Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging.

To systematically characterize the loss of tissue integrity and organ dysfunction resulting from aging, we produced an in-depth spatial transcriptomic profile of nine tissues in male mice during aging. We showed that senescence-sensitive spots (SSSs) colocalized with elevated entropy in organizational structure and that the aggregation of immunoglobulin-expressing cells is a characteristic feature of the microenvironment surrounding SSSs. Immunoglobulin G (IgG) accumulated across the aged tissues in both male and female mice, and a similar phenomenon was observed in human tissues, suggesting the potential of the abnormal elevation of immunoglobulins as an evolutionarily conserved feature in aging.

Decoding aging-dependent regenerative decline across tissues at single-cell resolution.

Regeneration across tissues and organs exhibits significant variation throughout the body and undergoes a progressive decline with age. To decode the relationships between aging and regenerative capacity, we conducted a comprehensive single-cell transcriptome analysis of regeneration in eight tissues from young and aged mice. We employed diverse analytical models to study tissue regeneration and unveiled the intricate cellular and molecular mechanisms underlying the attenuated regenerative processes observed in aged tissues.

SIRT2 counteracts primate cardiac aging via deacetylation of STAT3 that silences CDKN2B.

Aging is a major risk factor contributing to pathophysiological changes in the heart, yet its intrinsic mechanisms have been largely unexplored in primates. In this study, we investigated the hypertrophic and senescence phenotypes in the hearts of aged cynomolgus monkeys as well as the transcriptomic and proteomic landscapes of young and aged primate hearts. SIRT2 was identified as a key protein decreased in aged monkey hearts, and engineered SIRT2 deficiency in human pluripotent stem cell-derived cardiomyocytes recapitulated key senescence features of primate heart aging.

Single-nucleus transcriptomics reveals a gatekeeper role for FOXP1 in primate cardiac aging.

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age.

Heterochronic parabiosis induces stem cell revitalization and systemic rejuvenation across aged tissues.

The young circulatory milieu capable of delaying aging in individual tissues is of interest as rejuvenation strategies, but how it achieves cellular- and systemic-level effects has remained unclear. Here, we constructed a single-cell transcriptomic atlas across aged tissues/organs and their rejuvenation in heterochronic parabiosis (HP), a classical model to study systemic aging. In general, HP rejuvenated adult stem cells and their niches across tissues.

Vibration Property of a Cryogenic Optical Resonator within a Pulse-Tube Cryostat.

Cryogenic ultrastable laser cavities push laser stability to new levels due to their lower thermal noise limitation. Vibrational noise is one of the major obstacles to achieve a thermal-noise-limited cryogenic ultrastable laser system. Here, we carefully analyze the vibrational noise contribution to the laser frequency.

A human circulating immune cell landscape in aging and COVID-19.

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19.

Caloric Restriction Reprograms the Single-Cell Transcriptional Landscape of Rattus Norvegicus Aging.

Aging causes a functional decline in tissues throughout the body that may be delayed by caloric restriction (CR). However, the cellular profiles and signatures of aging, as well as those ameliorated by CR, remain unclear. Here, we built comprehensive single-cell and single-nucleus transcriptomic atlases across various rat tissues undergoing aging and CR.

Ectopic hTERT expression facilitates reprograming of fibroblasts derived from patients with Werner syndrome as a WS cellular model.

The induced pluripotent stem cell (iPSC) technology has provided a unique opportunity to develop disease-specific models and personalized treatment for genetic disorders, and is well suitable for the study of Werner syndrome (WS), an autosomal recessive disease with adult onset of premature aging caused by mutations in the RecQ like helicase (WRN) gene. WS-derived fibroblasts were previously shown to be able to generate iPSCs; however, it remains elusive how WS-derived iPSCs behave and whether they are able to mimic the disease-specific phenotype. The present study was designed to address these issues.

Vitamin C alleviates aging defects in a stem cell model for Werner syndrome.

Werner syndrome (WS) is a premature aging disorder that mainly affects tissues derived from mesoderm. We have recently developed a novel human WS model using WRN-deficient human mesenchymal stem cells (MSCs). This model recapitulates many phenotypic features of WS.

Pressure-induced K-Λ crossing in monolayer WSe2.

The energy band structures and related room temperature exciton transitions of monolayer and bilayer tungsten diselenide (WSe2) are investigated using photoluminescence (PL) spectra under hydrostatic pressure up to 5.42 GPa. For monolayer WSe2, it is found that the conduction band Λ valley is 70 ± 30 meV higher than the K valley at zero pressure, and the K-Λ valley crossover happens at a pressure of approximately 2.

B cells biology in systemic lupus erythematosus-from bench to bedside.

Systemic lupus erythematosus (SLE) is a debilitating autoimmune disease that can involve multi-organs. B cells play a central role in the immunopathogenesis via antibody-dependent and antibody-independent ways. Excessive autoantibodies production, hyperresponsiveness and prolonged survival of autoreactive B cells are characteristics of SLE.

