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Limertinib (ASK120067) is a newly developed third-generation EGFR tyrosine kinase inhibitor targeting both sensitizing EGFR and EGFR Thr790Met (T790M) mutations. This study aimed to evaluate the efficacy and safety of limertinib in patients with locally advanced or metastatic EGFR T790M-mutated NSCLC.This is a single-arm, open-label, phase 2b study conducted at 62 hospitals across the People's Republic of China. Patients with locally advanced or metastatic NSCLC with centrally confirmed EGFR T790M mutations in tumor tissue or blood plasma who progressed after first- or second-generation EGFR tyrosine kinase inhibitors or with primary EGFR T790M mutations were enrolled. Patients received limertinib 160 mg orally twice daily until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) assessed by independent review committee per the Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included disease control rate, progression-free survival (PFS), duration of response (DoR), overall survival, and safety. Safety was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.From July 16, 2019, to March 10, 2021, a total of 301 patients were enrolled and started the treatment of limertinib. All patients entered the full analysis set and safety set. By the data cutoff date on September 9, 2021, 76 (25.2%) remained on treatment. The median follow-up time was 10.4 months (range: 0.3-26.3). On the basis of full analysis set, the independent review committee-assessed ORR was 68.8% (95% confidence interval [CI]: 63.2%-74.0%) and disease control rate was 92.4% (95% CI: 88.8%-95.1%). The median PFS was 11.0 months (95% CI: 9.7-12.4), median DoR was 11.1 months (95% CI: 9.6-13.8), and median OS was not reached (95% CI 19.7 months-not evaluable). Objective responses were achieved across all prespecified subgroups. For 99 patients (32.9%) with central nervous system (CNS) metastases, the ORR was 64.6% (95% CI: 54.4%-74.0%), median PFS was 9.7 months (95% CI: 5.9-11.6), and median DoR was 9.6 months (95% CI: 8.1-15.2). For 41 patients who had assessable CNS lesion, the confirmed CNS-ORR was 56.1% (95% CI: 39.7%-71.5%) and median CNS-PFS was 10.6 months (95% CI: 5.6-not evaluable). In safety set, 289 patients (96.0%) experienced at least one treatment-related adverse event (TRAE), with the most common being diarrhea (81.7%), anemia (32.6%), rash (29.9%), and anorexia (28.2%). Grade ≥3 TRAEs occurred in 104 patients (34.6%), with the most common including diarrhea (13.0%), hypokalemia (4.3%), anemia (4.0%), and rash (3.3%). TRAEs leading to dose interruption and dose discontinuation occurred in 24.6% and 2% of patients, respectively. No TRAE leading to death occurred.Limertinib (ASK120067) was found to have promising efficacy and an acceptable safety profile for the treatment of patients with locally advanced or metastatic EGFR T790M-mutated NSCLC.NCT03502850.

PURPOSE Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor approved in China. This double-blind phase III trial evaluated the efficacy and safety of aumolertinib compared with gefitinib as a first-line treatment for locally advanced or metastatic EGFR-mutated non–small-cell lung cancer (NSCLC; ClinicalTrials.gov identifier: NCT03849768 ). METHODS Patients at 53 sites in China were randomly assigned 1:1 to receive either aumolertinib (110 mg) or gefitinib (250 mg) once daily. The primary end point was progression-free survival (PFS) per investigator assessment. RESULTS A total of 429 patients who were naïve to treatment for locally advanced or metastatic NSCLC were enrolled. PFS was significantly longer with aumolertinib compared with gefitinib (hazard ratio, 0.46; 95% CI, 0.36 to 0.60; P < .0001). The median PFS with aumolertinib was 19.3 months (95% CI, 17.8 to 20.8) versus 9.9 months with gefitinib (95% CI, 8.3 to 12.6). Objective response rate and disease control rate were similar in the aumolertinib and gefitinib groups (objective response rate, 73.8% and 72.1%, respectively; disease control rate, 93.0% and 96.7%, respectively). The median duration of response was 18.1 months (95% CI, 15.2 to not applicable) with aumolertinib versus 8.3 months (95% CI, 6.9 to 11.1) with gefitinib. Adverse events of grade ≥ 3 severity (any cause) were observed in 36.4% and 35.8% of patients in the aumolertinib and gefitinib groups, respectively. Rash and diarrhea (any grade) were observed in 23.4% and 16.4% of patients who received aumolertinib compared with 41.4% and 35.8% of those who received gefitinib, respectively. CONCLUSION Aumolertinib is a well-tolerated third-generation epidermal growth factor receptor tyrosine kinase inhibitor that could serve as a treatment option for EGFR-mutant NSCLC in the first-line setting.

