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[Objective] The relationship between farming and herding households’ livelihood capital and livelihood strategies was studied, and the spatial differences of farming and herding households’ livelihood capital and the transformation between livelihood strategies were analyzed in order to provide a theoretical basis for reducing farming and herding households’ livelihood vulnerability and ultimately achieving sustainable development. [Methods] Starting from the theoretical framework of sustainable livelihood analysis, a household questionnaire survey was used to analyze the key factors of livelihood capital and livelihood strategy transformation for farming and herding households in the national sandy land enclosed reserves in Maqu, Minqin, Shandan County, and Liangzhou District in Gansu Province, which were approved to be established in 2017, by combining a Logistic regression model and one-way analysis of variance (ANOVA). [Results] Financial capital was the most abundant form of livelihood capital, while natural capital was the least abundant form of livelihood capital for the farmers and herdsmen in the enclosed reserves of desertified land. There were significant differences in the distribution of livelihood capital among farmers and herdsmen with different livelihood strategies, and the livelihood capital of non-agricultural farmers and herdsmen was better than that of purely farming households. Cultivated (or grassland) area, cultivated (or grassland) quality, and production tools had significant positive effects on the choice of purely farming households. The size of the family labor force, the education level and the total household income had a significant negative impact on the choice of purely farming livelihood strategy. [Conclusion] The following countermesures should be promoted in the future. Those are increasing the publicity of ecological environmental protection in enclosed protected areas, strengthening the awareness of ecological protection among farmers and herdsmen, accelerating the development of agricultural mechanization, and encouraging the transformation of the remaining labor force to non-agricultural industries, thereby achieving diversification of livelihoods.

Drought stress is a predominant abiotic factor leading to decreased alfalfa yield. Genomic ploidy differences contribute to varying adaptation mechanisms of different alfalfa cultivars to drought conditions. This study employed a multi‐omics approach to characterize the molecular basis of drought tolerance in a tetraploid variant of alfalfa (Medicago sativa, Xinjiang‐Daye). Under drought treatment, a total of 4446 genes, 859 proteins, and 524 metabolites showed significant differences in abundance. Integrative analysis of the multi‐omics data revealed that regulatory modules involved in flavonoid biosynthesis, plant hormone signalling transduction, linoleic acid metabolism, and amino acid biosynthesis play crucial roles in alfalfa adaptation to drought stress. The severity of drought led to the substantial accumulation of flavonoids, plant hormones, free fatty acids, amino acids, and their derivatives in the leaves. Genes such as PAL, 4CL, CHI, CHS, PP2C, ARF_3, and AHP_4 play pivotal regulatory roles in flavonoid biosynthesis and hormone signalling pathways. Differential expression of the LOX gene emerged as a key factor in the elevated levels of free fatty acids. Upregulation of P5CS_1 and GOT1/2 contributed significantly to the accumulation of Pro and Phe contents. ERF19 emerged as a principal positive regulator governing the synthesis of the aforementioned compounds. Furthermore, observations suggest that Xinjiang‐Daye alfalfa may exhibit widespread post‐transcriptional regulatory mechanisms in adapting to drought stress. The study findings unveil the critical mechanisms by which Xinjiang‐Daye alfalfa adapts to drought stress, offering novel insights for the improvement of alfalfa germplasm resources. [ABSTRACT FROM AUTHOR]

Key Points: Question: Among patients with non–small cell lung cancer with the epidermal growth factor receptor (EGFR) variant who experienced resistance to EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment, does the addition of ivonescimab (a bispecific antibody targeting programmed cell death 1 protein and vascular endothelial growth factor) to chemotherapy improve progression-free survival compared with chemotherapy alone? Findings: In this phase 3 trial that enrolled 322 patients whose disease progressed while receiving EGFR-TKI treatment, ivonescimab plus chemotherapy significantly improved progression-free survival compared with placebo plus chemotherapy. Median progression-free survival was 7.06 months with ivonescimab vs 4.80 months with placebo. Meaning: Ivonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in patients with non–small cell lung cancer who previously underwent EGFR-TKI treatment and may offer a new treatment option for patients with TKI resistance. Importance: For