Application of Bifacial Semitransparent CuInSe2 Absorber to the Bottom Cell in Bifacial Semitransparent Perovskite/CuInSe2 Tandem Solar Cell for Albedo Environment.

Although various types of bifacial solar cells exist, few studies have been conducted on bifacial semitransparent CuInSe2 solar cells (BS-CISe SCs) despite the attractive potential in power generation from both sides in an albedo environment. The optimized BS-CISe SCs with 300 and 800 nm-thick absorber via a streamlined single-stage co-evaporation process exhibit a power conversion efficiency (PCE) of 6.32% and 10.6%, respectively. When double-sided total 2.0 sun illumination is assumed in an albedo environment, the bifacial power generation densities (BPGD) of them increases to 9.41% and 13.9%. Four-terminal bifacial semitransparent tandem solar cells (4T-BST SCs) are fabricated to increase the BPGD by mechanically stacking a BS-perovskite (PVK) top cell on top of a BS-CISe bottom cell with the 300 and 800 nm-thick absorber layers. When summed up, the best top and bottom cell PCEs of the 4T-BST SC with 300 and 800 nm-thick BS-CISe SC are 18.8% and 21.1%, respectively. However, the practical BPGD values of the 4T-BST SC under total 2 sun illumination are interestingly 23.4% and 24.4%, respectively. This is because the BS-CISe bottom cell's thickness affects how much rear-side illumination is transmitted to the BS-PVK top cell, increasing its current density and BPGD.

Observation of Vacuum-Induced Collective Quantum Beats.

We demonstrate collectively enhanced vacuum-induced quantum beat dynamics from a three-level V-type atomic system. Exciting a dilute atomic gas of magneto-optically trapped ^{85}Rb atoms with a weak drive resonant on one of the transitions, we observe the forward-scattered field after a sudden shut-off of the laser. The subsequent radiative dynamics, measured for various optical depths of the atomic cloud, exhibits superradiant decay rates, as well as collectively enhanced quantum beats. Our work is also the first experimental illustration of quantum beats arising from atoms initially prepared in a single excited level as a result of the vacuum-induced coupling between excited levels.

Increased sesqui- and triterpene production by co-expression of HMG-CoA reductase and biotin carboxyl carrier protein in tobacco (Nicotiana benthamiana).

Terpenoids are the most diverse natural products with many industrial applications and are all synthesized from simple precursors, isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP). In plants, IPP is synthesized by two distinct metabolic pathways - cytosolic mevalonate (MVA) pathway for C15 sesquiterpene and C30 triterpene, and plastidic methylerythritol phosphate (MEP) pathway for C10 monoterpene and C20 diterpene. A number of studies have altered the metabolic gene expressions in either the MVA or MEP pathway to increase terpene production; however, it remains unknown if the alteration of the acetyl-CoA pool in plastid fatty acid biosynthesis can influence terpenoid flux. Here, we focused on the fact that acetyl-CoA is the precursor for both fatty acid biosynthesis in plastid and terpene biosynthesis in cytosol, and the metabolic impact of increased plastidic acetyl-CoA level on the cytosolic terpene biosynthesis was investigated. In tobacco leaf infiltration studies, the acetyl-CoA carboxylase complex (the enzyme supplying malonyl-CoA in plastid) was partially inhibited by overexpressing the inactive form of biotin carboxyl carrier protein (BCCP) by a negative dominant effect. Overexpression of BCCP showed 1.4-2.4-fold increase of sesquiterpenes in cytosol; however, surprisingly overexpression of BCCP linked to truncated HMG-CoA reductase (tHMGR) by a cleavable peptide 2A showed 20-40-fold increases of C15 sesquiterpenes (α-bisabolol, amorphadiene, and valerenadiene) and a 6-fold increase of C30 ß-amyrin. α-Bisabolol and ß-amyrin production reached 28.8 mg g-1 and 9.8 mg g-1 dry weight, respectively. Detailed analyses showed that a large increase in flux was achieved by the additive effect of BCCP- and tHMGR-overexpression, and an enhanced tHMGR activity by 2A peptide tag. Kinetic analyses showed that tHMGR-2A has a three-fold higher kcat value than tHMGR. The tHMGR-2A-BCCP1 co-expression strategy in this work provides a new insight into metabolic cross-talks and can be a generally applicable approach to over-produce sesqui- and tri-terpene in plants.

