Pseudomonas fluorescens P34 colonization impacts expression changes in wheat roots, reshapes rhizosphere microbial communities and promotes wheat plant growth.

Plant growth-promoting rhizobacteria (PGPR) can stimulate crop growth and performance through multiple mechanisms, making them promising bioinoculants for sustainable agriculture. Among known PGPR species, Pseudomonas fluorescens has attracted considerable attention because of its superior growth-promoting mechanisms and broad adaptability. Although P.

Efficacy and Safety of Extending Dosing Interval of Stapokibart in Patients with Atopic Dermatitis.

Stapokibart is a novel anti-interleukin-4 receptor α subunit monoclonal antibody approved for moderate-to-severe atopic dermatitis (AD) in adults. To evaluate the feasibility of extending dosing interval of stapokibart based on efficacy response in AD. In this ongoing, multicenter, open-label, single-arm trial (NCT06116565), stapokibart 300 mg was administered subcutaneously every 2 weeks (Q2W) for 12 weeks, followed by dosing interval adjustments at weeks 12 and 36.

Patient-Reported Outcomes in Adults with Moderate-to-Severe Atopic Dermatitis Treated with Stapokibart over 52 weeks: A Post Hoc Analysis of a Phase 3 Trial.

Introduction: Atopic dermatitis (AD) significantly impairs quality of life and requires long-term management. This post hoc analysis aimed to evaluate the effect of stapokibart (an anti-IL-4Rα antibody) on patient-reported outcomes (PROs) in adults with moderate-to-severe AD from a phase 3 trial (NCT05265923).

Methods: Eligible patients were randomized 1:1 to receive stapokibart 300 mg (loading dose 600 mg) (n = 251) or placebo (n = 249) every 2 weeks (Q2W) for 16 weeks.

PLAA/UFD-3 regulates P-bodies through its intrinsic disordered domain.

Regulation of proteome homeostasis is crucial for the survival and adaptation to changing environments for all species. In eukaryotes, this process is finely tuned through regulation at the level of transcription, translation, protein modification, and protein degradation. The phospholipase A2 activating protein (PLAA) is present in all eukaryotes and believed to be a key player in ubiquitin-dependent protein sorting and degradation via its interactions with ubiquitin and/or the AAA+ ATPase, valosin-containing protein (VCP/p97).

Discovery of acylsulfenic acid-featuring natural product sulfenicin and characterization of its biosynthesis.

Life's organic molecules are built with diverse functional groups that enable various importance biological functions. As such, the discovery of unique functional groups in nature can expand our understanding of the natural world. Here we report the genome-aided discovery of sulfenicin, a polyketide-non-ribosomal peptide hybrid natural product from a marine Streptomyces bacterium bearing a unique acylsulfenic acid functionality.

Optimizing Protein Production in the One-Pot PURE System: Insights into Reaction Composition and Expression Efficiency.

The One-Pot PURE (rotein synthesis sing ecombinant lements) system simplifies the preparation of traditional PURE systems by coculturing and purifying 36 essential proteins for gene expression in a single step, enhancing accessibility and affordability for widespread laboratory adoption and customization. However, replicating this protocol to match the productivity of traditional PURE systems can take considerable time and effort due to uncharacterized variability. In this work, we observed unstable PURE protein expression in the original One-Pot PURE strains, M15/pREP4 and BL21(DE3), and addressed this issue using glucose-mediated catabolite repression to minimize burdensome background expression.

Long-Term Stapokibart Treatment Induces Sustained Clinical Improvements in Patients With Moderate-to-Severe Atopic Dermatitis.

Stapokibart has been approved for the treatment of adults with atopic dermatitis (AD) in China. To report long-term efficacy of stapokibart in patients with moderate-to-severe AD. This post hoc analysis included 237 adult patients from a phase 3 trial (NCT05265923) who received stapokibart 300 mg (loading dose, 600 mg) every 2 weeks during the 16-week double-blind period and continued with the same dose of stapokibart in the subsequent 36-week maintenance period.

In-Depth Comparison of Reagent-Based Digestion Methods and Two Commercially Available Kits for Bottom-Up Proteomics.

Proteomic analysis plays an essential role in biology with several methodologies available for sample preparation and analysis. This study evaluates and compares various cell lysis and protein digestion protocols for bottom-up proteomics using HeLa S3 cells. We assessed two physical disruption methods to homogenize cells-sonication and BeatBox-alongside four digestion protocols.

Proteomics analysis reveals the differential impact of the p97 inhibitor CB-5083 on protein levels in various cellular compartments of the HL-60 cell line.

