Standardized framework for assessing soil quality at antimony smelting site by considering microbial-induced resilience and heavy metal contamination.

Antimony smelting activities damage the soil and vegetation surroundings while generating economic value. However, no standardized methods are available to diagnose the extent of soil degradation at antimony smelting sites. This study developed a standardized framework for assessing soil quality by considering microbial-induced resilience and heavy metal contamination at Xikuangshan antimony smelting site. The soil resilience index (SRI) and soil contamination index (SCI) were calculated by Minimum Data Set and geo-accumulation model, respectively. After standardized by a multi-criteria quantitative procedure of modified Nemerow's pollution index (NPI), the integrated assessment of soil quality index (SQI), which is the minimum of SRINPI and SCINPI, was achieved. The results showed that Sb and As were the prominent metal(loid) pollutants, and significant correlations between SQI and SRI indicated that the poor soil quality was mainly caused by the low level of soil resilience. The primary limiting factors of SRI were Fungi in high and middle contaminated areas, and Skermanella in low contaminated area, suggesting that the weak soil resilience was caused by low specific microbial abundances. Microbial regulation and phytoremediation are greatly required to improve the soil quality at antimony smelting sites from the perspectives of pollution control and resilience improvement. This study improves our understanding of ecological effects of antimony smelting sites and provides a theoretical basis for ecological restoration and sustainable development of mining areas.

Deciphering the Dynamics of EGFR-TKI Resistance in Lung Cancer: Insights from Bibliometric Analysis.

Background: EGFR-TKI resistance poses a significant challenge in the treatment landscape of non-small cell lung cancer (NSCLC), prompting extensive research into mechanisms and therapeutic strategies. In this study, we conduct a bibliometric analysis to elucidate evolving research hotspots and trends in EGFR-TKI resistance, offering insights for clinical interventions and scientific inquiries. Methods: Publications spanning from 1996 to 2024, focusing on EGFR-TKI resistance in NSCLC, were sourced from the Web of Science Core Collection. Utilizing VOSviewer 1.6.19, CiteSpace 6.2. R2, and Scimago Graphica 1.0.35, we analyzed these articles to identify countries/regions and institutions, Journals, publications, key contributors, collaborations, and emerging topics. Results: An analysis of 8051 articles by 38,215 researchers from 86 countries shows growing interest in EGFR-TKI resistance mechanisms. Since 1996, publications have steadily increased, surpassing 500 per year after 2016, with a sharp rise in citations. Research articles make up 84% of publications, emphasizing scholarly focus. Global collaboration, especially among researchers in China, the US, and Japan, is strong. Leading institutions like Dana-Farber and Harvard, along with journals such as "Lung Cancer", are key in sharing findings. Professors Yi-Long Wu and William Pao are prominent contributors. Keyword analysis reveals core themes, including first-generation EGFR-TKIs, emerging agents like osimertinib, and research on the T790M mutation. Conclusion: EGFR-TKI resistance remains a critical issue in NSCLC treatment, driving ongoing research efforts worldwide. Focusing future research on clear identification of resistance mechanisms will guide post-resistance treatment strategies, necessitating further exploration, alongside the validation of emerging drugs through clinical trials. Moreover, "chemo+" treatments following EGFR-TKI resistance require more clinical data and real-world evidence for assessing safety and patient outcomes. As research advances, a multidisciplinary approach will be key to overcoming these challenges. Continued innovation in treatment could greatly enhance patient survival and quality of life.

CoNglyPred: Accurate Prediction of N-Linked Glycosylation Sites Using ESM-2 and Structural Features With Graph Network and Co-Attention.

N-Linked glycosylation is crucial for various biological processes such as protein folding, immune response, and cellular transport. Traditional experimental methods for determining N-linked glycosylation sites entail substantial time and labor investment, which has led to the development of computational approaches as a more efficient alternative. However, due to the limited availability of 3D structural data, existing prediction methods often struggle to fully utilize structural information and fall short in integrating sequence and structural information effectively. Motivated by the progress of protein pretrained language models (pLMs) and the breakthrough in protein structure prediction, we introduced a high-accuracy model called CoNglyPred. Having compared various pLMs, we opt for the large-scale pLM ESM-2 to extract sequence embeddings, thus mitigating certain limitations associated with manual feature extraction. Meanwhile, our approach employs a graph transformer network to process the 3D protein structures predicted by AlphaFold2. The final graph output and ESM-2 embedding are intricately integrated through a co-attention mechanism. Among a series of comprehensive experiments on the independent test dataset, CoNglyPred outperforms state-of-the-art models and demonstrates exceptional performance in case study. In addition, we are the first to report the uncertainty of N-linked glycosylation predictors using expected calibration error and expected uncertainty calibration error.

