Integrating Artificial Intelligence for Advancing Multiple-Cancer Early Detection via Serum Biomarkers: A Narrative Review.

The concept and policies of multicancer early detection (MCED) have gained significant attention from governments worldwide in recent years. In the era of burgeoning artificial intelligence (AI) technology, the integration of MCED with AI has become a prevailing trend, giving rise to a plethora of MCED AI products. However, due to the heterogeneity of both the detection targets and the AI technologies, the overall diversity of MCED AI products remains considerable. The types of detection targets encompass protein biomarkers, cell-free DNA, or combinations of these biomarkers. In the development of AI models, different model training approaches are employed, including datasets of case-control studies or real-world cancer screening datasets. Various validation techniques, such as cross-validation, location-wise validation, and time-wise validation, are used. All of the factors show significant impacts on the predictive efficacy of MCED AIs. After the completion of AI model development, deploying the MCED AIs in clinical practice presents numerous challenges, including presenting the predictive reports, identifying the potential locations and types of tumors, and addressing cancer-related information, such as clinical follow-up and treatment. This study reviews several mature MCED AI products currently available in the market, detecting their composing factors from serum biomarker detection, MCED AI training/validation, and the clinical application. This review illuminates the challenges encountered by existing MCED AI products across these stages, offering insights into the continued development and obstacles within the field of MCED AI.

Histone deacetylase OsHDA706 orchestrates rice broad-spectrum antiviral immunity and is impeded by a viral effector.

Lysine acetylation is a dynamic post-translational modification of proteins. Extensive studies have revealed that the acetylation modulated by histone acetyltransferases and histone deacetylases (HDACs) plays a crucial role in regulating protein function. However, there has been limited focus on how HDACs regulate jasmonic acid (JA) biosynthesis in plants. Here, we uncover that the protein stability of OsLOX14, a critical enzyme involved in JA biosynthesis, is regulated by a histone deacetylase, OsHDA706, and is hindered by a viral protein. Our results show that OsHDA706 deacetylates OsLOX14 and enhances the stability of OsLOX14, leading to JA accumulation and an improved broad-spectrum rice antiviral defense. Furthermore, we found that the viral protein P2, encoded by the destructive rice stripe virus, disrupts the association of OsHDA706-OsLOX14, promoting viral infection. Overall, our findings reveal how HDAC manipulates the interplay of deacetylation and protein stability of a JA biosynthetic enzyme to enhance plant antiviral responses.

Two different viral proteins suppress NUCLEAR FACTOR-YC-mediated antiviral immunity during infection in rice.

Plant viruses have multiple strategies to counter and evade the host's antiviral immune response. However, limited research has been conducted on the antiviral defense mechanisms commonly targeted by distinct types of plant viruses. In this study, we discovered that NUCLEAR FACTOR-YC (NF-YC) and NUCLEAR FACTOR-YA (NF-YA), 2 essential components of the NF-Y complex, were commonly targeted by viral proteins encoded by 2 different rice (Oryza sativa L.) viruses, rice stripe virus (RSV, Tenuivirus) and southern rice black streaked dwarf virus (SRBSDV, Fijivirus). In vitro and in vivo experiments showed that OsNF-YCs associate with OsNF-YAs and inhibit their transcriptional activation activity, resulting in the suppression of OsNF-YA-mediated plant susceptibility to rice viruses. Different viral proteins RSV P2 and SRBSDV SP8 directly disrupted the association of OsNF-YCs with OsNF-YAs, thereby suppressing the antiviral defense mediated by OsNF-YCs. These findings suggest an approach for conferring broad-spectrum disease resistance in rice and reveal a common mechanism employed by viral proteins to evade the host's antiviral defense by hindering the antiviral capabilities of OsNF-YCs.

Kmer-Node2Vec: a Fast and Efficient Method for Kmer Embedding from the Kmer Co-occurrence Graph, with Applications to DNA Sequences.

Learning low-dimensional continuous vector representation for short k-mers divided from long DNA sequences is key to DNA sequence modeling that can be utilized in many bioinformatics investigations, such as DNA sequence retrieval and classification. DNA2Vec is the most widely used method for DNA sequence embedding. However, it poorly scales to large data sets due to its extremely long training time in kmer embedding. In this paper, we propose a novel efficient graph-based kmer embedding method, named Kmer-Node2Vec, to tackle this concern. Our method converts the large DNA corpus into one kmer co-occurrence graph, and extracts kmer relation on the graph by random walks to learn fast and high-quality kmer embedding. Extensive experiments show that our method is faster than DNA2Vec by 29 times for training on a 4GB data set, and on par with DNA2Vec in terms of task-specific accuracy of sequence retrieval and classification.

