PerR functions as a redox-sensing transcription factor regulating metal homeostasis in the thermoacidophilic archaeon Saccharolobus islandicus REY15A.

Thermoacidophilic archaea thrive in environments with high temperatures and low pH where cells are prone to severe oxidative stress due to elevated levels of reactive oxygen species (ROS). While the oxidative stress responses have been extensively studied in bacteria and eukaryotes, the mechanisms in archaea remain largely unexplored. Here, using a multidisciplinary approach, we reveal that SisPerR, the homolog of bacterial PerR in Saccharolobus islandicus REY15A, is responsible for ROS response of transcriptional regulation.

Approaches to improve the translation of safety, pharmacokinetics and therapeutic index of ADCs.

1. Antibody-drug conjugates (ADCs) are an important class of cancer therapies. They are complex molecules, comprising an antibody, a cytotoxic payload, and a linker.

A three-dimensional (3D) liver-kidney on a chip with a biomimicking circulating system for drug safety evaluation.

The liver and kidney are the major detoxifying organs in the human body and play an important role in pharmacokinetics. Drug-induced hepatotoxicity and nephrotoxicity can cause irreversible damage to the liver and kidney and are a major cause of drug failure in later stages. Both animal models and conventional cell culture have a number of limitations, such as animal ethics and gene mismatching and there is an urgent need to develop a new drug toxicity evaluation approach.

Adavosertib and beyond: Biomarkers, drug combination and toxicity of WEE1 inhibitors.

WEE1 kinase is renowned as an S-G2 checkpoint inhibitor activated by ATR-CHK1 in response to replication stress. WEE1 inhibition enhances replication stress and effectively circumvents checkpoints into mitosis, which triggers significant genetic impairs and culminates in cell death. This approach has been validated clinically for its promising anti-tumor efficacy across various cancer types, notably in cases of ovarian cancers.

The canonical single-stranded DNA-binding protein is not an essential replication factor but an RNA chaperon in .

Single-stranded DNA-binding proteins (SSBs) have been regarded as indispensable replication factors. Herein, we report that the genes encoding the canonical SSB (SisSSB) and the non-canonical SSB (SisDBP) in REY15A are not essential for cell viability. Interestingly, at a lower temperature (55°C), the protein level of SisSSB increases and the growth of Δ and ΔΔ is retarded.

The FHA domain protein ArnA functions as a global DNA damage response repressor in the hyperthermophilic archaeon .

Forkhead-associated (FHA) domain proteins specifically recognize phosphorylated threonine via the FHA domain and are involved in signal transduction in various processes especially DNA damage response (DDR) and cell cycle regulation in eukaryotes. Although FHA domain proteins are found in prokaryotes, archaea, and bacteria, their functions are far less clear as compared to the eukaryotic counterparts, and it has not been studied whether archaeal FHA proteins play a role in DDR. Here, we have characterized an FHA protein from the hyperthermophilic Crenarchaeon (SisArnA) by genetic, biochemical, and transcriptomic approaches.

Quantitative analysis of a novel DNA hypermethylation panel using bronchial specimen for lung cancer diagnosis.

Non-diagnostic findings are common in transbronchial lung biopsy (TBLB) and endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB). One of the challenges is to improve the detection of lung cancer using these techniques. To address this issue, we utilized an 850 K methylation chip to identify methylation sites that distinguish malignant from benign lung nodules.

A DNA methylation signature for the prediction of tumour recurrence in stage II colorectal cancer.

Background: A major challenge in stage II colorectal carcinoma is to identify patients with increased risk of recurrence. Biomarkers that distinguish patients with poor prognosis from patients without recurrence are currently lacking. This study aims to develop a robust DNA methylation classifier that allows the prediction of recurrence and chemotherapy benefit in patients with stage II colorectal cancer.

A novel RHH family transcription factor aCcr1 and its viral homologs dictate cell cycle progression in archaea.

Cell cycle regulation is of paramount importance for all forms of life. Here, we report that a conserved and essential cell cycle-specific transcription factor (designated as aCcr1) and its viral homologs control cell division in Sulfolobales. We show that the transcription level of accr1 reaches peak during active cell division (D-phase) subsequent to the expression of CdvA, an archaea-specific cell division protein.

International consortium for innovation and quality: An industry perspective on the nonclinical and early clinical development of intravitreal drugs.

The eye, which is under constant exposure to environmental pathogens, has evolved various anatomic and immunological barriers critical to the protection of tissues lacking regenerative capacity, and the maintenance of a clear optic pathway essential to vision. By bypassing the ocular barriers, intravitreal (IVT) injection has become the mainstay for the delivery of drugs to treat conditions that affect the back of the eye. Both small molecules and biotherapeutics have been successfully administered intravitreally, and several drugs have been approved for the treatment of (wet) age-related macular degeneration and diabetic macular edema.

The archaeal KEOPS complex possesses a functional Gon7 homolog and has an essential function independent of the cellular tA modification level.

Kinase, putative Endopeptidase, and Other Proteins of Small size (KEOPS) is a multisubunit protein complex conserved in eukaryotes and archaea. It is composed of Pcc1, Kae1, Bud32, Cgi121, and Gon7 in eukaryotes and is primarily involved in N-threonylcarbamoyl adenosine (tA) modification of transfer RNAs (tRNAs). Recently, it was reported that KEOPS participates in homologous recombination (HR) repair in yeast.

Water-Air Interface Imaging: Recovering the Images Distorted by Surface Waves via an Efficient Registration Algorithm.

Imaging through the wavy water-air interface is challenging since the random fluctuations of water will cause complex geometric distortion and motion blur in the images, seriously affecting the effective identification of the monitored object. Considering the problems of image recovery accuracy and computational efficiency, an efficient reconstruction scheme that combines lucky-patch search and image registration technologies was proposed in this paper. Firstly, a high-quality reference frame is rebuilt using a lucky-patch search strategy.