Quantum state transition is the core content of quantum control. This paper presents a control scheme of the state evolution path based on feedback control and reverse engineering design. To achieve high-precision state transition, we first adopt a homodyne-based feedback control strategy to form a closed-loop system. Then, based on the idea of reverse engineering design, the state evolution path of the system is planned and designed by considering the influence of environment decoherence on the state evolution. Numerical simulation results show that the control pulse based on planning design can drive the system from any initial state to the desired target state, and the coherence of the system is effectively protected during state transition.

Tomato mottled mosaic virus (ToMMV) was first identified in tomato in Mexico (Li et al. 2013). It belongs to the genus Tobamovirus and family Virgaviridae, and is a positive-sense single-stranded RNA virus. The viral genome contains about 6400 nucleotides, encoding four proteins, including the 126 K protein, 183 K protein, movement protein (MP) and coat protein (CP) (Tu et al. 2021). ToMMV mainly poses a serious risk to solanaceous crops. The virus-infected plants appear stunted growth and top necrosis, and the disease leaves show mottled, shrinkage and necrosis symptoms, resulting in a significant decline in tomato fruit yield and quality (Li et al. 2017; Tu et al. 2021). Chinese snake gourd (Trichosanthes kirilowii Maxim) is a perennial climbing herb in the family Cucurbitaceae, and the fruit, seed, peel and root can all be used as traditional Chinese medicine. In May of 2021, twenty-seven symptomless seedlings (developed from tissue culture plantlets) were randomly collected from nursery in Fengyang, Anhui Province. Total RNA of each sample was extracted, and RT-PCR was performed using degenerate tobamovirus primers Tob-Uni1 (5′-ATTTAAGTGGASGGAAAAVCACT-3′) and Tob-Uni2 (5′-GTYGTT GATGAGTTCRTGGA-3′) (Letschert et al. 2002). Amplicons with expected size were obtained from 6 of 27 samples and sequenced. Alignment results showed that the nucleotide sequence identities ranged from 98.7 to 100% with all ToMMV isolates deposited in NCBI GenBank. Then, ToMMV coat protein (CP) gene was amplified using specific primers CP-F (5′-ATGTCTTACGCTATTACTT CTCCG-3′) and CP-R (5′-TTAGGACGCTGGCGCAGAAG-3′). The CP fragment was obtained and sequenced. Sequence alignment indicated that CP sequence of isolate FY (GenBank accession no. ON924176) exhibited a 100% identity with ToMMV isolate LN (MN853592.1). The anti-ToMMV polyclonal antibody (PAb) was prepared by the author (S.L.) by immunizing rabbit with purified virus from Nicotiana benthamiana, and serological tests (dot-enzyme linked immunosorbent assay, Dot-ELISA) of RNA-positive T. kirilowii leaf samples using anti-ToMMV PAb were also positive. To fulfill a Koch’s postulate, a pure culture of ToMMV was obtained from N. benthamiana using infectious cDNA clone of ToMMV (Tu et al. 2021), and then healthy T. kirilowii plants were mechanically inoculated with a prepared inoculum from ToMMV-infected N. benthamiana, as described previously (Sui et al. 2017). T. kirilowii seedlings showed chlorosis and leaf tip necrosis symptoms at 10 and 20 day post-inoculation respectively, and ToMMV infection on symptomatic plants was also verified by RT-PCR detection using primers CP-F and CP-R. These results demonstrated that T. kirilowii is a host of ToMMV under natural conditions, which might threaten the production of this medicinal plant. The seedlings from nursery appeared to be asymptomatic, but the plants showed chlorosis and necrosis symptoms after indoor inoculation. In qRT-PCR analysis, viral accumulation level in greenhouse-inoculated plants was a 25.6-fold of that in field-collected samples, which may be the reason of different symptom expression between field samples and inoculated samples. ToMMV has now been detected from the solanaceous (tomato, pepper and eggplant) and leguminous (pea) crops in the field (Li et al. 2014; Ambrós et al. 2017; Zhang et al. 2022). To our knowledge, this is the first report of natural infection of ToMMV in T. kirilowii as well as its natural infection on Cucurbitaceae plants.

