Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB-D melanoma: a phase 1/2 trial.

Neoadjuvant immunotherapies have shown antitumor activity in melanoma. Substudy 02C of the global, rolling-arm, phase 1/2, adaptive-design KEYMAKER-U02 trial is evaluating neoadjuvant pembrolizumab (anti-PD-1) alone or in combination, followed by adjuvant pembrolizumab, for stage IIIB-D melanoma. Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy.

Heterogeneous Cardiac-Derived and Neural Crest-Derived Aortic Smooth Muscle Cells Exhibit Similar Transcriptional Changes After TGFβ Signaling Disruption.

Background: Smooth muscle cells (SMCs) of cardiac and neural crest origin contribute to the developing proximal aorta and are linked to disease propensity in adults.

Methods: We analyzed single-cell transcriptomes of aortic SMCs from adult mice to determine basal states and changes after disrupting TGFβ (transforming growth factor-β) signaling necessary for aortic homeostasis.

Results: A minority of Myh11 lineage-marked SMCs differentially expressed genes suggestive of embryological origin.

Construction of ultrathin solid electrolyte interface on Zn anode within 1 min for high current operating condition.

Organic acid treatment can facilitate the in-situ formation of a solid electrolyte interface (SEI) on Zn foil protecting the anode from corrosion. However, the generation of hydrogen (H) during this process is inevitable, which is often considered detrimental to getting compact SEI. Herein, a H film-assisted method is proposed under concentrated Amino-Trimethylene-Phosphonic-Acid to construct ultrathin and dense SEI within 1 min.

Biohydrogen utilization in legume-rhizobium symbiosis reveals a novel mechanism of accelerated tetrachlorobiphenyl transformation.

Symbiosis between Glycine max and Bradyrhizobium diazoefficiens were used as a model system to investigate whether biohydrogen utilization promotes the transformation of the tetrachlorobiphenyl PCB77. Both a H uptake-positive (Hup) strain (wild type) and a Hup strain (a hupL deletion mutant) were inoculated into soybean nodules. Compared with Hup nodules, Hup nodules increased dechlorination significantly by 61.

Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis.

Background: Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects.

A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models.

Idiopathic pulmonary fibrosis (IPF) is an aggressive interstitial lung disease with a high mortality rate. Putative drug targets in IPF have failed to translate into effective therapies at the clinical level. We identify TRAF2- and NCK-interacting kinase (TNIK) as an anti-fibrotic target using a predictive artificial intelligence (AI) approach.

Loss of Myo19 increases metastasis by enhancing microenvironmental ROS gradient and chemotaxis.

Tumor metastasis involves cells migrating directionally in response to external chemical signals. Reactive oxygen species (ROS) in the form of HO has been demonstrated as a chemoattractant for neutrophils but its spatial characteristics in tumor microenvironment and potential role in tumor cell dissemination remain unknown. Here we investigate the spatial ROS distribution in 3D tumor spheroids and identify a ROS concentration gradient in spheroid periphery, which projects into a HO gradient in tumor microenvironment.

A HO-specific fluorescent probe for evaluating oxidative stress in pesticides-treated cells, rice roots and zebrafish.

Hydrogen peroxide (HO) plays an irreplaceable role in the evaluation of the redox status in versatile circumstances. The levels of HO can be affected by both internal and external stimuli, including environmental hazards. Abnormal production of HO is a common characteristic of pesticide-caused damage.

Coumarin-Conjugated Macromolecular Probe for Sequential Stimuli-Mediated Activation.

Protein bioconjugation has emerged as one of the most valuable tools for the development of protein-based biochemical assays. Here, we report a fluorescent macromolecular material, , in which the coumarin derivative is specifically conjugated onto HaloTag protein to achieve a dual-stimuli-mediated fluorescence response. is first obtained by installing a HO-sensitive boron cage onto the C7 hydroxy moiety of the coumarin fluorophore with a HaloTag ligand attaching to the pH-labile 1,3-dioxane moiety.

A pilot study to assess the feasibility of a remotely monitored high-intensity interval training program prior to allogeneic hematopoietic stem cell transplantation.

Introduction: Although allogeneic hematopoietic stem cell transplantation (HCT) can be a curative therapy for hematologic disorders, it is associated with treatment-related complications and losses in cardiorespiratory fitness and physical function. High-intensity interval training (HIIT) may be a practical way to rapidly improve cardiorespiratory fitness and physical function in the weeks prior to HCT. The primary aim of this study was to assess the feasibility of implementing a pre-HCT home-based HIIT intervention.

In-situ spectroscopic probe of the intrinsic structure feature of single-atom center in electrochemical CO/CO reduction to methanol.

While exploring the process of CO/CO electroreduction (CORR) is of great significance to achieve carbon recycling, deciphering reaction mechanisms so as to further design catalytic systems able to overcome sluggish kinetics remains challenging. In this work, a model single-Co-atom catalyst with well-defined coordination structure is developed and employed as a platform to unravel the underlying reaction mechanism of CORR. The as-prepared single-Co-atom catalyst exhibits a maximum methanol Faradaic efficiency as high as 65% at 30 mA/cm in a membrane electrode assembly electrolyzer, while on the contrary, the reduction pathway of CO to methanol is strongly decreased in CORR.

A strong bimetal-support interaction in ethanol steam reforming.

