Browse Articles

Adjuvant Pembrolizumab plus Belzutifan for Renal-Cell Carcinoma

Application of ephrin-B2 loaded glycol chitosan-silk fibroin hydrogel in the treatment of diabetic refractory wounds

Abstract Diabetic skin ulcers are a major cause of disability, yet effective treatments remain limited due to microvascular dysfunction. This study investigated the effects of a glycol chitosan-silk fibroin hydrogel loaded with Ephrin-B2 (GCS-SF-B2 Gel) on the healing of full-thickness skin wounds in a diabetic mouse model. We prepared the hydrogel by mixing glycol chitosan and silk fibroin solutions, followed by lyophilization and adsorption of Ephrin-B2. The GCS-SF-B2 Gel exhibited a porous structure with a swelling capacity of up to 1600% and a moisturizing duration of up to 12 h. In vitro assays demonstrated that the hydrogel significantly promoted the proliferation and migration of NIH 3T3 cells. In a diabetic mouse model with full-thickness skin defects, the GCS-SF-B2 Gel demonstrated superior therapeutic efficacy compared to control, evidenced by macroscopic healing, increased fibroblast accumulation, improved collagen deposition, and significant angiogenesis at the wound site. These findings suggest that GCS-SF-B2 Gel is a promising candidate for promoting the healing of refractory diabetic wounds.

Safety and efficacy of intratumoural anti-CTLA4 with intravenous anti-PD1

Abstract Intravenous administration of anti-CTLA4 with anti-PD1 provides durable tumour responses but causes severe treatment-related adverse events in patients with cancer 1 . Intratumoural administration at lower doses but high local concentrations could enhance antitumour efficacy while minimizing systemic exposure and toxicity. Here we report the randomized multicentre phase 1b NIVIPIT trial (ClinicalTrials.gov: NCT02857569 ), which enrolled 61 patients with untreated metastatic melanoma, randomly assigned 2:1 to receive intravenous nivolumab (anti-PD1; 1 mg kg −1 ) combined with either intratumoural ipilimumab (anti-CTLA4; 0.3 mg kg −1 ) or intravenous ipilimumab (3 mg kg −1 ). The primary end-point was met with significantly lower incidence of grade 3 or 4 treatment-related adverse events at 6 months in the intratumoural versus intravenous arm (22.6% versus 57.1%), equivalent to anti-PD1 monotherapy. RECIST (response evaluation criteria in solid tumours) best objective response rate reached 65.7% for anti-CTLA4 injected lesions and 50% for uninjected lesions, confirming the relationship between intratumoural exposure to anti-CTLA4 and efficacy. Baseline tumour immune profiling revealed that protumoural activated regulatory T (T reg ) cells and M2 macrophages predict durable clinical benefit, regardless of the anti-CTLA4 administration route. A decrease in activated intratumoural T reg cells occurred only in patients who showed durable clinical benefit, who also presented high intratumoural Fcγ receptor (FcγR) expression. Our results provide a rationale for intratumoural anti-CTLA4 strategies in oligometastatic and early-stage cancers and indicate that high intratumoural activated T reg cell and FcγR + M2 macrophage numbers are prerequisites for efficacy of combined anti-CTLA4 and anti-PD1.

Somatic Genetic Rescue of Immunodeficiency in WHIM Syndrome

Integrated metabolomic, cytotoxic, and computational investigation of Caralluma tuberculata extract in breast cancer cells

I study World Cup penalty shoot-outs: they say a lot about the psychology of performance under pressure

Transparent fish takes center stage in $1 billion neuroscience initiative

The once-obscure Danionella fish will be the focus of an ambitious new Howard Hughes Medical Institute project

Synthesis, characterization, shelf life and optimization of process parameter of plasma-activated hydrogel production for Staphylococcus aureus Inhibition

Alternating atomic-dipole layers and switching dynamics in Al _1-x Sc _x N ferroelectrics

Wurtzite Al 1-x Sc x N ferroelectrics exhibit exceptional polarization and thermal stability, making them highly promising for a wide range of electronic applications. However, a more profound understanding is required regarding the atomic-scale mechanism through which cation substitution lowers the switching energy barrier and thus reduces the coercive field. We used spherical aberration–corrected transmission electron microscopy to reveal a periodic modulation of cation-anion spacing along the polarization direction, forming alternating atomic dipole layers. This modulation arises from energetically favorable chemical ordering of aluminum and scandium atoms between adjacent layers, with layer-resolved asymmetry in atomic arrangement. In situ imaging directly captures atomic-scale, noncollective, stepwise polarization switching, revealing intermediate states and local spacing fluctuations. Compositional inhomogeneity in these dipole layers creates multiple transient states that reduce the switching energy barrier. Our findings connect atomic-scale dipole structures to polarization switching kinetics, enabling the rational design of wurtzite ferroelectrics.

