First report of potato virus H infecting tomato (Solanum lycopersicum) in China.

Potato virus H (PVH), belonging to the genus Carlavirus in the family Betaflexiviridae, was initially discovered in potato plants in Inner Mongolia, China (Li et al., 2013). Subsequently, it was documented to infect pepino, a perennial shrub of the Solanaceae family like potatoes (Abouelnasr et al., 2014). Tomato (Solanum lycopersicum L.), a major global crop, faces threats from various plant viruses. In an open field survey in Yunnan, China during July 2023, tomatoes (cultivar: Liangsi) showed typical virus symptoms: leaf yellowing, curling, mottling, and fruit with abnormal shape and color. Eleven symptomatic tomato samples were collected for high-throughput sequencing to identify the potential pathogen. RNA sequencing libraries were prepared using the TruSeq RNA sample prep kit (Illumina, San Diego, CA, USA), followed by RNA-seq sequencing on an Illumina HiSeq4000 platform (LC Sciences, USA). Approximately 77,928,560 paired-end reads (150-bp each) were generated. After quality control, 75,808,296 reads were retained and subjected to de novo assembly using Trinity (version 2.8.5). The assembled contigs, ranging from 198 nt to 15865 nt, were used as queries to search against the NCBI non-redundant protein sequence database (NR) or nucleotide sequence database (NT) to detect the potential pathogens using BLASTx and BLASTn program with a cutoff e-value of 10-5. As a consequence, certain contigs were assigned to 3 plant viruses, including PVH (the highest RdRp blastx identity to UAD82396.1: 97.8%), Capsicum chlorosis virus (CaCV, the highest RdRp blastx identity to APQ31267.1: 98.4%), and southern tomato virus (STV, the highest CP-RdRp fusion protein blastx identity to QOW17541.1: 99.74%). The presence of the identified 3 viruses was subsequently screened in the 11 tomato samples originally collected from the corresponding field. Notably, the specific detection primers for the PVH genome was designed from the newly assembled PVH genome (Forward primer: 5'- ATAGTTGTGCACTGTGTGCCTG-3'; Reverse primer: 5'-GCTTAAGGTTCTTAGCGTATTC-3'), targeting ~1.1kb. Consequently, PVH was detected in 3 out of 11 samples: 2 leaf samples and 1 fruit sample, with one leaf sample showing a single infection. The complete genome sequence of PVH in tomatoes (PVH-tomato) was successfully obtained by assembling nine overlapping regions spanning the entire PVH-tomato genome, following the RT-PCR and the 5' RACE and 3' RACE approaches, and deposited in NCBI nucleotide database with accession number OR397130.1Phylogenetic analysis based on the full genome sequences of PVH-tomato and other publicly available PVH isolates revealed that PVH-tomato was closely related to a PVH isolate found in potatoes in Yunnan (blastn similarity: 97.76%) (Fig. S1A). To test PVH-tomato infectivity and pathogenicity, four healthy Nicotiana benthamiana and four healthy tomato plants were mechanically inoculated with PVH-infected leaf sap; controls used sap from healthy plants. Three weeks post-inoculation, all N. benthamiana (4/4) and three tomato plants (3/4) were PVH-positive by RT-PCR. Symptoms were milder in N. benthamiana, and only two tomato plants (2/4) showed leaf curling. No PVH was detected in control samples (Figure S1B, S1C). Sanger sequencing confirmed the amplicons' expected length of 1093 bp. Previously, PVH was documented only in potato and pepino. This is the first report of tomatoes as natural PVH hosts and PVH infecting N. benthamiana under lab conditions.

Utilizing Food Waste in 3D-Printed PLA Formulations to Achieve Sustainable and Customizable Controlled Delivery Systems.

