Identification of apoptosis-related gene signatures as potential biomarkers for differentiating active from latent tuberculosis via bioinformatics analysis.

Background: Apoptosis is associated with the pathogenesis of Mycobacterium tuberculosis infection. This study aims to identify apoptosis-related genes as biomarkers for differentiating active tuberculosis (ATB) from latent tuberculosis infection (LTBI). Methods: The tuberculosis (TB) datasets (GSE19491, GSE62525, and GSE28623) were downloaded from the Gene Expression Omnibus (GEO) database. The diagnostic biomarkers differentiating ATB from LTBI were identified by combining the data of protein-protein interaction network, differentially expressed gene, Weighted Gene Co-Expression Network Analysis (WGCNA), and receiver operating characteristic (ROC) analyses. Machine learning algorithms were employed to validate the diagnostic ability of the biomarkers. Enrichment analysis for biomarkers was established, and potential drugs were predicted. The association between biomarkers and N6-methyladenosine (m6A) or 5-methylated cytosine (m5C) regulators was evaluated. Results: Six biomarkers including CASP1, TNFSF10, CASP4, CASP5, IFI16, and ATF3 were obtained for differentiating ATB from LTBI. They showed strong diagnostic performances, with area under ROC (AUC) values > 0.7. Enrichment analysis demonstrated that the biomarkers were involved in immune and inflammation responses. Furthermore, 24 drugs, including progesterone and emricasan, were predicted. The correlation analysis revealed that biomarkers were positively correlated with most m6A or m5C regulators. Conclusion: The six ARGs can serve as effective biomarkers differentiating ATB from LTBI and provide insight into the pathogenesis of Mycobacterium tuberculosis infection.

Food manufacturer willingness to employ blockchain technology system under the social Co-governance framework: China's situation.

The blockchain technology system has gradually come to be employed in the food supply chain system, and it has emerged that the system offers the unique function of effectively curbing counterfeiting by food manufacturers. Unlike previous research on adoption by enterprises of new technology, this paper probes into the specific evolutionary routes of game subjects from the perspective of the precondition for enterprises' willingness to employ blockchain technology on the basis of China's social co-governance framework and by establishing a tripartite evolutionary game model of food manufacturer, government and consumer. The study then tests and verifies the stability conditions of equilibrium points and the relationship between these equilibrium points and the social co-governance level through numerical simulation analysis. On the above basis, the expected market proceeds of food producers employing blockchain technology and the influence of government and consumer behavior on enterprises' selection of a behavior strategy and the level of social co-governance are analyzed. The results show that every subject selects their own behavior strategy on the basis of the balance of their respective interests, and the final stability condition of the system is independent of their initial intentions. Rather, the expected sales volume of foods employing blockchain technology, governmental behavior (e.g., supervision, casual inspection, economic punishment, and fiscal subsidies), and complaints made by consumers constitute the main factors that influence food enterprises' selection of a behavior strategy. The level of social co-governance and the behavior of both government and consumers will ultimately be accomplished by influencing enterprises' expected economic returns, and the selection of an enterprise behavior strategy internally depends on the expected economic returns from producing foods employing blockchain technology. Therefore, this paper makes relevant proposals in an attempt to assist the Chinese government to better promote and popularize the blockchain technology system among food manufacturing enterprises.

A robust and efficient AI assistant for breast tumor segmentation from DCE-MRI via a spatial-temporal framework.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows screening, follow up, and diagnosis for breast tumor with high sensitivity. Accurate tumor segmentation from DCE-MRI can provide crucial information of tumor location and shape, which significantly influences the downstream clinical decisions. In this paper, we aim to develop an artificial intelligence (AI) assistant to automatically segment breast tumors by capturing dynamic changes in multi-phase DCE-MRI with a spatial-temporal framework. The main advantages of our AI assistant include (1) robustness, i.e., our model can handle MR data with different phase numbers and imaging intervals, as demonstrated on a large-scale dataset from seven medical centers, and (2) efficiency, i.e., our AI assistant significantly reduces the time required for manual annotation by a factor of 20, while maintaining accuracy comparable to that of physicians. More importantly, as the fundamental step to build an AI-assisted breast cancer diagnosis system, our AI assistant will promote the application of AI in more clinical diagnostic practices regarding breast cancer.