patients with non–small cell lung cancer whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, particularly third-generation TKIs, optimal treatment options remain limited. Objective: To compare the efficacy of ivonescimab plus chemotherapy with chemotherapy alone for patients with relapsed advanced or metastatic non–small cell lung cancer with the epidermal growth factor receptor (EGFR) variant. Design, Setting, and Participants: Double-blind, placebo-controlled, randomized, phase 3 trial at 55 sites in China enrolled participants from January 2022 to November 2022; a total of 322 eligible patients were enrolled. Interventions: Participants received ivonescimab (n = 161) or placebo (n = 161) plus pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy of ivonescimab plus pemetrexed or placebo plus pemetrexed. Main Outcomes and Measures: The primary end point was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors version 1.1. The results of the first planned interim analysis are reported. Results: Among 322 enrolled patients in the ivonescimab and placebo groups, the median age was 59.6 vs 59.4 years and 52.2% vs 50.9% of patients were female. As of March 10, 2023, median follow-up time was 7.89 months. Median progression-free survival was 7.1 (95% CI, 5.9-8.7) months in the ivonescimab group vs 4.8 (95% CI, 4.2-5.6) months for placebo (difference, 2.3 months; hazard ratio [HR], 0.46 [95% CI, 0.34-0.62]; P <.001). The prespecified subgroup analysis showed progression-free survival benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including patients whose disease progressed while receiving third-generation EGFR-TKI therapy (HR, 0.48 [95% CI 0.35-0.66]) and those with brain metastases (HR, 0.40 [95% CI, 0.22-0.73]). The objective response rate was 50.6% (95% CI, 42.6%-58.6%) with ivonescimab and 35.4% (95% CI, 28.0%-43.3%) with placebo (difference, 15.6% [95% CI, 5.3%-26.0%]; P =.006). The median overall survival data were not mature; at data cutoff, 69 patients (21.4%) had died. Grade 3 or higher treatment-emergent adverse events occurred in 99 patients (61.5%) in the ivonescimab group vs 79 patients (49.1%) in the placebo group, the most common of which were chemotherapy-related. Grade 3 or higher immune-related adverse events occurred in 10 patients (6.2%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Grade 3 or higher vascular endothelial growth factor–related adverse events occurred in 5 patients (3.1%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Conclusions: Ivonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in TKI-treated non–small cell lung cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT05184712 This randomized clinical trial examines the efficacy of ivonescimab plus chemotherapy vs chemotherapy alone for patients with advanced or metastatic non–small cell lung cancer with the epidermal growth factor receptor (EGFR) variant. [ABSTRACT FROM AUTHOR]

For the preservation of ecosystems, including the enhancement of ecological strategies, examining the temporal and geographical variance in ecosystem services (ESs) and land use/land cover change (LUCC) is crucial. Gannan is situated on the upper Yellow River, which is a notable water conservation region with excellent ecological quality, but in the background of the local traditional production mode and rapid economic development, natural disasters, grassland degradation, and other ecological problems occur frequently. The integrated valuing of ecosystem services and tradeoffs (InVEST) model and the patch-generating land use simulation (PLUS) model are combined in this work to assess the spatiotemporal variance in ESs in Gannan. We set up three scenarios in modeling future land use—ecological protection (EP), natural development (ND), and economic development (ED) in 2050—and analyzed and evaluated the drivers of the variation in ESs. In order to reveal the LUCC in Gannan between 1990 and 2020, we predicted the LUCC and ESs spatial distribution characteristics in 2050, explored the correlation between its driving factors, and comprehensively analyzed and propose optimization measures and protection strategies. Through several simulation experiments, the findings indicate the following: (1) the largest percentage of land expansion for construction in Gannan between 1990 and 2020 is 74.53%, and the most noticeable percentage of shrinkage in the sand area is 20.67%; (2) from 1990 to 2020, Gannan's water yield, carbon storage, soil retention, and habitat quality all changed, by 60 × 108 m3, 0.04 × 108 t, −10.66 × 108 t, and −0.02, respectively; (3) ESs are influenced by a variety of natural and societal variables: the southern and southwestern regions of Gannan are home to the majority of ESs hot spot areas, while the northern region is home to the majority of cold spot areas. This study contributes to the analysis of the developmental traits of Gannan ecosystems and can serve as a model for the preservation of terrestrial ecosystems with comparable environmental traits. [ABSTRACT FROM AUTHOR]