Molecular cloning and functional characterization of three terpene synthases from unripe fruit of black pepper (Piper nigrum).

To identify terpene synthases (TPS) responsible for the biosynthesis of the sesquiterpenes that contribute to the characteristic flavors of black pepper (Piper nigrum), unripe peppercorn was subjected to the Illumina transcriptome sequencing. The BLAST analysis using amorpha-4,11-diene synthase as a query identified 19 sesquiterpene synthases (sesqui-TPSs), of which three full-length cDNAs (PnTPS1 through 3) were cloned. These sesqui-TPS cDNAs were expressed in E. coli to produce recombinant enzymes for in vitro assays, and also expressed in the engineered yeast strain to assess their catalytic activities in vivo. PnTPS1 produced ß-caryophyllene as a main product and humulene as a minor compound, and thus was named caryophyllene synthase (PnCPS). Likewise, PnTPS2 and PnTPS3 were, respectively, named cadinol/cadinene synthase (PnCO/CDS) and germacrene D synthase (PnGDS). PnGDS expression in yeast yielded ß-cadinene and α-copaene, the rearrangement products of germacrene D. Their kcat/Km values (20-37.7 s-1 mM-1) were comparable to those of other sesqui-TPSs. Among three PnTPSs, the transcript level of PnCPS was the highest, correlating with the predominant ß-caryophyllene biosynthesis in the peppercorn. The products and rearranged products of three PnTPSs could account for about a half of the sesquiterpenes in number found in unripe peppercorn.

Decreased expression of VLDLR is inversely correlated with miR-200c in human colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers and has a high rate of morbidity and mortality worldwide. Very-low-density-lipoprotein receptor (VLDLR), a member of the low-density-lipoprotein receptor (LDLR) superfamily, is a multifunctional receptor that regulates cellular signaling by binding numerous ligands. Several studies reported the altered expression of VLDLR and suggested that VLDLR may play a critical role in tumor development by affecting cell proliferation and metastasis. However, the function of VLDLR and regulation of its expression by miRNAs have not been investigated in CRC. In the present study, we investigated the expression of VLDLR in CRC patients and found it to be significantly decreased in tumors in comparison with paired adjacent non-tumor tissues. Moreover, VLDLR over-expression inhibited the proliferation and migration of CRC cells. We also found that VLDLR expression was negatively regulated by miR-200c in CRC cells and that their expression levels were inversely correlated in CRC patients. These data suggest that VLDLR down-regulation mediated by the increased expression of miR-200c may be involved in the development of CRC.

Ultrafast and Efficient Transport of Hot Plasmonic Electrons by Graphene for Pt Free, Highly Efficient Visible-Light Responsive Photocatalyst.

We report that reduced graphene-coated gold nanoparticles (r-GO-AuNPs) are excellent visible-light-responsive photocatalysts for the photoconversion of CO2 into formic acid (HCOOH). The wavelength-dependent quantum and chemical yields of HCOOH shows a significant contribution of plasmon-induced hot electrons for CO2 photoconversion. Furthermore, the presence and reduced state of the graphene layers are critical parameters for the efficient CO2 photoconversion because of the electron mobility of graphene. With an excellent selectivity toward HCOOH (>90%), the quantum yield of HCOOH using r-GO-AuNPs is 1.52%, superior to that of Pt-coated AuNPs (quantum yield: 1.14%). This indicates that r-GO is a viable alternative to platinum metal. The excellent colloidal stability and photocatalytic stability of r-GO-AuNPs enables CO2 photoconversion under more desirable reaction conditions. These results highlight the role of reduced graphene layers as highly efficient electron acceptors and transporters to facilitate the use of hot electrons for plasmonic photocatalysts. The femtosecond transient spectroscopic analysis also shows 8.7 times higher transport efficiency of hot plasmonic electrons in r-GO-AuNPs compared with AuNPs.

Control of dental-derived induced pluripotent stem cells through modified surfaces for dental application.