Assessment of ferroptosis-associated gene signatures as potential biomarkers for differentiating latent from active tuberculosis in children.

Ferroptotic cell death is a regulated process that is governed by iron-dependent membrane lipid peroxide accumulation that plays a pathogenic role in several disease-related settings. The use of ferroptosis-related genes (FRGs) to distinguish active tuberculosis (ATB) from latent tuberculosis infection (LTBI) among children, however, remains to be analysed. Tuberculosis-related gene expression data and FRG lists were obtained, respectively, from Gene Expression Omnibus (GEO) and FerrDb. Differentially expressed FRGs (DE-FRGs) detected when comparing samples from paediatric ATB and LTBI patients were explored using appropriate bioinformatics techniques, after which enrichment analyses were performed for these genes and hub genes were identified, with these genes then being used to explore potential drug interactions and construct competing endogenous RNA (ceRNA) networks. The GSE39939 dataset yielded 124 DE-FRGs that were primarily related to responses to oxidative, chemical and extracellular stimulus-associated stress. In total, the LASSO and SVM-RFE algorithms enabled the identification of nine hub genes (MAPK14, EGLN2, IDO1, USP11, SCD, CBS, PARP8, PARP16, CDC25A) that exhibited good diagnostic utility. Functional enrichment analyses of these genes suggested that they may govern ATB transition from LTBI through the control of many pathways, including the immune response, DNA repair, transcription, RNA degradation, and glycan and energy metabolism pathways. The CIBERSORT algorithm suggested that these genes were positively correlated with inflammatory and myeloid cell activity while being negatively correlated with the activity of lymphocytes. A total of 50 candidate drugs targeting 6 hub DE-FRGs were also identified, and a ceRNA network was used to explore the complex interplay among these hub genes. The nine hub FRGs defined in this study may serve as valuable biomarkers differentiating between ATB and LTBI in young patients.

The impact of capitalist profit-seeking behavior by online food delivery platforms on food safety risks and government regulation strategies.

Capital monopolized platforms that have emerged based on the new "Internet Plus" economic form will undoubtedly distort market competition. Taking the Meituan online food delivery platform in China as an example, this study (1) investigates the game of interests between the platform and restaurants and the resulting impact on food safety risks, and (2) explores the interactions among government regulations, platform profit strategy, and restaurant behavior. An evolutionary game model between the capital-monopolized online food delivery platform and the restaurants was developed with an optional promotion fee and government regulation level as variables. Analysis of four equilibrium situations derived from the evolutionary game model showed that the platform always pursued high overall profit in every equilibrium situation. This capitalist profit-seeking behavior will most likely reduce the profit margins and even the survival space of restaurants on the platform, forcing them to engage in opportunistic behavior and illegal production, thereby resulting in increased food safety risks in online food delivery and consequently increased government regulation costs. Although increased government regulation can change the production strategy of restaurants, it cannot change the platform's capitalist profit-seeking behavior. The platform's overall payoff is not reduced due to increased regulation, which once again proves the profit-seeking nature of capital. The strategy of low commissions but high promotion fees may require greater government regulation to restrain the opportunistic behavior of restaurants. Therefore, the Chinese government regulators can achieve a win-win situation of improved government regulation efficiency and reduced regulation costs by designing new regulatory strategies that do not reduce the platform's overall payoff.

Study on effect of collaborative governance participation willingness of online food delivery platform restaurants and consumers from perspective of control theory: Based on moderating effects of perceived risks.

