Poniard Pharmaceuticals · 小分子 · 小分子
Tc 99m nofetumomab merpentan 是一种小分子，由Poniard Pharmaceuticals研发。该药已获批，用于治疗相关适应症，给药途径：Injectable (Others)。
| 商品名 | Verluma |
| 公司 | Poniard Pharmaceuticals |
| 药物类别 | 小分子, 影像药物 |
| 给药途径 | Injectable (Others) |
| 状态 | Approved |
Tc 99m nofetumomab merpentan 针对 2 个适应症，涉及 1 个治疗领域。
| 治疗领域 | 疾病/病症 | 分期 |
|---|---|---|
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Small cell lung cancer recurrent | ✓ Approved |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Uterine cancer | ✓ Approved |
Dewarrat Natacha N, Auf der Springe Katharina K, Grandoni Francesco F, Hajri Rami R et al.
Qiu Zhengyang Z, Chen Junfeng J, Semenok Dmitrii V DV, Zhong Qingyi Q et al.
Systematically controlling the superconducting transition temperature (Tc) in the bilayer Ruddlesden-Popper nickelate La3Ni2O7 remains a significant challenge. Here, we address this by synthesizing high-quality polycrystalline La3-xNdxNi2O7 (0 ≤ x ≤ 2.4) with record-level rare-earth substitution. Nd doping compresses the lattice and enhances the spin density wave (SDW) transition temperature, and elevates the pressure required for the orthorhombic-to-tetragonal structural transition. Superconductivity is observed across all doping levels in high-pressure electronic transport measurements, with the onset Tc rising to ~ 93 K and the resistance derivative indicating the signature of superconductivity reaching 96-97 K for x = 2.1 and 2.4. Using the radio-frequency transmission technique, recently applied to nickelate superconductors, we detect signatures of superconductivity at 100.5 K in the x = 2.1 compound, pushing the Tc frontier further. Our work reveals the critical role of magnetism and provides a structural descriptor for elevating Tc in Ruddlesden-Popper nickelates.
Li Zhenkuo Z, Xie Peng P, Yang Cheng C, Xia Lei L et al.
Treatment-Resistant Schizophrenia (TRS) in males with agitation/excitement poses a clinical challenge. The pathophysiological mechanisms of agitation/excitement in Male TRS remain unclear. This study explores these mechanisms and investigates potential biomarkers for agitation/excitement. 180 Male TRS patients and 100 healthy controls were enrolled. Psychiatric symptoms and agitation/excitement were assessed using the Positive and Negative Syndrome Scale 5-factor model (PANSS-5F) and the PANSS-Excited Component (PANSS-EC). Patients were divided into Male TRS with agitation/excitement (n=80) and without agitation/excitement (n=100). Demographic data and lipid profiles (triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein) were collected for both groups. Statistical analyses assessed the relationship between lipid profiles and agitation/excitement. A negative correlation was found between total cholesterol (TC) levels and agitation/excitement in Male TRS. Those with agitation/excitement had worse educational and marital status and more severe cognitive impairment. TC levels and hypercholesterolemia were higher in Male TRS compared to healthy controls. Lower TC levels in Male TRS with agitation/excitement are associated with higher agitation/excitement risk. TC may be an associated factor for agitation/excitement in this population. https://chictr.org.cn, identifier ChiCTR2200063407.
Chen Shandong S, Miao Yan Y, Yin Jiayu J, Zhou Zexun Z et al.
