Controllable Synthesis of Manganese Organic Phosphate with Different Morphologies and Their Derivatives for Supercapacitors.

Morphological control of metal-organic frameworks (MOFs) at the micro/nanoscopic scale is critical for optimizing the electrochemical properties of them and their derivatives. In this study, manganese organic phosphate (Mn-MOP) with three distinct two-dimensional (2D) morphologies was synthesized by varying the molar ratio of Mn2+ to phenyl phosphonic acid, and one of the morphologies is a unique palm leaf shape. In addition, a series of 2D Mn-MOP derivatives were obtained by calcination in air at different temperatures. Electrochemical studies showed that 2D Mn-MOP derivative calcined at 550 °C and exhibited a superior specific capacitance of 230.9 F g-1 at 0.5 A g-1 in 3 M KOH electrolyte. The aqueous asymmetric supercapacitor and the constructed flexible solid-state device demonstrated excellent rate performance. This performance reveals the promising application of 2D Mn-MOP materials for energy storage.

Untargeted metabolomics combined with chemometrics reveals distinct metabolic profiles across two sparkling cider fermentation stages.

This study aimed to examine the metabolic profiles of Saccharomyces cerevisiae yeasts (WLS21 and Y41) in two phases of sparkling cider making (normal and pressure fermentation) by combining untargeted metabolomic with chemometrics. The results showed that of the 634 nonvolatile metabolites identified using LC-MS and 83 volatile metabolites identified by GC-MS, the differential metabolites were 226 and 54, respectively. Metabolic pathway and correlation analyses showed that aspartic acid, phenylalanine and tyrosine, glutamic acid and purine metabolism were associated with flavor formation. The pressure fermentation process increased apigenin, naringenin, toxifolin, pyridoxine and thiamine contents in the final cider. These findings provide useful information and new research ideas for the formation of flavor in sparkling cider and the regulation of phenolic and vitamin production by microbial stress fermentation.

Retrospective Analysis: Preserving More Subcutaneous Tissue Shows no Increase the Risk of Breast Cancer Recurrence.

BACKGROUND: Radical mastectomy remains the cornerstone procedure for the treatment of breast cancer (BC). However, traditional radical surgeries often lead to complications such as local numbness, pulling sensations, and atrophy of the pectoralis major muscle. In contrast, BC radical surgeries that preserve more tissue have shown potential in reducing these complications. This retrospective study aims to analyze case data from our institution, focusing on the methods of surgeries that preserve more tissue and evaluating the safety and reliability of the follow-up results. METHODS: A retrospective observational study was conducted on cases diagnosed with BC between May 2018 and July 2019 at our institution. The cases were divided into three different surgical groups and followed up for a period of 5 years. The follow-up results were then discussed within each group. RESULTS: A total of 315 cases diagnosed with BC underwent regular follow-ups. The statistical analysis revealed an average age of 45 years and an average tumor size slightly over 2.2 cm, with early-stage BC (Stage I and II) accounting for 90.2% of the cases. The overall survival (OS) and disease-free survival times in the group undergoing total mastectomy with tissue preservation were comparable to those in the traditional radical mastectomy group and the breast-conserving plus radiotherapy group. Moreover, the complication rate, particularly the incidence of chest wall numbness and pulling sensations, was lower in the total mastectomy with tissue preservation group compared to the traditional radical mastectomy group. The overall average follow-up time was 64.4 months, with a recurrence and metastasis rate of 15.6% and an OS rate of 92.7%. CONCLUSION: Based on our follow-up results, total mastectomy with more tissue preservation demonstrates comparable efficacy to breast-conserving surgery and traditional radical mastectomy. It can reduce some complications associated with traditional radical mastectomy and is beneficial for subsequent immediate and delayed breast reconstruction. This approach may be suitable for most patients with early to mid-stage breast cancer who do not wish to undergo breast-conserving surgery.

Plasma exosome-derived miR-455-5p targets RPS6KB1 to regulate cartilage homeostasis in valgus-varus deformity (Gallus gallus).

