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Abstract In response to the challenge of telomere attrition during DNA replication, cancer cells predominantly employ telomerase or, in 10–15% of cases, the alternative lengthening of telomeres (ALT). The intricate details of ALT, however, remain elusive. In this study, we unveil that the knockdown of lamina-associated polypeptide 2 alpha (LAP2α) in ALT cells results in telomere dysfunction, triggering a notable increase in ALT-associated hallmarks, including high frequencies of PML bodies (APBs), C-rich extrachromosomal circles (C-circles), and telomere sister chromatid exchange (T-SCE). Furthermore, LAP2α emerges as a crucial player in break-induced telomere replication for telomerase-positive cells following telomeric double-strand breaks. Mechanistically, our investigation suggests that LAP2α may influence the regulation of the heterochromatic state of telomeres, thereby affecting telomeric accessibility. In line with our findings, LAP2α expression is markedly reduced in ALT-positive osteosarcoma. And the use of methotrexate (MTX) can restore the heterochromatin state altered by LAP2α depletion. This is evidenced by a significant inhibition of tumor proliferation in ALT-positive patient-derived xenograft (PDX) mouse models. These results indicate the important role of LAP2α in regulating ALT activity and offer insights into the interplay between lamina-associated proteins and telomeres in maintaining telomere length. Importantly, our findings may help identify a more appropriate target population for the osteosarcoma therapeutic drug, MTX.

Abstract The genetic analysis of potato is hampered by the complexity of tetrasomic inheritance. An ongoing effort aims to transform the clonally propagated tetraploid potato into a seed-propagated diploid crop, which would make genetic analyses much easier owing to disomic inheritance. Here, we construct and report the large-scale genetic and heterotic characteristics of a diploid F2 potato population derived from the cross of two highly homozygous inbred lines. We investigate 20,382 traits generated from multi-omics dataset and identify 25,770 quantitative trait loci (QTLs). Coupled with gene expression data, we construct a systems-genetics network for gene discovery in potatoes. Importantly, we explore the genetic basis of heterosis in this population, especially for yield and male fertility heterosis. We find that positive heterotic effects of yield-related QTLs and negative heterotic effects of metabolite QTLs (mQTLs) contribute to yield heterosis. Additionally, we identify a PME gene with a dominance heterotic effect that plays an important role in male fertility heterosis. This study provides genetic resources for the potato community and will facilitate the application of heterosis in diploid potato breeding.

Abstract The surge in advanced imaging techniques has generated vast biomedical image data with diverse dimensions in space, time and spectrum, posing big challenges to conventional compression techniques in image storage, transmission, and sharing. Here, we propose an intelligent image compression approach with the first-proved semantic redundancy of biomedical data in the implicit neural function domain. This Semantic redundancy based Implicit Neural Compression guided with Saliency map (SINCS) can notably improve the compression efficiency for arbitrary-dimensional image data in terms of compression ratio and fidelity. Moreover, with weight transfer and residual entropy coding strategies, it shows improved compression speed while maintaining high quality. SINCS yields high quality compression with over 2000-fold compression ratio on 2D, 2D-T, 3D, 4D biomedical images of diverse targets ranging from single virus to entire human organs, and ensures reliable downstream tasks, such as object segmentation and quantitative analyses, to be conducted at high efficiency.

Abstract Clarification of the cytotoxic function of T cells is crucial for understanding human immune responses and immunotherapy procedures. Here, we report a high-throughput Bessel oblique plane microscopy (HBOPM) platform capable of 3D live imaging and phenotyping of chimeric antigen receptor (CAR)-modified T-cell cytotoxicity against cancer cells. The HBOPM platform has the following characteristics: an isotropic subcellular resolution of 320 nm, large-scale scouting over 400 interacting cell pairs, long-term observation across 5 hours, and quantitative analysis of the Terabyte-scale 3D, multichannel, time-lapse image datasets. Using this advanced microscopy platform, several key subcellular events in CAR-T cells are captured and comprehensively analyzed; these events include the instantaneous formation of immune synapses and the sustained changes in the microtubing morphology. Furthermore, we identify the actin retrograde flow speed, the actin depletion coefficient, the microtubule polarization and the contact area of the CAR-T/target cell conjugates as essential parameters strongly correlated with CAR-T-cell cytotoxic function. Our approach will be useful for establishing criteria for quantifying T-cell function in individual patients for all T-cell-based immunotherapies.

Highlights FGN-182 electrolytes exhibit highly reversible Li plating/stripping with an average Coulombic efficiency reaching up to 99.56% determined from Auerbach’s test. The gas-evolution process of LiNO3 in high-voltage lithium cobalt oxide (LCO) cathodes is revealed by in situ differential electrochemical mass spectrometry. Pouch cells equipped with high-loading LCO (3 mAh cm−2) cathodes, ultrathin Li chips (25 μm), and lean electrolytes (5 g Ah−1) using optimized electrolyte (FGN-182 + 1%HTCN) demonstrate outstanding cycling performance.

Abstract Background Ornithine carbamoyltransferase deficiency (OTCD) is a kind of X-linked metabolic disease caused by a deficiency in ornithine transcarbamylase leading to urea cycle disorders. The main reason is that the OTC gene variants lead to the loss or decrease of OTC enzyme function, which hinders the ammonia conversion to urea, resulting in hyperammonemia and severe neurological dysfunction. Here, we studied one Chinese family of three generations who consecutively gave birth to two babies with OTCD. This study aims to explore the pathogenicity of two missense variants in the OTC gene and investigate the application of preimplantation genetic testing for monogenic (PGT-M) for a family troubled by Ornithine carbamoyltransferase deficiency (OTCD). Methods The retrospective method was used to classify the pathogenicity of two missense variants in the OTC gene in a family tortured by OTCD. Sanger sequencing was used to validate the variants in the OTC gene, and then the pathogenicity of variants was confirmed through family analysis and bioinformatics software. We used PGT-M to target the OTC gene and select a suitable embryo for transplantation. Prenatal diagnosis was recommended to confirm previous results using Sanger sequencing and karyotyping at an appropriate gestational stage. Tandem mass spectrometry (MS-MS) and gas chromatography-mass spectrometry (GC-MS) were used to detect fetal metabolism after birth. The number of the study cohort is ChiCTR2100053616. Results Two missense variants, c.959G > C (p.Arg320Pro) and c.634G > A (p.Gly212Arg), were validated in the OTC gene in this family. According to the ACMG genetic variation classification criteria, the missense variant c.959G > C can be considered as “pathogenic”, and the missense variant c.634G > A can be regarded as “likely benign.” PGT-M identified a female embryo carrying the heterozygous variant c.959G > C (p.Arg320Pro), which was selected for transplantation. Prenatal diagnosis revealed the same variant in the fetus, and continued pregnancy was recommended. A female baby was born, and her blood amino acid testing and urine organic acid testing were regular. Follow-up was conducted after six months and indicated the girl was healthy. Conclusion Our research first validated the segregation of both c.959G > C and c.634G > A variants in the OTC gene in a Chinese OTCD family. Then, we classified variant c.959G > C as “pathogenic” and variant c.634G > A as “likely benign”, providing corresponding theoretical support for genetic counseling and fertility guidance in this family. PGT-M and prenatal diagnosis were recommended to help the couple receive a female baby successfully with a six-month follow-up.