Transcriptome analysis reveals candidate miRNAs involved in skin color differentiation of juvenile Plectropomus leopardus in response to different background colors.

Red skin color in Plectropomus leopardus is important to its ornamental and economic value. However, the color of P. leopardus can change during the rearing process, darkening and turning black due to the influence of environmental background color. The underlying molecular mechanisms that regulate this phenomenon remain unclear. MicroRNAs (miRNAs) are endogenous, small non-coding RNAs that play important roles in numerous biological processes, such as skin differentiation and color formation in many animals. Therefore, we performed miRNA sequencing of P. leopardus skin before (initial) and after rearing with three different background colors (white, black, and blue) using Illumina sequencing to identify candidate miRNAs that may contribute to skin color differentiation. In total, 154,271,376 clean reads were obtained, with over 92 % of them successfully mapped to the P. leopardus reference genome. The miRNA length distributions of all samples displayed peaks around a typical length of 22 nt. Within these sequences, 243 known and 287 novel miRNAs were identified. A total of 65 significantly differentially expressed miRNAs (DEMs) were identified (P < 0.05), including 40 known DEMs and 25 novel DEMs. These DEMs included novel_561, miR-141-3p, and miR-129-5p, whose target genes were primarily associated with pigmentation related processes, including tyrosine metabolism, melanogenesis, and the Wnt signaling pathway. These findings shed light on the potential roles of miRNAs in the darkening of skin color in P. leopardus, thus enhancing our understanding of the molecular mechanisms involved in skin pigmentation differentiation in this species.

Weighted correlation network analysis of the genes in the eyes of juvenile Plectropomus leopardus provide novel insights into the molecular mechanisms of the adaptation to the background color.

Plectropomus leopardus is a valuable marine fish whose skin color is strongly affected by the background color. However, the influence of the visual sense on the skin color variation of P. leopardus remains unknown. In the present study, transcriptome analysis was used to examine the visual response mechanism under different background colors. Paraffin sections of the eyes showed that the background color caused morphological changes in the pigment cells (PCs) and outer nuclear layer (ONL) and the darkening of the iris color. The transcriptome analysis results indicated that the gene expressions in the eyes of P. leopardus were significantly different for different background colors. We identified 4845, 3069, 5874, and 6309 differentially expressed genes (DEGs) in the pairwise comparisons of white vs. initial, blue vs. initial, red vs. initial, and black vs. initial groups, respectively. Some hub genes and key pathways regulating the adaptive mechanism of P. leopardus's eyes to the background color were identified, i.e., the JAK-STAT, mTOR, and Ras signaling pathways, and the ndufb7, slc6a13, and novel.3553 gene. This adaptation was achieved through the synthesis of stress proteins and energy balance supply mediated by hub genes and key pathways. In addition, the phenylalanine metabolism, tyrosine metabolism, and actin cytoskeleton-related processes or pathways and genes were responsible for iris and skin color adaptation. In summary, we inferred that stress protein synthesis, phenylalanine metabolism, and energy homeostasis were critical stress pathways for P. leopardus to adapt its skin color to the environment. These new findings indicate that the P. leopardus skin color variation may have been caused by the environmental adaption of the eyes. The results provide new insights into the molecular mechanisms underlying the skin color adaptation of P. leopardus.

Different viral effectors suppress hormone-mediated antiviral immunity of rice coordinated by OsNPR1.

Salicylic acid (SA) and jasmonic acid (JA) are plant hormones that typically act antagonistically in dicotyledonous plants and SA and JA signaling is often manipulated by pathogens. However, in monocotyledonous plants, the detailed SA-JA interplay in response to pathogen invasion remains elusive. Here, we show that different types of viral pathogen can disrupt synergistic antiviral immunity mediated by SA and JA via OsNPR1 in the monocot rice. The P2 protein of rice stripe virus, a negative-stranded RNA virus in the genus Tenuivirus, promotes OsNPR1 degradation by enhancing the association of OsNPR1 and OsCUL3a. OsNPR1 activates JA signaling by disrupting the OsJAZ-OsMYC complex and boosting the transcriptional activation activity of OsMYC2 to cooperatively modulate rice antiviral immunity. Unrelated viral proteins from different rice viruses also interfere with the OsNPR1-mediated SA-JA interplay to facilitate viral pathogenicity, suggesting that this may be a more general strategy in monocot plants. Overall, our findings highlight that distinct viral proteins convergently obstruct JA-SA crosstalk to facilitate viral infection in monocot rice.

Independently evolved viral effectors convergently suppress DELLA protein SLR1-mediated broad-spectrum antiviral immunity in rice.