Valgus-varus deformity (VVD) is a common long bone deformity in broilers. Imbalance in cartilage homeostasis is the main feature of leg disease. Exosomes act as an important intercellular communication vector that regulates chondrogenesis by encapsulating specific nucleic acids and proteins. However, the exact mechanism of how plasma exosomal miRNAs regulate cartilage homeostasis in VVD broilers remains unclear. This study first demonstrated the structural disorder, growth retardation, and reduced proliferative capacity of VVD cartilage in vitro and in vivo. Subsequently, VVD and Normal broiler plasma exosomes were collected for miRNA sequencing. Cartilage-specific miR-455-5p was extraordinarily emphasized by performing bioinformatics analysis on differential miRNA target genes and further validated by tissue expression profiling. PKH67 fluorescently labeled plasma exosomes were shown to be taken up by chondrocytes, deliver miR-455-5p, inhibit chondrocyte proliferation, and disrupt their homeostasis, and these effects could be inhibited by the miR-inhibitors. Mechanistically, MiR-455-5p targets Ribosomal Protein S6 Kinase B1 (RPS6KB1) to inhibit RPS6 phosphorylation and reduce the synthesis of key proteins for cartilage proliferation, which in turn inhibits cartilage proliferation and disrupts its homeostasis. In conclusion, the present study identified abnormalities in VVD cartilage tissue and clarified the specific mechanism by which plasma exosome-derived miR-455-5p regulates cartilage homeostasis.

Paxbp1 is indispensable for the maintenance of epidermal homeostasis.

The mammalian epidermis is a structurally complex tissue that serves critical barrier functions, safeguarding the organism from the external milieu. The development of the epidermis is governed by sophisticated regulatory processes. However, the precise mechanism maintaining epidermal homeostasis remains incompletely elucidated. Recent studies have identified Paxbp1, an evolutionarily conserved protein, as being involved in the developmental regulation of various cells, tissues, and organs. Nonetheless, its role in skin development has not been explored. Here, we report that the targeted deletion of Paxbp1 in epidermal keratinocytes mediated by Keratin14-Cre leads to severe disruption in skin architecture. Mice deficient in Paxbp1 exhibited a substantially reduced epidermal thickness and pronounced separation at the dermo-epidermal junction upon birth. Mechanistically, we demonstrate that the absence of Paxbp1 hinders cellular proliferation, marked by a halt in cell cycle transition, suppressed gene expression of proliferation, and a compromised DNA replication pathway in basal keratinocytes, resulting in the thinning of the skin epidermis. Moreover, molecules and pathways associated with hemidesmosome assembly were impaired in Paxbp1-deficient keratinocytes, culminating in the detachment of the skin epidermal layer. Therefore, our study highlights an indispensable role of Paxbp1 in the maintenance of epidermal homeostasis.

Spontaneous assembly of a class of small molecule prodrugs directed by SN38.

Small molecule self-assembling prodrugs (SAPDs) are an emerging class of amphiphilic monomers that can aggregate into supramolecular nanostructures with high drug loading identical to that of the individual prodrug. Despite great progress in creating nanodrugs via nanoprecipitation, the direct self-assembly of small molecule SAPDs in aqueous solution remains challenging, as the proper hydrophilic-hydrophobic balance and intermolecular interactions have to be rationally considered. We report a class of small molecule SAPDs by conjugating the anticancer drug SN38 as the structure-directing component with various hydrophilic auxiliaries (i.e., oligo ethylene glycol (OEG) of different lengths, amino, and carboxyl groups) via a self-immolative disulfanyl-ethyl carbonate linker. Driven by π-π interactions between SN38 units, these SAPDs spontaneously assembled into well-defined fibrous nanostructures. Variations in hydrophilic domains can robustly regulate the hydrophobicity of SAPDs, as well as the morphologies and surface features of supramolecular filaments, subsequently influencing cellular internalization behaviors. Furthermore, our study also reveals that the parent drug can be efficiently and controllably released in the presence of glutathione (GSH), exhibiting high in vitro toxicity against colorectal cancer cells. In this work, we present a delicate platform to design small molecule SAPDs that can spontaneously self-assemble into supramolecular filamentous assemblies directed by aromatic interaction of the parent drugs, providing a new strategy to optimize supramolecular drug delivery systems.

Cardiac magnetic resonance imaging for discrimination of hypertensive heart disease and hypertrophic cardiomyopathy: a systematic review and meta-analysis.

