Synergistic Enhancement of Ferroptosis via Mitochondrial Accumulation and Photodynamic-Controlled Release of an Organogold(I) Cluster Prodrug.

Effective delivery and controlled release of metallo-prodrugs with sustained activation and rapid response feed the needs of precise medicine in metal chemotherapeutics. However, gold-based anticancer drugs often suffer from detoxification binding and extracellular transfer by sulfur-containing peptides. To address this challenge, we integrate a thiol-activated prodrug strategy of newly prepared hypercoordinated carbon-centered gold(I) clusters (HCGCs) with their photosensitization character to augment the mitochondrial release of Au(I) in tumors.

Modeling of Jet Lag and Searching for an Optimal Light Treatment.

The role of the hierarchical organization of the suprachiasmatic nucleus (SCN) in its functioning, jet lag, and the light treatment of jet lag remains poorly understood. Using the core-shell model, we mimic collective behavior of the core and shell populations of the SCN oscillators in transient states after rapid traveling east and west. The existence of a special region of slow dynamical states of the SCN oscillators can explain phenomena such as the east-west asymmetry of jet lag, instances when entrainment to an advance is via delay shifts, and the dynamics of jet lag recovery time.

High-Performance TiCT-MXene/Mycelium Hybrid Membrane for Efficient Lead Remediation: Design and Mechanistic Insights.

This study presents a hybrid microfiltration technology designed for high-performance lead (Pb(II)) remediation, especially from aqueous solutions with high Pb(II) concentrations, by utilizing two-dimensional (2D) TiCT-MXene layers deposited on dry mycelium membranes. The hybrid TiCT-MXene/mycelium (MyMX) membranes were fabricated via a single-step electrochemical deposition (ECD) technique, which enabled a uniform coating of 2D TiCT-MXene onto individual hyphal fibers of a prefabricated mycelium membrane. Optimized ECD parameters for high Pb(II) uptake were identified using scanning electron microscopy and energy-dispersive X-ray spectroscopy.

Acceptability and Future Considerations for Telegenetic Counseling After the COVID Pandemic: Interviews with Genetic Counselors, Clinicians, and Patients.

While telegenetic counseling has increased substantially since the start of the COVID-19 pandemic, previous studies reported concerns around building rapport, nonverbal communication, and the patient-counselor relationship. This qualitative evaluation elicited feedback from genetic counselors, referring clinicians, and patients from a single healthcare organization to understand the user-driven reasons for overall satisfaction and experience. We conducted 22 in-depth, semi-structured interviews with participants from all 3 groups between February 2022 and February 2023.

Role of Ciliary Neurotrophic Factor in Angiotensin II-Induced Hypertension.

Background: Ciliary neurotrophic factor (CNTF), mainly known for its neuroprotective properties, belongs to the IL-6 (interleukin-6) cytokine family. In contrast to IL-6, the effects of CNTF on the vasculature have not been explored. Here, we examined the role of CNTF in AngII (angiotensin II)-induced hypertension.

Atrial Fibrillation Related Titin Truncation Is Associated With Atrial Myopathy in Patient-Derived Induced Pluripotent Stem Cell Disease Models.

Background: Protein-truncating mutations in the titin gene are associated with increased risk of atrial fibrillation. However, little is known about the underlying pathophysiology.

Methods: We identified a heterozygous titin truncating variant (TTNtv) in a patient with unexplained early onset atrial fibrillation and normal ventricular function.

Playing a serious game to increase fertility awareness: perceptions of adolescents, parents and teachers.

Infertility is increasing globally, affecting one in six adults due to factors like delayed childbearing and lifestyle changes. Despite the recognition of the importance of increasing fertility awareness, levels remain low. This study evaluated the perceptions of 'FActs!', a serious game aimed at improving adolescents' fertility awareness.

Directed Evolution of AAV9 for Efficient Gene Expression in Cardiomyocytes and .