GeneCompass: deciphering universal gene regulatory mechanisms with a knowledge-informed cross-species foundation model.

Deciphering universal gene regulatory mechanisms in diverse organisms holds great potential for advancing our knowledge of fundamental life processes and facilitating clinical applications. However, the traditional research paradigm primarily focuses on individual model organisms and does not integrate various cell types across species. Recent breakthroughs in single-cell sequencing and deep learning techniques present an unprecedented opportunity to address this challenge. In this study, we built an extensive dataset of over 120 million human and mouse single-cell transcriptomes. After data preprocessing, we obtained 101,768,420 single-cell transcriptomes and developed a knowledge-informed cross-species foundation model, named GeneCompass. During pre-training, GeneCompass effectively integrated four types of prior biological knowledge to enhance our understanding of gene regulatory mechanisms in a self-supervised manner. By fine-tuning for multiple downstream tasks, GeneCompass outperformed state-of-the-art models in diverse applications for a single species and unlocked new realms of cross-species biological investigations. We also employed GeneCompass to search for key factors associated with cell fate transition and showed that the predicted candidate genes could successfully induce the differentiation of human embryonic stem cells into the gonadal fate. Overall, GeneCompass demonstrates the advantages of using artificial intelligence technology to decipher universal gene regulatory mechanisms and shows tremendous potential for accelerating the discovery of critical cell fate regulators and candidate drug targets.

PBLD promotes IRF3 mediated the type I interferon (IFN-I) response and apoptosis to inhibit viral replication.

Recent studies have implicated the phenazine biosynthesis-like domain-containing protein (PBLD) in the negative regulation of the development and progression of various cancers. However, its function in viral infection remains unknown. In this study, we found that PBLD plays important roles in multiple virus infections including BPIV3, SeV, VSV, and HSV-1. Our study revealed that PBLD enhances the expression of type I interferon (IFN-I) and ISGs through interferon regulatory factor 3 (IRF3). Further study indicated that PBLD promotes transcriptional phosphorylation of IRF3 (S385/386), thereby facilitating virus-induced IFN-I production. Interestingly, PBLD mediates virus-triggered mitochondrial apoptosis through its dependence on IRF3 (K313/315). Mechanistically, PBLD facilitated virus-induced apoptosis by recruiting the Puma protein to the mitochondria via IRF3. Additionally, we performed mutational analyses of IRF3, showing that its loss of either transcriptional or apoptotic function markedly increased viral replication. Moreover, macrophages with PBLD deficiency during viral infection exhibited decreased the IFN-I and ISGs expression, exacerbating viral infection. Importantly, mice deficient in PBLD exhibited increased viral replication and susceptibility to SeV infection, leading to decreased survival. Notably, Cedrelone, a chemical activator of PBLD, has the ability to reduce SeV replication. Collectively, we first discovered the new function of PBLD in viral infection, broadening our understanding of potential therapeutic targets and offering new insights for antiviral drug development.

The mediating effect of social connectedness between internet gaming disorder and somatic symptoms in adolescents: a large sample cross-sectional study.