Wheat (Triticum aestivum L.) is an important cereal crop widely cultivated worldwide. Viral disease is a major threat to wheat yield. In April 2022, fifteen winter wheat plants with yellowing and stunting symptoms were collected from wheat fields in Jingjiang, Jiangsu Province. Total RNA of each sample was extracted, and RT-PCR was performed using two pairs of degenerate luteovirus primers Lu-F (5′-CCAGTGGTTRTGGTC-3′) and Lu-R (5′-GTCTACCTATTTGG-3′), Leu-F (5′-GCTCTAGAATTGTTAATGARTACGGTCG-3′) and Leu-R (5′-CACGCGTCN ACCTATTTNGGRTTNTG-3′). Amplicons with the expected size were obtained from 10 of the 15 samples (using primers Lu-F/Lu-R) and 3 of the 15 samples (using primers Leu-F/Leu-R), respectively. These amplicons were cloned into the pDM18-T vector (TaKaRa) for sequencing. Blastn alignment showed that 10 amplicons (531 bp) from Lu-F/Lu-R primers were essentially identical to one another, which shared 99.62% nucleotide sequence identity to barley yellow dwarf virus-PAV (BYDV-PAV) isolate GJ1 from Avena sativa in South Korea (LC550014). Three amplicons (635 bp) from Leu-F/Leu-R primers had 99.68% nucleotide identity to the corresponding part of an isolate of beet western yellows virus (BWYV) from saffron (Crocus sativus) in China (MG002646). Among the 13 virus-positive samples, none were co-infected by BYDV-PAV and BWYV. Then, amplification using BWYV-specific primers (BWYV-F: 5′-TGCTCCGGTTTTGACTGGAGTGT-3′, BWYV-R: 5′-CGTCTACCT ATTTTGGGTTGTGG-3′) generated a 1409 bp product, corresponding to the partial sequence of the viral RNA-dependent RNA polymerase gene and complete sequence of the coat protein (CP) gene. The sequences (GenBank accession no. ON924175) of amplicons from 3 BWYV samples were identical to one another, which shared 98.41% nucleotide identity to BWYV isolate Hs from Japanese hop (Humulus scandens) in China (KC210049). The predicted coat protein of the BWYV wheat isolate had 99.51% nucleotide and 100% amino acid identity to BWYV isolate Hs. BWYV infection on wheat samples was also verified by dot-nucleic acid hybridization using a digoxigenin-labeled cDNA probe against the CP gene, as described previously (Liu et al. 2007). Further, RNA-positive samples were tested by enzyme-linked immunosorbent assay (ELISA) using the ELISA reagent kit for BWYV (Catalog No. KS19341, Shanghai Keshun Biotech, Shanghai, China); test results were also BWYV-positive, confirming that both BWYV nucleic and coat protein are present in these wheat samples. BYDV-PAV is a common wheat virus (Chay et al. 1996), while BWYV has never been reported to infect wheat. BWYV, an aphid-transmitted virus belonging to the Polerovirus genus, has an extensive host range, including over 150 plant species from 23 dicotyledonous families, such as Beta vulgaris, Spinacia oleracea, Lactuca sativa, and Brassica oleracea var. italica (Duffus 1964, 1973; Russell 1965; Beuve et al. 2008). In addition, BWYV was reported to infect a monocotyledonous plant, Crocus sativus (Iridaceae) (Zheng et al. 2018). To our knowledge, this is the first report of BWYV in wheat or any other Gramineae crop. The result also implies that BWYV has a potential risk to cereal crops in the field.