This is the first study that explores blending polylactic acid (PLA) with various biomasses, including food wastes-brewer's spent grain (BSG), spent coffee grounds (SCG), sesame cake (SC), and thermoplastic starch (TPS) biomass to create composite gastric floating drug delivery systems (GFDDS) through 3D printing. The aim is to investigate the influence of biomass percentage, biomass type, and printing parameters on their corresponding drug release profiles. 3D-printed (3DP) composite filaments were prepared by blending biomasses and PLA before in vitro drug release studies were performed using hydrophilic and hydrophobic model drugs, metoprolol tartrate (MT), and risperidone (RIS). The data revealed that release profiles were influenced by composite compositions and wall thicknesses of 3DP GFDDS capsules. Up to 15% of food waste could be blended with PLA for all food waste types tested. Delivery studies for PLA-food wastes found that MT was fully released by 4 h, exhibiting burst release profiles after a lag time of 0.5 to 1.5 h, and RIS could achieve a sustained release profile of approximately 48 h. PLA-TPS was utilized as a comparison and demonstrated variable release profiles ranging from 8 to 120 h, depending on the TPS content. The results demonstrated the potential for adjusting drug release profiles by incorporating affordable biomasses into GFDDS. This study presents a promising direction for creating delivery systems that are sustainable, customizable, and cost-effective, utilizing sustainable materials that can also be employed for agricultural, nutraceutical, personal care, and wastewater treatment applications.

Highly Reversible and Dendrite-Free Zinc Anodes Enabled by PEDOT Nanowire Interfacial Layers for Aqueous Zinc-Ion Batteries.

The aqueous zinc-ion batteries (ZIBs) have gained increasing attention because of their high specific capacity, low cost, and good safety. However, side reactions, hydrogen evolution reaction, and uncontrolled zinc dendrites accompanying the Zn metal anodes have impeded the applications of ZIBs in grid-scale energy storage. Herein, the poly(3,4-ethylenedioxythiophene) (PEDOT) nanowires as an interfacial layer on the Zn anode (Zn-PEDOT) are reported to address the above issues. Our experimental results and density functional theory simulation reveal that the interactions between the Zn2+ and S atoms in thiophene rings of PEDOT not only facilitate the desolvation of hydrated Zn2+ but also can regulate the diffusion of Zn2+ along the thiophene molecular chains and induce the dendrite-free deposition of Zn along the (002) surface. Consequently, the Zn||Cu-PEDOT half-cell exhibits highly reversible plating/stripping behavior with an average Coulombic efficiency of 99.7% over 2500 cycles at 1 mA cm-2 and a capacity of 0.5 mAh cm-2. A symmetric Zn-PEDOT cell can steadily operate over 1100 h at 1 mA cm-2 (1 mAh cm-2) and 470 h at 10 mA cm-2 (2 mAh cm-2), outperforming the counterpart bare Zn anodes. Besides, a Zn-PEDOT||V2O5 full cell could deliver a specific capacity of 280 mAh g-1 at 1 A g-1 and exhibits a decent cycling stability, which are much superior to the bare Zn||V2O5 cell. Our results demonstrate that PEDOT nanowires are one of the promising interfacial layers for dendrite-free aqueous ZIBs.

Multiple myeloma exosomal miRNAs suppress cGAS-STING antiviral immunity.

DNA virus infection is a significant cause of morbidity and mortality in patients with multiple myeloma (MM). Monocyte dysfunction in MM patients plays a central role in infectious complications, but the precise molecular mechanism underlying the reduced resistance of monocytes to viruses in MM patients remains to be elucidated. Here, we found that MM cells were able to transfer microRNAs (miRNAs) to host monocytes/macrophages via MM cell-derived exosomes, resulting in the inhibition of innate antiviral immune responses. The screening of miRNAs enriched in exosomes derived from the bone marrow (BM) of MM patients revealed five miRNAs that negatively regulate the cGAS-STING antiviral immune response. Notably, silencing these miRNAs with antagomiRs in MM-bearing C57BL/KaLwRijHsd mice markedly reduced viral replication. These findings identify a novel mechanism whereby MM cells possess the capacity to inhibit the innate immune response of the host, thereby rendering patients susceptible to viral infection. Consequently, targeting the aberrant expression patterns of characteristic miRNAs in MM patients is a promising avenue for therapeutic intervention. Considering the miRNA score and relevant clinical factors, we formulated a practical and efficient model for the optimal assessment of susceptibility to DNA viral infection in patients with MM.