BACKGROUND: Previous studies have indicated that social connectedness can serve as a protective buffer against negative outcomes associated with online victimization. However, the role of social connectedness between Internet gaming disorder and somatic symptoms is still unclear. This study aims to examine the mediating effect of social connectedness on the association between Internet gaming disorder and somatic symptoms. METHODS: A cross-sectional design was utilized, using questionnaires for data collection and multi-stage stratified cluster sampling. The general demographic questionnaire, Nine-Item Internet Gaming Disorder Scale-Short Form, Social Connectedness Scale-Revised and Patient Health Questionnaire Physical Symptoms were used to collect data. We adopted Pearson's correlation analysis and the PROCESS Macro Model in regression analysis to explore the relationships among Internet gaming disorder, social connectedness and somatic symptoms. RESULTS: Internet gaming disorder was positively correlated with somatic symptoms (r = 0.20, P < 0.001), while network (r=-0.08, P < 0.001) and real-life social connectedness (r=-0.31, P < 0.001) negatively affected somatic symptoms. The network social connectedness and the real-life social connectedness played a chain mediating role in the development of Internet gaming disorder to somatic symptoms [95%CI: 0.073, 0.088], explaining 45.25% of the total effect value. The difference of real-life social connectedness and network social connectedness played a partial mediating role between Internet gaming disorder and somatic symptoms [95% CI:0.050, 0.062], accounting for 31.28% of the total effect value. CONCLUSIONS: Real-life social connectedness, network social connectedness, and their disparity all mediated the relationship between Internet gaming disorder and somatic symptoms. Real-life social connectedness acted as a protective factor, while network social connectedness served as a risk factor. Encouraging offline activities and guiding teenagers to use the internet responsibly may help prevent and reduce physical symptoms linked to Internet gaming disorder.

PocketDTA: An advanced multimodal architecture for enhanced prediction of drug-target affinity from 3D structural data of target binding pockets.

MOTIVATION: Accurately predicting the drug-target binding affinity (DTA) is crucial to drug discovery and repurposing. Although deep learning has been widely used in this field, it still faces challenges with insufficient generalization performance, inadequate use of three-dimensional (3D) information and poor interpretability. RESULTS: To alleviate these problems, we developed the PocketDTA model. This model enhances the generalization performance by pre-trained models ESM-2 and GraphMVP. It ingeniously handles the first three (top-3) target binding pockets and drug 3D information through customized GVP-GNN Layers and GraphMVP-Decoder. Additionally, it employs a bilinear attention network to enhance interpretability. Comparative analysis with state-of-the-art (SOTA) methods on the optimized Davis and KIBA datasets reveals that the PocketDTA model exhibits significant performance advantages. Further, ablation studies confirm the effectiveness of the model components, whereas cold-start experiments illustrate its robust generalization capabilities. In particular, the PocketDTA model has shown significant advantages in identifying key drug functional groups and amino acid residues via molecular docking and literature validation, highlighting its strong potential for interpretability. AVAILABILITY AND IMPLEMENTATION: Code and data are available at: Https://github.com/zhaolongNCU/PocketDTA.

The impact of different dietary flavonoids on the risk of coronary heart disease in cancer patients and that on the prognosis of patients with cancer and coronary heart disease.

The purpose of this study is to explore the risk of coronary heart disease (CHD) in cancer patients who consume different flavonoids, and the impact of flavonoids on the prognosis of cancer patients with CHD. We extracted dietary flavonoids data on 1454 patients diagnosed with cancer from the National Health and Nutrition Examination Survey and Food and Nutrient Database for Dietary Studies. Logistic regression analysis was used to explore the relationship between the intake of flavonoids and the risk of CHD. Cox proportional hazard model was used to explore the impact of flavonoids intake on prognosis in 148 patients with cancer and CHD. Malvidin intake increased the risk of CHD by 1% [odds ratio (OR) = 1.01, 95% confidence interval (CI): 1.00-1.02, P < 0.05] in cancer patients, while epicatechin and isorhamnetin reduced the risk of CHD by 3% (OR = 0.97, 95% CI: 0.94-1.00, P < 0.05) and 15% (OR = 0.85, 95% CI: 0.72-1.00, P < 0.05), respectively. Adjusted by age, sex, and race, malvidin intake increased the risk of CHD in cancer patients by 1% (OR = 1.01, 95% CI: 1.00-1.02, P < 0.05), isorhamnetin decreased the risk by 15% (OR = 0.85, 95% CI: 0.72-1.00, P < 0.05), and epicatechin showed no effect on the risk of CHD (P > 0.05). No flavonoids had impact on the prognosis of patients with cancer and CHD (P > 0.05). For patients with cancer, consuming malvidin increases the risk of CHD, while isorhamnetin reduces the risk. Consuming flavonoids has no impact on the prognosis of patients with cancer and CHD.