Human p97/VCP is a vital AAA ATPase (ATPase associated with diverse cellular activity) that plays critical roles in protein homeostasis by regulating autophagy, endosomal trafficking, and the ubiquitin-proteasome system. Global proteomics analysis of p97/VCP inhibition with CB-5083 has been performed in HCT116 colon cells. Here, we examined the impact of CB-5083 treatment in another cancer model, the HL-60 acute myeloid leukemia cell line, employing subcellular fractionation combined with label-free proteomics to analyze changes in protein levels across cytoplasmic, nuclear, and insoluble membrane protein compartments.

Combined tofacitinib citrate and 308-nm excimer laser treatment for vitiligo: a pilot study.

Background: Vitiligo is a clinically prevalent acquired skin disorder characterized by depigmentation. Currently, the therapeutic options for vitiligo are restricted, and numerous issues exist, such as a prolonged treatment course, unsatisfactory therapeutic efficacy, adverse reactions and a high propensity for recurrence after treatment cessation.

Objectives: To assess the safety and efficacy of combined treatment involving oral tofacitinib citrate (TC) and a 308-nm excimer laser (EL), with the aim of discovering a rapid and effective treatment approach to minimize the side-effects of various drugs.

Ni Vacancy and the Se/S Ratio Regulate the p-Band Center of Hollow NiSSe/Phase Junction CdS to Achieve High Efficiency and Broad-Spectrum Photocatalytic Performance.

Rational design of defect engineering and interfacial built-in electric fields of photocatalysts is imperative for renewable energy conversion. Herein, a multi-strategy involving the introduction of Ni vacancies, the adjustment of the Se/S ratio, and the construction of dual junctions are employed to simultaneously realize NiSSe/phase junction CdS (HCC) an excellent photocatalytic activity and broad light absorption. With the help of V and the regulation of S/Se, the local electrons are redistributed to occupy more antibonding orbitals and adjust the p-band center, thus optimizing the H adsorption energy of the catalyst to accelerate the photocatalytic reaction kinetics.

PA-824 inhibits porcine epidemic diarrhea virus infection and by inhibiting p53 activation.

Porcine epidemic diarrhea virus (PEDV) is a type A coronavirus that causes severe watery diarrhea in piglets, resulting in severe economic losses worldwide. Therefore, new approaches to control PEDV infection are essential for a robust and sustainable pig industry. We screened 314 small-molecule drug libraries provided by Selleck and found that four drugs had obviously inhibitory effects on PEDV in Vero cells.

Increasing Proteome Coverage Through a Reduction in Analyte Complexity in Single-Cell Equivalent Samples.

The advancement of sophisticated instrumentation in mass spectrometry has catalyzed an in-depth exploration of complex proteomes. This exploration necessitates a nuanced balance in experimental design, particularly between quantitative precision and the enumeration of analytes detected. In bottom-up proteomics, a key challenge is that oversampling of abundant proteins can adversely affect the identification of a diverse array of unique proteins.

Hollow cubic CuSe@CdS with tunable size for plasmon-induced Vis-NIR driven photocatalytic properties.

The rational design of the dimension and geometry of a plasmonic semiconductor cocatalyst is vitally important for efficient utilization of near-infrared (NIR) light and superior photocatalytic hydrogen generation. Herein, hollow cubic CuSe@CdS composites with different sizes and strong localized surface plasmon resonance (LSPR) were prepared by selenizing size-tunable CuO templates and loading CdS nanoparticles. The size of hollow cubic CuSe can affect the surface area and the conduction band potential through the size effect, regulating the carrier behavior of the CuSe@CdS heterojunction.

Biocatalytic Fluoroalkylation Using Fluorinated -Adenosyl-l-methionine Cofactors.

Modification of organic molecules with fluorine functionalities offers a critical approach to develop new pharmaceuticals. Here, we report a multienzyme strategy for biocatalytic fluoroalkylation using -adenosyl-l-methionine (SAM)-dependent methyltransferases (MTs) and fluorinated SAM cofactors prepared from ATP and fluorinated l-methionine analogues by an engineered human methionine adenosyltransferase hMAT2A. This work introduces the first example of biocatalytic 3,3-difluoroallylation.

Inhibitory effect of Buddlejasaponin IVb on porcine epidemic diarrhea virus in vivo and in vitro.

Porcine epidemic diarrhea virus (PEDV) is one of the main pathogens causing severe diarrhea in piglets. Infection of the host induces apoptosis, causing huge economic losses to the pig industry. At present, the preventive and therapeutic effects of commercial vaccines are not satisfactory, and it is necessary to develop new anti-PEDV drugs.

Health-related quality of life in patients with relapsed/refractory multiple myeloma treated with pomalidomide and dexamethasone ± subcutaneous daratumumab: Patient-reported outcomes from the APOLLO trial.

