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Acral melanoma (AM) has unique biology as an aggressive subtype of melanoma. It is a common subtype of melanoma in races with darker skin tones usually diagnosed at a later stage, thereby presenting a worse prognosis compared to cutaneous melanoma. The pathogenesis of acral melanoma differs from cutaneous melanoma, and trauma promotes its development. Compared to cutaneous melanomas, acral melanomas have a significantly lighter mutational burden with more copy number variants. Most acral melanomas are classified as triple wild-type. In contrast to cutaneous melanomas, acral melanomas have a suppressive immune microenvironment. Herein, we reviewed the clinical features, genetic variants, and immune microenvironmental characteristics of limbic melanomas to summarise their unique features.

The relationship between Ki-67 expression and clinical prognosis in patients with resectable acral melanoma (AM) remains unclear. This study explores the prognostic role of Ki-67 in AM using data from 324 patients across five Chinese centers. Patients were divided into low Ki-67 expression and high Ki-67 expression groups based on pathological reports. The log-rank test was used to compare disease-free survival (DFS) and overall survival (OS), and the Cox proportional hazards regression model was employed to identify prognostic factors. Among the 324 patients included in the study, 181 (55.8%) were in the low Ki-67 expression group, and 143 (44.2%) were in the high Ki-67 expression group. The high Ki-67 expression group exhibited a higher incidence of tumor thickness > 4 mm (45.5% vs 24.3%, P  < 0.001), ulceration (65.7% vs 54.1%, P  = 0.035), stage III (31.5% vs 16.0%, P  < 0.001), LDH ≥ 250 U/L (14.0% vs. 6.6%, P  = 0.028), and positive sentinel lymph nodes (28.0% vs 11.1%, P  = 0.029). High Ki-67 predicted shorter DFS (26.8 vs 74.1 months, P  = 0.025) and OS (52.1 months vs NR, P  < 0.001). Multivariate analysis identified Ki-67, age, stage and LDH as independent OS predictors.

Melanoma of unknown primary (MUP) is a rare subtype of melanoma, with its low incidence posing challenges for clinical management. This systematic review integrates recent advances in MUP research, with a focus on pathogenesis, molecular characteristics, and therapeutic strategies. The proposed pathogenesis involves spontaneous regression of the primary lesion, potentially driven by sequential immune responses mediated by T cells and natural killer (NK) cells. At the molecular level, whole-exome/genome analyses reveal that MUP and cutaneous melanoma (CMM) share a highly concordant UV damage-driven mutational landscape; nevertheless, MUP exhibits distinct genomic alterations, including recurrent mutations in the telomerase reverse transcriptase (TERT) promoter, protein phosphatase 6 catalytic subunit (PPP6C), and isocitrate dehydrogenase 1 (IDH1). Current therapeutic approaches are similar to those for advanced melanoma, encompassing surgery, immune checkpoint inhibitors (ICIs), and targeted therapies. While ICIs have demonstrated significant improvements in survival, the clinical efficacy of targeted therapies in MUP remains to be fully established. By consolidating current knowledge, this review provides insights to guide diagnosis, treatment, and future research in MUP.

Patients with early-stage COPD were assigned to usual care plus tiotropium or placebo. Tiotropium resulted in better FEV 1 values. The annual decline in the prebronchodilator FEV 1 was similar in the two groups, but a benefit from tiotropium was seen in postbronchodilator FEV 1 .

Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV 1 ] to forced vital capacity ratio <0.70 and an FEV 1  ≥ 50% predicted value after bronchodilator use). The coprimary outcomes were the annual rate of total exacerbations and the between-group difference in the change from baseline to 24 months in FEV 1 before bronchodilator use. COPD exacerbation was defined as the appearance or worsening of at least two major symptoms (cough, expectoration, purulent sputum, wheezing, or dyspnoea) persisting for at least 48 hours. Assessment of exacerbations was conducted every three months, and lung function was performed annually after enrolment. The difference between the N-acetylcysteine group and the placebo group in the annual rate of total exacerbation were not significant (0.65 vs. 0.72 per patient-year; relative risk [RR], 0.90; 95% confidence interval [CI], 0.80–1.02; P  = 0.10). There was no significant difference in FEV 1 before bronchodilator use at 24 months. Long-term treatment with high-dose N-acetylcysteine neither significantly reduced the annual rate of total exacerbations nor improved lung function in patients with mild-to-moderate COPD. Chinese Clinical Trial Registration: ChiCTR-IIR-17012604. Evidence for the treatment of patients with mild-to-moderate COPD is limited. Here, the authors show that long-term treatment with high-dose N-acetylcysteine neither significantly reduced the annual rate of total exacerbations nor improve lung function in patients with mild-tomoderate COPD.

Addressing issues such as susceptibility to background interference and variability in feature scales of fine-grained defects on metal surfaces, as well as the relatively poor versatility of the baseline model YOLOv8n, this study proposes a YOLO-ADS algorithm for metal surface defect detection. Firstly, a novel CSPNet with Average SPP-Fast Block (ASPPFCSPC) module is proposed to enhance the model’s fusion and representation ability between local features and global background information. Secondly, the newly improved module C2f_SimDCNv2 is utilized to improve the ability of the model to extract multi-scale features. Finally, the Space-to-Depth (SPD) layer is introduced to prevent the loss of fine-grained information from small target features and reduce the redundancy between convolution operations. Experimental results demonstrate that the mean Average Precision (mAP) and Precision of the YOLO-ADS algorithm on the steel strip surface defect dataset NEU-DET reach 81.4% and 79.7%, which are severally increased by 3.5% and 6.1%, and the Frames Per Second (FPS) reaches 140.4. Meanwhile, the versatility and robustness of the model are verified on the industrial steel surface defect dataset GC10-DET, the industrial aluminum surface defect dataset APSPC and even the larger public benchmark dataset VOC2012, the mAP is respectively increased by 3.7%, 3.4% and 4.3%. Compared with the mainstream detection algorithms, YOLO-ADS algorithm is ahead of a certain advanced level in detection accuracy while maintaining a good real-time performance, which provides an efficient and feasible solution for the field of metal surface defect detection.

Aim The purpose of this study was to determine whether diabetes mellitus is associated with an increased risk of colorectal cancer. Methods Relevant studies were identified in MEDLINE and EMBASE (up until November 1st, 2011). Inclusion criteria were original, peer-reviewed publications, with case–control and cohort studies (for studies on diabetes mellitus and colorectal cancer). Summary relative risks with 95% confidence intervals were calculated with a random-effects model. Results Twenty-four studies including eight case–control and 16 cohort studies, with a total of 3,659,341 participants, were included in this updated systematic review and meta-analysis, and all involved diabetes mellitus and colorectal cancer risk. Meta-analysis of the 24 included studies indicated that diabetes was associated with an increased risk of colorectal cancer, compared with no diabetes (summary RR of colorectal cancer incidence = 1.26, 95% CI = 1.20–1.31), without heterogeneity between studies ( P heterogeneity  = 0.296). Sub-group analyses found that these results were consistent between case–control and cohort studies and among studies conducted in different areas. The association between diabetes and colorectal cancer incidence did not differ significantly by sex and sub-sites. Insulin therapy was also positively associated with risk of colorectal cancer (summary RR = 1.61, 95% CI 1.18–1.35), with evidence of heterogeneity between studies ( P heterogeneity  = 0.014). Conclusions Our findings further support a relationship between diabetes and increased risk of colon and rectal cancer in both women and men, and insulin therapy for diabetes may increase this risk.

