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Abstract Neuroblastoma, the deadliest solid tumor in children, exhibits alarming mortality rates, particularly among high-risk cases. To enhance survival rates, a more precise risk stratification for patients is imperative. Utilizing proteomic data from 34 cases with or without N-Myc amplification, we identified 28 differentially expressed ubiquitination-related proteins (URGs). From these, a prognostic signature comprising 6 URGs was constructed. A nomogram incorporating clinical-pathological parameters yielded impressive AUC values of 0.88, 0.93, and 0.95 at 1, 3, and 5 years, respectively. Functional experiments targeting the E3 ubiquitin ligase FBXO42, a component of the prognostic signature, revealed its TP53-dependent promotion of neuroblastoma cell proliferation. In conclusion, our ubiquitination-related prognostic model robustly predicts patient outcomes, guiding clinical decisions. Additionally, the newfound pro-proliferative role of FBXO42 offers a novel foundation for understanding the molecular mechanisms of neuroblastoma.

Abstract Body heat, a clean and ubiquitous energy source, is promising as a renewable resource to supply wearable electronics. Emerging tough thermogalvanic device could be a sustainable platform to convert body heat energy into electricity for powering wearable electronics if its Carnot-relative efficiency (η r ) reaches ~5%. However, maximizing both the η r and mechanical strength of the device are mutually exclusive. Here, we develop a rational strategy to construct a flexible thermogalvanic armor (FTGA) with a η r over 8% near room temperature, yet preserving mechanical robustness. The key to our design lies in simultaneously realizing the thermosensitive-crystallization and salting-out effect in the elaborately designed ion-transport highway to boost η r and improve mechanical strength. The FTGA achieves an ultrahigh η r of 8.53%, coupling with impressive mechanical toughness of 70.65 MJ m−3 and substantial elongation (~900%) together. Our strategy holds sustainable potential for harvesting body heat and powering wearable electronics without recharging.

A common life-threatening hereditary disease, Cystic Fibrosis (CF), affects primarily Caucasian infants. High sweat-salt levels are observed as a result of a single autosomal mutation in chromosome 7 that affects the critical function of the cystic fibrosis transmembrane regulator (CFTR). For establishing tailored treatment strategies, it is important to understand the broad range of CFTR mutations and their impacts on disease pathophysiology. This study thoroughly investigates the six main classes of classification of CFTR mutations based on their functional effects. Each class is distinguished by distinct molecular flaws, such as poor protein synthesis, misfolding, gating defects, conduction defects, and decreased CFTR expression at the apical membrane. Furthermore, this paper focuses on the emerging field of CFTR modulators, which intend to restore CFTR function or mitigate its consequences. These modulators, which are characterized by the mode of action and targeted mutation class, have the potential to provide personalized therapy regimens in CF patients. This review provides valuable insights into the genetic basis of CF pathology, and highlights the potential for precision medicine methods in CF therapy by thoroughly investigating CFTR mutation classification and related modulators.

Highlights A carbon free self supported Mott-Schottky heterostructure was constructed as an efficient cathode catalyst for lithium oxygen batteries, achieving homogeneous contact between the two materials for strong interfacial interactions. The heterostructure triggered interfacial perturbations and band structure changes, which accelerated oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) kinetics, resulting in an extremely long cycle life of 800 cycles and an extremely low overpotential of 0.73 V. Combined with advanced characterization techniques and density functional theory calculations, the underlying mechanism behind the boosted ORR/OER activities and the electrocatalytic mechanism were revealed.

