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Abstract Background Salidroside (SAL), derived from Rhodiola, shows protective effects in pulmonary arterial hypertension (PAH) models, but its mechanisms are not fully elucidated. Objectives Investigate the therapeutic effects and the mechanism of SAL on PAH. Methods Monocrotaline was used to establish a PAH rat model. SAL’s impact on oxidative stress and inflammatory responses in lung tissues was analyzed using immunohistochemistry, ELISA, and Western blot. Untargeted metabolomics explored SAL’s metabolic regulatory mechanisms. Results SAL significantly reduced mean pulmonary artery pressure, right ventricular hypertrophy, collagen deposition, and fibrosis in the PAH rats. It enhanced antioxidant enzyme levels, reduced inflammatory cytokines, and improved NO bioavailability by upregulating endothelial nitric oxide synthase (eNOS), soluble guanylate cyclase (sGC), cyclic guanosine monophosphate (cGMP), and protein kinase G (PKG) and decreases the expression of endothelin-1 (ET-1). Metabolomics indicated SAL restored metabolic balance in PAH rats, particularly in arginine metabolism. Conclusions SAL alleviates PAH by modulating arginine metabolism, enhancing NO synthesis, and improving pulmonary vascular remodeling.

Abstract GDP-l-galactose phosphorylase (GGP) is a key rate-limiting enzyme in plant ascorbic acid synthesis, which plays an important role in plant growth and development as well as stress response. However, the presence of GGP and its function in potato and pepper are not known. In this study, we first identified two GGP genes in each potato and pepper genomes using a genome-wide search approach. We then analyzed their physicochemical properties, conserved domains, protein structures and phylogenetic relationships. Phylogenetic tree analysis revealed that members of the potato and pepper GGP gene families are related to eggplant (Solanum melongena L.), Arabidopsis (Arabidopsis thaliana L.), tobacco (Nicotiana tabacum L.) and tomato (Solanum lycopersicum L.), with tomato being the most closely related. The promoter sequences mainly contain homeopathic elements such as light-responsive, hormone-responsive and stress-responsive, with light-responsive elements being the most abundant. By analyzing the structure of the genes, it was found that there is no transmembrane structure or signal peptide in the GGP gene family of potatoes and peppers, and that all of its members are hydrophilic proteins. The expression profiles of different tissues show that StGGP1 has the highest expression levels in leaves, StGGP2 has the highest expression levels in stamens, and CaGGPs have the highest expression levels in the early stages of fruit development (Dev1). It was found that StGGPs and CaGGPs genes showed different response to phytohormones and abiotic stresses. Abscisic acid (ABA) treatment induced the most significant change in the expression of StGGPs, while the expression of CaGGPs showed the most pronounced change under methyl jasmonate (MeJA) treatment. StGGPs responded mainly to dark treatment, whereas CaGGPs responded mainly to NaCl stress. These results provide an important basis for a detailed study about the functions of GGP homologous genes in potato and pepper in response to abiotic stresses.

The nanoscale confinement is of great important for the industrial applications of molecular sieve, desalination, and also essential in biological transport systems. Massive efforts have been devoted to the influence of restricted spaces on the properties of confined fluids. However, the situation of channel-wall is crucial but attracts less attention and remains unknown. To fundamentally understand the mechanism of channel-walls in nanoconfinement, we investigated the interaction between the counter-force of the liquid and interlamellar spacing of nanochannel walls by considering the effect of both spatial confinement and surface wettability. The results reveal that the nanochannel stables at only a few discrete spacing states when its confinement is within 1.4 nm. The quantized interlayer spacing is attributed to water molecules becoming laminated structures, and the stable states are corresponding to the monolayer, bilayer and trilayer water configurations, respectively. The results can potentially help to understand the characterized interlayers spacing of graphene oxide membrane in water. Our findings are hold great promise in design of ion filtration membrane and artificial water/ion channels.