Defective PTEN regulation contributes to B cell hyperresponsiveness in systemic lupus erythematosus.

PTEN regulates normal signaling through the B cell receptor (BCR). In systemic lupus erythematosus (SLE), enhanced BCR signaling contributes to increased B cell activity, but the role of PTEN in human SLE has remained unclear. We performed fluorescence-activated cell sorting analysis in B cells from SLE patients and found that all SLE B cell subsets, except for memory B cells, showed decreased expression of PTEN compared with B cells from healthy controls.

Icaritin exhibits anti-inflammatory effects in the mouse peritoneal macrophages and peritonitis model.

Icaritin, an intestinal metabolite of prenylflavonoids from Herba Epimedii, has been known to regulate many cellular processes. The purpose of this study was to investigate the protective effects of icaritin on inflammation in lipopolysaccharide (LPS) stimulated mouse peritoneal macrophages in vitro and zymosan induced peritonitis model in vivo. The release of Nitric oxide (NO) was measured by a Griess reagent system.

Topographical and biological evidence revealed FTY720-mediated anergy-polarization of mouse bone marrow-derived dendritic cells in vitro.

Abnormal inflammations are central therapeutic targets in numerous infectious and autoimmune diseases. Dendritic cells (DCs) are involved in these inflammations, serving as both antigen presenters and proinflammatory cytokine providers. As an immuno-suppressor applied to the therapies of multiple sclerosis and allograft transplantation, fingolimod (FTY720) was shown to affect DC migration and its crosstalk with T cells.

Bererine induces peripheral lymphocytes immune regulations to realize its neuroprotective effects in the cerebral ischemia/reperfusion mice.

Previous studies have shown that Bererine (Ber) has significant neuroprotective effects and the present article aimed to investigate its mechanism from the aspect of peripheral immune system. We evaluated the effects of Ber 24 h after cerebral ischemia/reperfusion (I/R) on histologic injury in BALB/C mice and NOD-SCID (severe combined immunodeficient) mice lacking T and B cells. Infarct volume, neurological scores and brain water content were strikingly reduced by Ber in BALB/C mice versus NOD-SCID mice.

FTY720 mediates activation suppression and G(0)/G (1) cell cycle arrest in a concanavalin A-induced mouse lymphocyte pan-activation model.

Objective: FTY720 is a potent drug for multiple sclerosis treatment. To biologically address its possible applications to more generalized diseases with aberrant inflammation, we are testing whether FTY720 can function as a lymphocyte cell cycle blocker and activation suppressor via a concanavalin A (ConA)-mediated mouse lymphocyte pan-activation model.

Methods: Mouse lymphocytes were obtained from lymph nodes and subjected to ConA and/or FTY720 treatment.

Calcium influx blocked by SK&F 96365 modulates the LPS plus IFN-γ-induced inflammatory response in murine peritoneal macrophages.

A rise in intracellular Ca(2+) ([Ca(2+)](i)) is crucial for the activation of macrophages, however, the mechanisms and consequences of this [Ca(2+)](i) increase remain unclear. This study investigated the role of calcium in mouse peritoneal macrophages stimulated with LPS plus IFN-γ by using the store-operated Ca(2+) channel (SOCC) blocker SK&F 96365. Our results showed that SK&F 96365 pretreatment significantly inhibited the elevation of [Ca(2+)](i) induced by ionomycin, thapsigargin, and LPS plus IFN-γ, respectively.

The anti-inflammatory effect of the SOCC blocker SK&F 96365 on mouse lymphocytes after stimulation by Con A or PMA/ionomycin.

SK&F 96365, 51-(beta-[3-(p-methoxyphenyl)-propyloxy]-p-methoxyphenethyl)-1H-imidazole hydrochloride, has emerged as a useful pharmacological tool in the study of store-operated Ca²⁺ entry (SOCE). But the precise molecular mechanism and effect of SK&F 96365 on mouse lymphocytes are still not well determined. This study investigated the pharmacological profile of SK&F 96365 on mouse lymphocytes stimulated by mitogen concanavalin A (Con A) or by a combination of a protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA) and a calcium ionophore, ionomycin in vitro.

Anti-inflammatory and immunosuppressive effect of phloretin.

This study investigated the effect of phloretin (Ph) on the proliferation, activation, and cell-cycle distribution of mouse T lymphocytes and NO production and phagocytosis of macrophages. Carboxyfluorescein diacetatesuccinimidyl ester (CFDA-SE) staining plus flow cytometry assay was employed to obtain the proliferation-related index (PI) of lymphocytes. The expression levels of CD69 and CD25 on T lymphocytes stimulated with Con A were evaluated with flow cytometry after staining with fluorescent monoclonal antibody.