Abstract The rice blast fungus Magnaporthe oryzae stands as a formidable adversary to one of the world’s most important crops, rice, which feeds over half of the global population. Its ability to rapidly evolve and adapt underscores the urgent need for a comprehensive understanding of its infection strategies. In a large-scale study published in Cell, Cruz-Mireles et al. (Cell 187:2557-73, 2024) utilized phosphoproteomics to globally map the phosphorylation landscape during the infection-related development by M. oryzae, identifying 2062 activated phosphoproteins carrying 8005 phosphosites. A subset of these phosphosites were conserved in the proteins of diverse fungal pathogens and appeared to be associated with biotrophic and hemibiotrophic infection. Thirty-two of these phosphoproteins are regulated by pathogenicity mitogen-activated kinase 1 (Pmk1), a central component of the MAPK signaling pathway, including VTi 1–2 suppressor, whose regulation by Pmk1 is essential for rice blast disease. Together, this global phosphorylation atlas offers a rich tapestry of potential therapeutic targets for developing green agrochemicals to control fungal diseases of plants.

Abstract Along with the constantly evolving functional microsystems toward more diversification, the more rigorous design deliberation of pursuing higher mass‐loading of electrode materials and low‐temperature fabrication compatibility have imposed unprecedented demand on integrable all‐solid‐state thin‐film microbatteries. While the classic thin‐film intercalation cathode prepared by vacuum‐based techniques inevitably encountered a post‐annealing process, tape‐casting technologies hold great merits both in terms of high‐mass loading and low‐temperature processing. In this work, a novel microbattery configuration is developed by the combination of traditional tape‐casting thick electrodes and sputtered inorganic thin‐film solid electrolytes (~3 μm lithium phosphorus oxynitride). Enabled by physically pressed or vapor‐deposited Li as an anode, solid‐state batteries with tape‐casted LiFePO4 electrodes exhibit outstanding cyclability and stability. To meet integration requirements, LiFePO4/LiPON/Si microbatteries were successfully fabricated at low temperatures and found to achieve a wide operating temperature range. This novel configuration has good prospects in promoting the thin‐film microbattery enabling a paradigm shift and satisfying diversified requirements.

Abstract Background Association between glucose and inflammatory bowel disease (IBD) was found in previous observational studies and in cohort studies. However, it is not clear whether these associations reflect causality. Thus, this study investigated whether there is such a causal relation between elevated glucose and IBD, Crohn’s disease (CD) and ulcerative colitis (UC). Methods We performed a two-sample Mendelian Randomization (MR) with the independent genetic instruments identified from the largest available genome-wide association study (GWAS) for IBD (5,673 cases; 213,119 controls) and its main subtypes, CD and UC. Summarized data for glucose which included 200,622 cases and glycemic traits including HbA1c and type 2 diabetes(T2DM) were obtained from different GWAS studies. Primary and secondary analyses were conducted by preferentially using the radial inverse-variance weighted (IVW) approach. A number of other meta-analysis approach and sensitivity analyses were carried out to assess the robustness of the results. Results We did not find a causal effect of genetically predicted glucose on IBD as a whole (OR 0.858; 95% CI 0.649–1.135; P = 0.286). In subtype analyses glucose was also suggestively not associated with Crohn’s disease (OR 0.22; 95% CI 0.04-1.00; P = 0.05) and ulcerative colitis (OR 0.940; 95% CI 0.628–1.407; P = 0.762). In the other direction, IBD and its subtypes were not related to glucose and glycemic traits. Conclusions This MR study is not providing any evidence for a causal relationship between genetically predicted elevated glucose and IBD as well as it’s subtypes UC and CD. Regarding the other direction, no causal associations could be found. Future studies with robust genetic instruments are needed to confirm this conclusion.

Abstract A novel two‐stage profile maximum likelihood estimator is proposed to estimate the source location and the systematic errors jointly, with the aim of addressing the problem of source localisation using angle‐only measurements from a single sensor with unknown sensor altitude and systematic measurement errors. The proposed two‐stage profile maximum likelihood estimator algorithm is capable of decoupling the azimuth and elevation angle measurements while transforming the original maximum likelihood optimisation problem into two sub‐problems, that is, two‐dimensional‐projected maximum likelihood estimator and relative altitude maximum likelihood estimator. In terms of the two‐dimensional‐projected maximum likelihood estimator, an algorithm combining pseudo‐linear estimating and Kalman filtering is proposed to generate an initial estimate. Subsequently, a Gauss–Newton iterative method is developed to estimate the two‐dimensional‐projected target location and the azimuth systematic error jointly. The relative height maximum likelihood estimator is initialised using a pseudo‐linear estimator. Next, a Gauss–Newton iterative algorithm is adopted to estimate the elevation systematic error and the relative height. As indicated by the result of the simulation studies, the proposed algorithm exhibits an estimation performance close to the Cramér–Rao lower bound with unknown sensor altitude and systematic measurement errors.

