Successful Induction Research Articles

Dry Medical Thoracoscopy with Artificial Pneumothorax Induction Using Veress Needle.

In the absence of, or minimal-volume pleural effusion, conventional medical thoracoscopy (MT) is often precluded by the risk of lung injury. Dry medical thoracoscopy (dry MT) aims to ameliorate these dangers by inducing an artificial pneumothorax via needle insufflation or blunt dissection. Veress needle is a device used by surgeons to induce pneumoperitoneum before laparoscopic surgeries, but is not commonly reported in dry MT. We present data from a series of 31 patients in which dry MT with artificial pneumothorax induction using Veress needle were performed under thoracic ultrasonography (TUS) guidance. Procedures were deemed technically successful if all the following criteria were met: (i) successful pneumothorax induction, allowing smooth insertion of semi-rigid thoracoscope during the procedure; (ii) no immediate significant procedural-related complications; and (iii) no delayed complications such as persistent air leak, defined as leakage lasting more than 5 days necessitating prolonged chest tube placement. Complete pneumothorax induction was successful in 25 cases (80.6% technical success rate); nevertheless, biopsies were successfully performed in all cases. The most common histopathological diagnosis was malignancy (n=9, 29.0%), followed by inflammatory pleuritis (n=8, 25.8%) and tuberculosis (n=8, 25.8%). No complications were reported secondary to the procedure. These findings suggest that TUS-guided dry MT with a Veress needle is technically feasible and safe in the hands of experienced MT performers who are competent in TUS.

Laser-Induced Graphene on Novel Crosslinked Poly(dimethylsiloxane)/Triton X-100 Composites for Improving Mechanical, Electrical and Hydrophobic Properties

Laser-induced graphene (LIG) has become a highly promising material for flexible functional devices due to its robust mechanical stability, excellent electrical properties, and ease of fabrication. Most research has been focused on LIG production on rigid or flexible substrates, with an obvious gap in laser induction of graphene on elastic, stretchable substrates, which limits the scope of application of LIG in flexible electronics. We demonstrate laser induction of graphene on a novel, cross-linked poly(dimethylsiloxane) (PDMS)/Triton X-100 composite substrates. The effect of varying Triton content (1–30 wt.%) on the structural, thermal, surface, nanomechanical, and electrical properties of LIG was systematically studied. Physicochemical characterization confirmed the successful induction of LIG on the surface of PDMS/Triton composites. A higher content of Triton in the PDMS matrix improves the quality of LIG, increases stiffness and hydrophobicity, and somewhat decreases sheet resistance. Similar thermal properties and super-hydrophobicity were observed for LIG/PDMS/Triton materials as compared to their counterparts without LIG. Direct laser irradiation of graphene on the surface of PDMS/Triton composites results in the formation of extremely promising materials, which have great potential for use in flexible electronic devices.

Adenoviral delivery of the CIITA transgene induces T-cell-mediated killing in glioblastoma organoids.

The immunosuppressive nature of the tumor microenvironment poses a significant challenge to effective immunotherapies against glioblastoma (GB). Boosting the immune response is critical for successful therapy. Here, we adopted a cancer gene therapy approach to induce T-cell-mediated killing of the tumor through increased activation of the immune system. Patient-based three-dimensional (3D) GB models were infected with a replication-deficient adenovirus (AdV) armed with the class II major histocompatibility complex (MHC-II) transactivator (CIITA) gene (Ad-CIITA). Successful induction of surface MHC-II was achieved in infected GB cell lines and primary human GB organoids. Infection with an AdV carrying a mutant form of CIITA with a single amino acid substitution resulted in cytoplasmic accumulation of CIITA without subsequent MHC-II expression. Co-culture of infected tumor cells with either peripheral blood mononuclear cells (PBMCs) or isolated T-cells led to dramatic breakdown of GB organoids. Intriguingly, both wild-type and mutant Ad-CIITA, but not unarmed AdV, triggered immune-mediated tumor cell death in the co-culture system, suggesting an at least partially MHC-II-independent process. We further show that the observed cancer cell killing requires the presence of either CD8+ or CD4+ T-cells and direct contact between GB and immune cells. We did not, however, detect evidence of activation of canonical T-cell-mediated cell death pathways. Although the precise mechanism remains to be determined, these findings highlight the potential of AdV-mediated CIITA delivery to enhance T-cell-mediated immunity against GB.

