Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B.

Background: Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.

Methods: We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.

Trehalose Interferes with the Photosynthetic Electron Transfer Chain of Permeating the Bacterial Chromatophore Membrane.

Disaccharide trehalose has been proven in many cases to be particularly effective in preserving the functional and structural integrity of biological macromolecules. In this work, we studied its effect on the electron transfer reactions that occur in the chromatophores of the photosynthetic bacterium . In the presence of a high concentration of trehalose, following the activation of the photochemistry by flashes of light, a slowdown of the electrogenic reactions related to the activity of the photosynthetic reaction center and cytochtome (cyt) complexes is observable.

Detecting Xe in an atmospheric tracer experiment.

The Xcounts algorithm for calculating air concentrations of radioactive xenon isotopes (Eslinger et al., 2023) has been extended to estimate Xe in addition to Xe, Xe, Xe, and Xe. The algorithm was applied to 119 samples collected with a SAUNA Q system (Ringbom et al.

Towards designing improved cancer immunotherapy targets with a peptide-MHC-I presentation model, HLApollo.

Based on the success of cancer immunotherapy, personalized cancer vaccines have emerged as a leading oncology treatment. Antigen presentation on MHC class I (MHC-I) is crucial for the adaptive immune response to cancer cells, necessitating highly predictive computational methods to model this phenomenon. Here, we introduce HLApollo, a transformer-based model for peptide-MHC-I (pMHC-I) presentation prediction, leveraging the language of peptides, MHC, and source proteins.

Photosynthetic response of Solidago gigantea Aition and Calamagrostis epigejos L. (Roth) to complex environmental stress on heavy metal contaminated sites.

Studies of in situ plant response and adaptation to complex environmental stresses, are crucial for understanding the mechanisms of formation and functioning of ecosystems of anthropogenically transformed habitats. We study short- and long-term responses of photosynthetic apparatus (PSA) and anti-oxidant capacity to complex abiotic stresses of common plants Calamagrostis epigejos and Solidago gigantea in semi-natural (C) and heavy metal contaminated habitats (LZ). We found significant differences in leaf pigment content between both plant species growing on LZ plots and their respective C populations.

Comparative Effectiveness of Cell-Based Versus Egg-Based Influenza Vaccines in Prevention of Influenza Hospitalization During the 2022-2023 Season Among Adults 18-64 Years.

This retrospective cohort study evaluated the comparative vaccine effectiveness (cVE) of licensed standard-dose cell-based versus egg-based influenza vaccines in preventing influenza hospitalization among adults 18-64 years during the 2022-2023 season. The cohort included eligible Kaiser Permanente Southern California members who received ≥ 1 dose of influenza vaccine (n = 848,334). The adjusted cVE against influenza hospitalization was -10.

Redesign of the Chlamydomonas reinhardtii Q binding niche reveals photosynthesis works in the absence of a driving force for Q-Q electron transfer.

An in silico redesign of the secondary quinone electron acceptor (Q) binding pocket of the D1 protein of Photosystem II (PSII) suggested that mutations of the F265 residue would affect atrazine binding. Chlamydomonas reinhardtii mutants F265T and F265S were produced to obtain atrazine-hypersensitive strains for biosensor applications, and the mutants were indeed found to be more atrazine-sensitive than the reference strain IL. Fluorescence and thermoluminescence data agree with a weak driving force and confirm slow electron transfer but cannot exclude an additional effect on protonation of the secondary quinone.

Architecture and functional regulation of a plant PSII-LHCII megacomplex.

Photosystem II (PSII) splits water in oxygenic photosynthesis on Earth. The structure and function of the CSM-type PSII-LHCII (light-harvesting complex II) megacomplexes from the wild-type and PsbR-deletion mutant plants are studied through electron microscopy (EM), structural mass spectrometry, and ultrafast fluorescence spectroscopy [time-resolved fluorescence (TRF)]. The cryo-EM structure of a type I CSM megacomplex demonstrates that the three domains of PsbR bind to the stromal side of D1, D2, and CP43; associate with the single transmembrane helix of the redox active Cyt ; and stabilize the luminal extrinsic PsbP, respectively.

Contribution of Protonation to the Dielectric Relaxation Arising from Bacteriopheophytin Reductions in the Photosynthetic Reaction Centers of .

The pH dependence of the free energy level of the flash-induced primary charge pair PI was determined by a combination of the results from the indirect charge recombination of PQ and from the delayed fluorescence of the excited dimer (P*) in the reaction center of the photosynthetic bacterium , where the native ubiquinone at the primary quinone binding site Q was replaced by low-potential anthraquinone (AQ) derivatives. The following observations were made: (1) The free energy state of PI was pH independent below pH 10 (-370 ± 10 meV relative to that of the excited dimer P*) and showed a remarkable decrease (about 20 meV/pH unit) above pH 10. A part of the dielectric relaxation of the PI charge pair that is not insignificant (about 120 meV) should come from protonation-related changes.

Adjuvant Immune Checkpoint Inhibitors for Muscle-Invasive Urothelial Carcinoma: An Updated Systematic Review, Meta-analysis, and Network Meta-analysis.

