New cheaper human papilloma virus mass screening strategy reduces cervical cancer incidence in Changsha city: A clinical trial.

Background: Cervical cancer is the second leading cause of death in women worldwide, second only to breast cancer. Around 80% of women have been infected with human papillomavirus (HPV) in their lifetime. Early screening and treatment are effective means of preventing cervical cancer, but due to economic reasons, many parts of the world do not have free screening programs to protect women's health.

Prospects for PARG inhibitors in cancer therapy.

Poly(ADP-ribose) glycosylhydrolase (PARG) is an enzyme involved in hydrolyzing the ribose-ribose bonds present in poly(ADP-ribose) (PAR), which are primarily found in the nucleus. Along with poly(ADP-ribose) polymerase (PARP), PARG regulates the level of PAR in cells, playing a crucial role in DNA maintenance and repair processes. Recent studies have revealed elevated levels of PARG in various cancers, such as breast, liver, prostate, and esophageal cancers, indicating a link to unfavorable cancer outcomes.

Prognostic impact and reasons for variability by tumor location in gastric cancer.

Background: Gastric cancer (GC) is a highly prevalent gastrointestinal tract tumor. Several trials have demonstrated that the location of GC can affect patient prognosis. However, the factors determining tumor location remain unclear.

Connexin 43 Deficiency Confers Resistance to Immunotherapy in Lung Cancer via Inhibition of the Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Pathway.

Immune checkpoint inhibitors (ICIs), especially PD-1 inhibitors, are among the first-line therapeutic drugs for the treatment of advanced non-small cell lung cancer (NSCLC). However, most patients are not sensitive to PD-1 inhibitors, and prolonged exposure can lead to acquired resistance. Thus, it is urgent to elucidate the mechanism underlying the resistance of NSCLC to ICIs.

Polyvinyl chloride nanoplastics suppress homology-directed repair and promote oxidative stress to induce esophageal epithelial cellular senescence and cGAS-STING-mediated inflammation.

Nanoplastics (NPs), which are characterized by plastic particles smaller than 1 μm, have emerged as pervasive environmental pollutants, raising concerns about their potential toxicity to living organisms. Numerous investigations have highlighted the tendency of NPs to accumulate in organs, resulting in toxic effects. Despite polyvinyl chloride (PVC) being one of the most prevalent NPs, its impact on the esophagus and the associated underlying mechanisms remain largely unknown.

PMMA nanoplastics induce gastric epithelial cellular senescence and cGAS-STING-mediated inflammation via ROS overproduction and NHEJ suppression.

The increasing environmental presence of nanoplastics (NPs) has raised concerns about their potential impact on biological systems. We investigated the repercussions of polymethyl methacrylate (PMMA) NPs exposure on normal gastric epithelial cells and revealed a pronounced increase in senescence-associated β-galactosidase activity and G1 phase cell cycle arrest. Our study demonstrated a dose-dependent increase in reactive oxygen species (ROS) and DNA damage, underscoring the pivotal role of ROS in PMMA NPs-mediated effects, a novel contribution to the existing body of knowledge dominated by polystyrene particles.

Orphan gene positively regulates bolting resistance through the vernalization pathway in Chinese cabbage.

Orphan genes () are unique to the specific species or lineage, and whose homologous sequences cannot be found in other species or lineages. Furthermore, these genes lack recognizable domains or functional motifs, which make their characterization difficult. Here, we identified a   named () that could positively modulate bolting resistance.

PRL1 and PRL3 promote macropinocytosis via its lipid phosphatase activity.

PRL1 and PRL3, members of the protein tyrosine phosphatase family, have been associated with cancer metastasis and poor prognosis. Despite extensive research on their protein phosphatase activity, their potential role as lipid phosphatases remains elusive. We conducted comprehensive investigations to elucidate the lipid phosphatase activity of PRL1 and PRL3 using a combination of cellular assays, biochemical analyses, and protein interactome profiling.

Discovery of novel macrocyclic derivatives as potent and selective cyclin-dependent kinase 2 inhibitors.

