APC/CCDC20 targets SCFFBL17 to activate replication stress responses in Arabidopsis.

DNA replication stress threatens genome stability and affects plant growth and development. How plants resolve replication stress is poorly understood. The protein kinase WEE1-mediated cell cycle arrest is required for replication stress responses. The E3 ubiquitin ligases anaphase-promoting complex/cyclosome (APC/C) and Skp1/Cullin 1/F-box (SCF) are essential regulators of the cell cycle. Here, we show that APC/CCDC20 mediates the degradation of SCFFBL17 during replication stress responses in Arabidopsis thaliana. Biochemically, WEE1 interacts with and phosphorylates the APC/C co-activator APC10, which enhances the interaction between F-BOX-LIKE17 (FBL17) and CELL DIVISION CYCLE 20 (CDC20), an activator of APC/C. Both APC10 and CDC20 are required for the polyubiquitination and degradation of FBL17. Genetically, silencing CDC20 or APC10 confers plant hypersensitivity to replication stress, which is suppressed by loss of FBL17. Collectively, our study suggests that WEE1 activates APC/C to inhibit FBL17, providing insight into replication stress responses in plants.

The Effects of Simultaneous Aerobic Exercise and Video Game Training on Executive Functions and Brain Connectivity in Older Adults.

OBJECTIVE: The study was designed to examine the effects of simultaneous combination of aerobic exercise and video game training on executive functions (EFs) and brain functional connectivity in older adults. DESIGN: A four-armed, quasi-experimental study. SETTING AND PARTICIPANTS: Community-dwelling adults aged 55 years and older. METHODS: A total of 97 older adults were divided into one of four groups: aerobic exercise (AE), video game (VG), combined intervention (CI), and passive control (PC). Participants in intervention groups received 32 sessions of training over a 4-month period at a frequency of twice a week. EFs was evaluated using a composite score derived from a battery of neuropsychological tests. The Montreal Cognitive Assessment (MoCA) was employed to evaluate overall cognitive function, while the 6-Minute Walking Test (6MWT) was utilized to gauge physical function. Additionally, the functional connectivity (FC) of the frontal-parietal networks (FPN) was examined as a neural indicator of cognitive processing and connectivity changes. RESULTS: In terms of EFs, both VG and CI groups demonstrated improvement following the intervention. This improvement was particularly pronounced in the CI group, with a large effect size (Hedge's g = 0.83), while the VG group showed a medium effect size (Hedge's g = 0.56). A significant increase in MoCA scores was also observed in both the VG and CI groups, whereas a significant increase in 6MWT scores was observed in the AE and CI groups. Although there were no group-level changes observed in FC of the FPN, we found that changes in FC was behaviorally relevant as increased FC was associated with greater improvement in EFs. CONCLUSION: The study offers preliminary evidence that both video game training and combined intervention could enhance EFs in older adults. Simultaneous combined intervention may hold greater potential for facilitating EFs gains. The initial evidence for correlated changes in brain connectivity and EFs provides new insights into understanding the neural basis underlying the training gains.

Whole-exome sequencing as the first-tier test for patients in neonatal intensive care unit: a Chinese single-center study.

BACKGROUND: Genetic disorders significantly affect patients in neonatal intensive care units, where establishing a diagnosis can be challenging through routine tests and supplementary examinations. Whole-exome sequencing offers a molecular-based approach for diagnosing genetic disorders. This study aimed to assess the importance of whole-exome sequencing for neonates in intensive care through a retrospective observational study within a Chinese cohort. METHODS: We gathered data from neonatal patients at Tianjin Children's Hospital between January 2018 and April 2021. These patients presented with acute illnesses and were suspected of having genetic disorders, which were investigated using whole-exome sequencing. Our retrospective analysis covered clinical data, genetic findings, and the correlation between phenotypes and genetic variations. RESULTS: The study included 121 neonates. Disorders affected multiple organs or systems, predominantly the metabolic, neurological, and endocrine systems. The detection rate for whole-exome sequencing was 52.9% (64 out of 121 patients), identifying 84 pathogenic or likely pathogenic genetic variants in 64 neonates. These included 13 copy number variations and 71 single-nucleotide variants. The most frequent inheritance pattern was autosomal recessive (57.8%, 37 out of 64), followed by autosomal dominant (29.7%, 19 out of 64). In total, 40 diseases were identified through whole-exome sequencing. CONCLUSION: This study underscores the value and clinical utility of whole-exome sequencing as a primary diagnostic tool for neonates in intensive care units with suspected genetic disorders. Whole-exome sequencing not only aids in diagnosis but also offers significant benefits to patients and their families by providing clarity in uncertain diagnostic situations.

