Cohort profile: Beijing Healthy Aging Cohort Study (BHACS).

The Beijing Healthy Aging Cohort Study (BHACS) was established to supplement the limited data of a large representative cohort of older people based on the general population and was designed to evaluate the prevalence, incidence, and natural history of cognitive decline, functional disability, and conventional vascular risk factors. The aim was to determine the evolution of these conditions by estimating the rates and determinants of progression and regression to adverse outcomes, including dementia, cardiovascular events, cancer, and all-cause death. It can therefore provide evidence to help policy makers develop better policies to promote healthy aging in China. BHACS consisted of three cohorts (BLSA, CCHS-Beijing, and BECHCS) in Beijing with a total population of 11 235 (6281 in urban and 4954 in rural areas) and an age range of 55 years or older (55-101 years) with a mean age of 70.35 ± 7.71 years (70.69 ± 7.62 years in urban and 69.92 ± 7.80 years in rural areas). BHACS-BLSA conducted the baseline survey in 2009 with a multistage stratification-random clustering procedure for people aged 55 years or older; BHACS-CCHS-Beijing conducted the baseline survey in 2013-2015 with a stratified multistage cluster random sampling method for people aged 55 years or older; and BHACS-BECHCS conducted the baseline survey in 2010-2014 with two-stage cluster random sampling method for people aged 60 years or older. Data were collected through questionnaires, physical measurements, and laboratory analyses. Topics covered by BHACS include a wide range of physical and mental health indicators, lifestyles and personal, family, and socio-economic determinants of health. There are no immediate plans to make the cohort data freely available to the public, but specific proposals for further collaboration are welcome. For further information and collaboration, please contact the corresponding author Yao He (e-mail: yhe301@x263.net).

Smoking cessation and mortality risk reduction in older adults with long-term smoking history.

BACKGROUND: The association between smoking cessation and decreased mortality existed among former smokers has been well documented. However, evidence is limited for smokers with long-term exposure. This study aims to quantify the association between smoking cessation and mortality by years since quitting in older adults with long-term smoking history. METHODS: Data from Beijing Healthy Aging Cohort Study (BHACS), conducted among communities aged over 55 years old at recruitment, were collected via questionnaire between July 2009 and September 2015 and followed up for all-cause and cancer mortality until March 2021. Self-reported smoking status and years since quitting were collected at baseline. Cox proportional hazards models were used to examine the association between smoking cessation and all-cause and cancer mortality. RESULTS: A total of 11 235 participants (43.9% male) were included, with a mean age of 70.35 (SD 7.71) years. Former smokers comprised 31.7% of the cohort, with a median smoking duration of 43 (IQR: 34-50) years. During 71 573 person-years of follow-up, there were 1 617 deaths (14.4% of the total cohort), of which 872 (17.7%) occurred among male participants. Compared with never smokers, HR (95%CI) for participants who current smoked was 2.898 (2.092-4.013); quit smoking less than 10 years (medians [quartiles] 4 [1, 7] years) before recruitment was 2.738(1.972-3.802); 10 to 20 years (16 [13, 20] years), 1.807(1.286-2.540); and 20 years or more (30 [25, 37] years), 1.293(0.981-1.705). The risk of all-cause and cancer mortality decreased gradually over years since quitting. Quitting less than 10 years, 10 to 20 years and 20 years or more, former smokers avoided an estimated 8.4%, 57.5% and 84.6% of excess all-cause mortality associated with current smoking, respectively. The association between smoking cessation and decreased mortality was observed among former smokers regardless of smoking history. CONCLUSIONS: In this study, current smoking was associated with nearly triple the mortality risk compared to never smoking. Smoking cessation, even after a long-term smoking history, was associated with significant decreases in the relative excess mortality linked to continuing smoking. The association were more pronounced in men.

Precursor Induced Assembly of Si Nanoparticles Encapsulated in Graphene/Carbon Matrices and the Influence of Al2 O3 Coating on their Properties as Anode for Lithium-Ion Batteries.

