Return to the Best of Bethesda homepage here. Accounting Firm (Local) Winner: Councilor, Buchanan & Mitchell Finalists: Antiques and Vintage Store Winner: My Big Finds Finalists: Auto Dealership Winner: Chevy Chase Acura Finalists: Bike Store Winner: Griffin Cycle Finalists: Children’s Boutique Winner: Rue + Roe Finalists: Commercial Real Estate Firm Winner: AMR Commercial Finalists: Community […]

Best of Bethesda 2026 Readers’ Picks: Food & Drink. Read about the best bagels, brunches, burgers and more in Montgomery County.

Eight people were killed in the collapse of a five-storey residential building in Egypt’s Giza governorate, south of Cairo, local media reported on Thursday. According to news website Ahram Online, which provided the updated toll, rescue teams recovered the body of the last missing person after two days of search and debris-removal operations. The building …

Discover the finches of North America through clear identification tips, habitat use, and behaviors that help with field recognition.

The Tianshan Shengli Tunnel in China, measuring 22.13 km in length and the longest highway tunnel in the world, was officially opened to traffic on Friday. Crossing the central section of the Tianshan Mountains in the Xinjiang Uygur Autonomous Region in northwest China, the tunnel reduces a mountainous journey that previously took several hours to …

An earthquake with a provisional magnitude of 5.6 on the open Richter scale struck Aomori Prefecture in northern Japan in the early hours of Friday, according to the country’s meteorological agency. The tremor occurred at 1:17 a.m. local time off the Pacific coast of Aomori, at a depth of 40 km, with an intensity of …

Silver on Friday surpassed the symbolic threshold of $75 an ounce for the very first time, as precious and industrial metals reach unprecedented highs at year-end, driven in particular by economic and geopolitical uncertainty. Silver climbed to a peak of $75.1515 an ounce (31.1 g) on Friday. Gold also hit a record high at $4,531.04 …

The Japanese government approved on Friday a record budget for the next fiscal year, aimed at financing both increased defense spending and rising social security costs, as persistent inflation continues to weigh on consumption. The budget, totaling 122.3 trillion yen (about $785 billion) for the fiscal year starting on April 1, 2026, allocates around 9 …

Fourteen people were injured in a stabbing attack in a factory in central Japan during which an unspecified liquid was also sprayed, an emergency services official said on Friday (Dec 26). “Fourteen people are subject to transportation by emergency services,” Tomoharu Sugiyama, a firefighting department official in the city of Mishima, Shizuoka region, told AFP. He …

The Istanbul public prosecutor’s office announced on Friday the arrest of nearly thirty figures from Turkish football, including fourteen players and a former official of Istanbul-based club Galatasaray, accused of betting on matches. The wide-ranging investigation by the Istanbul prosecutor, which has shaken Turkish football for several months, had already led in early November to …

Iceland recorded a historic temperature peak on Wednesday, exceeding 19 degrees Celsius, the highest December reading since records began, local media reported on Friday. It was a year‑end that Icelanders will remember for a long time. On 24 December, traditionally associated with snow, cold and ice, Iceland registered a temperature of 19.8°C in the town …

Plus: A perfect, purple way to spend NYE, RIP Jellybean Johnson of the Time, Say She She, Altın Gün, more music news.

A year of devastating cuts, wild uncertainty, and unexpected departures left their marks on the SF scene.

Jumping, Horse Show NFS

A Film by Dalila Droege No More Time Starring Jennifer Harlow, Mark Reeb, Tunde Adebimpe, David Sullivan, w/ Amy Seimetz and Jim Beaver On Digital Platforms Starting December 19th A couple seeks refuge in a remote mountain town to escape a mysterious disease that makes some people disappear and others turn into hateful murderers. As the stakes grow higher and the dangers draw closer,

Crowd Supply recently featured LeafKVM, a compact wireless KVM-over-IP device that provides remote access to computers, servers, and HDMI video sources without requiring software on the target system. It captures HDMI video and audio, emulates USB keyboard, mouse, and storage devices, and streams output directly to a web browser. The hardware platform is based on […]

The NeoEyes NE301 by CamThink is described as a low-power edge AI camera built around STMicroelectronics’ STM32N6 microcontroller. The camera combines on-device neural network inference, a built-in web interface, and modular hardware design aimed at battery-powered and outdoor deployments. The camera is based on the STM32N6570 MCU, which integrates an Arm Cortex-M55 core with Helium […]