For many years, the Weihe River Basin (WRB) has struggled to achieve a balance between ecological protection and economic growth. Constructing an Ecological Security Pattern (ESP) is extremely important for ensuring ecological security (ES). This study employed a coupling of multi-objective programming (MOP) and the patch-generating land use simulation (PLUS) model to project land use change (LUCC) in 2040 across three scenarios. Leveraging circuit theory, we generated ecological corridors and identified key ecological nodes, enabling a comparative analysis of ESPs within the WRB. The main results showed that: (1) The Ecological Protection (EP) scenario showed the highest proportions of forestland, grassland, and water, indicating an optimal ecological environment. Conversely, the Economic Development (ED) scenario features the greatest proportion of construction land, particularly evident in the rapid urban expansion. The Natural Development (ND) scenario exhibits a more balanced change, aligning closely with historical trends. (2) The ecological source areas in the EP scenario is 13,856.70 km2, with the largest and most intact patch area. The ecological source patches that have been identified in the ED scenario exhibit fragmentation and dispersion, encompassing a total area of 8018.82 km2. The ecological source areas in the ND scenario is most similar to the actual situation in 2020, encompassing 8474.99 km2. (3) The EP scenario demonstrates minimal landscape fragmentation. The ED scenario presents a more intricate corridor pattern, hindering species and energy flow efficiency. The ND scenario is more similar to the actual distribution in 2020. Protecting and restoring key ecological nodes, and ensuring the integrity and connectivity of ecological sources are crucial for ESP optimization in various scenarios. Combining all results, we categorize the WRB's spatial pattern into "three zones, three belts, and one center" and offer strategic suggestions for ecological preservation, promoting sustainable local ecological and socioeconomic development. [Display omitted] • Simulated and predicted land use in the Weihe River Basin using a coupled MOP and PLUS model. • The proportion structure of land use types differs significantly under different scenarios. • The EP scenario identified new ecological sources in the northern Weihe River Basin. • The EP scenario showed a more concise ESP. • Based on the research results, the plan of "three zones, three belts, and one center" for the Weihe River Basin is proposed. [ABSTRACT FROM AUTHOR]

Traditional antibody drug conjugates (ADC) combine monoclonal antibodies with cytotoxic drugs to accurately strike cancer cells, but there are still many shortcomings in stability, targeting, efficacy, and safety. Novel ADC, such as bi-specific, site-specific, dual-payload, and pro-drug type ADC, can be optimized by simultaneously binding 2 different antigens or epitopes, selecting more stable linkers, coupling with specific amino acid sites of antibodies, carrying different drug payloads, and adopting prodrug strategies, while retaining the characteristics of traditional ADC. Significantly improving the stability, targeting, efficacy and safety of drugs can better meet the needs of clinical treatment. Novel ADC will play a more important role in cancer treatment in the future. Discussing the progress of novel ADC in cancer treatment and analyzing their advantages and challenges can provide theoretical support for the development of anti-cancer strategies and provide directions for drug research and development.

Background: The combination of immune-checkpoint inhibitors and antiangiogenic agents can synergistically modulate the tumor microenvironment and represents a promising treatment option. Here, we evaluated the efficacy and safety of camrelizumab plus famitinib (a receptor tyrosine kinase inhibitor) as a first-line treatment for advanced or metastatic NSCLC patients with a programmed death ligand-1 (PD-L1) tumor proportion score (TPS) of ≥1%, in an open-label, multicenter, phase 2 basket trial., Methods: Eligible patients received camrelizumab (200 mg once every 3 weeks via intravenous infusion) plus oral famitinib at an initial dose of 20 mg once daily. The primary endpoint was the objective response rate (ORR), as assessed by the investigator per Response Evaluation Criteria in Solid Tumors V.1.1. Key secondary endpoints included disease control rate (DCR), duration of respons, progression-free survival (PFS), overall survival (OS), 12-month OS rate, and safety profile., Results: Of the enrolled 41 patients, 21 (51.2%) had a PD-L1 TPS of 1-49%. As of the cut-off date on June 22, 2022, the combination regimen of camrelizumab and famitinib achieved an ORR of 53.7% (95% CI 37.4% to 69.3%) and a DCR of 92.7% (95% CI 80.1% to 98.5%). The median PFS was 16.6 months (95% CI 8.3 to not reached), and OS data were not yet mature, with an estimated 12-month OS rate of 76.8% (95% CI 60.0% to 87.3%). The most common