The theoretical capacity of pristine silicon as anodes for lithium-ion batteries (LIBs) can reach up to 4200 mAh g-1 , however, the low electrical conductivity and the huge volume expansion limit their practical application. To address this challenge, a precursor strategy has been explored to induce the curling of graphene oxide (GO) flakes and the enclosing of Si nanoparticles by selecting protonated chitosan as both assembly inducer and carbon precursor. The Si nanoparticles are dispersed first in a slurry of GO by ball milling, then the resulting dispersion is dried by a spray drying process to achieve instantaneous solution evaporation and compact encapsulation of silicon particles with GO. An Al2 O3 layer is constructed on the surface of Si@rGO@C-SD composites by the atomic layer deposition method to modify the solid electrolyte interface. This strategy enhances obviously the electrochemical performance of the Si as anode for LIBs, including excellent long-cycle stability of 930 mAh g-1 after 1000 cycles at 1000 mA g-1 , satisfied initial Coulomb efficiency of 76.7%, and high rate ability of 806 mAh g-1 at 5000 mA g-1 . This work shows a potential solution to the shortcomings of Si-based anodes and provides meaningful insights for constructing high-energy anodes for LIBs.

Quantum Criticality of Liquid-Gas Transition in a Binary Bose Mixture.

Quantum liquid, in the form of a self-bound droplet, is stabilized by a subtle balance between the mean-field contribution and quantum fluctuations. While a liquid-gas transition is expected when such a balance is broken, it remains elusive whether liquid-gas critical points exist in the quantum regime. Here, we study the quantum criticality in a binary Bose mixture undergoing the liquid-gas transition. We show that, beyond a narrow stability window of the self-bound liquid, a liquid-gas coexistence persists, which eventually transits into a homogeneous mixture. Importantly, we identify two distinct critical points where the liquid-gas coexistence terminates. These critical points are characterized by rich critical behaviors in their vicinity, including divergent susceptibility, unique phonon-mode softening, and enhanced density correlations. The liquid-gas transition and the critical points can be readily explored in ultracold atoms confined to a box potential. Our work highlights the thermodynamic approach as a powerful tool in revealing the quantum liquid-gas criticality, and paves the way for further studies of critical phenomena in quantum liquids.

Effect of simvastatin on osteogenesis of the extremity bones in aging rats.

PURPOSE: Simvastatin is a prodrug of the potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. The main purpose of the current study is to assess the accurate function of simvastatin on osteoporosis of extremity bones in aging rats. MATERIALS AND METHODS: Fifty 15-month-old SD rats were divided into five groups (four simvastatin groups and one control group). The rats in four simvastatin groups were fed with different doses of simvastatin (5, 10, 20, and 40 mg/kg/d, respectively) for 3 months, whereas the rats in control group were fed the equal physiological saline. Calcium (Ca), phosphorus (P), and the lipid spectrum in serum were measured. Biochemical markers of bone metabolism, osteocalcin (OC), and tartrate-resistant acid phosphatase (Trap-5b), were analyzed using ELISA. The content of adipocytes in bone marrow was analyzed by histological staining. Finally, the bone quality of the femur and tibia were evaluated using dual-energy X-ray absorptiometry (DEXA), peri-quantity CT (pQCT), and the 3-point bending biomechanical test. RESULTS: Simvastatin reduced serum triglycerides (TG), and 10 mg/kg/d of simvastatin significantly reduced the content of adipocytes in bone marrow compared to the control group. However, statistically significant differences between the simvastatin groups and the control group were not found in the CA, P, OC, Trap-5b, or the evaluation indexes of bone quality from DEXA, pQCT, and biomechanical tests. CONCLUSION: Simvastatin could not prevent osteoporosis of the extremity bones in aging rats.

Healthy and unhealthy low-carbohydrate diets and plasma markers of cardiometabolic risk.

