Background
Patients with extensive‐stage small cell lung cancer (ES‐SCLC) have an exceptionally poor prognosis and immune checkpoint inhibitors (ICIs) combined with etoposide‐platinum is recommended ...as standard first‐line therapy. However, which combination pattern is the best still remains unknown. This network meta‐analysis was performed to compare the efficacy and safety of currently available patterns including an antiangiogenic agent containing regimen and probed into the most appropriate therapy for patients.
Methods
Hazard ratios (HRs) and odds ratios (ORs) were generated using R software. The outcomes of overall survival (OS), progression‐free survival (PFS), objective response rate (ORR), and adverse events of grade 3 or higher (grade ≥ 3 adverse events AEs) were analyzed.
Results
A total of 10 randomized controlled trials (RCTs) involving 5544 patients were included for analysis. Drug combination patterns included adebrelimab, atezolizumab, durvalumab, durvalumab plus tremelimumab, ipilimumab, pembrolizumab, serplulimab, benmelstobart plus anlotinib, tislelizumab, tiragolumab plus atezolizumab and toripalimab in combination with chemotherapy. The novel antiangiogenic agent containing regimen benmelstobart + anlotinib + chemotherapy showed the highest possibility to present the best PFS and OS versus chemotherapy. Compared with ICI plus chemotherapy, it also achieved significantly better PFS and presented a tendency of OS benefit. As for safety and toxicity, patients treated with benmelstobart + anlotinib + chemotherapy and durvalumab + tremelimumab + chemotherapy suffered a higher likelihood of more grade ≥ 3 AEs without unexpected AEs.
Conclusion
PD‐1/PD‐L1 inhibitors‐based combinations are associated with significant improvement in both PFS and OS for treatment‐naïve ES‐SCLC patients. Benmelstobart plus anlotinib with chemotherapy (CT) yielded better survival benefit versus CT alone or other ICIs + CT with caution for more adverse effects along with the addition of an antiangiogenic agent.
We compared the efficacy and safety of currently available ICI‐based regimens, and investigated the most appropriate therapy for treatment‐naïve ES‐SCLC patients. PD‐1/PD‐L1 inhibitors‐based combinations are associated with significant improvement in both PFS and OS. The novel antiangiogenic agent containing regimen benmelstobart, anlotinib and chemotherapy further improved survival with more but manageable adverse events.
miR171 belongs to a highly conserved and ubiquitously expressed microRNA gene family across species that play a critical role in controlling plant growth and development through the regulation of the ...miR171-SCL (scarecrow-like proteins) module. There is limited research available on the evolutionary relationship and functional diversification of miR171 members. In this study, we identified eight miR171 genes in the mulberry genome by bioinformatics analysis that were subsequently used to compare the evolutionary levels and explore abiotic stress mechanisms mediated by mno-miR171s (Morus notabilis miR171s). The results of phylogenetic analysis showed that the mature mno-miR171 sequences have strong sequence conservation, but their critical sites also exhibit high variation leading to functional diversification. Through quantitative real-time PCR, the expression profile of each mno-miR171 was analyzed under different stress treatments. All mno-miR171s, apart from mno-miR171h, were found to be significantly up-regulated under salt and drought stress conditions. The target genes of mno-miR171a namely, Morus020885 and Morus011800, were predicted and verified using the plural RNA method. 5′-rapid amplification of complementary DNA ends assays further to reveal that the target genes could be degraded by mno-miR171a post-transcriptionally. Overexpression of mno-miR171a in Arabidopsis improved the percentage of seed germination when the seeds were grown in NaCl- and mannitol-containing media. Transgenic plants were observed to grow better under drought conditions. The expression of various stress genes was significantly higher in transgenic plants than in wild type, except ERF11. Taken together, our study confirmed that mno-miR171a enhanced plant resistance to adverse stress environments via the regulation of the SCL targets.
This study examines the dynamic changes in groundwater levels and their spatial distribution in the Minqin Basin after the diversion of water from the ecosystem. It selected monitoring wells in ...different regions of the basin and analyzed the annual and seasonal fluctuations in groundwater levels before and after the water diversion. According to the findings, there is a notable shift in the rate of change in groundwater levels of the irrigated areas of the Minqin Basin: from an average of 0.62 m per year between 2001 and 2007 to a mere 0.01 m per year between 2008 and 2022. Since 2010, the groundwater level in the Qingtu Lake has increased by 1.01 m. The decline of Minqin Basin’s groundwater levels slowed down, and some places even witnessed rises in the groundwater level. The water levels in the region are generally stable.
The paper considers the ant colony optimization (ACO) methodology for designing an active debris removal mission. The goal is to optimize a sequence of transfers using an orbital transfer vehicle to ...rendezvous with multiple pieces of debris for the purpose of removal. The methodology consists of two phases: the first phase obtains an optimal removal sequence, and the second phase is related to transfer trajectory optimization. During the sequence planning process, a refined approximation is proposed to estimate the transfer times and necessary costs of individual transfers. The problem can then be mapped into a variant of the traveling salesman problem (TSP). To solve it, an enhanced ACO and the inver-over algorithm are proposed. The effectiveness of the ACO heuristic is proved over a set of instances with different sizes ranging from 100 to 2000. In the second phase, each transfer leg in the optimal sequence is verified using the continuous ACO proposed. The computational results show that the methodology proposed can optimally select targets from a debris archive of considerable size (i.e., up to 2000 debris pieces). Additionally, the mitigation of 13–20 objects, with total ΔV below 1 km/s, is feasible in less than a year.