Abstract Head and neck squamous cell carcinoma (HNSCC) is characterized by high recurrence or distant metastases rate and the prognosis is challenging. There is mounting evidence that tumor-infiltrating B cells (TIL-Bs) have a crucial, synergistic role in tumor control. However, little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade. Using single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, the study identified distinct gene expression patterns in TIL-Bs. HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering. This classification was further validated with TCGA HNSCC data, correlating with patient prognosis, immune cell infiltration, and response to immunotherapy. We found that the B cells activation group exhibited a better prognosis, higher immune cell infiltration, and distinct immune checkpoint levels, including elevated PD-L1. A prognostic model was also developed and validated, highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients. Overall, this study provides a foundational approach for B cells-based tumor classification in HNSCC, offering insights into targeted treatment and immunotherapy strategies.

Abstract Rice blast caused by Pyricularia oryzae (syn., Magnaporthe oryzae) was one of the most destructive diseases of rice throughout the world. Genome assembly was fundamental to genetic variation identification and critically impacted the understanding of its ability to overcome host resistance. Here, we report a gapless genome assembly of rice blast fungus P. oryzae strain P131 using PacBio, Illumina and high throughput chromatin conformation capture (Hi-C) sequencing data. This assembly contained seven complete chromosomes (43,237,743 bp) and a circular mitochondrial genome (34,866 bp). Approximately 14.31% of this assembly carried repeat sequences, significantly greater than its previous assembled version. This assembly had a 99.9% complement in BUSCO evaluation. A total of 14,982 genes protein-coding genes were predicted. In summary, we assembled the first telomere-to-telomere gapless genome of P. oryzae, which would be a valuable genome resource for future research on the genome evolution and host adaptation.

Abstract Interplay between innate and adaptive immune cells is important for the antitumor immune response. However, the tumor microenvironment may turn immune suppressive, and tumor associated macrophages are playing a role in this transition. Here, we show that CD276, expressed on tumor-associated macrophages (TAM), play a role in diminishing the immune response against tumors. Using a model of tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in BLCA male mice we show that genetic ablation of CD276 in TAMs blocks efferocytosis and enhances the expression of the major histocompatibility complex class II (MHCII) of TAMs. This in turn increases CD4 + and cytotoxic CD8 + T cell infiltration of the tumor. Combined single cell RNA sequencing and functional experiments reveal that CD276 activates the lysosomal signaling pathway and the transcription factor JUN to regulate the expression of AXL and MerTK, resulting in enhanced efferocytosis in TAMs. Proving the principle, we show that simultaneous blockade of CD276 and PD-1 restrain tumor growth better than any of the components as a single intervention. Taken together, our study supports a role for CD276 in efferocytosis by TAMs, which is potentially targetable for combination immune therapy.