Development and applications of graduate outcome-based curriculum for basic medical education.

Introduction: Outcome-based education (OBE) leads to revolutionary change in medical education, but each medical school is acknowledged to develop suited framework based on specific positioning, educational philosophy and expected outcomes. Methods: Based on the graduate outcomes of basic medical education in China released by Working Committee for the Accreditation of Medical Education (WCAME) which officially recognized by World Federation for Medical Education (WFME), Taizhou University re-documented the overall organization of the curriculum and classified the courses as "Crucial, Supporting and Associated (CSA)" categories to connect the graduate outcomes and course objectives. Results: We redefined the standard for graduates in Taizhou University Medical School including 34 items in four domains and redesigned the curriculum with 76 courses classified as CSA. Empirical data reveals a substantial improvement in students' performance on Standardized Competence Test for Clinical Medicine Undergraduates in China (SCTCMU) by implementing the CSA system between 2022 and 2023. Notably, in 2023, Taizhou University's students achieved pass rates more than 20 percentage points higher than the national average, demonstrating a profound and unprecedented impact. Conclusion: The CSA classification system provides a notably clear and structured framework for categorizing courses based on their direct or indirect relevance to educational objectives, which provides clarity to educators and empowers students with a more purposeful approach to their studies.

Phenotypic spectrum of iron-sulfur cluster assembly gene IBA57 mutations: c.286 T > C identified as a hotspot mutation in Chinese patients with a stable natural history.

Mutations in IBA57 disrupt iron-sulfur clusters maturation, causing a rare mitochondrial disease. Clinical manifestations vary from neonatal lethality to childhood-onset spastic paraparesis, yet the ethnic heterogeneity and natural history remain unclear, necessitating further exploration. This study aimed to delineate the genotype-phenotype correlation of IBA57 mutations by analyzing diverse clinical presentations. We report 11 Chinese patients and include literature-reported cases, totaling 61 patients enrolled for analysis. Clinical, neuroimaging, genetic, and disease progression information were collected. Among these, 46 presented as multiple mitochondrial dysfunctions syndrome 3 (MMDS3), with 58.7% originating from Chinese population. Based on disease course, we propose three clinical subtypes: neonatal, infant and childhood subtypes. Neonatal cases universally displayed hypotonia and respiratory distress at presentation, deceased within three months. Most infancy and childhood cases exhibited developmental regression and impaired motor function. Cavitating leukoencephalopathy was a typical neuroimaging finding in MMDS3 patients. The c.286 T > C mutation was reported in 85.2% of Chinese patients. A significantly lower mortality rate was observed compared to the non-Chinese group (P = 0.002), with a survival rate exceeding 90% at 5 years, indicating a relatively stable disease progression. Fifteen cases from three families manifested the spastic paraplegia 74 phenotype, demonstrating normal development before onset, with common clinical manifestations including spastic paraplegia (14/15), visual impairment (10/13), and peripheral neuropathy (9/13). In conclusion, this study indicates a hotspot mutation in Chinese and analyses the disease progression with different clinical subtypes.

Hue-change coupled with CRISPR-Cas12a lateral flow assay for the semiquantitative detection of Salmo salar adulteration.

Salmo salar is one of the most popular salmon species due to its meaty texture and quality protein. Oncorhynchus mykiss, which has a muscle texture similar to that of Salmo salar and is less expensive, is often used as a substitute for Salmo salar. As Salmo salar and Oncorhynchus mykiss belong to the same subfamily of Salmonidae, traditional methods are ineffective in the specific detection of the two. In this study, we combined hue-change with CRISPR/Cas12a lateral flow assay to detect the Salmo salar adulteration. This method detected S. salar genomic DNA at a vLOD of 5 copies, and was able to accurately identify adulterated samples containing 5 % w/w Salmo salar within one hour. In addition, the detection of Salmo salar in processed food products was achieved with the naked-eye at a concentration range of 0 % âˆ¼ 70 % w/w, and the detection accuracy is between 93.3 % âˆ¼ 100 %.

Differential response of subterranean microbiome to exogenous organic matter input in a cave ecosystem.