A model of lymphocryptovirus-associated post-transplant lymphoproliferative disorder in immunosuppressed Mauritian cynomolgus macaques.

Immunocompromised individuals are at risk for developing lymphocryptovirus-associated lymphoproliferative diseases, such as Epstein Barr virus (EBV)-associated B cell lymphomas and post-transplant lymphoproliferative disorder (PTLD). We previously reported development of cynomolgus lymphocryptovirus (CyLCV)-associated PTLD in Mauritian cynomolgus macaques (MCMs) undergoing hematopoietic stem cell transplantation (HSCT), which mirrored EBV-PTLD in transplant patients. Here, we sought to develop a MCM model of lymphocryptovirus-associated lymphoproliferative disease in immunosuppressed MCMs without HSCT. Five simian immunodeficiency virus (SIV)-infected, CD8α+ cell-depleted MCMs received an infusion of autologous B-lymphoblastoid cells transformed with CyLCV, followed by varying degrees of immunosuppression. Four of five infused macaques developed masses coincident with increasing CyLCV plasma viremia, and necropsies confirmed the presence of multicentric lymphomas, which most commonly manifested in lymph nodes, gastrointestinal tract, adrenal glands, and pancreas. Affected tissues harbored neoplastic lymphocytes double-positive for CD20 and CyLCV EBNA2 antigen, large frequencies of proliferating B cells, and high levels of cell-associated CyLCV DNA. In addition, longitudinal 18F-fluorodeoxyglucose positron-emission tomography (18F-FDG PET) of one MCM successfully detected lymphoproliferative disease in the adrenal glands prior to clinical signs of disease. These data demonstrate successful induction of lymphocryptovirus-associated PTLD-like disease in 4 of 5 MCMs, and thus support the use of MCMs as a preclinical NHP model of EBV-associated lymphoproliferative disease that could be employed to test novel diagnostic and therapeutic modalities.

A single-cell transcriptomic map of the murine and human multiple myeloma immune microenvironment across disease stages

BackgroundThe long-term effectiveness of immunotherapies against Multiple Myeloma (MM) remains elusive, demonstrated by the inevitable relapse in patients. This underscores the urgent need for an in-depth analysis of the MM tumor-immune microenvironment (TME). Hereto, a representative immunocompetent MM mouse model can offer a valuable approach to study the dynamic changes within the MM-TME and to uncover potential resistance mechanisms hampering effective and durable therapeutic strategies in MM.MethodsWe generated a comprehensive single-cell RNA-sequencing atlas of the MM-TME in bone marrow and spleen encompassing different stages of disease, using the immunocompetent 5T33MM mouse model. Through comparative analysis, we correlated our murine dataset with the pathogenesis in MM patients by reanalyzing publicly available datasets of human bone marrow samples across various disease stages. Using flow cytometry, we validated the dynamic changes upon disease progression in the 5T33MM model. Furthermore, interesting target populations, as well as the immune-boosting anti-CD40 agonist (αCD40) therapy were tested ex vivo on murine and human primary samples and in vivo using the 5T33MM model.ResultsIn this study, we identified the heterogenous and dynamic changes within the TME of murine and human MM. We found that the MM-TME was characterized by an increase in T cells, accompanied with an exhausted phenotype. Although neutrophils appeared to be rather innocuous at early disease stages, they acquired a pro-tumorigenic phenotype during MM progression. Moreover, conventional dendritic cells (cDCs) showed a less activated phenotype in MM, underscoring the potential of immune-boosting therapies such as αCD40 therapy. Importantly, we provided the first pre-clinical evaluation of αCD40 therapy and demonstrated successful induction of cDC- and T-cell activation, accompanied by a significant short-term anti-tumor response.ConclusionsThis resource provides a comprehensive and detailed immune atlas of the evolution in human and murine MM disease progression. Our findings can contribute to immune-based patient stratification and facilitate the development of novel and durable (immune) therapeutic strategies in MM.

