An intervention trial targeting methadone maintenance treatment providers to improve clients' treatment retention in China.

BackgroundService providers including doctors, nurses, and other healthcare professionals play an essential role in methadone maintenance treatment (MMT). This study evaluated the impact of an intervention targeting MMT providers on their clients' treatment retention.MethodsThis study was conducted in 68 MMT clinics in five provinces of China with 36 clients randomly selected from each clinic. The clinics were randomized to intervention or control condition. The MMT CARE intervention started with group sessions to enhance providers' communication skills. The trained providers were encouraged to conduct individual sessions with clients to promote treatment engagement. The outcomes, which include client retention (main outcome) and their reception of provider-delivered individual sessions (process outcome), were measured over a 24-month period.ResultsSignificantly fewer intervention clients dropped out from MMT than control clients during the study period (31% vs. 41%; p < 0.0001). Dropout hazard was significantly lower in the intervention condition compared to the control condition (HR = 0.71, 95% CI: 0.57, 0.89). More intervention clients had individual sessions than control clients (93% vs. 70%; p < 0.0001). Having individual sessions was associated with a significantly lower dropout hazard (HR = 0.30, 95% CI: 0.23, 0.40). The intervention clients had a significantly lower dropout hazard than the control clients if they started the individual sessions during the first six months (HR = 0.68, 95% CI: 0.51, 0.90).ConclusionsThe MMT CARE intervention focusing on provider capacity building has demonstrated efficacy in reducing clients' treatment dropout. This study sheds light on MMT service improvement in China and other global community-based harm reduction programs

PtoMYB031, the R2R3 MYB transcription factor involved in secondary cell wall biosynthesis in poplar

IntroductionThe biosynthesis of the secondary cell wall (SCW) is orchestrated by an intricate hierarchical transcriptional regulatory network. This network is initiated by first-layer master switches, SCW-NAC transcription factors, which in turn activate the second-layer master switches MYBs. These switches play a crucial role in regulating xylem specification and differentiation during SCW formation. However, the roles of most MYBs in woody plants are yet to be fully understood.MethodsIn this study, we identified and isolated the R2R3-MYB transcription factor, PtoMYB031, from Populus tomentosa. We explored its expression, mainly in xylem tissues, and its role as a transcriptional repressor in the nucleus. We used overexpression and RNA interference techniques in poplar, along with Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays, to analyze the regulatory effects of PtoMYB031.ResultsOverexpression of PtoMYB031 in poplar significantly reduced lignin, cellulose, and hemicellulose content, and inhibited vascular development in stems, resulting in decreased SCW thickness in xylem tissues. Gene expression analysis showed that structural genes involved in SCW biosynthesis were downregulated in PtoMYB031-OE lines. Conversely, RNA interference of PtoMYB031 increased these compounds. Additionally, PtoMYB031 was found to recruit the repressor PtoZAT11, forming a transcriptional inhibition complex.DiscussionOur findings provide new insights into how PtoMYB031, through its interaction with PtoZAT11, forms a complex that can suppress the expression of key regulatory genes, PtoWND1A and PtoWND2B, in SCW biosynthesis. This study enhances our understanding of the transcriptional regulation involved in SCW formation in poplar, highlighting the significant role of PtoMYB031

Ectopic Expression of PtoMYB74 in Poplar and Arabidopsis Promotes Secondary Cell Wall Formation

In vascular plants, R2R3-MYB transcription factors are important regulators of secondary cell wall formation. Although 192 annotated R2R3 MYB genes were identified in the poplar genome, only a few members were characterized to participate in the regulation of the secondary cell wall biosynthesis. In this paper, we identify an R2R3-MYB transcription factor, PtoMYB74, which is predicted to be an ortholog of Arabidopsis AtMYB61, a transcription activator that regulates the secondary cell wall formation, lignin biosynthesis, stomatal aperture, and the mucilage of seed coat. PtoMYB74 is mainly expressed in the stems, especially in the xylem tissues and organs. PtoMYB74 as a transcriptional activator is localized to the nucleus. The overexpression of PtoMYB74 increased the secondary cell wall thickness of vessels in transgenic poplar and changed the secondary cell wall compositions. The expression levels of lignin and cellulose biosynthetic genes were elevated in the transgenic poplar overexpressing PtoMYB74 compared to the wild type, while there was no change in the xylan biosynthetic genes. Transcriptional activation assays demonstrated that PtoMYB74 could activate the promoters of structural genes in the lignin and cellulose biosynthetic pathways. Taken together, our data show that PtoMYB74 positively regulates the secondary cell wall biosynthesis in poplar