As a recurrent climatic phenomenon in the context of climate change, extreme rainstorms induce vertical translocation of organic matter and increase moisture content in terrestrial ecosystems. However, it remains unclear whether heavy rainstorms can impact microbial communities in the deep biosphere by modulating organic matter input. In this study, we present findings on the different responses of bacterial and fungal communities in a subsurface cave to rainstorms and moisture variations through field surveys and microcosm experiments. During periods of rainstorms, the influx of dissolved organic matter (DOM) from soil overlying the cave into cave sediments significantly enhanced the correlation between core bacteria and environmental factors, particularly fluorescence spectral indices. The resource utilization of core bacteria was diminished, while the functional diversity of core fungi remained relatively unaltered. We also performed simulated experiments with restricted external DOM inputs, in which DOM content was observed to decrease and microbial diversity increase in response to artificially increased moisture content (MC). The niche breadth of core bacteria decreased and became more closely associated with DOM as the MC increased, while the niche breadth of core fungi remained predominantly unchanged. Compared to fungi, cave bacteria exhibited higher sensitivity towards variations in DOM. The core microbiome can efficiently utilize the available organic matter and participate in nitrogen- and sulfur-related metabolic processes. The study systematically revealed distinct microbial responses to rainstorm events, thereby providing valuable insights for future investigations into energy utilization within deep biospheres.

Handgrip strength: A simple and effective tool to recognize decreased intrinsic capacity in Chinese older adults.

OBJECTIVES: Intrinsic capacity impairment results in poor outcomes among older adults. Here we tested handgrip strength as a screening tool for IC impairment in community-dwelling older adults in Xinjiang, China. We assessed the diagnostic accuracy and established optimal cut-off points for handgrip strength in the detection of intrinsic capacity impairment. METHODS: In total, 1072 participants were included using a multilevel random sampling method. Intrinsic capacity was constructed according to the definition of the Integrated Care for Older People screening tool proposed by the WHO. RESULTS: Altogether, 73.4 % (787/1072) participants had intrinsic capacity impairment. The prevalence of intrinsic capacity impairment for hearing, vision, mobility, cognition, psychological, and vitality domains was 8.6 %, 4.8 %, 39.6 %, 47.3 %, 12.0 %, and 18.8 %, respectively. The adjusted odds ratios [95 % confidence interval) for handgrip strength was 0.935 [0.914-0.956]. The area under the curve of the receiver operating characteristic curve for handgrip strength of older men, and handgrip strength of older women with intrinsic capacity impairment were 0.7278, and 0.7534, respectively. The handgrip strength cut-off points were 28.47 kg (60-69 years), 25.76 kg (70-79 years), and 24.45 kg (≥80 years) for men, and 20.75 kg (60-69 years), 19.90 kg (70-79 years), and 16.17 kg (≥80 years) for women. CONCLUSIONS: Handgrip strength can be used as a convenient tool for evaluating intrinsic capacity. Weak handgrip strength and low education level were associated with intrinsic capacity impairment in community-dwelling older adults in Xinjiang. Using the cut-off points of handgrip strength for different age groups and genders, older adults with impaired intrinsic capacity can be identified, which may reduce the occurrence of adverse outcomes.

Tumor­associated macrophages activated in the tumor environment of hepatocellular carcinoma: Characterization and treatment (Review).

Hepatocellular carcinoma (HCC) tissue is rich in dendritic cells, T cells, B cells, macrophages, natural killer cells and cellular stroma. Together they form the tumor microenvironment (TME), which is also rich in numerous cytokines. Tumor­associated macrophages (TAMs) are involved in the regulation of tumor development. TAMs in HCC receive stimuli in different directions, polarize in different directions and release different cytokines to regulate the development of HCC. TAMs are mostly divided into two cell phenotypes: M1 and M2. M1 TAMs secrete pro­inflammatory mediators, and M2 TAMs secrete a variety of anti­inflammatory and pro­tumorigenic substances. The TAM polarization in HCC tumors is M2. Both direct and indirect methods for TAMs to regulate the development of HCC are discussed. TAMs indirectly support HCC development by promoting peripheral angiogenesis and regulating the immune microenvironment of the TME. In terms of the direct regulation between TAMs and HCC cells, the present review mainly focuses on the molecular mechanism. TAMs are involved in both the proliferation and apoptosis of HCC cells to regulate the quantitative changes of HCC, and stimulate the related invasive migratory ability and cell stemness of HCC cells. The present review aims to identify immunotherapeutic options based on the mechanisms of TAMs in the TME of HCC.

