Plasmonic materials can generate strong electromagnetic fields to boost the Raman scattering of surrounding molecules, known as surface-enhanced Raman scattering. However, these electromagnetic fields are heterogeneous, with only molecules located at the \'hotspots\', which account for ≈ 1% of the surface area, experiencing efficient enhancement. Herein, we propose patterned plasmonic trimers, consisting of a pair of plasmonic dimers at the bilateral sides and a trap particle positioned in between, to address this challenge. The trimer configuration selectively directs probe molecules to the central traps where \'hotspots\' are located through chemical affinity, ensuring a precise spatial overlap between the probes and the location of maximum field enhancement. We investigate the Raman enhancement of the Au@Al2O3-Au-Au@Al2O3 trimers, achieving a detection limit of 10-14 M of 4-methylbenzenethiol, 4-mercaptopyridine, and 4-aminothiophenol. Moreover, single-molecule SERS sensitivity is demonstrated by a bi-analyte method. Benefiting from this sensitivity, our approach is employed for the early detection of lung tumors using fresh tissues. Our findings suggest that this approach is sensitive to adenocarcinoma but not to squamous carcinoma or benign cases, offering insights into the differentiation between lung tumor subtypes.

BACKGROUND: Acquired resistance still inevitably occurs in patients treated with third-generation TKI osimertinib. Although the EGFR L718Q mutation has been reported as a scarce mechanism of osimertinib resistance, advanced therapeutic strategies are still in development. In this report, we included 2 cases of patients who acquired EGFR L858R/L718Q mutation after osimertinib and were overcome by dacomitinib.
METHODS: Case 1: A 77-year-old woman was diagnosed with stage IV lung adenocarcinoma. Case 2: A 64-year-old woman was diagnosed with stage IV lung adenocarcinoma.
METHODS: Case 1: The patient was diagnosed with adenocarcinoma with EGFR L858R mutation. Since then, treatment with gefitinib was administrated, leading to a progression-free survival of 18 months. The treatment was switched to osimertinib based on the detection of EGFR T790M mutation, resulting in a progression-free survival of 24 months. Subsequently, EGFR L718Q mutation was detected. Case 2: The patient was diagnosed with adenocarcinoma with EGFR L858R mutation. Icotinib was used as the first-line treatment for 7 months. Osimertinib was applied as the second-line treatment for 13 months based on the EGFR T790M mutation. Subsequently, EGFR L718Q mutation was detected.
METHODS: Case 1: Dacomitinib was administered. Case 2: Dacomitinib was administered.
RESULTS: Case 1:The progression-free survival was 8 months. Case 2: The progression-free survival was 3 months.
CONCLUSIONS: Dacomitinib is a potential treatment option for NSCLC patients with EGFR L718Q mutation after resistance to Osimertinib. Further research is needed to validate the efficacy of Dacomitinib in this context.

Up-front osimertinib leads to clinical benefit in EGFR V834L and L858R comutated NSCLC.

Intracellular Ca2+ can be conveniently monitored by sensitive Ca2+ fluorescent dyes in live cells. The Gαq involved lipid signaling pathways and, thus, can be studied by intracellular Ca2+ imaging. Here we describe the protocols to measure intracellular Ca2+ for studying PEG2-EP1 activity in esophageal smooth muscle cells. The ratiometric Fura-2 imaging provides quantitative data, and the Fluo-4 confocal microscopic imaging has high-spatial resolution.

