[Skin lesion classification with multi-level fusion of Swin-T and ConvNeXt].

Skin cancer is a significant public health issue, and computer-aided diagnosis technology can effectively alleviate this burden. Accurate identification of skin lesion types is crucial when employing computer-aided diagnosis. This study proposes a multi-level attention cascaded fusion model based on Swin-T and ConvNeXt. It employed hierarchical Swin-T and ConvNeXt to extract global and local features, respectively, and introduced residual channel attention and spatial attention modules for further feature extraction. Multi-level attention mechanisms were utilized to process multi-scale global and local features. To address the problem of shallow features being lost due to their distance from the classifier, a hierarchical inverted residual fusion module was proposed to dynamically adjust the extracted feature information. Balanced sampling strategies and focal loss were employed to tackle the issue of imbalanced categories of skin lesions. Experimental testing on the ISIC2018 and ISIC2019 datasets yielded accuracy, precision, recall, and F1-Score of 96.01%, 93.67%, 92.65%, and 93.11%, respectively, and 92.79%, 91.52%, 88.90%, and 90.15%, respectively. Compared to Swin-T, the proposed method achieved an accuracy improvement of 3.60% and 1.66%, and compared to ConvNeXt, it achieved an accuracy improvement of 2.87% and 3.45%. The experiments demonstrate that the proposed method accurately classifies skin lesion images, providing a new solution for skin cancer diagnosis.

Oxford Nanopore Technologies (ONT) Full-length Transcriptomics Shows Electroacupuncture ameliorates Lipid Metabolic Disorder through Suppressing Hepatic Pdia3/Perk/Qrich1 Expression in Rats.

BACKGROUND: The incidence of dyslipidemia increases after menopause. Electroacupuncture (EA) has been recommended for menopause-related disease. However, the positive effect on lipid metabolism disorders is still unclear. OBJECTIVES: To investigate the underlying mechanism of EA treatment on lipid metabolism disorders through ONT full-length transcriptome sequencing Methods: Adult female SD rats were randomly divided into Ctrl, sham operation+high-fat feed(Sham+HFD), Ovariectomized+high-fat feed (OVX+HFD), Ovariectomized+high-fat feed + Atorvastatin (OVX+HFD+ATO) and OVX+HFD+EA groups. Periovarian adipose tissue around the bilateral ovaries of rats in the Sham+HFD group was resected. Rats in the OVX+HFD, OVX+HFD+ATO and OVX+HFD+EA groups were subjected to bilateral oophorectomy to prepare the ovariectomized rat model. Treatment was applied to rats in the OVX+HFD+EA group. ST36, PC6, SP6, BL18 and ST40 were the selected acupoints. Daily food intake and body weights of rats were recorded. The samples were collected 30 days after treatment. The serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein (HDL-C) were detected to assess the improvement of lipid metabolism disorders. HE and oil red O staining were used to stain the liver tissues. Total RNA was extracted from liver tissues, and its transcriptional changes were determined by high-throughput sequencing. Additionally, RTÁqPCR and immunofluorescence staining were used to verify the crucial signal pathway screened by the ONT fullÁlength transcriptome sequencing. RESULTS: EA treatment resulted in a lowered weight of perirenal fat and liver and a significant improvement in the color of the liver. In addition, EA could improve the lipid profile and hepatic steatosis in OVX+HFD rats. According to fullÁlength transcriptome sequencing, 2292 genes showed differential expression in the OVX+HFD group; of these, 1121 were upregulated and 1171 down-regulated. 609 DEGs were found in the OVX+HFD+EA group compared to the OVX+HFD group; 235 up-regulated and 374 down-regulated. We also found that 77 genes are significantly upregulated after EA intervention through Venn map analysis (including Agtr1a, Pdia3, etc.), which may be the targeted genes for EA treatment of lipid metabolism disorders. Finally, we verified the expression of Pdia3, Perk and Qrich1 levels in liver tissues. HFD feeding could increase the expression of Pdia3 and its downstream signal pathways molecular Perk and Qrich1. But these effects were reversed by EA treatment, the results demonstrated that the expression of pdia3, Perk, as well as Qrich1 of OVX+HFD rats had a decreasing trend after EA treatment. CONCLUSIONS: EA could ameliorate lipid metabolic disorder in OVX+HFD rats. The Pdia3/Perk/Qrich1 signal pathway may play crucial roles in the improvement of lipid metabolism disorder of OVX+HFD rats after EA treatment.

