With the rapid development of modern technology, more and more electronic equipment had entered people’s life, causing serious electromagnetic pollution. In this study, a lightweight, ultra-thin and ...high electromagnetic shielding film was fabricated by copper electroless deposition after solution immersion coating method combining chitosan (CTS) and reduced graphene oxide on glass fabric (Cu/RGO-CTS-coated glass fabric). Chitosan and RGO had synergistic effect for copper deposition, enhancing electrical conductivity and electromagnetic shielding property. The prepared fabric showed superb conductivity of 8589.3 S/cm and the shielding effectiveness of the Cu/RGO-CTS-coated glass fabric showed as high as 93.6 dB at ultra-thin thickness of 92.4 μm (SSE/t = 3868.8 dB cm
2
g
−1
). Thermal conductivity, antibacterial and hydrophobic properties were also studied. Compared with untreated glass fabric, thermal conductivity of Cu/RGO-CTS-coated glass fabric increased by 437%, protecting electronic equipment from adverse effects at high temperature. Cu/RGO-CTS-coated glass fabric had inhibitory effect on
Staphylococcus aureus
and
Escherichia coli
, which could prolong the service life and maintain the appearance of the fabric. Cu/RGO-CTS-coated glass fabric also showed hydrophobicity with self-cleaning function, making it possible for the composite material to be used in many fields such as aerospace industry, microelectronic devices, and transportation to resist electromagnetic interference in high humidity and high pollution environment.
The development of efficient and stable organic photovoltaic (OPV) systems for commercial applications has long been a primary objective. While single-component material systems have demonstrated ...promising operational and thermal stability, their efficiency still lags behind that of multicomponent bulk heterojunction devices due to limitations in scarce building blocks, complex synthesis processes, and challenges in controlling morphology. In this work, we present a novel approach by introducing a fused-ring electron acceptor as a pendant segment, which offers new possibilities for the development of double-cable single-component copolymers. This innovative strategy not only broadens their spectral absorption but also simplifies their synthesis complexity. Through careful adjustment of molecular weight, we achieved an outstanding power conversion efficiency of 9.35% and a minimized energy loss of 0.517 eV, which is one of the best results reported for structure well-defined double-cable copolymer-based OPVs. Impressively, the designed double-cable polymers exhibit excellent photo, thermal, and mechanical stabilities, further highlighting their potential for practical applications.
Many Gram-negative bacterial pathogens utilize the type III secretion system (T3SS) to inject virulence factors, named effectors, into host cells. These T3SS effectors manipulate host cellular ...signaling pathways to facilitate bacterial pathogenesis. Death receptor signaling plays an important role in eukaryotic cell death pathways. NleB from enteropathogenic
(EPEC) and SseK1/3 from
serovar Typhimurium (
. Typhimurium) are T3SS effectors. They are defined as a family of arginine GlcNAc transferase to modify a conserved arginine residue in the death domain (DD) of the death receptor TNFR and their corresponding adaptors to hijack death receptor signaling. Here we identified that these enzymes, NleB, SseK1, and SseK3 could catalyze auto-GlcNAcylation. Residues, including Arg13/53/159/293 in NleB, Arg30/158/339 in SseK1, and Arg153/184/305/335 in SseK3 were identified as the auto-GlcNAcylation sites by mass spectrometry. Mutation of the auto-modification sites of NleB, SseK1, and SseK3 abolished or attenuated the capability of enzyme activity toward their death domain targets during infection. Loss of this ability led to the increased susceptibility of the cells to TNF- or TRAIL-induced cell death during bacterial infection. Overall, our study reveals that the auto-GlcNAcylation of NleB, SseK1, and SseK3 is crucial for their biological activity during infection.
Species of the tribe Delphinieae (Ranunculaceae) have long been the focus of morphological, ecological, and evolutionary studies due to their highly specialized, nearly zygomorphic (bilaterally ...symmetrical) spiral flowers with nested petal and sepal spurs and reduced petals. The mechanisms underlying the development and evolution of Delphinieae flowers, however, remain unclear. Here, by conducting extensive phylogenetic, comparative transcriptomic, expression, and functional studies, we clarified the evolutionary histories, expression patterns, and functions of floral organ identity and symmetry genes in Delphinieae. We found that duplication and/or diversification of APETALA3-3 (AP3-3), AGAMOUS-LIKE6 (AGL6), CYCLOIDEA (CYC), and DIVARICATA (DIV) lineage genes was tightly associated with the origination of Delphinieae flowers. Specifically, an AGL6-lineage member (such as the Delphinium ajacis AGL6-1a) represses sepal spur formation and petal development in the lateral and ventral parts of the flower while determining petal identity redundantly with AGL6-1b. By contrast, two CYC2-like genes, CYC2b and CYC2a, define the dorsal and lateral-ventral identities of the flower, respectively, and form complex regulatory links with AP3-3, AGL6-1a, and DIV1. Therefore, duplication and diversification of floral symmetry genes, as well as co-option of the duplicated copies into the preexisting floral regulatory network, have been key for the origin of Delphinieae flowers.