Human developmental biology - a global perspective.

In the companion Perspective 'Past and future of human developmental biology' (Hopwood, 2024), historian Nick Hopwood proposes that the field of human developmental biology has gone through periods of attention and neglect. Development invited researchers from the field to respond to this idea. In this article, published to coincide with the 10th anniversary of Development's 'From Stem Cells to Human Development' meeting, researchers from eight countries comment on how they believe their local legal, political, regulatory, societal and technological frameworks are influencing the field's trajectory.

Recent Advances and Insights in Designing ZnxCd1-xS-Based Photocatalysts for Hydrogen Production and Synergistic Selective Oxidation to Value-Added Chemical Production.

Combining the hydrogen (H2) extraction process and organic oxidation synthesis in photooxidation-reduction reactions mediated by semiconductors is a desirable strategy because rich chemicals are evolved as byproducts along with hydrogen in trifling conditions upon irradiation, which is the only effort. The bifunctional photocatalytic strategy facilitates the feasible formation of a C═O/C─C bond from a large number of compounds containing a X-H (X = C, O) bond; therefore, the production of H2 can be easily realized without support from third agents like chemical substances, thus providing an eco-friendly and appealing organic synthesis strategy. Among the widely studied semiconductor nanomaterials, ZnxCd1-xS has been continuously studied and explored by researchers over the years, and it has attracted much consideration owing to its unique advantages such as adjustable band edge position, rich elemental composition, excellent photoelectric properties, and ability to respond to visible light. Therefore, nanostructures based on ZnxCd1-xS have been widely studied as a feasible way to efficiently prepare hydrogen energy and selectively oxidize it into high-value fine chemicals. In this Review, first, the crystal and energy band structures of ZnxCd1-xS, the model of twin nanocrystals, the photogenerated charge separation mechanism of the ZB-WZ-ZB homojunction with crisscross bands, and the Volmer-Weber growth mechanism of ZnxCd1-xS are described. Second, the morphology, structure, modification, synthesis, and vacancy engineering of ZnxCd1-xS are surveyed, summarized, and discussed. Then, the research progress in ZnxCd1-xS-based photocatalysis in photocatalytic hydrogen extraction (PHE) technology, the mechanism of PHE, organic substance (benzyl alcohol, methanol, etc.) dehydrogenation, the factors affecting the efficiency of photocatalytic discerning oxidation of organic derivatives, and selective C-H activation and C-C coupling for synergistic efficient dehydrogenation of photocatalysts are described. Conclusively, the challenges in the applicability of ZnxCd1-xS-based photocatalysts are addressed for further research development along this line.

The relationship between the tertiary lymphoid structure and immune-infiltrating cells in gastrointestinal cancers: A systematic review and meta-analysis.

OBJECTIVES: This study systematically evaluated the relationship between tertiary lymphoid structures (TLS) and clinical pathological features as well as immune infiltrating cells in gastrointestinal cancers. METHODS: We searched Web of science, Pubmed, Embase, and Cochrane Library for studies that met the requirements as of July 1, 2023, and the odds ratio, the corresponding 95% confidence interval or mean and standard deviation, were included in the analysis. FINDINGS: We eventually included 20 studies, involving a total of 4856 patients. TLS were found to be significantly associated with T stage, N stage, TNM stage, and tumor size. Moreover, patients with positive TLS showed significantly elevated expression of T-cell related markers, including CD3, CD4, CD8, CD45RO; B-cell related markers, such as CD11c and CD20; and dendritic cell-related marker CD103. On the other hand, positive TLS correlated significantly with low expression of FOXP3 and CD68. Additionally, there was a significant positive association between TLS and overall infiltration of tumor-infiltrating lymphocytes. CONCLUSION: The presence of TLS is significantly correlated with the infiltration of various immune cells in gastrointestinal cancers. To determine the ideal balance between the presence of mature TLS and appropriate immune cell infiltration, further high-quality and multicenter clinical studies need to be conducted.