Effects of slightly acidic electrolyzed water on the quality and antioxidant capacity of fresh red waxy corn during postharvest cold storage.

Fresh red waxy corn is consumed worldwide because of its unique flavor and rich nutrients, but it is susceptible to deterioration with a short shelf life. This study explored the effect of slightly acidic electrolyzed water (SAEW) treatment on the quality and antioxidant capacity of fresh red waxy corn during postharvest cold storage up to 40 d. The SAEW treatment exhibited lower weight loss, softer firmness, and higher total soluble solids (TSS) and moisture content than the control group. Correspondingly, the SAEW maintained the microstructure of endosperm cell wall and starch granules of fresh red waxy corn kernels well, contributing to good sensory quality. Furthermore, SAEW effectively reduced the accumulation of H2O2 content, elevated the O2 -· scavenging ability, maintained higher CAT and APX activities, and decreased the decline of the flavonoids and anthocyanin during the storage. These results revealed that the SAEW treatment could be a promising preservation method to maintain higher-quality attributes and the antioxidant capacity of fresh red waxy corn during postharvest cold storage.

The association of maternal smoking around birth with chronic respiratory diseases in adult offspring: A Mendelian randomization study.

INTRODUCTION: Maternal smoking during pregnancy disturbs fetal lung development, and induces in their offspring childhood respiratory diseases. Whether it has a continued impact on offspring adult lung health and exerts a casual effect of chronic respiratory diseases (CRDs), remains uncertain. We seek to determine the causal relationships between maternal smoking around birth and offspring adult CRDs, using summary data from previously described cohorts. METHODS: Mendelian randomization (MR) study was used to analyze the genome-wide associations of maternal smoking around birth and offspring adult CRDs, including respiratory insufficiency, chronic obstructive pulmonary disease (COPD), related respiratory insufficiency, emphysema, COPD, COPD hospital admissions, early onset of COPD, later onset of COPD, asthma, idiopathic pulmonary fibrosis (IPF), lung cancer (LC), small cell lung carcinoma (SCLC), and lung squamous cell carcinoma (LUSC). RESULTS: After removing single-nucleotide polymorphisms (SNPs) associated with smoking by the offspring, maternal smoking around birth was associated with increased risk of offspring adult respiratory diseases (OR=1.14; 95% CI: 1.013-1.284; p=0.030), respiratory insufficiency (OR=2.413; 95% CI: 1.039-5.603; p=0.040), COPD (OR=1.14; 95% CI: 1.013-1.284; p=0.003), and asthma (OR=1.336; 95% CI: 1.161-1.538; p<0.001). Besides, maternal smoking during pregnancy was associated with a greater risk of LUSC (OR=1.229; 95% CI: 0.992-1.523; p=0.059) than the risk of IPF (OR=1.001; 95% CI: 0.999-1.003; p=0.224), LC (OR=1.203; 95% CI: 0.964-1.501; p=0.103), or SCLC (OR=1.11; 95% CI: 0.77-1.601; p=0.577). CONCLUSIONS: In this MR analysis, maternal smoking around birth caused a strong risk factor for the offspring to develop lung problems and CRDs in adulthood. The policy related to smoking cessation for mothers during pregnancy should be encouraged.

Comparative efficacy of modified Noel's technique and matrix phenolization on onychocryptosis: a retrospective study.

BACKGROUND: Onychocryptosis is a common pathological condition requiring clinical intervention. Selecting an appropriate and effective treatment based on individual patient circumstances is crucial. METHODS: We compared the efficacy and safety of the modified Noel's technique and matrix phenolization in 107 participants with onychocryptosis. Participants were divided into two groups: 75 nails (73 patients) were treated with the modified Noel's technique (modified Noel's group), while 42 nails (34 patients) were treated with matrix phenolization (Phenol group). Outcomes on clinical cure rates and postoperative complications from both groups were collected. Additionally, the efficacy of the modified Noel's technique was assessed in 31 nails with stage IV onychocryptosis. RESULTS: After 18 months, among the remaining 102 patients (110 nails), the modified Noel's group exhibited fewer complications (5.88% vs. 45.2%, P < 0.001) with similar cure rates (P = 0.62). Furthermore, there was a shorter healing time in the modified Noel's group (13.5 ± 1.4 vs. 27.6 ± 2.3 days, P < 0.001). Postoperative pain was notable in the modified Noel's group on the first postoperative day (P < 0.001), with a significant decrease in the pain score 2 weeks after surgery (P = 0.407). Postoperative nail plate narrowing was observed in the Phenol group (33%). Moreover, the modified Noel's technique achieved a 100% cure rate in stage IV patients. CONCLUSIONS: The modified Noel's technique, offering precise excision of the proliferative nail fold and strategic suturing, is suitable for stage IV patients and for those who find significant aesthetic impact unacceptable following narrowed plate postmatrix phenolization.