BACKGROUND: Patients with advanced non-small-cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) gene are a heterogeneous population who often develop brain metastases (BM). The optimal management of patients with asymptomatic brain metastases is unclear given the activity of newer-generation targeted therapies in the central nervous system. We present a protocol for an individual patient data (IPD) prospective meta-analysis to evaluate whether the addition of stereotactic radiosurgery (SRS) before osimertinib treatment will lead to better control of intracranial metastatic disease. This is a clinically relevant question that will inform practice.
METHODS: Randomised controlled trials will be eligible if they include participants with BM arising from EGFR-mutant NSCLC and suitable to receive osimertinib both in the first-line and second-line settings (P); comparisons of SRS followed by osimertinib versus osimertinib alone (I, C) and intracranial disease control included as an endpoint (O). Systematic searches of Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), PsychInfo, ClinicalTrials.gov and the WHO\'s International Clinical Trials Registry Platform\'s Search Portal will be undertaken. An IPD meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome is intracranial progression-free survival, as determined by response assessment in neuro-oncology-BM criteria. Secondary outcomes include overall survival, time to whole brain radiotherapy, quality of life, and adverse events of special interest. Effect differences will be explored among prespecified subgroups.
BACKGROUND: Approved by each trial\'s ethics committee. Results will be relevant to clinicians, researchers, policymakers and patients, and will be disseminated via publications, presentations and media releases.
UNASSIGNED: CRD42022330532.

Effective elimination of heavy metals from complex wastewater is of great significance for industrial wastewater treatment. Herein, bimetallic adsorbent Fe3O4-CeO2 was prepared, and H2O2 was added to enhance Sb(V) adsorption by Fe3O4-CeO2 in complex wastewater of Sb(V) and aniline aerofloat (AAF) for the first time. Fe3O4-CeO2 showed good adsorption performance and could be rapidly separated by external magnetic field. After five adsorption/desorption cycles, Fe3O4-CeO2 still maintained good stability. The maximum adsorption capacities of Fe3O4-CeO2 in single Sb(V), AAF + Sb(V), and H2O2+AAF + Sb(V) systems were 77.33, 70.14, and 80.59 mg/g, respectively. Coexisting AAF inhibited Sb(V) adsorption. Conversely, additional H2O2 promoted Sb(V) removal in AAF + Sb(V) binary system, and made the adsorption capacity of Fe3O4-CeO2 increase by 14.90%. H2O2 could not only accelerate the reaction rate, but also reduce the optimal amount of adsorbent from 2.0 g/L to 1.2 g/L. Meanwhile, coexisting anions had little effect on Sb(V) removal by Fe3O4-CeO2+H2O2 process. The adsorption behaviors of Sb(V) in three systems were better depicted by pseudo-second-order kinetics, implying that the chemisorption was dominant. The complexation of AAF with Sb(V) hindered the adsorption of Sb(V) by Fe3O4-CeO2. The complex Sb(V) was oxidized and decomposed into free state by hydroxyl radicals produced in Fe3O4-CeO2+H2O2 process. Then the free Sb(V) was adsorbed by Fe3O4-CeO2 mostly through outer-sphere complexation. This work provides a new tactic for the treatment of heavy metal-organics complex wastewater.