Insulin/insulin growth factor signaling is a conserved pathway that regulates lifespan. However, long-lived loss-of-function mutants often produce insulin resistance, slow growth, and impair reproduction. Recently, a gain-of-function mutation in the kinase insert domain (KID) of the Drosophila insulin/IGF receptor was seen to dominantly extend lifespan without impairing insulin sensitivity, growth, or reproduction. This substitution occurs within residues conserved in mammalian insulin receptor (IR) and insulin growth factor-1 receptor (IGF-1R). We produced 2 knock-in mouse strains that carry the homologous KID Arg/Cys substitution in murine IR or IGF-1R, and we replicated these genotypes in human cells. Cells with heterodimer receptors of IR or IGF-1R induce receptor phosphorylation and phospho-Akt when stimulated with insulin or IGF. Heterodimer receptors of IR fully induce pERK, but ERK was less phosphorylated in cells with IGF-1R heterodimers. Adults with a single KID allele (producing heterodimer receptors) have normal growth and glucose regulation. At 4 months, these mice variably display hormonal markers that associate with successful aging counteraction, including elevated adiponectin and FGF21, as well as reduced leptin and IGF-1. Livers of IGF-1R females show decreased transcriptome-based biological age, which may point toward delayed aging and warrants an actual lifespan experiment. These data suggest that KID mutants may slow mammalian aging while they avoid the complications of insulin resistance.

Reproductive disorders can result from a defective action of the neuropeptide gonadotropin-releasing hormone (GnRH), the master regulator of reproduction. We have previously shown that selenoprotein T (SELENOT), a newly described thioredoxin-like selenoprotein highly expressed in endocrine and neuroendocrine cells, plays a role in hormone secretion and neuroprotection. However, whether SELENOT is involved in neuroendocrine regulation in vivo is totally unknown. We found that SELENOT deficiency in the brain impaired sexual behavior, leading to a decline in fertility in both male and female mice. Biochemical and histological analyses of the gonadotrope axis of these mice revealed a higher expression of GnRH, which is associated with circulating luteinizing hormone (LH) excess, and elevated steroid hormones in males and a polycystic ovary syndrome–like phenotype in females. In addition, SELENOT deficiency impaired LH pulse secretion in both male and female mice. These changes were reverted after administration of a GnRH antagonist. Together, our data demonstrate for the first time to our knowledge the role of a selenoprotein in the central control of sexual behavior and reproduction, and identify a redox effector of GnRH neuron activity impacting both male and female reproductive function.

Saturated fatty acids impose lipotoxic stress on pancreatic β cells, leading to β cell failure and diabetes. In this study, we investigate the critical role of organellar Ca2+ disturbance on defective autophagy and β cell lipotoxicity. Palmitate, a saturated fatty acid, induced perilysosomal Ca2+ elevation, sustained mTOR complex 1 (mTORC1) activation on the lysosomal membrane, suppression of the lysosomal transient receptor potential mucolipin 1 (TRPML1) channel, and accumulation of undigested autophagosomes in β cells. These Ca2+ aberrations with autophagy defects by palmitate were prevented by an mTORC1 inhibitor or a mitochondrial superoxide scavenger. To alleviate perilysosomal Ca2+ overload, strategies such as lowering extracellular Ca2+, employing voltage-gated Ca2+ channel blocker or ATP-sensitive K+ channel opener, effectively abrogated mTORC1 activation and preserved autophagy. Furthermore, redirecting perilysosomal Ca2+ into the endoplasmic reticulum (ER), with an ER Ca2+ ATPase activator, restored TRPML1 activity, promoted autophagic flux, and improved survival of β cells exposed to palmitate-induced lipotoxicity. Our findings suggest oxidative stress/Ca2+ overload/mTORC1 pathway involvement in TRPML1 suppression and defective autophagy during β cell lipotoxicity. Restoring perilysosomal Ca2+ homeostasis emerges as a promising therapeutic strategy for metabolic diseases.

TLR7 agonists are promising immunostimulatory agents for the treatment of chronic infections and cancer. However, their systemic toxicity remains a challenge. In this study, SA-5, a potentially novel liver-targeted, orally available TLR7 agonist, was evaluated for pharmacokinetics, safety, and efficacy in young and aged macaques across 1–10 mg/kg repeated doses. Safety was evaluated through hematologic, biochemical, and flow cytometric profiling, while efficacy was assessed via IFN-α production, gene expression of IFN-stimulated genes, and plasmacytoid dendritic cell activation. A principal component analysis–based (PCA-based) composite scoring system was used to integrate multimodal parameters. SA-5 induced dose-dependent type I IFN with limited systemic inflammation, with 3 mg/kg showing optimal balance. SA-5 had comparable immunostimulatory activity to GS-9620 but with reduced adverse biomarker shifts. In aged macaques, efficacy was maintained with modestly increased safety responses. These findings support SA-5 as a safer next-generation TLR7 agonist effective across age groups, highlighting integrated biomarker profiling in preclinical immunomodulatory drug development.