Background The number of patients undergoing joint replacement procedures is continuously increasing. Tele-equipment is progressively being employed for postrehabilitation of total hip and knee replacements. Gaining a comprehensive understanding of the experiences and requirements of patients undergoing total hip and knee arthroplasty who participate in telerehabilitation can contribute to the enhancement of telerehabilitation programs and the overall rehabilitation and care provided to this specific population. Objective To explore the needs and experiences of total hip and knee arthroplasty patients with telerehabilitation. Design Systematic review and qualitative synthesis. Methods Electronic databases PubMed, Web of Science, The Cochrane Library, Embase, CINAHL, Scopus, ProQuest, CNKI, Wanfang Data, VIP, and SinoMed were systematically searched for information on the needs and experiences of telerehabilitation for patients with total hip arthroplasty and total knee arthroplasty in qualitative studies. The search period was from the creation of the database to March 2024. Literature quality was assessed using the 2016 edition of the Australian Joanna Briggs Institute Centre for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research. A pooled integration approach was used to integrate the findings inductively. Results A total of 11 studies were included and 4 themes were identified: the desire to communicate and the need to acquire knowledge; accessible, high-quality rehabilitation services; positive psychological experiences; the dilemmas of participating in telerehabilitation. Conclusions This study's findings emphasize that the practical needs and challenges of total hip and knee arthroplasty patients’ participation in telerehabilitation should be continuously focused on, and the advantages of telerehabilitation should be continuously strengthened to guarantee the continuity of patients’ postoperative rehabilitation and to promote their postoperative recovery.

Abstract Background Numerous studies have demonstrated that brain metastases patients may benefit from intracranial radiotherapy combined with immune checkpoint inhibitors (ICIs). However, it is unclear whether this treatment is effective for patients with small cell lung cancer brain metastases (SCLC‐BMs). Methods We conducted a retrospective study by analyzing medical records of patients with SCLC‐BMs from January 1, 2017 to June 1, 2022. Data related to median overall survival (mOS), median progression‐free survival (mPFS), and intracranial progression‐free survival (iPFS) were analyzed. Results A total of 109 patients were enrolled, of which 60 received WBRT and 49 received WBRT‐ICI. Compared to the WBRT alone cohort, the WBRT‐ICI cohort showed longer mOS (20.4 months vs. 29.3 months, p = 0.021), mPFS (7.9 months vs. 15.1 months, p

Stem mustard, the main raw material for pickled mustard tuber, is widely planted in Chongqing, China, and is an important local cash crop. Under the working conditions of sticky and wet soil in the Chongqing area, conventional furrow seeding has problems such as soil sticking to the furrow opener, poor mulching effect, etc. In this regard, this paper proposes the use of non-contact, soil-based, pneumatic shot seeding, in which seeds are shot into the soil to a predetermined depth by a high-speed air stream. The diameter of stem mustard seeds was found to be 1.33 mm, with a spherical rate of 95.32% using physical and mechanical properties. The high-speed camera test was used to determine the air pressure at the appropriate sowing depth, and the seed entry process was simulated by EDEM 2021 software, which analysed the movement process of the seed after entering the soil, and the structure of the seeder was designed based on the resulting test data. The structural parameters of the shot seeding device were analysed by a hydrodynamic simulation using Fluent 2022 R1 software and the following results were obtained: an outlet pipe diameter DC of 2 mm, mixing zone length H of 10 mm, mixing zone inlet diameter D of 15 mm, and steady-state gas flow rate of 80 m/s. Simulation seeding verification was conducted on the final determined structural parameters of the seeding device, and the simulation results showed that the seed velocity could reach 32.3 m/s. In actual experiments, it was found that when the vertical velocity of the seeds was greater than or equal to 26.59 m/s, the seeds could be completely and stably seeded into the soil. Therefore, the designed seeding device can meet the conditions of actual seeding experiments. In conclusion, this research offers a practical guideline for the rapid and precise sowing of stem mustard.