Biomaterials as a new option for treating sensorineural hearing loss.

Sensorineural hearing loss (SNHL) usually involves damage to complex auditory pathways such as inner ear cells and auditory nerves. The highly intricate and nuanced characteristics of these cells render their repair and regeneration extremely challenging, making it difficult to restore hearing to normal levels once it has been compromised. The effectiveness of traditional drugs is so minimal that they provide little help with the treatment. Fortunately, extensive experiments have demonstrated that combining biomaterials with conventional techniques significantly enhances drug effectiveness. This article reviews the research progress of biomaterials in protecting hair cells and the auditory nerve, repairing genes related to hearing, and developing artificial cochlear materials. By organizing the knowledge presented in this article, perhaps new insights can be provided for the clinical management of SNHL.

3D printing tissue-engineered scaffolds for auricular reconstruction.

Congenital microtia is the most common cause of auricular defects, with a prevalence of approximately 5.18 per 10,000 individuals. Autologous rib cartilage grafting is the leading treatment modality at this stage of auricular reconstruction currently. However, harvesting rib cartilage may lead to donor site injuries, such as pneumothorax, postoperative pain, chest wall scarring, and deformity. Therefore, in the pursuit of better graft materials, biomaterial scaffolds with great histocompatibility, precise control of morphology, non-invasiveness properties are gradually becoming a new research hotspot in auricular reconstruction. This review collectively presents the exploit and application of 3D printing biomaterial scaffold in auricular reconstruction. Although the tissue-engineered ear still faces challenges before it can be widely applied to patients in clinical settings, and its long-term effects have yet to be evaluated, we aim to provide guidance for future research directions in 3D printing biomaterial scaffold for auricular reconstruction. This will ultimately benefit the translational and clinical application of cartilage tissue engineering and biomaterials in the treatment of auricular defects.

Fabrication of a Terbium-Functionalized Cadmium Organic Framework with Proper Energy Levels as a Ratiometric Probe of an Anthrax Biomarker.

Anthrax bacillus is a very dangerous zoonotic pathogen that seriously endangers public health. Rapid and accurate qualitative and quantitative detection of its biomarkers, 2,6-dipicolinic acid (DPA), is crucial for the prevention and treatment of this pathogenic bacterium. In this work, a novel Cd-based MOF (TTCA-Cd) has been synthesized from a polycarboxylate ligand, [1,1':2',1″-terphenyl]-4,4',4″,5'-tetracarboxylic acid (H4TTCA), and further doped with Tb(III), forming a dual-emission lanthanide-functionalized MOF hybrid (TTCA-Cd@Tb). TTCA-Cd@Tb can be developed as a high-performance ratiometric fluorescent sensor toward DPA with a very low detection limit of 7.14 nM and high selectivity in a wide detection range of 0-200 µM, demonstrating a big advancement and providing a new option for the detection of DPA.

Study of the Rolling Effect on MoS2-Carbon Fiber Density and Its Consequences for the Functionality of Li-Ion Batteries.

In this study, an electrode slurry composed of molybdenum disulfide (MoS2) and vapor-grown carbon fiber (VGCF) prepared through a solid-phase synthesis method was blade-coated onto copper foil to form a thick film as the anode for lithium-ion batteries. In previously reported work, MoS2-based lithium-ion batteries have experienced gradual deformation, fracture, and pulverization of electrode materials during the charge and discharge cycling process. This leads to an unstable electrode structure and rapid decline in battery capacity. Furthermore, MoS2 nanosheets tend to aggregate over charge and discharge cycles, which diminishes the surface activity of the material and results in poor electrochemical performance. In this study, we altered the density of the MoS2-carbon fiber/Cu foil anode electrode by rolling. Three different densities of electrode sheets were obtained through varying rolling repetitions. Our study shows the best electrochemical performance was achieved at a material density of 2.2 g/cm3, maintaining a capacity of 427 mAh/g even after 80 cycles.

Hydrazone-Linked Covalent Organic Frameworks.