OBJECTIVE: The aim of this study is to investigate the behaviour of iPSc derived from dental stem cells in terms of initial adhesion, differentiation potential on differently surface-treated titanium disc. MATERIALS AND METHODS: iPSc derived from human gingival fibroblasts (hGFs) were established using 4-reprogramming factors transduction with Sendai virus. The hGF-iPSc established in this study exhibited the morphology and growth properties similar to human embryonic stem (ES) cells and expressed pluripotency makers. Alkaline Phosphatase (AP) staining, Embryoid Body (EB) formation and in vitro differentiation and karyotyping further confirmed pluripotency of hGF-iPSc. Then, hGF-iPSc were cultured on machined- and Sandblasted and acid etched (SLA)-treated titanium discs with osteogenic induction medium and their morphological as well as quantitative changes according to different surface types were investigated using Alizrin Red S staining, Scanning electron microscopy (SEM), Flow cytometry and RT-PCR. RESULTS: Time-dependent and surface-dependent morphological changes as well as quantitative change in osteogenic differentiation of hGF-iPSc were identified and osteogenic gene expression of hGF-iPSc cultured on SLA-treated titanium disc found to be greater than machined titanium disc, suggesting the fate of hGF-iPSc may be determined by the characteristics of surface to which hGF-iPSc first adhere. CONCLUSIONS: iPSc derived from dental stem cell can be one of the most promising and practical cell sources for personalized regenerative dentistry and their morphological change as well as quantitative change in osteogenic differentiation according to different surface types may be further utilized for future clinical application incorporated with dental implant.

Effect of Serial Use of Bone Morphogenetic Protein 2 and Fibroblast Growth Factor 2 on Periodontal Tissue Regeneration.

PURPOSE: This study evaluates the synergistic effect of serial application of bone morphogenetic protein 2 (BMP2) and fibroblast growth factor 2 (FGF2) on both new bone formation and periodontal tissue regeneration using 1-wall intrabony defect in mongrel dogs. MATERIALS AND METHODS: One-wall defects were created at the mesial aspect of the mandibular first molars of 6 male mongrel dogs. Each mandibular defect received 1 of the 2 experimental treatments randomly (BMP2 or BMP2 + FGF2), and it was allowed to heal for either 4 or 8 weeks postoperatively. Histologic and histomorphometric analyses were performed for the evaluation of the overall healing patterns of new bone formation and periodontal tissue regeneration. RESULTS: The results showed that after 8 weeks, serial application of BMP2 and FGF2 significantly improved the periodontal tissue regeneration, whereas application of BMP2 only showed greater new bone formation after 4 weeks. CONCLUSIONS: The serial application of BMP2 and FGF2 may have synergistic effects on periodontal tissue regeneration over time.

Incidence and Mortality after Distal Radius Fractures in Adults Aged 50 Years and Older in Korea.

The purpose of this study was to assess the incidence and mortality of distal radius fracture among patients 50 years of age and older with diagnosis code (ICD10; S52.5, S52.6) and treatment code using a nationwide claims database from 2008 to 2012. All patients were followed using patient identification code to identify deaths. Standardized mortality ratios (SMRs) of distal radius fracture were calculated based on age and gender-specific rates in the entire Korean population. The number of distal radius fractures increased by 54.2% over the 5-year study (48,145 in 2008 and 74,240 in 2012). The incidence of distal radius fracture increased from 367.4/100,000 in 2008 to 474.1/100,000 in 2012. The cumulative mortality rate over the first 12 months after distal radius fracture was decreased from 2.0% (968/48,145) in 2008 to 1.4% (1,045/74,240) in 2012. The mean year mortality over 5 years in men (2.6%, 1,279/50,128) over the first 12 months was 1.7-times higher than in women (1.5%, 3,952/257,045). The mean of SMR of distal radius fracture at 1 year post-fracture was 1.45 in men and 1.17 in women. This study using a nationwide database demonstrates that the distal radius fractures are increasing with a decreasing mortality in Korea.

Trends of Incidence, Mortality, and Future Projection of Spinal Fractures in Korea Using Nationwide Claims Data.