The popularization of the Internet and the convenience of e-commerce are driving the online restaurant industry's rapid development of worldwide. However, serious information asymmetries in online food delivery (OFD) transactions not only aggravate food safety risks, resulting in simultaneous government and market failures, but also intensify consumers' perceived risks. This paper innovatively constructs a research framework for the governance participation willingness of OFD platform restaurants and consumers under the moderating effects of perceived risks from the perspective of control theory and then develops scales for analyzing the governance willingness of both restaurants and consumers. Using data collected through a survey, this paper explores the effect of control elements on governance participation by restaurants and consumers and analyzes the moderating effects of perceived food safety risks. Results showed that both government regulations and restaurant reputation (formal control elements) and online complaints and restaurant management response (informal control elements) can increase governance participation willingness among both platform restaurants and consumers. The moderating effects of perceived risks are partially significant. When the risks perceived by restaurants and consumers are strong, government regulation and online complaints can more effectively boost the governance participation willingness of restaurants and consumers, respectively. At this moment, consumers' willingness to pursue problem solving through online complaints is evidently enhanced. Accordingly, the perceived risks and the online complaints jointly motivate restaurants and consumers to participate in governance activities.

Nutritional quality and consumer health perception of online delivery food in the context of China.

BACKGROUND: Today, the popularization of mobile internet technology has enabled the public's need for food convenience and diversity arising from modern fast-paced lifestyles to be met at a relatively low cost. The digital age of the restaurant industry has arrived. Online food delivery (OFD) is rapidly developing globally. However, the public's awareness of the nutritional quality of food through OFD and their knowledge of dietary nutrition remain to be investigated. METHODS: In the context of China, this study attempts to evaluate the nutritional quality of best-selling OFD set meals (i.e., meal combos) based on the current official Chinese dietary guidelines 2022. It accomplishes this by collecting data on popular OFD restaurants among consumers in 115 Chinese universities from the restaurants' delivery addresses. Moreover, 20,430 valid questionnaires were collected online from undergraduates, graduate students, and other young groups aged 18-30 throughout China for descriptive analysis to investigate consumers' perceptions of the nutritional quality of food through OFD and its health impact. RESULTS: The results of the nutritional quality evaluation of the OFD set meals ranged widely from 15 to 85, with a mean of 36.57 out of a possible maximum score of 100; and 89.56% scored less than 50. The nutritional quality of OFD foods was thus generally low. The nutritional quality of foods was negatively correlated with their popularity among consumers. CONCLUSIONS: Young OFD consumers generally paid low attention to dietary nutrition knowledge and seldom paid attention to nutritional quality when choosing OFD foods while the nutritional quality of OFD foods was generally low. Respondents subjectively reported that long-term consumption of OFD food caused weight gain, increased blood lipids, and gastrointestinal discomfort. They thought that the reason might be excessive oil, salt, and sugar in the food, while ignoring the balance between different types of food.

Decoding the byssus fabrication by spatiotemporal secretome analysis of scallop foot.

Secretome is involved in almost all physiological, developmental, and pathological processes, but to date there is still a lack of highly-efficient research strategy to comprehensively study the secretome of invertebrates. Adhesive secretion is a ubiquitous and essential physiological process in aquatic invertebrates with complicated protein components and unresolved adhesion mechanisms, making it a good subject for secretome profiling studies. Here we proposed a computational pipeline for systematic profiling of byssal secretome based on spatiotemporal transcriptomes of scallop. A total of 186 byssus-related proteins (BRPs) were identified, which represented the first characterized secretome of scallop byssal adhesion. Scallop byssal secretome covered almost all of the known structural elements and functional domains of aquatic adhesives, which suggested this secretome-profiling strategy had both high efficiency and accuracy. We revealed the main components of scallop byssus (including EGF-like domain containing proteins, the Tyr-rich proteins and 4C-repeats containing proteins) and the related modification enzymes primarily contributing to the rapid byssus assembly and adhesion. Spatiotemporal expression and co-expression network analyses of BRPs suggested a simultaneous secretion pattern of scallop byssal proteins across the entire region of foot and revealed their diverse functions on byssus secretion. In contrast to the previously proposed "root-initiated secretion and extension-based assembly" model, our findings supported a novel "foot-wide simultaneous secretion and in situ assembly" model of scallop byssus secretion and adhesion. Systematic analysis of scallop byssal secretome provides important clues for understanding the aquatic adhesive secretion process, as well as a common framework for studying the secretome of non-model invertebrates.

