Hybrid Decay: A Transgenerational Epigenetic Decline in Vigor and Viability Triggered in Backcross Populations of Teosinte with Maize.

In the course of generating populations of maize with teosinte chromosomal introgressions, an unusual sickly plant phenotype was noted in individuals from crosses with two teosinte accessions collected near Valle de Bravo, Mexico. The plants of these Bravo teosinte accessions appear phenotypically normal themselves and the F1 plants appear similar to typical maize × teosinte F1s. However, upon backcrossing to maize, the BC1 and subsequent generations display a number of detrimental characteristics including shorter stature, reduced seed set, and abnormal floral structures. This phenomenon is observed in all BC individuals and there is no chromosomal segment linked to the sickly plant phenotype in advanced backcross generations. Once the sickly phenotype appears in a lineage, normal plants are never again recovered by continued backcrossing to the normal maize parent. Whole-genome shotgun sequencing reveals a small number of genomic sequences, some with homology to transposable elements, that have increased in copy number in the backcross populations. Transcriptome analysis of seedlings, which do not have striking phenotypic abnormalities, identified segments of 18 maize genes that exhibit increased expression in sickly plants. A de novo assembly of transcripts present in plants exhibiting the sickly phenotype identified a set of 59 upregulated novel transcripts. These transcripts include some examples with sequence similarity to transposable elements and other sequences present in the recurrent maize parent (W22) genome as well as novel sequences not present in the W22 genome. Genome-wide profiles of gene expression, DNA methylation, and small RNAs are similar between sickly plants and normal controls, although a few upregulated transcripts and transposable elements are associated with altered small RNA or methylation profiles. This study documents hybrid incompatibility and genome instability triggered by the backcrossing of Bravo teosinte with maize. We name this phenomenon "hybrid decay" and present ideas on the mechanism that may underlie it

Exploring Contextual Relationships for Cervical Abnormal Cell Detection

Cervical abnormal cell detection is a challenging task as the morphological discrepancies between abnormal and normal cells are usually subtle. To determine whether a cervical cell is normal or abnormal, cytopathologists always take surrounding cells as references to identify its abnormality. To mimic these behaviors, we propose to explore contextual relationships to boost the performance of cervical abnormal cell detection. Specifically, both contextual relationships between cells and cell-to-global images are exploited to enhance features of each region of interest (RoI) proposals. Accordingly, two modules, dubbed as RoI-relationship attention module (RRAM) and global RoI attention module (GRAM), are developed and their combination strategies are also investigated. We establish a strong baseline by using Double-Head Faster R-CNN with feature pyramid network (FPN) and integrate our RRAM and GRAM into it to validate the effectiveness of the proposed modules. Experiments conducted on a large cervical cell detection dataset reveal that the introduction of RRAM and GRAM both achieves better average precision (AP) than the baseline methods. Moreover, when cascading RRAM and GRAM, our method outperforms the state-of-the-art (SOTA) methods. Furthermore, we also show the proposed feature enhancing scheme can facilitate both image-level and smear-level classification. The code and trained models are publicly available at https://github.com/CVIU-CSU/CR4CACD.Comment: 10 pages, 14 tables, and 3 figure

Oral GS-441524 derivatives: Next-generation inhibitors of SARS‐CoV‐2 RNA‐dependent RNA polymerase

GS-441524, an RNA‐dependent RNA polymerase (RdRp) inhibitor, is a 1′-CN-substituted adenine C-nucleoside analog with broad-spectrum antiviral activity. However, the low oral bioavailability of GS‐441524 poses a challenge to its anti-SARS-CoV-2 efficacy. Remdesivir, the intravenously administered version (version 1.0) of GS-441524, is the first FDA-approved agent for SARS-CoV-2 treatment. However, clinical trials have presented conflicting evidence on the value of remdesivir in COVID-19. Therefore, oral GS-441524 derivatives (VV116, ATV006, and GS-621763; version 2.0, targeting highly conserved viral RdRp) could be considered as game-changers in treating COVID-19 because oral administration has the potential to maximize clinical benefits, including decreased duration of COVID-19 and reduced post-acute sequelae of SARS-CoV-2 infection, as well as limited side effects such as hepatic accumulation. This review summarizes the current research related to the oral derivatives of GS-441524, and provides important insights into the potential factors underlying the controversial observations regarding the clinical efficacy of remdesivir; overall, it offers an effective launching pad for developing an oral version of GS-441524