Adeno-associated viral (AAV) vectors are increasingly used for preclinical and clinical cardiac gene therapy approaches. However, gene transfer to cardiomyocytes poses a challenge due to differences between AAV serotypes in terms of expression efficiency and . For example, AAV9 vectors work well in rodent heart muscle cells but not in cultivated neonatal rat ventricular cardiomyocytes (NRVCMs), necessitating the use of AAV6 vectors for studies.

Schistosomiasis treatment in young children: a welcome step towards deployment of the paediatric praziquantel formulation.

It is an awkward fact that effective public health control of schistosomiasis in Africa has yet to deliver a fully comprehensive intervention for appropriate anthelmintic treatment of those preschool-age children and infants with active infection(s) and/or insidious disease. Over the last decade, despite the steady progress of the Pediatric Praziquantel Consortium in developing a monoenantiomeric oral dispersible tablet, future challenges remain in securing its deployment and implementation at scale. This commentary provides a forward-looking critique for the international community, reminding us of this unfortunate treatment gap, and seeks to encourage commensurate action on ameliorating this overlooked medical inequity.

Two cGMP-dependent protein kinases have opposing effects on molt-inhibiting hormone regulation of Y-organ ecdysteroidogenesis.

Decapod crustaceans regulate molting through steroid molting hormones, ecdysteroids, synthesized by the molting gland (Y-organ, YO). Molt-inhibiting hormone (MIH), a neuropeptide synthesized and secreted by the eyestalk ganglia, negatively regulates YO ecdysteroidogenesis. MIH signaling is mediated by cyclic nucleotide second messengers.

The Carnivoran Adaptive Landscape Reveals Trade-offs among Functional Traits in the Skull, Appendicular, and Axial Skeleton.

Analyses of form-function relationships are widely used to understand links between morphology, ecology, and adaptation across macroevolutionary scales. However, few have investigated functional trade-offs and covariance within and between the skull, limbs, and vertebral column simultaneously. In this study, we investigated the adaptive landscape of skeletal form and function in carnivorans to test how functional trade-offs among these skeletal regions contribute to ecological adaptations and the topology of the landscape.

Local adaptation and phenotypic plasticity in two forest understorey herbs in response to forest management intensity.

Local adaptation is a common phenomenon that helps plant populations to adjust to broad-scale environmental heterogeneity. Given the strong effect of forest management on the understorey microenvironment and often long-term effects of forest management actions, it seems likely that understorey herbs may have locally adapted to the practiced management regime and induced environmental variation. We investigated the response of and to forest management using a transplant experiment along a silvicultural management intensity gradient.

Floral traits underlying mating system differentiation in the wind-pollinated sister species and .

The shift from outcrossing to predominantly selfing is one of the most common transitions in plant evolution. This evolutionary shift has received considerable attention from biologists; however, this work has almost exclusively been focused on animal-pollinated systems. Despite the seminal ecological and economic importance of wind-pollinated species, the mechanisms controlling the degree of outcrossing in wind-pollinated taxa remain poorly understood.

Tropical tree species with high wood specific gravity have higher concentrations of wood phosphorus and are more efficient at resorbing it.

Phosphorus (P) and potassium (K) play important roles in plant metabolism and hydraulic balance, respectively, while calcium (Ca) and magnesium (Mg) are important components of cell walls. Although significant amounts of these nutrients are found in wood, relatively little is known on how the wood concentrations of these nutrients are related to other wood traits, or on the factors driving the resorption of these nutrients within stems. We measured wood nutrient (i.

Modified Gegen Qinlian Decoction Ameliorates DSS-Induced Colitis in Mice via the Modulation of NF-B and Nrf2/HO-1 Pathways.

This study aims to reveal the potential molecular mechanisms of modified Gegen Qinlian decoction (MGQD) in relieving ulcerative colitis (UC). C57BL/6J mice were used to establish experimental colitis via dextran sodium sulfate (DSS). Body weight, disease activity index (DAI), spleen weight, colon length, and histopathologic features were measured to evaluate the therapeutic effects of MGQD on mice with UC.

The role of ferroptosis in colorectal cancer and its potential synergy with immunotherapy.