Spinal fractures have been recognized as a major health concern. Our purposes were to evaluate the trends in the incidence and mortality of spinal fractures between 2008 and 2012 and predict the number of spinal fractures that will occur in Korea up to 2025, using nationwide data from the National Health Insurance Service (NHIS). A nationwide data set was evaluated to identify all new visits to medical institutes for spinal fractures in men and women aged 50 years or older between 2008 and 2012. The incidence, mortality rates and estimates of the number of spinal fractures were calculated using Poisson regression. The number of spinal fractures increased over the time span studied. Men and women experienced 14,808 and 55,164 vertebral fractures in 2008 and 22,739 and 79,903 in 2012, respectively. This reflects an increase in the incidence of spinal fractures for both genders (men, 245.3/100,000 in 2008 and 312.5/100,000 in 2012; women, 780.6/100,000 in 2008 and 953.4/100,000 in 2012). The cumulative mortality rate in the first year after spinal fractures decreased from 8.51% (5,955/69,972) in 2008 to 7.0% (7,187/102,642) in 2012. The overall standardized mortality ratio (SMR) of spinal fractures at 1 year post-fracture was higher in men (7.76, 95% CI: 7.63-7.89) than in women (4.70, 95% CI: 4.63-4.76). The total number of spinal fractures is expected to reach 157,706 in 2025. The incidence of spinal fractures increased in Korea in the last 5 years, and the socioeconomic burden of spinal fractures will continue to increase in the near future.

p53 signalling mediates acupuncture-induced neuroprotection in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with a selective loss of dopamine (DA) neurons in the substantia nigra of the midbrain. Recently, it has been demonstrated that acupuncture treatment has protective effects in PD. However, to date, the molecular mechanisms underlying acupuncture's effect on DA neuronal protection are largely unknown. In this study, we report that p53 signalling mediates the protective effects of acupuncture treatment in a mouse model of PD. We found that the acupuncture treatment in the mouse PD model results in significant recovery to the normal in the context of behaviour and molecular signatures. We found that the gene network associated with p53 signalling is closely involved in the protective effects of acupuncture treatment in PD. Consistent with this idea, we demonstrated that specific knockout of the p53 gene in the midbrain DA neurons abrogates the acupuncture induced protective effects in the mouse model of PD. Thus, these data suggest that p53 signalling mediates the protective effects of acupuncture treatment in PD.

Wear behavior of human enamel against lithium disilicate glass ceramic and type III gold.

STATEMENT OF PROBLEM: The wear behavior of human enamel that opposes different prosthetic materials is still not clear. PURPOSE: The purpose of this in vitro study was to investigate and compare the friction and wear behavior of human tooth enamel that opposes 2 indirect restorative materials: lithium disilicate glass ceramic and Type III gold. MATERIAL AND METHODS: Friction-wear tests on human enamel (n=5) that opposes lithium disilicate glass ceramic (n=5) and Type III gold (n=5) were conducted in a ball-on-flat configuration with a reciprocating wear testing apparatus. The wear pairs were subjected to a normal load of 9.8 N, a reciprocating amplitude of approximately 200 µm, and a reciprocating frequency of approximately 1.6 Hz for up to 1100 cycles per test under distilled water lubrication. The frictional force of each cycle was recorded, and the corresponding friction coefficient for different wear pairs was calculated. After wear testing, the wear scars on the enamel specimens were examined under a scanning electron microscope. RESULTS: Type III gold had a significantly lower steady-state friction coefficient (P=.009) and caused less wear damage on enamel than lithium disilicate glass ceramic. Enamel that opposed lithium disilicate glass ceramic exhibited cracks, plow furrows, and surface loss, which indicated abrasive wear as the prominent wear mechanism. In comparison, the enamel wear scar that opposed Type III gold had small patches of gold smear adhered to the surface, which indicated a predominantly adhesive wear mechanism. CONCLUSIONS: A lower friction coefficient and better wear resistance were observed when human enamel was opposed by Type III gold than by lithium disilicate glass ceramic in vitro.

Adult Child Financial Disadvantage and the Cognitive Trajectories among Older Parents in the United States.