Explainable & Deterministic Intrusion Detection for CAN-FD: A Logic Extraction Framework

Orbital magnetoresistance in the antiferromagnet CoO driven by dynamic orbital angular momentum

Recent predictions of orders of magnitude larger orbital current effects compared with spin currents have attracted considerable interest. However, orbital currents must first be converted into spin currents to interact with the static magnetization dominated by spin angular momentum in conventional magnets. By using a magnet dominated by orbital angular momentum (OAM), we demonstrate a 70-fold enhancement in orbital Hall magnetoresistance in cobalt II oxide/copper (CoO/Cu*), compared with spin Hall magnetoresistance in cobalt II oxide/platinum (CoO/Pt). This arises from interactions between dynamic OAM from surface-oxidized Cu* and static OAM in the antiferromagnetic insulator CoO. Our results show how by using OAM-dominated materials, we can harness the benefits of giant orbital currents that have not been possible using conventional spin-dominated magnets.

Time-course changes in fluid balance following ingestion of a novel glycerol-electrolyte solution in a randomized trial

Abstract This randomized trial tested the effects of a novel glycerol-electrolyte solution (GES) compared with placebo on fluid balance for 8 h. Twenty-five (12 female, 13 male) healthy, active adults (30 ± 7 y, 76.91 ± 13.27 kg) completed two trials in a randomized, counterbalanced order. After arriving at the laboratory euhydrated, participants emptied their bladder, then had baseline body mass measured. Participants consumed 1 L of GES (0.75% glycerol, 40 mmol/L sodium, 15 mmol/L potassium, 8 mmol/L magnesium, 5 mg calcium) or placebo (water with flavor and sweetness matched to GES) followed by urine collection and body mass measurements for 8 h. A two-way repeated-measures ANOVA (beverage × time) was conducted, followed by Tukey’s HSD test. Values are difference between beverages ± 95% CI. There was a significant effect of beverage, with fluid balance higher (0.15 ± 0.03%, p  < 0.001) and urine output lower (-112 ± 23 g, p  < 0.001) in the GES versus placebo trials across the 8-h observation period. There was also a beverage-by-time interaction effect: fluid balance was higher and urine output was lower 2 h (0.23 ± 0.14% and − 159 ± 98 g, p  < 0.001), 3 h (0.19 ± 0.15% and − 144 ± 110 g, p  = 0.001), and 4 h (0.18 ± 0.15% and − 137 ± 117 g, p  < 0.01) with GES versus placebo. In summary, GES supported greater net fluid balance than placebo. The strongest pairwise differences occurred at 2–4 h, while the overall beverage effect was present across the full 8 h.

Continental breakup–driven uplift instigated East Antarctic Ice Sheet formation

Why Antarctica became glaciated ∼34 million years ago (Ma) remains debated, as relatively warm climates and sea temperatures appear inconsistent with ice sheet formation. Although a critical decline in CO 2 is considered primarily responsible, evidence suggests that other factors were important, too. We investigated whether regional topographic uplift, rooted in Jurassic continental breakup and mantle-surface feedbacks, enabled nucleation of the East Antarctic Ice Sheet (EAIS). By integrating geodynamic-topographic models with ice sheet and energy balance models, we show that progressive plateau growth in East Antarctica, including Eocene uplift of the Gamburtsev Mountains, pushed landscapes above the threshold for ice sheet nucleation by ∼45 Ma. Uplift enabled EAIS growth under warmer-than-expected climates, producing hemispheric asymmetry in early glaciation and reconciling Oligocene polar warmth with the onset of the modern icehouse world.

Steady-state temperature field of multilayer overlying strata under an equivalent fixed-wall-temperature heat source: similarity experiments and 3D simulation

CRISPR’s next act: the companies editing the epigenome to treat disease

The invisible hand

Microbiota have a hidden role in mosquito-borne disease

CCDC25 regulates sepsis-associated liver injury via neutrophil extracellular traps

Observation of quantum vortex core fractionalization and skyrmion formation in a superconductor

Magnetic fields can penetrate a superconductor in the form of quantum vortices, which consist of a core singularity with circulating currents. London’s quantization implies that there is one core singularity per quantum of magnetic flux in single-component superconductors. In this study, we report signatures of quantum vortex core fractionalization on the potassium-terminated surface of a multiband superconductor, KFe 2 As 2 . The observed splitting of single integer–flux vortices into several fractional vortices results in a disparity between the numbers of flux quanta and vortex cores. These fractional vortices often arrange in chains, which calculations show are characterized by a ℂP 2 skyrmionic topological invariant; this constitutes a different type of topological defect: the chiral skyrmion. The disparate natures of integer and fractional vortices comprising skyrmions lead to distinct spectroscopic signatures.

Clinical drug report generation using multi-phase prompt large language models

From Edison’s Invention Factory to the new architecture of innovation

Shifts reflect the maturation of institutions surrounding science