Human endogenous retroviruses (HERVs) are derived from the infection and integration of exogenetic retroviruses. HERVs account for 8% of human genome, and the majority of HERVs are solitary LTRs (solo-LTRs) due to homologous recombination. Multiple findings have showed that solo-LTRs could provide an enormous reservoir of transcriptional regulatory sequences involved in diverse biological processes, especially carcinogenesis and cancer development. The link between solo-LTRs and human diseases still remains poorly understood. This review focuses on the regulatory modules of solo-LTRs, which contribute greatly to the diversification and evolution of human genes. More importantly, although inactivating mutations, insertions and deletions have been identified in solo-LTRs, the inherited regulatory elements of solo-LTRs initiate the expression of chimeric lncRNA transcripts, which have been reported to play crucial roles in human health and disease. These findings provide valuable insights into the evolutionary and functional mechanisms underlying the presence of HERVs in human genome. Taken together, in this review, we will present evidences showing the regulatory and encoding capacity of solo-LTRs as well as the significant impact on various aspects of human biology.

Endogenous retroviruses (ERVs) originate from ancestral germline infections caused by exogenous retroviruses. Throughout evolution, they have become fixed within the genome of the animals into which they were integrated. As ERV elements coevolve with the host, they are normally epigenetically silenced and can become upregulated in a series of physiological and pathological processes. Generally, a detailed ERV profile in the host genome is critical for understanding the evolutionary history and functional performance of the host genome. We previously characterized and cataloged all the ERV-K subtype HML-8 loci in the human genome; however, this has not been done for the chimpanzee, the nearest living relative of humans. In this study, we aimed to catalog and characterize the integration of HML-8 in the chimpanzee genome and compare it with the integration of HML-8 in the human genome. We analyzed the integration of HML-8 and found that HML-8 pervasively invaded the chimpanzee genome. A total of 76 proviral elements were characterized on 23/24 chromosomes, including detailed elements distribution, structure, phylogeny, integration time, and their potential to regulate adjacent genes. The incomplete structure of HML-8 proviral LTRs will undoubtedly affect their activity. Moreover, the results indicated that HML-8 integration occurred before the divergence between humans and chimpanzees. Furthermore, chimpanzees include more HML-8 proviral elements (76 vs. 40) and fewer solo long terminal repeats (LTR) (0 vs. 5) than humans. These results suggested that chimpanzee genome activity is less than the human genome and that humans may have a better ability to shape and screen integrated proviral elements. Our work is informative in both an evolutionary and a functional context for ERVs.

The HIV-1 provirus mainly consists of internal coding region flanked by 1 long terminal repeats (LTRs) at each terminus. The LTRs play important roles in HIV-1 reverse transcription, integration, and transcription. However, despite of the significant study advances of the internal coding regions of HIV-1 by using definite reference classification, there are no systematic and phylogenetic classifications for HIV-1 5' LTRs, which hinders our elaboration on 5' LTR and a better understanding of the viral origin, spread and therapy. Here, by analyzing all available resources of 5' LTR sequences in public databases following 4 recognized principles for the reference classification, 83 representatives and 14 consensus sequences were identified as representatives of 2 groups, 6 subtypes, 6 sub-subtypes, and 9 CRFs. To test the reliability of the supplemented classification system, the constructed references were applied to identify the 5' LTR assignment of the 22 clinical isolates in China. The results revealed that 16 out of 22 tested strains showed a consistent subtype classification with the previous LTR-independent classification system. However, 6 strains, for which recombination events within 5' LTR were demonstrated, unexpectedly showed a different subtype classification, leading a significant change of binding sites for important transcription factors including SP1, p53, and NF-κB. The binding change of these transcriptional factors would probably affect the transcriptional activity of 5' LTR. This study supplemented a unified classification system for HIV-1 5' LTRs, which will facilitate HIV-1 characterization and be helpful for both basic and clinical research fields.