Plant viruses adopt diverse virulence strategies to inhibit host antiviral defense. However, general antiviral defense directly targeted by different types of plant viruses have rarely been studied. Here, we show that the single rice DELLA protein, SLENDER RICE 1 (SLR1), a master negative regulator in Gibberellin (GA) signaling pathway, is targeted by several different viral effectors for facilitating viral infection. Viral proteins encoded by different types of rice viruses all directly trigger the rapid degradation of SLR1 by promoting association with the GA receptor OsGID1. SLR1-mediated broad-spectrum resistance was subverted by these independently evolved viral proteins, which all interrupted the functional crosstalk between SLR1 and jasmonic acid (JA) signaling. This decline of JA antiviral further created the advantage of viral infection. Our study reveals a common viral counter-defense strategy in which different types of viruses convergently target SLR1-mediated broad-spectrum resistance to benefit viral infection in the monocotyledonous crop rice.

Transcriptome Analysis Reveals the Complex Regulatory Pathway of Background Color in Juvenile Plectropomus leopardus Skin Color Variation.

Fish skin color is often strongly affected by background color. We hypothesized that the regulatory mechanism of variations in skin color in P. leopardus is linked to the background color. In this study, we conducted transcriptome analysis of Plectropomus leopardus cultured under different background colors to compare gene expression levels and the important signaling pathways. The RNA-seq analysis yielded 26,675 known mRNAs, 3278 novel mRNAs, and 3179 differentially expressed genes (DEGs). The DEGs related to melanin synthesis were screened out. Some key melanin-related genes were identified, specifically tyr, slc7a11, mc1r, ednrb, dct, tat, and wnt1. These DEGs were mainly involved in melanogenesis, including tyrosine metabolism, the Wnt signaling pathway, and the cAMP signaling pathway. The expression levels of some key genes were upregulated when background color deepened, such as α-msh, wnt, and gf. The α-MSH/cAMP-dependent, Wnt/ß-catenin, and PI3K/Akt signaling pathways were activated, resulting in the accumulation of intracellular mitf. mitf promoted melanin production by binding to the tyr/tyrp1/dct promoter region. In the present study, we explored the molecular mechanism underlying the darkened skin color pattern of P. leopardus, providing a theoretical basis for the molecular mechanism underlying pigmentation in P. leopardus.

A film-lever actuated switch technology for multifunctional, on-demand, and robust manipulation of liquids.

A lab-on-a-chip system with Point-of-Care testing capability offers rapid and accurate diagnostic potential and is useful in resource-limited settings where biomedical equipment and skilled professionals are not readily available. However, a Point-of-Care testing system that simultaneously possesses all required features of multifunctional dispensing, on-demand release, robust operations, and capability for long-term reagent storage is still a major challenge. Here, we describe a film-lever actuated switch technology that can manipulate liquids in any direction, provide accurate and proportional release response to the applied pneumatic pressure, as well as sustain robustness during abrupt movements and vibrations. Based on the technology, we also describe development of a polymerase chain reaction system that integrates reagent introduction, mixing and reaction functions all in one process, which accomplishes "sample-in-answer-out" performance for all clinical nasal samples from 18 patients with Influenza and 18 individual controls, in good concordance of fluorescence intensity with standard polymerase chain reaction (Pearson coefficients > 0.9). The proposed platform promises robust automation of biomedical analysis, and thus can accelerate the commercialization of a range of Point-of-Care testing devices.

Insights Into the Effect of Rice Stripe Virus P2 on Rice Defense by Comparative Proteomic Analysis.

Rice stripe virus (RSV) has a serious effect on rice production. Our previous research had shown that RSV P2 plays important roles in RSV infection, so in order to further understand the effect of P2 on rice, we used Tandem Mass Tag (TMT) quantitative proteomics experimental system to analyze the changes of protein in transgenic rice expressing P2 for the first time. The results of proteomics showed that a total of 4,767 proteins were identified, including 198 up-regulated proteins and 120 down-regulated proteins. Functional classification results showed that differentially expressed proteins (DEPs) were mainly localized in chloroplasts and mainly involved in the metabolic pathways. Functional enrichment results showed that DEPs are mainly involved in RNA processing and splicing. We also verified the expression of several DEPs at the mRNA level and the interaction of a transcription factor (B7EPB8) with RSV P2. This research is the first time to use proteomics technology to explore the mechanism of RSV infection in rice with the RSV P2 as breakthrough point. Our findings provide valuable information for the study of RSV P2 and RSV infection mechanism.

NF-YA transcription factors suppress jasmonic acid-mediated antiviral defense and facilitate viral infection in rice.