Neuro-regeneration or Repair: Cell Therapy of Neurological Disorders as A Way Forward.

The human central nervous system (CNS) has a limited capacity for regeneration and repair, as many other organs do. Partly as a result, neurological diseases are the leading cause of medical burden globally. Most neurological disorders cannot be cured, and primary treatments focus on managing their symptoms and slowing down their progression. Cell therapy for neurological disorders offers several therapeutic potentials and provides hope for many patients. Here we provide a general overview of cell therapy in neurological disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Wilson's disease (WD), stroke and traumatic brain injury (TBI), involving many forms of stem cells, including embryonic stem cells and induced pluripotent stem cells. We also address the current concerns and perspectives for the future. Most studies for cell therapy in neurological diseases are in the pre-clinical stage, and there is still a great need for further research to translate neural replacement and regenerative therapies into clinical settings.

Enhancing Hi-C contact matrices for loop detection with Capricorn: a multiview diffusion model.

MOTIVATION: High-resolution Hi-C contact matrices reveal the detailed three-dimensional architecture of the genome, but high-coverage experimental Hi-C data are expensive to generate. Simultaneously, chromatin structure analyses struggle with extremely sparse contact matrices. To address this problem, computational methods to enhance low-coverage contact matrices have been developed, but existing methods are largely based on resolution enhancement methods for natural images and hence often employ models that do not distinguish between biologically meaningful contacts, such as loops and other stochastic contacts. RESULTS: We present Capricorn, a machine learning model for Hi-C resolution enhancement that incorporates small-scale chromatin features as additional views of the input Hi-C contact matrix and leverages a diffusion probability model backbone to generate a high-coverage matrix. We show that Capricorn outperforms the state of the art in a cross-cell-line setting, improving on existing methods by 17% in mean squared error and 26% in F1 score for chromatin loop identification from the generated high-coverage data. We also demonstrate that Capricorn performs well in the cross-chromosome setting and cross-chromosome, cross-cell-line setting, improving the downstream loop F1 score by 14% relative to existing methods. We further show that our multiview idea can also be used to improve several existing methods, HiCARN and HiCNN, indicating the wide applicability of this approach. Finally, we use DNA sequence to validate discovered loops and find that the fraction of CTCF-supported loops from Capricorn is similar to those identified from the high-coverage data. Capricorn is a powerful Hi-C resolution enhancement method that enables scientists to find chromatin features that cannot be identified in the low-coverage contact matrix. AVAILABILITY AND IMPLEMENTATION: Implementation of Capricorn and source code for reproducing all figures in this paper are available at https://github.com/CHNFTQ/Capricorn.

Plasma amyloid beta X-42/X-40 ratio and cognitive decline in suspected early and preclinical Alzheimer's disease.

INTRODUCTION: Blood-based biomarkers are a cost-effective and minimally invasive method for diagnosing the early and preclinical stages of amyloid positivity (AP). Our study aims to investigate our novel immunoprecipitation-immunoassay (IP-IA) as a test for predicting cognitive decline. METHODS: We measured levels of amyloid beta (Aß)X-40 and AßX-42 in immunoprecipitated eluates from the DELCODE cohort. Receiver-operating characteristic (ROC) curves, regression analyses, and Cox proportional hazard regression models were constructed to predict AP by Aß42/40 classification in cerebrospinal fluid (CSF) and conversion to mild cognitive impairment (MCI) or dementia. RESULTS: We detected a significant correlation between AßX-42/X-40 in plasma and CSF (r = 0.473). Mixed-modeling analysis revealed a substantial prediction of AßX-42/X-40 with an area under the curve (AUC) of 0.81 for AP (sensitivity: 0.79, specificity: 0.74, positive predictive value [PPV]: 0.71, negative predictive value [NPV]: 0.81). In addition, lower AßX-42/X-40 ratios were associated with negative PACC5 slopes, suggesting cognitive decline. DISCUSSION: Our results suggest that assessing the plasma AßX-42/X-40 ratio via our semiautomated IP-IA is a promising biomarker when examining patients with early or preclinical AD. HIGHLIGHTS: New plasma Aß42/Aß40 measurement using immunoprecipitation-immunoassay Plasma Aß42/Aß40 associated with longitudinal cognitive decline Promising biomarker to detect subjective cognitive decline at-risk for brain amyloid positivity.