Electroacupuncture alleviated post-stroke cognitive impairment via the mTOR/NLRP3-mediated autophagy-inflammatory pathway

BackgroundPost-stroke cognitive impairment (PSCI) severely reduces quality of life of patients with stroke. This study aimed to assess the effects of electroacupuncture (EA) on PSCI and the role of the mTOR/NLRP3-mediated autophagy-inflammatory pathway in this process.MethodsThe rat focal cerebral ischemia model was established using middle cerebral artery occlusion (MCAO). Following successful induction of the model, EA was applied to the bilateral Fengchi, Fengfu, and Dazhui acupoints, and brain tissue samples were collected on day 15. Cognitive function was assessed using the Morris water maze test. Cerebral infarct volume was quantified by Triphenyltetrazolium chloride (TTC) staining. Hematoxylin–eosin and TUNEL staining were performed to evaluate pathological changes and apoptosis rates. Apoptosis-, inflammation-, and autophagy-related biomarkers were measured, and autophagosomes were visualized using transmission electron microscopy.ResultsMCAO rats exhibited slower weight gain, reduced mobility, increased infarct size, pathological damage, and apoptosis, confirming successful establishment of the MCAO rat model. Following EA treatment, MCAO rats displayed faster weight gain, improved mobility, and shorter escape latency. EA also reduced the area of cerebral infarction and alleviated pathological damage and apoptosis in MCAO rats. Furthermore, EA downregulated IL-1β, IL-18, NLRP3, and LC3 II/LC3 I expression and upregulated p62, mTOR, and Beclin-1 expression in MCAO rats. EA treatment also decreased the number of autophagosomes in these rats.ConclusionsEA effectively mitigates post-stroke cognitive impairment by reducing apoptosis, inflammation, and autophagy through the regulation of the mTOR/NLRP3-mediated autophagy-inflammatory pathway, offering valuable therapeutic insights for stroke rehabilitation.

Induction and Characteristics of Callus Cultures of the Medicinal Plant Tussilago farfara L.

Tussilago farfara L. is a traditional medicinal plant valued for its potentially health-promoting metabolites. Its herbal raw material has been recognized and used since ancient times and continues to be widely used in traditional medicine. Introducing this plant species to in vitro cultivation is a challenging task, but once the protocol is developed, such cultures can provide an abundant and inexhaustible source of plant material. In this study, we report the successful induction and growth of vigorous T. farfara callus in vitro. Callus induction was achieved on MS solid media with the combination of indole-3-acetic acid (3 mg/L) and benzyl aminopurine (2 mg/L) in darkness, whereas it appeared inefficient under light conditions and in suspension culture. We present a detailed description of callus growth kinetics, morphological analysis, photosynthetic activity, and biochemical parameters (including protein content and photosynthetic pigments) supported by histological studies. Furthermore, we observed the potential for organogenesis and somatic embryogenesis. This method for the in vitro propagation of T. farfara, along with callus culture maintenance, offers a wide range of applications in pharmacy for the production of valuable metabolites. Moreover, it could benefit the environment by reducing the depletion of natural populations of this species and may serve as an alternative strategy for species conservation in light of global warming.

Non-coding RNA alterations in occlusal disharmony-induced anxiety-like behaviour.

Occlusal disharmony (OD) may induce anxiety-like behaviours; however, the underlying mechanism remains unclear. Herein, we explored the expression profiles of non-coding RNAs (ncRNAs), along with their biological function and regulatory network, in anxiety-like behaviour induced by OD. Occlusal disharmony was produced by anterior crossbite of C57BL/6 mice. Behavioural tests, corticosterone (CORT) and serotonin (5-HT) levels were used to measure anxiety. In addition, RNA sequencing was used to screen all differentially expressed (DE) ncRNAs. Moreover, the RNA-binding proteins interacting with ncRNAs were predicted by the ENCORI database and confirmed using western blots. The significant differences in behavioural tests and CORT suggested the successful induction of anxiety-like behaviour by OD. In OD mice, ncRNAs were significantly dysregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that the DE ncRNAs were enriched in anxiety-related pathways. CircRNA10039 was upregulated, and PTBP1 was predicted to interact with circRNA10039. In addition, KEGG pathway analysis showed that PTBP1 may be associated with messenger RNA biogenesis and spliceosomes. OD induced by anterior crossbite can lead to the anxiety-like behaviours. During this process, ncRNA also changes. CircRNA10039 and PTBP1 may play a role in OD-induced anxiety-like behaviours.