Abstract The relationship between bone mineral density and type 2 diabetes is still controversial. The aim of this study is to investigate the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) in elderly men and postmenopausal women. The participants in this study included 692 postmenopausal women and older men aged ≥ 50 years, who were divided into the T2DM group and non-T2DM control group according to whether or not they had T2DM. The data of participants in the two groups were collected from the inpatient medical record system and physical examination center systems, respectively, of the Tertiary Class A Hospital. All data analysis is performed in SPSS Software. Compared with all T2DM group, the BMD and T scores of lumbar spines 1–4 (L1–L4), left femoral neck (LFN) and all left hip joints (LHJ) in the non-T2DM group were significantly lower than those in the T2DM group (P

Abstract Background This study aims to investigate relative peripheral refractive (RPR) characteristics in children with non-amblyopic myopic anisometropia and explore potential associations between relative peripheral refractive errors (RPRE) and myopia. Methods Relative peripheral refractive errors were assessed in 64 children diagnosed with non-amblyopic myopic anisometropia utilizing multispectral refraction topography (MRT). Two eyes of each patient were divided into into the more myopia eyes group (ME) and the fellow eyes group (FE). Evaluated parameters encompassed total defocus values (TRDV), defocus values at eccentricities spanning 0 to 15 degrees (RDV-15), 0 to 30 degrees (RDV-30), 0 to 45 degrees (RDV-45), as well as superior (RDV-S), inferior (RDV-I), temporal (RDV-T), and nasal (RDV-N) positions. Results The study revealed a noteworthy contrast in TRDV values between Group ME (0.52 ± 0.36) and Group FE (0.17 ± 0.41), with a substantial significance (P 0.05), a meaningful RDV-30 difference existed between Group ME (0.11 ± 0.14) and Group FE (0.03 ± 0.19) (P = 0.0017). A significant discrepancy in RDV-45 was also observed between Group ME (0.39 ± 0.29) and Group FE (0.13 ± 0.34) (P 0.05). Conclusion Eyes exhibiting greater myopia manifested more hyperopic peripheral defocus in the context of anisometropia. MRT as a novel ophthalmic evaluation technique, holds promising potential for broader clinical applications in the future.

Abstract Background Male infertility has become a global health problem, and genetic factors are one of the essential causes. Y chromosome microdeletion is the leading genetic factor cause of male infertility. The objective of this study is to investigate the correlation between male infertility and Y chromosome microdeletions in Hainan, the sole tropical island province of China. Methods We analyzed the semen of 897 infertile men from Hainan in this study. Semen analysis was measured according to WHO criteria by professionals at the Department of Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, where samples were collected. Y chromosome AZF microdeletions were confirmed by detecting six STS markers using multiple polymerase chain reactions on peripheral blood DNA. The levels of reproductive hormones, including FSH, LH, PRL, T, and E2, were quantified using the enzyme-linked immunosorbent assay (ELISA). Results The incidence of Y chromosome microdeletion in Hainan infertile men was 7.13%. The occurrence rate of Y chromosome microdeletion was 6.69% (34/508) in the oligozoospermia group and 7.71% (30/389) in the azoospermia group. The deletion of various types in the AZF subregion was observed in the group with azoospermia, whereas no AZFb deletion was detected in the oligozoospermia group. Among all patients with microdeletions, the deletion rate of the AZFc region was the higher at 68.75% (44 out of 64), followed by a deletion rate of 6.25% (4 out of 64) for the AZFa region and a deletion rate of 4.69% (3 out of 64) for the AZFb region. The deletion rate of the AZFa region was significantly higher in patients with azoospermia than in patients with oligozoospermia (0.51% vs. 0.39%, p

As the global incidence of breast cancer continues to surge, the pursuit of novel, low-toxicity, and highly efficacious therapeutic strategies has emerged as a pivotal research focus. Curcumin (CUR), an active constituent of traditional Chinese medicine (TCM) renowned for its antimicrobial, anti-inflammatory, antioxidant, and antitumor properties, exhibits immense potential in breast cancer therapy. Nevertheless, CUR's poor water solubility, chemical instability, and unfavorable pharmacokinetics have impeded its clinical utilization. To address these challenges, nano-delivery systems have been extensively exploited for CUR administration, enhancing its in vivo stability and bioavailability, and facilitating precise targeting of breast cancer lesions. Therefore, we elaborate on CUR's chemical foundations, drug metabolism, and safety profile, and elucidate its potential mechanisms in breast cancer therapy, encompassing inducing apoptosis and autophagy, blocking cell cycle, inhibiting breast cancer metastasis, regulating tumor microenvironment and reversing chemotherapy resistance. The review primarily emphasizes recent advancements in CUR-based nano-delivery systems for the treatment and diagnosis of breast cancer. Liposomes, nanoparticles (encompassing polymer nanoparticles, solid lipid nanoparticles, mesoporous silica particles, metal/metal oxide nanoparticles, graphene nanomaterials, albumin nanoparticles, etc.), nanogels, and nanomicelles can serve as delivery carriers for CUR, exhibiting promising anti-breast cancer effects in both in vivo and in vitro experiments. Furthermore, nano-CUR can be integrated with fluorescence imaging, magnetic resonance imaging, computed tomography imaging, ultrasound, and other techniques to achieve precise localization and diagnosis of breast cancer masses. While this article has summarized the clinical studies of nano-curcumin, it is noteworthy that the research literature on nano-CUR applied to breast cancer diagnosis and the translation of nano-CUR clinical studies in BC patients remain limited. Therefore, future research should intensify exploration in this direction.

The indiscriminate use of antibiotics has resulted in a growing resistance to drugs in Pseudomonas aeruginosa. The identification of antibiotic resistance genes holds considerable clinical significance for prompt diagnosis. In this study, we established and optimized a Recombinase-Aided Amplification (RAA) assay to detect two genes associated with drug resistance, oprD and arr, in 101 clinically collected P. aeruginosa isolates. Through screening for the detection or absence of oprD and arr, the results showed that there were 52 Imipenem-resistant P. aeruginosa (IRPA) strains and 23 Rifampin-resistant P. aeruginosa (RRPA) strains. This method demonstrated excellent detection performance even when the sample concentration is 10 copies/μL at isothermal conditions and the results could be obtained within 20 minutes. The detection results were in accordance with the results of conventional PCR and Real-time PCR. The detection outcomes of the arr gene were consistently with the resistance spectrum. However, the antimicrobial susceptibility results revealed that 65 strains were resistant to imipenem, while 49 strains sensitive to imipenem with oprD were identified. This discrepancy could be attributed to genetic mutations. In summary, the RAA has higher sensitivity, shorter time, and lower-cost instrument requirements than traditional detection methods. In addition, to analyze the epidemiological characteristics of the aforementioned drug-resistant strains, we conducted Multilocus Sequence Typing (MLST), virulence gene, and antimicrobial susceptibility testing. MLST analysis showed a strong correlation between the sequence types ST-1639, ST-639, ST-184 and IRPA, while ST-261 was the main subtype of RRPA. It was observed that these drug-resistant strains all possess five or more virulence genes, among which exoS and exoU do not coexist, and they are all multidrug-resistant strains. The non-coexistence of exoU and exoS in P.aeruginosa is related to various factors including bacterial regulatory mechanisms and pathogenic mechanisms. This indicates that the relationship between the presence of virulence genes and the severity of patient infection is worthy of attention. In conclusion, we have developed a rapid and efficient RAA (Recombinase-Aided Amplification) detection method that offers significant advantages in terms of speed, simplicity, and cost-effectiveness (especially in time and equipment aspect). This novel approach is designed to meet the demands of clinical diagnostics.

