Protocol for oral fecal gavage to reshape the gut microbiota in mice.

Fecal microbiota transplantation (FMT) is clinically applied, while oral FMT (oral fecal gavage [OFG]) is preferred for experimental mice. Here, we present a protocol for OFG in antibiotic-pretreated mice, demonstrating the progressive, time-dependent evolution of the gut microbiota in the recipients. We describe steps for fecal sample collection and preparation procedures, oral gavage, and monitoring gut microbiota changes.

Regulation of interferon alpha production by the MAGUK-family protein CASK under H5N1 infection.

CASK, a MAGUK family scaffold protein, regulates gene expression as a transcription co-activator in neurons. However, the mechanism of CASK nucleus translocation and the regulatory function of CASK in myeloid cells remains unclear. Here, we investigated its role in H5N1-infected macrophages.

Co-precipitating calcium phosphate as oral detoxification of cadmium.

Bone-eating (also known as osteophagia), found in wild animals, is primarily recognized as a means to supplement phosphorus and calcium intake. Herein, we describe a novel function of bone-eating in detoxifying heavy metal ions through the dissolution and co-precipitation of bone minerals as they travel through the gastrointestinal (GI) tract. In this study, cadmium (Cd), a heavy metal ion, served as a toxic model.

Novel Inhibitors for MDM2-MDM4 E3 Ligase Potently Induce p53-Indepedent Apoptosis in Drug-Resistant Leukemic Cells.

MDM2 and MDM4 are major negative regulators of tumor suppressor p53. Beyond regulating p53, MDM2 possesses p53-independent activity in promoting cell cycle progression and tumorigenesis via its RING domain ubiquitin E3 ligase activity. MDM2 and MDM4 form heterodimer polyubiquitin E3 ligases via their RING domain interaction.

Chronic Hepatitis B Genotype C Mouse Model with Persistent Covalently Closed Circular DNA.

Hepatitis B virus (HBV) can cause chronic infections, significantly increasing the risk of death from cirrhosis and hepatocellular carcinoma (HCC). A key player in chronic HBV infection is covalently closed circular DNA (cccDNA), a stable episomal form of viral DNA that acts as a persistent reservoir in infected hepatocytes and drives continuous viral replication. Despite the development of several animal models, few adequately replicate cccDNA formation and maintenance, limiting our understanding of its dynamics and the evaluation of potential therapeutic interventions targeting cccDNA.

Deciphering the fate of replication-induced DNA double-strand breaks.

In this issue of Molecular Cell, studies by Xu et al., Kimble et al., and Elango et al.

Male preference for TERT alterations and HBV integration in young-age HBV-related HCC: implications for sex disparity.

Background/aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC.

Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data.

Significance of cycle 1 bone marrow biopsy in predicting outcomes and toxicities of venetoclax-based therapy for myeloid malignancies.

For older unfit patients receiving venetoclax-based induction, data on the significance of interim bone marrow biopies (BMBx) findings on clinical outcomes is lacking. We retrospectively evaluated interim BMBx results performed on Cycle 1 days 21-28 of venetoclax-based therapy in 69 adults with myeloid malignancies to determine whether blast clearance was associated with overall survival (OS) and overall response rate (ORR). Median age was 75 years (range 69-78).

Improved survival with second-line hepatic arterial infusion chemotherapy after atezolizumab-bevacizumab failure in hepatocellular carcinoma.

Background: There is no established second-line treatment for hepatocellular carcinoma (HCC) following atezolizumab-bevacizumab (ate-beva) failure. This study assessed the efficacy of hepatic arterial infusion chemotherapy (HAIC) as a salvage therapy by comparing survival outcomes and treatment responses between HAIC as a first-line treatment and as a second-line option after ate-beva failure.

Materials And Methods: We retrospectively analyzed 100 patients with advanced HCC treated with HAIC between March 2022 and July 2024.

Structures of Polyacetoxybriaranes Extracted from the Sea Whip Octocoral Junceella fragilis.

In the present study, an algae-containing octocoral, Junceella fragilis, was subjected to chemical screening. The analysis resulted in the extraction of six polyacetoxybriaranes: a new compound, identified as fragilide Z (1), alongside previously identified analogs, which included 12-epi-fragilide G (2), fragilide P (3), junceellolide D (4), junceellonoid A (5), and juncin ZI (6). The structures of compounds 2-6 were investigated through single-crystal X-ray diffraction analysis, whereas that of 1 was examined through two-dimensional nuclear magnetic resonance analysis.

Prognostic significance of combined PD-L1 expression in malignant and infiltrating cells in hepatocellular carcinoma treated with atezolizumab and bevacizumab.

Background: Programmed death-ligand 1 (PD-L1) expression is abundant not only in malignant cells but also in infiltrating cells within the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). This study explored the association between PD-L1 expression in TME and outcomes in HCC patients treated with atezolizumab plus bevacizumab (AB), emphasizing the implications of PD-L1 expression in both malignant and tumor-infiltrating cells.

Methods: This study included 72 patients with HCC who underwent percutaneous core needle liver biopsy before AB treatment between September 2020 and December 2023.

Performance of Noninvasive Indices for Discrimination of Metabolic Dysfunction-Associated Steatotic Liver Disease in Young Adults.