In the phase 3 APOLLO trial, daratumumab in combination with pomalidomide and dexamethasone (D-Pd) significantly reduced the rate of disease progression or death by 37% relative to Pd alone in patients with relapsed/refractory multiple myeloma (RRMM) who had received ≥1 prior line of therapy including lenalidomide and a proteasome inhibitor. Here, we present patient-reported outcomes (PROs) from APOLLO. Median treatment duration was 11.

Aggregation-induced emission luminogen with excellent triplet-triplet upconversion efficiency for highly efficient non-doped blue organic light-emitting diodes.

By combining aggregation-induced emission (AIE) effect and a triplet-triplet upconversion (TTU) process, a blue emitter with excellent photoluminescence quantum efficiency and high upconversion efficiency in the film state is developed, from which a highly efficient non-doped blue TTU organic light-emitting diode (TTU-OLED) was realized.

Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial.

Background: In a phase 1b study, intravenous daratumumab plus pomalidomide and dexamethasone induced a very good partial response or better rate of 42% and was well tolerated in patients with heavily pretreated multiple myeloma. We aimed to evaluate whether daratumumab plus pomalidomide and dexamethasone would improve progression-free survival versus pomalidomide and dexamethasone alone in patients with previously treated multiple myeloma.

Methods: In this ongoing, open-label, randomised, phase 3 trial (APOLLO) done at 48 academic centres and hospitals across 12 European countries, eligible patients were aged 18 years or older, had relapsed or refractory multiple myeloma with measurable disease, had an Eastern Cooperative Oncology Group performance status of 0-2, had at least one previous line of therapy, including lenalidomide and a proteasome inhibitor, had a partial response or better to one or more previous lines of antimyeloma therapy, and were refractory to lenalidomide if only one previous line of therapy was received.

Functionalization of Silk by AIEgens through Facile Bioconjugation: Full-Color Fluorescence and Long-Term Bioimaging.

Silkworm silk is a promising natural biopolymer for textile and biomedical applications for its remarkable flexibility, excellent biocompatibility and controllable biodegradability. The functionalization of silks makes them more versatile for flexible displays and visible bioscaffolds. However, fluorescent silks are normally fabricated through unstable physical absorption or complicated chemical reactions under harsh conditions.

Formation of an aminovinyl-cysteine residue in thioviridamides occurs through a path independent of known lanthionine synthetase activity.

2-Aminovinyl-cysteine (AviCys) is a thioether amino acid shared by a variety of ribosomally synthesized and posttranslationally modified peptides (RiPPs). Based on investigations into the biosynthesis of thioviridamide RiPPs in Streptomyces sp. NRRL S-87, we here report a path for the formation of this unusual thioether residue.

Pharmacokinetics and Safety of Posaconazole Tablet Formulation in Chinese Participants at High Risk for Invasive Fungal Infection.

Introduction: This study characterized the multidose pharmacokinetic (PK) characteristics of posaconazole tablets used as prophylactic antifungal therapy in Chinese patients with acute myelogenous leukemia (AML) at risk for invasive fungal infection (IFI).

Methods: Participants in this open-label, single-arm, phase 1b study received posaconazole 300 mg twice daily on day 1 and then once daily for up to 28 days. In the intensive PK sampling subgroup, posaconazole was administered under fasting conditions on days 1 and 8, and blood samples were regularly collected over 24 h.

A Heterotrimeric Dehydrogenase Complex Functions with 2 Distinct YcaO Proteins to Install 5 Azole Heterocycles into 35-Membered Sulfomycin Thiopeptides.

Sulfomycins are sulfur-rich, ribosomally synthesized, and post-translationally modified peptides (RiPPs) that are characterized by a 35-membered macrocyclic ring system with a pyridine domain central to five azoles and additional dehydroamino acids. The pathway through which these large thiopeptide antibiotics are formed in remains elusive. Starting with the cloning of the biosynthetic gene cluster of sulfomycins, we here dissect a two-stage process in which an unusual dehydrogenase heterotrimer functions with two distinct YcaO proteins to install five azole heterocycles into the core peptide sequence of the precursor peptide.

An AIE-Active Conjugated Polymer with High ROS-Generation Ability and Biocompatibility for Efficient Photodynamic Therapy of Bacterial Infections.

New, biocompatible materials with favorable antibacterial activity are highly desirable. In this work, we develop a unique conjugated polymer featuring aggregation-induced emission (AIE) for reliable bacterial eradication. Thanks to the AIE and donor-π-acceptor structure, this polymer shows a high reactive oxygen species (ROS)-generation ability compared to a low-mass model compound and the common photosensitizer Chlorin E6.