BackgroundRenal ischemia reperfusion injury (IRI) is one of the pivotal event of acute kidney injury (AKI), and they are unavoidable in the process of kidney transplantation, which eventually leads to the loss of renal allograft. Ferroptosis is a newly identified programmed cell death. Recent studies have suggested that ferroptosis may participate in the pathophysiological process of renal IRI. Therefore, we aimed to determine biomarkers associated with ferroptosis during renal IRI and their impact on renal allografts.MethodsWe conducted a comprehensive bioinformatics analysis and established an IRI-AKI animal model to illustrate the critical role of ferroptosis-related hub genes (FRHGs) in IRI-AKI and their potential impact on kidney transplantation.ResultsIn this study, we identified 60 ferroptosis-related genes (FRGs) in renal IRI based on the GSE148420 dataset and FerrDb database. And then we performed functional annotation analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Protein-protein interaction (PPI) network was constructed by online tool String. EZH2, CDKN1A, PPARA, EGR1, ATF3, and CD44 were identited as six ferroptosis-related hubgenes (FRHGs) using four methods, including MMC, Degree, DMNC, and EPC. FRHGs expression level were verified by the validation sets GSE58438 and GSE126805. Protein expression level of FRHGs verified by Proteomics and Western blot. Cibersort was utilized to analyze immune cell infiltration during renal IRI as well as the correlation between FRHGs and immune cells. The GSE21374 dataset was used for renal allografts survival analysis. Finally, We induced the IRI-AKI animal model and illustrated the importance of FRGHs CD44 in ferroptosis and the accumulation of macrophages.ConclusionWe identified 6 FRHGs. We found that FRHGs not only exhibited significant correlation with immune cells but also directly influenced the survival of transplanted kidneys in the human population. Among six FRHGs, only CD44 was overexpressed at both the gene and protein levels. Anti-CD44 exerts a protective effect by inhibiting ferroptosis and the accumulation of M1 macrophages during renal IRI. This study provided new insights into the pathogenesis of renal IRI and provided new evidence for its treatment.

Background: Colorectal cancer (CRC) is the most common gastrointestinal malignancy. Doxorubicin (DOX) is a widely utilized chemotherapy drug, but its efficacy is limited due to dose-dependent toxicity. Here, we aim to explore the effect of indole-3-carboxylic acid on DOX-induced senescence of CRC. Methods: Healthy adult rats and aged rats were compared in terms of their metabolites and functions through non-targeted metabolomics. LS180 cells were treated with DOX to induce senescence, followed by indole-3-carboxylic acid. The effects of this combination were evaluated in xenograft tumor mice. Cell viability, proliferation, and cell cycle were assessed with the Cell Counting Kit-8, colony formation assays, and flow cytometry. The levels of senescence-associated heterochromatin foci (SAHF) were detected by immunofluorescence. Senescence-associated-beta-galactosidase (SA-β-gal) expression was assessed by SA-β-gal staining and immunohistochemistry. Western blot was used to detect the expression of p21 and p53. Results: Compared to healthy adult rats, the serum metabolome in aging rats was altered, and the abundance of indole metabolites, including indoxyl sulfate, indole-3-carboxylic acid, and indole-5-carboxylic acid, was decreased significantly. In LS180 cells, indole-3-carboxylic acid amplified DOX-induced cell senescence, inhibiting cell proliferation and promoting cell cycle arrest. It also boosted DOX-triggered upregulation of SA-β-gal, SAHF, and p21. In nude mice, indole-3-carboxylic acid increased the inhibitory effect of DOX on xenograft tumors. Conclusion: Indole-3-carboxylic acid enhances the cellular senescence and growth arrest induced by DOX, suppressing mouse tumor growth. These findings suggest that a combined treatment of indole-3-carboxylic acid and DOX could be an effective strategy for CRC treatment.

Abstract The genome of faba bean was first published in 2023. To promote future molecular breeding studies, we improved the quality of the faba genome based on high-density genetic maps and the Illumina and Pacbio RNA-seq datasets. Two high-density genetic maps were used to conduct the scaffold ordering and orientation of faba bean, culminating in an increased length (i.e., 14.28 Mbp) of chromosomes and a decrease in the number of scaffolds by 45. In gene model mining and optimisation, the PacBio and Illumina RNA-seq datasets from 37 samples allowed for the identification and correction 121,606 transcripts, and the data facilitated a prediction of 15,640 alternative splicing events, 2,148 lncRNAs, and 1,752 fusion transcripts, thus allowing for a clearer understanding of the gene structures underlying the faba genome. Moreover, a total of 38,850 new genes including 56,188 transcripts were identified compared with the reference genome. Finally, the genetic data of the reference genome was integrated and a comprehensive and complete faba bean transcriptome sequence of 103,267 transcripts derived from 54,753 uni-genes was formed.

Abstract Background Different metabolic compounds give pepper leaves and fruits their diverse colors. Anthocyanin accumulation is the main cause of the purple color of pepper leaves. The light environment is a critical factor affecting anthocyanin biosynthesis. It is essential that we understand how to use light to regulate anthocyanin biosynthesis in plants. Result Pepper leaves were significantly blue–purple only in continuous blue light or white light (with a blue light component) irradiation treatments, and the anthocyanin content of pepper leaves increased significantly after continuous blue light irradiation. This green-to-purple phenotype change in pepper leaves was due to the expression of different genes. We found that the anthocyanin synthesis precursor-related genes PAL and 4CL, as well as the structural genes F3H, DFR, ANS, BZ1, and F3’5’H in the anthocyanin synthesis pathway, had high expression under continuous blue light irradiation. Similarly, the expression of transcription factors MYB1R1-like, MYB48, MYB4-like isoform X1, bHLH143-like, and bHLH92-like isoform X3, and circadian rhythm-related genes LHY and COP1, were significantly increased after continuous blue light irradiation. A correlation network analysis revealed that these transcription factors and circadian rhythm-related genes were positively correlated with structural genes in the anthocyanin synthesis pathway. Metabolomic analysis showed that delphinidin-3-O-glucoside and delphinidin-3-O-rutinoside were significantly higher under continuous blue light irradiation relative to other light treatments. We selected 12 genes involved in anthocyanin synthesis in pepper leaves for qRT-PCR analysis, and the accuracy of the RNA-seq results was confirmed. Conclusions In this study, we found that blue light and 24-hour irradiation together induced the expression of key genes and the accumulation of metabolites in the anthocyanin synthesis pathway, thus promoting anthocyanin biosynthesis in pepper leaves. These results provide a basis for future study of the mechanisms of light quality and photoperiod in anthocyanin synthesis and metabolism, and our study may serve as a valuable reference for screening light ratios that regulate anthocyanin biosynthesis in plants.

