Safety, tolerability, pharmacokinetic, pharmacodynamic and immunogenicity profiles of Exendin-4-IgG4-Fc in healthy subjects: A phase 1, single-centre, randomized, double-blind, dose escalation study.

AIM: Novel long-acting drugs for type 2 diabetes mellitus may optimize patient compliance and glycaemic control. Exendin-4-IgG4-Fc (E4F4) is a long-acting glucagon-like peptide-1 receptor agonist. This first-in-human study investigated the safety, tolerability, pharmacokinetic, pharmacodynamic and immunogenicity profiles of a single subcutaneous injection of E4F4 in healthy subjects. METHODS: This single-centre, randomized, double-blind, placebo-controlled phase 1 clinical trial included 96 subjects in 10 sequential cohorts that were provided successively higher doses of E4F4 (0.45, 0.9, 1.8, 3.15, 4.5, 6.3, 8.1, 10.35, 12.6 and 14.85 mg) or placebo (ChinaDrugTrials.org.cn: ChiCTR2100049732). The primary endpoint was safety and tolerability of E4F4. Secondary endpoints were pharmacokinetic, pharmacodynamic and immunogenicity profiles of E4F4. Safety data to day 15 after the final subject in a cohort had been dosed were reviewed before commencing the next dose level. RESULTS: E4F4 was safe and well tolerated among healthy Chinese participants in this study. There was no obvious dose-dependent relationship between frequency, severity or causality of treatment-emergent adverse events. Cmax and area under the curve of E4F4 were dose proportional over the 0.45-14.85 mg dose range. Median Tmax and t1/2 ranged from 146 to 210 h and 199 to 252 h, respectively, across E4F4 doses, with no dose-dependent trends. For the intravenous glucose tolerance test, area under the curve of glucose in plasma from time 0 to 180 min showed a dose-response relationship in the 1.8-10.35 mg dose range, with an increased response at the higher doses. CONCLUSION: E4F4 exhibited an acceptable safety profile and linear pharmacokinetics in healthy subjects. The recommended phase 2 dose is 4.5-10.35 mg once every 2 weeks.

Anti-inflammatory Activities and Mechanisms of New Compounds Isolated from the Fruits of Foeniculum vulgare Mill.

Forty-nine compounds, including six previously unknown together with forty-three known ones, were isolated from the fruits of Foeniculum vulgare Mill. Their structures were elucidated using high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), infrared spectroscopy (IR), ultraviolet-visible spectroscopy (UV), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD) methods. All isolates were evaluated their anti-inflammatory activity. The results indicated that compounds 1, 6, 35 and 45 inhibit lipopolysaccharide(LPS)-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 17.13 ± 0.74, 14.40 ± 0.54, 112.13 ± 2.08 and 77.02 ± 3.62 µg/mL, respectively. Moreover, the potential targets of the four active ingredients were explored through network pharmacology, revealing that SRC, TP53, AKT1, and PIK3CA may serve as key anti-inflammatory targets. To confirm the potential binding mode, molecular docking was employed, which demonstrated that all active targets except SRC exhibited favorable binding energy with compound 35. Additionally, the anti-inflammatory activities of compounds 1-6 were first observed in this experiment.

[Clinical study on the treatment of premature ejaculation with Nailifu Spray].

OBJECTIVE: To observe the effect of Nailifu Spray on the treatment of premature ejaculation. METHODS: A total of 90 patients were included in this study from January 1, 2022 to January 1, 2023. Nailifu spray was used to spray the surface of penile skin once a day, 2 sprays per session for 4 weeks.And the patients' premature ejaculation diagnostic tool (PEDT) scores, intravaginal ejaculation latency time (IELT), and international index of erectile function-5 (IIEF-5) scores were collected before and after treatment, respectively. RESUTS: The median (P25,P75) PEDT scores was 16.0(15.0,18.0) scores before treatment and 10.0(10.0,10.0) scores after treatment. The median (P25,P75) of IELT was 20.0 (10.0,30.0) s before treatment and 240.0 (180.0,300.0) s after treatment. The median (P25,P75) of IIEF-5 scores was 21.0 (21.0,22.0) scores before treatment and 21.0 (21.0,21.0) scores after treatment. Compared with baseline levels, IELT was significantly longer and PEDT scores were significantly lower, with statistically significant differences. No significant changes in IIEF-5 scores were seen. CONCLUSION: Nailifu spray treatment of premature ejaculation is accurate and effective, worthy of clinical promotion.

