Complement classical and alternative pathway activation contributes to diabetic kidney disease progression: a glomerular proteomics on kidney biopsies.

Increasing evidence points toward an essential role for complement activation in the pathogenesis of diabetic kidney disease (DKD). However, the precise molecular mechanisms remain unclear, and the pathway predominantly contributing to complement activation in DKD is of particular interest. In this study, the glomerular proteome, especially the profiles of the complement proteins, was analyzed in kidney biopsies from 40 DKD patients and 10 normal controls using laser microdissection-assisted liquid chromatography-tandem mass spectrometry (LMD-LC-MS/MS).

ABCF1-K430-Lactylation promotes HCC malignant progression via transcriptional activation of HIF1 signaling pathway.

Lysine lactylation plays critical roles in various diseases, including cancer. Our previous study showed that lactylation of non-histone ABCF1 may be involved in hepatocellular carcinoma (HCC) progression. In this study, we evaluated the prognostic value of ABCF1-K430la in HCC using immunohistochemical staining and performed amino acid point mutations, multi-omics crossover, and biochemical experiments to investigate its biological role and underlying mechanism.

ATM and IRAK1 orchestrate two distinct mechanisms of NF-κB activation in response to DNA damage.

DNA damage in cells induces the expression of inflammatory genes. However, the mechanism by which cells initiate an innate immune response in the presence of DNA lesions blocking transcription remains unknown. Here we find that genotoxic stresses lead to an acute activation of the transcription factor NF-κB through two distinct pathways, each triggered by different types of DNA lesions and coordinated by either ataxia-telangiectasia mutated (ATM) or IRAK1 kinases.

NUFIP1 integrates amino acid sensing and DNA damage response to maintain the intestinal homeostasis.

Nutrient availability strongly affects intestinal homeostasis. Here, we report that low-protein (LP) diets decrease amino acids levels, impair the DNA damage response (DDR), cause DNA damage and exacerbate inflammation in intestinal tissues of male mice with inflammatory bowel disease (IBD). Intriguingly, loss of nuclear fragile X mental retardation-interacting protein 1 (NUFIP1) contributes to the amino acid deficiency-induced impairment of the DDR in vivo and in vitro and induces necroptosis-related spontaneous enteritis.

Roles of sensory receptors in non-sensory organs: the kidney and beyond.

Olfactory receptors (ORs), taste receptors and opsins are well-known for their pivotal roles in mediating the senses of smell, taste and sight, respectively. However, in the past two decades, research has shown that these sensory receptors also regulate physiological processes in a variety of non-sensory tissues. Although ORs, taste receptors and opsins have all been shown to have physiological roles beyond their traditional locations, most work in the kidney has focused on ORs.

The optimal neoadjuvant treatment strategy for HR+/HER2 + breast cancer: a network meta-analysis.

The efficacy of neoadjuvant therapy varies significantly with hormone receptor (HR) status for patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer (BC). Despite extensive research on HER2 + BC, the optimal neoadjuvant strategy for HR+/HER2 + BC remains inconclusive. This study aimed to identify the optimal neoadjuvant regimen for HR+/HER2 + BC treatment.

Effects of RARα ligand binding domain mutations on breast fibroepithelial tumor function and signaling.

Point mutations in the ligand binding domain of retinoic acid receptor alpha (RARα) are linked to breast fibroepithelial tumor development, but their role in solid tumorigenesis is unclear. In this study, we assessed the functional effects of known RARα mutations on retinoic acid signaling using biochemical and cellular assays. All tested mutants exhibited reduced transcriptional activity compared to wild-type RARα and showed a dominant negative effect, a feature associated with developmental defects and tumor formation.

Structural insights into the LGR4-RSPO2-ZNRF3 complexes regulating WNT/β-catenin signaling.

WNT/β-catenin signaling plays key roles in development and cancer. ZNRF3/RNF43 modulates Frizzleds through ubiquitination, dampening WNT/β-catenin signaling. Conversely, RSPO1-4 binding to LGR4-6 and ZNRF3/RNF43 enhances WNT/β-catenin signaling.

Cryo-EM structure and oligomerization of the human planar cell polarity core protein Vangl1.

Vangl is a planar cell polarity (PCP) core protein essential for aligned cell orientation along the epithelial plane perpendicular to the apical-basal direction, which is important for tissue morphogenesis, development and collective cell behavior. Mutations in Vangl are associated with developmental defects, including neural tube defects (NTDs), according to human cohort studies of sporadic and familial cases. The complex mechanisms underlying Vangl-mediated PCP signaling or Vangl-associated human congenital diseases have been hampered by the lack of molecular characterizations of Vangl.

Nucleosome wrapping states encode principles of 3D genome organization.

Nucleosome is the basic structural unit of the genome. During processes like DNA replication and gene transcription, the conformation of nucleosomes undergoes dynamic changes, including DNA unwrapping and rewrapping, as well as histone disassembly and assembly. However, the wrapping characteristics of nucleosomes across the entire genome, including region-specificity and their correlation with higher-order chromatin organization, remains to be studied.

Oral applause sign in progressive supranuclear palsy.

The applause sign (AS) is a recognized phenomenon observed in progressive supranuclear palsy (PSP) and other neurological conditions where individuals produce over three claps following a request to clap only thrice after a demonstration. In this study, we introduced a novel linguistic phenomenon termed the oral applause sign (OAS) associated with the AS. The OAS is characterized by increased repetition counts of Japanese repetitive onomatopoeic words, such as uttering "pata-pata-pata" instead of the expected "pata-pata.

Tumor-intrinsic regulators of the immune-cold microenvironment of prostate cancer.

Prostate cancer (PC) is a notoriously immune-cold tumor in that it often lacks substantial infiltration by antitumor immune cells, and in advanced diseases such as neuroendocrine PC, it could be devoid of immune cells. A majority of PC patients thus have, unfortunately, been unable to benefit from recent advances in immunotherapies. What causes this immunosuppressive microenvironment around PC? In this review, we discuss various genetic and epigenetic regulators intrinsic to prostate tumor cells that could have profound effects on the tumor microenvironment, thus contributing to this immune-cold status.

Gentrification, gun violence, and disparities in access to care for shooting victims.

Background: Gentrification is associated with redistribution of shootings but impacts on access to care are unknown. We evaluate the association of gentrification with shooting rates, transport times, and survival in Boston.

Methods: Gentrification was defined using income, housing, and educational attainment from the 2010-2020 census.

Twenty years of experience with lesions involving the temporomandibular joint and adjacent structures complex.

With their close anatomical relationship, the temporomandibular joint (TMJ), mandibular ramus, skull base, ear, and infratemporal fossa make up a complex structure that may collectively be referred to as the 'TMJ and adjacent structures complex' (TASC). This study presents the neoplasms that may be encountered in the TASC region and their classification, which may be useful for the surgical treatment. Data of 1022 consecutive patients treated with resection of TASC neoplasms from May 2000 to October 2022 were reviewed.