BACKGROUND Platelets are increasingly recognized as active participants in immune signaling and systemic inflammation. Upon activation, platelets form monocyte platelet aggregates (MPA) representing the crossroads of thrombosis and inflammation. We hypothesized that platelet transcriptomics could capture this thromboinflammatory axis and identify individuals at elevated cardiovascular risk.METHODS: MPA levels, defined as CD14+CD61+ cells, were measured using flow cytometry at 2 time points, 4 weeks apart, in healthy individuals Platelets were isolated and sequenced. Individuals were categorized as MPAhi or MPAlo based on consistently high or low MPA levels across time points.RESULTS Among 149 participants (median age 52 years, 57% female, 50% non-White), MPAhi individuals exhibited increased expression of platelet activation markers P-selectin (P < 0.001), PAC-1 (P = 0.021), and CD40L (P < 0.001) and enriched immune signaling pathways. Informed by MPA levels and derived from the platelet transcriptome, we developed a 42-gene thromboinflammation platelet signature (TIPS), which correlated with MPA levels in multiple cohorts and was reproducible over time. TIPS was elevated in patients with COVID-19 (P = 0.0002) and myocardial infarction (Padj = 0.008), and as in predicted future cardiovascular events in patients who underwent lower extremity revascularization after a median follow-up of 18 months (adjusted for age, sex, race, and ethnicity [adjHR] 1.55, P = 0.006). Notably, TIPS was modifiable by ticagrelor (P = 0.002) but not aspirin.CONCLUSION These findings establish MPA as a biomarker of thromboinflammation and introduce TIPS, a platelet RNA signature, that captures thromboinflammation and provides a promising tool for cardiovascular risk stratification and a potential therapeutic target.TRIAL REGISTRATION NCT04369664FUNDING NIH R35HL144993, NIH R01HL139909, and AHA 16SFRN2873002 to JSB, DFG Walter-Benjamin-Programme 537070747 to AB.

Host factors influencing susceptibility to rhinovirus-induced asthma exacerbations remain poorly characterized. Using organotypic bronchial epithelial cultures from well-characterized children with asthma and healthy children, this study investigated viral load kinetics and resultant host responses by bulk and single-cell transcriptomics and targeted protein analyses. Bronchial epithelium from exacerbation-prone children exhibited greater rhinovirus replication and a cascade of exaggerated downstream interferon (IFN), inflammatory, epithelial stress, and remodeling responses. These transcriptional patterns were confirmed and further refined using single-cell transcriptomics, revealing cell type–specific contributions — particularly from non-ciliated cell populations including secretory immune response, tuft, and basal cells. We observed that these post-infection differences were associated with lower pre-infection IFN-stimulated gene (ISG) expression and protein levels of the ISG CXCL10. Prophylactic IFN-β treatment reduced viral replication and normalized downstream responses, supporting low baseline (pre-infection) IFN tone as a modifiable causal determinant of host susceptibility to adverse rhinovirus-induced responses in exacerbation-prone children with asthma.

BACKGROUND Predictive biomarkers to guide chemotherapy decisions for metastatic castration–resistant prostate cancer (mCRPC) are lacking. Preclinical studies indicate that circulating tumor cell (CTC) studies of chromosomal instability (CTC-CIN) can predict taxane resistance.METHODS The CARD trial randomized individuals with mCRPC progressing within a year of treatment with an androgen receptor pathway inhibitor (ARPI; enzalutamide or abiraterone acetate plus prednisolone/prednisone) to cabazitaxel or the alternative ARPI. As a preplanned biomarker analysis, CTCs were isolated from blood samples obtained at baseline, cycle 2, and the end of treatment. Associations between baseline CTC and CTC-CIN counts with imaging-based progression-free survival (ibPFS), overall survival (OS), time to prostate-specific antigen (PSA) progression, RECIST 1.1 objective response rate (ORR), and PSA50 response rate were assessed. RESULTS High baseline CTC-CIN counts significantly associated with worse OS after adjustment for confounding variables (median OS, 15.3 vs. 8.9 months; univariate HR, 2.16; 95% CI, 1.52–3.06; P < 0.001; multivariate HR, 1.56; 95% CI, 1.01–2.43; P = 0.047). Detectable CTC-CIN counts at baseline may predict a lack of ibPFS and OS benefit when comparing cabazitaxel with ARPI. CONCLUSION This preplanned analysis of biomarker data from the CARD trial confirms that CTC-CIN counts are a clinically useful prognostic and predictive biomarker of taxane resistance in mCRPC. Detectable CTC-CIN at baseline defines a patient subpopulation with unmet clinical needs in which alternative therapeutics should be tested.TRIAL REGISTRATION ClinicalTrials.gov number NCT02485691.FUNDING Funded by Sanofi and Epic Sciences.