Despite studies investigating the publication rates and factors influencing publication outcomes of clinical trials in some disease fields, there is a notable lack of research focusing on chronic ...obstructive pulmonary disease (COPD) clinical trials. This study aims to explore the characteristics of COPD-related clinical trials and identify factors associated with publication status and publication time.
A systematic search was conducted on the World Health Organization International Clinical Trials Registry Platform on April 28, 2022, to identify completed interventional clinical trials related to COPD. Various trial features were analyzed, and factors influencing publication status and time were examined.
A total of 2577 completed interventional clinical trials focusing on COPD were identified. A total of 42.76% of trials enrolled ≤50 participants. The majority of trials were randomized (81.72%), blind (57.39%), parallel-assignment (59.14%), single-center (51.30%), multi-arm (83.86%), nonindustry funded (52.00%), and conducted for therapeutic purposes (73.11%). The 2-year cumulative publication rate was found to be 27.9%. The median time of study duration, dissemination lag, and publication lag were 17.27, 21.07, and 24.70 months, respectively. Multivariate analysis revealed that sample size, blind design, and study phase significantly influenced the likelihood of publication, while intervention model, primary purpose, study phase, funder, and study duration were significant factors affecting publication time.
The findings highlight the inadequacy of large multi-center interventional clinical trials for COPD and indicate a low 2-year cumulative publication rate. Strengthening collaboration among investigators and adopting scientifically robust designs for larger phase 3 clinical trials are crucial to advancing COPD research and enhancing publication outcomes.
Iruplinalkib (WX-0593) is a new-generation, potent ALK tyrosine kinase inhibitor (TKI) that has been found to have systemic and central nervous system (CNS) efficacy in ALK-positive NSCLC. We ...compared the efficacy and safety of iruplinalkib with crizotinib in patients with ALK TKI-naive, locally advanced or metastatic ALK-positive NSCLC.
In this open-label, randomized, multicenter, phase 3 study, patients with ALK-positive NSCLC were randomly assigned to receive iruplinalkib 180 mg once daily (7-d run-in at 60 mg once daily) or crizotinib 250 mg twice daily. The primary end point was progression-free survival (PFS) assessed by Independent Review Committee (IRC) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included PFS by investigator, objective response rate (ORR), time to response, duration of response, intracranial ORR and time to CNS progression by IRC and investigator, overall survival, and safety. An interim analysis was planned after approximately 70% (134 events) of all 192 expected PFS events assessed by IRC were observed. Efficacy was analyzed in the intention-to-treat population. Safety was assessed in the safety population, which included all randomized patients who received at least one dose of the study drugs. This study is registered with Center for Drug Evaluation of China National Medical Products Administration (CTR20191231) and Clinicaltrials.gov (NCT04632758).
From September 4, 2019, to December 2, 2020, a total of 292 patients were randomized and treated; 143 with iruplinalkib and 149 with crizotinib. At this interim analysis (145 events), the median follow-up time was 26.7 months (range: 3.7–37.7) in the iruplinalkib group and 25.9 months (range: 0.5–35.9) in the crizotinib group. The PFS assessed by IRC was significantly longer among patients in the iruplinalkib group (median PFS, 27.7 mo 95% confidence interval (CI): 26.3–not estimable versus 14.6 mo 95% CI: 11.1–16.5 in the crizotinib group; hazard ratio, 0.34 98.02% CI: 0.23–0.52, p < 0.0001). The ORR assessed by IRC was 93.0% (95% CI: 87.5–96.6) in the iruplinalkib group and 89.3% (95% CI: 83.1–93.7) in the crizotinib group. The intracranial ORR was 90.9% (10 of 11, 95% CI: 58.7–99.8) in the iruplinalkib group and 60.0% (nine of 15, 95% CI: 32.3–83.7) in the crizotinib group for patients with measurable baseline CNS metastases. Incidence of grade 3 or 4 treatment-related adverse events was 51.7% in the iruplinalkib group and 49.7% in the crizotinib group.
Iruplinalkib was found to have significantly improved PFS and improved intracranial antitumor activity versus crizotinib. Iruplinalkib may be a new treatment option for patients with advanced ALK-positive and ALK TKI-naive NSCLC.
This study was funded by Qilu Pharmaceutical Co., Ltd., Jinan, People’s Republic of China, and partly supported by the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).
The thylakoid membrane lipid sulfoquinovosyldiacylglycerol (SQDG) is an anionic molecule that functions in stabilizing the thylakoid membranes and photosystem (PS) supercomplexes. In this study, we ...characterized the function of GreenCut protein CrLPB1, which encodes UDP-glucose pyrophosphorylase (UGP3), an enzyme involved in SQDG biosynthesis. The lpb1 mutants had reduced levels of SQDG, grew more slowly than wild type cells or the complemented strain under photoautotrophic conditions and were impacted in its rate of oxygen evolution and photosystem II (PSII) activity, especially electron transfer from QA− to QB. Furthermore, the structure of the PSII supercomplex and morphology of the thylakoid membranes were also both altered in lpb1. In conclusion, LPB1 is involved in SQDG biosynthesis, which in turn appears to be critical in maintaining normal thylakoid membrane structure and PSII activity/stability.
