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Targeting ERK-MYD88 interaction leads to ERK dysregulation and immunogenic cancer cell death
The quest for targeted therapies is critical in the battle against cancer. The RAS/ MAP kinase pathway is frequently implicated in neoplasia, with ERK playing a crucial role as the most distal kinase in the RAS signaling cascade. Our previous research demonstrated that the interaction between ERK and MYD88, an adaptor protein in innate immunity, is crucial for RAS-dependent transforma- tion and cancer cell survival. In this study, we examine the biological con- sequences of disrupting the ERK-MYD88 interaction through the ERK D-recruitment site (DRS), while preserving ERK ' s kinase activity. Our results indicate that EI-52, a small-molecule benzimidazole targeting ERK-MYD88 interaction induces an HRI-mediated integrated stress response (ISR), resulting in immunogenic apoptosis speci fi c to cancer cells. Additionally, EI-52 exhibits anti-tumor ef fi cacy in patient-derived tumors and induces an anti-tumor T cell response in mice in vivo. These fi ndings suggest that inhibiting the ERK-MYD88 interaction may be a promising therapeutic approach in cancer treatment.
南卡罗来纳州高级弹性能源（“ SC Nexus”）技术中心指定应用
摘要：Nexus对高级弹性能量的野心（“ SC Nexus”）1是在核心技术中创造全球领先的枢纽驱动创新，该核心技术能够在清洁，分布，分布和网格刻度范围内实现端到端的弹性，可持续的能量生态系统。The Hub will leverage the region's dynamic and growing manufacturing base, superior research capabilities, and demonstrated record of public-private collaboration to develop exportable electricity technologies alongside testing and deployment of those technologies, which will accelerate high-quality job growth for a diverse workforce, address the US' focus on climate and environmental responsibility, help to close infrastructure gaps in rural and distressed communities, and ensure the US grows未来的竞争性和全球领先的电力技术和行业。这项工作由南卡罗来纳州商务部领导，汇集了30多个成员，包括公共机构（HBCUS，R1大学，政府机构），私营企业和萨凡纳河国家实验室。
遗传癌的基因检测
Individual has a personal history of a Primary Solid Tumor cancer (excluding basal or squamous cell skin cancer) and at least one of the following: o A BRCA1/2 pathogenic variant was detected in tumor tissue o Tumor tissue testing demonstrated that the cancer was MSI-high or had immunohistochemical staining showing the absence of one or more mismatch repair proteins ( MLH1, MSH2, MSH6, or PMS2 ) o Individual has a Tyrer-Cuzick, BRCAPro, or Penn11 Score of 2.5% or greater for a BRCA1/2 pathogenic variant o Individual has a PREMM 5 , MMRpro, or MMRpredict Score of 2.5% or greater for having a Lynch syndrome gene mutation Individuals With No Personal History of a Primary Solid Tumor Cancer Genetic testing with a Multi-Gene hereditary cancer Panel or testing of BRCA1/2对于没有原发性实质性癌症病史（不包括基底或鳞状细胞皮肤癌）的个体，如果满足以下至少一个标准，则证明并且在医学上是必不可少的：
PARP抑制剂维持疗法的功效和安全性...