The multi-BRCT domain protein DDRM2 promotes the recruitment of RAD51 to DNA damage sites to facilitate homologous recombination.

DNA double-strand breaks (DSBs) are the most toxic form of DNA damage in cells. Homologous recombination (HR) is an error-free repair mechanism for DSBs as well as a basis for gene targeting using genome-editing techniques. Despite the importance of HR, the HR mechanism in plants is poorly understood. Through genetic screens for DNA damage response mutants (DDRMs), we find that the Arabidopsis ddrm2 mutant is hypersensitive to DSB-inducing reagents. DDRM2 encodes a protein with four BRCA1 C-terminal (BRCT) domains and is highly conserved in plants including bryophytes, the earliest land plant lineage. The plant-specific transcription factor SOG1 binds to the promoter of DDRM2 and activates its expression. In consistence, the expression of DDRM2 is induced by DSBs in a SOG1-dependent manner. In support, genetic analysis suggests that DDRM2 functions downstream of SOG1. Similar to the sog1 mutant, the ddrm2 mutant shows dramatically reduced HR efficiency. Mechanistically, DDRM2 interacts with the core HR protein RAD51 and is required for the recruitment of RAD51 to DSB sites. Our study reveals that SOG1-DDRM2-RAD51 is a novel module for HR, providing a potential target for improving the efficiency of gene targeting.

Genetic variation in the glycine-rich protein gene BnGRP1 contributes to low phosphorus tolerance in Brassica napus.

Lack of phosphorus (P) is a major environmental factor affecting rapeseed (Brassica napus. L) root growth and development. For breeding purposes, it is crucial to identify the molecular mechanisms underlying root system architecture traits that confer low-P tolerance in rapeseed. Natural variations in the glycine-rich protein gene BnGRP1 were analysed in the natural population of 400 rapeseed cultivars under low-P stress through genome-wide association study and transcriptome analysis. Based on 11 single nucleotide polymorphism mutations in the BnGRP1 sequence, 10 haplotypes (Hap) were formed. Compared with the other types, the cultivar BnGRP1Hap1 in the panel demonstrated the longest root length and heaviest root weight. BnGRP1Hap1 overexpression in rapeseed led to enhanced low-P tolerance. CRISPR/Cas9-derived BnGRP1Hap4 knockout mutations in rapeseed can lead to sensitivity to low-P stress. Furthermore, BnGRP1Hap1 influences the expression of the phosphate transporter 1 gene (PHT1) associated with P absorption. Overall, the findings of this study highlight new insights into the mechanisms of GRP1 enhancement of low-P tolerance in rapeseed.

PB-LNet: a model for predicting pathological subtypes of pulmonary nodules on CT images.