IAPs Gene Expansion in the Scallop Patinopecten yessoensis and Their Expression Profiles After Exposure to the Toxic Dinoflagellate.

Inhibitors of apoptosis proteins (IAPs) are conserved regulators involved in cell cycle, cell migration, cell death, immunity and inflammation, should be due to the fact that they can assist with the ability to cope with different kinds of extrinsic or intrinsic stresses. Bivalve molluscs are well adapted to highly complex marine environments. As free-living filter feeders that may take toxic dinoflagellates as food, bivalves can accumulate and put up with significant levels of paralytic shellfish toxins (PSTs). PSTs absorption and accumulation could have a deleterious effect on bivalves, causing negative impact on their feeding and digestion capabilities. In the present study, we analyzed IAP genes (PyIAPs) in Yesso scallop (Patinopecten yessoensis), a major fishery and aquaculture species in China. Forty-seven PyIAPs from five sub-families were identified, and almost half of the PyIAP genes were localized in clusters on two chromosomes. Several sites under positive selection was revealed in the significantly expanded sub-families BIRC4 and BIRC5. After exposure to PST-producing dinoflagellates, Alexandrium catenella, fourteen PyIAPs showed significant responses in hepatopancreas and kidney, and more than eighty-five percent of them were from the expanded sub-families BIRC4 and BIRC5. The regulation pattern of PyIAPs was similar between the two tissues, with more than half exhibited expression suppression within three days after exposure. In contrast to hepatopancreas, more acute changes of PyIAPs expression could be detected in kidney, suggesting the possible involvement of these PyIAPs in tissue-specific PST tolerance. These findings also imply the adaptive expansion of bivalve IAP genes in response to algae derived biotoxins.

A novel fluorescent probe with extremely low background fluorescence for sensing hypochlorite in zebrafish.

Development of an efficient fluorescent probe for sensing hypochlorite in water samples and biological samples is highly demanded. However, the currently reported fluorescent probes for hypochlorite frequently suffered from the problem of high background fluorescence. Herein, based on the combined effect of two different fluorescence quenching groups, we rationally developed a novel fluorescent probe for hypochlorite with extremely low background fluorescence. Notably, due to the doubly quenching groups, the probe could even keep low background fluorescence in a solution with high viscosity. Furthermore, the probe displayed highly sensitive and selective response to hypochlorite, with the detection limits calculated to be 10.5 nM. Practical application demonstrated that the probe was able to quantitatively detect hypochlorite in various water samples with good recovery. Significantly, the probe showed extremely low background fluorescence in living cells and was capable of detecting minor variation of endogenous hypochlorite in RAW 264.7 cells. Moreover, the fluorescence imaging different concentration of hypochlorite in zebrafish has been successfully conducted. The probe developed herein will be widely used as a reliable tool to accurately monitor the variation of hypochlorite in living organism.

Publisher Correction: Evolutionary transcriptomics of metazoan biphasic life cycle supports a single intercalation origin of metazoan larvae.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Evolutionary transcriptomics of metazoan biphasic life cycle supports a single intercalation origin of metazoan larvae.