OBJECTIVES: Adult child socioeconomic status (SES) has been identified as a predictor of older parents' cognitive aging. However, studies have primarily relied on educational attainment as the sole measure of adult child SES. We evaluated the relationship between adult children's financial disadvantage and cognitive outcomes of older parents in the United States. METHODS: We used data from U.S. Health and Retirement Study (2000-2014, n = 15,053 respondents > 50 years with at least one adult child). Adult child financial disadvantage was measured with three indicators of extremely low income, unemployment, and lack of home ownership. We used linear mixed models to estimate the association between adult child financial disadvantage and the rate of decline in verbal memory scores, controlling for respondents' socio-demographic characteristics. RESULTS: Having at least one adult child (vs. no adult children) with extremely low income was found to be associated with lower verbal memory (b = -0.041, 95% CI: -0.043, -0.039) at baseline. There was a small but significant association with the rate of decline in verbal memory z-scores (b = 0.004, 95% CI: 0.000, 0.008) and some evidence of heterogeneity by parent gender, marital status, and SES. DISCUSSION: Offspring financial disadvantage may be influential for older parents' initial level of memory function, although evidence of associations with memory decline was weak. Public policy interventions aimed at improving the economic conditions of adult children may indirectly benefit the late-late cognitive performance of disadvantaged parents.

State home and community-based services expenditures and unmet care needs in the United States: Has everyone benefitted equally?

OBJECTIVE: To test whether the impacts of Medicaid's Home and Community-Based Services (HCBS) expenditures have been equitable. DATA SOURCES AND STUDY SETTING: This is a secondary data analysis. We linked annual data on state-level Medicaid HCBS expenditures with individual data from U.S. Health and Retirement Study (HRS; 2006-2016). STUDY DESIGN: We evaluated the association between state-level HCBS expenditure quartiles and the risk of experiencing challenges in basic or instrumental activities of daily living (I/ADLs) without assistance (unmet needs for care). We fitted generalized estimating equations (GEE) with a Poisson distribution, log link function, and an unstructured covariance matrix. We controlled demographics, time, and place-based fixed effects and estimated models stratified by race and ethnicity, gender, and urbanicity. We tested the robustness of results with negative controls. DATA COLLECTION/EXTRACTION METHODS: Our analytic sample included HRS Medicaid beneficiaries, aged 55+, who had difficulty with ≥1 I/ADL (n = 2607 unique respondents contributing 4719 person-wave observations). PRINCIPAL FINDINGS: Among adults with IADL difficulty, higher quartiles of HCBS expenditure (vs. the lowest quartile) were associated with a lower overall prevalence of unmet needs for care (e.g., Prevalence Ratio [PR], Q4 vs. Q1: 0.91, 95% CI: 0.84-0.98). This protective association was concentrated among non-Hispanic white respondents (Q4 vs. Q1: 0.82, 95% CI: 0.73-0.93); estimates were imprecise for Hispanic individuals and largely null for non-Hispanic Black participants. We found no evidence of heterogeneity by gender or urbanicity. Negative control robustness checks indicated that higher quartiles of HCBS expenditure were not associated with (1) the risk of reporting I/ADL difficulty among 55+ Medicaid beneficiaries, and (2) the risk of unmet care needs among non-Medicaid beneficiaries. CONCLUSION: The returns to higher state-level HCBS expenditures under Medicaid for older adults with I/ADL disability do not appear to have been equitable by race and ethnicity.

Associations between Osteosarcopenia and Falls, Fractures, and Frailty in Older Adults: Results From the Canadian Longitudinal Study on Aging (CLSA).

