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Nitrogen is the primary limiting factor for crop yield formation. However, excessive application of nitrogen fertilizer not only leads to a decrease in nitrogen utilization efficiency, but also causes serious environmental problems. Therefore, how to balance environmental protection and crop yield when applying nitrogen fertilizer is an important challenge currently faced in agricultural production. Biochar, as a soil amendment, has been widely used in agricultural production. This study used ‘Longyan 101’ tobacco as the experimental material and explored the effects of nitrogen reduction treatment (reducing conventional nitrogen application by half) and combined application of biochar (20 kg/hm2) on tobacco photosynthesis under field experimental conditions. Transcriptome sequencing technology was used to study the changes in the expression levels of photosynthesis-related genes. The results indicate that: reducing the application of nitrogen fertilizer reduces the photosynthetic capacity of tobacco and inhibits its growth, while applying biochar can to some extent alleviate the adverse effects of insufficient nitrogen fertilizer. The results of this experiment have laid the foundation for the rational application of nitrogen fertilizer and the green development of tobacco agriculture.

Cold environmental conditions may often lead to the early flowering of plants, and the mechanism by cold-induced flowering remains poorly understood. Microscopy analysis in this study demonstrated that cold conditioning led to early flower bud differentiation in two tobacco strains and an Agilent Tobacco Gene Expression microarray was adapted for transcriptomic analysis on the stem tips of cold treated tobacco to gain insight into the molecular process underlying flowering in tobacco. The transcriptomic analysis showed that cold treatment of two flue-cured tobacco varieties (Xingyan 1 and YunYan 85) yielded 4176 and 5773 genes that were differentially expressed, respectively, with 2623 being commonly detected. Functional distribution revealed that the differentially expressed genes (DEGs) were mainly enriched in protein metabolism, RNA, stress, transport, and secondary metabolism. Genes involved in secondary metabolism, cell wall, and redox were nearly all up-regulated in response to the cold conditioning. Further analysis demonstrated that the central genes related to brassinosteroid biosynthetic pathway, circadian system, and flowering pathway were significantly enhanced in the cold treated tobacco. Phytochemical measurement and qRT-PCR revealed an increased accumulation of brassinolide and a decreased expression of the flowering locus c gene. Furthermore, we found that overexpression of NtBRI1 could induce early flowering in tobacco under normal condition. And low-temperature-induced early flowering in NtBRI1 overexpression plants were similar to that of normal condition. Consistently, low-temperature-induced early flowering is partially suppressed in NtBRI1 mutant. Together, the results suggest that cold could induce early flowering of tobacco by activating brassinosteroid signaling.

Key message: ABA and ET signal transduction play key roles in Populus simonii × Populus nigra response to NaHCO3 stress. Populus simonii × Populus nigra is a fast-growing and resilient poplar variety widely promoted in northern China. However, its proliferation is significantly hindered in the Songnen Plain region of northern China due to the prevalence of soda saline-alkali lands primarily composed of NaHCO3. Current research on the response and adaptation of Populus simonii × Populus nigra to saline-alkali stress primarily focuses on neutral salts, with limited exploration into the physiological and molecular mechanisms in response to alkaline salt NaHCO3. This study utilized physiological and transcriptomic techniques to investigate the effects of different concentrations (0, 100, 200, and 300 mM) of NaHCO3 stress on the photosynthetic function and antioxidant mechanism of Populus simonii × Populus nigra. Additionally, the key molecular mechanisms underlying its salt-alkali tolerance were explored using WGCNA. The results indicate that, compared to non-stress conditions, under NaHCO3 stress, differentially expressed genes (DEGs) in Populus simonii × Populus nigra leaves are significantly enriched in KEGG pathways such as Photosynthesis and Plant hormone signal transduction. At 100 mM NaHCO3, there is no significant impact on the photosynthetic function of Populus simonii × Populus nigra, with a notable upregulation of numerous DEGs associated with photosynthetic electron transport, suggesting strong resistance of Populus simonii × Populus nigra to NaHCO3 stress, with hormone signal transduction activation playing a crucial role in its adaptation to NaHCO3 stress. At high concentration (300 mM) NaHCO3, although it inhibits the photosynthetic function of Populus simonii × Populus nigra and leads to severe oxidative damage, KEGG pathways related to antioxidant mechanisms such as Glutathione metabolism and Flavonoid biosynthesis are also significantly enriched. Populus simonii × Populus nigra can mitigate excessive reactive oxygen species (ROS) by increasing the activity of antioxidant enzymes such as Catalase (CAT) and Peroxidase (POD), and the accumulation of the osmotic regulator substance Proline (Pro) also plays a positive role in Populus simonii × Populus nigra's adaptation to NaHCO3 stress. Utilizing WGCNA, a module highly correlated with salt tolerance physiological indicators, represented by the "Mediumorchid" module, was identified. The KEGG enrichment analysis of DEGs in this module significantly enriched pathways closely associated with Plant hormone signal transduction, particularly the MAPK signaling pathway–plant pathway. Numerous genes in this pathway are involved in the synthesis and signal transduction pathways of Abscisic acid (ABA) and Ethylene (ET). Additionally, the most significantly enriched pathway in the GO functional enrichment analysis of DEGs in this module is “transcription regulator activity”, with the highest number of transcription factors belonging to the ET signal-related ERF family transcription factors (15), and the five highest connectivity hub genes also belong to the ERF family transcription factors, showing significant upregulation induced by NaHCO3. In conclusion, Populus simonii × Populus nigra is a poplar variety with strong adaptability to NaHCO3 stress. The activation of ABA and ET signal transduction-related pathways is a key mechanism for Populus simonii × Populus nigra's adaptation to NaHCO3 stress, especially the ERF family transcription factors, which can serve as candidate genes for studying the salt-alkali resistance function of poplar. [ABSTRACT FROM AUTHOR]