Introduction: Differentiating hypertensive heart disease (HHD) from hypertrophic cardiomyopathy (HCM) is crucial yet challenging due to overlapping clinical and morphological features. Recent studies have explored the use of various cardiac magnetic resonance (CMR) parameters to distinguish between these conditions, but findings have remained inconclusive. This study aims to identify which CMR parameters effectively discriminate between HHD and HCM and to investigate their underlying pathophysiological mechanisms through a meta-analysis. Methods: The researchers conducted a systematic and comprehensive search for all studies that used CMR to discriminate between HHD and HCM and calculated the Hedges'g effect size for each of the included studies, which were then pooled using a random-effects model and tested for the effects of potential influencing variables through subgroup and regression analyses. Results: In this review, 26 studies encompassing 1,349 HHD and 1,581 HCM cases were included for meta-analysis. Analysis revealed that HHD showed a significant lower in T1 mapping (g = -0.469, P < 0.001), extracellular volume (g = -0.417, P = 0.024), left ventricular mass index (g = -0.437, P < 0.001), and maximal left ventricular wall thickness (g = -2.076, P < 0.001), alongside a significant higher in end-systolic volume index (g = 0.993, P < 0.001) and end-diastolic volume index (g = 0.553, P < 0.001), compared to HCM. Conclusion: This study clearly demonstrates that CMR parameters can effectively differentiate between HHD and HCM. HHD is characterized by significantly lower diffuse interstitial fibrosis and myocardial hypertrophy, along with better-preserved diastolic function but lower systolic function, compared to HCM. The findings highlight the need for standardized CMR protocols, considering the significant influence of MRI machine vendors, post-processing software, and study regions on diagnostic parameters. These insights are crucial for improving diagnostic accuracy and optimizing treatment strategies for patients with HHD and HCM. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023470557, PROSPERO (CRD42023470557).

The Ultrasound Perspective for Sternoclavicular Joint in Spondyloarthritis.

Spondyloarthritis (SpA) is a prevalent genetic disorder that significantly impairs mobility, particularly in the spine, sacroiliac, and peripheral joints. Recent evidence highlights early involvement of the sternoclavicular joint in SpA, which may serve as an initial indicator. Diagnosis often relies on CT and MRI, neglecting ultrasound's potential in identifying SpA-related sternoclavicular arthritis. This review focuses on the joint's anatomy, exploring ultrasound's diagnostic and therapeutic role in SpA-related sternoclavicular arthritis, aiming to provide insights for future ultrasound applications in SpA management.

CRISPR/Cas13a-based rapid detection method for porcine deltacoronavirus.

Background: Porcine deltacoronavirus (PDCoV) is a newly discovered porcine intestinal pathogenic coronavirus with a single-stranded positive-sense RNA genome and an envelope. PDCoV infects pigs of different ages and causes acute diarrhea and vomiting in newborn piglets. In severe cases, infection leads to dehydration, exhaustion, and death in sick piglets, entailing great economic losses on pig farms. The clinical symptoms of PDCoV infection are very similar to those of other porcine enteroviruses. Although it is difficult to distinguish these viral infections without testing, monitoring PDCoV is very important because it can spread in populations. The most commonly used methods for the detection of PDCoV is qPCR, which is time-consuming and require skilled personnel and equipment. Many farms cannot meet the conditions required for detection. Therefore, it is necessary to establish a faster and more convenient method for detecting PDCoV. Aims: To establish a rapid and convenient detection method for PDCoV by combining RPA (Recombinase Polymerase Isothermal Amplification) with CRISPR/Cas13a. Methods: Specific RPA primers and crRNA for PDCoV were designed, and the nucleic acids in the samples were amplified with RPA. Fluorescent CRISPR/Cas13a detection was performed. We evaluated the sensitivity and specificity of the RPA-CRISPR/Cas13a assay using qPCR as the control method. Results: CRISPR/Cas13a-assisted detection was completed within 90 min. The minimum detection limit of PDCoV was 5.7 × 101 copies/µL. A specificity analysis showed that the assay did not cross-react with three other porcine enteroviruses. Conclusion: The RPA-CRISPR/Cas13a method has the advantages of high sensitivity, strong specificity, fast response, and readily accessible results, and can be used for the detection of PDCoV.

Whole genome sequencing insight into carbapenem-resistant and multidrug-resistant Acinetobacter baumannii harboring chromosome-borne blaOXA-23.