Hydrazone-linked covalent organic frameworks (COFs) with structural flexibility, heteroatomic sites, post-modification ability and high hydrolytic stability have attracted great attention from scientific community. Hydrazone-linked COFs, as a subclass of Schiff-base COFs, was firstly reported in 2011 by Yaghi's group and later witnessed prosperous development in various aspects. Their adjustable structures, precise pore channels and plentiful heteroatomic sites of hydrazone-linked structures possess much potential in diverse applications, for example, adsorption/separation, chemical sensing, catalysis and energy storage, etc. Up to date, the systematic reviews about the reported hydrazone-linked COFs are still rare. Therefore, in this review, we will summarize their preparation methods, characteristics and related applications, and discuss the opportunity or challenge of hydrazone-linked COFs. We hope this review could provide new insights about hydrazone-linked COFs for exploring more appealing functions or applications.

T-bet deficiency and Hic1 induction override TGF-ß-dependency in the formation of CD103+ intestine-resident memory CD8+ T cells.

Transforming growth factor ß (TGF-ß) represents a well-established signal required for tissue-resident memory T cell (TRM) formation at intestinal surfaces, regulating the expression of a large collection of genes coordinately promoting intestinal TRM differentiation. The functional contribution from each TGF-ß-controlled transcription factor is not entirely known. Here, we find that TGF-ß-induced T-bet downregulation and Hic1 induction represent two critical events during intestinal TRM differentiation. Importantly, T-bet deficiency significantly rescues intestinal TRM formation in the absence of the TGF-ß receptor. Hic1 induction further strengthens TRM maturation in the absence of TGF-ß and T-bet. Our results reveal that provision of certain TGF-ß-induced molecular events can partially replace TGF-ß signaling to promote the establishment of intestinal TRMs, which allows the functional dissection of TGF-ß-induced transcriptional targets and molecular mechanisms for TRM differentiation.

Revealing intact neuronal circuitry in centimeter-sized formalin-fixed paraffin-embedded brain.

Tissue-clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.

Molecular mechanisms of secretory autophagy and its potential role in diseases.

Autophagy is a cellular degradation system that recycles or degrades damaged organelles, viral particles, and aggregated proteins through the lysosomal pathway. Autophagy plays an indispensable role in cellular homeostasis and communication processes. An interesting aspect is that autophagy also mediates the secretion of cellular contents, a process known as secretory autophagy. Secretory autophagy differs from macroautophagy, which sequesters recruited proteins, organelles, or viral particles into autophagosomes and degrades these sequesters in lysosomes, while the secretory autophagy pathway participates in the extracellular export of cellular contents sequestered by autophagosomes through autophagy and endosomal modulators. Recent evidence reveals that secretory autophagy is pivotal in the occurrence and progression of diseases. In this review, we summarize the molecular mechanisms of secretory autophagy. Furthermore, we review the impact of secretory autophagy on diseases, including cancer, viral infectious diseases, neurodegenerative diseases, and cardiovascular diseases. Considering the pleiotropic actions of secretory autophagy on diseases, studying the mechanism of secretory autophagy may help to understand the relevant pathophysiological processes.

Epidemiology and risk factors of bloodstream infections among adolescents and young adults with acute lymphoblastic leukaemia: An 11-year retrospective cohort study.

Adolescent and young adults (AYAs) belong to a unique category of patients diagnosed with acute lymphoblastic leukaemia (ALL). Bloodstream infection (BSI) is a leading cause of treatment-related mortality in ALL patients. However, the epidemiology and risk factors for mortality from BSIs in AYA patients remain unclear. In this study, we analysed these aspects in AYAs patients and compared similarities and differences with children (<15 years old) and older adults (>39 years old). We analysed the pathogenic epidemiology, antibiotic resistance and BSI risk factors of 73 children, 180 AYAs, and 110 older adults with ALL in three comprehensive hospitals from January 2010 to August 2021. The data on BSIs in AYAs were compared to that of the other two groups. In this study, the epidemiology of BSIs in AYAs was similar to that of older adult patients. Concerning clinical characteristics, most AYAs and older adults with BSIs were in a relapsed or uncontrolled state (34.5% vs. 35.4%, p = 0.861). In terms of pathogen distribution, Gram-negative bacteria (GNB) were the most common causative pathogens in AYAs and older adult groups. Extended-spectrum beta-lactamase (ESBL)-producing bacteria were more commonly found in AYAs than in children (32.8% vs. 16.4%, p = 0.09). Regarding risk factors, the length of hospitalization (>14 days) and renal inadequacy (creatinine ≥ 177 µmol/L) were influencing factors for 30-day mortality in AYAs patients with BSIs. In our study, AYA patients with BSIs showed clinical characteristics and pathogen distributions similar to those of older adult patients but quite different from those of children.

