged 8 days after operation. Further investigation is needed whether multiple defects in this patient are independent diseases or a part of possible recessive syndrome.