Background/aims: Although numerous noninvasive steatosis indices have been developed to assess hepatic steatosis, whether they can be applied to young adults in the evaluation of metabolic dysfunction-associated steatotic liver disease (MASLD) remains uncertain.

Methods: Data from patients under 35 years of age who visited the Liver Health Clinic at the Armed Forces Goyang Hospital between July 2022 and January 2024 were retrospectively collected. Steatosis was diagnosed on the basis of a controlled attenuation parameter score ≥250 dB/m.

Functional Limitations and Depressive Symptoms Among Older Adults in Korea: Gender Differences in the Moderating Roles of Relationship Satisfaction With Family, Friends, and Neighbors.

Objectives: This study investigated the association between functional limitations and depressive symptoms among older adults in South Korea, focusing on gender differences in the moderating roles of relationship satisfaction with family, friends, and neighbors.

Methods: Fixed-effect models were applied to five waves of data from the Korean Retirement and Income Study, encompassing 19,180 observations.

Results: Increases in functional limitations were associated with higher levels of depressive symptoms, regardless of gender.

Real world virologic outcomes in patients with elevated body mass index receiving long acting cabotegravir/rilpivirine.

Background: The first long-acting injectable antiretroviral, cabotegravir/rilpivirine (LA-CAB/RPV), was FDA approved in January 2021 for persons with HIV suppressed on their current regimen. Body mass index (BMI) ≥30 kg/m2 has been identified as a risk factor for virologic failure, however data is limited due to small sample sizes. The aim of this study was to evaluate the impact of BMI on the efficacy of LA-CAB/RPV in a real-world setting.

Sharing in Caring: Family Caregiving Task-Sharing Patterns for Older Adults in Singapore.

Objectives: Research on family caregiving for older adults has largely focused on primary caregivers. We identify caregiving task-sharing patterns among multiple caregivers, including family members and live-in hired workers. In addition, we investigate caregiver and care-recipient characteristics associated with these patterns.

Shock wave-pretreated ADMSCs of cell-sheet scaffold (CSS) patched on the left ventricular wall (LVW) inhibited LVW remodeling in mini-pig MI: role of CSS on counteracting Laplace's Law of LVW stress - experimental study.

Background: We investigated whether shock wave (SW)-pretreated autologous adipocyte-derived mesenchymal stem cells (ADMSCs) seeded in the cell-sheet scaffold (CSS) could inhibit left ventricular (LV) remodeling and improve LV ejection fraction (LVEF) in old myocardial infarction (MI).

Methods: Mini-pigs ( n =20) were divided into group 1 (sham-operated control), group 2 (old MI), group 3 (old MI + autologous ADMSCs/1.0×10 7 in CSS on LV myocardium), and group 4 [old MI + SW (0.

Tumour-intrinsic PDL1 signals regulate the Chk2 DNA damage response in cancer cells and mediate resistance to Chk1 inhibitors.

Background: Aside from the canonical role of PDL1 as a tumour surface-expressed immune checkpoint molecule, tumour-intrinsic PDL1 signals regulate non-canonical immunopathological pathways mediating treatment resistance whose significance, mechanisms, and therapeutic targeting remain incompletely understood. Recent reports implicate tumour-intrinsic PDL1 signals in the DNA damage response (DDR), including promoting homologous recombination DNA damage repair and mRNA stability of DDR proteins, but many mechanistic details remain undefined.

Methods: We genetically depleted PDL1 from transplantable mouse and human cancer cell lines to understand consequences of tumour-intrinsic PDL1 signals in the DNA damage response.

Implications for fall efficacy strategies on center of pressure and center of gravity sway distances in adults with chronic low back pain.

Background: Although chronic low back pain (LBP) is a complex condition often associated with altered motor control and compensatory postural adjustments, existing literature provides inconsistent reports on the underlying control mechanisms for maintaining balance.

Purpose: This study aimed to compare differences in sway distances between the center of pressure (COP) and the center of gravity (COG), while considering limb dominance, in adults with and without LBP.

Methods: There were 26 subjects with LBP and 39 control subjects who performed three repeated unilateral standing tasks on a force platform.

Combined dapagliflozin and roxadustat effectively protected heart and kidney against cardiorenal syndrome-induced damage in rodent through activation of cell stress-Nfr2/ARE signalings and stabilizing HIF-1α.

Background: This study tested whether combined dapagliflozin (DAPA) and roxadustat (ROX) therapy was superior to a singular therapy in protecting heart and kidney functions in rats with cardiorenal syndrome (CRS).

Methods And Results: An in vitro study demonstrated that the cell survival (PI3K/Akt/mTOR)/cell stress (ERK1/2, JNK/p-38) signaling was significantly activated by combination therapy with ROX-DAPA (all p<0.001).

Distinct roles of the two BRCA2 DNA binding domains in DNA damage repair and replication fork preservation.

Homologous recombination (HR) is a highly conserved tool for the removal of DNA double-strand breaks (DSBs) and the preservation of stalled and damaged DNA replication forks. Successful completion of HR requires the tumor suppressor BRCA2. Germline mutations in BRCA2 lead to familial breast, ovarian, and other cancers, underscoring the importance of this protein for maintaining genome stability.