OBJECTIVE: To investigate the correlation between CT imaging features and pathological subtypes of pulmonary nodules and construct a prediction model using deep learning. METHODS: We collected information of patients with pulmonary nodules treated by surgery and the reference standard for diagnosis was post-operative pathology. After using elastic distortion for data augmentation, the CT images were divided into a training set, a validation set and a test set in a ratio of 6:2:2. We used PB-LNet to analyze the nodules in pre-operative CT and predict their pathological subtypes. Accuracy was used as the model evaluation index and Class Activation Map was applied to interpreting the results. Comparative experiments with other models were carried out to achieve the best results. Finally, images from the test set without data augmentation were analyzed to judge the clinical utility. RESULTS: Four hundred seventy-seven patients were included and the nodules were divided into six groups: benign lesions, precursor glandular lesions, minimally invasive adenocarcinoma, invasive adenocarcinoma Grade 1, Grade 2 and Grade 3. The accuracy of the test set was 0.84. Class Activation Map confirmed that PB-LNet classified the nodules mainly based on the lungs in CT images, which is in line with the actual situation in clinical practice. In comparative experiments, PB-LNet obtained the highest accuracy. Finally, 96 images from the test set without data augmentation were analyzed and the accuracy was 0.89. CONCLUSIONS: In classifying CT images of lung nodules into six categories based on pathological subtypes, PB-LNet demonstrates satisfactory accuracy without the need of delineating nodules, while the results are interpretable. A high level of accuracy was also obtained when validating on real data, therefore demonstrates its usefulness in clinical practice.

Integrated analysis of the lncRNA/circRNA-miRNA-mRNA expression profiles reveals novel insights into potential mechanisms in response to root-knot nematodes in peanut.

BACKGROUND: Peanut is the most essential oil and food crop globally due to its high oil and protein content. Root-knot nematode infects peanut roots, causing poor development and severely limiting peanut yields worldwide. The discovery of peanut genome identified a considerable number of genetic loci controlling the peanut root-knot nematode; however, the molecular mechanism of root-knot nematode remains unknown. RESULTS: The heterogeneous response to root-knot nematode stress in peanut roots was identified using whole-transcriptome RNA-seq. A total of 430 mRNAs, 111 miRNAs, 4453 lncRNAs, and 123 circRNAs were found to have differential expression between infected and non-infected peanuts. The expression profiles of the lncRNA/circRNA-miRNA-mRNA network were developed to understand the potential pathways that lead to root-knot nematodes in peanut roots. During root-knot nematodes stress, a total of 10 lncRNAs, 4 circRNAs, 5 miRNAs, and 13 mRNAs can create competing endogenous RNA and participate in the oxidation-reduction process as well as other biological metabolism processes in peanuts. The findings will highlight the role of peanut ceRNAs in response to root-knot nematodes. CONCLUSION: The GO classification and KEGG pathway enrichment study of core regulatory networks revealed that ceRNAs are involved in oxidation-reduction, peroxidase activity, lignin synthesis in the xylem, and flavonoid synthesis. Overall, these findings may help researchers better understand the role of non-coding RNAs in response to root-knot nematodes.

Transcription factor BZR2 activates chitinase Cht20.2 transcription to confer resistance to wheat stripe rust.

The brassinosteroid pathway promotes a variety of physiological processes in plants and the brassinosteroid insensitive1-ethylmethane sulfonate suppressor (BES)/brassinazole-resistant (BZR) functions as one of its key regulators. We previously showed that the BES/BZR-type transcription factor TaBZR2 mediates the drought stress response in wheat (Triticum aestivum) by directly upregulating the transcriptional activity of glutathione S-transferase 1. However, the function of TaBZR2 in plants under biotic stresses is unknown. In this study, we found that transcript levels of TaBZR2 were upregulated in response to inoculation with wheat stripe rust fungus (Puccinia striiformis f. sp. tritici, Pst) and treatment with flg22 or an elicitor-like protein of Pst, Pst322. Wheat lines overexpressing TaBZR2 conferred increased resistance, whereas TaBZR2-RNAi lines exhibited decreased resistance to multiple races of Pst. TaBZR2 targeted the promoter of the chitinase gene TaCht20.2, activating its transcription. Knockdown of TaCht20.2 in wheat resulted in enhanced susceptibility to Pst, indicating the positive role of TaCht20.2 in wheat resistance. Upon Pst infection in vivo, the overexpression of TaBZR2 increased total chitinase activity, whereas RNAi-mediated silencing of TaBZR2 reduced total chitinase activity. Taken together, our results suggest that TaBZR2 confers broad-spectrum resistance to the stripe rust fungus by increasing total chitinase activity in wheat.