BMSCs-EVs Alleviate Pelvic Floor Dysfunction in Mice by Reducing Inflammation and Promoting Tissue Regeneration.

Pelvic floor dysfunctions (PFDs), which encompass pelvic organ prolapse (POP), stress urinary incontinence (SUI), and anal incontinence (AI), are common degenerative diseases in women. Bone marrow mesenchymal stem cells (BMSCs) hold promise for the treatment of PFDs. Extracellular vesicles (EVs) derived from BMSCs, have displayed an extensive role in intercellular communication and tissue repair. However, efficacy of the treatment using EVs originated from BMSCs on mouse models of PFD remains unknown. This study investigated the therapeutic potential of BMSC-derived EVs in a female PFD mouse model induced by vaginal distension (VD). Flow cytometry analysis confirmed the positive expression of BMSC-related markers, and successful induction of multilineage differentiation further validated their characteristics. As expected, the EVs extracted from BMSCs exhibited typical cup-shaped and circular-shaped structures. In the PFD model, BMSC-derived EVs significantly reduced the levels of inflammatory cytokines (p<0.05), improved tissue repair, and mitigated neutrophil infiltration. Furthermore, EVs promoted cell proliferation, decreased expression of relaxin receptors, increased expression of elastin, and elevated collagen content in the anterior vaginal wall tissue (p<0.05), suggesting beneficial effects on tissue regeneration and connective tissue restoration in PFD. BMSC-derived EVs effectively reduce tissue inflammation, promote tissue regeneration and connective tissue reconstruction, and improve pelvic support deficiency, thereby alleviating PFD induced by vaginal distension (VD) in vivo.

CAR Treg synergy with anti-CD154 mediates infectious tolerance to dictate heart transplant outcomes.

Successful allograft specific tolerance induction would eliminate the need for daily immunosuppression and improve post-transplant quality of life. Adoptive cell therapy with regulatory T cells expressing donor-specific Chimeric Antigen Receptors (CAR-Tregs) is a promising strategy, but as monotherapy, cannot prolong the survival with allografts with multiple MHC mismatches. Using an HLA-A2-transgenic haplo-mismatched heart transplantation model in immunocompetent C57Bl/6 recipients, we show that HLA-A2-specific (A2) CAR Tregs was able to synergize with low dose of anti-CD154 to enhance graft survival. Using haplo-mismatched grafts expressing the 2W-OVA transgene and tetramer-based tracking of 2W- and OVA-specific T cells, we showed that in mice with accepted grafts, A2.CAR Tregs inhibited endogenous non-A2 donor- specific T cell, B cell and antibody responses, and promoted a significant increase in endogenous FoxP3 + Tregs with indirect donor-specificity. By contrast, in mice where A2.CAR Tregs failed to prolong graft survival, FoxP3 neg A2.CAR T cells preferentially accumulated in rejecting allografts and endogenous donor-specific responses were not controlled. This study therefore provides the first evidence for synergy between A2.CAR Tregs and CD154 blockade to promote infectious tolerance in immunocompetent recipients of haplo-mismatched heart grafts and defines features of A2.CAR Tregs when they fail to reshape host immunity towards allograft tolerance.

Maintaining Skill Development of Newly Qualified Physical Education Teachers

High percentages of newly qualified teachers drop out during their first 5 years of teaching in the classroom. Often, formal support systems are put in place to overcome ‘practice shock’. Yet this practice shock is generally associated with traditional academic subjects such as mathematics, humanities and science. The often-marginalised subject of physical education can be largely neglected when newly qualified teachers are considered. One strategy to reduce practice shock is that of an established mentoring program. The large volume of literature on mentoring across an array of education subjects suggests that mentoring is a valued skill. However, while mentoring is acknowledged as an essential prerequisite for successful teacher induction, its effectiveness in physical education may vary depending on the mentor’s quality of support and the mentee’s initial professional beliefs. This article draws on a structured analysis of research-based articles on mentoring for newly graduated physical education teachers and explores the discipline between mentee and mentor to make more valid inferences about the roles, responsibilities and outcomes of mentoring. The need for clarity around a physical education teacher’s role as a mentor and associated responsibilities relative to the provision of emotional support and guidance are examined along with suggestions for explicit transmission-oriented mentoring approaches to support beginning teachers’ professional development.