The metal-support interaction (MSI) in heterogeneous catalysts plays a crucial role in reforming reaction to produce renewable hydrogen, but conventional objects are limited to single metal and support. Herein, we report a type of RhNi/TiO catalysts with tunable RhNi-TiO strong bimetal-support interaction (SBMSI) derived from structure topological transformation of RhNiTi-layered double hydroxides (RhNiTi-LDHs) precursors. The resulting 0.

GYY4137, a HS donor, ameliorates kidney injuries in diabetic mice by modifying renal ROS-associated enzymes.

Diabetic nephropathy (DN) is a common microvascular complication of both type 1 and type 2 diabetes mellitus and often advances to end-stage renal disease. Oxidative stress plays an important role in the pathogenesis and progress of DN. Hydrogen sulfide (HS) is considered as a promising candidate for the management of DN.

FN (Fibronectin)-Integrin α5 Signaling Promotes Thoracic Aortic Aneurysm in a Mouse Model of Marfan Syndrome.

Background: Marfan syndrome, caused by mutations in the gene for fibrillin-1, leads to thoracic aortic aneurysms (TAAs). Phenotypic modulation of vascular smooth muscle cells (SMCs) and ECM (extracellular matrix) remodeling are characteristic of both nonsyndromic and Marfan aneurysms. The ECM protein FN (fibronectin) is elevated in the tunica media of TAAs and amplifies inflammatory signaling in endothelial and SMCs through its main receptor, integrin α5β1.

Stille type P-C coupling polycondensation towards phosphorus-crosslinked polythiophenes with P-regulated photocatalytic hydrogen evolution.

Recently, exploring new type polymerization protocols has been a major driving force in advancing organic polymers into highly functional materials. Herein we report a new polycondensation protocol to implant the phosphorus (P) atom in the main backbone of crosslinked polythiophenes. The polycondensation harnesses a Stille phosphorus-carbon (P-C) coupling reaction between phosphorus halides and aryl stannanes that has not been reported previously.

Promoting Electrocatalytic Hydrogenation of Oxalic Acid to Glycolic Acid via an Al Ion Adsorption Strategy Coupled with Ethylene Glycol Oxidation.

Electrocatalytic hydrogenation (ECH) of oxalic acid (OX) to produce glycolic acid (GA), an important building block of biodegradable polymers as well as application in various branches of chemistry, has attracted extensive attention in the industry, while it still encounters challenges of low reaction rate and selectivity. Herein, we reported a cation adsorption strategy to realize the efficient ECH of OX to GA by adsorbing Al ions on an anatase titanium dioxide (TiO) nanosheet array, achieving 2-fold enhanced GA productivity (1.3 vs 0.

Stimulus-Responsive Zwitterionic Prodrug Delivery System with Sustained Release of Hydrogen Sulfide for Protective Aortic Dissection.

Aortic dissection (AD) is one of the most frequent types of aortic disease with extremely poor prognosis. The biological signaling gas hydrogen sulfide (HS) has exhibited protective effects in various types of cardiovascular diseases. However, as a toxic, colorless gas, the application of HS is immensely hampered due to the lack of ideal donors.

Nanozyme-reinforced hydrogel as a HO-driven oxygenerator for enhancing prosthetic interface osseointegration in rheumatoid arthritis therapy.

Stem cell-based therapy has drawn attention for enhancing the osseointegration efficiency after joint replacement in the rheumatoid arthritis (RA). However, therapeutic efficacy of this approach is threatened by the accumulated reactive oxygen species (ROS) and poor oxygen supply. Herein, we develop a nanozyme-reinforced hydrogel for reshaping the hostile RA microenvironment and improving prosthetic interface osseointegration.

Blood pressure-independent renoprotective effects of small interference RNA targeting liver angiotensinogen in experimental diabetes.

Background And Purpose: Small interfering RNA (siRNA) targeting liver angiotensinogen lowers blood pressure, but its effects in hypertensive diabetes are unknown.

Experimental Approach: To address this, TGR (mRen2)27 rats (angiotensin II-dependent hypertension model) were made diabetic with streptozotocin over 18 weeks and treated with either vehicle, angiotensinogen siRNA, the AT antagonist valsartan, the ACE inhibitor captopril, valsartan + siRNA or valsartan + captopril for the final 3 weeks. Mean arterial pressure (MAP) was measured via radiotelemetry.

Microbial degradation of aristolochic acid I by endophytic fungus A.h-Fs-1 of .

Asari Radix et Rhizoma is commonly used in classic prescriptions of herbal medicine in several Asian countries for resuscitation, pain relief, and sore treatment, and () is an important source material of Asari Radix et Rhizoma. However, the plants of the Asari Radix et Rhizoma and some plants in spp. contain aristolochic acid I (AAI), which is considered as a carcinogen.

mRNA vaccine boosting enhances antibody responses against SARS-CoV-2 Omicron variant in individuals with antibody deficiency syndromes.

Individuals with primary antibody deficiency (PAD) syndromes have poor humoral immune responses requiring immunoglobulin replacement therapy. We followed individuals with PAD after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination by evaluating their immunoglobulin replacement products and serum for anti-spike binding, Fcγ receptor (FcγR) binding, and neutralizing activities. The immunoglobulin replacement products tested have low anti-spike and receptor-binding domain (RBD) titers and neutralizing activity.