NF-Y transcription factors are known to play many diverse roles in the development and physiological responses of plants but little is known about their role in plant defense. Here, we demonstrate the negative roles of rice NF-YA family genes in antiviral defense against two different plant viruses, Rice stripe virus (RSV, Tenuivirus) and Southern rice black-streaked dwarf virus (SRBSDV, Fijivirus). RSV and SRBSDV both induced the expression of OsNF-YA family genes. Overexpression of OsNF-YAs enhanced rice susceptibility to virus infection, while OsNF-YAs RNAi mutants were more resistant. Transcriptome sequencing showed that the expression of jasmonic acid (JA)-related genes was significantly decreased in plants overexpressing OsNF-YA when they were infected by viruses. qRT-PCR and JA sensitivity assays confirmed that OsNF-YAs play negative roles in regulating the JA pathway. Further experiments showed that OsNF-YAs physically interact with JA signaling transcription factors OsMYC2/3 and interfere with JA signaling by dissociating the OsMYC2/3-OsMED25 complex, which inhibits the transcriptional activation activity of OsMYC2/3. Together, our results reveal that OsNF-YAs broadly inhibit plant antiviral defense by repressing JA signaling pathways, and provide new insight into how OsNF-YAs are directly associated with the JA pathway.

Thermosensitive Injectable Chitosan/Collagen/ß-Glycerophosphate Composite Hydrogels for Enhancing Wound Healing by Encapsulating Mesenchymal Stem Cell Spheroids.

Chronic wounds caused by diabetic or venous diseases remain a social and healthcare burden. In this work, a new strategy is proposed in which injectable thermosensitive chitosan/collagen/ß-glycerophosphate (ß-GP) hydrogels were combined with three-dimensional mesenchymal stem cell (3D MSC) spheroids to accelerate chronic wound healing by enhanced vascularization and paracrine effects. Chitosan/collagen/ß-GP solution mixed with 3D MSC spheroids was rapidly transformed to a gel at body temperature by physical cross-linking, then overlapped the wounds fully and fitted to any shape of the wound. The results showed that the combination therapy exhibited a markedly therapeutic effect than the hydrogel-loaded two-dimensional (2D) MSCs or 2D MSCs alone. The hydrogel could provide an environment conductive to the attachment and proliferation of encapsulated MSCs, especially accelerating the proliferation and paracrine factor secretion of 3D MSC spheroids. These results supplied a novel alternative approach to treat chronic wounds caused by diabetic or venous diseases.

Propagation analysis and prediction of the COVID-19.

Based on the official data modeling, this paper studies the transmission process of the Corona Virus Disease 2019 (COVID-19). The error between the model and the official data curve is quite small. At the same time, it realized forward prediction and backward inference of the epidemic situation, and the relevant analysis help relevant countries to make decisions.

Conductive and Elastic 3D Helical Fibers for Use in Washable and Wearable Electronics.

Due to the intrinsic properties of fabrics, fabric-based wearable systems have certain advantages over elastomeric material-based stretchable electronics. Here, a method to produce highly stretchable, conductive, washable, and solderable fibers that consist of elastic polyurethane (PU) fibers and conductive Cu fibers, which are used as interconnects for wearable electronics, is reported. The 3D helical shape results from stress relaxation of the prestretched PU fiber and the plasticity of the Cu fiber, which provides a predictable way to manipulate the morphology of the 3D fibers. The present fibers have superior mechanical and electrical properties to many other conductive fibers fabricated through different approaches. The 3D helical fibers can be readily integrated with fabrics and other functional components to build fabric-based wearable systems.

PVAm Nanofibers Fabricated by Rotary Jet Wet Spinning and Applied to Bisphenol A Recognition.

Poly(vinylamine) (PVAm) is an important polymer with the highest content of primary amine groups of any polymer. PVAm has a great potential in selective separation and smart materials. It is difficult to fabricate pure PVAm nanofibers by electrospinning and rotary jet spinning (RJS) without additional polymers. In this work, rotary jet wet spinning (RJWS) was applied to fabricate molecular imprinting nanofibers (MINFs) with polyelectrolyte for the first time. Initially, optimal parameters of spinning are investigated, including coagulation bath, solution viscosity, and rotation speed. The PVAm aqueous solution is sensitive to alcohol. To demonstrate RJWS application, PVAm-based MINFs for bisphenol A (one endocrine disruptor) recognition are prepared by adding dummy template, cross-linking, and template elution. The association constant (8.6 mg/L), equilibrium time (30 min), and binding sites utilization rate (80%) of MINFs are evaluated. Its adsorption amount and selectivity are little lower than those of MIPs prepared by bulk polymerization; however, its adsorption speed is faster than that of MIPs.