QP (Quenching and Partitioning) steel, the third generation of advanced high-strength steel, has garnered significant attention due to its exceptional mechanical performance. This paper investigates the interplay of grain rotation, slip transfer, and back stress strengthening through quasi in-situ deformation scanning electron microscope (SEM), electron backscatter diffraction (EBSD), and load-unload-reload (LUR) cycle tests. The findings reveal the substantial differences between QP980 and QP1180. QP980, characterized by heterostructures, exhibits non-uniform deformation characteristics. In regions with heterostructures, grain rotation inhibits slip transfer, leading to the accumulation of geometrically necessary dislocations (GNDs) and the formation of dislocation substructures (walls and cells), resulting in significant back stress strengthening. Conversely, due to the lack of heterogeneous structural regions, QP1180 displays uniform deformation characteristics, grain rotation and slip transfer promote each other, showing a weaker and different back stress strengthening compared to QP980. The interplay of grain rotation, slip transmission, and dislocation substructure formation influences the back stress behavior, impacting the mechanical properties and deformation behavior of the materials. This research provides a novel perspective on plastic deformation and strengthening theory, and serves as a valuable reference for material design and performance optimization.

Abstract Background Chorioamnionitis (CA) can cause multiple organ injuries in premature neonates, particularly to the lungs. Different opinions exist regarding the impact of intrauterine inflammation on neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD). We aim to systematically review the relationship between CA or Funisitis (FV) and lung injury among preterm infants. Methods We electronically searched PubMed, EMbase, the Cochrane library, CNKI, and CMB for cohort studies from their inception to March 15, 2023. Two reviewers independently screened literature, gathered data, and did NOS scale of included studies. The meta-analysis was performed using RevMan 5.3. Results Sixteen observational studies including 68,397 patients were collected. Meta-analysis showed CA or FV increased the lung injury risk (OR = 1.43, 95%CI: 1.06–1.92). Except for histological chorioamnionitis (HCA) (OR = 0.72, 95%CI: 0.57–0.90), neither clinical chorioamnionitis (CCA) (OR = 1.86, 95%CI: 0.93–3.72) nor FV (OR = 1.23, 95%CI: 0.48–3.15) nor HCA with FV (OR = 1.85, 95%CI: 0.15–22.63) had statistical significance in NRDS incidence. As a result of stratification by grade of HCA, HCA (II) has a significant association with decreased incidence of NRDS (OR = 0.48, 95%CI: 0.35–0.65). In terms of BPD, there is a positive correlation between BPD and CA/FV (CA: OR = 3.18, 95%CI: 1.68–6.03; FV: OR = 6.36, 95%CI: 2.45–16.52). Among CA, HCA was positively associated with BPD (OR = 2.70, 95%CI: 2.38–3.07), whereas CCA was not associated with BPD (OR = 2.77, 95%CI: 0.68–11.21). HCA and moderate to severe BPD (OR = 25.38, 95%CI: 7.13–90.32) showed a positive correlation, while mild BPD (OR = 2.29, 95%CI: 0.99–5.31) did not. Conclusion Currently, evidence suggests that CA or FV increases the lung injury incidence in premature infants. For different types of CA and FV, HCA can increase the incidence of BPD while decreasing the incidence of NRDS. And this “protective effect” only applies to infants under 32 weeks of age. Regarding lung injury severity, only moderate to severe cases of BPD were positively correlated with CA.

The two primary types of non-puerperal mastitis (NPM) are granulomatous lobular mastitis (GLM) and plasma cell mastitis (PCM). Existing research indicates that immune inflammatory response is considered to be the core of the pathogenesis of GLM and PCM, and both innate and adaptive immune responses play an important role in the pathophysiology of PCM and GLM. However, the regulatory balance between various immune cells in these diseases is still unclear. Consequently, we present a comprehensive summary of the immune-related variables and recent advances in GLM and PCM.

Abstract Entanglement entropy is a fundamental concept with rising importance in various fields ranging from quantum information science, black holes to materials science. In complex materials and systems, entanglement entropy provides insight into the collective degrees of freedom that underlie the systems’ complex behaviours. As well-known predictions, the entanglement entropy exhibits area laws for systems with gapped excitations, whereas it follows the Gioev-Klich-Widom scaling law in gapless fermion systems. However, many of these fundamental predictions have not yet been confirmed in experiments due to the difficulties in measuring entanglement entropy in physical systems. Here, we report the experimental verification of the above predictions by probing the nonlocal correlations in phononic systems. We obtain the entanglement entropy and entanglement spectrum for phononic systems with the fermion filling analog. With these measurements, we verify the Gioev-Klich-Widom scaling law. We further observe the salient signatures of topological phases in entanglement entropy and entanglement spectrum.

Polypropylene (PP)-based recyclable materials have attracted tremendous interest for HVDC cable insulation applications due to their superior electrical properties, e.g., high thermal stability and superior recyclability. Compared with crosslinked polyethylene (XLPE), PP-based materials exhibit the advantages of not only higher working temperatures but also facile and efficient cable manufacturing with reduced costs, which are highly desirable in HVDC cable manufacturing. Considering their promising advantages, PP-based materials have received significant attention from both academia and industry in the field of HVDC cable insulation. In order to adopt PP as a cable insulation material, the mechanical flexibility of PP should be improved. However, regulations of the mechanical properties inevitably influences the electrical properties of PP. So extensive research has been conducted on the regulation of the mechanical and electrical properties of PP. This review summarizes the research progress on recyclable PP-based materials for HVDC cable insulation applications. Particular attention is placed on the electrical property regulations and material structure-property relationships. The challenges that remain to be addressed and the opportunities for future studies on PP-based recyclable HVDC cable insulation materials are also presented.

Polypropylene (PP) is considered to be a rather promising material for HVDC cable insulation. Grafting modi-fication has proved to be an effective method on the electrical property improvements of PP. This paper reports on the highly-enhanced electrical properties of styrene-grafted polypropylene (PP-g-St) and their related mechanism. The influence of grafting styrene on crystallization structures, thermal properties and electrical properties of PP-g-St are characterized and analyzed. These results show that PP-g-St exhibits remarkably enhanced DC volume resistivity, suppressed space charge accumulation and improved DC breakdown strengths as compared to PP. Crystallization observation shows PP-g-St has small, imperfect spherulites with indistinct boundaries, which is strongly correlated to enhanced electrical properties. This study provides an effective grafting strategy to design high-performance HVDC cable insulation materials for bulk power transmission systems.

Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.

Objective To investigate the expression levels of type 2 inflammatory cytokines, IL-4 and IL-13, in the serum and blister fluid of patients with bullous pemphigoid (BP). Methods The serum or blister fluid was collected from BP patients (49 cases) and healthy individuals (33 cases). ELISA was used to measure the concentrations of IL-4 and IL-13. The expression levels of IL-4 and IL-13 were compared between the BP patients and healthy controls. The correlations of IL-4 and IL-13 with total serum IgE levels, eosinophils, skin erythema score and pruritus severity (NRS) in BP patients were analyzed. Moreover, the associations of BP180 and BP230 IgG antibodies with IL-4, IL-13 and total serum IgE levels, and eosinophils were determined. Results The concentrations of IL-4 and IL-13 in the blister fluid, but not in the serum, were significantly higher in the BP patients than in the healthy controls (P

Abstract Paeniclostridium sordellii lethal toxin (TcsL) is a potent exotoxin that causes lethal toxic shock syndrome associated with fulminant bacterial infections. TcsL belongs to the large clostridial toxin (LCT) family. Here, we report that TcsL with varied lengths of combined repetitive oligopeptides (CROPs) deleted show increased autoproteolysis as well as higher cytotoxicity. We next present cryo-EM structures of full-length TcsL, at neutral (pH 7.4) and acidic (pH 5.0) conditions. The TcsL at neutral pH exhibits in the open conformation, which resembles reported TcdB structures. Low pH induces the conformational change of partial TcsL to the closed form. Two intracellular interfaces are observed in the closed conformation, which possibly locks the cysteine protease domain and hinders the binding of the host receptor. Our findings provide insights into the structure and function of TcsL and reveal mechanisms for CROPs-mediated modulation of autoproteolysis and cytotoxicity, which could be common across the LCT family.

