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Background Male sex and old age are risk factors for severe coronavirus disease 2019, but the intersection of sex and aging on antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has not been characterized. Methods Plasma samples were collected from older adults (aged 75–98 years) before and after 3 doses of SARS-CoV-2 mRNA vaccination, and from younger adults (aged 18–74 years) post-dose 2, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S receptor-binding domain, and nucleocapsid), functional activity against S, and live-virus neutralization were measured against the vaccine virus and the Alpha, Delta, and Omicron variants of concern (VOCs). Results Vaccination induced greater antibody titers in older females than in older males, with both age and frailty associated with reduced antibody responses in males but not females. Responses declined significantly in the 6 months after the second dose. The third dose restored functional antibody responses and eliminated disparities caused by sex, age, and frailty in older adults. Responses to the VOCs, particularly the Omicron variant, were significantly reduced relative to the vaccine virus, with older males having lower titers to the VOCs than older females. Older adults had lower responses to the vaccine and VOC viruses than younger adults, with greater disparities in males than in females. Conclusions Older and frail males may be more vulnerable to breakthrough infections owing to low antibody responses before receipt of a third vaccine dose. Promoting third dose coverage in older adults, especially males, is crucial to protecting this vulnerable population.

In this paper, the pore structure characteristics of shales and its controlling factors were analyzed by means of total organic carbon (TOC) analysis, X-ray diffraction (XRD) analysis, field emission scanning electron microscopy (FE-SEM) and low-pressure N2 adsorption (LPNA) analysis. Based on the grey relational analysis, the controlling factors of pore structure parameters were discussed. The results showed that the TOC contents range from 2.98 to 4.97%, the main minerals of shales are quartz and clay minerals with an average of 41.62 and 30.98%, respectively. The organic matter pores, the interparticle pores, the intraparticle pores, and the micro-fractures are the main pore types determined by the FE-SEM observation. The pore volume of shales is between 0.0637 and 0.1053 cm3/g, the specific surface area ranges from 16.44 to 37.61 m2/g, the average pore size is between 11.20 and 15.50 nm. The organic matter and the quartz have a positive influence on the specific surface area and total pore volume, whereas the clay minerals have a negative impact. The shales have a wide range of pore size, and the mesopores and macropores are the dominant contributor to the total pore volume while the mesoporous contribute the main specific surface area. The TOC contents and quartz contents have the most significant effect on the total pore volume and specific surface area, and the average pore size is mainly controlled by the quartz contents.

The international genetically engineered machine (iGEM) competition is a global top college academic competition in synthetic biology. The iGEM competition has exhibited extensive international influence and attracted teams from more than 40 countries and regions around the world to participate in. The annual iGEM outputs have attracted the attention of top academic journals or international media such as

BackgroundMale sex and old age are risk factors for severe COVID-19, but the intersection of sex and aging on antibody responses to SARS-CoV-2 vaccines has not been characterized.MethodsPlasma samples were collected from older adults (75-98 years) before and after three doses of SARS-CoV-2 mRNA vaccination, and from younger adults (18-74 years) post-dose two, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S-receptor binding domain [S-RBD], and nucleocapsid [N]) and functional activity against S were measured against the vaccine virus and variants of concern (VOC).ResultsVaccination induced greater antibody titers in older females than males, with both age and frailty associated with reduced antibody responses to vaccine antigens in males, but not females. ACE2 binding inhibition declined more than anti-S or anti-S-RBD IgG in the six months following the second dose (28-fold vs. 12- and 11-fold decreases in titer). The third dose restored functional antibody responses and eliminated disparities caused by sex, age, and frailty in older adults. Responses to the VOC were significantly reduced relative to the vaccine virus, with older males having lower titers to the VOC than females. Older adults had lower responses to the vaccine and VOC viruses than younger adults, with disparities being greater in males than females.ConclusionOlder and frail males may be more vulnerable to breakthrough infections due to low antibody responses before receipt of a third vaccine dose. Promoting third dose coverage in older adults, especially males, is crucial to protecting this vulnerable population.Brief summarySARS-CoV-2 mRNA vaccination induces greater antibody response in older females than males, and age and frailty reduce responses in males only. These effects are eliminated by a third vaccine dose, highlighting the need for third dose coverage, especially in older males.