Cyclin-dependent kinase 2 (CDK2) is a member of CDK family of kinases (CDKs) that regulate the cell cycle. Its inopportune or over-activation leads to uncontrolled cell cycle progression and drives numerous types of cancers, especially ovarian, uterine, gastric cancer, as well as those associated with amplified CCNE1 gene. However, developing selective lead compound as CDK2 inhibitors remains challenging owing to similarities in the ATP pockets among different CDKs.

Advancements and Obstacles of PARP Inhibitors in Gastric Cancer.

Gastric cancer (GC) is a common and aggressive cancer of the digestive system, exhibiting high aggressiveness and significant heterogeneity. Despite advancements in improving survival rates over the past few decades, GC continues to carry a worrisome prognosis and notable mortality. As a result, there is an urgent need for novel therapeutic approaches to address GC.

Progress on plant orphan genes.

Orphan genes are located in a special evolutionary branch and have no significant sequence similarity with any other identified genes. Orphan genes are prevalent in every species, comparative genomics analyses found that all sequenced species contained a portion of orphan genes, and the number of orphan genes obtained by distinct screening conditions is different. Orphan genes are often associated with various stress responses, species-specific evolution and substance metabolism regulation.

Function and Molecular Mechanism of the DNA Damage Response in Immunity and Cancer Immunotherapy.

The DNA damage response (DDR) is an organized network of multiple interwoven components evolved to repair damaged DNA and maintain genome fidelity. Conceptually the DDR includes damage sensors, transducer kinases, and effectors to maintain genomic stability and accurate transmission of genetic information. We have recently gained a substantially improved molecular and mechanistic understanding of how DDR components are interconnected to inflammatory and immune responses to stress.

Cholesterol-enriched membrane micro-domaindeficiency induces doxorubicin resistancevia promoting autophagy in breast cancer.

Drug resistance has become one of the largest challenges for cancer chemotherapies. Under certain conditions, cancer cells hijack autophagy to cope with therapeutic stress, which largely undermines the chemo-therapeutic efficacy. Currently, biomarkers indicative of autophagy-derived drug resistance remain largely inclusive.

PRL-3 dephosphorylates p38 MAPK to promote cell survival under stress.

Hypoxia within the tumor microenvironment, which leads to excessive ROS and genomic instability, is one of the hallmarks of cancer, contributing to self-renewal capability, metastasis, and radio-chemotherapy resistance. PRL-3 is an oncoprotein involved in various pro-survival signaling pathways, such as Ras/Erk, PI3K/Akt, Src/STAT, mTORC1 and JAK/STAT. However, there is little evidence connecting PRL-3-mediated apoptosis resistance to tumor microenvironmental stress.

GRB2 enforces homology-directed repair initiation by MRE11.

DNA double-strand break (DSB) repair is initiated by MRE11 nuclease for both homology-directed repair (HDR) and alternative end joining (Alt-EJ). Here, we found that GRB2, crucial to timely proliferative RAS/MAPK pathway activation, unexpectedly forms a biophysically validated GRB2-MRE11 (GM) complex for efficient HDR initiation. GRB2-SH2 domain targets the GM complex to phosphorylated H2AX at DSBs.

PRL3 induces polypoid giant cancer cells eliminated by PRL3-zumab to reduce tumor relapse.

PRL3, a unique oncotarget, is specifically overexpressed in 80.6% of cancers. In 2003, we reported that PRL3 promotes cell migration, invasion, and metastasis.

Heritable pattern of oxidized DNA base repair coincides with pre-targeting of repair complexes to open chromatin.

Human genome stability requires efficient repair of oxidized bases, which is initiated via damage recognition and excision by NEIL1 and other base excision repair (BER) pathway DNA glycosylases (DGs). However, the biological mechanisms underlying detection of damaged bases among the million-fold excess of undamaged bases remain enigmatic. Indeed, mutation rates vary greatly within individual genomes, and lesion recognition by purified DGs in the chromatin context is inefficient.

Author Correction: PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.