Context: Adjuvant immune checkpoint inhibitors (ICIs) have recently emerged as guideline-recommended treatments of high-risk muscle-invasive urothelial carcinoma (MIUC). However, there is limited evidence regarding the optimal candidates and the differential efficacy of adjuvant ICI regimens.

Objective: To synthesize and compare the efficacy and safety of adjuvant ICIs for high-risk MIUC using updated data from phase III randomized controlled trials.

Promising strategies for the prevention of alcohol-related brain damage through optimised management of acute alcohol withdrawal: A focussed literature review.

There is an increasing awareness of the link between chronic alcohol consumption and the development of cognitive, behavioural and functional deficits. Currently, preventative strategies are limited and require engagement in dedicated long-term rehabilitation and sobriety services, the availability of which is low. The acute alcohol withdrawal syndrome is an episode of neurochemical imbalance leading to autonomic dysregulation, increased seizure risk and cognitive disorientation.

Reaction Mechanism of the Terminal Plastoquinone Q in Photosystem II as Revealed by Time-Resolved Infrared Spectroscopy.

The secondary plastoquinone (PQ) electron acceptor Q in photosystem II (PSII) undergoes a two-step photoreaction through electron transfer from the primary PQ electron acceptor Q, converting into plastoquinol (PQH). However, the detailed mechanism of the Q reactions remains elusive. Here, we investigated the reaction mechanism of Q in cyanobacterial PSII core complexes using two time-revolved infrared (TRIR) methods: dispersive-type TRIR spectroscopy and rapid-scan Fourier transform infrared spectroscopy.

Phe265 of the D1 protein is required to stabilize plastoquinone binding in the Q-binding site of photosystem II in Synechocystis sp. PCC 6803.

In Photosystem II electrons from water splitting pass through a primary quinone electron acceptor (Q) to the secondary plastoquinone (Q). The D2 protein forms the Q-binding site and the D1 protein forms the Q-binding site. A non-heme iron sits between Q and Q resulting in a quinone-Fe-acceptor complex that must be activated before assembly of the oxygen-evolving complex can occur.

Variability in Lipid Profiles During Young Adulthood and the Risk of Coronary Artery Calcium Incidence in Midlife: Insights From the CARDIA Study.

Background: Intraindividual variability in lipid profiles is recognized as a potential predictor of cardiovascular events. However, the influence of early adulthood lipid profile variability along with mean lipid levels on future coronary artery calcium (CAC) incidence remains unclear.

Methods: A total of 2395 participants (41.

Quantitative and comparative assessment of dyes and protocols for rapid ex vivo microscopy of fresh tissues.

Using ex vivo microscopy, virtual pathology can improve histological procedures by providing pathology images in near real-time without tissue destruction. Several emerging and promising approaches leverage fast-acting small-molecule fluorescent stains to replicate traditional pathology structural contrast, combined with rapid optical sectioning microscopes. However, several vital challenges must be addressed to translate virtual pathology into the clinical environment.

Safe and effective in vivo delivery of DNA and RNA using proteolipid vehicles.

Genetic medicines show promise for treating various diseases, yet clinical success has been limited by tolerability, scalability, and immunogenicity issues of current delivery platforms. To overcome these, we developed a proteolipid vehicle (PLV) by combining features from viral and non-viral approaches. PLVs incorporate fusion-associated small transmembrane (FAST) proteins isolated from fusogenic orthoreoviruses into a well-tolerated lipid formulation, using scalable microfluidic mixing.

Zinc and methyl jasmonate improve sugar beet tolerance to high boron stress by enhanced leaf photochemical performance.

Nutrient imbalances, such as high boron (B) stress, occur within, as well as across, agricultural systems worldwide and have become an important abiotic factor that reduces soil fertility and inhibits plant growth. Sugar beet is a B-loving crop and is better suited to be grown in high B environments, but the methods and mechanisms regarding the enhancement of high-B stress tolerance traits are not clear. The main objective of this research was to elucidate the effects of the alone and/or combined foliar spraying of zinc sulfate (ZnSO) and methyl jasmonate (MeJA) on the growth parameters, tolerance, and photochemical performance of sugar beet under high-B stress.

Effect of the insecticide clothianidin on the photosynthetic electron transport chain in pea.

Clothianidin (CL) is a neonicotinoid insecticide widely used in crop protection against insect pests. However, its effects on photosynthesis remain largely unknown. Here, by investigating the influence of CL at the concentrations of 22 and 110 μg/L on the primary processes of photosynthesis, membrane fluidity and structural changes of pea chloroplasts, we located several primary binding sites of this pesticide.

D1-Tyr246 and D2-Tyr244 in photosystem II: Insights into bicarbonate binding and electron transfer from Q to Q.

In photosystem II (PSII), D1-Tyr246 and D2-Tyr244 are symmetrically located at the binding site of the bicarbonate ligand of the non-heme Fe complex. Here, we investigated the role of the symmetrically arranged tyrosine pair, D1-Tyr246 and D2-Tyr244, in the function of PSII, by generating four chloroplast mutants of PSII from Chlamydomonas reinhardtii: D1-Y246F, D1-Y246T, D2-Y244F, and D2-Y244T. The mutants exhibited altered photoautotrophic growth, reduced PSII protein accumulation, and impaired O-evolving activity.