Recent advances in three-dimensional (3D) printing and augmented reality (AR) have expanded anatomical modeling possibilities for caregiver craniosynostosis education. The purpose of this study is to characterize caregiver preferences regarding these visual models and determine the impact of these models on caregiver understanding of craniosynostosis.The authors constructed 3D-printed and AR craniosynostosis models, which were randomly presented in a cross-sectional survey. Caregivers rated each model's utility in learning about craniosynostosis, learning about skull anatomy, viewing an abnormal head shape, easing anxiety, and increasing trust in the surgeon in comparison to a two-dimensional (2D) diagram. Furthermore, caregivers were asked to identify the fused suture on each model and indicate their preference for generic versus patient-specific models.A total of 412 craniosynostosis caregivers completed the survey (mean age 33 years, 56% Caucasian, 51% male). Caregivers preferred interactive, patient-specific 3D-printed or AR models over 2D diagrams (mean score difference 3D-printed to 2D: 0.16, P 0.05; mean score difference AR to 2D: 0.17, P 0.01) for learning about craniosynostosis, with no significant difference in preference between 3D-printed and AR models. Caregiver detection accuracy of the fused suture on the sagittal model was 19% higher with the 3D-printed model than with the AR model (P 0.05) and 17% higher with the 3D-printed model than with the 2D diagram (P 0.05).Our findings indicate that craniosynostosis caregivers prefer 3D-printed or AR models over 2D diagrams in learning about craniosynostosis. Future craniosynostosis skull models with increased user interactivity and patient-specific components can better suit caregiver preferences.

Mitochondria are critical regulators of cellular function and survival. We have previously demonstrated that functional angiotensin receptors embedded within the inner mitochondrial membrane modulate mitochondrial energy production and free radical generation. The expression of mitochondrial angiotensin II type-1 receptors increases during aging, with a complementary decrease in angiotensin II type-2 receptor density. To address this age-associated mitochondrial dysfunction, we have developed a mitochondria-targeted delivery system to effectively transport angiotensin type-1 receptor blocker—Losartan (mtLOS) into the inner mitochondrial membrane. We engineered mtLOS to become active within the mitochondria after cleavage by mitochondrial peptidases. Our data demonstrate effective and targeted delivery of mtLOS into the mitochondria, compared to a free Losartan, or Losartan conjugated to a scrambled mitochondrial target signal peptide, with significant shifts in mitochondrial membrane potential upon mtLOS treatment. Furthermore, engineered mitochondrial-targeting modalities could open new avenues to transport nonmitochondrial proteins into the mitochondria, such as other macromolecules and therapeutic agents.

Postoperative chylothorax is a rare complication after pulmonary resection. Thoracic duct variations may play a key role in postoperative chylothorax occurrence and make treatment difficult. No studies in the literature have reported the successful treatment of chylothorax second to thoracic duct variation by lipiodol-based lymphangiography.A 63-year-old male and a 28-year-old female with primary lung adenocarcinoma were treated by video-assisted thoracoscopic cancer resection, and suffered postoperative chylothorax. Conservative treatment was ineffective, including nil per os, persistent thoracic drainage, fatty food restriction, and somatostatin administration.Postoperative chylothorax.Patients received lipiodol-based lymphangiography under fluoroscopic guidance. Iatrogenic injuries were identified at thoracic duct variations, including an additional channel in case 1 and the lymphatic plexus instead of the thoracic duct in case 2.Thoracic duct variations were identified by lipiodol-based lymphangiography, and postoperative chylothorax was successfully treated by lipiodol embolizing effect.Thoracic duct variations should be considered after the failure of conservative treatment for postoperative chylothorax secondary to pulmonary resection. Lipiodol-based lymphangiography is valuable for identifying the thoracic duct variations and embolizing chylous leakage.