Abstract Telomere length (TL) shortening is a pivotal indicator of biological aging and is associated with many human diseases. The genetic determinates of human TL have been widely investigated, however, most existing studies were conducted based on adult tissues which are heavily influenced by lifetime exposure. Based on the analyses of terminal restriction fragment (TRF) length of telomere, individual genotypes, and gene expressions on 166 healthy placental tissues, we systematically interrogate TL-modulated genes and their potential functions. We discover that the TL in the placenta is comparatively longer than in other adult tissues, but exhibiting an intra-tissue homogeneity. Trans-ancestral TL genome-wide association studies (GWASs) on 644,553 individuals identify 20 newly discovered genetic associations and provide increased polygenic determination of human TL. Next, we integrate the powerful TL GWAS with placental expression quantitative trait locus (eQTL) mapping to prioritize 23 likely causal genes, among which 4 are functionally validated, including MMUT, RRM1, KIAA1429, and YWHAZ. Finally, modeling transcriptomic signatures and TRF-based TL improve the prediction performance of human TL. This study deepens our understanding of causal genes and transcriptomic determinants of human TL, promoting the mechanistic research on fine-grained TL regulation.

Highlights All-organic polymer composites for high-temperature capacitive energy storage. Zero-dimensional polymer dots with high electron affinity are used as fillers. Deep charge traps from UV-irradiated films reduce the high-field conduction loss.

AimsProstate cancer patients face impaired body image and psychological distress during the diagnosis and treatment of the disease, which leads to changes in mood, cognition and behavior. Psychological resilience has been shown to buffer shocks and stresses from the disease. Therefore, this study investigates the relationship between family functioning and psychological resilience in prostate cancer patients and the mediating role of self-efficacy between family functioning and psychological resilience to provide a relevant theoretical basis for improving patients' psychological status by providing relevant theoretical basis.MethodUsing a cross-sectional design, participants were 215 patients with prostate cancer admitted to and treated in a tertiary hospital in Jiangsu province, China. Questionnaires were administered using the general information questionnaire, the Connor-Davidson Resilience Scale (CD-RISC), the Family Adaptation, Partnership, Growth, Affection, and Resolution Index (APGAR), and the General Self-efficacy Scale (GSES). Data were analyzed using descriptive and correlational analyses and the bootstrap mediation test was used to test the effect relationship between the variables.ResultsFamily functioning, self-efficacy and psychological resilience were significantly and positively correlated (r = 0.526, P < 0.01; r = 0.378, P < 0.01; r = 0.358, P < 0.01). The mediating effect of psychological resilience between family functioning and psychological resilience was significant, accounting for 42.56%.ConclusionFamily function and self-efficacy have been shown to increase the level of psychological resilience in prostate cancer patients. Attention should be paid to the mental health problems of prostate cancer patients, early screening and intervention, and the use of patients' family resources to improve their confidence in recovering from the disease, thus increasing their psychological resilience and improving their mental health.

Summary: N6-methyladenosine (m6A) modification has been implicated in many cell processes and diseases. YTHDF1, a translation-facilitating m6A reader, has not been previously shown to be related to allergic airway inflammation. Here, we report that YTHDF1 is highly expressed in allergic airway epithelial cells and asthmatic patients and that it influences proinflammatory responses. CLOCK, a subunit of the circadian clock pathway, is the direct target of YTHDF1. YTHDF1 augments CLOCK translation in an m6A-dependent manner. Allergens enhance the liquid-liquid phase separation (LLPS) of YTHDF1 and drive the formation of a complex comprising dimeric YTHDF1 and CLOCK mRNA, which is distributed to stress granules. Moreover, YTHDF1 strongly activates NLRP3 inflammasome production and interleukin-1β secretion leading to airway inflammatory responses, but these phenotypes are abolished by deleting CLOCK. These findings demonstrate that YTHDF1 is an important regulator of asthmatic airway inflammation, suggesting a potential therapeutic target for allergic airway inflammation.

【Objective】In modern vegetable facility cultivation, the quality of vegetable seedlings plays a very important role in the economic benefits of subsequent agricultural production. Continuous light is a common special light mode in artificial light plant factory. Exploring the effect of continuous light combined with light quality on the growth and development of pepper seedlings could provide an important technical reference for efficiently improving the resistance of pepper seedlings.【Method】The pepper backbone parent '6421' was used as the test material, and 6 light treatment groups were set up: normal white light irradiation group (CW), normal blue light irradiation group (CB), normal red light irradiation group (CR), continuous white light irradiation group (TW), continuous blue light irradiation group (TB) and continuous red light irradiation group (TR). The effects of continuous photoperiod treatment combined with red and blue light on the growth and physiological characteristics of pepper seedlings were studied.【Result】(1) TR significantly increased the plant height and stem diameter of pepper seedlings by 20.5% and 10.6%, respectively, compared with the CW group. After TR treatment, the seedling index increased significantly by 2.38 times, while TB significantly reduced the plant height and stem diameter of pepper seedlings by 17.1% and 14.3%, and the root-shoot ratio increased significantly by 2.62 times. (2) There was no significant difference in Pn and Gs of pepper seedling leaves between TR and TB, but Tr and Ci of TB were significantly lower than those of TR. Compared with CW, Tr and Ci of TB were significantly reduced by 62.5% and 51.1%. The chlorophyll fluorescence parameters of pepper seedling leaves showed opposite results after different light treatments. The Fv/Fm, Fv/Fo, NPQ and qP values of pepper seedling leaves in TB group were significantly higher than those in TR group. The qP of TB and TR was significantly higher than that of CW, increasing by 36.1% and 26.1%, respectively. (3) The antioxidant enzyme activity and osmotic substances of pepper seedlings were significantly different after continuous red light treatment and continuous blue light treatment. TB significantly increased SOD, POD and CAT in leaves of pepper seedlings. The POD and CAT activities of pepper seedling leaves were also significantly increased after TR treatment, while the MDA content of pepper leaves after TB and TR treatments was significantly reduced by 55%-56% compared with that of CW.【Conclusion】Continuous light conditions have a positive effect on the growth and development of pepper seedlings at the seedling stage, and the antioxidant enzyme activity and osmotic substances of pepper seedlings under continuous light irradiation combined with monochromatic red and monochromatic blue light treatments increase to different degrees to better counteract the light stress environment and improve the adaptability of pepper seedlings.