Programmed cell death ligand 1 inhibitors combined with chemotherapy has changed the approach to first-line treatment in patients with extensive-stage small cell lung cancer (SCLC). It remained unknown whether adding a programmed cell death 1 (PD-1) inhibitor to chemotherapy provided similar or better benefits in patients with extensive-stage SCLC, which would add evidence on the efficacy of checkpoint inhibitors in the treatment of extensive-stage SCLC.To evaluate the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with extensive-stage SCLC.This international, double-blind, phase 3 randomized clinical trial (ASTRUM-005) enrolled patients at 114 hospital sites in 6 countries between September 12, 2019, and April 27, 2021. Of 894 patients who were screened, 585 with extensive-stage SCLC who had not previously received systemic therapy were randomized. Patients were followed up through October 22, 2021.Patients were randomized 2:1 to receive either 4.5 mg/kg of serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks. All patients received intravenous carboplatin and etoposide every 3 weeks for up to 12 weeks.The primary outcome was overall survival (prespecified significance threshold at the interim analysis, 2-sided P .012). There were 13 secondary outcomes, including progression-free survival and adverse events.Among the 585 patients who were randomized (mean age, 61.1 [SD, 8.67] years; 104 [17.8%] women), 246 (42.1%) completed the trial and 465 (79.5%) discontinued study treatment. All patients received study treatment and were included in the primary analyses. As of the data cutoff (October 22, 2021) for this interim analysis, the median duration of follow-up was 12.3 months (range, 0.2-24.8 months). The median overall survival was significantly longer in the serplulimab group (15.4 months [95% CI, 13.3 months-not evaluable]) than in the placebo group (10.9 months [95% CI, 10.0-14.3 months]) (hazard ratio, 0.63 [95% CI, 0.49-0.82]; P .001). The median progression-free survival (assessed by an independent radiology review committee) also was longer in the serplulimab group (5.7 months [95% CI, 5.5-6.9 months]) than in the placebo group (4.3 months [95% CI, 4.2-4.5 months]) (hazard ratio, 0.48 [95% CI, 0.38-0.59]). Treatment-related adverse events that were grade 3 or higher occurred in 129 patients (33.2%) in the serplulimab group and in 54 patients (27.6%) in the placebo group.Among patients with previously untreated extensive-stage SCLC, serplulimab plus chemotherapy significantly improved overall survival compared with chemotherapy alone, supporting the use of serplulimab plus chemotherapy as the first-line treatment for this patient population.ClinicalTrials.gov Identifier: NCT04063163.

PURPOSE To investigate the efficacy of PD-1/PD-L1 inhibitors plus chemotherapy versus anti–PD-1/PD-L1 monotherapy in advanced microsatellite instability (MSI)/mismatch repair-deficient (dMMR) gastrointestinal cancers. METHODS We retrospectively recruited patients with MSI/dMMR gastrointestinal cancer who received anti–PD-1/PD-L1 with or without chemotherapy and compared objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of PD-1/PD-L1 inhibitor plus chemotherapy (chemo-anti–PD-1/PD-L1 group) and PD-1/PD-L1 inhibitor alone (anti–PD-1/PD-L1 group). Propensity score–based overlap weighting analysis was conducted to adjust the baseline covariable imbalance. Sensitivity analysis was performed to confirm the stability of the results by propensity score matching and multivariable Cox and logistic regression models. RESULTS A total of 256 patients were eligible, with 68 and 188 receiving chemo-anti–PD-1/PD-L1 and anti–PD-1/PD-L1, respectively. The chemo-anti–PD-1/PD-L1 group showed significant improvements versus the anti–PD-1/PD-L1 group in ORR (61.8% v 38.8%; P = .001), DCR (92.6% v 74.5%; P = .002), PFS (median PFS [mPFS], not reached [NR] v 27.9 months; P = .004), and OS (median OS [mOS], NR v NR; P = .014). After overlap weighting, the improvements tended to be more significant with chemo-anti–PD-1/PD-L1 versus anti–PD-1/PD-L1 in ORR (62.5% v. 38.3%; P < .001), DCR (93.8% v 74.2%; P < .001), PFS (mPFS, NR v 26.0 months; P = .004), and OS (mOS, NR v NR; P = .010). These results were solidified through sensitivity analysis. CONCLUSION Chemo-anti–PD-1/PD-L1 is superior to anti–PD-1/PD-L1 in MSI/dMMR gastrointestinal cancers with improved efficacy.