Induction of factor VIII tolerance by hemophilia gene transfer to eradicate factor VIII inhibitors

Patients with hemophilia A can develop anti-factor antibodies to factor VIII. The incidence is ∼30% and such patients suffer worse morbidity and mortality. The only proven method to eradicate these inhibitors is via immune tolerance induction therapy which consists of infusing factor VIII concentrates at a regular intervals. This approach is effective ∼65% of the time leaving at least a third of patients who develop inhibitors with this lifelong problem. Although emicizumab has greatly improved the quality of life of inhibitor patients, eradicating the inhibitor remains an important treatment goal. Animal models have shown the potential for gene therapy to induce tolerance. A recent abstract describing a study in humans demonstrated the potential for successful tolerance induction. This article will describe the rationale for utilizing gene therapy to induce tolerance and provide this author's viewpoint on the importance and possible historic significance of attempting to eradicate inhibitors with this approach.

Cumulative rabbit anti-human thymocyte globulin dose to recipient weight during the peri-operative period is an independent risk factor for early postoperative urinary tract infection after kidney transplantation

Anti-human thymocyte globulin-Fresenius (ATG-F) is frequently utilized to achieve successful induction for kidney transplantation recipients. This study aimed to examine the association between the ATG-F dose-to-recipient-weight ratio (ADR) and the risk of developing urinary tract infections (UTIs) following kidney transplantation. Data of kidney transplant recipients who underwent ATG-F-induction peri-operatively in a medical center were retrospectively collected, and the incidence of UTIs during the first postoperative year was also recorded. The risk of UTI associated with ADR was analyzed, and receiver operating characteristic curves were drawn to determine the optimal ADR, followed by Cox regression models. In total, 131 recipients were included, with an UTI incidence of 19.08% and a mean interval of 3.08 months. The optimal ADR was 6.34, involving 41 and 90 patients in the low ADR and high ADR groups, respectively. The UTI-free rate in the low ADR group was significantly higher than that in the high ADR group (p = 0.007). Cox regression analysis indicated that a high ADR independently increased the risk of UTI following kidney transplantation (hazard ratio: 5.306, 95% confidence interval: 1.243–22.660, p = 0.024). There was no significant difference in rejection rate between the high ADR and low ADR groups. In conclusion, a high ADR increased the incidence of early postoperative UTI among kidney transplant recipients.

Prediction of the chance of successful immune tolerance induction in persons with severe hemophilia A and inhibitors: a clinical prediction model

BackgroundInhibitor eradication to restore factor VIII (FVIII) efficacy is the treatment goal for persons with severe hemophilia A (HA) and inhibitors. Immune tolerance induction (ITI) is demanding and successful in about 70% of people. Until now, it has remained difficult to quantify the probability of ITI success or failure, complicating the decision to initiate or not initiate ITI. Estimating the individual chance of ITI success allows clinicians, patients, and their families to support shared decision-making. ObjectiveWe aimed to identify clinical predictors of ITI success and to develop a clinical prediction model to estimate the chance of successful ITI in persons with severe HA. MethodsThis multicenter study included persons with severe HA who received ITI. Clinical data were collected. Successful ITI was defined by a negative inhibitor titer and an adequate response to FVIII concentrates. A multivariable logistic regression model was developed. Model performance and internal validation were performed. ResultsOf 206 participants with median age of 19.8 months (IQR 12.1-38.8) at ITI start, 148 (71.8%) achieved ITI success. Our clinical prediction model included four predictors of ITI success: cumulative number of FVIII exposure days at inhibitor development, peak inhibitor titer, ethnicity, and F8 mutation type. The C-statistic was 0.801 (95% CI, 0.70-0.87). ConclusionIn our study including 206 people with severe HA and inhibitors, we developed a clinical prediction model to estimate the chance of successful ITI. After future external validation, this clinical prediction model may be useful for informing clinicians and families.