Somatosensory game intervention experience among prefrail older adults in the community: A qualitative study.

BACKGROUND: Somatosensory game interventions have been used to rehabilitate hospitalized older adults. However, their application in prefrail older adults in the community is poorly understood, hindering the development of effective intervention strategies and exercise diversification. OBJECTIVES: This study aimed to explore the experiences of prefrail Chinese older adults engaging in somatosensory gaming interventions and thus develop tailored intervention frameworks and support strategies. METHODS: We conducted semistructured interviews with 12 prefrail older adults who participated in a 12-week sensory game intervention study from August to September 2022. The interviews were analyzed using Nvivo 11.0 software following Colaizzi's seven-step analysis method. RESULTS: Somatosensory game intervention experiences were classified into four main themes and 11 subthemes: health intervention effects (enhanced limb muscle strength, improved reaction capacity, alleviated negative emotions), positive experiences (enhanced self-achievement, increased exercise motivation, elevated social engagement), negative experiences (frustration from unmet score expectations, initial discomfort), and intervention requirements (sustained interventions, technical support, personalized content). CONCLUSION: The findings have implications for somatosensory game interventions targeting prefrail older adults in the community.

Dual polarization-enabled ultrafast bulk photovoltaic response in van der Waals heterostructures.

The bulk photovoltaic effect (BPVE) originating from spontaneous charge polarizations can reach high conversion efficiency exceeding the Shockley-Queisser limit. Emerging van der Waals (vdW) heterostructures provide the ideal platform for BPVE due to interfacial interactions naturally breaking the crystal symmetries of the individual constituents and thus inducing charge polarizations. Here, we show an approach to obtain ultrafast BPVE by taking advantage of dual interfacial polarizations in vdW heterostructures. While the in-plane polarization gives rise to the BPVE in the overlayer, the charge carrier transfer assisted by the out-of-plane polarization further accelerates the interlayer electronic transport and enhances the BPVE. We illustrate the concept in MoS2/black phosphorus heterostructures, where the experimentally observed intrinsic BPVE response time achieves 26 ps, orders of magnitude faster than that of conventional non-centrosymmetric materials. Moreover, the heterostructure device possesses an extrinsic response time of approximately 2.2 ns and a bulk photovoltaic coefficient of 0.6 V-1, which is among the highest values for vdW BPV devices reported so far. Our study thus points to an effective way of designing ultrafast BPVE for high-speed photodetection.

A novel surgical scheme for hepatectomy in hepatocellular carcinoma patients with clinically significant portal hypertension.

OBJECTIVE: Clinically significant portal hypertension (CSPH) seriously affects the feasibility and safety of surgical treatment for hepatocellular carcinoma (HCC) patients. The aim of this study was to establish a new surgical scheme defining risk classification of post-hepatectomy liver failure (PHLF) to facilitate the surgical decision-making and identify suitable candidates for individual hepatectomy among HCC patients with CSPH. BACKGROUNDS: Hepatectomy is the preferred treatment for HCC. Surgeons must maintain a balance between the expected oncological outcomes of HCC removal and short-term risks of severe PHLF and morbidity. CSPH aggravates liver decompensation and increases the risk of severe PHLF thus complicating hepatectomy for HCC. METHODS: Multivariate logistic regression and stochastic forest algorithm were performed, then the independent risk factors of severe PHLF were included in a nomogram to determine the risk of severe PHLF. Further, a conditional inference tree (CTREE) through recursive partitioning analysis validated supplement the misdiagnostic threshold of the nomogram. RESULTS: This study included 924 patients, of whom 137 patients (14.8%) suffered from mild-CSPH and 66 patients suffered from (7.1%) with severe-CSPH confirmed preoperatively. Our data showed that preoperative prolonged prothrombin time, total bilirubin, indocyanine green retention rate at 15 min, CSPH grade, and standard future liver remnant volume were independent predictors of severe PHLF. By incorporating these factors, the nomogram achieved good prediction performance in assessing severe PHLF risk, and its concordance statistic was 0.891, 0.850 and 0.872 in the training cohort, internal validation cohort and external validation cohort, respectively, and good calibration curves were obtained. Moreover, the calculations of total points of diagnostic errors with 95% CI were concentrated in 110.5 (range 76.9-178.5). It showed a low risk of severe PHLF (2.3%), indicating hepatectomy is feasible when the points fall below 76.9, while the risk of severe PHLF is extremely high (93.8%) and hepatectomy should be rigorously restricted at scores over 178.5. Patients with points within the misdiagnosis threshold were further examined using CTREE according to a hierarchic order of factors represented by the presence of CSPH grade, ICG-R15, and sFLR. CONCLUSION: This new surgical scheme established in our study is practical to stratify risk classification in assessing severe PHLF, thereby facilitating surgical decision-making and identifying suitable candidates for individual hepatectomy.