Background Previous studies have demonstrated the preclinical pharmacological and toxicological consistency, and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab (Avastin). This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first‐line treatment of Chinese patients with advanced or recurrent non‐squamous non‐small cell lung cancer (NSCLC). Methods Stage IIIB‐IV NSCLC patients with evaluable lesions, good physical status, and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin (combined treatment) for 4‐6 cycles, followed by maintenance monotherapy with LY01008 until disease progression, intolerable toxicity, or death. The primary endpoint was objective response rate (ORR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by independent radiological review committees (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression‐free survival (PFS), overall survival (OS), and safety. This study was registered in ClinicalTrials.gov (NCT03533127). Results Between December 15th, 2017, and May 15th, 2019, a total of 649 patients were randomized to the LY01008 (n = 324) or Avastin (n = 325) group. As of September 25th, 2019 for primary endpoint analysis, 589 patients received ORR evaluation, with a median number of combined treatment cycles of 5 (range 1‐6) and median duration of treatment of 3.0 (range 0.0‐5.1) months. ORR of response‐evaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%, respectively. The stratified ORR ratio was 0.91 (90% CI 0.80‐1.04, within the prespecified equivalence margin of 0.75‐1.33). Up to May 15th, 2020, with a median follow‐up of 13.6 (range 0.8‐28.4) months, no notable differences in DCR, median DoR, median PFS, median OS, and 1‐year OS rate were observed between the LY01008 and Avastin groups. There were no clinically meaningful differences in safety and immunogenicity across treatment groups. Conclusions LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non‐squamous NSCLC. LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable, metastatic, or recurrent non‐squamous NSCLC patients in the first‐line setting., This study demonstrated similarity between LY01008 and reference bevacizumab (Avastin) in terms of efficacy, safety, and immunogenicity in combination with paclitaxel and carboplatin as first‐line treatment in Chinese patients with advanced non‐squamous NSCLC.

Background: The ORIENT-15 study (NCT03748134) evaluated sintilimab (anti-PD-1 antibody) plus chemotherapy (Sin+Chemo) versus placebo plus chemotherapy (Chemo) as first-line (1L) treatment of unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC). At the prespecified interim analysis, this study met the primary endpoints of overall survival (OS) in all patients (pts) (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.51-0.78; P Methods: Eligible pts were randomized 1:1 to receive sintilimab/placebo (3 mg/kg in pts weighing Results: Overall, 690 pts (median age 63.0; 85.5% male; 93.3% Asian and 4.9% White; 24.3% liver metastasis; 90.7% TP regimen) were randomized and received Sin+Chemo (341 pts) or Chemo (349 pts). As of data cutoff date (Aug 28, 2022), the median follow-up was 32.2 months (interquartile range 28.0-35.8); 231 OS events were observed in Sin+Chemo group and 278 in Chemo group. Sin+Chemo continued to demonstrate an OS benefit vs Chemo in all pts (median OS 17.4 [95% CI 16.0-19.8] vs 12.8 [95% CI 11.3-14.5] months; HR 0.661 [95% CI: 0.554-0.788]; P Conclusions: Sin+Chemo continued to demonstrate significant OS benefits in advanced ESCC in both overall and PD-L1 CPS ≥10 populations with an acceptable safety profile over time. These data further support the use of Sin+Chemo as a standard of care for 1L treatment in these patients. Citation Format: Zhihao Lu, Junye Wang, Yongqian Shu, Li Kong, Buhai Wang, Lei Yang, Guochun Cao, Guogui Sun, Yinghua Ji, Hu Liu, Tongjian Cui, Wensheng Qiu, Aziz Zaanan, Roberto Pazo Cid, Hui Zhou, Xing Sun, Yan Wang, Yuling Chen, Haoyuan Li, Lishi Zhang, Lin Shen. Updated overall survival outcomes from a randomized, double-blind phase III study of sintilimab versus placebo in combination with chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma (ORIENT-15) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT075.

We investigate the dynamical behaviors of quantum-memory-assisted entropic uncertainty relation (QMA-EUR) and quantum correlation (both quantum entanglement and quantum discord) for a two-qubit system coupled to a spin environment by a z–x-type interaction. Our purpose is to find out how the QMA-EUR and quantum correlations are affected by the pre-designed factors of the environment, including initial spin environmental states and the coupling constants. The numerical results show that the initial environmental state has significant effect on the dynamics of quantum correlations of the central spin system. We find that the environment should be prepared in a block entangled state with Bell state. This option is beneficial to reducing entropic uncertainty and inhibits the damping of quantum correlation. We also find that the high frequency particles in a spin bath can significantly enhance the robustness of quantum correlation of the system.