Abstract Background Herbal nanoparticles are made from natural herbs/medicinal plants, their extracts, or a combination with other nanoparticle carriers. Compared to traditional herbs, herbal nanoparticles lead to improved bioavailability, enhanced stability, and reduced toxicity. Previous research indicates that herbal medicine nanomaterials are rapidly advancing and making significant progress; however, bibliometric analysis and knowledge mapping for herbal nanoparticles are currently lacking. We performed a bibliometric analysis by retrieving publications related to herbal nanoparticles from the Web of Science Core Collection (WoSCC) database spanning from 2004 to 2023. Data processing was performed using the R package Bibliometrix, VOSviewers, and CiteSpace. Results In total, 1876 articles related to herbal nanoparticles were identified, originating from various countries, with China being the primary contributing country. The number of publications in this field increases annually. Beijing University of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, and Saveetha University in India are prominent research institutions in this domain. The Journal “International Journal of Nanomedicine” has the highest number of publications. The number of authors of these publications reached 8234, with Yan Zhao, Yue Zhang, and Huihua Qu being the most prolific authors and Yan Zhao being the most frequently cited author. “Traditional Chinese medicine,” “drug delivery,” and “green synthesis” are the main research focal points. Themes such as “green synthesis,” “curcumin,” “wound healing,” “drug delivery,” and “carbon dots” may represent emerging research areas. Conclusions Our study findings assist in identifying the latest research frontiers and hot topics, providing valuable references for scholars investigating the role of nanotechnology in herbal medicine. Graphical Abstract

IntroductionDue to its remarkable anti-inflammatory pharmacological activity, Farfarae Flos has gained extensive usage in the treatment of various inflammatory diseases such as bronchitis, pneumonia, prostatitis and colitis. And Farfarae Flos come in two color types depending on the color of the flowers: yellowish-white (YW), and purplish-red (PR). However, the difference in anti-inflammatory activity and metabolic profiles between the two flower colors remains unexplored.MethodsThis study aims to explore the difference in the anti-inflammatory potential between YW and PR variants of Farfarae Flos and unravel the mechanisms responsible for the observed differences in anti-inflammatory activity through an integrated approach encompassing untargeted metabolomics and in vivo/vitro experimental studies. Initially, we verified the contrasting effects of YW and PR on the inhibition of the inflammatory factors interleukin-6 (IL-6) and nitric oxide (NO) by utilizing an in vitro RAW 264.7 cell inflammation model. Subsequently, a comprehensive evaluation of the systemic inhibitory capacity of YW and PR on IL-6, Interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) was conducted using a validated whole-body mouse model, followed by the analysis of inflammatory factors and histological examination of collected serum, liver, and spleen after 7 days. Furthermore, non-targeted metabolomics profiling was employed to analyze the metabolite profiles of Farfarae Flos with different colors, and quantitative analysis was conducted to identify differential metabolites between YW and PR. The correlation between the anti-inflammatory activities of differentially accumulated metabolites (DAMs) and Farfarae Flos was investigated, resulting in the identification of 48 compounds exhibiting significant anti-inflammatory activity. Additionally, KEGG pathway enrichment analysis was performed to elucidate the underlying mechanisms.ResultsOur findings demonstrate that both YW and PR possess anti-inflammatory abilities, with PR exhibiting significantly superior efficacy. The integration of in vivo/vitro experiments and non-targeted metabolomics confirmed the exceptional anti-inflammatory potential of PR and solidified its classification as the “purplish-red better” of Farfarae Flos.DiscussionThis study provides valuable insights into the breeding and medical transformation of Farfarae Flos varieties, along with a scientific basis for the establishment of quality standards and the development of new drugs utilizing Farfarae Flos.