The transient larva-bearing biphasic life cycle is the hallmark of many metazoan phyla, but how metazoan larvae originated remains a major enigma in animal evolution. There are two hypotheses for larval origin. The 'larva-first' hypothesis suggests that the first metazoans were similar to extant larvae, with later evolution of the adult-added biphasic life cycle; the 'adult-first' hypothesis suggests that the first metazoans were adult forms, with the biphasic life cycle arising later via larval intercalation. Here, we investigate the evolutionary origin of primary larvae by conducting ontogenetic transcriptome profiling for Mollusca-the largest marine phylum characterized by a trochophore larval stage and highly variable adult forms. We reveal that trochophore larvae exhibit rapid transcriptome evolution with extraordinary incorporation of novel genes (potentially contributing to adult shell evolution), and that cell signalling/communication genes (for example, caveolin and innexin) are probably crucial for larval evolution. Transcriptome age analysis of eight metazoan species reveals the wide presence of young larval transcriptomes in both trochozoans and other major metazoan lineages, therefore arguing against the prevailing larva-first hypothesis. Our findings support an adult-first evolutionary scenario with a single metazoan larval intercalation, and suggest that the first appearance of proto-larva probably occurred after the divergence of direct-developing Ctenophora from a metazoan ancestor.

A quality improvement method for lung LDCT images.

BACKGROUND: Low dose computed tomography (LDCT) reduces radiation damage to patients. However, with the decrease of radiation dose, LDCT images of the lung often appear some serious problems such as poor contrast, noise and streak artifacts. OBJECTIVE: To improve the quality of lung LDCT images, this study proposed and investigated a new denoising method based on classification training structure combined dictionary for lung LDCT images. METHODS: First, top-hat transform and anisotropic diffusion with a shock filter (ADSF) algorithm are used to enhance the image contrast and image details. Second, an adaptive dictionary is trained and used for noise reduction. Third, more image details are extracted from the residual image by using the atom activity measurement. The final result is obtained by combining the dictionary denoising result with the extracted detail information. The proposed method is then validated by both simulated and clinical lung LDCT images. Four metrics including Contrast-to-Noise Ratio (CNR), Noise Suppression Index (NSI), Edge Preserving Index (EPI), and Blurring Index (BI) are computed to quantitatively evaluate image quality. RESULTS: The results showed that the CNR, NSI, EPI, and BI of our method reached 8.953, 0.9500, 0.7230 and 0.0170, respectively. Noise and streak artifacts can be removed from lung LDCT images while keeping and retaining more details. CONCLUSIONS: Comparing with the results of other methods tested using the same dataset, this study demonstrated that our new method significantly improved quality of the lung LDCT images.

Integration of Biochemical, Cellular, and Genetic Indicators for Understanding the Aging Process in a Bivalve Mollusk Chlamys farreri.

The major causal factors for the irreversible decline in physical vitality during organismal aging are postulated to be a chronic state of cellular redox imbalance, metabolic toxicity, and impaired energy homeostasis. We assessed whether the relevant enzyme activity, oxidative stress, and intracellular ATP might be causally involved in the aging of short-lived Chlamys farreri (life span 4~5 years). A total of eight related biochemical and cellular indicators were chosen for the subsequent analysis. All the indicators were measured in seven different tissues from scallops aged one to four years, and our data support that the aging of C. farreri is associated with attenuated tissue enzyme activity as well as a decreased metabolic rate. Through principal component analysis, we developed an integrated vigor index for each tissue for comprehensive age-related fitness evaluation. Remarkably, all tissue-integrated vigor indexes significantly declined with age, and the kidney was observed to be the most representative tissue. Further transcriptional profiling of the enzymatic genes provided additional detail on the molecular responses that may underlie the corresponding biochemical results. Moreover, these critical molecular responses may be attributed to the conserved hierarchical regulators, e.g., FOXO, AMPKs, mTOR, and IGF1R, which were identified as potentially novel markers for chronic fitness decline with age in bivalves. The present study provides a systematic approach that could potentially benefit the global assessment of the aging process in C. farreri and provide detailed evaluation of the biochemical, cellular, and genetic indicators that might be involved. This information may assist in a better understanding of bivalve adaptability and life span.