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•LPB1 may affect photosynthesis by regulating the biosynthesis of SQDG.•PSII activity of lpb1 is diminished, especially, electron transfer from QA- to QB and the oxygen evolving rate indicating that photosynthesis is affected in lpb1.•The content of PSII-LHCII supercomplex in lpb1 is decreased, indicating that the stability of PSII-LHCII supercomplex is affected.•The structure of thylakoid membrane in lpb1 was also altered both during growth in photoautotrophic and mixotrophic growth medium, which may be the primary reason for the decreased of stability of the PSII-LHCII supercomplex.
•A high-throughput identification technique that simultaneously detects six major swine pathogens was developed.•This techenique was based on multiplex PCR system and microarry.•Pathogens involved in ...this study including APP, HPS, PRRSV, Mhp, PCV-2 and CSFV.
In order to establish a high-throughput identification technique that simultaneously detects six major pathogens including APP, HPS, PRRSV, Mhp, PCV-2 and CSFV, six pairs of primers and probes were designed based on the specific conservative sequences of the pathogens, a multiplex PCR system was developed, hybrid parameters were optimized, and evaluation of the technology was performed. The results showed that the present detection method had a sensitivity of 5.8 × 102copies/μL for APP, 7.8 × 103 copies/μL for HPS, 6.8 × 103 copies/μL for Mhp, 6.3 × 102 copies/μL for PCV-2, 4.8 × 103 copies/μL for PRRSV, and 5.5 × 102 copies/μL for CSFV, respectively; and it produced no cross reaction against the other nine pathogens like swine-origin pseudorabies virus, porcine parvovirus, Japanese B encephalitis virus, swine vesicular disease virus, vesicular stomatitis virus, foot-and-mouth disease virus, bluetongue virus, peste des petits ruminants virus and salmonella. Application of the multiplex oligonucleotide microarray established here to testing 285 clinical blood samples indicated a single infection rate of 18.2 % (52/285) and a mixed infection rate of 6.3 % (18/285) which were consistent with the results of the sequencing verification. This technique might serve as a rapid and high-throughput method of detection for epidemic investigation and clinical diagnosis of multiple pathogens.
Background Iruplinalkib (WX-0593) is an anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1) tyrosine kinase inhibitor. Here we reported the single-arm, phase II study (INTELLECT) results of the ...efficacy and safety of iruplinalkib for ALK-positive crizotinib-resistant advanced non-small cell lung cancer (NSCLC) patients. Methods ALK-positive crizotinib-resistant advanced NSCLC patients aged greater than or equal to18 years, with Eastern Cooperative Oncology Group performance status of 0-2 were eligible. Patients received iruplinalkib 180 mg orally once daily for a 21-day cycle with a 7-day lead-in phase at 60 mg orally once daily. The primary endpoint was the independent review committee (IRC)-assessed objective response rate (ORR). Results From August 7, 2019, to October 30, 2020, 146 patients were included. As of the data cut-off date on November 30, 2021, the median follow-up time was 18.2 months (95% confidence interval CI 16.8-18.8). IRC-assessed ORR and disease control rate (DCR) were 69.9% (95% CI 61.7-77.2%) and 96.6% (95% CI 92.2-98.9%), respectively. Investigator-assessed ORR and DCR were 63.0% (95% CI 54.6-70.8%) and 94.5% (95% CI 89.5-97.6%), respectively. Investigator-assessed median duration of response and progression-free survival (the same as median time to progression) were 13.2 months (95% CI 10.4-17.7) and 14.5 months (95% CI 11.7-20.0), respectively. Corresponding IRC-assessed results were 14.4 months (95% CI 13.1-not evaluable NE), 19.8 months (95% CI 14.5-NE), and NE (95% CI 14.5-NE), respectively. Investigator-assessed intracranial ORRs were 46% (41/90, 95% CI 35-56%) in patients with central nervous system metastases and 64% (27/42, 95% CI 48-78%) in patients with measurable intracranial lesions. Overall survival data were immature. Treatment-related adverse events (TRAEs) occurred in 136/146 (93.2%) patients. The most common TRAEs were aspartate aminotransferase increased (63 43.2%), alanine aminotransferase increased (54 37.0%), and blood creatine phosphokinase increased (51 34.9%). Dose interruption, reduction, and discontinuation due to TRAEs occurred in 21 (14.4%), 16 (11.0%), and four (2.7%) patients, respectively. Conclusions In this study, iruplinalkib (WX-0593) demonstrated favorable efficacy and manageable safety profiles in patients with ALK-positive crizotinib-resistant advanced NSCLC. Iruplinalkib could be a new treatment option for this patient population. Trial registration Center for Drug Evaluation of National Medical Products Administration of China: CTR20190789, registered on April 28, 2019; ClinicalTrials.gov: NCT04641754, registered on November 24, 2020. Keywords: Iruplinalkib, WX-0593, Non-small cell lung cancer, Anaplastic lymphoma kinase, Tyrosine kinase inhibitor
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