Objective: To explore the correlation between hepatocellular carcinoma (HCC) gene variation profile and clinical characteristics in Han nationality with HBV infection in Sichuan province. Methods: The clinical data and HCC tissues were obtained from the enrolled patients. Whole exome sequencing and bioinformatics analysis were performed on formalin-fixed and paraffin-embedded samples from HCC. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. Results: Sixteen high-frequency mutated genes with differential expressions were identified by WES. SMG1 gene variation could be positively correlated with satellite lesions. AMY2B and RGPD4 gene mutation seemed to have a greater chance of vascular invasion. The patients with TATDN1 variation have bigger diameters and greater chances of vascular and microvascular invasion (all P

Abstract Improving the human reliability of the human–machine interface (HMI) of deep-sea manned submersible is of great importance for the development of the deep-sea field. Based on the SHEL (Software S, Hardware H, Environment E, Liveware L) model, this study classifies the performance shaping factors (PSF) that affect the human reliability of submersible HMIs and builds a PSF system. The interpretative structural model (ISM) is used to matrix the interactions between the elements that make up the system of PSF. A multi-level recursive structure is obtained by building the corresponding adjacency matrix. The Noisy-OR model is introduced to construct a Bayesian network in order to build a new HMI evaluation method. A real case of Bayesian network causal inference verifies the validity of the built method. This study proposes a set of HMI human reliability evaluation methods applicable to deep-sea manned submersible, which provides a new idea for human reliability assessment.

Abstract Post-transcriptional methylation modifications, such as the N7-methylguanosine (m7G) modification, are increasingly acknowledged for their role in the development and resistance to chemotherapy in acute myeloid leukemia (AML). This study employed MeRIP-seq technology to investigate the m7G sites within circular RNAs (circRNAs) derived from human AML cells and drug-resistant AML cells, in order to identify these sites more comprehensively. In addition, a detailed analysis of the relationship between m7G and drug-resistant AML was conducted. The bioinformatics analysis was utilized to predict the functions of specific methylated transcripts. The findings revealed a significant difference in m7G level between AML cells and drug-resistant AML cells, suggesting a potentially critical role of m7G in circRNAs in drug-resistant AML development. The methylation of M7G could affect the circRNA-miRNA-mRNA co-expression during the development of AML resistance, which could further influence the regulation of resistance-associated target genes in AML. Furthermore, gene ontology analysis indicated that the distinct distribution pattern of circRNAs with m7G methylation in drug-resistant AML cells was correlated with metabolism-related pathways. These results suggested a potential association between drug-resistant AML and m7G methylation of circRNAs. Moreover, the results revealed a novel role of m7G RNA methylation in circRNAs in the progression of AML chemoresistance.

In conventional lithium-ion batteries (LIBs), the active lithium from the lithium-containing cathode is consumed by the formation of a solid electrolyte interface (SEI) at the anode during the first charge, resulting in irreversible capacity loss. Prelithiation additives can provide additional active lithium to effectively compensate for lithium loss. Lithium oxalate is regarded as a promising ideal cathode prelithiation agent; however, the electrochemical decomposition of lithium oxalate is challenging. In this work, a hollow and porous composite microsphere was prepared using a mixture of lithium oxalate, Ketjen Black and transition metal oxide catalyst, and the formulation was optimized. Owing to the compositional and structural merits, the decomposition voltage of lithium oxalate in the microsphere was reduced to 3.93 V; when being used as an additive, there is no noticeable side effect on the performance of the cathode material. With 4.2% of such an additive, the first discharge capacity of the LiFePO4‖graphite full cell increases from 139.1 to 151.9 mAh g−1, and the coulombic efficiency increases from 88.1% to 96.3%; it also facilitates the formation of a superior SEI, leading to enhanced cycling stability. This work provides an optimized formula for developing an efficient prelithiation agent for LIBs.

Abstract The bat coronaviruses (CoV) BANAL-20-52 and BANAL-20-236 are two newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) closely related coronaviruses (SC2r-CoV) and the genome of BANAL-20-52 shares the highest homology with SARS-CoV-2. However, the risk of their potential zoonotic transmission has not been fully evaluated. Here, we determined their potential host susceptibility among 13 different bat species and 26 different animal species, and found that both might have extensive host ranges, indicating high zoonotic transmission potential. We also determined the cryo-EM structures of BANAL-20-52 and BANAL-20-236 S proteins at pH 5.5 and the complex of BANAL-20-236 S1 and Rhinolophus affinis ACE2, and found that both trimeric S proteins adopt all three receptor binding domains (RBDs) in “closed” conformation and are more compact than SARS-CoV-2. Strikingly, the unique sugar moiety at N370 of bat SC2r-CoVs acts like a “bolt” and crosses over two neighboring subunits, facilitating the S proteins in the locked conformation and underpinning the architecture stability. Removal of the glycosylation at N370 by a T372A substitution substantially enhances virus infectivity but becomes highly sensitive to trypsin digestion at pH 5.5, a condition roughly mimicking the insectivorous bat’s stomach digestion. In contrast, WT S proteins of SC2r-CoVs showed considerable resistance to trypsin digestion at pH 5.5, indicating that the highly conserved T372 in bat CoVs might result from the selective advantages in stability during the fecal-oral transmission over A372. Moreover, the results of cross-immunogenicity among S proteins of SARS-CoV-2, BANAL-20-52, and BANAL-20-236 showed that A372 pseudoviruses are more sensitive to anti-S sera than T372, indicating that immune evasion might also play a role in the natural selection of T372 over A372 during evolution. Finally, residues 493 and 498 of the S protein affect host susceptibility, and residue 498 also influences the immunogenicity of the S protein. Together, our findings aid a better understanding of the molecular basis of CoV entry, selective evolution, and immunogenicity and highlight the importance of surveillance of susceptible hosts of these viruses to prevent potential outbreaks.

Abstract Background Growing evidence indicates that RNA methylation plays a fundamental role in epigenetic regulation, which is associated with the tumorigenesis and drug resistance. Among them, acute myeloid leukemia (AML), as the top acute leukemia for adults, is a deadly disease threatening human health. Although N7-methylguanosine (m7G) has been identified as an important regulatory modification, its distribution has still remained elusive. Methods The present study aimed to explore the long non-coding RNA (lncRNA) functional profile of m7G in AML and drug-resistant AML cells. The transcriptome-wide m7G methylation of lncRNA was analyzed in AML and drug-resistant AML cells. RNA MeRIP-seq was performed to identify m7G peaks on lncRNA and differences in m7G distribution between AML and drug-resistant AML cells. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to predict the possible roles and m7G-associated pathway. Results Using m7G peak sequencing, it was found that a sequence motif was necessary for m7G methylation in drug-resistant AML lncRNA. Unsupervised hierarchical cluster analysis confirmed that lncRNA m7G methylation occurred more frequently in drug-resistant AML cells than in AML cells. RNA sequencing demonstrated that more genes were upregulated by methylation in drug-resistant AML cells, while methylation downregulated more genes in AML cells. The GO and KEGG pathway enrichment analyses revealed that genes having a significant correlation with m7G sites in lncRNA were involved in drug-resistant AML signaling pathways. Conclusion Significant differences in the levels and patterns of m7G methylation between drug-resistant AML cells and AML cells were revealed. Furthermore, the cellular functions potentially influenced by m7G in drug-resistant AML cells were predicted, providing evidence implicating m7G-mediated lncRNA epigenetic regulation in the progression of drug resistance in AML. These findings highlight the involvement of m7G in the development of drug resistance in AML.