Previous studies have reported inconsistent associations between low-carbohydrate diets (LCD) and plasma lipid profile. Also, there is little evidence on the role of the quality and food sources of macronutrients in LCD in cardiometabolic health. We investigated the cross-sectional associations between LCD and plasma cardiometabolic risk markers in a nationwide representative sample of the US population. Diet was measured through two 24-h recalls. Overall, healthy (emphasising unsaturated fat, plant protein and less low-quality carbohydrates) and unhealthy (emphasising saturated fat, animal protein and less high-quality carbohydrate) LCD scores were developed according to the percentage of energy as total and subtypes of carbohydrate, protein and fat. Linear regression was used to estimate the percentage difference of plasma marker concentrations by LCD scores. A total of 34 785 participants aged 18-85 years were included. After adjusting for covariates including BMI, healthy LCD was associated with lower levels of insulin, homoeostatic model assessment for insulin resistance (HOMA-IR), C-reactive protein (CRP) and TAG, and higher levels of HDL-cholesterol, with the percentage differences (comparing extreme quartile of LCD score) of -5·91, -6·16, -9·13, -9·71 and 7·60 (all Ptrend < 0·001), respectively. Conversely, unhealthy LCD was associated with higher levels of insulin, HOMA-IR, CRP and LDL-cholesterol (all Ptrend < 0·001). Our results suggest that healthy LCD may have positive, whereas unhealthy LCD may have negative impacts on CRP and metabolic and lipid profiles. These findings underscore the need to carefully consider the quality and subtypes of macronutrients in future LCD studies.

Association between time-restricted eating and non-alcoholic fatty liver disease in a nationwide cross-sectional study.

The association between time-restricted eating (TRE) and the risk of non-alcoholic fatty liver disease (NAFLD) is less studied. Moreover, whether the association is independent of physical exercise or diet quality or quantity is uncertain. In this nationwide cross-sectional study of 3813 participants, the timing of food intakes was recorded by 24-h recalls; NAFLD was defined through vibration-controlled transient elastography in the absence of other causes of chronic liver disease. OR and 95 % CI were estimated using logistic regression. Participants with daily eating window of ≤ 8 h had lower odds of NAFLD (OR = 0·70, 95 % CI: 0·52, 0·93), compared with those with ≥ 10 h window. Early (05.00-15.00) and late TRE (11.00-21.00) showed inverse associations with NAFLD prevalence without statistical heterogeneity (Pheterogeneity = 0·649) with OR of 0·73 (95 % CI: 0·36, 1·47) and 0·61 (95 % CI: 0·44, 0·84), respectively. Such inverse association seemed stronger in participants with lower energy intake (OR = 0·58, 95 % CI: 0·38, 0·89, Pinteraction = 0·020). There are no statistical differences in the TRE-NAFLD associations according to physical activity (Pinteraction = 0·390) or diet quality (Pinteraction = 0·110). TRE might be associated with lower likelihood of NAFLD. Such inverse association is independent of physical activity and diet quality and appears stronger in individuals consuming lower energy. Given the potential misclassification of TRE based on one- or two-day recall in the analysis, epidemiological studies with validated methods for measuring the habitual timing of dietary intake are warranted.

Associations of healthful and unhealthful plant-based diets with plasma markers of cardiometabolic risk.

PURPOSE: Plant-based diets, particularly when rich in healthy plant foods, have been associated with a lower risk of type 2 diabetes and cardiovascular disease. However, the impact of plant-based diets that distinguish between healthy and unhealthy plant foods on cardiometabolic biomarkers remains unclear. METHODS: Dietary information was collected by two 24-h recalls among 34,785 adults from a nationwide cross-sectional study. Plasma levels of insulin, C-peptide, glucose, C-reactive protein (CRP), white blood cell (WBC) count, triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) were measured. Linear regression was used to evaluate the percentage difference in plasma marker concentrations by three plant-based diet indices, namely the overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI). RESULTS: Greater hPDI-adherence scores (comparing extreme quartiles) were associated with lower levels of insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), TG/HDL-C ratio, CRP, WBC count, and TG, and higher levels of HDL-C, with the percentage differences of - 14.55, - 15.72, - 11.57, - 14.95, - 5.26, - 7.10, and 5.01, respectively (all Ptrend ≤ 0.001). Conversely, uPDI was associated with higher levels of insulin, C-peptide, HOMA-IR, TG/HDL-C ratio, CRP, WBC count, and TG, but lower HDL-C, with the percentage differences of 13.71, 14.00, 14.10, 10.43, 3.32, 8.00, and - 4.98 (all Ptrend ≤ 0.001), respectively. Overall PDI was only associated with lower levels of CRP and WBC count (all Ptrend ≤ 0.001). CONCLUSION: Our findings suggest that hPDI may have positive, whereas uPDI may have negative impacts on multiple cardiometabolic risk markers, and underscore the need to consider the quality of plant foods in future PDI studies.