Carbapenem-resistant Acinetobacter baumannii (CRAB) poses a significant threat to hospitalized patients as effective therapeutic options are scarce. Based on the genomic characteristics of the CRAB strain AB2877 harboring chromosome-borne blaOXA-23, which was isolated from the bronchoalveolar lavage fluid (BALF) of a patient in a respiratory intensive care unit (RICU), we systematically analyzed antibiotic resistance genes (ARGs) and the genetic context associated with ARGs carried by CRAB strains harboring chromosome-borne blaOXA-23 worldwide. Besides blaOXA-23, other ARGs were detected on the chromosome of the CRAB strain AB2877 belonging to ST208/1806 (Oxford MLST scheme). Several key genetic contexts associated with the ARGs were identified on the chromosome of the CRAB strain AB2877, including (1) the MDR region associated with blaOXA-23, tet(B)-tetR(B), aph(3'')-Ib, and aph(6)-Id (2); the resistance island AbGRI3 harboring armA and mph(E)-msr(E) (3); the Tn3-like composite transposon containing blaTEM-1D and aph(3')-Ia; and (4) the structure "ISAba1-blaADC-25." The first two genetic contexts were most common in ST195/1816, followed by ST208/1806. The last two genetic contexts were found most frequently in ST208/1806, followed by ST195/1816.IMPORTANCEThe blaOXA-23 gene can be carried by plasmid or chromosome, facilitating horizontal genetic transfer and increasing carbapenem resistance in healthcare settings. In this study, we focused on the genomic characteristics of CRAB strains harboring the chromosome-borne blaOXA-23 gene, and the important genetic contexts associated with blaOXA-23 and other ARGs were identified, and their prevalent clones worldwide were determined. Notably, although the predominant clonal CRAB lineages worldwide containing the MDR region associated with blaOXA-23, tet(B)-tetR(B), aph(3'')-Ib, and aph (6)-Id was ST195/1816, followed by ST208/1806, the CRAB strain AB2877 in our study belonged to ST208/1806. Our findings contribute to the knowledge regarding the dissemination of CRAB strains and the control of nosocomial infection.

DNA hydrogels and their derivatives in biomedical engineering applications.

Deoxyribonucleotide (DNA) is uniquely programmable and biocompatible, and exhibits unique appeal as a biomaterial as it can be precisely designed and programmed to construct arbitrary shapes. DNA hydrogels are polymer networks comprising cross-linked DNA strands. As DNA hydrogels present programmability, biocompatibility, and stimulus responsiveness, they are extensively explored in the field of biomedicine. In this study, we provide an overview of recent advancements in DNA hydrogel technology. We outline the different design philosophies and methods of DNA hydrogel preparation, discuss its special physicochemical characteristics, and highlight the various uses of DNA hydrogels in biomedical domains, such as drug delivery, biosensing, tissue engineering, and cell culture. Finally, we discuss the current difficulties facing DNA hydrogels and their potential future development.

A ternary heterostructure aptasensor based on metal-organic framework and polydopamine nanoparticles for fluorescent detection of sulfamethazine.

Residue of sulfamethazine (SMZ), a typical short-acting drug to prevent bacterial infections, in food is a threat to human health. A ternary heterogeneous metal-organic framework hybrid (Zn/Fe-MOF@PDANSs) of Zn-TCPP-MOF, MIL-101 (Fe) and polydopamine nanoparticles (PDANSs) was proposed to establish an aptasensor for the sensitive and selective detection of SMZ. In this sensor, Zn-TCPP-MOF and FAM emitted fluorescence at 609 nm and 523 nm, respectively, and the fluorescence of FAM-ssDNA could be quenched when it was adsorbed on the surface of MOF hybrid. In the presence of SMZ, the fluorescence of FAM-ssDNA recovered due to the dropping from MOF hybrid, while the fluorescence of MOF hybrid remained. With this strategy, a wide concentration range and high sensitivity of SMZ were detection. And the ternary Zn/Fe-MOF@PDANSs sensor exhibited more excellent performance than binary Zn/Fe-MOF aptasensor. In addition, the sensor showed pleasurable selectivity, and was utilized for SMZ determination in authentic chicken and pork samples, implying the fascinating potential in practical application.

Pharmacokinetics and safety of mavacamten in healthy Chinese participants with different CYP2C19 phenotypes.