结果：这项荟萃分析涉及20个RCT，涉及7,832名参与者。The overall analysis demonstrated that maintenance therapy with PARP inhibitors led to signi fi cant improvements in PFS (HR: 0.398, 95% CI = 0.339 – 0.467, 95% PI = 0.219 – 0.724), OS (HR: 0.677, 95% CI = 0.582 – 0.788, 95% PI = 0.546 – 0.839), CFI (HR: 0.417, 95% CI = 0.368 – 0.472, 95% PI = 0.265 – 0.627), TFST (HR: 0.441, 95% CI = 0.391 – 0.498, 95% PI = 0.308 – 0.632), and TSST (HR: 0.574, 95% CI = 0.507 – 0.649,与安慰剂相比，95％PI = 0.488 - 0.674）。亚组分析进一步表明，无论同源重组状态如何，PARP抑制剂维持治疗显着改善了PFS（所有P <0.05）。但是，任何等级的风险（RR = 1.046，95％CI = 1.032 - 1.059，95％PI = 1.028 - 1.055）和≥3级茶（RR = 2.931，95％CI = 2.641 - 2.641 - 3.253，95％PI = 2.253，95％PI = 2.128 –3.792）。
服务/工作描述：也门Wadi Tuban的水文研究数据收集
2。背景 /项目描述水资源管理是也门的一个紧迫问题，由于其干旱的气候和有限的水可用性。也门在这方面面临重大挑战，包括有限的农业生产力，高水平的营养不良和易受自然灾害的脆弱性。通过德国开发银行（KFW）的BMZ资金，也门开发署和肯德基建立了致力于增强该国水资源管理和粮食安全的伙伴关系。这种合作旨在应对也门在这些领域面临的关键挑战，并为可持续发展做出贡献。此外，肯德基和开发计划署也门也承认解决该国粮食安全问题的重要性。为了解决这些问题，肯德基-Undp的合作伙伴关系致力于促进可持续的农业实践，支持小规模的农民并加强当地粮食系统。通过提高农业生产力并确保获得营养食品，这些举措有助于减少也门的饥饿和贫困。认识到迫切需要应对这些挑战的需要，肯德基和开发计划署已联手实施了一个综合的水资源管理项目，旨在增强也门农业和粮食安全的弹性。项目（综合水资源管理以增强农业的弹性（ERA）和粮食安全）包括水基础设施的建设和康复，以增加农业生产，促进对也门农业价值链中的妇女的能力。该项目的总体目标是对也门的贫困，他们的生计取决于主要水源的生产用途，以便能够通过开发和恢复水基础设施来增强其生计弹性，从而增强水基础设施，从而增强水的可用性，以支持对可持续农业的水基础，从而在集水集水集水集水区中实施了可持续的农业。该项目将对图班进行集水水平评估，并将在侦察水平上对图班主要集水区的水资源进行水文评估，并对位于Taiz和Lahj州的目标地区的四个子流域进行详细评估。The importance of these envisaged assessments is to ensure sustainability of interventions and to monitor impact related to enhanced water sources, improvement in groundwater recharge, reduced sectoral conflicts between upstream and downstream governorates, demonstrated coordinated planning between districts (Al-Mawaset and Al-Selw- upstream and Al-Mosaymer and Tuban downstream) and enhance social cohesion from demonstrated co-dependency of受益人通过参与式计划。
通过靶向分子药物和放射疗法对无法手术的Her2阳性乳腺癌的疾病控制：病例报告
局部控制以前被认为是老年人乳腺癌治疗的主要目标，肿瘤壳或全乳房切除术是日本的主要治疗方法。7然而，80岁妇女的平均预期寿命为12.3岁，而85岁和90岁的非常年老的女性的预期寿命分别为8.8和5.9岁。8因此，我们认为系统治疗对于解决遥远转移的可能性是必要的。然而，接受化疗的老年乳腺癌患者的比例显着低，并且由于单独年龄而省略化疗，这可能导致治疗不足。9 Although comorbidities such as heart diseases can make the use of anthracyclines and taxanes difficult, a randomized controlled trial of trastuzumab with or without chemotherapy in the postoperative adjuvant treatment of elderly HER2-positive early stage breast cancer demonstrated the absence of non-inferiority of trastuzumab alone and the OS difference to be of 1 month at 3 years, reducing side effects and preserving healthy QoL.10我们认为，对于患有合并症的老年乳腺癌患者而言，HER基和每个基于每项疗法可能是可行的选择，表现出身体和认知能力下降。
将最新的生物学进步整合到食品包装生命周期的关键步骤
本文献评论的重点是将最新的科学和技术进步整合到生物学领域的潜力，以改善食品包装生命周期的关键步骤：生产，使用，使用后和长期命运。A case study of such multi-biological food packaging is demonstrated based on the use of PHAs (polyhydroxyalkanoates) polymer, a microbiologically produced polymer from non-food renewable resources, activated by the use of bioactive components to enhance its usage benefits by reducing food loss and waste, displaying potential for reusability, compostability as post-usage, and finally, being ultimately在最常见的自然条件下，可生物降解可大大减少持续塑料对环境的负面影响。我们讨论设计安全有效的多“生物”食品包装如何意味着在有时矛盾的功能性能之间找到妥协。例如，活性抗菌剂有助于保存食物，但会阻碍聚合物的最终生物降解速率。本综述介绍了这种拮抗作用以及技术（例如涂料，纳米封装）和工具（例如，释放动力学），这些技术可以帮助设计优化，安全和有效的活性食品包装。
