Multiomics profiling reveals the benefits of gamma-delta (γδ) T lymphocytes for improving the tumor microenvironment, immunotherapy efficacy and prognosis in cervical cancer.

Background: As an unconventional subpopulation of T lymphocytes, γδ T cells can recognize antigens independently of major histocompatibility complex restrictions. Recent studies have indicated that γδ T cells play contrasting roles in tumor microenvironments-promoting tumor progression in some cancers (eg, gallbladder and leukemia) while suppressing it in others (eg, lung and gastric). γδ T cells are mainly enriched in peripheral mucosal tissues.

DNA-Based Nonviral Gene Therapy─Challenging but Promising.

Over the past decades, significant progress has been made in utilizing nucleic acids, including DNA and RNA molecules, for therapeutic purposes. For DNA molecules, although various DNA delivery systems have been established, viral vector systems are the go-to choice for large-scale commercial applications. However, viral systems have certain disadvantages such as immune response, limited payload capacity, insertional mutagenesis and pre-existing immunity.

Specific targeting of the NRF2/β-TrCP axis promotes beneficial effects in NASH.

Non-alcoholic steatohepatitis (NASH) is a common chronic liver disease that compromises liver function, for which there is not a specifically approved medicine. Recent research has identified transcription factor NRF2 as a potential therapeutic target. However, current NRF2 activators, designed to inhibit its repressor KEAP1, exhibit unwanted side effects.

Ascorbate and its transporter SVCT2: The dynamic duo's integrated roles in CNS neurobiology and pathophysiology.

Ascorbate is a small antioxidant molecule essential for the proper development and function of the brain. Ascorbate is transported into the brain and between brain cells via the Sodium vitamin C co-transporter 2 (SVCT2). This review provides an in-depth analysis of ascorbate's physiology, including how ascorbate is absorbed from food into the CNS, emphasizing cellular mechanisms of ascorbate recycling and release in different CNS compartments.

Notch activation defines immune-suppressive subsets of ccRCCs with unfavorable benefits from immunotherapy over VEGFR/mTOR inhibitors.

The evolutionarily conserved Notch pathway, involved in cancer stem cell capacity and cancer immunity, may predict the benefit from immune checkpoint inhibitors (ICIs) in clear cell renal cell carcinoma (ccRCC). In the TCGA dataset, mRNA expression of Notch pathway genes identified three clusters with different prognoses and molecular characteristics. Based on the differentially expressed Notch pathway genes between clusters, we constructed the Notch-score, correlated with Notch activation, angiogenesis, PI3K-AKT-mTOR activity, and sensitivities to VEGFR/mTOR inhibitors.

Methotrimeprazine is a neuroprotective antiviral in JEV infection via adaptive ER stress and autophagy.

Japanese encephalitis virus (JEV) pathogenesis is driven by a combination of neuronal death and neuroinflammation. We tested 42 FDA-approved drugs that were shown to induce autophagy for antiviral effects. Four drugs were tested in the JE mouse model based on in vitro protective effects on neuronal cell death, inhibition of viral replication, and anti-inflammatory effects.

RlmQ: a newly discovered rRNA modification enzyme bridging RNA modification and virulence traits in .

rRNA modifications play crucial roles in fine-tuning the delicate balance between translation speed and accuracy, yet the underlying mechanisms remain elusive. Comparative analyses of the rRNA modifications in taxonomically distant bacteria could help define their general, as well as species-specific, roles. In this study, we identified a new methyltransferase, RlmQ, in responsible for the Gram-positive specific mG2601, which is not modified in (G2574).

Fatty acid synthase (FASN) signalome: A molecular guide for precision oncology.