384 Background: CAP 02 study (NCT03736863) is a single-arm phase 2 study to evaluate the efficacy and safety of camrelizumab plus apatinib (a VEGFR2 inhibitor) as second-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). Cohort 1 has been published recently, which enrolled patients who progressed after or were intolerant to first-line chemotherapy. The results showed an encouraging median overall survival (OS) of 15.8 months. Here, we reported the preliminary results of cohort 2. Methods: Cohort 2 enrolled unresectable locally advanced, locally recurrent, or metastatic ESCC patients aged 18-75 years with ECOG performance status of 0-1 who had progression on or were intolerant to first-line immunochemotherapy. The disease should be controlled without progression for at least three months during the first-line treatment. Patients received camrelizumab (200 mg Q2W) and apatinib (250 mg QD) until disease progression, intolerable toxicity, or withdrawal for other reasons. The primary endpoint was the objective response rate (ORR). Secondary endpoints included disease control rate, progression-free survival (PFS), duration of response, time to response, OS, 3/6-month PFS rates, 6/9/12-month OS rates, and safety. Results: At the data cutoff (Sep 21, 2022), 33 of the planned 40 patients with an average of 68 years old had been enrolled, including 24 (73%) males and 24 (73%) patients with an ECOG PS score of 1. Twenty-one patients (64%) were previously treated with camrelizumab combined chemotherapy and 12 with other immunochemotherapy. Among the 17 evaluable patients, seven had the best overall response of partial response and nine with stable disease; the ORR was 41%. A total of 22 patients (67%) had treatment-related adverse events (TRAEs), with 12 patients (36%) with grade≥3. The most common TRAEs included white blood cell count decreased (11 patients, 33%), hypokalaemia (9, 27%), and alanine aminotransferase increased (8, 24%). Conclusions: Current results suggested the preliminary efficacy of second-line camrelizumab plus apatinib in patients with immunochemotherapy-treated advanced ESCC, with an acceptable safety profile. The study enrollment is ongoing, and further survival and safety data will be reported in the future. Clinical trial information: NCT03736863 .

In this paper, we focus on studying how to enhance the precision of parameter estimation by dynamical decoupling (DD) pulses in an open system. Our results show that, when a qubit is subjected to a zero-temperature Ohmic-like dephasing reservoir, the quantum Fisher information (QFI) is determined by the decoherence function of this qubit. If the appropriate DD pulse frequency is selected, the decoherence in noisy environment can be effectively suppressed and the precision in parameter estimation can be enhanced. Moreover, we make a further comparison for the control effects between Uhrig dynamical decoupling (UDD) sequence and periodic dynamic decoupling (PDD) sequence in the sub-Ohmic and super-Ohmic environments. We find that, when the same DD pulses are applied to this qubit, UDD has obvious advantages over PDD in terms of improving precision of parameter estimation. This is because UDD can completely eliminate the adverse effect of environmental decoherence on parameter estimation.

We investigate the dynamical behaviors of quantum-memory-assisted entropic uncertainty under the quantum-jump-based feedback control in open systems containing two qubits, and analyze the influence of feedback modes and coefficients on the entropic uncertainty. Numerical investigations indicate that: under quantum-jump-based feedback control, no matter whether qubits A and B are both or alone suffering from the environmental decoherence, when the feedback coefficient is the integer multiples of π/2, the entropic uncertainty of the system is a minimum value, which is far less than that without feedback control. As the dissipative coefficient γ decreases, namely the environmental decoherence decreases, the entropic uncertainty can be greatly improved under the quantum-jump-based feedback control.

It has long been interest to control the transfer of population between specified quantum states and protect the coherence of the system at the same time. In this paper, we investigate a scheme to improve the strategy of state transfer for open quantum systems using no-knowledge measurement-based feedback control and reverse engineering. In order to ensure that the system can process information effectively, we first design the control pulse in advance from the perspective of population and coherence and then verify it through numerical simulations. The research results show that, based on the designed control pulse, we can indeed drive the system from any initial state to the desired target state, and the coherence of the system can be effectively protected during the state transition.