Genome-wide identification and expression profiling of the Wnt gene family in three bivalve molluscs.

Cellular signaling initiated by various secreted, cysteine-rich Wnt proteins plays essential roles in regulating animal development and cell stemness. By virtue of its functional diversity and importance, the Wnt gene family has received substantial research interests in a variety of animal species, from invertebrates to vertebrates. However, for bivalve molluscs, one of the ancient bilaterian groups with high morphological diversity, systematic identification and analysis of the Wnt gene family remain lacking. To shed some light on the evolutionary dynamics of this gene family and obtain a more comprehensive understanding, we analyzed the characteristics of the Wnt gene family in three bivalve molluscs, with both genome and extensive transcriptomic resources. Investigation of genomic signatures, functional domains as well as phylogenetic relationships was conducted, and 12, 11, 12 subfamilies were identified in Yesso scallop, Zhikong scallop and Pacific oyster respectively. Spatiotemporal expression profiling suggested that, some bivalve Wnts might coordinate and participate in adult organ/tissue morphogenesis and homeostasis as well as early embryonic development. The transcriptional regulation of oyster Wnt genes showed dynamic and responsive patterns under different environmental stresses, indicating that Wnts may play a role in coping with challenging intertidal environments in bivalves. To our best knowledge, this study presents the first genome-wide study of Wnt gene family in bivalves, and our findings would assist in better understanding of Wnt function and evolution in bivalve molluscs.

The discovered chimeric protein plays the cohesive role to maintain scallop byssal root structural integrity.

Adhesion is essential for many marine sessile organisms. Unraveling the compositions and assembly of marine bioadheisves is the fundamental to understand their physiological roles. Despite the remarkable diversity of animal bioadhesion, our understanding of this biological process remains limited to only a few animal lineages, leaving the majority of lineages remain enigmatic. Our previous study demonstrated that scallop byssus had distinct protein composition and unusual assembly mechanism apart from mussels. Here a novel protein (Sbp9) was discovered from the key part of the byssus (byssal root), which contains two Calcium Binding Domain (CBD) and 49 tandem Epidermal Growth Factor-Like (EGFL) domain repeats. Modular architecture of Sbp9 represents a novel chimeric gene family resulting from a gene fusion event through the acquisition of CBD2 domain by tenascin like (TNL) gene from Na+/Ca2+ exchanger 1 (NCX1) gene. Finally, free thiols are present in Sbp9 and the results of a rescue assay indicated that Sbp9 likely plays the cohesive role for byssal root integrity. This study not only aids our understanding of byssus assembly but will also inspire biomimetic material design.

Characterization of an Atypical Metalloproteinase Inhibitors Like Protein (Sbp8-1) From Scallop Byssus.

Adhesion is a vital physiological process for many marine molluscs, including the mussel and scallop, and therefore it is important to characterize the proteins involved in these adhesives. Although several mussel byssal proteins were identified and characterized, the study for scallop byssal proteins remains scarce. Our previous study identified two foot-specific proteins (Sbp7, Sbp8-1), which were annotated as the tissue inhibitors of metalloproteinases (TIMPs). Evolutionary analysis suggests that the TIMP genes of Chlamys farreri had gone through multiple gene duplications during evolution, and their potential functional roles in foot may have an ancient evolutionary origin. Focusing on the Sbp8-1, the sequence alignment and biochemical analyses suggest that Sbp8-1 is an atypical TIMP. One significant feature is the presence of two extra free Cys residues at its C-terminus, which causes the Sbp8-1 polymerization. Considering the fact that the no inhibitory activity was observed and it is mainly distributed in byssal thread and plaque, we proposed that this atypical Sbp8-1 may play as the cross-linker in scallop byssus. This study facilitates not only the understanding of scallop byssus assembly, also provides the inspiration of water-resistant materials design.