Browse Articles

Ancient genomes reveal trans-Eurasian connections between the European Huns and the Xiongnu Empire

The Huns appeared in Europe in the 370s, establishing an Empire that reshaped West Eurasian history. Yet until today their origins remain a matter of extensive debate. Traditional theories link them to the Xiongnu, the founders of the first nomadic empire of the Mongolian steppe. The Xiongnu empire dissolved, however, ~300 y before the Huns appeared in Europe, and there is little archaeological and historical evidence of Huns in the steppe during this time gap. Furthermore, despite the rich 5th to 6th centuries current era (CE) archaeological record of the Carpathian Basin, the cultural elements of connections with the steppe are limited to few findings and even fewer solitary eastern-type burials. In this study, we coanalyze archaeological evidence with 35 newly sequenced and published genomic data for a total of 370 individuals—from 5th to 6th century CE contexts in the Carpathian Basin including 10 Hun-period eastern-type burials, 2nd to 5th century sites across Central Asia and 2nd c. before current era (BCE) to 1st c. CE Xiongnu period sites across the Mongolian steppe. We find no evidence for the presence of a large eastern/steppe descent community among the Hun- and post-Hun-period Carpathian Basin population. We also observe a high genetic diversity among the eastern-type burials that recapitulates the variability observed across the Eurasian Steppe. This suggests a mixed origin of the incoming steppe conquerors. Nevertheless, long-shared genomic tracts provide compelling evidence of genetic lineages directly connecting some individuals of the highest Xiongnu-period elite with 5th to 6th century CE Carpathian Basin individuals, showing that some European Huns descended from them.

Follicular regulatory T cells restrain kidney allograft rejection in mice by suppressing alloreactive B cells

Leukocyte-specific protein 1 is associated with the stage and tumor immune infiltration of cervical cancer

Abstract Cervical cancer (CC) is a leading cause of cancer-related mortality among women and is strongly associated with persistent infection by high-risk human papillomavirus (HR-HPV), particularly the HPV16 subtype. Existing detection methods have limitations in meeting clinical requirements. This study aims to identify biomarkers that can aid in the staging and prognosis of cervical cancer. Cervical epithelial exfoliated cell samples were collected from three groups: HPV16-negative normal cervix, HPV16-positive normal cervix, and HPV16-positive cervical cancer. Differential expression proteins (DEPs) were identified using TMT-LC–MS/MS technology, and their associations with tumor-infiltrating lymphocytes (TILs) and immune regulatory molecules were analyzed. Leukocyte-specific protein 1 (LSP1), an intracellular F-actin-binding protein predominantly expressed in macrophages, neutrophils, B cells, and T cells, was identified as a potential biomarker. The expression levels of LSP1 were evaluated and validated using the Human Protein Atlas (HPA) database, immunohistochemistry (IHC), Western blotting (WB), and real-time quantitative PCR (RT-qPCR). Multiplex fluorescence immunohistochemistry (mIHC) was employed to assess the co-localization of LSP1 with CD4+ and CD8+ T cells. Results indicated that both protein and mRNA levels of LSP1 were significantly elevated in cervical cancer tissues compared to adjacent non-tumor tissues. Notably, LSP1 expression was higher in early-stage cervical cancer (Stage IB) than in advanced-stage disease (Stage IIIC). Furthermore, LSP1 was predominantly localized in CD4+ and CD8+ T cells with low TIM-3 expression. Analysis of public databases (GEPIA, TIMER2.0, and TISIDB) revealed that higher LSP1 mRNA levels correlated with better patient outcomes. LSP1 expression was positively associated with the abundance of major TILs and immune regulatory molecules, particularly activated B cells, CD8+ T cells, and CD4+ T cells, while negatively correlated with M2 macrophages and myeloid-derived suppressor cells. These findings indicate that the expression levels of LSP1 in cervical tissues are correlated with cancer staging and patient prognosis, potentially reflecting both tumor immune infiltration and T-cell exhaustion within the tumor microenvironment (TME).

Robust encoding of stimulus–response mapping by neurons in visual cortex

Neural activity in sensory cortex is modulated by behavioral and cognitive factors, and this modulation is thought to contribute to the selection of specific sensory information needed to achieve behavioral goals. In contrast, more abstract behavioral variables that are independent of stimulus selection, such as stimulus–response mapping, are thought to be encoded by neurons outside of sensory cortex. We show that information about such mapping is robustly encoded in the responses of neurons in primate visual cortex. Monkeys were trained to alternate between two tasks that differed in the rule governing the mapping of a remembered visual cue onto an eye movement response. During the memory-delay period, neurons in area V4 reliably signaled the remembered cue location in both tasks. However, the encoding of cue location depended critically on the stimulus–response mapping rule. Thus, V4 delay activity encoded the mapping rule and signaled the preparation of the appropriate motor response rather than spatial working memory per se, contrary to previous assumptions. In addition, we probed the origins of motor-related delay activity and found that it was reduced during local inactivation of the frontal eye field (FEF). The results demonstrate that behavioral modulation of visual cortical activity is not solely related to the selection of sensory stimuli but instead reflects a distinct mechanism for sensory-guided motor output.