Rice black-streaked dwarf disease, caused by rice black-streaked dwarf virus (RBSDV), is a serious constraint in Chinese rice production. Breeding disease-resistant varieties through multigene aggregation is considered an effective way to control diseases, but few disease-resistant resources have been characterized thus far. To develop novel resources for resistance to RBSDV through CRISPR/Cas9-mediated genome editing, a guide RNA sequence targeting exon 1 of eIF4G was designed and cloned into a binary vector, pHUE401. This recombinant vector was used to generate mutations in the rice cultivar Nipponbare via Agrobacterium-mediated transformation. This approach produced heritable homozygous mutations in the transgene-free T1 generation. Sequence analysis of the eIF4G target region from T1 transgenic plants identified 3 bp deletion mutants, and analysis of the predicted amino acid sequence identified one amino acid deletion in mutants that possess near full-length eIF4G. Furthermore, our data suggest that eIF4G may plays an important role in rice normal development, as there were no eIF4G knock-out homozygous mutants in T1 generation plants. When homozygous mutant lines were inoculated with RBSDV, they exhibited enhanced tolerance to virus infection, without visibly affecting plant growth and development. However, the eif4g mutant plants showed the same sensitivity to rice stripe virus (RSV) infection as wild-type plants. Notably, the wild-type and mutant N-termini of eIF4G interacted directly with RBSDV P8 in yeast and in planta. Additionally, compared to wild-type plants, the eIF4G transcript level was reduced twofold in the mutant plants. These results indicate that site-specific mutation of rice eIF4G successfully conferred partial resistance specific to RBSDV associated with less transcription of eIF4G in mutants. Therefore, this study demonstrates that the novel eIF4G alleles generated by CRISPR/Cas9 represent valuable disease-resistant resources that can be used to develop RBSDV-resistant varieties.

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancers. Chemotherapy is the most important therapeutic option for TNBC, and chemotherapy-induced nausea and vomiting (CINV) is inevitable. Metoclopramide is a good and cost-effective therapeutic option for chemotherapy-induced nausea and vomiting. However, it is not commonly used in breast cancer because it can increase serum prolactin levels by blocking dopamine D2 receptor. This study aimed at elucidating the effect of metoclopramide on triple-negative breast cancer, MDA-MB-231 cells were treated with various concentrations of metoclopramide, the cell proliferation was detected by MTT method, the apoptosis rate was detected by Annexin V/PI double staining method, the expression change of death-related protein was detected by Western Blot. We found that metoclopramide inhibits cell proliferation and induces cell apoptosis of MDA-MB-231 in a concentration-dependent manner, and the Bcl family was involved in this process.

In this paper, we propose a closed-loop real-time feedback design for manipulating a quantum state to a target eigenstate via sequential measurements. To this end, based on the Lyapunov stability theorem, considering the controllability and convergence of the system, we select one measured observable and two control channels, which feedback part of the output signal to the input end, forming a closed-loop control. By dynamical programming, we find the optimal parameters to achieve state transfer with a high probability by real-time feedback control. Numerical simulation experiments show that, in a stochastic quantum system with non-Markovian noise, the real-time control strategy moves the system from initial state to the target eigenstate with fast convergence.

We investigate the dynamics of quantum-memory-assisted entropic uncertainty relations under two typical categories of noise: phase damping channel and amplitude damping channel. It is shown that, the entropic uncertainty monotonically increases and tends to a steady-state value with the increase of decoherence in phase damping channel, and can always keep its lower bound during the evolution when the initial state is the maximum entangled state. In contrast, under the amplitude damping channel with memory, the entropic uncertainty always fails to reach its lower bound, even in the decoherence-free subspace formed by it. Besides, the entropic uncertainty and its lower bound firstly increase with time, then turn down and tend to steady-state values. Our investigations might offer an insight into the dynamics of the measurement uncertainty under decoherence, and are important to quantum precision measurement in open systems.

We investigate the quantum-memory-assisted entropic uncertainty relation between coupled qubits which are initially in entangled mixed states in squeezed vacuum reservoir. We find that the uncertainty of quantum system is dependent on the squeezing effect of optical field. In the squeezed vacuum reservoir, the smaller the squeezed amplitude parameter is, the smaller the entropic uncertainties and its lower bound are, the more favorable to improve the accuracy of quantum measurement. Through optimizing the parameters of the initial quantum state, the measurement precision of observable mechanical quantity can be improved. In particular, when the relative phase of the initial quantum state is an integer multiple of ⁡ π , the lower bound of the entropic uncertainty reaches a minimum.

