Luyao Wang

Peptostreptococcus stomatis (P. stomatis) is enriched in colorectal cancer (CRC), but its causality and translational implications in CRC are unknown. Here, we show that P. stomatis accelerates colonic tumorigenesis in ApcMin/+ and azoxymethane/dextran sodium sulfate (AOM-DSS) models by inducing cell proliferation, suppressing apoptosis, and impairing gut barrier function. P. stomatis adheres to CRC cells through its surface protein fructose-1,6-bisphosphate aldolase (FBA) that binds to the integrin α6/β4 receptor on CRC cells, leading to the activation of ERBB2 and the downstream MEK-ERK-p90 cascade. Blockade of the FBA-integrin α6/β4 abolishes ERBB2-mitogen-activated protein kinase (MAPK) activation and the protumorigenic effect of P. stomatis. P. stomatis-driven ERBB2 activation bypasses receptor tyrosine kinase (RTK) blockade by EGFR inhibitors (cetuximab, erlotinib), leading to drug resistance in xenograft and spontaneous CRC models of KRAS-wild-type CRC. P. stomatis also abrogates BRAF inhibitor (vemurafenib) efficacy in BRAFV600E-mutant CRC xenografts. Thus, we identify P. stomatis as an oncogenic bacterium and a contributory factor for non-responsiveness to RTK inhibitors in CRC.

Leucine restriction (LR) improves insulin resistance and promotes white adipose tissue browning. However, the effect of LR on obesity-associated cognitive impairment remains unclear. The present study found that an 8-week LR dramatically improved high-fat diet (HFD)-induced cognitive decline by preventing synaptic dysfunction, increasing the expressions of neurotrophic factors, and inhibiting neuroinflammation in memory-related brain regions. Moreover, LR notably reshaped the structure of gut microbiota, which was manifested by downregulating the Firmicutes/Bacteroidetes ratio, reducing the relative abundance of inflammation-related bacteria including Acetatifactor, Helicobacter, Mucispirillum, and Oscillibacter but increasing short-chain fatty acid (SCFA)-producing bacterial genera including Alistipes, Allobaculum, Odoribacter, and Olsenella. Notably, HFD-caused SCFA reduction, gut barrier damage, and LPS leakage were recovered by LR. Our findings suggested that LR could serve as an effective approach to attenuate obesity-induced cognitive deficits, which may be achieved by balancing gut microbiota homeostasis and enhancing SCFA production.

BACKGROUND: Subjective cognitive decline (SCD) has been recognized as a potential risk stage for progression to Alzheimer's disease (AD), while glymphatic dysfunction is considered an important characteristic of AD. We hypothesize that glymphatic dysfunction occurs during the SCD stage, aiming to discover potential biomarkers for SCD. METHODS: Participants from two independent studies, Sino Longitudinal Study on Cognitive Decline (SILCODE, n = 654) and the Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 650), representing different ethnicities and disease stages, were included to assess glymphatic function using diffusion tensor image analysis along the perivascular space (DTI-ALPS). RESULTS: = 0.797). Lower ALPS index indicates higher risk of cognitive progression, which is negatively correlated with Subjective Cognitive Decline Questionnaire 9 scores and amyloid positron emission tomography burden. DISSCUSION: Our study suggests the ALPS index has the potential to serve as a biomarker for SCD. HIGHLIGHTS: Glymphatic function characterized by the analysis along the perivascular space (ALPS) index becomes abnormal in subjective cognitive decline (SCD), the earliest symptomatic manifestation and preclinical stage of Alzheimer's disease (AD). The ALPS index demonstrates excellent classification performance for SCD and normal controls in the East Asian and Western cohorts. Participants with a lower ALPS index show a higher risk of clinical progression. The ALPS index is closely associated with serval cognitive scales and amyloid beta burden.

Abstract Cubic half‐ and full‐Heusler compounds with respectively 18 and 24 valence electrons exhibit semiconducting behaviors according to the Slater–Pauling rule. In this work, a half‐Heusler‐like ZrRu 1.5 Sb semiconductor with the space group F 3 m is discovered based on the Slater–Pauling rule. The ZrRu 1.5 Sb compound has 21 valence electrons per chemical formula and each atom has six valence electrons on average, showing a p‐type conduction with a dimensionless thermoelectric figure of merit zT ≈0.2 at 973 K. By adjusting the Ru content, both p‐type ( x ≤ 0.5) and n‐type ( x > 0.5) semiconductors are realized in the ZrRu 1+ x Sb solid solution. Following this way, other half‐Heusler‐like semiconductors, such as ZrRu 1.30 Ni 0.10 Sb, ZrRu 1.40 Ni 0.05 Sb, and ZrRu 1.30 Ni 0.05 Sb, are also successfully designed and synthesized, demonstrating the effectiveness and practicality of our strategy to explore Slater–Pauling semiconductors. Furthermore, these half‐Heusler‐like semiconductors show promising potential as thermoelectric materials. The p‐type ZrRu 1.4 Sb and n‐type ZrRu 1.7 Sb samples have zT values of 0.38 at 973 K and 0.25 at 773 K, respectively, offering superior base materials for further optimizing their thermoelectric properties. The discovery of ZrRu 1.5 Sb‐based thermoelectric semiconductors demonstrates the great potential to design Slater–Pauling phases with exotic physical properties.