Obstructive hypertrophic cardiomyopathy (oHCM) is a subtype of HCM characterized by left ventricular outflow tract obstruction resulting from cardiac muscle hypertrophy and anatomic alterations in the mitral valve and apparatus. Mavacamten, a cardiac myosin inhibitor metabolized primarily by CYP2C19 in the liver, is the first and only targeted medication approved for the treatment of symptomatic New York Heart Association (NYHA) class II-III oHCM. Previous pharmacokinetic (PK) results of mavacamten in healthy Caucasian, Japanese, and Asian participants demonstrated that mavacamten exposure was affected by CYP2C19 metabolism status. This open-label, parallel-group, phase I trial aimed to determine the PK and safety of mavacamten in healthy Chinese participants with different CYP2C19 genotypes. The primary outcome was to define the PK of mavacamten in healthy Chinese participants; the secondary outcome was to examine safety and tolerability. After a single oral dose of 15 or 25 mg mavacamten in fasted healthy adult Chinese individuals, Cmax was reached within a median Tmax of 0.6-1.5 h, indicating rapid absorption. Inter-individual variability was moderate, and individuals carrying non-functional CYP2C19 alleles (*2/*2, *3/*3, or *2/*3) exhibited longer half-life and increased total exposure. After stratification of CYP2C19 genotypes, total mavacamten exposures were similar among different ethnic groups when compared with prior PK studies. No significant adverse events were observed in this study. Single oral administration of mavacamten at 15 mg was well tolerated across all CYP2C19 genotypes, and 25 mg dose was well tolerated in healthy participants with CYP2C19 genotypes UM/RM/NM. The PK profile of mavacamten in the healthy Chinese population was consistent with that in other healthy populations.

Achieved High-Sensitivity Single-Band Ratiometric Optical Thermometry by Manipulating the Intervalence Charge-Transfer Band Position.

Currently, optical thermometry has received widespread attention because of its noncontact and wide temperature range, but most of them are based on the application of dual-band optical ratiometric thermometry, so the development of a single-band ratiometric (SBR) optical thermometry, which is easier to analyze and use, is particularly important. In this work, the position of the intervalence charge-transfer (IVCT) band for Na2Gd2-xLaxTi3O10:Pr3+ (x = 0, 0.5, 1.0, 1.5, 2.0) was modulated using Gd/La substitution, enhancing the thermal response difference of Pr3+ 1D2 → 3H4 under charge-transfer band (CTB) and IVCT band excitation, thereby achieving high-sensitivity SBR optical thermometry, and the maximum relative sensitivity (Sr-max) reached 2.95% (at 298 K). In addition, this series of phosphors has high-color-purity red emission, indicating that it has potential for multifield applications.

Identification of differential m6A RNA methylomes and ALKBH5 as a potential prevention target in the developmental neurotoxicity induced by multiple sevoflurane exposures.

Sevoflurane, as a commonly used inhaled anesthetic for pediatric patients, has been reported that multiple sevoflurane exposures are associated with a greater risk of developing neurocognitive disorder. N6-Methyladenosine (m6A), as the most common mRNA modification in eukaryotes, has emerged as a crucial regulator of brain function in processes involving synaptic plasticity, learning and memory, and neurodevelopment. Nevertheless, the relevance of m6A RNA methylation in the multiple sevoflurane exposure-induced developmental neurotoxicity remains mostly elusive. Herein, we evaluated the genome-wide m6A RNA modification and gene expression in hippocampus of mice that received with multiple sevoflurane exposures using m6A-sequencing (m6A-seq) and RNA-sequencing (RNA-seq). We discovered 19 genes with differences in the m6A methylated modification and differential expression in the hippocampus. Among these genes, we determined that a total of nine differential expressed genes may be closely associated with the occurrence of developmental neurotoxicity induced by multiple sevoflurane exposures. We further found that the alkB homolog 5 (ALKBH5), but not methyltransferase-like 3 (METTL3) and Wilms tumor 1-associated protein (WTAP), were increased in the hippocampus of mice that received with multiple sevoflurane exposures. And the IOX1, as an inhibitor of ALKBH5, significantly improved the learning and memory defects and reduced neuronal damage in the hippocampus of mice induced by multiple sevoflurane exposures. The current study revealed the role of m6A methylated modification and m6A-related regulators in sevoflurane-induced cognitive impairment, which might provide a novel insight into identifying biomarkers and therapeutic strategies for inhaled anesthetic-induced developmental neurotoxicity.

Establishing carbon dots assisted high speed countercurrent chromatography and its application for efficient separation of rare earth element ions.