Multi-threshold splitting tree algorithm to reduce the number of filters in programmable hyperspectral imaging for fast multi-target classification.

Programmable hyperspectral imaging is a promising and efficient technique for fast target classification by coding hyperspectral post-processing algorithms as spectral transmittances, which enables such post-processing to be directly performed by special optical dispersive element during the process of optical imaging. Compared with conventional hyperspectral imaging and post-processing techniques, it shows significant advantages of fast image acquisition, post-processing free, and a much lower load of data transmission and storage. However, when multi-target classification tasks are encountered, the speed would decrease seriously due to the requirement of a large number of filters. In this study, a novel splitting strategy is proposed to reduce the number of filters in programmable hyperspectral imaging for fast multi-target classification while maintaining the classification performance. Numerical simulation experiments were performed on six publicly available hyperspectral data sets. Compared with the conventional splitting strategies, the proposed splitting strategy can reduce the number of filters by 25% to 80% and achieve similar classification performance, which is of great significance to improve the speed of multi-target classification with programmable hyperspectral imaging technique.

Genotoxicity, oxidative stress and transcriptomic effects of Nitenpyram on human bone marrow mesenchymal stem cells.

Despite of the global contamination and ubiquitous exposure to nitenpyram (NIT), little knowledge is available on the adverse effects to human health, with some evidence referring to its genotoxic potency to non-target organisms and esophageal squamous papilloma in rats. Human bone marrow mesenchymal stem cells (hBMSCs) was employed as an in vitro model more relevant to humans to assess the potential genotoxicity of NIT and to understand the underlying mechanisms at cellular and molecular levels. Noncytotoxic concentrations of NIT, 50-2500 µg/mL, dose-dependently elevated micronucleus (MN) and nuclear bud (NB) frequencies to 8.7-29‰ and 15-35‰, respectively. Additional metabolism by rat liver S9 fraction decreased chromosome impairment by 27-52% on MN frequencies and 63-76% on NB frequencies. A commercial NIT product, containing 20% of NIT and 60% of pymetrozine, caused higher cytotoxicity and chromosome impairment in comparison with NIT alone. Expressions of genes responses to DNA damage, ATM, ATR, p53, p21, Bax, H2AX, and GADD45A were disturbed by NIT treatment. Reactive oxygen species (ROS) amount and superoxide dismutase (SOD) activity were enhanced by NIT. Comet assay showed that lower concentrations of NIT, 12.5-100 µg/mL, induced the DNA damage. Transcriptomic analysis identified 468 differentially expressed genes (p < 0.05, |log2(Foldchange)| ≥ 1), from which 22 pathways were enriched. Multiple affected pathways were related to cancer including viral carcinogenesis and bladder cancer. NIT may produce genotoxicity via inducing oxidative stress and deregulating PI3K/Akt, AMPK and mTOR signaling pathways, associated with carcinogenetic potency. While environmental levels of NIT alone may pose little risk to human health, attention should be paid to the health risk arose from the synergistic or additive effects that may exist among NEOs and other types of pesticides.

Melatonin mediates reactive oxygen species homeostasis via SlCV to regulate leaf senescence in tomato plants.

Melatonin (MT) functions in removing reactive oxygen species (ROS) and delaying plant senescence, thereby acting as an antioxidant; however, the molecular mechanism underlying the specific action of MT is unclear. Herein, we used the mutant plants carrying the MT decomposition gene melatonin 3-hydroxylase (M3H) in tomato to elucidate the specific mechanism of action of MT. SlM3H-OE accelerated senescence by decreasing the content of endogenous MT in plants. SlM3H is a senescence-related gene that positively regulates aging. MT inhibited the expression of the senescence-related gene SlCV to scavenge ROS, induced stable chloroplast structure, and delayed leaf senescence. Simultaneously, MT weakened the interaction between SlCV and SlPsbO/SlCAT3, reduced ROS production in photosystem II, and promoted ROS elimination. In conclusion, MT regulates ROS homeostasis and delays leaf aging in tomato plants through SlCV expression modulation.