Empowering personalized pharmacogenomics with generative AI solutions.

OBJECTIVE: This study evaluates an AI assistant developed using OpenAI's GPT-4 for interpreting pharmacogenomic (PGx) testing results, aiming to improve decision-making and knowledge sharing in clinical genetics and to enhance patient care with equitable access. MATERIALS AND METHODS: The AI assistant employs retrieval-augmented generation (RAG), which combines retrieval and generative techniques, by harnessing a knowledge base (KB) that comprises data from the Clinical Pharmacogenetics Implementation Consortium (CPIC). It uses context-aware GPT-4 to generate tailored responses to user queries from this KB, further refined through prompt engineering and guardrails. RESULTS: Evaluated against a specialized PGx question catalog, the AI assistant showed high efficacy in addressing user queries. Compared with OpenAI's ChatGPT 3.5, it demonstrated better performance, especially in provider-specific queries requiring specialized data and citations. Key areas for improvement include enhancing accuracy, relevancy, and representative language in responses. DISCUSSION: The integration of context-aware GPT-4 with RAG significantly enhanced the AI assistant's utility. RAG's ability to incorporate domain-specific CPIC data, including recent literature, proved beneficial. Challenges persist, such as the need for specialized genetic/PGx models to improve accuracy and relevancy and addressing ethical, regulatory, and safety concerns. CONCLUSION: This study underscores generative AI's potential for transforming healthcare provider support and patient accessibility to complex pharmacogenomic information. While careful implementation of large language models like GPT-4 is necessary, it is clear that they can substantially improve understanding of pharmacogenomic data. With further development, these tools could augment healthcare expertise, provider productivity, and the delivery of equitable, patient-centered healthcare services.

Development and application of emotion recognition technology - a systematic literature review.

BACKGROUND: There is a mutual influence between emotions and diseases. Thus, the subject of emotions has gained increasing attention. OBJECTIVE: The primary objective of this study was to conduct a comprehensive review of the developments in emotion recognition technology over the past decade. This review aimed to gain insights into the trends and real-world effects of emotion recognition technology by examining its practical applications in different settings, including hospitals and home environments. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines and included a search of 4 electronic databases, namely, PubMed, Web of Science, Google Scholar and IEEE Xplore, to identify eligible studies published between 2013 and 2023. The quality of the studies was assessed using the Critical Appraisal Skills Programme (CASP) criteria. The key information from the studies, including the study populations, application scenarios, and technological methods employed, was summarized and analyzed. RESULTS: In a systematic literature review of the 44 studies that we analyzed the development and impact of emotion recognition technology in the field of medicine from three distinct perspectives: "application scenarios," "techniques of multiple modalities," and "clinical applications." The following three impacts were identified: (i) The advancement of emotion recognition technology has facilitated remote emotion recognition and treatment in hospital and home environments by healthcare professionals. (ii) There has been a shift from traditional subjective emotion assessment methods to multimodal emotion recognition methods that are grounded in objective physiological signals. This technological progress is expected to enhance the accuracy of medical diagnosis. (iii) The evolving relationship between emotions and disease throughout diagnosis, intervention, and treatment processes holds clinical significance for real-time emotion monitoring. CONCLUSION: These findings indicate that the integration of emotion recognition technology with intelligent devices has led to the development of application systems and models, which provide technological support for the recognition of and interventions for emotions. However, the continuous recognition of emotional changes in dynamic or complex environments will be a focal point of future research.

Cost-utility analysis of treating mild stage normal tension glaucoma by surgery in China: a decision-analytic Markov model.