A longevity level-oriented wellness target area identification method: a case study of Yunnan Province, China.

Background: Aging, as a global demographic issue, is characterized by its rapid growth, which drives an increase in people's healthcare awareness. The emergence of wellness bases caters to this market demand. Therefore, the identification of potential areas suitable for wellness activities and the construction of wellness bases, referred to as Wellness Target Areas (WTAs), becomes a crucial first step. Currently, commonly used identification methods are mostly based on traditional statistical approaches, which are often complex, cumbersome, and subject to potential risks of subjective assumptions, affecting the reliability of WTAs identification results. Longevity level serves as a comprehensive indicator reflecting the natural and socio-economic environment of a region, making it the most indicative of the regional wellness environment status. Methods: This study proposes using longevity level as the benchmark for WTAs identification to simplify the identification process and reduce the impact of subjective bias on the results. The study focuses on 129 county-level units in Yunnan Province. Firstly, the Geodetector (GD) is utilized to explore the complex interaction between the longevity level and the geographical environment to determine regional wellness factors. Secondly, using ArcGIS and geographical weighted regression (GWR), the study investigates the role of different wellness factors, ultimately classifying and grading the WTAs. Results: The longevity level in Yunnan Province exhibits a pattern of multi-point clustering, forming three major longevity regions. Factors that significantly influence longevity level include annual average precipitation, sunshine duration, PM2.5 content, per capita disposable income, density of tourist attractions, and distance from residential areas to hospitals. Based on the degree of longevity and the contribution rate of influencing factors, Yunnan Province's WTAs are classified into three levels and two types (natural and comprehensive). Conclusion: Our study aims to establish a connection between longevity level and the selection of wellness bases, exploring regional wellness factors through the relationship between longevity phenomena and geographical environment, identifying potential construction areas for wellness bases (i.e., WTAs), providing new insights for the precise selection of wellness bases, effectively enhancing the scientificity of site selection, promoting population health, and contributing to the global aging process with better health.

Invasive assessment of coronary microvascular dysfunction and cardiovascular outcomes across the full spectrum of CHD: a meta-analysis.

INTRODUCTION AND OBJECTIVES: Coronary microvascular dysfunction (CMD) is highly prevalent and is recognized as an important clinical entity in patients with coronary heart disease (CHD). Nevertheless, the association of CMD with adverse cardiovascular events in the spectrum of CHD has not been systemically quantified. METHODS: We searched electronic databases for studies on patients with CHD in whom coronary microvascular function was measured invasively, and clinical events were recorded. The primary endpoint was major adverse cardiac events (MACE), and the secondary endpoint was all-cause death. Estimates of effect were calculated using a random-effects model from published risk ratios. RESULTS: We included 27 studies with 11 404 patients. Patients with CMD assessed by invasive methods had a higher risk of MACE (RR, 2.18; 95%CI, 1.80-2.64; P<.01) and all-cause death (RR, 1.88; 95%CI, 1.55-2.27; P<.01) than those without CMD. There was no significant difference in the impact of CMD on MACE (interaction P value=.95) among different invasive measurement modalities. The magnitude of risk of CMD assessed by invasive measurements for MACE was greater in acute coronary syndrome patients (RR, 2.84, 95%CI, 2.26-3.57; P<.01) than in chronic coronary syndrome patients (RR, 1.77, 95%CI, 1.44-2.18; P<.01) (interaction P value<.01). CONCLUSIONS: CMD based on invasive measurements was associated with a high incidence of MACE and all-cause death in patients with CHD. The magnitude of risk for cardiovascular events in CMD as assessed by invasive measurements was similar among different methods but varied among CHD populations.