A sexually and vegetatively reproducible diploid seedless watermelon inducer via ClHAP2 mutation.

Seedless watermelon production relies on triploid cultivation or the application of plant growth regulators. However, challenges such as chromosomal imbalances in triploid varieties and concerns about food safety with growth regulator application impede progress. To tackle these challenges, we developed a sexually and vegetatively reproducible inducer line of diploid seedless watermelon by disrupting the double fertilization process. This innovative approach has enabled the successful induction of diploid seedless watermelon across diverse varieties.

A comparative study between modified Bishop score and transvaginal sonography to predict successful induction of labor

ABSTRACT Background: Modified Bishop score (MBS) and cervical length determination by transvaginal sonography (TVS) are the two methods for predicting successful vaginal delivery based on pre-induction favourability of the cervix. Aims and Objectives: This study compared both methods for predicting successful vaginal delivery. The primary objective was to compare the predictive value of MBS and TVS in predicting successful induction of labor. The secondary objective was to obtain the cut-off score of MBS and TVS for successful induction of labor. Methods: A prospective study was done involving 100 pregnant women admitted for induction of labor. TVS was done to measure the cervical length before induction of labor. MBS was also calculated for all the patients. Labor was induced with prostaglandins. Labor induction was considered successful if there was an onset of uterine contractions and cervical dilatation within 24 h of induction. Results: For successful induction of labor, the cutoff of cervical length by TVS and MBS was 2.5 cm and 6, respectively. Cervical length assessment by TVS performed better than the MBS (sensitivity 61.8% vs. 28.9%, Specificity 95.8% vs. 100%). Conclusion: MBS and cervical length measurement by sonography both are good predictors of successful induction of labor. Cervical length measurement by TVS provides a better prediction of the likelihood of vaginal delivery.

Gonadotropins combined with and without 100mg Clomiphene Citrate drug on ovulation induction and role of epidural analgesia in pregnancy outcome of infertility women.

Successful ovulation induction can overcome the common condition of infertility associated with ovulatory dysfunction. Monotherapy of clomiphene citrate (CC) or combined with gonadotrophins are the best treatment modalities for ovulation induction with a successful outcome. We concentrated on evaluating the effects of 100 mg Clomiphene Citrate, both with and without gonadotrophins, on ovulation induction and the outcome of labor analgesia in women with infertility. This prospective cohort consists of 136 women with infertility who were medicated with 100 mg of clomiphene citrate alone and 100 mg of clomiphene citrate with gonadotropins. We recorded the endometrial thickness, details of the dominant follicle, and the incidence of a positive pregnancy rate. Women with positive pregnancy were managed with epidural labor with labor analgesia to relieve labor pain and evaluated the foetal outcome. In CC alone, the ovulation rate was 57%, while in CC with gonadotrophins, it was 81%. The mean dominant follicle size and endometrial thickness were high in CC with gonadotrophins (p &lt; 0.05). The overall incidence of positive pregnancies was 28.98%. Levobupivacaine with dexmedetomidine significantly reduced the mean VAS score from baseline, resulting in a higher foetal body weight. Taking 100 mg of Clomiphene citrate with gonadotropins works better than taking Clomiphene citrate by itself at starting ovulation, increasing the size of the dominant follicle, and improving the thickness of the endometrium. With levobupivacaine plus dexmedetomidine, the labor analgesia showed better stability in hemodynamic parameters and effective control on labor pain scores.

Mirikizumab for the treatment of chronic antibiotic-refractory pouchitis.

The current standard of care for the definitive surgical treatment of complicative ulcerative colitis is a continence-preserving proctocolectomy with the creation of an ileal pouch anal anastomosis. In addition to structural and functional disorders, pouchitis of the J-pouch is a common phenomenon, typically well responsive to antimicrobial therapy. However, sometimes chronic antibiotic-refractory pouchitis occurs, most often due to not completely understood multifactorial pathomechanisms. While high-quality evidence is available only for anti-integrin therapy, the role of advanced therapy, i.e., cytokine-antibodies or small molecules in the treatment of chronic antibiotic-refractory pouchitis (CARP), is emerging.This case demonstrates a successful induction treatment of CARP with the novel p19-selective IL-23-targeted antibody mirikizumab.