Dynamics and drivers of tidal flat morphology in China

Author Correction: Genotoxic impact of agricultural insecticides as contaminants of river Teesta on the resident fish Pethia Conchonius

RORγt-expressing dendritic cells are functionally versatile and evolutionarily conserved antigen-presenting cells

Conventional dendritic cells (cDCs) are potent antigen-presenting cells (APCs) that integrate signals from their environment allowing them to direct situation-adapted immunity. Thereby they harbor great potential for being targeted in vaccination, autoimmunity, and cancer. Here, we use fate mapping, functional analyses, and comparative cross-species transcriptomics to show that RORγt + DCs are a conserved, functionally versatile, and transcriptionally distinct type of DCs. RORγt + DCs entail various populations described in different contexts including Janus cells/RORγt-expressing extrathymic Aire-expressing cells (eTACs), subtypes of Thetis cells, RORγt + -DC (R-DC) like cells, cDC2C and ACY3 + DCs. We show that in response to inflammatory triggers, RORγt + DCs can migrate to lymph nodes and in the spleen can activate naïve CD4 + T cells. These findings expand the functional repertoire of RORγt + DCs beyond the known role of eTACs and Thetis cells in inducing T cell tolerance to self-antigens and intestinal microbes in mice. We further show that RORγt + DCs with proinflammatory features accumulate in autoimmune neuroinflammation in mice and men. Thus, our work establishes RORγt + DCs as immune sentinel cells that exhibit a broad functional spectrum ranging from inducing peripheral T cell tolerance to T cell activation depending on signals they integrate from their environment.

Inhibition of the STAT3/Fanconi anemia axis is synthetic lethal with PARP inhibition in breast cancer

Abstract The targeting of cancer stem cells (CSCs) has proven to be an effective approach for limiting tumor progression, thus necessitating the identification of new drugs with anti-CSC activity. Through a high-throughput drug repositioning screen, we identify the antibiotic Nifuroxazide (NIF) as a potent anti-CSC compound. Utilizing a click chemistry strategy, we demonstrate that NIF is a prodrug that is specifically bioactivated in breast CSCs. Mechanistically, NIF-induced CSC death is a result of a synergistic action that combines the generation of DNA interstrand crosslinks with the inhibition of the Fanconi anemia (FA) pathway activity. NIF treatment mimics FA-deficiency through the inhibition of STAT3, which we identify as a non-canonical transcription factor of FA-related genes. NIF induces a chemical HRDness (Homologous Recombination Deficiency) in CSCs that (re)sensitizes breast cancers with innate or acquired resistance to PARP inhibitor (PARPi) in patient-derived xenograft models. Our results suggest that NIF may be useful in combination with PARPi for the treatment of breast tumors, regardless of their HRD status.

Eating distractions as predictors of ultra-processed food consumption and Mediterranean diet adherence in adolescents

Experimental consequences of disorder at an antiferromagnetic quantum phase transition

Comprehensive assessment of heavy metal (HMs) contamination and associated health risks in agricultural soils and groundwater proximal to industrial sites

A metamaterial scaffold beyond modulus limits: enhanced osteogenesis and angiogenesis of critical bone defects

Tracking CO2 migration and accumulation in the Subei Basin using geochronology and fluid inclusion quantitative analysis

A metabolic synthetic lethality of phosphoinositide 3-kinase-driven cancer

Abstract The deregulated activation of the phosphoinositide 3-kinase (PI3K) pathway is a hallmark of aggressive tumors with metabolic plasticity, eliciting their adaptation to the microenvironment and resistance to chemotherapy. A significant gap lies between the biological features of PI3K-driven tumors and the specific targeting of their vulnerabilities. Here, we explore the metabolic liabilities of PI3K-altered T-cell acute lymphoblastic leukemia (T-ALL), an aggressive hematological cancer with dismal outcomes. We report a metabolic crosstalk linking glutaminolysis and glycolysis driven by PI3K signaling alterations. Pharmaceutical inhibition of mTOR reveals the singular plasticity of PI3K-altered cells toward the mobilization of glutamine as a salvage pathway to ensure their survival. Subsequently, the combination of glutamine degradation and mTOR inhibition demonstrates robust cytotoxicity in PI3K-driven solid and hematological tumors in pre-clinical and clinical settings. We propose a novel therapeutic strategy to circumvent metabolic adaptation and efficiently target PI3K-driven cancer.

Multi-gas dual-comb spectroscopy with tunable gain-switched laser diodes

Janus hydrogel microrobots with bioactive ions for the regeneration of tendon-bone interface

Analysis of rabbiteye blueberry metabolomes and transcriptomes reveals mechanisms underlying potassium-induced anthocyanin production

Cultivated autologous limbal epithelial cell (CALEC) transplantation for limbal stem cell deficiency: a phase I/II clinical trial of the first xenobiotic-free, serum-free, antibiotic-free manufacturing protocol developed in the US

BRPF1 inhibition reduces migration and invasion of metastatic ovarian cancer cells, representing a potential therapeutic target

Coupling nitrogen removal and watershed management to improve global lake water quality

Abstract Lakes play a vital role in nitrogen (N) removal and water quality improvement, yet their efficiency varies due to differing watershed N input and lake characteristics, complicating management efforts. Here we established the N budget for 5768 global lakes using a remote sensing model. We found that watershed N input reduction and lake water quality improvement are nonlinearly related and depends on lake N removal efficiency. A 30% reduction in N loading in watersheds with high N removal efficiencies can improve cumulative water quality by over 70%. Stricter reduction could accelerate achieving water quality goal (≤1 mg N L–1), shortening the time by up to 30 years for most lakes. However, heavily polluted lakes with low N removal efficiencies (50 of 534 lakes with >1 mg N L–1) may not achieve the UN’s clean water SDG by 2030, even with a 100% N input reduction. Our research highlights the need for targeted N management strategies to improve global lake water quality.