Background: Sorafenib (Sor) represents a first-line therapy for hepatocellular carcinoma (HCC); however, its efficacy is constrained by secondary failure, which limits its clinical use. Recent studies have indicated that the suppression of Programmed cell death-Ligand 1 (PD-L1) may potentiate Sor's anti-liver cancer effects; furthermore, PD-L1 expression is known to be regulated by NF-κB. Previous research has demonstrated that paeoniflorin (PF) downregulates the NF-κB axis, nevertheless, current research has not yet determined whether PF can synergistically enhance the efficacy of Sor against HCC by modulating the NF-κB/PD-L1 pathway. Methods: The study employed a H22 hepatoma-bearing mouse model, which was treated with PF, Sor, and their combination over a period of 12 days. The impact of PF and Sor on tumor growth, proliferation, apoptosis, T-cell subsets, IL-2 and IFN-γ production, and NF-κB and PD-L1 expression was assessed. Moreover, Splenic lymphocyte from normal mice and tumor cells from model mice were co-cultured in vitro, and the tumor-specific cytotoxic T lymphocyte activity was analyzed. In the final phase of the study, Huh-7 cells were stimulated with PF in combination with an NF-κB activator or inhibitor, and the subsequent production of NF-κB and PD-L1 was investigated. Results: PF and Sor exhibit a synergistic anti-tumor effect, compared to the use of Sor alone, the combined use of PF and Sor significantly increased the number of CD4+ and CD8+ T cells in tumor tissue, markedly enhanced the cytotoxic activity of tumor-specific cytotoxic T lymphocytes, and reversed the depletion of interleukin-2 and the increase in PD-L1 expression following Sor intervention. This combination also further reduced the level of IFN-γ in peripheral blood and the expression of NF-κB and PD-L1 in tumor tissue. Additionally, in vitro experiments confirmed that PF reduces the expression of PD-L1 in Huh-7 liver cancer cells by inhibiting NF-κB. Conclusions: PF plays a synergistic role of Sor inhibiting HCC progression by regulating the NF-κB/PD-L1 pathway.

In response to the practical production challenges posed by the unreliable operation of the V-shaped squeezing soil-covering and -pressing device (VCP) for planters under clay soil conditions in Northeast China, incomplete seed furrow closure, and severe soil adhesion on pressing wheels, this study proposes a device with star-toothed concave discs for soil-covering and -pressing (STCP) with the aim of enhancing the soil-covering quality of planters. The main working principles of STCP were expounded, and its main structural and installation parameters were determined and designed. Based on bionics, with the dung beetle’s protruding head structure as the research object and UHMWPE as the material, an optimized protuberance-type bionic pressing wheel was designed. A Box–Behnken experiment was conducted by taking the width of the compression wheel, the spring deformation, and the installation angle as experimental factors, as well as the weight of the soil adhered to the surface of the pressing wheel (SW) and the soil compactness (SC) as the evaluation indicators. The optimal structural parameters of the pressing device were determined as follows: the width of the pressing wheel was 60.57 mm, the spring deformation was 55.19 mm, and the installation angle was 10.70°. The field comparison tests of soil covering performance showed that the star-tooth concave disc soil-covering device can effectively solve the problem of seed “hanging” and “drying”. The average covered soil weight of the star-tooth concave disc soil-covering device was 241.46 g, and the average covered soil weight of VCP was 223.56 g. Compared with VCP, the average covered soil weight of STCP increased by 8.01%. The variation coefficient of covered soil weight after the operation of the star-tooth concave disc soil-covering device was 3.71%, which was more uniform than VCP. The field comparison tests of soil-covering thickness showed that the uniformity of soil-covering thickness can be significantly improved by adding a star-tooth concave disc soil-covering device to VCP. The comparative tests of soil anti-adhesive showed that the convex hull type pressing wheels optimized by bionics had better soil anti-adhesive performance, and the soil adhesion weight was reduced by 43.68% compared with VCP. The field comparative tests of seedling emergence showed that the seedling emergence rate after STCP operation was 3.9% higher than that of VCP.