Rare earth elements with unique magnetic properties and optical properties, known as the 'industrial vitamin', has a very high commercial value. As a secondary resource of rare earth elements, low-concentration solution includes mixed rare earth ions, which need to realize efficient separation and recovery urgently. High speed countercurrent chromatography is suitable for the separation and purification of rare earth element ions due to its advantages of large loading, good tolerance to samples, and simple pretreatment. In this study, a carbon dots assisted high speed countercurrent chromatography method was designed and established, the carbon dots were applied to the mobile phase of high speed countercurrent chromatography for the first time. The low concentration of REEs solution was enriched, and the effective separation of La (III), Ce (III), Gd (III) and Er (III) was successfully achieved. The complete separation of La (III), Ce (III), Gd (III) and Er (III) was achieved with a solvent system of 0.05 mol L-1 P507 (PE), 0.05 mol L-1 HNO3, and 0.1 mol L-1 CDs2 carbon dots (1:1:0.01, v/v/v), the upper phase as stationary phase, the lower phase as mobile phase. Density functional theory result showed that the binding energy of REEs (III)-CDs2 was larger than that of REEs (III)-P507, so the affinity of CDs2 to REEs (III) was stronger than that of P507. Therefore, with the addition of CDs2, the ability of mobile phase to elute REEs from the stationary phase was enhanced, and the separation effect was improved.

Confining Iodine into Metal-Organic Framework Derived Metal-Nitrogen-Carbon for Long-Life Aqueous Zinc-Iodine Batteries.

Aqueous zinc-iodine batteries (AZIBs) are highly appealing for energy requirements owing to their safety, cost-effectiveness, and scalability. However, the inadequate redox kinetics and severe shuttling effect of polyiodide ions impede their commercial viability. Herein, several Zn-MOF-derived porous carbon materials are designed, and the further preparation of iron-doped porous carbon (Fe-N-C, M9) with varied Fe doping contents is optimized based on a facile self-assembly/carbonization approach. M9, with atomic Fe coordinated to nitrogen atoms, is employed as an efficient cathode host for AZIBs. Functional modifications of porous carbon hosts involving the doping species and levels are investigated. The adsorption tests, in situ Raman spectroscopy, and in situ UV-vis results demonstrate the adsorption capability and charge-discharge mechanism for the iodine species. Furthermore, experimental findings and theoretical analyses have proven that the redox conversion of iodine is enhanced through a physicochemical confinement effect. This study offers basic principles for the strategic design of single-atom dispersed carbon as an iodine host for high-performance AZIBs. Flexible soft-pack battery and wearable microbattery applications also have implications for future long-life aqueous battery designs.

AI-Based multimodal Multi-tasks analysis reveals tumor molecular heterogeneity, predicts preoperative lymph node metastasis and prognosis in papillary thyroid carcinoma: A retrospective study.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the predominant form of thyroid cancer globally, especially when lymph node metastasis (LNM) occurs. Molecular heterogeneity, driven by genetic alterations and tumor microenvironment components, contributes to the complexity of PTC. Understanding these complexities is essential for precise risk stratification and therapeutic decisions. METHODS: This study involved a comprehensive analysis of 521 patients with PTC from our hospital and 499 patients from The Cancer Genome Atlas (TCGA). The real-world cohort 1 comprised 256 patients with stage I-III PTC. Tissues from 252 patients were analyzed by DNA-based next-generation sequencing, and tissues from four patients were analyzed by single-cell RNA sequencing (scRNA-seq). Additionally, 586 PTC pathological sections were collected from TCGA, and 275 PTC pathological sections were collected from the real-world cohort 2. A deep learning multimodal model was developed using matched histopathology images, genomic, transcriptomic, and immune cell data to predict LNM and disease-free survival (DFS). RESULTS: This study included a total of 1,011 PTC patients, comprising 256 patients from cohort 1, 275 patients from cohort 2, and 499 patients from TCGA. In cohort 1, we categorized PTC into four molecular subtypes based on BRAF, RAS, RET, and other mutations. BRAF mutations were significantly associated with LNM and impacted DFS. ScRNA-seq identified distinct T cell subtypes and reduced B cell diversity in BRAF-mutated PTC with LNM. The study also explored cancer-associated fibroblasts and macrophages, highlighting their associations with LNM. The deep learning model was trained using 405 pathology slides and RNA sequences from 328 PTC patients and validated with 181 slides and RNA sequences from 140 PTC patients in the TCGA cohort. It achieved high accuracy, with an AUC of 0.86 in the training cohort, 0.84 in the validation cohort, and 0.83 in the real-world cohort 2. High-risk patients in the training cohort had significantly lower DFS rates (P<0.001). Model AUCs were 0.91 at 1 year, 0.93 at 3 years, and 0.87 at 5 years. In the validation cohort, high-risk patients also had lower DFS (P<0.001); the AUCs were 0.89, 0.87, and 0.80 at 1, 3, and 5 years. We utilized the GradCAM algorithm to generate heatmaps from pathology-based deep learning models, which visually highlighted high-risk tumor areas in PTC patients. This enhanced clinicians' understanding of the model's predictions and improved diagnostic accuracy, especially in cases with lymph node metastasis. CONCLUSION: The AI-based analysis uncovered vital insights into PTC molecular heterogeneity, emphasizing BRAF mutations' impact. The integrated deep learning model shows promise in predicting metastasis, offering valuable contributions to improved diagnostic and therapeutic strategies.