Abstract Polymerase 1 and transcript release factor (PTRF, encoding by Cavin-1) regulates interleukin 33 (IL-33) release, which is implicated in asthma development. Z-DNA binding protein 1 (ZBP1)-sensing Z-RNAs induces necroptosis which causes inflammatory diseases. House dust mite (HDM) is the major source of allergen in house dust and is strongly associated with the development of asthma. Whether PTRF via IL-33 and ZBP1 mediates HDM-induced macrophage necroptosis and airway inflammation remains unclear. Here, we found that deficiency of PTRF could reduce lung IL-33, ZBP1, phosphor-receptor-interacting protein kinase 3 (p-RIPK3), and phosphor-mixed lineage kinase domain-like (p-MLKL) (necroptosis executioner), and airway inflammation in an HDM-induced asthma mouse model. In HDM-treated macrophages, ZBP1, p-RIPK3, and p-MLKL levels were markedly increased, and these changes were reversed by deletion of Cavin-1. Deletion of Il33 also reduced expression of ZBP1, p-RIPK3, and p-MLKL in HDM-challenged lungs. Moreover, IL-33 synergizing with HDM boosted expression of ZBP1, p-RIPK3, and p-MLKL in macrophages. In bronchial epithelial cells rather than macrophages and vascular endothelial cells, PTRF positively regulates IL-33 expression. Therefore, we conclude that PTRF mediates HDM-induced macrophage ZBP1/necroptosis and airway inflammation, and this effect could be boosted by bronchial epithelial cell-derived IL-33. Our findings suggest that PTRF-IL33-ZBP1 signaling pathway might be a promising target for dampening airway inflammation.

Abstract Aim The aim of the study was to develop and psychologically test the mobile health information‐seeking behaviour (MHISB) questionnaire in people with cancer. Design Instrument development. Methods The study was conducted in three phases in a southeastern city of China from May 2017 to April 2018. In phase one, an item pool was constructed based on a literature review and semistructured interviews. In phase two, expert evaluation and cognitive interviews were used to evaluate the content validity of the questionnaire. In phase three, a cross‐sectional study was conducted with people with cancer. Cronbach's α was calculated for reliability analysis. Validity evaluation included content validity and construct validity. Results The developed MHISB questionnaire has four dimensions (information‐seeking frequency, information‐seeking self‐efficacy, health information evaluation and information‐seeking willingness) and 25 items. Psychometric findings were satisfactory and supported the questionnaire's reliability. Conclusions The construction process of the MHISB questionnaire was scientific and feasible. The MHISB questionnaire had acceptable validity and reliability, and it requires further improvement in future studies.

Abstract Background Pregnancy begins with a fertilized ovum that normally attaches to the uterine endometrium. However, an ectopic pregnancy can occur when a fertilized egg implants and grows outside the uterine cavity. Tubal ectopic pregnancy is the most common type (over 95%), with ovarian, abdominal, cervical, broad ligament, and uterine cornual pregnancy being less common. As more cases of ectopic pregnancy are diagnosed and treated in the early stages, the survival rate and fertility retention significantly improve. However, complications of abdominal pregnancy can sometimes be life-threatening and have severe consequences. Case presentation We present a case of intraperitoneal ectopic pregnancy with fetal survival. Ultrasound and magnetic resonance imaging showed a right cornual pregnancy with a secondary abdominal pregnancy. In September 2021, we performed an emergency laparotomy, along with additional procedures such as transurethral ureteroscopy, double J-stent placement, abdominal fetal removal, placentectomy, repair of the right uterine horn, and pelvic adhesiolysis, in the 29th week of pregnancy. During laparotomy, we diagnosed abdominal pregnancy secondary to a rudimentary uterine horn. The mother and her baby were discharged eight days and 41 days, respectively, after surgery. Conclusions Abdominal pregnancy is a rare condition. The variable nature of ectopic pregnancy can cause delays in timely diagnosis, resulting in increased morbidity and mortality, especially in areas with inadequate medical and social services. A high index of suspicion, coupled with appropriate imaging studies, can help facilitate its diagnosis in any suspected case.

Chylous leakage is an uncommon and serious clinical condition, especially occurring after retroperitoneal operations. Here, we report a case of cervical chylous leakage combined with chylothorax in a 57-year-old woman postretroperitoneal surgery, and our conservative approach led to resolution/clinical improvement. The causes of this rare complication are discussed. We considered that the venous thrombosis, the increased intra-abdominal pressure, or the patient positioning during the surgery may lead to the chylous particles leakage and chylothorax. Because of its rarity, we hope this case report will improve clinicians’ understanding of cervical chylous leakage combined with chylothorax and provide suitable treatment options for future clinical reference.

Bladder cancer has recently seen an alarming increase in global diagnoses, ascending as a predominant cause of cancer-related mortalities. Given this pressing scenario, there is a burgeoning need to identify effective biomarkers for both the diagnosis and therapeutic guidance of bladder cancer. This study focuses on evaluating the potential of high-definition computed tomography (CT) imagery coupled with RNA-sequencing analysis to accurately predict bladder tumor stages, utilizing deep residual networks. Data for this study, including CT images and RNA-Seq datasets for 82 high-grade bladder cancer patients, were sourced from the TCIA and TCGA databases. We employed Cox and lasso regression analyses to determine radiomics and gene signatures, leading to the identification of a three-factor radiomics signature and a four-gene signature in our bladder cancer cohort. ROC curve analyses underscored the strong predictive capacities of both these signatures. Furthermore, we formulated a nomogram integrating clinical features, radiomics, and gene signatures. This nomogram’s AUC scores stood at 0.870, 0.873, and 0.971 for 1-year, 3-year, and 5-year predictions, respectively. Our model, leveraging radiomics and gene signatures, presents significant promise for enhancing diagnostic precision in bladder cancer prognosis, advocating for its clinical adoption.

BackgroundDisulfidptosis, a newly defined type of programmed cell death, has emerged as a significant regulatory process in the development and advancement of malignant tumors, such as lower-grade glioma (LGG). Nevertheless, the precise biological mechanisms behind disulfidptosis in LGG are yet to be revealed, considering the limited research conducted in this field.MethodsWe obtained LGG data from the TCGA and CGGA databases and performed comprehensive weighted co-expression network analysis, single-sample gene set enrichment analysis, and transcriptome differential expression analyses. We discovered nine genes associated with disulfidptosis by employing machine learning methods like Cox regression, LASSO regression, and SVM-RFE. These were later used to build a predictive model for patients with LGG. To confirm the expression level, functional role, and impact on disulfidptosis of ABI3, the pivotal gene of the model, validation experiments were carried out in vitro.ResultsThe developed prognostic model successfully categorized LGG patients into two distinct risk groups: high and low. There was a noticeable difference in the time the groups survived, which was statistically significant. The model’s predictive accuracy was substantiated through two independent external validation cohorts. Additional evaluations of the immune microenvironment and the potential for immunotherapy indicated that this risk classification could function as a practical roadmap for LGG treatment using immune-based therapies. Cellular experiments demonstrated that suppressing the crucial ABI3 gene in the predictive model significantly reduced the migratory and invasive abilities of both SHG44 and U251 cell lines while also triggering cytoskeletal retraction and increased cell pseudopodia.ConclusionThe research suggests that the prognostic pattern relying on genes linked to disulfidptosis can provide valuable insights into the clinical outcomes, tumor characteristics, and immune alterations in patients with LGG. This could pave the way for early interventions and suggests that ABI3 might be a potential therapeutic target for disulfidptosis.