全身免疫炎症指数与糖尿病之间的关联：涉及NHANES肥胖指标的调解分析
虽然DM的精确病因和机制仍然没有完全阐明，但毫不含糊地炎症在DM的发生和发展中起关键作用（3，4）。Research has demonstrated that pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF- α ) and interleukin-6 (IL-6), induce insulin resistance in target tissues such as muscle and liver by disrupting insulin signaling pathways, consequently impairing glucose uptake and utilization, ultimately elevating blood glucose levels ( 5 , 6 ).此外，炎症细胞因子可以诱导β细胞应激和凋亡，从而导致胰岛素产生和分泌减少（6）。全身免疫炎症指数（SII）是一个关键指标，它通过结合外周血的各种成分来反映系统性炎症状态，从而对全身炎症进行了全面评估（7）。SII水平升高表示促炎性状态，该状态与几种慢性疾病的风险更高有关（8，9）。因此，了解SII在DM研究中的重要性至关重要，因为它为炎症状态及其在疾病的发展和发展中的潜在作用提供了全面的看法。
CADTH Reimbursement Recommendation
One double-blind, phase 2/3, randomized controlled trial (RCT) (N-MOmentum, N = 230) in patients with NMOSD demonstrated that, among AQP4 seropositive patients (N = 213) treatment with inebilizumab likely results in a clinically meaningful increase in time to first relapse and a reduction in the proportion of patients with worsening in Expanded Disability Status Scale (EDSS) compared to treatment with placebo after 197 days of treatment. Among AQP4 seropositive patients, the hazard ratio (HR) for time to first Adjudication Committee (AC)–determined NMOSD attack was 0.28 (95% confidence interval [CI]: 0.12 to 0.42, P < 0.0001) and at day 197, 87.6% of patients in the inebilizumab group were attack-free compared to 56.6% in the placebo group, which equated to a 77.3% reduction in the risk of AC-determined NMOSD attack. The CADTH review of the sponsor's submitted indirect treatment comparisons concluded that inebilizumab did not offer a benefit relative to eculizumab, and that imprecision in the estimated HR prevented a definitive conclusion from being reached in the comparison with satralizumab.
遗传癌的基因检测
Individual has a personal history of a Primary Solid Tumor (excluding basal or squamous cell skin cancer) and at least one of the following: o A pathogenic variant was detected in tumor tissue that has clinical implications if detected in the germline (e.g., BRCA1, BRCA2, BRIP1, MLH1, MSH2, MSH6, MUTYH, PALB2, PMS2, RAD51C, RAD51D, RET, SDHAF2, SDHB, SDHC, SDHD, TMEM127, TSC2, VHL APC, PTEN, RB1, and TP53 ) o Tumor tissue testing demonstrated that the cancer was MSI-high or had immunohistochemical staining showing the absence of one or more mismatch repair (MMR) proteins ( MLH1, MSH2, MSH6, or PMS2 ) o Individual has a Tyrer-Cuzick, BRCAPro, or Penn11 Score of 2.5% or greater for a BRCA1/2 pathogenic variant o Individual has a PREMM 5 , MMRpro, or MMRpredict Score of 2.5% or greater for having a Lynch syndrome gene mutation Individuals With No Personal History of a Primary Solid Tumor Genetic testing with a Multi-Gene hereditary cancer Panel or testing of BRCA1/2 for individuals如果符合以下至少一个标准之一，则没有原发性实体瘤的个人病史（不包括基底或鳞状细胞皮肤癌），并且在医学上是必不可少的：