The initial excitement generated more than two decades ago by the discovery of drugs targeting fatty acid synthase (FASN)-catalyzed de novo lipogenesis for cancer therapy was short-lived. However, the advent of the first clinical-grade FASN inhibitor (TVB-2640; denifanstat), which is currently being studied in various phase II trials, and the exciting advances in understanding the FASN signalome are fueling a renewed interest in FASN-targeted strategies for the treatment and prevention of cancer. Here, we provide a detailed overview of how FASN can drive phenotypic plasticity and cell fate decisions, mitochondrial regulation of cell death, immune escape and organ-specific metastatic potential.

Shear Bond Strength of Simulated Single-Retainer Resin-Bonded Bridges Made of Four CAD/CAM Materials for Maxillary Lateral Incisor Agenesis Rehabilitation.

Objectives:  Maxillary lateral incisor agenesis (MLIA), treated orthodontically by space opening, requires complimentary aesthetic rehabilitation. Resin-bonded bridges (RBBs) can be equated as interim rehabilitation until skeletal maturity is achieved to place an implant-supported crown or as definitive rehabilitation in case of financial restrictions or implant contraindications. Scientific evidence of the best material must be confirmed in specific clinical situations.

Doxycycline hydrochloride inhibits the progress of malignant rhabdoid tumor of kidney by targeting MMP17 and MMP1 through PI3K-Akt signaling pathway.

Objective: To identify therapeutic targets for malignant rhabdoid tumors of kidney (MRTK) and to investigate the effects and underlying mechanism of doxycycline hydrochloride on these tumors.

Methods: Gene expression and clinical data of MRTK were retrieved from the TARGET database. Differentially expressed genes (DEGs) and prognostic-related genes (PRGs) were selected through a combination of statistical analyses.

Case report: SAF-189s is a potent inhibitor in a lorlatinib-resistant NSCLC patient with acquired compound mutations ALK L1196M and D1203N.

Acquired anaplastic lymphoma kinase (ALK) mutation is the major resistant mechanism to ALK tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients. At present, treatment options after acquiring secondary ALK mutations are still limited. Here, we report on a patient with metastatic ALK-rearranged NSCLC who was sequentially treated with ALK TKIs, from crizotinib to lorlatinib, and developed rare acquired compound ALK mutations (L1196M and D1203N) that confer resistance to lorlatinib.

The age-related obesity paradigm: results from two large prospective cohort studies.

Background: The obesity paradigm has been a health concern globally for many years, its meaning is controversial. In this study, we assess the characteristics and causes of obesity paradigm and detail the mediation of obesity and inflammation on survival.

Methods: The original cohort included participants from the US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, a prospective cohort of a nationally representative sample of adult participants; the oncology validation cohort included patients from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) from 2013 to 2021, a prospective cohort of Chinese patients with cancer.

The role of macrophages in gastric cancer.

As one of the deadliest cancers of the gastrointestinal tract, there has been limited improvement in long-term survival rates for gastric cancer (GC) in recent decades. The poor prognosis is attributed to difficulties in early detection, minimal opportunity for radical resection and resistance to chemotherapy and radiation. Macrophages are among the most abundant infiltrating immune cells in the GC stroma.

Genetic counselling supervision: Luxury or necessity? A qualitative study with genetic healthcare professionals in Portugal.

In recent years, there has been a significant technological evolution in the field of genetics, leading to an increase in the number of professionals working in medical genetics and, consequently, a tremendous growth in genetic counselling. At the same time, there has been a growing recognition of the parameters on which to base a safe practice, not only regarding the technical skills of the professional but also regarding their counselling skills, including relational and empathy skills and the acknowledgement of the emotional impact that genetic counselling practice can have. However, despite this growing knowledge, there are still significant differences between the various European countries, and one area where this discrepancy is particularly evident is genetic counselling supervision.

Microrheological characterisation of Cyanoflan in human blood plasma.

Naturally occurring polysaccharidic biopolymers released by marine cyanobacteria are of great interest for numerous biomedical applications, such as wound healing and drug delivery. Such polymers generally exhibit high molecular weight and an entangled structure that impact the rheology of biological fluids. However, biocompatibility tests focus not so much on rheological properties as on immune response.