Nocardioides imazamoxiresistens sp. nov. Isolated from the Activated Sludge.

A Gram-staining-positive actinomycete named YZH12T was isolated from the sediment of the Yangtze River in Nanjing, Jiangsu province, China. Cells were aerobic, non-spore forming, non-motile, short rod (0.4-0.6 × 0.5-1.0 µm) or coccus (0.4-0.6 µm in diameter). Colonies were circular, smooth, and beige to yellowish. Growth occurred at 15-42 °C (optimal 28 °C), pH 5.0-9.0 (optimal 7.0), and 0-10% (w/v) NaCl (optimal 2%). The strain could tolerate 1500 mg/L of imazamox. Strain YZH12T showed 98.7% 16S rRNA gene sequence similarity Nocardioides zeae JM-1068T and less than 97% similarities with other type strains in the genus Nocardioides. Phylogenetic analysis based on genome and 16S rRNA gene sequences indicated that strain YZH12T was phylogenetically affiliated to the genus Nocardioides and formed a subclade with N. zeae JM-1068T and N. alkalitolerans DSM 16699T. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between YZH12T and closely related type strain N. zeae JM-1068T were 79.9% and 35.2%, respectively. The major fatty acids (> 5%) were C18: 1ω9c, iso-C16: 0, C16: 0, C17: 1ω8cand C18: 0; the major respiratory quinone was MK-8(H4); and the polar lipids profiles were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), glycolipid (GL), two aminophospholipids (APL1, APL2), and an unknown polar lipid (L). The genomic DNA G + C content is 73.5%. Based on the phenotypic, chemotaxonomic, phylogenetic analyses, and genomic data, strain YZH12T represents a novel species of the genus Nocardioides, for which the name Nocardioides imazamoxiresistens YZH12T is proposed, with strain YZH12T (= KCTC 49964T = MCCC 1K0892T) as the type strain.

Prognostic implication and immunotherapy response prediction of a novel ubiquitination-related gene signature in liver cancer.

HCC, also known as hepatocellular carcinoma, is a frequently occurring form of cancer with an unfavorable prognosis. This research constructed a prognostic signature related to ubiquitination and investigated its correlation with the response to immunotherapy in HCC. The Molecular Signatures Database provided a compilation of genes associated with ubiquitination. A gene signature related to ubiquitination was obtained through Cox regression using the Least Absolute Shrinkage and Selection Operator method. The genetic factors CPY26B1, MCM10, SPINK4, and TRIM54 notably impacted the outcomes of HCC. The patients were divided into two groups: one group had a high risk of poor survival while the other had a low risk but a greater chance of controlling HCC progression. Both univariate and multivariate analyses using Cox regression found the risk score to be an independent predictor of HCC prognosis. Gene set enrichment analysis (GSEA) indicated enrichment in cell cycle and cancer-related microRNAs in high-risk groups. The tumor microenvironment (TME), response to immunotherapy, and effectiveness of chemotherapy medications positively correlated with the risk score. In the high-risk group, erlotinib showed higher IC50 values compared to the low-risk group which exhibited higher IC50 values for VX-11e, AKT inhibitor VIII, AT-7519, BMS345541, Bortezomib, CP466722, FMK, and JNK-9L. The results of RT-qPCR revealed that the expression of four UEGs was higher in tumor tissue as compared to normal tissue. Based on the genes that were expressed differently and associated with ubiquitination-related tumor categorization, we have developed a pattern of four genes and a strong nomogram that can predict the prognosis of HCC, which could be useful in identifying and managing HCC.

Temporal-spatial variability of grazing behaviors of yaks and the drivers of their intake on the eastern Qinghai-Tibetan Plateau.