Application of machine learning models for predicting acute kidney injury following donation after cardiac death liver transplantation.

BACKGROUND: Acute kidney injury (AKI) is a common complication after liver transplantation (LT) and is an indicator of poor prognosis. The establishment of a more accurate preoperative prediction model of AKI could help to improve the prognosis of LT. Machine learning algorithms provide a potentially effective approach. METHODS: A total of 493 patients with donation after cardiac death LT (DCDLT) were enrolled. AKI was defined according to the clinical practice guidelines of kidney disease: improving global outcomes (KDIGO). The clinical data of patients with AKI (AKI group) and without AKI (non-AKI group) were compared. With logistic regression analysis as a conventional model, four predictive machine learning models were developed using the following algorithms: random forest, support vector machine, classical decision tree, and conditional inference tree. The predictive power of these models was then evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: The incidence of AKI was 35.7% (176/493) during the follow-up period. Compared with the non-AKI group, the AKI group showed a remarkably lower survival rate (P < 0.001). The random forest model demonstrated the highest prediction accuracy of 0.79 with AUC of 0.850 [95% confidence interval (CI): 0.794-0.905], which was significantly higher than the AUCs of the other machine learning algorithms and logistic regression models (P < 0.001). CONCLUSIONS: The random forest model based on machine learning algorithms for predicting AKI occurring after DCDLT demonstrated stronger predictive power than other models in our study. This suggests that machine learning methods may provide feasible tools for forecasting AKI after DCDLT.

Transcriptomic analysis reveals recovery strategies in strawberry roots after using a soil amendment in continuous cropping soil.

BACKGROUND: In strawberry cultivation, continuous cropping (CC) obstacles seriously threaten production. A patented soil amendment (SA) can effectively relieve the CC obstacles to strawberry cultivation, but knowledge of the recovery mechanisms underlying this phenomenon is limited. RESULTS: In this study, transcriptomic profiling of strawberry roots in soil with and without the SA was conducted using RNA-Seq technology to reveal gene expression changes in response to SA treatment. In total, 188 differentially expressed genes (DEGs), including 144 upregulated and 44 downregulated DEGs, were identified. SA treatment resulted in genotype-dependent responses, and the response pattern, including an overall increase in the expression of nutrient transport genes and a decrease in the expression of defense response genes, may be a possible mechanism underlying recovery strategies in strawberry roots after the application of the SA to CC soil. We also found that 9 Hsp genes involved in plant defense pathways were all downregulated in the SA-treated roots. CONCLUSIONS: This research indicated that strawberry plants reallocated defense resources to development when SA treatment alleviated the stress caused by a CC soil environment. The present study provides an opportunity to reveal the fundamental mechanisms of the tradeoff between growth and defense in strawberry.

Study on cyanidin metabolism in petals of pink-flowered strawberry based on transcriptome sequencing and metabolite analysis.

