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mannitol (Aridol / Osmohale)

✓ Approved

Syntara · 小分子 · 小分子

什么是 mannitol？

mannitol 是一种小分子，由Syntara研发。该药已获批，用于治疗相关适应症，给药途径：Inhaled。

药物档案

商品名Aridol, Osmohale
公司Syntara
药物类别小分子
给药途径Inhaled
状态Approved
来源： ClinicalTrials.gov, Syntara

治疗适应症

mannitol 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Respiratory, thoracic and mediastinal disordersRespiratory failure✓ Approved

相关研究文献

PubMedBiology open2026-08-05

The neurotrophin DNT-2 via the Toll-2 receptor regulates neuronal survival and morphology during visual system development.

Alshamsi Naser N, Rojo-Cortés Francisca F, Fernandes Jervis J, Perrett Callum C et al.

During vertebrate nervous system development, neurons are produced in excess and those receiving neurotrophin ligands are maintained, enabling neural circuit establishment. An apoptotic wave sweeps across the Drosophila pupal visual system, but whether neurotrophins participate in forming adult visual circuits remained unknown. Here, we show that Drosophila Neurotrophin-3 (spz-3) and DNT-2 (spz-5) are expressed in retinal cells and medulla neurons, and Toll receptors across the visual system. Using loss and gain of function conditions for DNT-3 (spz-3) and DNT-2 (spz-5) we show that they both can, and are required to, promote cell survival. Importantly, genetic interaction data show that DNT-2 can function together with Toll-2. DNT-2 neurons were identified as medulla Mi1 neurons that connect to lamina L1 neurons expressing Toll-2. Loss of function for DNT-2 or Toll-2 induced apoptosis, and Toll-2 knock-down prevented the pro-survival function of DNT-2. DNT-2 over-expression resulted in excess Toll-2 neurons, whereas most Toll-2 neurons were lost in DNT-2 mutants. Furthermore, DNT-2 and Toll-2 were required for appropriate L1 axonal columnar organisation and dendritic morphology. Altogether, evolutionarily conserved neurotrophin family ligands control neuronal number through Toll receptors during visual circuit development in Drosophila.

PMID 42552905
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PubMedFrontiers in immunology2026-08-05

Plasma levels of soluble Flt-1 and Tie-2 correlate with neovascularization in human carotid atherosclerotic plaques - a pilot study.

Zamani Mahtab M, Skagen Karolina K, Lindberg Beate B, Bjerkeli Vigdis V et al.

To determine whether circulating soluble Flt-1 (sFlt-1) and soluble Tie-2 (sTie-2) are associated with intraplaque neovascularization (IPN) in human carotid atherosclerotic plaques. Forty-four patients with ≥50% carotid stenosis underwent conventional carotid ultrasound and superb microvascular imaging (SMI); 29 had plasma collected and 11 provided carotid endarterectomy specimens for histology. IPN was quantified as neovessel counts in 2-minute SMI cine loops and as microvessel counts in excised plaques. Plasma VEGF-A/B/C/D, Ang-2, sFlt-1, and sTie-2 were measured by immunoassays. Public single-cell RNA-seq data from human carotid plaques were interrogated to map FLT1, TEK, VEGFA, ANGPT1, and ANGPT2 expression to specific plaque cell populations. IPN was detected in 33/44 (75%) patients, with 0-16 neovessels on SMI (median 4). Plasma sFlt-1 correlated with SMI neovessel counts (r=0.42, p=0.030), with a similar trend for sTie-2 (r=0.37, p=0.057), whereas VEGF-A/B/C/D and Ang-2 showed no significant relationships. In the surgical subgroup, histological neovessel counts correlated with sFlt-1 (r=0.65, p=0.030) and SMI neovessel count (r= 0.68, p =0.02) but not sTie-2. sFlt-1 and sTie-2 correlated with BMI (and sTie-2 also with age), yet log-sFlt-1 remained independently associated with SMI-derived neovessel counts after adjustment for age and BMI (B = 13.24, 95% CI 0.17-26.30, p=0.047; R²=0.18), while sTie-2 was not. No significant associations were observed between IPN or sFlt-1/sTie-2 and lipid profile, CRP, leukocyte counts, or other conventional risk factors. Single-cell transcriptomics showed FLT1 and ANGPT2 broadly expressed across endothelial, smooth-muscle, and myeloid clusters, with TEK largely confined to endothelial cells and ANGPT1 to smooth-muscle cells, supporting local activation of VEGF-FLT1 and Ang-TEK/Tie-2 signaling within plaques. In this pilot study, higher plasma sFlt-1, and, to a lesser degree sTie-2, correlated with carotid IPN on SMI and histology, independent of age and BMI. These findings suggest that soluble VEGF- and Ang/Tie-2-receptor pathways may serve as circulating, context-sensitive markers of intraplaque angiogenesis and plaque vulnerability, meriting evaluation in larger longitudinal cohorts.