Introduction: Grassland-livestock balance is an important principle of sustainable development of grassland livestock production and grassland ecosystem health. Grassland degradation becomes more serious at global scales and especially at the area that is sensitive to climate change and human activities. Decreases in pasture biomass and shifts in plant community composition in degraded grasslands can largely affect grazing behaviors of livestock. Up to date, however, it is unclear that whether livestock behaviors change across spatial and temporal scales and what key factors are to shape observed behavioral patterns of livestock. Methods: Here, yak behaviors including grazing, rumination and walking on the eastern Qinghai-Tibetan Plateau (QTP) were monitored by a continuous visual observation, to investigate temporal and spatial variations of grazing behavior of yaks (Bos grunniens); based on the data from public database in the past 18 years, a meta-analysis was conducted to examine the main factors that affect grazing behaviors and intake of yaks. Results: We showed that grazing behaviors of yaks differed significantly within hours, among hours of each day and among days as well as across different observation sites. Intake rate of yaks was higher in the morning than in the afternoon, but walking speed showed an inverse trend compared with intake rate. Resting, altitude, the mean annual precipitation (MAP), the mean annual temperature (MAT), forage ash, yak age and season were the main predictors for yak intake, and forage and yak individual characteristics had direct effects on grazing behaviors and intake of yaks. Discussion: The findings confirm that grazing behaviors of yaks can vary even at small temporal scales and regional scales, which is closely related to the shift in forage quality and biomass caused by environmental changes. The study suggests that multiple factors can be responsible for the variation in livestock behaviors and shifts in behavioral patterns may consequently lead to positive or negative feedback to grassland ecosystems through plant-animal interactions.

Fungal invasion-induced accumulation of salicylic acid promotes anthocyanin biosynthesis through MdNPR1-MdTGA2.2 module in apple fruits.

In the field, necrosis area induced by pathogens is usually surrounded by a red circle in apple fruits. However, the underlying molecular mechanism of this phenomenon remains unclear. In this study, we demonstrated that accumulated salicylic acid (SA) induced by fungal infection promoted anthocyanin biosynthesis through MdNPR1-MdTGA2.2 module in apple (Malus domestica). Inoculating apple fruits with Valsa mali or Botryosphaeria dothidea induced a red circle surrounding the necrosis area, which mimicked the phenotype observed in the field. The red circle accumulated a high level of anthocyanins, which was positively correlated with SA accumulation stimulated by fungal invasion. Further analysis showed that SA promoted anthocyanin biosynthesis in a dose-dependent manner in both apple calli and fruits. We next demonstrated that MdNPR1, a master regulator of SA signaling, positively regulated anthocyanin biosynthesis in both apple and Arabidopsis. Moreover, MdNPR1 functioned as a co-activator to interact with and enhance the transactivation activity of MdTGA2.2, which could directly bind to the promoters of anthocyanin biosynthetic and regulatory genes to promote their transcription. Suppressing expression of either MdNPR1 or MdTGA2.2 inhibited coloration of apple fruits, while overexpressing either of them significantly promoted fruit coloration. Finally, we revealed that silencing either MdNPR1 or MdTGA2.2 in apple fruits repressed SA-induced fruit coloration. Therefore, our data determined that fungal-induced SA promoted anthocyanin biosynthesis through MdNPR1-MdTGA2.2 module, resulting in a red circle surrounding the necrosis area in apple fruits.

Significance of Ribonucleoside-diphosphate Reductase Subunit M2 in Lung Adenocarcinoma.

INTRODUCTION: The Ribonucleoside-diphosphate Reductase subunit M2 (RRM2) is known to be overexpressed in various cancers, though its specific functional implications remain unclear. This aims to elucidate the role of RRM2 in the progression of Lung Adenocarcinoma (LUAD) by exploring its involvement and potential impact. METHODS: RRM2 data were sourced from multiple databases to assess its diagnostic and prognostic significance in LUAD. We evaluated the association between RRM2 expression and immune cell infiltration, analyzed its function, and explored the effects of modulating RRM2 expression on LUAD cell characteristics through laboratory experiments. RESULTS: RRM2 was significantly upregulated in LUAD tissues and cells compared to normal counterparts (p<0.05), with rare genetic alterations noted (approximately 2%). This overexpression clearly distinguished LUAD from normal tissue (area under the curve (AUC): 0.963, 95% confidence intervals (CI): 0.946-0.981). Elevated RRM2 expression was significantly associated with adverse clinicopathological characteristics and poor prognosis in LUAD patients. Furthermore, a positive association was observed between RRM2 expression and immune cell infiltration. Pathway analysis revealed a critical connection between RRM2 and the cell cycle signaling pathway within LUAD. Targeting RRM2 inhibition effectively suppressed LUAD cell proliferation, migration, and invasion while promoting apoptosis. This intervention also modified the expression of several crucial proteins, including the downregulation of CDC25A, CDC25C, RAD1, Bcl-2, and PPM1D and the upregulation of TP53 and Bax (p < 0.05). CONCLUSION: Our findings highlight the potential utility of RRM2 expression as a biomarker for diagnosing and predicting prognosis in LUAD, shedding new light on the role of RRM2 in this malignancy.