Endogenous retroviruses (ERVs) are related to long terminal repeat (LTR) retrotransposons, comprising gene sequences of exogenous retroviruses integrated into the host genome and inherited according to Mendelian law. They are considered to have contributed greatly to the evolution of host genome structure and function. We previously characterized HERV-K HML-9 in the human genome. However, the biological function of this type of element in the genome of the chimpanzee, which is the closest living relative of humans, largely remains elusive. Therefore, the current study aims to characterize HML-9 in the chimpanzee genome and to compare the results with those in the human genome. Firstly, we report the distribution and genetic structural characterization of the 26 proviral elements and 38 solo LTR elements of HML-9 in the chimpanzee genome. The results showed that the distribution of these elements displayed a non-random integration pattern, and only six elements maintained a relatively complete structure. Then, we analyze their phylogeny and reveal that the identified elements all cluster together with HML-9 references and with those identified in the human genome. The HML-9 integration time was estimated based on the 2-LTR approach, and the results showed that HML-9 elements were integrated into the chimpanzee genome between 14 and 36 million years ago and into the human genome between 18 and 49 mya. In addition, conserved motifs, cis-regulatory regions, and enriched PBS sequence features in the chimpanzee genome were predicted based on bioinformatics. The results show that pathways significantly enriched for ERV LTR-regulated genes found in the chimpanzee genome are closely associated with disease development, including neurological and neurodevelopmental psychiatric disorders. In summary, the identification, characterization, and genomics of HML-9 presented here not only contribute to our understanding of the role of ERVs in primate evolution but also to our understanding of their biofunctional significance.

Respiratory burst oxidase homologs (RBOHs), also known as NADPH oxidases, contribute significantly to the production of ROS in plants, alongside other major sources such as photosynthesis and electron transport in chloroplasts. It has been shown that plant RBOHs play an active role in plant adversity response and electron transport. However, the phylogenetic analysis and characterization of the SlRBOH gene family in tomatoes have not been systematically studied. This study identified 11 SlRBOH genes in the tomato genome using a genome-wide search approach. The physicochemical properties, chromosomal localization, subcellular localization, secondary structure, conserved motifs, gene structure, phylogenetics, collinear relationships, cis-acting elements, evolutionary selection pressures, tissue expressions, and expression patterns under exogenous phytohormones (ABA and MeJA) and different abiotic stresses were also analyzed. We found that the SlRBOHs are distributed across seven chromosomes, collinearity reflecting their evolutionary relationships with corresponding genes in Arabidopsis thaliana and rice. Additionally, all the SlRBOH members have five conserved domains and 10 conserved motifs and have similar gene structures. In addition, the results of an evolutionary selection pressure analysis showed that SlRBOH family members evolved mainly by purifying selection, making them more structurally stable. Cis-acting element analyses showed that SlRBOHs were responsive to light, hormone, and abiotic stresses. Tissue expression analysis showed that SlRBOH family members were expressed in all tissues of tomato to varying degrees, and most of the SlRBOHs with the strongest expression were found in the roots. In addition, the expressions of tomato SlRBOH genes were changed by ABA, MeJA, dark period extension, NaCl, PEG, UV, cold, heat, and H2O2 treatments. Specifically, SlRBOH4 was highly expressed under NaCl, PEG, heat, and UV treatments, while SlRBOH2 was highly expressed under cold stress. These results provide a basis for further studies on the function of SlRBOHs in tomato.

High thermal conductivity and a high breakdown field make diamond a promising candidate for high-power and high-temperature semiconductor devices. Diamond also has a higher radiation hardness than silicon. Recent studies show that diamond has exceptionally large electron and hole momentum relaxation times, facilitating compact THz and sub-THz plasmonic sources and detectors working at room temperature and elevated temperatures. The plasmonic resonance quality factor in diamond TeraFETs could be larger than unity for the 240–600 GHz atmospheric window, which could make them viable for 6G communications applications. This paper reviews the potential and challenges of diamond technology, showing that diamond might augment silicon for high-power and high-frequency compact devices with special advantages for extreme environments and high-frequency applications.