Abstract Lenvatinib, a multi-kinase inhibitor, has been approved as first-line treatment for advanced hepatocellular carcinoma (HCC), but its efficacy is limited. We have shown previously that lenvatinib and epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) combination therapy overcomes lenvatinib resistance in HCC with high level of EGFR expression (EGFRhigh). We present here the results of a single-arm, open-label, exploratory study of lenvatinib plus the EGFR-TKI gefitinib for patients with HCC resistance to lenvatinib (NCT04642547; n = 30). Only patients with EGFRhigh HCC and progressive disease after lenvatinib treatment were recruited in the study. The most frequent adverse events of all grades were fatigue (27 patients; 90%), followed by rash (25 patients; 83.3%), diarrhea (24 patients; 80%), and anorexia (12 patients; 40%). Among 30 patients, 9 (30%) achieved a confirmed partial response and 14 (46.7%) had stable disease according to mRECIST criteria. Based on RECIST1.1, 5 (16.7%) achieved a confirmed partial response and 18 (60%) had stable disease. The estimated median progression free survival (PFS) and overall survival (OS) time were 4.4 months (95% CI: 2.5 to 5.9) and13.7 months (95% CI: 9.0 to NA), respectively. The objective response rate (ORR) of the patients in the present study compares very favorable to that seen for the two approved second line treatments for HCC (cabozantinib ORR of 4%; regorafenib ORR of 11%). Given that this combination was well-tolerated, a further clinical study of this combination is warranted.

With the widespread adoption of ultrasound guidance, Seldinger puncture techniques, and intracardiac electrical positioning technology for the placement of peripherally inserted central catheters in recent years, an increasing number of medical staff and patients now accept peripheral placement of totally implantable venous access devices (TIVADs) in the upper arm. This approach has the advantage of completely avoiding the risks of hemothorax, pneumothorax, and neck and chest scarring. Medical specialties presently engaged in this study in China include internal medicine, surgery, anesthesiology, and interventional departments. However, command over implantation techniques, treatment of complications, and proper use and maintenance of TIVAD remain uneven among different medical units. Moreover, currently, there are no established quality control standards for implantation techniques or specifications for handling complications. Thus, this expert consensus is proposed to improve the success rate of TIVAD implantation via the upper-arm approach, reduce complication rates, and ensure patient safety. This consensus elaborates on the technical indications and contraindications, procedures and technical points, treatment of complications, and the use and maintenance of upper-arm TIVAD, thus providing a practical reference for medical staff.

In this paper, a fractional-order control method based on the twin-delayed deep deterministic policy gradient (TD3) algorithm in reinforcement learning is proposed. A fractional-order disturbance observer is designed to estimate the disturbances, and the radial basis function network is selected to approximate system uncertainties in the system. Then, a fractional-order sliding-mode controller is constructed to control the system, and the parameters of the controller are tuned using the TD3 algorithm, which can optimize the control effect. The results show that the fractional-order control method based on the TD3 algorithm can not only improve the closed-loop system performance under different operating conditions but also enhance the signal tracking capability.