Enhancing Layer-Engineered Interlayer Exciton Emission and Valley Polarization in van der Waals Heterostructures via Strain.

Layer-engineered interlayer excitons from heterostructures of transition-metal dichalcogenides (TMDCs) exhibit a rich variety of emissive states and intriguing valley spin-selection rules, the effective modulation of which is crucial for excitonic physics and related device applications. Strain or high pressure provides the possibility to tune the energy of the interlayer excitons; however, the reported emission intensity is substantially quenched, which greatly limits their practical application in optoelectronic devices. Here, via applying uniaxial strain based on polyvinyl alcohol (PVA) encapsulation technique, we report enhanced layer-engineered interlayer exciton emission intensity with largely modulated emission energy in WSe2/WS2 heterobilayer and heterotrilayer. Both momentum-direct and momentum-indirect interlayer excitons were observed, and their emission energies show an opposite shift tendency upon applied strain, which agrees with our DFT calculations. We further demonstrate that intralayer and interlayer exciton states with low phonon interactions can be modulated through the mechanical strain applied to the PVA substrate at low temperatures. Due to strain-induced breaking of the 3-fold rotational symmetry, we observe the enhanced valley polarization of interlayer excitons. Our study contributes to the understanding and modulation of the optical properties of interlayer excitons, which could be exploited for optoelectronic device applications.

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OBJECTIVES: To observe the effects of melatonin on autophagy in cortical neurons of neonatal rats with hypoxic-ischemic brain damage (HIBD) and to explore its mechanisms via the PI3K/AKT signaling pathway, aiming to provide a basis for the clinical application of melatonin. METHODS: Seven-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group, an HIBD group, and a melatonin group (n=9 each). The neonatal rat HIBD model was established using the classic Rice-Vannucci method. Neuronal morphology in the neonatal rat cerebral cortex was observed with hematoxylin-eosin staining and Nissl staining. Autophagy-related protein levels of microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunofluorescence staining and Western blot analysis. Phosphorylated phosphoinositide 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) protein expression levels were measured by immunohistochemistry and Western blot. The correlation between autophagy and the PI3K pathway in the melatonin group and the HIBD group was analyzed using Pearson correlation analysis. RESULTS: Twenty-four hours post-modeling, neurons in the sham operation group displayed normal size and orderly arrangement. In contrast, neurons in the HIBD group showed swelling and disorderly arrangement, while those in the melatonin group had relatively normal morphology and more orderly arrangement. Nissl bodies were normal in the sham operation group but distorted in the HIBD group; however, they remained relatively intact in the melatonin group. The average fluorescence intensity of LC3 and Beclin-1 was higher in the HIBD group compared to the sham operation group, but was reduced in the melatonin group compared to the HIBD group (P<0.05). The number of p-PI3K+ and p-AKT+ cells decreased in the HIBD group compared to the sham operation group but increased in the melatonin group compared to the HIBD group (P<0.05). LC3 and Beclin-1 protein expression levels were higher, and p-PI3K and p-AKT levels were lower in the HIBD group compared to the sham operation group (P<0.05); however, in the melatonin group, LC3 and Beclin-1 levels decreased, and p-PI3K and p-AKT increased compared to the HIBD group (P<0.05). The correlation analysis results showed that the difference of the mean fluorescence intensity of LC3 and Beclin-1 protein in the injured cerebral cortex between the melatonin and HIBD groups was negatively correlated with the difference of the number of p-PI3K+ and p-AKT+ cells between the two groups (P<0.05). CONCLUSIONS: Melatonin can inhibit excessive autophagy in cortical neurons of neonatal rats with HIBD, thereby alleviating HIBD. This mechanism is associated with the PI3K/AKT pathway.