Exploring environmentally friendly, efficient, cheap and recyclable catalysts are essential for the development of green, sustainable and mild processes for the liquid-phase Beckmann rearrangement. ...Herein, a novel caprolactam-based Brønsted acidic ionic liquid (CPL2MSA) was developed for the conversion of cyclohexanone oxime (CHO) to caprolactam (CPL), not only as a catalyst, but also as a mild reaction medium. Under the reaction conditions for the reaction temperature (90 °C), reaction time (2 h) and mole ratio (CPL2MSA: CHO = 3:1), CPL2MSA possesses plenty of high sulfonate groups, which exhibit high conversion (100%) and selectivity (95%) without any other co-catalysts or metals. Based on the thermogravimetric (TGA) and differential scanning calorimetry (DSC) analyses, the decomposition and glass transition temperatures are gradually increased with the increase in MSA mole content, revealing the existence of hydrogen-bonded clusters. Interestingly, the occurrent route of the liquid-phase Beckmann rearrangement for CHO in CPL2MSA is revealed by in situ FT-Raman. In addition, the dominating H-bond combination between CHO and CPL2MSA is further confirmed by COSMO-RS model. The activation energy (Ea) of the reaction is calculated by the first-order reaction kinetics. Thus, the CPL2MSA with plenty of acidic catalytic active species is an environmentally friendly and efficient candidate for the liquid-phase Beckmann rearrangement.
Closely located at the tumor suppressor locus 16q22.1, CKLF-like MARVEL transmembrane domain-containing member 3 and 4 (CMTM3 and CMTM4) encode two CMTM family proteins, which link chemokines and the ...transmembrane-4 superfamily. In contrast to the broad expression of both CMTM3 and CMTM4 in normal human adult tissues, only CMTM3 is silenced or down-regulated in common carcinoma (gastric, breast, nasopharyngeal, esophageal, and colon) cell lines and primary tumors. CMTM3 methylation was not detected in normal epithelial cell lines and tissues, with weak methylation present in only 5 of 35 (14%) gastric cancer adjacent normal tissues. Furthermore, immunohistochemistry showed that CMTM3 protein was absent in 12 of 35 (34%) gastric and 1 of 2 colorectal tumors, which was well correlated with its methylation status. The silencing of CMTM3 is due to aberrant promoter CpG methylation that could be reversed by pharmacologic demethylation. Ectopic expression of CMTM3 strongly suppressed the colony formation of carcinoma cell lines. In addition, CMTM3 inhibited tumor cell growth and induced apoptosis with caspase-3 activation. Thus, CMTM3 exerts tumor-suppressive functions in tumor cells, with frequent epigenetic inactivation by promoter CpG methylation in common carcinomas.
Transgenic plants overexpressing the vacuolar H+-pyrophosphatase are much more resistant to high concentrations of NaCl and to water deprivation than the isogenic wild-type strains. These transgenic ...plants accumulate more Na+and K+in their leaf tissue than the wild type. Moreover, direct measurements on isolated vacuolar membrane vesicles derived from the AVP1 transgenic plants and from wild type demonstrate that the vesicles from the transgenic plants have enhanced cation uptake. The phenotypes of the AVP1 transgenic plants suggest that increasing the vacuolar proton gradient results in increased solute accumulation and water retention. Presumably, sequestration of cations in the vacuole reduces their toxic effects. Genetically engineered drought- and salt-tolerant plants could provide an avenue to the reclamation of farmlands lost to agriculture because of salinity and a lack of rainfall.
Due to space limitations of transmission corridors, ultrahigh voltage (UHV) lines inevitably cross over other lines. UHV lines in a crossover section have a lightning shielding effect similar to that ...of a lightning conductor of lower lines. While, whether a 500-kV line below a crossover section meets the lightning protection requirements is unknown. Therefore, a calculation method for the shielding failure trip rate of transmission lines in a crossover section in a three-dimensional space is proposed. The calculation of the shielding failure trip rate of the 500-kV line without a ground wire below the UHV line was performed. The results revealed that the shielding failure rate of the lower line was positively correlated with the length of the lower line and was negatively correlated with the crossing angle and length of the upper line. The maximum traversal lengths for a 500-kV line without a ground wire below a UHV AC or DC line were 200 m and 150 m, respectively. These findings provide a scientific basis for lightning protection design of ultra-UHV line crossing areas.
Noncoherent early-late processing (NELP) code tracking loops are often implemented using digital hardware for digital global positioning system (GPS) receivers. Noncommensurate sampling technology is ...widely used because it is viewed as an effective solution to cope with the drawback of digital effects. However, the relationship between the sampling rate and auto-correlation function (ACF) is not adequately characterized by traditional analysis. The principles for selecting the sampling rate are still not apparent. In order to solve this problem, we first analyzed the effects of different sampling rates on ACF and obtained the analytical form of a discrete auto-correlation function (DACF) for a noncommensurate sampling rate. Based on the result, the relationship between the step variation in DACF and NELP parameters such as sampling rate, integration time, and correlator spacing was determined. The maximum step variation size of DACF was also determined. However, considering the actual situation, additional factors such as code Doppler shift, precorrelation filter, and thermal noise may degrade the step variation of DACF. The relationship between the step variation and these factors was analyzed separately. An appropriate sampling rate and appropriate correlator spacing were proposed to achieve the typical accuracy of measurement. The numerical simulation verified the validity of the above theoretical analyses, and finally, the conclusions and design constraints for the digital GPS receiver are summarized.
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