Neonatal acute ethanol intoxication during the epidemic of COVID-19: a case report.

BACKGROUND: After the outbreak of COVID-19, many families equip with 75% ethanol to inactivate the SARS-CoV-2, which increases the risk of exposure to ethanol. CASE PRESENTATION: We reported a 25-day-old newborn who was diagnosed with neonatal acute ethanol intoxication with a presenting complaint of accidental consumption about 15 ml formula milk containing 75% ethanol. His main clinical manifestations were irritability, flushed skin, tachycardia, tachypnea, and toxicology analysis detected ethanol. After timely gastric lavage and intravenous fluid replacement, he was cured and discharged. CONCLUSIONS: During the COVID-19 epidemic, high concentration ethanol used for inactivating SARS-COV-2 should be placed reasonably and neonatal feeding safety should be emphasized. Timely diagnosis and symptomatic treatment are essential for the prevention and management of acute ethanol intoxication in newborns.

Enhanced laccase production by mutagenized Myrothecium verrucaria using corn stover as a carbon source and its potential in the degradation of 2-chlorophen.

Chlorophenols are widely used in industry and are known environmental pollutants. The degradation of chlorophenols is important for environmental remediation. In this study, we evaluated the biodegradation of 2-chlorophenol using crude laccase produced by Myrothecium verrucaria. Atmospheric and room temperature plasma technology was used to increase laccase production. The culture conditions of the M-6 mutant were optimized. Our results showed that corn stover could replace glucose as a carbon source and promote laccase production. The maximum laccase activity of 30.08 U/mL was achieved after optimization, which was a 19.04-fold increase. The biodegradation rate of 2-chlorophenol using crude laccase was 97.13%, a positive correlation was determined between laccase activity and degradation rate. The toxicity of 2-CP was substantially reduced after degradation by laccase solution. Our findings show the feasibility of the use of corn stover in laccase production by M. verrucaria mutant and the subsequent biodegradation of 2-chlorophenol using crude laccase.

Water as a Probe for Standardization of Near-Infrared Spectra by Mutual-Individual Factor Analysis.

The standardization of near-infrared (NIR) spectra is essential in practical applications, because various instruments are generally employed. However, standardization is challenging due to numerous perturbations, such as the instruments, testing environments, and sample compositions. In order to explain the spectral changes caused by the various perturbations, a two-step standardization technique was presented in this work called mutual-individual factor analysis (MIFA). Taking advantage of the sensitivity of a water probe to perturbations, the spectral information from a water spectral region was gradually divided into mutual and individual parts. With aquaphotomics expertise, it can be found that the mutual part described the overall spectral features among instruments, whereas the individual part depicted the difference of component structural changes in the sample caused by operation and the measurement conditions. Furthermore, the spectral difference was adjusted by the coefficients in both parts. The effectiveness of the method was assessed by using two NIR datasets of corn and wheat, respectively. The results showed that the standardized spectra can be successfully predicted by using the partial least squares (PLS) models developed with the spectra from the reference instrument. Consequently, the MIFA offers a viable solution to standardize the spectra obtained from several instruments when measurements are affected by multiple factors.

A Visual Hydrogen Sensor Prototype for Monitoring Magnesium Implant Biodegradation.