The lotus-fish co-culture ponds (LP) is a widely applied integrated aquaculture system in China. However, research on the micro-ecology of aquaculture in lotus ponds is still insufficient. This study explored the dynamic patterns of organic matter composition, as well as algal and bacterial community structures in LP and MP. A total of six independent ponds were used in this study: three lotus ponds designated as the lotus-fish co-culture ponds group (A1, A2, A3), and the other three conventional earthen ponds serving as the fish monoculture ponds group (B1, B2, B3). Bacterial and algae community survey, environment factor survey, bacterial Biomarker selection, function prediction, and association analysis were used to analyze the effects of lotus-fish co-culture on algae, bacteria and sediment organic matter components of pond. The sediments of LP had lower concentrations of total nitrogen (TN), total phosphorus (TP), total carbon (TC) and organic matter (OM), and the chlorophyll-a (chla) content in the water was also relatively low. The algal community in LP exhibited seasonal variations, while MP was predominated by Chlorophyta and Cyanobacteriophyta. The dominant bacterial phyla were the same in both pond groups, yet their abundances varied across months. Bacterial biomarkers in LP was c_Alphaproteobacteria, c_Vicinamibacteria, etc. (sediments) and c_Gammaproteobacteria (water), whereas MP was c_Desulfobacteria, c_Dehalococcoidia, etc. (sediments), and c_Verrucomicrobiia, c_Mycobacteriales, etc. (water). Functional analysis suggested that bacterial communities in LP were enriched in methanotrophy, nitrogen fixation, whereas MP communities were more closely associated with anaerobic respiration and phototrophic processes. The bacterial network in LP exhibited a modular structure reliant on keystone taxa, whereas MP harbored highly interconnected and cooperative bacterial communities. In the LP sediments, TC, TN, and TP collectively drive the broad differentiation of bacterial modules. Total nitrogen (TN) played a vital role in bacterial assembly in MP sediments, while total phosphorus (TP) acted as the primary negative driving factor in MP sediments. FBL and FBW were significantly greater in LP than MP, while CF was lower. These findings indicate that microbial communities in LP and MP follow distinct assembly patterns, and they differ in core ecological functions and environmental preferences within their respective ecosystems.
Ning Haoming H, Yang Kejia K, Zhang Yu Y, Liu Junjun J et al.
APOBEC3B (A3B), a key driver of cancer mutagenesis, has emerged as a promising therapeutic target to be ablated to enhance antitumor immunity while reducing intestinal inflammation. Starting from SMC247 (3, 5-diiodotyrosine), a kelp-derived natural product, we identified the optimized analogue SMC247-9 as a potent A3B inhibitor, with an IC50 of 50 pM and KD value of 300 pM. SMC247-9 reduced cellular A3B abundance and promoted IL-15 expression in tumor cells, thereby relieving tumor cell-mediated suppression of CD8+ T cells in an IL-15-dependent manner. In immunocompetent mice, SMC247-9 suppressed tumor growth in the immune checkpoint blockade (ICB)-responsive MC38 model and synergized with anti-PD-L1 in the ICB-resistant TC-1 model. SMC247-9 also attenuated macrophage chemotaxis and ameliorated anti-PD-1-exacerbated DSS-induced colitis-like intestinal inflammation. These findings support A3B-targeted pharmacologic intervention as a strategy to enhance antitumor efficacy while reducing inflammatory toxicity in cancer immunotherapy.
Gao Ping P, Jiang Yingmin Y, Ha-Duong Tâp T, Nicolas Julien J
Thermosensitive vinyl polymers with an upper critical solution temperature (UCST) have gained particular attention in drug delivery applications. However, since the UCST is strongly influenced by various parameters (e.g., copolymer composition, molar mass, concentration, and presence of salt), exploring the full range of possibilities to develop effective polymer-based nanocarriers with precisely controlled UCST properties adapted to each biomedical application is very challenging. These developments, generally based on trial-and-error strategies, require extremely time- and resource-consuming experiments. In addition, vinyl copolymers are not degradable, which may hinder their clinical application. Recently, well-defined vinyl copolymers combining both degradability and thermosensitivity properties have been obtained by copolymerizing acrylamide (AAm) and 5,6-benzo-2-methylene-1,3-dioxepane (BMDO) as cyclic ketene acetals (CKA) comonomer, via radical ring-opening polymerization (rROP), leading to much faster degradation under physiological conditions than previously-developed CKA-containing copolymers and even aliphatic polyesters. Nevertheless, such an unprecedented step forward in the field of rROP was left unexplained. Herein, we employed coarse-grained (CG) molecular dynamics (MD) simulations to investigate the thermosensitive behavior and degradability of CKA-containing vinyl copolymers. Our simulations successfully: (i) reproduced the UCST behavior and transition temperature (Tc) value of P(AAm-co-BMDO) copolymers and (ii) revealed that local solvation environments and supramolecular organizations (e.g., aggregation state and steric hindrance) could drastically alter the accessibility of ester groups in P(AAm-co-BMDO), P(MMA-co-BMDO), and P(OEGMA-co-BMDO) copolymers, ultimately rationalizing their experimentally observed degradability under physiological conditions. This approach provides insight at the molecular level into the origin of the thermosensitive and degradable behaviors of CKA-containing vinyl copolymers and provides a predictive framework for the design of biodegradable polymer materials for biomedical applications.
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