Genetic variants of EML1 and HIST1H4E in myeloid cell-related pathway genes independently predict cutaneous melanoma-specific survival

Both in vivo and in vitro evidence has supported a key role of myeloid cells in immune suppression in melanoma and in promoting melanocytic metastases. Some single-nucleotide polymorphisms (SNPs) have been shown to predict cutaneous melanoma-specific survival (CMSS), but the association between genetic variation in myeloid cell-related genes and cutaneous melanoma (CM) patient survival remains unknown. Methods: we investigated associations between SNPs in myeloid cell-related pathway genes and CMSS in a discovery dataset of 850 CM patients and replicated the findings in another dataset of 409 CM patients. Results: we identified two SNPs (EML1 rs10151787 A>G and HIST1H4E rs2069018 T>C) as independent prognostic factors for CMSS, with adjusted allelic hazards ratios of 1.56 (95% confidence interval =1.19-2.05, P=0.001) and 1.66 (1.22-2.26, P=0.001), respectively; so were their combined unfavorable alleles in a dose-response manner in both discovery and replication datasets (P trendG and HIST1H4E rs2069018 T>C are independent prognostic biomarkers for CMSS

Novel genetic variants of PIP5K1C and MVB12B of the endosome-related pathway predict cutaneous melanoma-specific survival

Endosomes regulate cell polarity, adhesion, signaling, immunity, and tumor progression, which may influence cancer outcomes. Here we evaluated associations between 36,068 genetic variants of 228 endosome-related pathway genes and cutaneous melanoma disease-specific survival (CMSS) using genotyping data from two previously published genome-wide association studies. The discovery dataset included 858 CM patients with 95 deaths from The University of Texas MD Anderson Cancer Center, and the replication dataset included 409 CM patients with 48 deaths from the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). In multivariate Cox proportional hazards regression analysis, we found that two novel SNPs (PIP5K1C rs11666894 A>C and MVB12B rs12376285 C>T) predicted CMSS, with adjusted hazards ratios of 1.47 (95% confidence interval = 1.15-1.89 and P = 0.002) and 1.73 (1.30-2.31 and 0.0002), respectively. Combined analysis of risk genotypes of these two SNPs revealed a dose-dependent decrease in CMSS associated with an increased number of risk genotypes (P trend = 0.0002). Subsequent expression quantitative trait loci (eQTL) analysis revealed that PIP5K1C rs11666894 was associated with mRNA expression levels in lymphoblastoid cell lines from 373 European descendants (P<0.0001) and that MVB12B rs12376285 was associated with mRNA expression levels in cultured fibroblasts from 605 European-Americans (P<0.0001). Our findings suggest that novel genetic variants of PIP5K1C and MVB12B in the endosome-related pathway genes may be promising prognostic biomarkers for CMSS, but these results need to be validated in future larger studies

Microstructure and properties of a deformation-processed Cu-Cr-Ag in situ composite by directional solidification

Cu-7Cr-0.07Ag alloys were prepared by casting and directional solidification, from which deformation-processed in situ composites were prepared by thermo-mechanical processing. The microstructure, mechanical properties, and electrical properties were investigated using optical microscopy, scanning electronic microscopy, tensile testing, and a micro-ohmmeter. The second-phase Cr grains of the directional solidification Cu-7Cr-0.07Ag in situ composite were parallel to the drawing direction and were finer, which led to a higher tensile strength and a better combination of properties