Abstract Crowdfunding is an innovative strategy for financing a new business venture from the general public instead of seeking funds in traditional ways, such as issuing bonds or bank lending. This study aims to identify the determinants affecting the success of a crowdfunding campaign and how different measurements for crowdfunding success, different crowdfunding models, and the selection of subdivided determinants influence the determinants’ impacts on crowdfunding success. We set the disciplines in the search strategy to select studies related to crowdfunding success. Ultimately, 94 empirical papers are selected to reveal the different findings for the determinants of crowdfunding success; based on this information, we construct an integrated framework for future research. There has been much research on project- and creator-related factors; however, many of these factors have inconsistent relationships with crowdfunding success due to varying measurements of success. In particular, different measurements used within the same study for determinants or crowdfunding success may also produce inconsistent results. In addition, different crowdfunding models of a project have been found to induce additional findings. Our review of the determinants of crowdfunding success and the definitions of the determinants, as well as the proposed integrated framework, can help focus future work on relatively new or unique determinants rarely addressed in the existing literature. This work provides practical implications for both theory and practice, and directions for future research.

Connexins are membrane expressed proteins, which could assemble into hexamers to transfer metabolites and secondary messengers. However, its roles in pancreatic cancer metastasis remains unknown. In this study, by comparing the gene expression patterns in primary pancreatic cancer patients primary and liver metastasis specimens, we found that Gap Junction Protein Beta 3 (GJB3) significantly increased in Pancreatic ductal adenocarcinoma (PDAC) liver metastasis. Animal experiments verified that GJB3 depletion suppressed the hepatic metastasis of PDAC cancer cells. Further, GJB3 over expression increased the neutrophil infiltration. Mechanistic study revealed that GJB3 form channels between PDAC tumor cells and accumulated neutrophil, which transfer cyclic adenosine monophosphate (cAMP) from cancer to neutrophil cells, which supports the survival and polarization. Taken together, our data suggesting that GJB3 could act as a potential therapeutic target of PDAC liver metastasis.

Objective To establish the technique of intratumoral combination therapy of radiofrequency hyperthermia (RFH) with herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy for rat ovarian cancers. Material and methods This study consisted of three parts: (1) in vitro experiments to establish the ‘proof of principal’ that combination of RFH and HSV-TK gene therapy has the synergistic effect on human ovarian cancer cells; (2) creation of bioluminescence imaging-detectable rat ovarian cancer model; and (3) in vivo experiments using this rat model to validate the technical feasibility of the combination therapy. Cells and nude rats were divided into four groups: (i) combination therapy (HSV-TK/GCV + RFH); (ii) RFH; (iii) HSV-TK/GCV; and (iv) phosphate-buffered saline (PBS). Data were analyzed using Dunnett t-test or Kruskal–Wallis test. Results Cell proliferation assay demonstrated significantly greater reduction in viable cells with the combination therapy [0.52 (0.43, 0.61)] compared to other treatments [RFH 0.90 (0.84, 0.96), HSV-TK/GCV 0.71 (0.53, 0.88), PBS 1 (1, 1); p

Understanding drought resistance mechanisms is crucial for breeding poplar species suited to arid and semiarid regions. This study explored the drought responses of three newly developed 'Zhongxiong' series poplars using integrated transcriptomic and physiological analyses. Under drought stress, poplar leaves showed significant changes in differentially expressed genes linked to photosynthesis-related pathways, including photosynthesis-antenna proteins and carbon fixation, indicating impaired photosynthetic function and carbon assimilation. Additionally, drought stress triggered oxidative damage through increased reactive oxygen species production, leading to malondialdehyde accumulation. Weighted gene co-expression network analysis revealed that differentially expressed genes closely associated with physiological responses were enriched in cell redox homeostasis pathways, specifically the thioredoxin-peroxiredoxin pathway. Key genes in this pathway and in cyclic electron flow, such as PGR5-L1A, were downregulated, suggesting compromised reactive oxygen species scavenging and photoprotection under drought stress. Notably, ZX4 poplar exhibited higher drought tolerance, maintaining stronger activity in cyclic electron flow and the thioredoxin-peroxiredoxin pathway compared with ZX3 and ZX5. Genes like PGR5-L1A, 2-Cys Prx BAS1, PrxQ and TPX are promising candidates for enhancing drought resistance in poplars through genetic improvement, with potential applications for developing resilient forestry varieties., (© The Author(s) 2025. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)