We report a case of lupus erythematosus panniculitis misdiagnosed as vasculitis. A 7-year-old boy presented with a 2-year history of erythema and ulceration on the left lower abdomen and depressed skin on the left buttock. He had been diagnosed with vasculitis and skin infection in other hospitals for many times. Dermatological examination showed scattered dark erythema on the left lower abdomen, green bean to nail sized necrosis and ulcers with adhesive black crusts on some areas, and several porcelain-white mild atrophic scars. Non-atrophic band-like depression in normal color was observed on the left hip, ilium, left lower abdomen and the left groin. The skin could be pinched. Histopathological changes in the skin lesions included liquefaction degeneration of basal cells, pigment incontinence, infiltration of lymphocytes and plasma cells around dermal vessels and appendages, mucin deposition between collagen bundles, adipose atrophy, encapsulation of fatty lobules, and positive for Alcian blue staining. The final diagnosis was lupus erythematosus panniculitis. The patient was treated with oral hydroxychloroquine 0.1 g/qd and methylprednisolone 16 mg/qd, and topical mucopolysaccharide polysulfate cream, centella triterpenes cream and crisaborole ointment. Ulcers were healed without new lesion and erythema at one-year follow-up.

Abstract Background ABO blood groups has been associated with risk of several cancers; however, the results for an association with ovarian cancer are inconsistent and little is known about the expression of histo‐blood group (ABH) antigens and ABO gene in ovarian tumor tissues. Methods To assess the impact of genotype‐derived ABO blood types on the risk of EOC, we conducted a case–control study in 1,870 EOC and 4,829 controls. Expression of A and B antigen in 70 pairs of ovarian tumor tissues and adjacent normal tissues were detected by immunohistochemistry. Gene expression and DNA methylation profiling was conducted in ovarian tumor tissues. Results We identified that blood group A was associated with increased risk for EOC compared to blood group O (OR = 1.18, 95% CI = 1.03–1.36, p = 0.019). Increased frequency of aberrant expression of histo‐blood group antigens was observed in patients with blood group A (76.5%) compared to patients with blood group O (21.1%) and B (5.0%) by immunohistochemistry (p

Here the authors used an evidence-based strategy to prioritize causal pleiotropic variants of autoimmune diseases, and revealed that rs4728142 modulates aberrant IRF5 alternative promoter usage by ZBTB3-mediated chromatin looping.

Hurricanes Ian and Nicole caused devastating destruction across Florida in September and November 2022, leaving widespread damage in their wakes. This study focuses on the assessment of barrier islands’ shorelines, encompassing natural sand dunes and dune vegetation as well as armored dunes with man-made infrastructure such as seawalls. High-resolution satellite imagery from Planet was used to assess the impacts of these hurricanes on the beach shorelines of Volusia, Flagler, and St. Johns Counties on the Florida Central East Coast. Shorefront vegetation was classified into two classes. Normalized Difference Vegetation Index (NDVI) values were calculated before the hurricanes, one month after Hurricane Ian, one month after Hurricane Nicole, and one-year post landfall. LiDAR (Light Detection and Ranging) was incorporated to calculate vertical changes in the shorelines before and after the hurricanes. The results suggest that natural sand dunes were more resilient as they experienced less impact to vegetation and elevation and more substantial recovery than armored dunes. Moreover, the close timeframe of the storm events suggests a compound effect on the weakened dune systems. This study highlights the importance of understanding natural dune resilience to facilitate future adaptive management efforts because armored dunes may have long-term detrimental effects on hurricane-prone barrier islands.

Trichomes are specialized organs located in the plant epidermis that play important defense roles against biotic and abiotic stresses. However, the mechanisms regulating the development of pepper epidermal trichomes and the related regulatory genes at the molecular level are not clear. Therefore, we performed transcriptome analyses of A114 (less trichome) and A115 (more trichome) to dig deeper into the genes involved in the regulatory mechanisms of epidermal trichome development in peppers. In this study, the epidermal trichome density of A115 was found to be higher by phenotypic observation and was highest in the leaves at the flowering stage. A total of 39,261 genes were quantified by RNA-Seq, including 11,939 genes not annotated in the previous genome analysis and 18,833 differentially expressed genes. Based on KEGG functional enrichment, it was found that DEGs were mainly concentrated in three pathways: plant–pathogen interaction, MAPK signaling pathway-plant, and plant hormone signal transduction. We further screened the DEGs associated with the development of epidermal trichomes in peppers, and the expression of the plant signaling genes GID1B-like (Capana03g003488) and PR-6 (Capana09g001847), the transcription factors MYB108 (Capana05g002225) and ABR1-like (Capana04g001261), and the plant resistance genes PGIP-like (Capana09g002077) and At5g49770 (Capana08g001721) in the DEGs were higher at A115 compared to A114, and were highly expressed in leaves at the flowering stage. In addition, based on the WGCNA results and the establishment of co-expression networks showed that the above genes were highly positively correlated with each other. The transcriptomic data and analysis of this study provide a basis for the study of the regulatory mechanisms of pepper epidermal trichomes.

Breast cancer is currently the most common malignancy and has a high mortality rate. Ginsenosides, the primary bioactive constituents of ginseng, have been shown to be highly effective against breast cancer both in vitro and in vivo. This study aims to comprehensively understand the mechanisms underlying the antineoplastic effects of ginsenosides on breast cancer. Through meticulous bibliometric analysis and an exhaustive review of pertinent research, we explore and summarize the mechanism of action of ginsenosides in treating breast cancer, including inducing apoptosis, autophagy, inhibiting epithelial-mesenchymal transition and metastasis, and regulating miRNA and lncRNA. This scholarly endeavor not only provides novel prospects for the application of ginsenosides in the treatment of breast cancer but also suggests future research directions for researchers.

With the aim to investigate the active chemical constituents for the roots of Indigofera stachyodes, the petroleum ether part of this plant was separated and purified using silica gel column chromatography, Sephadex LH-20 column chromatography, semi-preparative high performance liquid chromatography, and recrystallization methods. The structures of obtained monomeric compounds were identified through modern spectral techniques by detail analysis of their electrospray ionization mass spectrometry, hydrogen and carbon nuclear magnetic resonance spectra data, as well as compared with the reported references. The results were as follows: twenty-two natural compounds were identified as β-sitostenone (1), stigmasta-3,6-di-one (2), 6β-hydroxystigmast-4-en-3-one (3), (22E)-5α,8α-epidioxyergosta-6,22-dien-3β-ol (4), medicarpin (5), sativan (6), 2′,4′-dihydroxychaicone (7), 6,7-dimethoxy-4-hydroxy-1-naphthoic acid (8), p-hydroxybenzoic acid ethyl ester (9), 2,4-dihydroxybenzoic acid ethyl ester (10), (9E,11E)-13-oxo-9,11-ocatadecadienoic acid (11), (9E,11E)-13-oxo-9,11-octadecadienoic acid methyl ester (12), 9-oxo-10E,12E-octadecadienoic acid methyl ester (13), 9-hydroxy-10E,12Z-octadecadienoic acid methyl ester (14), pinellic acid (15) and 9-oxo-10E,12E-octadecadienoic acid-(2S)-2,3-dihydroxypropyl ester (16), β-sitosterol (17), betulinic acid (18), 3β-hydroxyolean-12-en-11-one (19), maackiain (20), phellopterin (21), palmitic acid (22). Of these compounds, ten compounds (compounds 1-3, 7, 11-16) were isolated from the Fabaceae for the first time; sixteen compounds (compounds 1-16) were obtained from Indigofera plant for the first time; at the same time, compounds 1-16, 18, 19, 21 were obtained from the roots of Indigofera stachyodes for the first time. Thus, the results of this research enrich the chemical structure types of roots of I. stachyodes, and afford a scientific foundation for its further rational use.