The genus Polygala (Polygalaceae), comprising about 670 species worldwide, has more than 40 species in China. The roots of Polygala tenuifolia Willd., Polygala sibirica L., and Polygala japonica Houtt. are recorded in the Chinese Pharmacopeia. Other closely related plants of the Polygala genus are also widely used in the folk medicine of southern China, such as Polygala fallax Hemsl., Polygala arvensis Willd., and Polygala glomerata Lour. To systematically compare the chemical compositional and elucidate characteristic compounds among the Polygala genus, six Polygala species, namely P. tenuifolia, P. sibirica, P. japonica, P. fallax, P. arvensis and P. glomerata, underwent comprehensive phytochemical studies using the ultra performance liquid chromatography-quadrupole time-of-flight tandem mass Spectrometry (UPLC-Q-TOF-MS/MS) technique, resulting in the identification of 154 compounds, consisting of 62 oligosaccharide esters (40.26 %), 58 saponins (37.66 %), 29 xanthones (18.83 %), and 5 other chemicals (3.25 %). Based on the Masslynx computational tool, a comprehensive comparative phytochemical profiling was achieved and revealed differences in composition among the six Polygala species. P. sibirica exhibited higher levels of specific compounds and was more closely related to P. tenuifolia. Meanwhile, P. japonica showed greater similarity to P. fallax, P. arvensis, and P. glomerata. Oligosaccharide esters and triterpene saponins were more abundant in P. sibirica and P. tenuifolia than in other species. Furthermore, the antioxidant activities (1,1-diphenyl-2-acrylohydrazide [DPPH], 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt [ABTS], copper ion reducing antioxidant capacity [CUPRAC], and ferric ion-reducing antioxidant power [FRAP]) of the six species were evaluated. Among them, P. tenuifolia demonstrated superior antioxidant potential, with a lower half-maximal inhibitory concentration (IC50) value for scavenging DPPH radicals and excellence in CUPRAC (119.85 ± 16.28 μM/0.01 g) compared to other plants. P. japonica showed higher ABTS (98.94 ± 0.03 μM/0.01 g) and FRAP (42.58 ± 0.08 μM/0.01 g). Total flavonoids showed remarkable antioxidant capabilities among the six medicinal plants. Total saponins and phenolics also contributed to the antioxidant potential of these plants. The systematic data and results obtained may provide methodological support for further evaluating the potential use of folk Polygala plants as new effective materials in various commercial sectors, including food, cosmetic, and pharmaceutical industries.

During the metamorphosis of anuran amphibians, the tail resorption process is a necessary and crucial change. One subject that has received relatively little or no attention is the expression patterns of proteins and metabolites in the different tail portions during metamorphosis, especially in highland amphibians. The mechanisms of tail resorption in three portions (the tip, middle and root) of the tail were investigated in N. pleskei G43 tadpole based on two omics (proteomic and metabolomic). Integrin αVβ3 was found to be high expressed in the distal portion of the tail, which could improve the sensitiveness to thyroid hormones in the distal portion of the tail. Muscle regression displayed a spatial pattern with stronger regression in distal and weaker one in proximal portion. Probably, this stronger regression was mainly performed by the proteases of proteasome from the active translation by ribosomes. The suicide model and murder model coexisted in the tail resorption. Meanwhile, fatty acids, amino acids, pyrimidine, and purine which derived from the breakdown of tissues can be used as building blocks or energy source for successful metamorphosis. Our data improved a better comprehension of the tail resorption mechanisms underlying the metamorphism of N. pleskei tadpole through identifying important participating proteins and metabolites.

Modifying surface characteristics and geometric structure to regulate heat transfer and flow fields is a classical issue. The study of wake dynamics and heat transfer efficiency in tandem grooved cylinders hold fundamental importance. This research proposes a configuration of tandem cylinders with triangle-grooved surfaces and numerical simulates the vorticity, fluid forces, Strouhal numbers, and convective heat transfer in tandem grooved cylinders. The parameters investigated include orientation angles θ = 0°, 30°, 45°, 60°, 90° and Reynolds numbers Re = 75, 100, 125, 150, 175, 200. This study focuses on how the triangle-grooved angle (θ) and Re affect wake dynamics and thermal performance. Numerical results are validated against available data in the literature for tandem smooth and tandem grooved cylinders. The results indicate that, compared to tandem smooth cylinders, the positive vorticity intensity of tandem grooved cylinders is 35.7 % higher, while the negative vorticity intensity is 23.5 % lower. Further observations show that at θ = 45°, the pressure variation on the upstream cylinder is most significant, approximately twice that at θ = 0° and θ = 90°. Notably, the variation values of the downstream cylinder (β = 0°) at θ = 0° and θ = 45° are triple and double that of the upstream cylinder in TF mode, respectively. Additionally, at θ = 0°, the root mean square lift coefficient of the downstream cylinder reaches the maximum value (Re = 75–100), approximately 1.34. When Re = 125, CL(rms),1 decreases by 15.7 % to 1.13. Particularly, when Re = 100–150, the time-averaged drag coefficient of the downstream cylinder shows a peak value of approximately 1.02. Interestingly, at Re = 200, a tadpole-shaped thermal distribution forms in the wake region of the upstream cylinder. Furthermore, the time-averaged Nusselt number ratio (θ = 0°) exhibits a trend opposite to other cases over a broader range (125 ≤ Re ≤ 200) and peaks at Re = 200, approximately 1.24.