Dissection of Functional Domains of Orc1-2, the Archaeal Global DNA Damage-Responsive Regulator.

Orc1-2 is a non-initiator ortholog of archaeal/eukaryotic Orc1 proteins, which functions as a global regulator in DNA damage-responsive (DDR) expression. As for Orc1 initiators, the DDR regulator harbors an AAA+ ATPase domain, an Initiator-Specific Motif (ISM) and a winged-helix (wH) DNA-binding domain, which are also organized in a similar fashion. To investigate how Orc1-2 mediates the DDR regulation, the mutants inactivating each of these functional domains were constructed with and genetically characterized.

Ca2.2-NFAT2-USP43 axis promotes invadopodia formation and breast cancer metastasis through cortactin stabilization.

Distant metastasis is the main cause of mortality in breast cancer patients. Using the breast cancer genomic data from The Cancer Genome Atlas (TCGA), we identified brain specific Ca2.2 as a critical regulator of metastasis.

Heparanase modulates the prognosis and development of BRAF V600E-mutant colorectal cancer by regulating AKT/p27Kip1/Cyclin E2 pathway.

BRAF V600E-mutant colorectal cancer (CRC) is a rare subtype of colorectal cancer with poor prognosis. Compelling evidence indicates that the heparanase (HPSE) gene has multiple functions in cancer, however, its role in BRAF V600E-mutant CRC remains elusive. Differentially expressed genes between BRAF V600E-mutant and wild-type patients were explored by analyzing public data from The Cancer Genome Atlas and the Gene Expression Omnibus.

Environmental Factors for Epstein-Barr Virus Reactivation in a High-Risk Area of Nasopharyngeal Carcinoma: A Population-Based Study.

Background: Epstein-Barr virus (EBV) reactivation from latent to lytic infection has been considered as a key step in nasopharyngeal carcinoma oncogenesis. However, epidemiological evidence regarding environmental risk factors for EBV reactivation on a population level remains largely lacking.

Methods: We enrolled 1916 randomly selected adults from the general population of Guangdong and Guangxi, China, from 2010 to 2014.

Discovery of efficacy biomarkers for non-small cell lung cancer with first-line anti-PD-1 immunotherapy by data-independent acquisition mass spectrometry.

First-line immune checkpoint inhibitors (ICIs) have greatly ameliorated outcomes in non-small cell lung cancer (NSCLC). However, approximately a quarter of patients receiving ICIs demonstrate long-term clinical benefit, and the true responders have not been fully clarified by the existing biomarkers. To discover potential biomarkers treatment-related outcomes in plasma, mass spectrometry assay for the data-independent acquisition was analyzed plasma samples collected before the anti-PD-1 treatment.

Long non-coding RNA MCM3AP antisense RNA 1 silencing upregulates microRNA-24-3p to accelerate proliferation and migration of vascular endothelial cells in myocardial infarction rats by reducing EIF4G2.

Long non-coding RNAs (lncRNAs) are crucial drivers in the progression of human diseases such as myocardial infarction (MI). However, the impact of lncRNA MCM3AP antisense RNA 1 (MCM3AP-AS1) on MI remains unknown. This research was determined to explore the effect of MCM3AP-AS1 modulating microRNA-24-3p (miR-24-3p) and eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) on MI.

Effects of Intravenous Infusion of Lidocaine on Short-Term Outcomes and Survival in Patients Undergoing Surgery for Ovarian Cancer: A Retrospective Propensity Score Matching Study.

Background: Intravenous lidocaine has been shown to reduce opioid consumption and is associated with favourable outcomes after surgery. In this study, we explored whether intraoperative lidocaine reduces intraoperative opioid use and length of stay (LOS) and improves long-term survival after primary debulking surgery for ovarian cancer and explored the correlation between SCN9A expression and ovarian cancer prognosis.

Methods: This retrospective study included patients who underwent primary debulking surgery(PDS) for ovarian cancer from January 2015 to December 2018.

Isolation of Protein Complexes Associated with Long Non-coding RNAs.

Long non-coding RNAs (lncRNAs) are a new class of regulatory genes that play critical roles in various processes ranging from normal development to human diseases. Recent studies have shown that protein complexes are required for the functions of lncRNAs. The identification of these proteins which are associated with lncRNAs is critical for the understanding of molecular mechanisms of lncRNAs in gene regulation and their functions.

Clinical features and risk factors of postoperative in-hospital mortality following surgical repair of Stanford type A acute aortic dissection.

Background: To investigate the clinical features of patients with Stanford type A acute aortic dissection (AAD) and analyze the risk factors affecting postoperative in-hospital mortality rate.

Methods: The demographic and clinical data were retrospectively collected and analyzed from 118 AAD patients admitted to the Affiliated Hospital of Hangzhou Normal University from June 2016 to April 2019. All patients underwent surgical treatment and were grouped into death and survival groups.

Comparison of new magnetic resonance imaging grading system with conventional endoscopy for the early detection of nasopharyngeal carcinoma.

Background: Although stratifying individuals with respect to nasopharyngeal carcinoma (NPC) risk with Epstein-Barr virus-based markers is possible, the performance of diagnostic methods for detecting lesions among screen-positive individuals is poorly understood.

Methods: The authors prospectively evaluated 882 participants aged 30 to 70 years who were enrolled between October 2014 and November 2018 in an ongoing, population-based NPC screening program and had an elevated NPC risk. Participants were offered endoscopy and magnetic resonance imaging (MRI), and lesions were identified either by biopsy at a follow-up endoscopy or further contact and linkage to the local cancer registry through December 31, 2019.