Distribution of pediatric keratoconus by different age and gender groups

PurposeTo evaluate the distribution of pediatric keratoconus patients and the disease severity based on different age and gender groups in China.Materials and methodsA total of 446 keratoconus eyes in 266 pediatric patients from January 2019 to January 2022 were included in the cross-sectional study. The clinical findings and severity of keratoconus were recorded and Kruskal–Wallis test, chi-squared test, and Cochran-Mantel-Haenszel (CMH) test were used to compare the parameters between different gender and age groups.ResultsThe male/female ratio was 353/93 (3.8:1), and the median age was 16 years (range: 6–17 years). Male patients were statistically younger than female patients (P = 0.041). The male/female ratio decreased with age (P for trend = 0.011). The distribution of the topographic keratoconus classification (TKC) stage was significantly different between gender and age groups (all P < 0.05). Male patients had a higher ratio of advanced keratoconus eyes (TKC ≥ 3) than female patients (P < 0.001), and CMH analysis indicated that being a male was a risk factor for advanced keratoconus after controlling for age (odds ratio: 2.581, P < 0.001).ConclusionMale keratoconus patients were younger, with a higher ratio of advanced keratoconus than female patients in the Chinese pediatric patients evaluated. Multicenter studies with larger sample sizes are necessary in the future

International expert consensus on diagnosis and treatment of lung cancer complicated by chronic obstructive pulmonary disease

Background: Lung cancer combined by chronic obstructive pulmonary disease (LC-COPD) is a common comorbidity and their interaction with each other poses significant clinical challenges. However, there is a lack of well-established consensus on the diagnosis and treatment of LC-COPD. Methods: A panel of experts, comprising specialists in oncology, respiratory medicine, radiology, interventional medicine, and thoracic surgery, was convened. The panel was presented with a comprehensive review of the current evidence pertaining to LC-COPD. After thorough discussions, the panel reached a consensus on 17 recommendations with over 70% agreement in voting to enhance the management of LC-COPD and optimize the care of these patients. Results: The 17 statements focused on pathogenic mechanisms (n=2), general strategies (n=4), and clinical application in COPD (n=2) and lung cancer (n=9) were developed and modified. These statements provide guidance on early screening and treatment selection of LC-COPD, the interplay of lung cancer and COPD on treatment, and considerations during treatment. This consensus also emphasizes patient-centered and personalized treatment in the management of LC-COPD. Conclusions: The consensus highlights the need for concurrent treatment for both lung cancer and COPD in LC-COPD patients, while being mindful of the mutual influence of the two conditions on treatment and monitoring for adverse reactions

Ecological security patterns of Chinese lakes based on ecosystem service values assessment and human threat factors evaluation

Sustainable provision of lake ecosystem services is essential for maintaining regional, national, and even global ecological security patterns. Scholars have been conducting in-depth research on the concept, assessment models, impact mechanisms, trade-offs, and optimization of ecosystem services. Integrating management decisions and policy design still presents significant challenges in various aspects. It is necessary to design a spatial security pattern and develop a hierarchical and classified control and protection system. This study establishes an assessment system of the ecosystem service values of Chinese lakes using meta-analysis and evaluates the spatial distribution of ecosystem services. We propose a method to build the protection security patterns of Chinese lakes based on the value of lake ecosystem services and the degree of human threats and establish a framework for evaluating the protection levels of lake ecosystems. Based on the dominant ecological functions, this study further determines the distribution of low, medium, and high-level security patterns in each lake region. Lakes within a low-level security pattern mean that higher protection levels are needed. In different ecological security patterns, this study proposes to determine the management indicators and monitoring intensity based on the ecological function types and human pressure threat levels of each lake region, to promote the improvement and healthy development of lake ecosystems. This study assesses the ecosystem service values of lakes as an entry point and establishes a framework for evaluating the protection level of lake ecosystems considering their human threat levels. The evaluation framework helps establish a hierarchical and classified control and protection system, which is of positive significance to the scientific, quantitative assessment, and standardization of territorial spatial planning processes