Molecular cloning and characterization of PtrLAR3, a gene encoding leucoanthocyanidin reductase from Populus trichocarpa, and its constitutive expression enhances fungal resistance in transgenic plants

The flavonoid-derived proanthocyanidins (PAs) are one class of the major defence phenolics in poplar leaves. Transcriptional activation of PA biosynthetic genes, resulting in PA accumulation in leaves, was detected following infection by the fungal Marssonina brunnea f.sp. multigermtubi using digital gene expression analysis. In order to study PA biosynthesis and its induction by fungi, a putative leucoanthocyanidin reductase gene, PtrLAR3, was isolated from Populus trichocarpa. Sequence comparison of PtrLAR3 with other known leucoanthocyanidin reductase proteins revealed high amino acid sequence similarity. Semi-quantitative reverse-transcription (RT) PCR and quantitative real-time PCR analysis demonstrated that PtrLAR3 was expressed in various tissues and the highest level of expression was observed in roots. Overexpression of PtrLAR3 in Chinese white poplar (Populus tomentosa Carr.) led to a significant plant-wide increase in PA levels. In vitro assays showed that crude leaf extracts from 35S:PtrLAR3 transformants were able to inhibit significantly the hyphal growth of M. brunnea f.sp. multigermtubi compared to the extracts from control plants. The transgenic 35S:PtrLAR3 poplar plants displayed a significant (P < 0.05) reduction in their disease symptoms compared with the control. RT-PCR analysis showed that PtrLAR3 expression was up-regulated in all transformants. These results suggested that constitutive expression of endogenous PtrLAR3 could be exploited to improve resistance to fungal pathogens in poplar

Molecular Cloning and Characterization of Two Genes Encoding Dihydroflavonol-4-Reductase from Populus trichocarpa

Dihydroflavonol 4-reductase (DFR, EC 1.1.1.219) is a rate-limited enzyme in the biosynthesis of anthocyanins and condensed tannins (proanthocyanidins) that catalyzes the reduction of dihydroflavonols to leucoanthocyanins. In this study, two full-length transcripts encoding for PtrDFR1 and PtrDFR2 were isolated from Populus trichocarpa. Sequence alignment of the two PtrDFRs with other known DFRs reveals the homology of these genes. The expression profile of PtrDFRs was investigated in various tissues of P. trichocarpa. To determine their functions, two PtrDFRs were overexpressed in tobacco (Nicotiana tabacum) via Agrobacterium-mediated transformation. The associated color change in the flowers was observed in all 35S:PtrDFR1 lines, but not in 35S:PtrDFR2 lines. Compared to the wild-type control, a significantly higher accumulation of anthocyanins was detected in transgenic plants harboring the PtrDFR1. Furthermore, overexpressing PtrDFR1 in Chinese white poplar (P. tomentosa Carr.) resulted in a higher accumulation of both anthocyanins and condensed tannins, whereas constitutively expressing PtrDFR2 only improved condensed tannin accumulation, indicating the potential regulation of condensed tannins by PtrDFR2 in the biosynthetic pathway in poplars

Qwen Technical Report

Large language models (LLMs) have revolutionized the field of artificial intelligence, enabling natural language processing tasks that were previously thought to be exclusive to humans. In this work, we introduce Qwen, the first installment of our large language model series. Qwen is a comprehensive language model series that encompasses distinct models with varying parameter counts. It includes Qwen, the base pretrained language models, and Qwen-Chat, the chat models finetuned with human alignment techniques. The base language models consistently demonstrate superior performance across a multitude of downstream tasks, and the chat models, particularly those trained using Reinforcement Learning from Human Feedback (RLHF), are highly competitive. The chat models possess advanced tool-use and planning capabilities for creating agent applications, showcasing impressive performance even when compared to bigger models on complex tasks like utilizing a code interpreter. Furthermore, we have developed coding-specialized models, Code-Qwen and Code-Qwen-Chat, as well as mathematics-focused models, Math-Qwen-Chat, which are built upon base language models. These models demonstrate significantly improved performance in comparison with open-source models, and slightly fall behind the proprietary models.Comment: 59 pages, 5 figure