Dietary restriction promote sperm remodeling in aged roosters based on transcriptome analysis.

BACKGROUND: The breeder rooster has played a pivotal role in poultry production by providing high-quality semen. Typically, fertility peaks between 30 and 40 weeks of age and then declines rapidly from 45 to 55 weeks of age. Research into improving fertility in aging roosters is essential to extend their productive life. While progress has been made, enhancing fertility in aging roosters remains a significant challenge. METHODS: To identify the genes related to promoting sperm remodeling in aged Houdan roosters, we combined changes in testis and semen quality with transcriptome sequencing (RNA-seq) to analyze the synchrony of semen quality and testis development. In this study, 350-day-old Houdan breeder roosters were selected for RNA-seq analysis in testis tissues from induced molting roosters (D group) and non-induced molting roosters (47DG group). All analyses of differentially expressed genes (DEGs) and functional enrichment were performed. Finally, we selected six DEGs to verify the accuracy of the sequencing by qPCR. RESULTS: Compared with the 47DG group, sperm motility (P < 0.05), sperm density (P < 0.01), and testis weight (P < 0.05) were significantly increased in roosters in the D group. Further RNA-seq analysis of the testis between the D group and 47DG group identified 61 DEGs, with 21 up-regulated and 40 down-regulated. Functional enrichment analysis showed that the DEGs were primarily enriched in the cytokine-cytokine receptor interaction, Wnt signaling pathway, MAPK signaling pathway, TGF-ß signaling pathway, and focal adhesion pathway. The qRT-PCR results showed that the expression trend of these genes was consistent with the sequencing results. WNT5A, FGFR3, AGTR2, TGFß2, ROMO1, and SLC26A7 may play a role in testis development and spermatogenesis. This study provides fundamental data to enhance the reproductive value of aging roosters.

High-Concentrated Binary-Salt Ether Electrolytes for High-Voltage Lithium Metal Batteries with Ni-Rich Cathode.

The incompatibility of ether electrolytes with a cathode dramatically limits its application in high-voltage Li metal batteries. Herein, we report a new highly concentrated binary salt ether-based electrolyte (HCBE, 1.25 M LiTFSI + 2.5 M LiFSI in DME) that enables stable cycling of high-voltage lithium metal batteries with the Ni-rich (NCM83, LiNi0.83Co0.12Mn0.05O2) cathode. Experimental characterizations and density functional theory (DFT) calculations reveal the special solvation structure in HCBE. A solvation structure rich in aggregates (AGGs) can effectively broaden the electrochemical window of the ether electrolyte. The anions in HCBE preferentially decompose under high voltage, forming a CEI film rich in inorganic components to protect the electrolyte from degradation. Thus, the high-energy-density Li||NCM83 cell has a capacity retention of ≈95% after 150 cycles. Significantly, the cells in HCBE have a high and stable average Coulombic efficiency of over 99.9%, much larger than that of 1 M LiPF6 + EC + EMC + DMC (99%). The result emphasizes that the anionic-driven formation of a cathode electrolyte interface (CEI) can reduce the number of interface side reactions and effectively protect the cathode. Furthermore, the Coulombic efficiency of Li||Cu using the HCBE is 98.5%, underscoring the advantages of using ether-based electrolytes. This work offers novel insights and approaches for the design of high-performance electrolytes for lithium metal batteries.