The MYB transcription factor PpMYB5 regulates Pp4CL1/Pp4CL2 expression to promote lignin biosynthesis of fruit russeting in the flat nectarine.

KEY MESSAGE: Transcription factor PpMYB5 promotes lignin synthesis by directly binding to the Pp4CL1/Pp4CL2 promoter and affecting their expression, which may be related to nectarine russeting formation. Nectarine russeting is usually considered to be a non-invasive physiological disease that usually occurs on late-maturing cultivars and seriously affects their appearance quality and commercial value. The cause of nectarine fruit rust is currently unknown. In this study, we compared two flat nectarine cultivars, 'zhongyoupanweidi' (HD; russeting-free cultivar) and 'zhongyoupanweihou' (TH; russeting-prone cultivar), with respect to nectarine russeting by means of microscopy, transcriptomics, and hormone analysis. Compared to HD fruits, TH fruits had a broken cuticle, missing wax layer, and heavy lignin deposition. RNA sequencing (RNA-seq) revealed significant alternations in the expression of genes related to lignin synthesis. Moreover, structure genes Pp4CL1 and Pp4CL2, MYB transcription factor (TF) gene PpMYB5 were identified through weighted gene co-expression network analysis (WGCNA). Molecular experiments and transgenic evidence suggested that PpMYB5 regulates Pp4CL1/Pp4CL2 expression to promote lignin synthesis. Overall, in addition to providing new insights into the formation of mechanisms for nectarine russeting, our study also establishes a foundation for nectarine russeting prevention.

Efficacy and safety of camrelizumab combined with chemotherapy in the first-line treatment of advanced gastric cancer: a single-arm, phase II study.

Background: Chemotherapy with SOX (S-1 and oxaliplatin) regimen showed good efficacy and a favorable safety profile in advanced gastric cancer. Anti-programmed cell death protein 1 (PD-1) antibody camrelizumab also demonstrated antitumor activity in this setting in a phase I study. However, the efficacy and safety of camrelizumab plus SOX for advanced gastric cancer have not been investigated. Thus, this study aimed to address this objective. Methods: This phase II study evaluated the efficacy and safety of camrelizumab plus SOX in previously untreated advanced gastric cancer. Patients received camrelizumab (200 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m2 orally twice daily on days 1-14; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) until disease progression, death, or intolerable toxicity. Camrelizumab was prescribed for up to a year. The primary endpoint was progression-free survival (PFS). The second endpoints were overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Results: A total of 25 patients were enrolled and received at least 1 dose of study drug. The median PFS was 7.4 months [95% confidence interval (CI): 5.6-16.4]. The median OS was 20.2 months (95% CI: 10.5-29.9); ORR was 36% (95% CI: 18.0-57.5%); DCR was 92% (95% CI: 74.0-99.0%). Among the 25 patients, 22 (88%) experienced any-grade adverse events (AEs), and 7 (28%) patients experienced grade ≥3 AEs. Conclusions: Camrelizumab plus SOX showed promising efficacy and an acceptable safety profile as the first-line treatment for advanced gastric cancer.

Precise pathogen quantification by CRISPR-Cas: a sweet but tough nut to crack.

Pathogen detection is increasingly applied in medical diagnosis, food processing and safety, and environmental monitoring. Rapid, sensitive, and accurate pathogen quantification is the most critical prerequisite for assessing protocols and preventing risks. Among various methods evolved, those based on clustered regularly interspaced short palindromic repeats (CRISPR)-associated proteins (Cas) have been developed as important pathogen detection strategies due to their distinct advantages of rapid target recognition, programmability, ultra-specificity, and potential for scalability of point-of-care testing (POCT). However, arguments and concerns on the quantitative capability of CRISPR-based strategies are ongoing. Herein, we systematically overview CRISPR-based pathogen quantification strategies according to the principles, properties, and application scenarios. Notably, we review future challenges and perspectives to address the of precise pathogen quantification by CRISPR-Cas. We hope the insights presented in this review will benefit development of CRISPR-based pathogen detection methods.