Colorectal cancer (CRC) is one of the most prevalent and deadly malignancies worldwide. Recently, ferroptosis, a novel form of regulated cell death characterized by iron dependency and lipid peroxidation, has garnered significant attention from researchers. The mechanisms underlying ferroptosis, including intracellular iron levels, lipid peroxidation, and antioxidant system regulation, offer new insights into cancer treatment strategies.

Squamate reptiles may have compensated for the lack of γδTCR with a duplication of the TRB locus.

Squamate reptiles are amongst the most successful terrestrial vertebrate lineages, with over 10,000 species across a broad range of ecosystems. Despite their success, squamates are also amongst the least studied lineages immunologically. Recently, a universal lack of γδ T cells in squamates due to deletions of the genes encoding the T cell receptor (TCR) γ and δ chains was discovered.

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.

HMGB1 lactylation drives neutrophil extracellular trap formation in lactate-induced acute kidney injury.

Rationale: Acute kidney injury (AKI) is a clinical syndrome associated with a multitude of conditions. Although renal replacement therapy (RRT) remains the cornerstone of treatment for advanced AKI, its implementation can potentially pose risks and may not be readily accessible across all healthcare settings and regions. Elevated lactate levels are implicated in sepsis-induced AKI; however, it remains unclear whether increased lactate directly induces AKI or elucidates the underlying mechanisms.

Subtype-specific human endogenous retrovirus K102 envelope protein is a novel serum immunosuppressive biomarker of cancer.

Immune dysfunction is one of the hallmarks of cancer and plays critical roles in immunotherapy resistance, but there is no serum biomarker that can be used to evaluate immune-dysfunction status of cancer patients. Here, we identified subtype-specific human endogenous retrovirus K102 envelope (HERV-K102-Env) with immunosuppressive activity in circulating blood as a novel serum immunosuppressive biomarker of cancer. We first generated monoclonal antibodies against K102-Env with high sensitivity and specificity, and we developed an ELISA assay to detect serum K102-Env.

ESAT-6 protein suppresses allograft rejection by inducing CD4Foxp3 regulatory T cells through IκBα/cRel pathway.

Background: Maintenance immunosuppression is required for suppression of alloimmunity or allograft rejection. However, continuous use of immunosuppressants may lead to various side effects, necessitating the use of alternative immunosuppressive drugs. The early secreted antigenic target of 6 kDa (ESAT-6) is a virulence factor and immunoregulatory protein of mycobacterium tuberculosis (Mtb), which alters host immunity through dually regulating development or activation of various immune cells.

Synergetic role of TRPV4 inhibitor and mechanical loading on reducing inflammation.

Resolution of inflammation is essential for normal tissue healing and regeneration, with macrophages playing a key role in regulating this process through phenotypic changes from a pro-inflammatory to an anti-inflammatory state. Pharmacological and mechanical (mechanotherapy) techniques can be employed to polarize macrophages toward an anti-inflammatory phenotype, thereby diminishing inflammation. One clinically relevant pharmacological approach is the inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4).

Corrigendum: Bi-specific autoantigen-T cell engagers as targeted immunotherapy for autoreactive B cell depletion in autoimmune diseases.

[This corrects the article DOI: 10.3389/fimmu.2024.

The role and therapeutic targeting of the CCL2/CCR2 signaling axis in inflammatory and fibrotic diseases.

CCL2, a pivotal cytokine within the chemokine family, functions by binding to its receptor CCR2. The CCL2/CCR2 signaling pathway plays a crucial role in the development of fibrosis across multiple organ systems by modulating the recruitment and activation of immune cells, which in turn influences the progression of fibrotic diseases in the liver, intestines, pancreas, heart, lungs, kidneys, and other organs. This paper introduces the biological functions of CCL2 and CCR2, highlighting their similarities and differences concerning fibrotic disorders in various organ systems, and reviews recent progress in the diagnosis and treatment of clinical fibrotic diseases linked to the CCL2/CCR2 signaling pathway.