Formulation Attributes Impact Immune Profile of an Oral and Thermostable COVID-19 Subunit Vaccine.

While approved vaccines for COVID-19 provide protection against severe disease and death, they have limited efficacy in the prevention of infection and virus transmission. Mucosal immunity is preferred over systemic immunity to provide protection at the point of entry against pathogens such as SARS-CoV-2. VaxForm has developed an oral vaccine delivery platform that elicits mucosal and systemic immune responses by targeting immune cells in the gut through C-type lectin receptors. The technology consists of microencapsulating the vaccine with an enteric polymer, which also results in enhanced thermostability. This article describes the formulation development and in vivo testing of a novel protein-based oral COVID-19 vaccine using this technology. Results demonstrate successful induction of immune response in mice and showed that the particle size of the vaccines following administration can impact the ratio of mucosal to systemic response. Immunogenicity and thermostability of liquid suspension and dry powder versions of the vaccine were compared in mice. The liquid suspension vaccine showed excellent heat resistance by maintaining immunogenicity after 14 days of storage at 60 °C. While further investigation is needed to determine correlates of protection and duration of response for mucosal immunity, this study demonstrates the vaccine's potential as a COVID-19 booster to enhance mucosal protection in humans and improve global access by lowering the cost of production, removing cold-chain requirements, and allowing self-administration.

Application of small animal ultrasound imaging technology for identification of polycystic ovary syndrome in a mouse model

Background and AimsPolycystic ovary syndrome (PCOS) is a hormonal disorder common among women of reproductive age, characterized by irregular menstrual periods, elevated levels of androgens, and polycystic ovaries, leading to various symptoms and complications such as infertility, metabolic issues, and increased risk of diabetes and heart disease. This study aimed to compare traditional histological methods and ultrasound imaging for consistency in identifying PCOS in a mouse model. The shortest time to construct the PCOS model using letrozole was determined. MethodsFemale C57/BL mice were randomly divided into three groups: Group A received normal saline and a regular diet; Group B received 1 mg/kg/day of letrozole with a regular diet; and Group C received 1 mg/kg/day of letrozole with a high-fat diet. All mice were administered letrozole by intragastric gavage daily for five weeks. The traditional identification method included measuring body weight, examining vaginal smears, monitoring the estrous cycle, measuring serum androgen levels, and performing H&E staining of ovarian tissues. The PCOS model was evaluated using ultrasound imaging to identify and monitor follicles. The significance of the difference between the traditional identification method and the ultrasonic method was calculated using the nonparametric McNemar test, and consistency between the two methods was assessed with the kappa-coefficient test. On this basis, the ultrasound imaging technology was used to monitor the model-making process for 2, 3 and 4 weeks, and to monitor the parameters of the ovary and follicles to judge the shortest time that gavage letrozole caused the appearance of vesicular follicles in the mouse ovary. ResultsThe traditional identification method showed no PCOS phenotype in group A mice, while groups B and C showed multiple ovarian cystic follicles, indicating successful model induction. The ultrasound imaging results were consistent with the traditional method, showing no PCOS in group A and multiple cystic follicles in groups B and C. The McNemar test revealed no significant difference between the traditional and ultrasonic identification methods. The kappa-coefficient test assessed consistency, yielding a value of 0.903, indicating strong agreement between the methods. The ovarian area, diameter, and the number and diameter of cystic follicles were not significantly changed at two weeks in the letrozole group compared with the control group. At three weeks, there were significant increases in the number and in the diameter of vesicular follicles compared with control cells. At four weeks, the number and diameter, the maximum cross-sectional area and diameter of the ovary were significantly increased compared with the control group. ConclusionsThe ultrasound and traditional methods provide consistent results for identifying PCOS in a mouse model. Construction of the PCOS model by letrozole gavage takes at least three weeks.