Association of cardiovascular health at old age with all-cause mortality: a prospective cohort study in China.

BACKGROUND: Cardiovascular disease has become the leading cause of death worldwide, but there is a lack of data on whether cardiovascular health (CVH) is associated with elderly mortality in China. We investigated the relationship between the ideal CVH score of Chinese elderly and the all-cause mortality. METHODS: The Beijing Elderly Comprehensive Health Cohort Study included a total of 4,499 participants aged 60 years and above. The CVH metric was calculated at baseline and had a score ranging from 0 to 12. The relationship of CVH metrics with all-cause mortality was investigated using Cox proportional hazard regression analysis. The robustness of results was tested using subgroup and sensitivity analysis. RESULTS: The median CVH score among participants was 8.00 (2.00), with only 8.0% scoring 11-12 points. 667 deaths were observed during an average follow-up time of 8.2 years. Participants with a CVH score of 11-12 had a decreased risk of all-cause mortality when compared to those with a CVH score of 0-4(HR = 0.584, 95% CI: 0.373-0.913). Participants had a 7.5% lower risk of all-cause death with each unit higher CVH score (HR = 0.925, 95%CI: 0.885-0.967) with a linearly decreasing trend (P nonlinear = 0.575). The relationships were greater in younger elderly people and stroke patients (P interaction = 0.011 and 0.037. respectively). The consistency of significant trends in sensitivity analysis shows the robustness of association (P trend < 0.001). CONCLUSIONS: Among the Chinese elderly, there was a linear relationship between improving CVH scores and a lower risk of all-cause mortality. Because of the enormous benefits brought by one point, strategies are essential for improving cardiovascular health attainment. TRIAL REGISTRATION: This study was registered at China Clinical Trial Registration Center (ChiCTR2100049866).

T1D patient-derived hematopoietic stem cells are programmed to generate Tph, Tfh, and autoimmunity-associated B cell subsets in human immune system mice.

Interactions between B cells and CD4+ T cells play a central role in the development of Type 1 Diabetes (T1D). Two helper cell subsets, follicular (Tfh) and peripheral (Tph) helper T cells, are increased in patients with T1D but their role in driving B cell autoimmunity is undefined. We used a personalized immune (PI) mouse model to generate human immune systems de novo from hematopoietic stem cells (HSCs) of patients with T1D or from healthy controls (HCs). Both groups developed Tfh and Tph-like cells, and those with T1D-derived immune systems demonstrated increased numbers of Tph-like and Tfh cells compared to HC-derived PI mice. T1D-derived immune systems included increased proportions of unconventional memory CD27-IgD- B cells and reduced proportions of naïve B cells compared to HC PI mice, resembling changes reported for patients with systemic lupus erythematosus. Our findings suggest that T1D HSCs are genetically programmed to produce increased proportions of T cells that promote the development of unconventional, possibly autoreactive memory B cells. PI mice provide an avenue for further understanding of the immune abnormalities that drive autoantibody pathogenesis and T1D.

Dynamic Signatures of Non-Hermitian Skin Effect and Topology in Ultracold Atoms.