ObjectiveThis study aimed to investigate the use of radiomics features and clinical information by four machine learning algorithms for predicting the prognosis of patients with hepatocellular carcinoma (HCC) who have been treated with transarterial chemoembolization (TACE).MethodsA total of 105 patients with HCC treated with TACE from 2002 to 2012 were enrolled retrospectively and randomly divided into two cohorts for training (n = 74) and validation (n = 31) according to a ratio of 7:3. The Spearman rank, random forest, and univariate Cox regression were used to select the optimal radiomics features. Univariate Cox regression was used to select clinical features. Four machine learning algorithms were used to develop the models: random survival forest, eXtreme gradient boosting (XGBoost), gradient boosting, and the Cox proportional hazard regression model. The area under the curve (AUC) and C-index were devoted to assessing the performance of the models in predicting HCC prognosis.ResultsA total of 1,834 radiomics features were extracted from the computed tomography images of each patient. The clinical risk factors for HCC prognosis were age at diagnosis, TNM stage, and metastasis, which were analyzed using univariate Cox regression. In various models, the efficacy of the combined models generally surpassed that of the radiomics and clinical models. Among four machine learning algorithms, XGBoost exhibited the best performance in combined models, achieving an AUC of 0.979 in the training set and 0.750 in the testing set, demonstrating its strong prognostic prediction capability.ConclusionThe superior performance of the XGBoost-based combined model underscores its potential as a powerful tool for enhancing the precision of prognostic assessments for patients with HCC.

Contribution: This research designs an experimental education project of an automatic material magnetism properties measurement system. It explores how the do-it-yourself (DIY), hands-on establishment, and hardware-software integration experiment system could be leveraged to enhance the understanding of the electromagnetism theory and nonelectrical quantity measurement application. Background: Designing and establishing a prototype of an automatic measurement system are essential, inspiring and beneficial to comprehending and consolidating the theoretical principles and simulations in electromagnetism and nonelectrical quantity measurement technology courses. Furthermore, in the vision of batch deployment and flexible group teaching, a cost-efficiency, hard/soft integration system for the electromagnetism property measurement definitely fits the aim of innovation laboratory education. Intended Outcomes: This project is intended to guide the students to finish a comprehensive research-oriented project loop for multiple skills training. It is also intended to encourage student motivation and confidence through theory investigation, hands-on group collaboration, and tunning for performance calibration. Application Design: The design of the proposed project includes the literature review, hardware selection and assembly, system integration, software programming, interface visualization, and system performance calibration. The participants are assessed with both objective exam questions and subjective open survey for training objectives to reveal their increased knowledge, interests, skill confidence, and creative thinking. Findings: The proposed project has been used in 4-year laboratory open experiments with students at different levels from freshmen undergraduates to 1st-year postgraduates. A use case and survey assessment demonstrate tremendous knowledge, skills, and confidence improvement among students in electromagnetism and measurement technology courses.

The treatment of glioblastoma, the most prevalent malignant tumor in the central nervous system, poses considerable challenges. Glioblastoma multiforme, classified as a grade Ⅳ highly malignant brain glioma by the World Health Organization, is typically managed through a combination of surgery, postoperative chemotherapy, and radiotherapy. The treatment of glioblastoma is complicated by its infiltrative nature, genetic heterogeneity, and presence of the blood-brain barrier. Almost all cases of glioblastoma experience recurrence despite aggressive therapy, exploring the development of updated molecular treatment strategies that can improve overall efficacy. A crucial aspect in modern neurosurgery is the precise delineation of brain regions in terms of their anatomy and function. It serves as the fundamental basis for investigating variations in the distribution of brain gliomas. Hence, this review will elucidate the origin of glioblastomas and analyze the potential factors contributing to the spatially specific distribution of gliomas on the basis of a theoretical framework of brain connectomics research. Molecular characteristics, information pathways, tumor microenvironment landscape, and immunology will inform the analysis. We aim to identify novel biomolecular targets and therapeutic pathways to gain scientific insights for effective glioblastoma treatment.