Background/Aims: Aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5) are secreted enzymes belonging to the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family that play significant roles in the progression of osteoarthritis (OA). Here, we aimed to determine whether the expression of ADAMTS-4/5 in chondrogenesis and inflammation is regulated by microRNA-92a-3p (miR-92a-3p). Methods: MiR-92a-3p and ADAMTS-4/5 expressions were determined by quantitative polymerase chain reaction (qPCR). To investigate the repressive effect of miR-92a-3p on ADAMTS-4/5 expression, chondrogenic human mesenchymal stem cells (hMSCs) and human chondrocytes were transfected with mature miR-92a-3p or an antisense inhibitor (anti-miR-92a-3p), respectively. ADAMTS-4/5 protein production was quantified by enzyme-linked immunosorbent assay (ELISA), and miR-92a-3p involvement in IL-1β-mediated catabolic effects was examined by immunoblotting. The roles of activated MAP kinases (MAPK) and nuclear factor (NF)-κB were evaluated by using specific inhibitors. Interaction between miR-92a-3p and its putative binding site in the 3′-untranslated region (3′-UTR) of ADAMTS-4/5 mRNA was confirmed by luciferase reporter assay. Results: miR-92a-3p expression was elevated in chondrogenic hMSCs, with significantly lower expression in OA cartilage than in normal cartilage. Stimulation with IL-1β significantly reduced miR-92a-3p expression in primary human chondrocytes (PHCs). Transfection of chondrocytes with miR-92a-3p downregulated IL-1β-induced ADAMTS-4/5 expression, and the activity of a reporter construct containing the 3′-UTR of human ADAMTS-4/5 mRNA. MiR-92a-3p expression was suppressed upon IL-1β-induced activation of MAPK and NF-κB in chondrocytes. Conclusion: MiR-92a-3p is an important regulator of ADAMTS-4/5 in human chondrocytes and may contribute to the development of OA.

Manganese-based oxides are considered as one of the most attractive cathode materials in aqueous zinc ion battery. However, the poor cycleability, inferior rate capability and associated with the ambiguous energy storage mechanisms seem to hinder its practical application. Herein, nitrogen-doped carbon-coated MnO (MnO@N-C) composite fibers were fabricated directly through an in situ strategy of electrospinning method, followed by two-step annealing processes. The results show that the cycling performances and rate capability of the as-prepared composite of MnO@N-C at 500 °C with graphite foil as the current collector (MnO@N-C-500-GF) are much better than that with stainless steel mesh (MnO@N-C-500-SSM). It delivers the reversible capacity of 176.3 mAh g−1 even after 200th cycles at 500 mA g−1 and 100.5 mAh g−1 at large current density of 1.2 A g−1 for the former. The electrochemical kinetics reveals that all the electrode reaction are mainly contributed by a diffusion-controlled process and partially dictated by the surface-controlled capacitive behavior. Significant insight into the energy storage mechanism is confirmed by ex situ X-ray diffraction. The detailed phase evolution process during the charge and discharge process indicates that MnO@N-C cathode with high reversibility and cycling stability experiences an insertion/extraction process of Zn2+ along with a dissolution/deposition mechanism due to Mn2+ dissolution.

Background Vitamin A deficiency (VAD) is a major public health problem in the developing world, leading to >3 million eye-related problems in preschool children. Nearly 250 million children have subclinical VAD, resulting in a 23% increase in childhood mortality. Difficulties in obtaining samples to assess VAD have hampered the detection, intervention, and surveillance of VAD. The use of dried blood spots (DBS) could ameliorate many problems of vitamin A assessment. Objective The objective of this study was to validate the use of retinol in DBS for vitamin A assessment by comparing it with venous and capillary serum retinol. Design Venous and capillary blood specimens were obtained simultaneously from 20 healthy adult volunteers. From each blood specimen, both DBS and liquid serum were prepared (a total of 80 samples). All specimens were maintained at -70 degrees C until HPLC analysis. Results The mean retinol concentrations in the 4 sample types were as follows: venous serum (2.02 +/- 0.42 micromol/L, or 58 +/- 12 microg/dL), capillary serum (2.06 +/- 0.42 micromol/L, or 59 +/- 12 microg/dL), venous DBS (2.06 +/- 0.49 micromol/L, or 59 +/- 14 microg/dL), and capillary DBS (2.09 +/- 0.45 micromol/L, or 60 +/- 13 microg/dL). Of the 6 possible 2-way combinations, the R(2) values ranged from 0.77 for capillary DBS versus venous DBS to 0.95 for venous serum versus capillary serum. Conclusions DBS retinol measured by HPLC is comparable with serum retinol. Thus, it is possible to compare and combine blood retinol concentration data obtained from DBS with current and historic measurements in serum.