OBJECTIVE: To explore if older adults with osteosarcopenia are at a greater risk of falls, fractures, frailty, and worsening life satisfaction and activities of daily living (ADL) compared to those with normal bone mineral density (BMD) and without sarcopenia. DESIGN: The baseline and 3-year follow-up of a longitudinal study. SETTING AND PARTICIPANTS: Community-dwelling people aged 65 years or older in Canada. METHODS: Caucasian participants 65 years or older that completed the Canadian Longitudinal Study on Aging (CLSA) 2015 baseline interview, physical measurements and 3-year follow-up were included. Osteopenia/osteoporosis was defined as BMD T score below -1 SD according to the World Health Organization, and sarcopenia was defined as low grip strength and/or low gait speed according to the Sarcopenia Definition Outcomes Consortium. Osteosarcopenia was defined as the coexistence of osteopenia/osteoporosis and sarcopenia. Self-reported incident falls and fractures in the last 12 months before the 3-year follow-up were measured. Frailty was assessed through the Rockwood Frailty Index (FI); life satisfaction through the Satisfaction With Life Scale (SWLS); and ADL through the Older American Resources and Services modules. Multivariable logistic and linear regression, including subgroup analyses by sex, were conducted. RESULTS: The sample of 8888 participants (49.1% females) had a mean age (SD) of 72.7 (5.6) years. At baseline, neither osteopenia/osteoporosis nor sarcopenia (reference group) was present in 30.1%, sarcopenia only in 18.4%, osteopenia/osteoporosis only in 29.2%, and osteosarcopenia in 22.3%. Osteosarcopenia was significantly associated with incident falls and fractures in males [adjusted odds ratio (aOR), 1.90, 95% CI 1.15, 3.14, and aOR 2.60, 95% CI 1.14, 5.91, respectively] compared to males without osteopenia/osteoporosis or sarcopenia. Participants with osteosarcopenia had worsening ADL of 0.110 (estimated ß coefficient 0.110, 95% CI 0.029, 0.192) and a decrease in their SWLS by 0.660 (estimated ß coefficient -0.660, 95% CI -1.133, -0.187), compared to those without. Osteosarcopenia was not associated with frailty for both males and females. CONCLUSIONS AND IMPLICATIONS: Osteosarcopenia was associated with self-reported incident falls and fractures in males and worse life satisfaction and ADL for all participants. Assessing and identifying osteosarcopenia is essential for preventing falls and fractures. Furthermore, it improves life satisfaction and ADL.

Correction: Associations between Social Isolation Index and changes in grip strength, gait speed, bone mineral density (BMD), and self-reported incident fractures among older adults: Results from the Canadian Longitudinal Study on Aging (CLSA).

[This corrects the article DOI: 10.1371/journal.pone.0292788.].

Scalable CIGS Solar Cells Employing a New Device Design of Nontoxic Buffer Layer and Microgrid Electrode.

The efficiency of copper indium gallium selenide (CIGS) solar cells that use transparent conductive oxide (TCO) as the top electrode decreases significantly as the device area increases owing to the poor electrical properties of TCO. Therefore, high-efficiency, large-area CIGS solar cells require the development of a novel top electrode with high transmittance and conductivity. In this study, a microgrid/TCO hybrid electrode is designed to minimize the optical and resistive losses that may occur in the top electrode of a CIGS solar cell. In addition, the buffer layer of the CIGS solar cells is changed from the conventional CdS buffer to a dry-processed wide-band gap ZnMgO (ZMO) buffer, resulting in increased device efficiency by minimizing parasitic absorption in the short-wavelength region. By optimizing the combination of ZMO buffer and the microgrid/TCO hybrid electrode, a device efficiency of up to 20.5% (with antireflection layers) is achieved over a small device area of 5 mm × 5 mm (total area). Moreover, CIGS solar cells with an increased device area of up to 20 mm × 70 mm (total area) exhibit an efficiency of up to 19.7% (with antireflection layers) when a microgrid/TCO hybrid electrode is applied. Thus, this study demonstrates the potential for high-efficiency, large-area CIGS solar cells with novel microgrid electrodes.

Unpacking the Broad Landscape of Intraoperative Stressors for Clinical Personnel: A Mixed-Methods Systematic Review.

Purpose: The main goals of this mixed-methods systematic review are to identify what types of intraoperative stressors for operating room personnel have been reported in collected studies and examine the characteristics of each intraoperative stressor. Methods: With a systematic literature search, we retrieved empirical studies examining intraoperative stress published between 2010 and 2020. To synthesize findings, we applied two approaches. First, a textual narrative synthesis was employed to summarize key study information of the selected studies by focusing on surgical platforms and study participants. Second, a thematic synthesis was employed to identify and characterize intraoperative stressors and their subtypes. Results: Ninety-four studies were included in the review. Regarding the surgical platforms, the selected studies mainly focused on minimally invasive surgery and few studies examined issues around robotic surgery. Most studies examined intra-operative stress from surgeons' perspectives but rarely considered other clinical personnel such as nurses and anesthetists. Among seven identified stressors, technical factors were the most frequently examined followed by individual, operating room environmental, interpersonal, temporal, patient, and organizational factors. Conclusion: By presenting stressors as multifaceted elements affecting collaboration and interaction between multidisciplinary team members in the operating room, we discuss the potential interactions between stressors which should be further investigated to build a safe and efficient environment for operating room personnel.