PMID 42553160
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PubMedDiseases of the colon and rectum2026-08-05

Trends in the Utilization of Two-Stage Versus Three-Stage Ileal Pouch Anal Anastomosis Among Privately Insured Patients With Ulcerative Colitis in the USA, 2007 to 2023.

Taylor Kathryn K KK, Kin Cindy J CJ, Kirilcuk Natalie N NN, Morris Arden M AM et al.

Ileal pouch anal anastomosis can be performed via 2- and 3-stage techniques, with similar short- and long-term clinical outcomes. 2-stage ileal pouch anal anastomosis became the predominant approach in the 2000s; whether this trend has continued remains unknown. To compare trends in the utilization of 3-stage, traditional 2-stage, and modified 2-stage IPAA for ulcerative colitis as well as markers of disease severity over time. Retrospective cohort. Privately insured patients from an administrative database. Non-elderly adults with a diagnosis of ulcerative colitis who underwent ileal pouch anal anastomosis between 2007 and 2023 and remained enrolled in their insurance plan for ≥ 6 months after surgery. Proportion of patients undergoing 3-stage, traditional 2-stage, and modified 2-stage ileal pouch anal anastomosis; annualized change in disease severity at the time of ileal pouch anal anastomosis creation. Four thousand thirty-nine patients underwent IPAA during the study period (2,179 traditional 2-stage; 1,107 3-stage; and 753 modified 2-stage). The proportion of patients undergoing a traditional 2-stage IPAAs decreased steadily (1.3% points per year [95% CI -1.7 to -0.9]) with a commensurate rise in both 3-stage (0.3% points per year [95% CI -0.02-0.7]) and modified 2-stage operations (0.9% points per year [95% CI 0.6-1.2]). Patients undergoing 3-stage or modified 2-stage IPAA had a more rapid increase in exposure to advanced therapies in the year before surgery (+ 2.9 vs + 2.0% points). Limitations: potential misclassification, generalizability. More patients are undergoing 3-stage and modified 2-stage operations than traditional 2-stage ileal pouch anal anastomosis. This shift parallels an increase in multiple markers of disease severity at IPAA creation, especially exposure to advanced therapies. See Video Abstract.

PMID 42554159
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PubMedBritish journal of cancer2026-08-05

A Phase 1/2 study of ontorpacept (TTI-621) in combination with doxorubicin in patients with unresectable or metastatic high-grade leiomyosarcoma.

Movva Sujana S, Allgood Victoria V, Chugh Rashmi R, Davis Lara E LE et al.

Ontorpacept, a recombinant signal regulatory protein alpha (SIRPα)-blocking fusion protein, has antitumour activity by disrupting CD47-SIRPα signalling. This Phase 1/2 study examined ontorpacept with doxorubicin in patients with leiomyosarcoma. Eligible patients were ≥18 years with metastatic or locally advanced high-grade soft-tissue sarcomas (high-grade leiomyosarcoma in Phase 2). In Phase 1, patients received escalating doses of ontorpacept plus doxorubicin. Phase 2 dose expansion evaluated ontorpacept doses 0.2, 1.0, and 2.0 mg/kg plus doxorubicin. The primary endpoints were safety (Phase 1); and objective response rate (ORR) (Phase 1/2). Seventy-six patients were enrolled (Phase 1, n = 9; Phase 2, n = 67). No dose-limiting toxicities occurred in Phase 1. The most common treatment-related adverse events were neutrophil count decreased/neutropenia (grade ≥3 in 66% of patients). In Phase 1, one patient receiving ontorpacept 2.0 mg/kg had a confirmed partial response. In Phase 2, six patients receiving ontorpacept 0.2 mg/kg (ORR, 18.8%; 95% CI, 7.2-36.4) and one patient receiving 2.0 mg/kg (ORR, 4.5%; 95% CI, 0.1-22.8) had confirmed partial responses. This first study of CD47 inhibition with chemotherapy in leiomyosarcomas shows manageable safety, supporting further investigation of ontorpacept dosing and schedule, in combination with doxorubicin and as monotherapy.

PMID 42552364
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PubMedAutism & developmental language impairments2026-08-05

Adaptive Functioning in Expressively Nonverbal and Minimally Verbal Autistic Children: Nonverbal Intelligence as a Predictive Factor.