Background Rice leaf blight, which is a devastating disease worldwide, is caused by the bacterium Xanthomonas oryzae pv . oryzae ( Xoo ). The upregulated by transcription activator-like 1 (UPT) effector box in the promoter region of the rice Xa13 gene plays a key role in Xoo pathogenicity. Mutation of a key bacterial protein-binding site in the UPT box of Xa13 to abolish PXO99-induced Xa13 expression is a way to improve rice resistance to bacteria. Highly efficient generation and selection of transgene-free edited plants are helpful to shorten and simplify the gene editing-based breeding process. Selective elimination of transgenic pollen of T0 plants can enrich the proportion of T1 transgene-free offspring, and expression of a color marker gene in seeds makes the selection of T2 plants very convenient and efficient. In this study, a genome editing and multiplexed selection system was used to generate bacterial leaf blight-resistant and transgene-free rice plants. Results We introduced site-specific mutations into the UPT box using CRISPR/Cas12a technology to hamper with transcription-activator-like effector (TAL) protein binding and gene activation and generated genome-edited rice with improved bacterial blight resistance. Transgenic pollen of T0 plants was eliminated by pollen-specific expression of the α-amylase gene Zmaa1 , and the proportion of transgene-free plants increased from 25 to 50% among single T-DNA insertion events in the T1 generation. Transgenic seeds were visually identified and discarded by specific aleuronic expression of DsRed, which reduced the cost by 50% and led to up to 98.64% accuracy for the selection of transgene-free edited plants. Conclusion We demonstrated that core nucleotide deletion in the UPT box of the Xa13 promoter conferred resistance to rice blight, and selection of transgene-free plants was boosted by introducing multiplexed selection. The combination of genome editing and transgene-free selection is an efficient strategy to accelerate functional genomic research and plant breeding.

Identifying suitable habitats for endangered species is critical in order to promote their recovery. However, conventional species distribution models (SDMs) need large amounts of labeled sample data to learn the relationship between species and environmental conditions, and are difficult to fully detangle the role of the environment in the distribution of the endangered species, which are very sparsely distributed and have environmental heterogeneity. This study’s first innovation used the semi-supervised model to accurately simulate the suitable habitats for endangered species with a small sample size. The model performance was compared with three conventional SDMs, namely Maxent, the generalized linear model, and a support vector machine. Applying the model to the endangered species Populus euphratica (P. euphratica) in the lower Tarim River basin (TRB), Northwest China. The results showed that the semi-supervised model exhibited better performance than conventional SDMs with an accuracy of 85% when only using 443 P. euphratica samples. All models developed using smaller sample sizes exhibit worse performance in the prediction of habitat suitability areas for endangered species while the semi-supervised model is still excellent. The results showed that the suitable habitat for P. euphratica is mainly near the river channel of the lower TRB, accounting for 13.49% of the study area. The lower Tarim River still has enormous land potential for the restoration of endangered P. euphratica . The model developed here can be used to evaluate a suitable habitat for endangered species with only a small sample size, and provide a basis for the conservation of endangered species.

Malignant pleural effusion (MPE), persistently generated by thorax tumor cells at the advanced stage, remains a major challenge for cancer therapy. Herein, we develop an ultra-sensitive piezoelectric nano-system by doping ytterbium in metal-organic framework (O 3 P@LPYU), which can be triggered by physiological intrapleural pressure during breath. Under the gently alterative pressure, the piezoelectric nanoparticles with notable peroxidase-like activity effectively produce a burst of reactive oxygen species and induce immunogenic cell death by catalysis of carried ozone as well as peroxide in interstitial fluid. A clear and sustained biodistribution is observed in thorax effusion and tumors upon intrapleural administration of particle. Remarkably, due to the abundant substrates in oxygen-rich environment of pleural cavity, O 3 P@LPYU particle provides a potent reduction of MPE volume and durable inhibition of tumor growth in thorax. Our work not only develops a bio-responsive piezoelectric nano-system, but also provides a strategy for persistent suppression of MPE in clinics. Malignant pleural effusion is a challenge for cancer therapy. Here, the authors report on a piezoelectric nano-system that inhibits tumor growth in the thoracic cavity by piezo-generated reactive oxygen species using the intrapleural pressure, triggering immunogenic cell death, to treat malignant pleural effusion.