The non-Hermitian skin effect (NHSE), the accumulation of eigen-wave functions at boundaries of open systems, underlies a variety of exotic properties that defy conventional wisdom. While the NHSE and its intriguing impact on band topology and dynamics have been observed in classical or photonic systems, their demonstration in a quantum gas system remains elusive. Here we report the experimental realization of a dissipative Aharonov-Bohm chain-non-Hermitian topological model with NHSE-in the momentum space of a two-component Bose-Einstein condensate. We identify signatures of the NHSE in the condensate dynamics, and perform Bragg spectroscopy to resolve topological edge states against a background of localized bulk states. Our Letter sets the stage for further investigation on the interplay of many-body statistics and interactions with the NHSE, and is a significant step forward in the quantum control and simulation of non-Hermitian physics.

A case report of renal calyceal diverticulum with hypertension in children and review of literature.

BACKGROUND: Renal calyx diverticulum refers to a cystic lesion covered with the transitional epithelium in the renal parenchyma. Although there is no clear evidence that calyx diverticulum can cause hypertension, there exists a close association between the two, and there are few related reports. Herein, we reported the case of a child with renal calyx diverticulum complicated with hypertension and summarized the diagnosis and treatment. CASE PRESENTATION: Physical examination of the patient, an 11-year-old child, revealed a left renal cyst with hypertension (155/116 mmHg). There were no related symptoms. Routine urine and blood biochemical examinations showed no abnormalities. Imaging revealed left renal cyst compression causing the hypertension. She underwent renal cyst fluid aspiration and injection of a sclerosing agent into the capsule, but her blood pressure increased again 3 days postoperatively. Color Doppler ultrasonography showed that the size of the left renal cyst was the same as that preoperatively. To further confirm the diagnosis, cystoscopic retrograde ureteropyelography was performed to confirm the diagnosis of renal calyx diverticulum. Subsequently, renal calyceal diverticulum resection and calyx neck enlargement were performed. The operation went smoothly and the blood pressure returned to normal postoperatively. No abnormalities were noted at the 7-month postoperative follow-up. CONCLUSION: There exists an association between renal calyx diverticulum and hypertension. Therefore, hypertension can be considered a surgical indication for renal calyx diverticulum. Moreover, renal calyceal diverticulum in children can be easily misdiagnosed as a renal cyst. Therefore, it is important to be vigilant to prevent a series of complications, such as postoperative urine leakage, in such cases.

Role of the thymus in spontaneous development of a multi-organ autoimmune disease in human immune system mice.

We evaluated the role of the thymus in development of multi-organ autoimmunity in human immune system (HIS) mice. T cells were essential for disease development and the same T cell clones with varying phenotypes infiltrated multiple tissues. De novo-generated hematopoietic stem cell (HSC)-derived T cells were the major disease drivers, though thymocytes pre-existing in grafted human thymi contributed if not first depleted. HIS mice with a native mouse thymus developed disease earlier than thymectomized mice with a thymocyte-depleted human thymus graft. Defective structure in the native mouse thymus was associated with impaired negative selection of thymocytes expressing a transgenic TCR recognizing a self-antigen. Disease developed without direct recognition of antigens on recipient mouse MHC. While human thymus grafts had normal structure and negative selection, failure to tolerize human T cells recognizing mouse antigens presented on HLA molecules may explain eventual disease development. These new insights have implications for human autoimmunity and suggest methods of avoiding autoimmunity in next-generation HIS mice.

Duplex kidney complicated with preoperative inferior nephroblastoma rupture in children: a case report and literature review.