Objective: This study aims to evaluate the safety and effectiveness of gilteritinib (Gilt) -based combination therapy bridging allo-HSCT for FLT3-ITD(+) R/R AML. Additionally, it aims to assess the impact of Gilt maintenance therapy on the prognosis of patients after allo-HSCT. Methods: The clinical data of 26 patients with FLT3-ITD(+) R/R AML treated at the First Affiliated Hospital of Soochow University from August 2019 to January 2023 were retrospectively analyzed. The analysis included an assessment of the composite complete remission rate (CRc), overall survival (OS) time, disease-free survival (DFS) time, and adverse events experienced by all enrolled patients. Results: A total of 26 patients with FLT3-ITD(+) R/R AML were enrolled, including 14 men and 12 women with a median age of 38 (18-65) years. A total of 18 cases were refractory, and eight cases were relapsed. The curative effect evaluation conducted between 14 and 21 days showed that the complete remission (CR) rate was 26.9% (7/26), the CR with hematology incomplete recovery was 57.7% (15/26), and the partial response (PR) rate was 7.7% (2/26). The CRc was 84.6% (22/26), and the minimal residual disease (MRD) negativity rate was 65.4%. The 12 month cumulative OS rate for all patients was 79.0%, and the 24 month cumulative OS rate was 72.0%. The median OS time was not determined. The median follow-up time was 16.0 months. Among the patients who responded to treatment, the 12 month cumulative DFS rate was 78.0%, and the 24 month cumulative DFS rate was 71.0%. The median DFS time was not determined. Patients who received allo-HSCT had a median OS time that was significantly longer than those who did not receive allo-HSCT (3.3 months, 95%CI 2.2-4.3 months, P=0.005). The median OS time of patients with or without Gilt maintenance therapy after allo-HSCT was not determined, but the OS time of patients with Gilt maintenance therapy after allo-HSCT treatment was longer than that of patients without Gilt maintenance therapy after allo-HSCT treatment (P=0.019). The FLT3-ITD mutation clearance rate in this study was 38.5%, and the median OS time of patients with FLT3-ITD mutation clearance was not determined but was significantly longer than the median OS of patients without FLT3-ITD mutation clearance (15.0 months; P=0.018). The most common grade 3 and above hematological adverse events of Gilt-based combination therapy included leukopenia (76.9%), neutropenia (76.9%), febrile neutropenia (61.5%), thrombocytopenia (69.2%), and anemia (57.7%). One patient developed differentiation syndrome during oral Gilt maintenance therapy after allo-HSCT treatment, but his condition improved after treatment. Conclusion: The Gilt-based combination therapy is highly effective in treating FLT3-ITD(+) R/R AML. It demonstrates a high CRc, MRD negativity rate, and rapid onset, leading to a significant improvement in patients\' survival. Furthermore, the clearance rate of FLT3-ITD mutation is notably high. Additionally, implementing bridging allo-HSCT and Gilt maintenance therapy after allo-HSCT treatment has considerably enhances patients\' survival. Closely monitoring and managing any adverse event that may occur during treatment are crucial.
目的： 探讨Gilteritinib（Gilt）为基础的方案桥接异基因造血干细胞移植（allo-HSCT）对伴FMS样酪氨酸激酶3（FLT3）基因内部串联重复（ITD）突变的复发难治性急性髓系白血病（R/R AML）患者的安全性、有效性，以及移植后Gilt维持治疗对FLT3-ITD阳性R/R AML患者预后的影响。 方法： 回顾性分析2019年8月至2023年1月苏州大学附属第一医院收治的26例伴FLT3-ITD突变的R/R AML患者。统计所有纳入患者的复合完全缓解（CRc）率、总生存（OS）期、无病生存（DFS）期和不良反应。 结果： 26例FLT3-ITD突变阳性R/R AML患者中，男14例，女12例，中位年龄38（18~65）岁。难治18例，复发8例。用药第14~21天疗效：完全缓解（CR）率为26.9%（7/26），CR伴血液学不完全恢复（CRi）率为57.7%（15/26），部分缓解（PR）率为7.7%（2/26），CRc率为84.6%（22/26），微小残留病（MRD）转阴率为65.4%。所有患者12、24个月累计OS率分别为79.0%和72.0%。中位OS期未达到。中位随访时间为16.0个月。全部治疗有效患者12、24个月累计DFS率分别为78.0%和71.0%。中位DFS期未达到。接受allo-HSCT的患者中位OS期未达到，较未接受allo-HSCT的患者（3.3个月，95%CI 2.2~4.3个月）显著延长（P=0.005）。移植后是否应用Gilt维持治疗的患者中位OS期均未达到，且移植后维持治疗的患者OS明显优于移植后未进行维持治疗的患者（P=0.019）。本研究中FLT3-ITD基因突变清除率为38.5%，且FLT3-ITD基因突变转阴的患者中位OS期未达到，明显长于未转阴的患者（15.0个月）（P=0.018）。Gilt为基础的方案最常见的3级及以上血液学不良反应包括白细胞减少（76.9%）、中性粒细胞减少（76.9%）、中性粒细胞减少性发热（61.5%）、血小板减少（69.2%）和贫血（57.7%）。其中1例患者在移植后口服Gilt维持治疗时出现分化综合征，治疗后好转。 结论： Gilt为基础的方案桥接allo-HSCT治疗FLT3-ITD突变阳性R/R AML患者的CRc率较高，MRD转阴率也较高，起效迅速，有效延长患者生存期。此外，FLT3-ITD基因突变清除率较高，且桥接移植和移植后Gilt维持治疗明显改善患者生存。治疗过程中不良事件的监测和管理至关重要。.