BACKGROUND: Pink-flowered strawberry is a promising new ornamental flower derived from intergeneric hybridization (Fragaria × Potentilla) with bright color, a prolonged flowering period and edible fruits. Its flower color ranges from light pink to red. Pigment compounds accumulated in its fruits were the same as in cultivated strawberry fruits, but different from that in its flowers. However, the transcriptional events underlying the anthocyanin biosynthetic pathway have not been fully characterized in petal coloration. To gain insights into the regulatory networks related to anthocyanin biosynthesis and identify the key genes, we performed an integrated analysis of the transcriptome and metabolome in petals of pink-flowered strawberry. RESULTS: The main pigments of red and dark pink petals were anthocyanins, among which cyanidins were the main compound. There were no anthocyanins detected in the white-flowered hybrids. A total of 50,285 non-redundant unigenes were obtained from the transcriptome databases involved in red petals of pink-flowered strawberry cultivar Sijihong at three development stages. Amongst the unigenes found to show significant differential expression, 57 were associated with anthocyanin or other flavonoid biosynthesis, in which they were regulated by 241 differentially expressed members of transcription factor families, such as 40 MYBs, 47 bHLHs, and 41 NACs. Based on a comprehensive analysis relating pigment compounds to gene expression profiles, the mechanism of flower coloration was examined in pink-flowered strawberry. A new hypothesis was proposed to explain the lack of color phenotype of the white-flowered strawberry hybrids based on the transcriptome analysis. The expression patterns of FpDFR and FpANS genes corresponded to the accumulation patterns of cyanidin contents in pink-flowered strawberry hybrids with different shades of pink. Moreover, FpANS, FpBZ1 and FpUGT75C1 genes were the major factors that led to the absence of anthocyanins in the white petals of pink-flowered strawberry hybrids. Meanwhile, the competitive effect of FpFLS and FpDFR genes might further inhibit anthocyanin synthesis. CONCLUSIONS: The data presented herein are important for understanding the molecular mechanisms underlying the petal pigmentation and will be powerful for integrating novel potential target genes to breed valuable pink-flowered strawberry cultivars.

Transient cardiac injury during H7N9 infection.

BACKGROUND: Recent reports have characterized virological and clinical features of the novel reassortant avian-origin influenza A (H7N9) virus. However, cardiovascular involvement during H7N9 infection is still unclear. In this study, we evaluate cardiac injury among H7N9-infected patients. MATERIALS AND METHODS: A total of 40 patients who were laboratory-confirmed with H7N9 infection were retrospectively included and grouped by Acute Physiology and Chronic Health Evaluation II (APACHE II) score into four subgroups I(0-10), II(11-20), III(21-30) and IV(31-71). Cardiovascular complications and markers of cardiac injury including creatinine kinase (CK), CK iso-enzyme (CK-MB), cardiac troponin I (cTNI) and brain natriuretic peptide (BNP) were assessed. Electrocardiogram (ECG) and echocardiography (ECHO) were also performed. RESULTS: Half of patients manifested with cardiovascular complications, with hypotension (47.5%) and heart failure (40.0%) the most prevalent. CK, CK-MB and cTNI showed marked increase with H7N9 virus infection but significantly decreased after H7N9 viral tests turned negative. More than half of patients presented with an abnormal ECG, but most of them are benign changes. ECHO examination showed different degree of impairment of cardiac function. Pulmonary artery systolic pressure was increased in all groups. Cardiac damage was more evident in patients with higher APACHE II score. CONCLUSIONS: H7N9 virus exerts a transient impairment on the cardiovascular system. Patients with a higher APACHE II score are more susceptible to cardiac damage.

Immunogenicity and safety of an enterovirus 71 vaccine in healthy Chinese children and infants: a randomised, double-blind, placebo-controlled phase 2 clinical trial.

BACKGROUND: Enterovirus 71 (EV71) outbreaks are a socioeconomic burden, especially in the western Pacific region. Results of phase 1 clinical trials suggest an EV71 vaccine has a clinically acceptable safety profile and immunogenicity. We aimed to assess the best possible dose and formulation, immunogenicity, and safety profile of this EV71 vaccine in healthy Chinese children. METHODS: This randomised, double-blind, placebo-controlled, phase 2 trial was undertaken at one site in Donghai County, Jiangsu Province, China. Eligible participants were healthy boys or girls aged 6­36 months. Participants were randomly assigned (1:1:1:1:1) to receive either 160 U, 320 U, or 640 U alum-adjuvant EV71 vaccine, 640 U adjuvant-free EV71 vaccine, or a placebo (containing alum adjuvant only), according to a blocked randomisation list generated by SAS 9.1. Participants and investigators were masked to the assignment. The primary endpoint was anti-EV71 neutralising antibody geometric mean titres (GMTs) at day 56, analysed according to protocol. The study is registered with ClinicalTrials.gov, number NCT01399853. FINDINGS: We randomly assigned 1200 participants, 240 (120 aged 6­11 months [infants] and 120 aged 12­36 months [children]) of whom were assigned to each dose. 1106 participants completed the study and were included in the according-to-protocol analysis. The main reasons for dropout were withdrawal of consent and refusal to donate a blood sample. Infants who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (742·2 [95% CI 577·3­954·3]), followed by those who received the 320 U formulation (497·9 [383·1­647·0]). For children, those who received the 320 U formulation had the highest GMTs on day 56 (1383·2 [1037·3­1844·5]). Participants who received the vaccine had significantly higher GMTs than did who received placebo (p<0·0001). For the subgroup of participants who were seronegative at baseline, both infants and children who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (522·8 [403·9­676·6] in infants and 708·4 [524·1­957·6] in children), followed by those who received the 320 U adjuvant vaccine (358·2 [280·5­457·5] in infants and 498·0 [383·4­646·9] in children). 549 (45·8%) of 1200 participants (95 CI 42·9­48·6%) reported at least one injection-site or systemic adverse reaction, but the incidence of adverse reactions did not differ significantly between groups (p=0·36). The 640 U alum-adjuvant vaccine group had a significantly higher incidence of induration than did the 640 U adjuvant-free group (p=0·001). INTERPRETATION: Taking immunogenicity, safety, and production capacity into account, the 320 U alum-adjuvant formulation of the EV71 vaccine is probably the best possible formulation for phase 3 trials. FUNDING: The National Science and Technology Major Project (2011ZX10004-902) of the Chinese Ministry of Science and Technology, China's 12­5 National Major Infectious Disease Program (2012ZX10002-001), and Beijing Vigoo Biological.

Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in China: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine. METHODS: We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6-35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01508247. FINDINGS: 10,245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1-96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2-90·8) against EV71-associated disease (p<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33). INTERPRETATION: EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity. FUNDING: China's 12-5 National Major Infectious Disease Program, Beijing Vigoo Biological.

[Smokeless tobacco extract affects biological properties of the pre-osteoblast cell line MC3T3-E1 ].

OBJECTIVE: To investigate the effects of smokeless tobacco extract (STE) on biological properties of osteoblast, and to identify possible pathological mechanisms of osseointegration. METHODS: MC3T3-E1 Sub-clone 14 cells were cultured in the presence of STE at 0 (control group),0. 01,0. 1,1,5,10 g/L. The cell proliferation was measured by MTT assay 1 d, 3 d, 5 d, and 7 d after exposure. The F-actin cytoskeleton of MC3T3 was stained with Rhodamine and DAPI, and then examined under a confocal laser scanning microscope 24 h after exposure to STE. The mRNA expressions of interleukin-6 (IL-6) and core-binding factor αl(Cbfαl) were quantified by real- time PCR (RT-qPCR) 48 h after exposure to STE. RESULTS: The MTT assay showed that 0. 01-10 g/L STE inhibited MC3T3 proliferation (P<0. 05). Prolonged time enabled 5-10 g/L STE to inhibit MC3T3 proliferation (P<0. 05). Network structure in F-actin cytoskeleton was demonstrated in the controls. In the cells exposed to STE, F-actin cytoskeleton started to change with disruptive structures. As the concentration of STE increased, the changes became more significant. STE increased the mRNA expression of IL-6 at the concentration of 5 g/L and 10 g/L (P<0.05), decreased the mRNA expression of Cbfα1 at the concentration of 0. 1-10 g/L (PO<0. 05). CONCLUSION: Tobacco may inhibit osteoblast proliferation, destroy F-actin cytoskeleton structure, increase the mRNA expression of IL-6 and decrease the mRNA expression of Cbfα1, and inhibit cell differentiation and adhesion accordingly. Smoking is a disadvantage to osseointegration.

Separation and purification of bovine nasal cartilage-derived chondroitin sulfate and evaluation of its binding to bovine serum albumin.

This study employs an optimized and environmentally friendly method to extract and purify chondroitin sulfate (CS) from bovine nasal cartilage using enzymatic hydrolysis, ethanol precipitation, and DEAE Sepharose Fast Flow column chromatography. The extracted CS, representing 44.67 % ± 0.0016 of the cartilage, has a molecular weight of 7.62 kDa. Characterization through UV, FT-IR, NMR spectroscopy, and 2-aminoacridone derivatization HPLC revealed a high content of sulfated disaccharides, particularly ΔDi4S (73.59 %) and ΔDi6S (20.61 %). Interaction studies with bovine serum albumin (BSA) using fluorescence spectroscopy and molecular docking confirmed a high-affinity, static quenching interaction with a single binding site, primarily mediated by van der Waals forces and hydrogen bonding. The interaction did not significantly alter the polarity or hydrophobicity of BSA aromatic amino acids. These findings provide a strong foundation for exploring the application of CS in tissue engineering and drug delivery systems, leveraging its unique interaction with BSA for targeted delivery and enhanced efficacy.