9096 Background: We previously reported (Lu, ASCO 2021, abstract # 9013) that treatment with aumolertinib (Au), a 3rd generation EGFR TKI, led to robust improvement in progression free survival (PFS) (median PFS 19.3 to 9.9 months, HR = 0.46, p < 0.0001) when compared to gefitinib (G) with a predictable and encouraging safety profile. This benefit was maintained across all prespecified stratification factors including the subset of ̃ 27% of patients (pts) with CNS metastases (HR = 0.38). Here we undertook this analysis to more fully characterize the activity and benefit of Au as compared to G in this clinically important subset of EGFR mutant NSCLC pts. Methods: Pts with previously untreated metastatic or locally advanced NSCLC with EGFR sensitizing mutations were enrolled and randomly assigned in a 1:1 ratio to receive either Au (110 mg QD) or G (250 mg QD). Predefined stratification factors were EGFR-mutated status (Ex19del vs L858R) and CNS metastases (yes vs no). Patients with stable, asymptomatic CNS metastases were eligible for enrollment. All pts had baseline brain imaging by magnetic resonance imaging or computed tomography. The primary endpoint was PFS assessed by investigator per RECIST v1.1 in full analysis set (systemic analysis). Independent CNS efficacy was performed both in pts with baseline CNS metastases (CNS full analysis set, cFAS) and in pts with baseline CNS target lesions (CNS evaluable-for-response set, cEFS) by blinded independent central neuroradiology review (BICR) per RECIST v1.1. Results: Of 429 pts, 106 pts (Au, n = 51; G, n = 55) were found to have CNS metastases (cFAS) and 61 pts (Au, n = 29; G, n = 32) had CNS target lesions as defined by RECIST 1.1 (cEFS) at baseline by BICR. At the cutoff date (Aug 6, 2021), based on cEFS, CNS PFS events were observed in 11 pts (38%) treated with Au versus 20 pts (63%) who were randomized to receive G. Treatment with Au significantly prolonged CNS median PFS compared with G (29.0 vs 8.3 months; HR = 0.300; 95% CI, 0.137-0.657; P = 0.0015). Estimated CNS PFS rate at 12 and 18 months were 71% and 62% in Au arm compared with 23% and 0% in G arm. The confirmed CNS ORR were 82.8% and 75.0% in pts treated with Au and G, respectively (odds ratio = 1.600; 95% CI, 0.457-5.597; P = 0.4621). Au also achieved longer CNS median PFS over G in cFAS (29.0 vs 8.3 months; HR = 0.323; 95% CI, 0.181-0.576; P < 0.0001). No new safety findings were observed. Conclusions: Au demonstrated superior clinical efficacy against CNS metastases over G as first-line therapy in EGFR-mutated advanced NSCLC, and the safety profile was consistent with that reported previously. Additional randomized studies of Au in pts with CNS metastases are ongoing (NCT04870190). Clinical trial information: NCT03849768.

e21011 Background: EGFR exon 20 mutations are associated with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). EGFR exon 20 mutations are usually not present alone, suggesting a more complex subtype of exon 20 mutations. Methods: In this study, we retrospectively analyzed the different subtypes and compound mutation profiles of EGFR 20 mutations. A total of 1,233 NSCLC patients’ tumors were collected and the mutations were detected by next-generation sequencing (NGS) from May 2020 to June 2021. Results: A total of 415 NSCLC patients' tumors harbored EGFR exon 20 mutations, accounting for 33.66% of the entire EGFR mutation cohort. Among these 415 patients, most of mutations were single-nucleotide variant (SNV) (379; 91.33%), and a few were indel or insertion mutations (39; 9.40%). The insertions were all in the back of exon 20, which were resistant to EGFR-TKIs. In addition, the subtypes of SNV were concentrated in T790M (270; 71.24%), S768I (48; 12.66%) and C797S (33; 8.71%), and all T790M mutations were accompanied by other mutations. Notably, the compound mutations of exon 20 have also been analyzed in this study. EGFR exon 20 combined with other EGFR mutations were detected in 345 patients. The compound mutations of exon 20-18, exon 20-19, exon 20-20 and exon 20-21 were detected in tumors from 52 (15.07%), 163 (47.25%), 43 (12.46%) and 140 (40.58%) patients respectively. Remarkably, the compound mutation subtype of exon 20-20 was T790M/C797X (29; 67.55%) and exon 20-21 was T790M/L858R (124; 88.57%). Conclusions: Diverse patterns of SNV mutations are seen in EGFR exon 20 mutations tumors. EGFR 20 mutations often accompany other mutations, which are associated with resistance to EGFR-TKIs. These data may help avoid the resistance of future adjuvant targeted therapy.