BACKGROUND: Many individuals suffer from normal tension glaucoma (NTG) in China. This study utilized Markov models to evaluate the cost-utility of applying many medications and surgery for mild-stage NTG when disease progression occurred at a mild stage. METHODS: A 10-year decision-analytic Markov model was developed for the cost-utility analysis of treating mild-stage NTG with surgery and increased application of medication. We hypothesized that all 100,000 samples with a mean age of 64 were in mild stages of NTG. Transitional probabilities from the mild to moderate to severe stages and the basic parameters acquired from the CNTGS were calculated. Incremental cost-utility ratios (ICUR) were calculated for treating all patients with NTG by probabilistic sensitivity analysis (PSA) and Monte Carlo simulation. One-way sensitivity analysis were conducted by adjusting the progression rate, cost of medications or trabeculectomy, cost of follow-up, and surgical acceptance rate. RESULTS: The ICUR of treating mild stage NTG with medication over 10 years was $12743.93 per quality-adjusted life years (QALYs). The ICUR for treating mild stage NTG patients with a 25% and 50% surgery rate with medication were $8798.93 and $4851.93 per QALYs, respectively. In this model, the cost-utility of treating NTG was sensitive to disease progression rate, surgical treatment rate, and medication costs. CONCLUSIONS: According to the results of the cost-utility analysis, it was a reasonable and advantageous strategy to administer a lot of medication and surgery for NTG in the mild stages of the disease. In the model, the greater the probability of patients undergoing surgery, the strategy becomes more valuable.

An HDBB-based fluorescent probe for the sensitive detection of human serum albumin.

The detection of human serum albumin (HSA) in bodily fluids is of great significance in the biomedical area because HSA in bodily fluids is commonly used as a biomarker for the early diagnosis of diseases. To detect HSA, we employed HDBB, 4,4'-(hydrazine-1,2-diylidene bis(methanylylidene)) bis(3-hydroxybenzoic acid), as a fluorescent probe with a large Stokes shift. HDBB had obvious excited state intramolecular proton transfer (ESIPT) and aggregation-induced emission (AIE) features. We elucidated the ESIPT characteristics of HDBB through the DFT approach. We also performed a molecular docking simulation between HDBB and HSA, showing that HDBB primarily bonded to HSA via hydrophobic force and hydrogen bonds. The FL intensities of HDBB with HSA concentrations had a linear range of 0.01-0.2 mg mL-1 (R2 = 0.9995), and the LOD was 1.104 µg mL-1. We also used the probe to detect HSA in urine, with spiked recoveries of 98.10-105.33%. Given its high selectivity and feasible synthesis, HDBB has potential applications in detecting HSA in real biological systems.

BHLHE40 Inhibits Ferroptosis in Pancreatic Cancer Cells via Upregulating SREBF1.

Pancreatic cancer (PCa) is one of the most fatal human malignancies. The enhanced infiltration of stromal tissue into the PCa tumor microenvironment limits the identification of key tumor-specific transcription factors and epigenomic abnormalities in malignant epithelial cells. Integrated transcriptome and epigenetic multiomics analyses of the paired PCa organoids indicate that the basic helix-loop-helix transcription factor 40 (BHLHE40) is significantly upregulated in tumor samples. Increased chromatin accessibility at the promoter region and enhanced mTOR pathway activity contribute to the elevated expression of BHLHE40. Integrated analysis of chromatin immunoprecipitation-seq, RNA-seq, and high-throughput chromosome conformation capture data, together with chromosome conformation capture assays, indicate that BHLHE40 not only regulates sterol regulatory element-binding factor 1 (SREBF1) transcription as a classic transcription factor but also links the enhancer and promoter regions of SREBF1. It is found that the BHLHE40-SREBF1-stearoyl-CoA desaturase axis protects PCa cells from ferroptosis, resulting in the reduced accumulation of lipid peroxidation. Moreover, fatostatin, an SREBF1 inhibitor, significantly suppresses the growth of PCa tumors with high expressions of BHLHE40. This study highlights the important roles of BHLHE40-mediated lipid peroxidation in inducing ferroptosis in PCa cells and provides a novel mechanism underlying SREBF1 overexpression in PCa.