An alarming increase in the use of pesticides and organoarsenic compounds and their toxic impacts on the environment have inspired us to develop a selective and highly sensitive sensor for the detection of these pollutants. Herein, a bio-friendly, low-cost Al-based luminescent metal-organic framework (1\')-based fluorescent material is demonstrated that helps in sustaining water quality by rapid monitoring and quantification of a long-established pesticide (pendimethalin) and a widely employed organoarsenic feed additive (roxarsone). A pyridine-functionalized porous aluminum-based metal-organic framework (Al-MOF) was solvothermally synthesized. After activation, it was used for fast (<10 s) and selective turn-off detection of roxarsone and pendimethalin over other competitive analytes. This is the first MOF-based recyclable sensor for pendimethalin with a remarkably low limit of detection (LOD, 14.4 nM). Real-time effectiveness in detection of pendimethalin in various vegetable and food extracts was successfully verified. Moreover, the aqueous-phase recyclable detection of roxarsone with an ultralow detection limit (13.1 nM) makes it a potential candidate for real-time application. The detection limits for roxarsone and pendimethalin are lower than the existing luminescent material based sensors. Furthermore, the detection of roxarsone in different environmental water and a wide pH range with a good recovery percentage was demonstrated. In addition, a cheap and bio-friendly 1\'@chitosan@paper strip composite was prepared and successfully employed for the hands-on detection of pendimethalin and roxarsone. The turn-off behavior of 1\' in the presence of pendimethalin and roxarsone was examined systematically, and plausible mechanistic pathways were proposed with the help of multiple experimental evidences.

Lung cancer is one of the most common and deadliest cancers. Preclinical models are essential to study new therapies and combinations taking tumor genetics into account. We have established cell lines expressing the luciferase gene from lines with varied genetic backgrounds, commonly encountered in patients with pulmonary adenocarcinoma. We have characterized these lines by testing their response to multiple drugs. Thus, we have developed orthotopic preclinical mouse models of NSCLC with very high engraftment efficiency. These models allow the easy monitoring of tumor growth, particularly in response to treatment, and of tumor cells dissemination in the body. We show that concomitant treatment with osimertinib (3rd generation tyrosine kinase inhibitor targeting mutated EGFR) and bevacizumab (anti-angiogenic targeting VEGF) can have a beneficial therapeutic effect on EGFR-mutated tumors. We also show that the addition of afatinib to osimertinib-treated tumors in escape leads to tumor growth inhibition. No such effect is observed with selumetinib or simvastatin. These preclinical mouse models therefore make it possible to test innovative therapeutic combinations and are also a tool of choice for studying resistance mechanisms.

Compound-specific isotope analysis (CSIA) is an established tool to track the in situ transformation of organic chemicals at contaminated sites. In this work, we evaluated the potential of multi-element CSIA to assess biodegradation of 2,3-dichloroaniline (2,3-DCA), which is a major industrial feedstock. Using controlled laboratory experiments, we determined, for the first time, negligible carbon (<0.5‰) and hydrogen (<10‰) isotope fractionation and a significant inverse nitrogen isotope fractionation (>10‰) during aerobic 2,3-DCA biodegradation by a mixed enrichment culture. The tentative identification of a glutamate conjugate of 2,3-DCA as a reaction intermediate indicates that the initial multistep enzymatic reaction may be rate-limiting. The formation of the glutamate adduct would increase the bond energy at the N atom, thus likely explaining the observed inverse N isotope fractionation. The corresponding nitrogen enrichment factor was +6.8 ± 0.6‰. This value was applied to investigate the in situ 2,3-DCA biodegradation at a contaminated site where the carbon and nitrogen isotope signatures from field samples suggested similar aerobic processes by native microorganisms. Under the assumption of the applicability of the Rayleigh model in a pilot wetland treating contaminated groundwater, the extent of biodegradation was estimated to be up to 80-90%. This study proposes multi-element CSIA as a novel application to study 2,3-DCA fate in groundwater and surface water and provides insights into biodegradation pathways.