Requirements for anti-aquaporin 5 autoantibody production in a mouse model.

Several oral bacteria, including Prevotella melaninogenica (Pm), have aquaporin (AQP) proteins homologous to human AQP5, a major water channel protein targeted in Sjogren's syndrome. This study aimed to understand the antigenic characteristics that induce autoantibodies against an AQP5 "E" epitope (AQP5E) in a mouse model using C57BL/6 mice. Immunization with a PmE-L peptide derived from Pm AQP, which contains amino acid mismatches both at the B- and T-cell epitopes, efficiently induced anti-AQP5E autoantibodies accompanied by increased germinal center (GC) B and follicular helper T cells in the draining lymph nodes. However, PmE, a peptide lacking a T-cell epitope, and AQP5E-L, an AQP5-derived self-peptide, hardly induced either anti-AQP5E autoantibodies or GC responses. Surprisingly, OTII-AQP5E, a peptide that replaced the self T-cell epitope of AQP5E-L with an ovalbumin-derived foreign T-cell epitope, was not any better than AQP5E-L in the induction of anti-AQP5E autoantibodies and GC response, despite the substantial expansion of CD4+ T cells and production of anti-OTII-AQP5E antibodies. The complex of biotinylated PmE-L peptide and highly immunogenic streptavidin (SA) induced a strong extrafollicular B-cell response skewed toward the expansion of SA-specific B cells. However, the expansion of AQP5E-specific GC B cells was limited, resulting in the inefficient induction of anti-AQP5E autoantibodies. Collectively, our results have demonstrated that anti-AQP5E autoantibody production is only allowed when foreign B- and T-cell epitopes drive a strong GC response of AQP5E-specific B cells for affinity maturation. This study helps explain why cross-reactive anti-AQP5 autoantibodies are not produced during the immune response to Pm in most healthy people.

Associations between Social Isolation Index and changes in grip strength, gait speed, bone mineral density (BMD), and self-reported incident fractures among older adults: Results from the Canadian Longitudinal Study on Aging (CLSA).

BACKGROUND: The aim is to investigate whether social isolation and loneliness are associated with changes in grip strength, gait speed, BMD, and fractures. METHODS: Canadian Longitudinal Study on Aging (CLSA) Comprehensive Cohort participants aged 65 years and older at baseline (2012-2015) who completed the three-year follow-up interview (2015-2018) were included in this analysis (n = 11,344). Social isolation and loneliness were measured using the CLSA social isolation index (CLSA-SII, range 0-10). We calculated absolute and percent change in grip strength (kg) and gait speed (m/s) and annualized absolute (g/cm2) and percent change in femoral neck and total hip BMD during the three-year follow-up. Self-reported incident fractures of all skeletal sites in the previous 12 months were measured at three-year follow-up. Multivariable analyses were conducted. Odd ratio (OR) and 95% confidence interval (CI) are reported. RESULTS: The mean age (standard deviation [SD]) was 72.9 (5.6) years and 49.9% were female. The mean (SD) of CLSA-SII at baseline was 3.5 (1.4). Mean absolute and percentage change (SD) in grip strength (kg) and gait speed (m/s) were -1.33 (4.60), -3.02% (16.65), and -0.05 (0.17), -3.06% (19.28) during the three-year follow-up, respectively. Mean annualized absolute (g/cm2) and percentage change (SD) in femoral neck and total hip BMD were -0.004 (0.010), -0.47% (1.43) and -0.005 (0.009), -0.57% (1.09), respectively. 345 (3.1%) participants had incident fractures. As CLSA-SII increased (per one unit change), participants had 1.13 (adjusted OR 1.13, 95% CI 1.01-1.27) times greater odds for incident fractures. The interaction term between the CLSA-SII and centre for epidemiology studies depression 9 scale (CES-D 9) for self-reported incident fractures was shown (interaction OR 1.02, 95% CI 1.00-1.04). CONCLUSIONS: Socially isolated and lonely older adults were more likely to have had incident fractures, but social isolation was not associated with the three-year changes in grip strength, gait speed, or BMD.