Advances in the potential of nebulized inhalation for the treatment of pulmonary arterial hypertension.

Pulmonary hypertension is a pathophysiologic manifestation of a heterogeneous group of diseases, with the main pathophysiologic mechanisms being persistent pulmonary vasoconstriction and irreversible vascular remodeling. The impact significantly affects the prognosis of patients with pulmonary hypertension. If it is not treated and intervened in time, it may lead to right ventricular failure and further endanger the patient's life. Within the past decade or so, nebulized inhalation therapy is considered to have advantages in the treatment of pulmonary hypertension as a safe, limited, and rapid therapy, for example, inhaled vasodilators (prostate analogs, nitroglycerin, carbon monoxide analogs sildenafil, and nitroprusside), inhaled anti-inflammatory and antiproliferative agents (simvastatin, and selatinib), and inhaled peroxides (levocetirizine) have been recognized as emerging therapeutic approaches in the treatment of pulmonary hypertension as emerging therapeutic approaches. Therefore, this article provides a brief review of recent advances in the potential of nebulized inhaled vasodilators, anti-inflammatory and antiproliferative agents, and anti-peroxides for the treatment of pulmonary hypertension, with the aim of providing different therapeutic options for the treatment of pulmonary hypertension, enhancing the quality of survival, alleviating symptoms, and improving the prognosis of patients with this condition.

A chondroitin sulfate purified from shark cartilage and bovine serum albumin interaction activity.

Chondroitin sulfate (CS) was extracted and purified from shark cartilage, and its interaction with bovine serum albumin (BSA) were studied. The content of chondroitin sulfate in shark cartilage was 29.97 % using the 1,9-dimethyl-methylene blue method. The molecular weight of CS was determined to be 62.464 kDa by high-performance gel permeation chromatography. UV and FT-IR spectroscopy identified the characteristics of CS and its functional group information. NMR spectroscopy and disaccharide derivatization revealed that CS was predominantly composed of disulfated disaccharides, specifically ΔDi4,6S. Fluorescence quenching experiments indicated that the interaction between CS and BSA exhibited static quenching, with a binding site number of 1. The binding process was primarily mediated by van der Waals forces and hydrogen bonds. Furthermore, synchronous and 3D fluorescence spectroscopy demonstrated that CS had minimal impact on the polarity and hydrophobicity of the microenvironment surrounding Tyr and Trp residues. UV-vis absorption and circular dichroism (CD) spectroscopy demonstrated the altered structure of BSA. The molecular docking analysis revealed that CS formed hydrogen bonds and salt bridges with BSA, predominantly binding to the IIA substructure domain of BSA. Investigating the interaction between CS and BSA holds the potential for enhancing its applications in drug delivery and tissue engineering endeavors.

[Effect of dual sustained-release nanofiber scaffolds embedded with BMP-2 protein nanospheres on the proliferation and differentiation of MC3T3-E1 cells].

PURPOSE: Electrospinning technology was used to construct PCL composite nanofiber scaffold material of BMP-2 sustained-release nanospheres, and the effect of this nanospheres on proliferation and differentiation of MC3T3-E1 cells was evaluated. METHODS: Solvent removal method and electrostatic self-assembly technology were used to prepare BMP-2 loaded chitosan nanospheres, the morphology, particle size and composition, BMP-2 protein encapsulation efficiency, and in vitro sustained release were tested. Electrospinning technology was ued to prepare PCL composite scaffold material containing BMP-2 nanospheres, and its morphology, hydrophilicity,and sustained release of BMP-2 protein were examined. In vitro cytology experiment was conducted to observe the growth of cells in the material, and the formation of ALP, related genes, and mineralized nodules during the process of osteogenic differentiation of the material were detected. SPSS 21.0 software package was used for statistical analysis. RESULTS: The nanospheres structure with stable structure was successfully prepared, with a high drug loading rate and sustained release of BMP-2. The PCL/BNPs scaffold material group had good hydrophilic properties and was conducive to cell proliferation and differentiation. The results of in vitro cell experiments showed that the cells spread well on the scaffold and the number of adhesions increased. ALP and related osteogenic genes COL1, OPN, RUNX2 increased, and the size and number of calcium nodules increased significantly. CONCLUSIONS: The polycaprolactone composite fiber scaffold material of BMP-2 sustained-release nanospheres can provide a new choice for the development of bone tissue engineering.