Alternative metals such as magnesium (Mg) and its alloys have been recently developed for clinical applications such as temporary implants for bone and tissue repair due to their desirable mechanical properties and ability to biodegrade harmlessly in vivo by releasing Mg2+, OH-, and H2 as biodegradation products. The current methods for monitoring in vivo Mg-alloy biodegradation are either invasive and/or costly, complex, or require large equipment and specially trained personnel, thus making real-time and point-of-care monitoring of Mg-alloy implants problematic. Therefore, innovative methods are critically needed. The objective of this research was to develop a novel, thin, and wearable visual H2 sensor prototype for noninvasive monitoring of in vivo Mg-implant biodegradation in medical research and clinical settings with a fast response time. In this work, we successfully demonstrate such a prototype composed of resazurin and catalytic bimetallic gold-palladium nanoparticles (Au-Pd NPs) incorporated into a thin agarose/alginate hydrogel matrix that rapidly changes color from blue to pink upon exposure to various levels of H2 at a constant flow rate. The irreversible redox reactions occurring in the sensor involve H2, in the presence of Au-Pd NPs, converting resazurin to resorufin. To quantify the sensor color changes, ImageJ software was used to analyze photographs of the sensor taken with a smartphone during H2 exposure. The sensor concentration range was from pure H2 down to limits of detection of 6 and 8 µM H2 (defined via two methods). This range is adequate for the intended application of noninvasively monitoring in vivo Mg-alloy implant biodegradation in animals for medical research and patients in clinical settings.

Identifying functioning and nonfunctioning adrenal tumors based on blood serum surface-enhanced Raman spectroscopy.

Adrenal tumors are common tumors in urology and they can be further divided into functioning and nonfunctioning tumors according to whether there is uncommon endocrine function. In clinical practice, the early identification and accurate assessment of adrenal tumors are essential for the guidance of subsequent treatment. However, a nonfunctioning adrenal tumor often lacks obvious clinical symptoms, making it difficult to be timely and precisely diagnosed by conventional examinations. Therefore, a rapid and accurate method for identifying the functioning and nonfunctioning adrenal tumors is urgently required to achieve precise treatment of adrenal tumors. In this study, surface-enhanced Raman spectroscopy was investigated as a diagnostic tool to identify the blood serum samples from healthy volunteers as well as the patients with functioning and nonfunctioning adrenal tumors. Based on the SERS peak analysis, abnormal glycolysis, DNA/RNA, and amino acid metabolites were found to be potential biomarkers for identifying patients with adrenal tumors, while metabolites related to disordered protein catabolism and excessive hormone secretion were expected to further differentiate functioning adrenal tumors from nonfunctioning adrenal tumors. In addition, principal component analysis followed by support vector machine (PCA-SVM) was further applied on those serum SERS measurements, and the classification accuracies of 96.8% and 84.5% were achieved for differentiating healthy group versus adrenal tumor group and functioning adrenal tumor group versus nonfunctioning adrenal tumor group, respectively. The results have demonstrated the prodigious potential of precise adrenal tumor diagnosis by using the blood serum surface-enhanced Raman spectroscopy technique.

Identifying benign and malignant thyroid nodules based on blood serum surface-enhanced Raman spectroscopy.

The aim of this study is to evaluate the feasibility of using blood serum surface-enhanced Raman spectroscopy (SERS) to identify benign and malignant thyroid nodules. Blood serum samples collected from three different groups including healthy volunteers (n = 22), patients with benign nodules (n = 19) and malignant nodules (n = 22) were measured by SERS. The spectral analysis results demonstrate that biomolecules in serum, such as amino acids, adenine and nucleic acid bases, change differently due to the different progression of nodules. By further combining with partial least square analysis and linear discriminant analysis (PLS-LDA) method, diagnostic accuracies of 93.65% and 82.93%, sensitivities of 92.68% and 81.82% and specificities of 95.45% and 84.21% can be achieved for differentiating healthy versus thyroid nodular groups and benign versus malignant groups, respectively. The above results have suggested that the blood serum SERS technique is helpful for precise diagnosis and timely treatment for patients with thyroid nodules.

BES/BZR Transcription Factor TaBZR2 Positively Regulates Drought Responses by Activation of TaGST1.