Rodríguez-Armendariz Ekaine E, Ábalos Zuriñe Z, Castroviejo Elena E, Vicente Agustín A

Adaptive functioning is a strong predictor of long-term outcomes for autistic individuals, yet evidence regarding its association with ADOS-2 comparison scores, nonverbal IQ (NVIQ), and early language development remains inconsistent. Findings on the contributions of IQ and ADOS-2 comparison scores are mixed, and early linguistic abilities have received comparatively less attention. This study examined how receptive language delay, NVIQ, and ADOS-2 comparison scores relate to later adaptivity in nonverbal and minimally verbal autistic children. Participants were 4- to 12-year-old autistic children (N = 44) who completed ADOS-2 Module 1 at baseline, indicating limited expressive language but variability in age and developmental profiles. Baseline assessments included ADOS-2 comparison scores, NVIQ (Leiter-3), and receptive vocabulary (PPVT-III). Adaptive functioning was measured 2 to 3 years later using Vineland-3 subscales. To examine the contribution of each variable, we fitted multiple linear regression models with Vineland-3 scores as the dependent variable and standardized test scores as continuous predictors, while controlling for children's age (in months) and the testing interval between the ADOS-2 and the Vineland-3. We first fitted separate models for each predictor, followed by additive models including the three predictors. Additional models included interaction terms between NVIQ and ADOS-2 comparison scores, PPVT-III scores and ADOS-2 scores, NVIQ and PPVT-III scores, and their three-way interaction. Model comparisons were conducted to determine which model provided a better fit for the data. NVIQ emerged as the only significant predictor of adaptive functioning. Although ADOS-2 comparison scores and receptive vocabulary were significantly associated with adaptivity in the simpler models, these effects were no longer significant once NVIQ was included, suggesting that their predictive value was largely accounted for by NVIQ. Unlike earlier reports, higher NVIQ in this sample was not associated with greater adaptive difficulties, which suggests this relationship is not uniform across subgroups of autistic children. Interaction analyses did not reveal significant moderation effects, although some interactions involving NVIQ or receptive language delay and ADOS-2 approached conventional significance thresholds. These effects require confirmation in larger samples. Adaptive functioning in autistic children with limited expressive language abilities is predicted more strongly by NVIQ than by ADOS-2 comparison scores, receptive language delay or the interaction of these three variables. These findings indicate that early NVIQ remains a meaningful predictor of adaptive functioning in minimally verbal autistic children, underscoring the importance of including nonverbal cognitive assessments in early prognostic evaluations. The absence of meaningful associations with ADOS-2 comparison scores and receptive vocabulary delay when NVIQ was accounted for suggests that adaptive outcomes may depend less on trait profile or linguistic comprehension than may be assumed, and that autistic children may successfully compensate for early marked autistic traits and comprehension difficulties.

PMID 42553549
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PubMedSmall (Weinheim an der Bergstrasse, Germany)2026-08-05

Pt Nanoparticles on Graphene Doped by Boron Carbide With Strong Electronic Metal-Support Interaction for Efficient Ultra-Low Pt Loading Proton Exchange Membrane Fuel Cells.

Tan Chengfu C, Hao Chao C, Lin Mingjie M, Xie Yulu Y et al.

Developing a durable cathode catalyst layer (CCL) with ultra-low Pt loading <50 µgPt cm-2 for oxygen reduction reaction (ORR) is essential to substantially advancing the wide adoption of proton exchange membrane fuel cells (PEMFCs). Herein, a robust CCL was developed based on a 3D porous boron carbide-doped graphene film synthesized by the arc discharge method as an integrated electrode framework. The specific boron carbide doping with B4C and BC3 dopants endows graphene with a highly graphitic lattice and abundant electron-deficient sites, which not only generates anchoring sites for the atomic layer deposition of highly dispersed Pt, but also induces strong electronic metal-support interactions via Pt (dx 2, dz 2)/B (px, py) orbital hybridization with a downshift of the Pt d-band center. As a result, the PEMFC with the CCL at 47.5 µgPt cm-2 delivers a high-power density of 1.12 W·cm-2 (H2/air at 150 kPa) with a 38% enhancement than that of the commercial Pt/C (200 µgPt cm-2) and an outstanding durability fully satisfying the 2025 technical targets of U.S. Department of Energy. This work provides a new approach of breaking the tradeoff between activity and durability for developing PEMFCs with <50 µgPt cm-2 via a strong electronic metal-support interaction.

PMID 42553009
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