S-nitrosoglutathione reductase (GSNOR) is a well-known regulator in controlling protein S-nitrosylation modification and nitric oxide (NO) homeostasis. Here, a GSNOR inhibitor N6022 and SlGSNOR silencing were applied to investigate the roles of SlGSNOR in tomato fruit postharvest ripening. We found that the application of N6022 and S-nitrosoglutathione (GSNO, a NO donor), and SlGSNOR silencing delayed the transition of fruit skin color by improving total chlorophyll level by 88.57%, 44.78%, and 91.03%, respectively. Meanwhile, total carotenoid and lycopene contents were reduced by these treatments. Concurrently, the activity of chlorophyll biosynthesis enzymes and the expression of related genes were upregulated, and the transcript abundances of total carotenoid bioproduction genes were downregulated, by N6022 and GSNO treatments and SlGSNOR silencing. In addition, fruit softening was postponed by N6022, GSNO, and SlGSNOR silencing, through delaying the decrease of firmness and declining cell wall composition; structure-related enzyme activity; and gene expression levels. Furthermore, N6022, GSNO, and SlGSNOR silencing enhanced the accumulation of titratable acid; ascorbic acid; total phenol; and total flavonoid, but repressed the content of soluble sugar and soluble protein accompanied with the expression pattern changes of nutrition-related genes. In addition, the endogenous NO contents were elevated by 197.55%; 404.59%; and 713.46%, and the endogenous SNOs contents were enhanced by 74.65%; 93.49%; and 94.85%; by N6022 and GSNO treatments and SlGSNOR silencing, respectively. Altogether, these results indicate that SlGSNOR positively promotes tomato postharvest fruit ripening, which may be largely on account of its negative roles in the endogenous NO level.

Fatty acids and their derivatives play a variety of roles in living organisms. Fatty acids not only store energy but also comprise membrane lipids and act as signaling molecules. There are three main proteins involved in the fatty acid β-oxidation pathway in plant peroxisomes, including acyl-CoA oxidase (ACX), multifunctional protein (MFP), and 3-ketolipoyl-CoA thiolase (KAT). However, genome-scale analysis of KAT and MFP has not been systemically investigated in tomatoes. Here, we conducted a bioinformatics analysis of KAT and MFP genes in tomatoes. Their physicochemical properties, protein secondary structure, subcellular localization, gene structure, phylogeny, and collinearity were also analyzed. In addition, a conserved motif analysis, an evolutionary pressure selection analysis, a cis-acting element analysis, tissue expression profiling, and a qRT-PCR analysis were conducted within tomato KAT and MFP family members. There are five KAT and four MFP family members in tomatoes, which are randomly distributed on four chromosomes. By analyzing the conserved motifs of tomato KAT and MFP family members, we found that both KAT and MFP members are highly conserved. In addition, the results of the evolutionary pressure selection analysis indicate that the KAT and MFP family members have evolved mainly from purifying selection, which makes them more structurally stable. The results of the cis-acting element analysis show that SlKAT and SlMFP with respect may respond to light, hormones, and adversity stresses. The tissue expression analysis showed that KAT and MFP family members have important roles in regulating the development of floral organs as well as fruit ripening. The qRT-PCR analysis revealed that the expressions of SlKAT and SlMFP genes can be regulated by ABA, MeJA, darkness, NaCl, PEG, UV, cold, heat, and H2O2 treatments. These results provide a basis for the involvement of the SlKAT and SlMFP genes in tomato floral organ development and abiotic stress response, which lay a foundation for future functional study of SlKAT and SlMFP in tomatoes.

Brassinosteroids (BRs) are a group of polyhydroxylated steroids for plant growth and development, regulating numerous physiological and biochemical processes and participating in multi-pathway signaling in plants. 24-Epibrassinolide (EBR) is the most commonly used BR for the investigation of the effects of exogenous steroidal phytohormones on plant physiology. Although SlSERK3B is considered a gene involved in the brassinosteroid (BR) signaling pathway, its specific role in plant growth and development has not been reported in detail. In this study, tomato (Solanum lycopersicum L.) seedlings treated with 0.05 μmol L−1 EBR showed a significant increase in plant height, stem diameter, and fresh weight, demonstrating that BR promotes the growth of tomato seedlings. EBR treatment increased the expression of the BR receptor gene SlBRI1, the co-receptor gene SlSERK3A and its homologs SlSERK3B, and SlBZR1. The SlSERK3B gene was silenced by TRV-mediated virus-induced gene silencing (VIGS) technology. The results showed that both brassinolide (BL) content and BR synthesis genes were significantly up-regulated in TRV-SlSERK3B-infected seedlings compared to the control seedlings. In contrast, plant height, stem diameter, fresh weight, leaf area and total root length were significantly reduced in silenced plants. These results suggest that silencing SlSERK3B may affect BR synthesis and signaling, thereby affecting the growth of tomato seedlings. Furthermore, the photosynthetic capacity of TRV-SlSERK3B-infected tomato seedlings was reduced, accompanied by decreased photosynthetic pigment content chlorophyll fluorescence, and photosynthesis parameters. The expression levels of chlorophyll-degrading genes were significantly up-regulated, and carotenoid-synthesising genes were significantly down-regulated in TRV-SlSERK3B-infected seedlings. In conclusion, silencing of SlSERK3B inhibited BR signaling and reduced photosynthesis in tomato seedlings, and this correlation suggests that SlSERK3B may be related to BR signaling and photosynthesis enhancement.