BRI1-EMS suppressor (BES)/brassinazole-resistant (BZR) family transcription factors are involved in a variety of physiological processes, but the biological functions of some BES/BZR transcription factors remain unknown; moreover, it is not clear if any of these proteins function in the regulation of plant stress responses. Here, wheat (Triticum aestivum) brassinazole-resistant 2 (TaBZR2)-overexpressing plants exhibited drought tolerant phenotypes, whereas downregulation of TaBZR2 in wheat by RNA interference resulted in elevated drought sensitivity. electrophoretic mobility shift assay and luciferase reporter analysis illustrate that TaBZR2 directly interacts with the gene promoter to activate the expression of T. aestivum glutathione s-transferase-1 (TaGST1), which functions positively in scavenging drought-induced superoxide anions (O2 -). Moreover, TaBZR2 acts as a positive regulator in brassinosteroid (BR) signaling. Exogenous BR treatment enhanced TaBZR2-mediated O2 - scavenging and antioxidant enzyme gene expression. Taken together, we demonstrate that a BES/BZR family transcription factor, TaBZR2, functions positively in drought responses by activating TaGST1 and mediates the crosstalk between BR and drought signaling pathways. Our results thus provide new insights into the mechanisms underlying how BES/BZR family transcription factors contribute to drought tolerance in wheat.

Immunogenicity and Safety of an F-Genotype Attenuated Mumps Vaccine in Healthy 8- to 24-Month-Old Children.

Background: Mumps vaccine immunizations have reduced the incidence of this disease. With the variation of mumps circulating strain, novel vaccine strains are always important. Methods: A 2-center parallel, randomized, double-blind noninferiority trial was performed to compare an F-genotype attenuated mumps vaccine (SP strain) to the A-genotype vaccine (S-79, Jeryl-Lynn strain) in 1080 healthy children aged 8-24 months in Hubei, China. Results: Participants were randomly assigned to receive a high or low dose of the SP or S79 vaccine and then assessed clinically at 30 minutes and 1-28 days postinoculation. No differences in local or systemic reactivity were observed. A similar incidence of severe adverse events associated with the vaccine was observed in the high-dose group and the positive control group. Based on throat swab collections, no viral shedding was present at the 4th and 10th days in any group. Neutralizing and hemagglutination-inhibiting antibody assays with the F- or A-genotype strains showed similar trends in geometric mean titers in the high-dose SP and S79 groups. Increased cytotoxic T lymphocyte responses were observed in all groups. Conclusions: The F-genotype attenuated mumps vaccine is safe, offers immunogenicity against a homologous virus, and is noninferior to the A-genotype vaccine in 8- to 24-month-old children.

Evaluation of Varicella-zoster virus-specific cell-mediated immunity by interferon-γ Enzyme-Linked Immunosorbent Assay in adults ≥50 years of age administered a herpes zoster vaccine.

Varicella-zoster virus (VZV)-specific cell-mediated immunity (CMI) is critical for preventing and controlling the onset of herpes zoster (HZ). To assess VZV CMI, an interferon-γ (IFN-γ) enzyme-linked immunosorbent assay (ELISA) was validated by examining the influence of VZV-specific antigen content, incubation time, and interval from whole blood collection on the assay. In phase II clinical trial, VZV-specific CMI in adults ≥50 years of age administered an HZ vaccine were evaluated by IFN-γ ELISA, as determined by measuring IFN-γ production in the whole blood in response to stimulation with ultraviolet light-inactivated VZV. The VZV-specific IFN-γ levels varied among individuals from prevaccination (baseline) to 6 weeks postvaccination. In most subjects, VZV-specific CMI was increased at 6 weeks postvaccination. The HZ vaccine elicited a significant increase in the VZV-specific CMI response as measured by ELISA; the geometric mean fold-rises from baseline to 6 weeks postvaccination were 3.50, 4.22, and 5.24 in the 4.3, 4.7, and 4.9 log plaque-forming unit vaccine groups, respectively, which was significantly higher than in the placebo group (P < 0.05). These results indicate that vaccination enhances the VZV-specific CMI responses in subjects; IFN-γ ELISA is an effective method for evaluating the CMI response and may be useful for identifying individuals at a high risk of HZ infection.