treatment-related adverse events of grade 3 or higher included hypertension (22.0%), increased alanine aminotransferase (12.2%), decreased neutrophil count (9.8%), proteinuria (7.3%), decrease platelet count (7.3%), and hypokalemia (7.3%). One (2.4%) patient died from grade 5 hemoptysis, which was considered possibly related to the study treatment by the investigator., Conclusion: Camrelizumab plus famitinib demonstrated promising antitumor activity in advanced or metastatic NSCLC patients and had an acceptable safety profile. These findings suggest that this combination regimen could be an alternative therapeutic option and warrant further investigation., Trial Registration Number: NCT04346381., Competing Interests: Competing interests: HD, SW, and XY report being employed by Jiangsu Hengrui Pharmaceuticals. The remaining authors declare no other competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background  The purpose of our study was to construct a prognostic model based on ferroptosis-related gene signature to improve the prognosis prediction of lung squamous carcinoma (LUSC). Methods  The mRNA expression profiles and clinical data of LUSC patients were downloaded. LUSC-related essential differentially expressed genes were integrated for further analysis. Prognostic gene signatures were identified through random forest regression and univariate Cox regression analyses for constructing a prognostic model. Finally, in a preliminary experiment, we used the reverse transcription-quantitative polymerase chain reaction assay to verify the relationship between the expression of three prognostic gene features and ferroptosis. Results  Fifty-six ferroptosis-related essential genes were identified by using integrated analysis. Among these, three prognostic gene signatures (HELLS, POLR2H, and POLE2) were identified, which were positively affected by LUSC prognosis but negatively affected by immune cell infiltration. Significant overexpression of immune checkpoint genes occurred in the high-risk group. In preliminary experiments, we confirmed that the occurrence of ferroptosis can reduce three prognostic gene signature expression. Conclusions  The three ferroptosis-related genes could predict the LUSC prognostic risk of antitumor immunity., Competing Interests: Conflicts of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Background: It has been proven that toll-like receptor 5 (TLR5) plaied an important role in the development of tumor. In our previous study, we found that the expression of TLR5 was remarkably higher in non-small cell lung cancer (NSCLC) tissues than that in normal tissues, but the activation of TLR5 signaling pathway in NSCLC was still unknown. The aim of this study is to investigate the expression of TLR5 in different types of NSCLC cell lines, and analyze the activity of the signaling pathway after stimulated by its specific exogenous ligand flagellin., Methods: The TLR5 protein was detected by immunofluorescence and Western blot in three kinds of NSCLC cell lines, and the TLR5 mRNA was detected by RT-PCR. Select the cell line of TLR5 highest expression as the research object, and select the suitable concentration of flagellin. NF-κB luciferase activity was detected to validate the TLR5 activation pathway through inhibitory signaling pathways by 0 μg/mL, 0.01 μg/mL, 0.1 μg/mL, 1 μg/mL, 10 μg/mL TLR5 antibody. The chosen cell line was transfected by TLR5 shRNA plasmid, and p-IKBα, IKBα, p-ERK1/2, ERK1/2 and p-JNK of untrasfected and transfected cells were detected in the activity of TLR5 signaling pathway by Western blot at 0 min, 10 min, 30 min and 60 min, respectively., Results: The expression of TLR5 was the highest in the lung adenocarcinoma cell line SPC-A-1 by immunofluorescence, mainly expressed on the cell membrane. NF-κB luciferase activity of SPC-A-1 cells was the highest, and the activity was increased in a dose-dependent manner. 0.1 μg/mL flagellin could significantly increase the NF-κB luciferase activity (P<0.05), while its activity could be inhibited by the TLR5 antibody in a negative correlation. Treated by 0.1 μg/mL flagellin, compared with that of 0 min group, the levels of p-IKBα, p-ERK1/2, p-JNK of SPC-A-1 cells increased significantly after 10 min, reached the peak at 30 min, and declined at 60 min (P<0.05). Compared with that of 10 min and 60 min group, the levels of p-IKBα, p-ERK1/2, p-JNK significantly increased at 30 min (P<0.05). While the levels of IKBα, ERK1/2 at 0 min, 10 min, 30 min and 60 min had no significant changes (P>0.05). SPC-A-1 cells transfected TLR5-shRNA were also stimulated by flagellin (0.1 μg/mL). At 0 min, 10 min, 30 min and 60 min, p-IKBα and p-JNK proteins could not be detected, and the levels of IKBα and ERK1/2 had no significant changes (P>0.05), but the levels of p-ERK1/2 significantly increased as time went on (P<0.05)., Conclusions: Exogenous ligand flagellin can activate TLR5 protein in NSCLC cell lines and initiate downstream signaling pathways. It may be relative to the development of NSCLC.