BACKGROUND: We admitted a child with a duplex kidney combined with preoperative rupture of nephroblastoma and used this case to discuss the clinical features and treatment of this disease. CASE PRESENTATION: We retrospectively analyzed the clinical data of a 5-year-old girl with preoperative duplex kidney rupture combined with inferior nephroblastoma who was admitted to the Fourth Hospital of Baotou. In addition, we reviewed the relevant literature. The patient's details were as follows: weight, 17 kg; height, 108 cm; and body surface area, 0.7 m2. Abdominal ultrasound for abdominal pain revealed the presence of a left-sided renal mass; enhanced abdominal computed tomography further confirmed it to be a left-sided duplex kidney measuring approximately 6 × 5 × 5 cm, with a rupture originating from the lower kidney. The PubMed database was searched from 2010 to 2020 for the terms "Wilms' tumor" and "Duplex" and "Wilms' tumor" and "Rupture." The treatment plan was preoperative chemotherapy (vincristine/dactinomycin, VA regimen) + left kidney tumor radical surgery + postoperative chemotherapy (actinomycin-D/VCR/doxorubicin, AVD regimen). Postoperative pathology revealed an International Society of Pediatric Oncology intermediate-risk stage-3 nephroblastoma (mixed type) in the left kidney. Literature review was performed with 71 cases meeting the set criteria with an aim to analyze and summarize the clinical characteristics and treatment of patients with ruptured nephroblastoma and duplex kidney combined with nephroblastoma. CONCLUSIONS: To our knowledge, no previous studies have reported preoperative duplex kidney combined with nephroblastoma rupture. In patients with this condition, preoperative chemotherapy is recommended when the vital signs are stable and tumor resection can be performed after the tumor has shrunk to prevent secondary spread. If the patient's vital signs are unstable, emergency exploratory surgery is needed. If the nephroblastoma rupture is old and limited, surgery can be performed when the tumor size is small.

Reduced positive selection of a human TCR in a swine thymus using a humanized mouse model for xenotolerance induction.

BACKGROUND: Tolerance-inducing approaches to xenotransplantation would be optimal and may be necessary for long-term survival of transplanted pig organs in human patients. The ideal approach would generate donor-specific unresponsiveness to the pig organ without suppressing the patient's normal immune function. Porcine thymus transplantation has shown efficacy in promoting xenotolerance in humanized mice and large animal models. However, murine studies demonstrate that T cells selected in a swine thymus are positively selected only by swine thymic epithelial cells, and therefore, cells expressing human HLA-restricted TCRs may not be selected efficiently in a transplanted pig thymus. This may lead to suboptimal patient immune function. METHODS: To assess human thymocyte selection in a pig thymus, we used a TCR transgenic humanized mouse model to study positive selection of cells expressing the MART1 TCR, a well-characterized human HLA-A2-restricted TCR, in a grafted pig thymus. RESULTS: Positive selection of T cells expressing the MART1 TCR was inefficient in both a non-selecting human HLA-A2- or swine thymus compared with an HLA-A2+ thymus. Additionally, CD8 MART1 TCRbright T cells were detected in the spleens of mice transplanted with HLA-A2+ thymi but were significantly reduced in the spleens of mice transplanted with swine or HLA-A2- thymi. [Correction added on October 15, 2019, after first online publication: The missing superscript values +, -, and bright have been included in the Results section.] CONCLUSIONS: Positive selection of cells expressing a human-restricted TCR in a transplanted pig thymus is inefficient, suggesting that modifications to improve positive selection of cells expressing human-restricted TCRs in a pig thymus may be necessary to support development of a protective human T-cell pool in future patients.

Author Correction: Plumbagin attenuates cancer cell growth and osteoclast formation in the bone microenvironment of mice.

During re-read of our previously article Plumbagin attenuates cancer cell growth and osteoclast formation in the bone microenvironment of micepublished in Acta Pharmacologica Sinica, we were regretted to point out a mistake shown in Fig. 2a. The representative figure chosen to indicate the inhibitory effect of 4 mg/kg of plumbagin treatment at 1 week against MDA-MB-231SArfp cells localization within bone environment was incorrect due to the mishandling in manuscript preparation. Although this correction does not affect the results and conclusion of the paper, all the authors agree on the correction of our negligence as providing the corrected Fig. 2a presented below. We feel sorry and apologize for all the inconvenience it caused.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Lanthanum Chloride Attenuates Osteoclast Formation and Function Via the Downregulation of Rankl-Induced Nf-κb and Nfatc1 Activities.