Electrochemical impedance spectroscopy, another arrow in the arsenal to study the biodegradability of two-dimensional materials.

Carbon nitride (CN) is an innovative material with a high potential in many applications including energy storage, catalysis, composites, and biomedicine. CN appears remarkably interesting not only for its properties but also because its simple preparation routes involve low-cost starting materials and reagents. However, there is still a lack of information on its degradability.

Cardiovascular challenges in the era of antiretroviral therapy for AIDS/ HIV: A comprehensive review of research advancements, pathophysiological insights, and future directions.

Cardiovascular disease, particularly coronary heart disease, is becoming more common among those living with HIV. Individuals with HIV face an increased susceptibility to myocardial infarction, also known as a heart attack, as compared to the general population in developed countries. This heightened risk can be attributed mainly to the presence of effective antiretroviral drugs and the resulting longer lifespan.

NAGPKin: Nucleation-and-growth parameters from the kinetics of protein phase separation.

The assembly of biomolecular condensate in eukaryotic cells and the accumulation of amyloid deposits in neurons are processes involving the nucleation and growth (NAG) of new protein phases. To therapeutically target protein phase separation, drug candidates are tested in in vitro assays that monitor the increase in the mass or size of the new phase. Limited mechanistic insight is, however, provided if empirical or untestable kinetic models are fitted to these progress curves.

Risk factors for parapharyngeal and retropharyngeal metastases in papillary thyroid cancer: a matched case-control study.

Purpose: To analyze risk factors for parapharyngeal (PP) and retropharyngeal (RP) metastases in papillary thyroid cancer (PTC).

Methods: A matched case-control study was conducted, comprising 130 age- and sex-matched cases of PTC. Among these cases, 50 had PP/RP metastases, 50 had central and/or lateral neck lymph node metastases, and 30 showed no lymph node metastases.

Organization of an Artificial Multicellular System with a Tunable DNA Patch on a Membrane Surface.

Coordinating multiple artificial cellular compartments into a well-organized artificial multicellular system (AMS) is of great interest in bottom-up synthetic biology. However, developing a facile strategy for fabricating an AMS with a controlled arrangement remains a challenge. Herein, utilizing DNA hybridization chain reaction on the membrane surface, we developed a DNA patch-based strategy to direct the interconnection of vesicles.

Catalytic and Electrocatalytic Mechanisms of Cytochromes P450 in the Development of Biosensors and Bioreactors.

Cytochromes P450 are a unique family of enzymes found in all Kingdoms of living organisms (animals, bacteria, plants, fungi, and archaea), whose main function is biotransformation of exogenous and endogenous compounds. The review discusses approaches to enhancing the efficiency of electrocatalysis by cytochromes P450 for their use in biotechnology and design of biosensors and describes main methods in the development of reconstituted and electrochemical catalytic systems based on the biochemical mechanism of cytochromes P450, as well as and modern trends for their practical application.

New Perspectives on Circulating Ferritin: Its Role in Health and Disease.

The diagnosis of iron disturbances usually includes the evaluation of serum parameters. Serum iron is assumed to be entirely bound to transferrin, and transferrin saturation-the ratio between the serum iron concentration and serum transferrin-usually reflects iron availability. Additionally, serum ferritin is commonly used as a surrogate of tissue iron levels.

Ataxia with giant axonopathy in Acbd5-deficient mice halted by adeno-associated virus gene therapy.

Acyl-CoA binding domain containing 5 (ACBD5) is a critical player in handling very long chain fatty acids (VLCFA) en route for peroxisomal β-oxidation. Mutations in ACBD5 lead to the accumulation of VLCFA and patients present retinal dystrophy, ataxia, psychomotor delay and a severe leukodystrophy. Using CRISPR/Cas9, we generated and characterized an Acbd5 Gly357* mutant allele.