How to manage isolated tension non-surgical pneumoperitonium during bronchoscopy? A case report.

BACKGROUND: Tension pneumoperitonium is a rare complication during bronchoscopy that can cause acute respiratory and hemodynamic failure, with fatal consequences. Isolated pneumoperitonium during bronchoscopy usually results from ruptures of the abdominal viscera that need surgical repair. Non-surgical pneumoperitoneum (NSP) refers to some pneumoperitoneum that could be relieved without surgery and only by conservative therapy. However, the clinical experience of managing tension pneumoperitonium during bronchoscopy is limited and controversial. CASE SUMMARY: A 51-year-old female was admitted to our hospital for cough with bloody sputum of seven days. On the 8th day of her admission, a bronchoscopy was arranged for bronchial-alveolar lavage to detect possible pathogens in the lower respiratory tract, as oxygen was delivered via a 12 F nasopharyngeal cannula, approximately 5-6 cm from the tip of the catheter, with a flow rate of 5-10 L/min. After four minutes of bronchoscopy, the patient suddenly vomited 20 mL of water, followed by severe abdominal pain, while physical examination revealed obvious abdominal distension, as well as hardness and tenderness of the whole abdomen, which was considered pneumoperitonium, and the bronchoscopy was terminated immediately. A computer tomography scan indicated isolated tension pneumoperitonium, and abdominal decompression was performed with a drainage tube, after which her symptoms were relieved. A multidisciplinary expert consultation discussed her situation and a laparotomy was suggested, but finally refused by her family. She had no signs of peritonitis and was finally discharged 5 d after bronchoscopy with a good recovery. CONCLUSION: The possibility of tension pneumoperitonium during bronchoscopy should be guarded against, and given its serious clinical consequences, cardiopulmonary instability should be treated immediately. Varied strategies could be adopted according to whether it is complicated with pneumothorax or pneumomediastinum, and the presence of peritonitis. When considering NSP, conservative therapy maybe a reasonable option with good recovery. An algorithm for the management of pneumoperitonium during bronchoscopy is proposed, based on the features of the case series reviewed and our case reported.

Immunogenicity and safety of NVSI-06-07 as a heterologous booster after priming with BBIBP-CorV: a phase 2 trial.

The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccination. We conducted a randomised, double-blinded, controlled, phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine (BBIBP-CorV) followed by a recombinant protein-based vaccine (NVSI-06-07), using homologous boost with BBIBP-CorV as control. Three groups of healthy adults (600 individuals per group) who had completed two-dose BBIBP-CorV vaccinations 1-3 months, 4-6 months and ≥6 months earlier, respectively, were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost. Immunogenicity assays showed that in NVSI-06-07 groups, neutralizing antibody geometric mean titers (GMTs) against the prototype SARS-CoV-2 increased by 21.01-63.85 folds on day 28 after vaccination, whereas only 4.20-16.78 folds of increases were observed in control groups. For Omicron variant, the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14, however, a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster. Similar results were obtained for other SARS-CoV-2 variants of concerns (VOCs), including Alpha, Beta and Delta. Both heterologous and homologous boosters have a good safety profile. Local and systemic adverse reactions were absent, mild or moderate in most participants, and the overall safety was quite similar between two booster schemes. Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs, including Omicron.

Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients in a randomized phase 2 trial.

NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluate the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in BBIBP-CorV recipients in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who have administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, are randomized 1:1 to receive either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The incidence of adverse reactions is low, and the overall safety profile is quite similar between two booster regimens. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster are significantly higher than those by BBIBP-CorV booster against not only SARS-CoV-2 prototype strain but also multiple variants of concerns (VOCs). Especially, the neutralizing antibody GMT against Omicron variant induced by heterologous NVSI-06-08 booster reaches 367.67, which is substantially greater than that boosted by BBIBP-CorV (GMT: 45.03). In summary, NVSI-06-08 is safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which is immunogenically superior to the homologous boost with another dose of BBIBP-CorV.

The complete mitochondrial genome sequence of Fragaria orientalis (Rosaceae).

Fragaria orientalis Lozinsk. is valuable germplasm material for cross breeding in Fragaria. In this study, we assembled the complete mitochondrial genome of F. orientalis using a combination of Illumina data and Nanopore data. The mitochondrial genome was 275,143 bp in length, including 29 protein-coding genes, 20 tRNA genes, and three rRNA genes, with a total GC content 45.23%. Seven protein-coding genes contained introns, and three were trans-spliced. Phylogenetic analysis indicated that F. orientalis is making a sister clade to the Amygdaloideae species. The complete mitochondrial genome of F. orientalis reported in this study will improve our understanding of Fragaria evolution.

Exploring the sulfate patterns of chondroitin sulfate/dermatan sulfate and keratan sulfate in human pancreatic cancer.

This study was designed to explore the sulfation patterns of chondroitin sulfate (CS)/dermatan sulfate (DS), and keratan sulfate (KS) and the expression of carbohydrate sulfotransferases (CHSTs) in 26 pancreatic tumor and normal tissues. CS/DS and KS profiles were simultaneously determined. Pancreatic tumor tissues exhibited increased ΔDi-0S, ΔDi-4S, and ΔDi-6S levels, with absolute ΔDi-4S content being highest, followed by ΔDi-6S. However, as for the contents of KS-6S and KS-6S,6'S, there were no significant regular change. The expression levels of CHST1 and CHST4 were 37 and 15 times higher than those in normal tissues. PCA and OPLS-DA revealed that ΔDi-4S and ΔDi-6S levels could be reliably used to differentiate between healthy and cancerous tissues. The up-regulation of CHST3, CHST12, CHST13, and CHST15 was directly correlated with C-4 and C-6 sulfation. These data provide a foundation for future studies of the role of ΔDi-4S and ΔDi-6S in the progression of pancreatic cancer.

[A method of measuring the displacement of the distal radioulnar joint on the three-dimensional CT imaging].

OBJECTIVES: To establish a clinical method for measuring the displacement of the distal radioulnar joint (DRUJ) precisely irrespective of ulnar variance, and to derive normal population translation references with palmar and dorsal stress. METHODS: Thirty-seven normal distal forearms were scanned with computed tomography using an apparatus designed by Pirela-Cruz. Each extremity was scanned in two positions: maximal ulnar palmar and dorsal stress. The digital imaging and communications in medicine (DICOM) CT images were then imported into Mimics 10.0 for three-dimensional reconstruction. On the DRUJs 3D images, choose the most prominent point of the palmar and dorsal margins of the sigmoid notch and the excavate ulna fovea as the reference points A, B and C. A perpendicular line was then drawn from the point C to a line connecting points A and B with the intersection D. Calculate the ratio of AD/AB and DB/AB. Two observers measured all the DRUJs independently and one repeated the measurements one month later to determine the interobserver and intraobserver reliability. RESULTS: The mean ratio values of palmar (AD/AB) and dorsal (DB/AB) translation were 0.39 ± 0.07 and 0.37 ± 0.07, and the normal references (x(-) ± 2 s) were from 0.25 to 0.50 and from 0.23 to 0.50, respectively. No significant differences were observed in terms of positions, genders and dominant hands. The intraclass correlation coefficient (ICC) values for interobserver and intraobserver reliability (DB/AB, AD/AB) were 0.84, 0.80, 0.93 and 0.92, respectively. CONCLUSIONS: This new method could accurately measure the displacement of DRUJs with acceptable reliability, even with ulna positive or negative variance. Instability of DRUJ may be indicated when AD/AB is less than 0.25 or BD/AB is less than 0.23.