The biological activities of lanthanum chloride (LaCl3 ) and the molecular mechanisms of action underlying its anti-inflammatory, anti-hyperphosphatemic, and osteoblast-enhancing effects have been studied previously, but less is known about the effects of LaCl3 on osteoclasts. The present study used in vivo and in vitro approaches to explore the effects of LaCl3 on osteoclasts and osteolysis. The results indicated that LaCl3 concentrations that were non-cytotoxic to mouse bone marrow-derived monocytes attenuated receptor activator of nuclear factor-κB ligand (RANKL)-stimulated osteoclastogenesis, bone resorption, mRNA expression of osteoclastogenic genes in these cells, including cathepsin K, calcitonin receptor, and tartrate-resistant acid phosphatase (TRAP). Further, LaCl3 inhibited RANKL-mediated activation of the nuclear factor-κB (NF-κB) signaling pathway, and downregulated mRNA and protein levels of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), and c-fos. In vivo, LaCl3 attenuated titanium (Ti) particle-induced bone loss in a murine calvarial osteolysis model. Histological analyses revealed that LaCl3 ameliorated bone destruction and decreased the number of TRAP-positive osteoclasts in this model. These results demonstrated that LaCl3 inhibited osteoclast formation, function, and osteoclast-specific gene expression in vitro, and attenuated Ti particle-induced mouse calvarial osteolysis in vivo, where the inhibition of NF-κB signaling and downregulation of NFATc1 and c-fos played an important role.

Xenograft tolerance and immune function of human T cells developing in pig thymus xenografts.

Transplantation of xenogeneic thymus tissue allows xenograft tolerance induction in the highly disparate pig-to-mouse model. Fetal swine thymus (SW THY) can support the generation of a diverse human T cell repertoire that is tolerant of the pig in vitro. We demonstrate that SW THY generates all human T cell subsets, including regulatory T cells (Tregs), in similar numbers as fetal human thymus (HU THY) grafts in immunodeficient mice receiving the same human CD34(+) cells. Peripheral T cells are specifically tolerant to the mouse and to the human and porcine donors, with robust responses to nondonor human and pig Ags. Specific tolerance is observed to pig skin grafts sharing the THY donor MHC. SW THY-generated peripheral Tregs show similar function, but include lower percentages of naive-type Tregs compared with HU THY-generated Tregs. Tregs contribute to donor-pig specific tolerance. Peripheral human T cells generated in SW THY exhibit reduced proportions of CD8(+) T cells and reduced lymphopenia-driven proliferation and memory-type conversion, accelerated decay of memory-type cells, and reduced responses to protein Ags. Thus, SW thymus transplantation is a powerful xenotolerance approach for human T cells. However, immune function may be further enhanced by strategies to permit positive selection by autologous HLA molecules.

Geraniin suppresses RANKL-induced osteoclastogenesis in vitro and ameliorates wear particle-induced osteolysis in mouse model.

Wear particle-induced osteolysis and subsequent aseptic loosening remains the most common complication that limits the longevity of prostheses. Wear particle-induced osteoclastogenesis is known to be responsible for extensive bone erosion that leads to prosthesis failure. Thus, inhibition of osteoclastic bone resorption may serve as a therapeutic strategy for the treatment of wear particle induced osteolysis. In this study, we demonstrated for the first time that geraniin, an active natural compound derived from Geranium thunbergii, ameliorated particle-induced osteolysis in a Ti particle-induced mouse calvaria model in vivo. We also investigated the mechanism by which geraniin exerts inhibitory effects on osteoclasts. Geraniin inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, evidenced by reduced osteoclast formation and suppressed osteoclast specific gene expression. Specially, geraniin inhibited actin ring formation and bone resorption in vitro. Further molecular investigation demonstrated geraniin impaired osteoclast differentiation via the inhibition of the RANKL-induced NF-κB and ERK signaling pathways, as well as suppressed the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Collectively, our data suggested that geraniin exerts inhibitory effects on osteoclast differentiation in vitro and suppresses Ti particle-induced osteolysis in vivo. Geraniin is therefore a potential natural compound for the treatment of wear particle induced osteolysis in prostheses failure.