Hepatitis E is a globally distributed infection that varies in seroprevalence between developed and developing regions. In the less developed regions of Asia and Africa, a high seropositivity rate has been reported for hepatitis E virus (HEV) antibodies. Although acute hepatitis E is often self-limited and has a favorable prognosis, some populations experience severe manifestations, which may progress to liver failure. Moreover, some immunocompromised patients are at risk of developing chronic HEV infection and cirrhosis. Proactive screening, reducing misdiagnosis, improving patient management, timely antiviral therapy for severe and chronic cases, and vaccination of high-risk groups are important measures to reduce the morbidity of hepatitis E. This review focused on the clinical presentation, management, and prevention of hepatitis E.

Abstract Some plant sensor nucleotide-binding leucine-rich repeat (NLR) receptors detect pathogen effectors through their integrated domains (IDs). Rice RGA5 sensor NLR recognizes its corresponding effectors AVR-Pia and AVR1-CO39 from the blast fungus Magnaporthe oryzae through direct binding to its heavy metal-associated (HMA) ID to trigger the RGA4 helper NLR-dependent resistance in rice. Here, we report a mutant of RGA5 named RGA5HMA5 that confers complete resistance in transgenic rice plants to the M. oryzae strains expressing the noncorresponding effector AVR-PikD. RGA5HMA5 carries three engineered interfaces, two of which lie in the HMA ID and the other in the C-terminal Lys-rich stretch tailing the ID. However, RGA5 variants having one or two of the three interfaces, including replacing all the Lys residues with Glu residues in the Lys-rich stretch, failed to activate RGA4-dependent cell death of rice protoplasts. Altogether, this work demonstrates that sensor NLRs require a concerted action of multiple surfaces within and outside the IDs to both recognize effectors and activate helper NLR-mediated resistance, and has implications in structure-guided designing of sensor NLRs.

Abstract Sirtuins, which are NAD+-dependent class III histone deacetylases, are involved in various biological processes, including DNA damage repair, immune inflammation, oxidative stress, mitochondrial homeostasis, autophagy, and apoptosis. Sirtuins are essential regulators of cellular function and organismal health. Increasing evidence suggests that the development of age-related diseases, including kidney diseases, is associated with aberrant expression of sirtuins, and that regulation of sirtuins expression and activity can effectively improve kidney function and delay the progression of kidney disease. In this review, we summarise current studies highlighting the role of sirtuins in renal diseases. First, we discuss sirtuin family members and their main mechanisms of action. We then outline the possible roles of sirtuins in various cell types in kidney diseases. Finally, we summarise the compounds that activate or inhibit sirtuin activity and that consequently ameliorate renal diseases. In conclusion, targeted modulation of sirtuins is a potential therapeutic strategy for kidney diseases. Video Abstract