Background A recent trial failed to show any benefit of stenting plus medical therapy over medical therapy alone in patients with symptomatic intracranial stenosis. We aimed to examine whether the symptomatic qualifying artery modifies the effect of stenting plus medical therapy. Methods This is a post-hoc analysis of the CASSISS trial that included patients with symptomatic intracranial stenosis, randomly assigned to undergo stenting plus medical therapy or medical therapy alone; 358/380 patients were included. Multivariable logistic regression analysis was used with an interaction term to estimate the altered treatment effect by the qualifying artery. The primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The five secondary outcomes included stroke or death related to the qualifying artery territory at 2 and 3 years. Results No significant treatment allocation-bystenosis site interaction was observed (Pinteraction=0.435). Compared with medical therapy alone, the adjusted ORs for stenting plus medical therapy were 2.73 (95% CI 0.42 to 17.65) for internal carotid artery stenosis, 1.20 (95% CI 0.29 to 4.99) for M1 stenosis, 0.23 (95% CI 0.02 to 2.31) for vertebral artery stenosis, and 1.33 (95% CI 0.34 to 5.28) for basilar artery stenosis. Of the five secondary outcomes, none showed a significant treatment allocation-by-stenosis site interaction including stroke in the qualifying artery territory at 2 years (Pinteraction=0.659) and 3 years (Pinteraction=0.493). Conclusions Among patients with transient ischemic attacks or ischemic stroke due to severe intracranial atherosclerotic stenosis, there was no evidence that the symptomatic qualifying artery could determine the addition of stenting to medical therapy. [ABSTRACT FROM AUTHOR]

Background Lawyer is one of the most stressful jobs, but lawyers' occupational stress is rather under-researched in China. Previous studies have shown that occupational stress and mental health are related to self-regulatory fatigue and health literacy in lawyers, but there is a lack of research on their interaction mechanism. Objective To explore the association of occupational stress and mental health in lawyers and the internal mechanism of action of self-regulatory fatigue and health literacy between them. Methods A convenience sample of 660 lawyers from 7 leading Chinese law firms were surveyed from May to June 2022 using questionnaires including a self-compiled Demographic Questionnaire, the Lawyers' Occupational Stress Scale, Symptom Checklist-90 (SCL-90), Self-regulatory Fatigue Scale (SRF-S) and National Residents' Health Literacy Surveillance Rapid Assessment Questionnaire (HLSRAQ). Stepwise regression was used to explore the mediating effect of self-regulatory fatigue between occupational stress and mental health, and bootstrap method was used to test the mediating effect of self-regulatory fatigue. Model 5 in PROCESS 3.4 was used to explore the moderated mediating effect of health literacy between occupational stress and mental health. Bootstrap method was used to test the moderating mediating effect of health literacy, and further simple slope test was used to test the moderating effect, and the effects of occupational stress on the mental health of lawyers with different health literacy levels were analyzed. Results Six hundred and fifty-six cases (99.39%) who effectively responded to the survey were included for final analysis. The average scores of occupational stress, SCL-90, SRF-S and HLSRAQ were (106.9±34.8), 39.0 (15.0, 84.0), (39.4±10.0) and (13.9±3.7), respectively. Stepwise regression analysis showed that occupational stress could positively predict mental health (β=0.36, t=13.40, P