Abstract Background Rheum palmatum L. has important medicinal value because it contains biologically active anthraquinones. However, the key genes and TFs involved in anthraquinone biosynthesis and regulation in R. palmatum remain unclear. Methods Based on full length transcriptome data, in this study, we screened the differentially expressed genes in the anthraquinone biosynthesis pathway. The R2R3-MYB family genes of R. palmatum were systematically identified based on full-length transcriptome sequencing followed by bioinformatics analyses. The correlation analysis was carried out by using co-expression analysis, protein interaction analysis, and real-time fluorescence quantitative analysis after MeJA treatment. The RpMYB81 and RpMYB98 genes were amplified by RT-PCR, and their subcellular localization and self-activation characteristics were analyzed. Results Comparative transcriptome analysis results revealed a total of 3525 upregulated and 6043 downregulated DEGs in the CK versus MeJA group; 28 DEGs were involved in the anthraquinone pathway. Eleven CHS genes that belonged to the PKS family were differentially expressed and involved in anthraquinone biosynthesis. Twelve differentially expressed MYBs genes were found to be co-expressed and interact with CHS genes. Furthermore, 52 MYB genes were identified as positive regulators of anthraquinone biosynthesis and were further characterized. Three MYB genes including RpMYB81, RpMYB98, and RpMYB100 responded to MeJA treatment in R. palmatum, and the levels of these genes were verified by qRT-PCR. RpMYB81 was related to anthraquinone biosynthesis. RpMYB98 had an interaction with genes in the anthraquinone biosynthesis pathway. RpMYB81 and RpMYB98 were mainly localized in the nucleus. RpMYB81 had self-activation activity, while RpMYB98 had no self-activation activity. Conclusion RpMYB81, RpMYB98, and RpMYB100 were significantly induced by MeJA treatment. RpMYB81 and RpMYB98 are located in the nucleus, and RpMYB81 has transcriptional activity, suggesting that it might be involved in the transcriptional regulation of anthraquinone biosynthesis in R. palmatum.

Improving tactile sensation by vibrating insoles was recommended to prevent foot ulcers in diabetic peripheral neuropathy (DPN). Lack of an insole design for diabetics was a challenge. Clinical trials on applying vibrating insoles with noise and stochastic resonance (SR) stimulating tactile were also required. In this study, vibrating foot orthoses (VFO) with a total contact design based on orthotics were proposed to provide proper insoles for diabetes. This study aimed to determine if VFO were beneficial at enhancing tactile in DPN. VFO were developed in combination with individual’s custom-made foot orthoses and stimulation signals—integrating random 0–100 Hz square wave pulse signals with pseudorandom white noise by a SR approach. Sixty patients with mild-to-severe DPN were randomized to conduct crossover experiments: using and without VFO for 60 minutes stimulation at 90% of individuals’ vibration perception threshold (VPT) level. VPT values when using VFO at the 1st and 5th metatarsophalangeal joints of the left foot decreased by 9.35% ( ${P} \lt $ .001); 9.04% ( ${P} \lt $ .001), and of the right foot decreased by 7.63% ( ${P} \lt $ .001); 7.24% ( ${P}~\lt $ .001), respectively. Without VFO, there was no significant difference. Subgroups of mild and moderate DPN tended to benefit greatly from utilizing VFO. VFO can improve tactile in DPN. VFO may contribute to restoring/prolonging tactile and protective sensations, also decreasing peripheral nervous system deterioration. VFO might be useful for neurorehabilitation, and help prevent foot ulcers and disabilities.

Scoliosis refers to the abnormal curvature of human spine, which is one of the most common deformities in children and adolescents. The Cobb angle is the gold standard for quantifying the severity of scoliosis and is used to assess the severity of scoliosis. Often the accuracy of the Cobb angle measurement relies on the subjective experience of the doctor and the process is very time consuming. In this study, we propose a new deep neural network, ATT UNet 3+, based on UNet 3+. Our approach incorporates a novel hybrid attention mechanism in the network’s upsampling process. This mechanism allows for the appropriate reweighting of fused multi-scale information and facilitates effective supervision of the final output results. The proposed neural network is trained, tested and validated on 155 X-ray ortho-slices. The deep learning network is compared with the more effective neural networks commonly used today. ATT UNet 3+ achieves the best performance in the segmentation evaluation results. Regarding the final Cobb angle calculations, the absolute mean error between the longest distance ellipsoidal point (LDEP) method and expert measurements amounted to 1.6°. ATT UNet 3+ provides a potential tool for segmenting the spine in X-ray, which can improve the efficiency and accuracy of doctors in processing scoliosis pathological images.