Notch-targeted Therapeutic in Colorectal Cancer by Notch1 Attenuation via Tumor Microenvironment-Responsive Cascade DNA Delivery.

The Notch signaling is a key molecular pathway that regulates cell fate and development. Aberrant Notch signaling can lead to carcinogenesis and progression of malignant tumors. However, current therapies targeting Notch pathway lack specificity and induce high toxicity. In this report, we design a tumor microenvironment-responsive and injectable hydrogel to load plasmid DNA complexes as a cascade gene delivery system to achieve precise Notch-targeted gene therapy of colorectal cancer (CRC). The hydrogels were prepared through cross-linking between phenylboric acid groups-containing poly(oligo(ethylene glycol)methacrylate) (POEGMA) and epigallocatechin gallate (EGCG), which were used to load the complexes between plasmid DNA encoding short hairpin RNAs of Notch1 (shNotch1) and fluorinated polyamidoamine (PAMAM-F) (PAMAM-F/shNotch1). In response to low pH and H2O2 in tumor microenvironment, the hydrogel can be dissociated and release the complexes for precise delivery of shNotch1 into tumor cells and inhibit Notch1 activity to suppress malignant biological behaviors of CRC. In the subcutaneous tumor model of CRC, PAMAM-F/shNotch1-loaded hydrogels can accurately attenuate Notch1 activity and significantly inhibit tumor growth without affecting Notch signal in adjacent normal tissues. Therefore, this therapeutic system can precisely inhibit Notch1 signal in CRC with high responsiveness and low toxicity, providing a promising Notch-targeted gene therapeutic for human malignancy. This article is protected by copyright. All rights reserved.

Film mulching counteracts the adverse effects of mild moisture deficiency, and improves the quality and yield of Cyperus esculentus. L grass and tuber in the oasis area of Tarim Basin.

Introduction: Plastic film mulching (PFM) and deficit irrigation (DI) are vital water-saving approaches in arid agriculture. Cyperus esculentus is a significant crop in dry zones. However, scant data exists on the impacts of these water-saving methods on C. esculentus yield and quality. Method: Using randomized block experiment design. Three irrigation strategies were tested: CK (standard irrigation), RW20 (20% water reduction), and RW40 (40% water reduction). Mulchin treatments included film mulching (FM) and no film mulching (NFM). Results: Results revealed substantial effects of film mulching and drip irrigation on soil nutrients and physical properties, with minor influence on grass, root, and tuber stoichiometry. PF treatment, DI treatments, and their interaction significantly affected C. esculentus forage and tuber yields. Initially, grass and tuber yields increased and then decreased with reduced irrigation. The highest yields were under RW20 (3716.31 and 4758.19 kg/ha). FM increased grass and tuber yield by 17.99% and 8.46%, respectively, over NFM. The water reduction augmented the biomass distribuiton of the leaf and root, while reducing the tuber biomass in NFM. FM significantely impacted grass ether extract content, while reduced water influenced grass and tuber crude protein and tuber ether extract content. Mild water stress increased ether extract, crude protein, and soluble matter in grass and tubers, while excessive RW decreased them. Conclusion: Integrating soil traits, nutrients, yield, and quality, findings indicate C. esculentus yield and quality primarily hinge on soil water content, pond hydrogenase, and electrical conductivity. Based on this results, the recommended strategy is to reduce irrigation by 20% for cultivating C. esculentus in this area.

A rare complex structural variant of novel intragenic inversion combined with reciprocal translocation t(X;1)(p21.2;p13.3) in Duchenne muscular dystrophy.

Structural variants (SVs) are infrequently observed in Duchenne muscular dystrophy (DMD), a condition mainly marked by deletions and point mutations in the DMD gene. SVs in DMD remain difficult to reliably detect due to the limited SV-detection capacity of conventionally used short-read sequencing technology. Herein, we present a family, a boy and his mother, with clinical signs of muscular dystrophy, elevated creatinine kinase levels, and intellectual disability. A muscle biopsy from the boy showed dystrophin deficiency. Routine molecular techniques failed to detect abnormalities in the DMD gene, however, dystrophin mRNA transcripts analysis revealed an absence of exons 59 to 79. Subsequent long-read whole-genome sequencing identified a rare complex structural variant, a 77 kb novel intragenic inversion, and a balanced translocation t(X;1)(p21.2;p13.3) rearrangement within the DMD gene, expanding the genetic spectrum of dystrophinopathy. Our findings suggested that SVs should be considered in cases where conventional molecular techniques fail to identify pathogenic variants.

Characterizing genetic variation on the Z chromosome in Schistosoma japonicum reveals host-parasite co-evolution.

BACKGROUND: Schistosomiasis is a neglected tropical disease that afflicts millions of people worldwide; it is caused by Schistosoma, the only dioecious flukes with ZW systems. Schistosoma japonicum is endemic to Asia; the Z chromosome of S. japonicum comprises one-quarter of the entire genome. Detection of positive selection using resequencing data to understand adaptive evolution has been applied to a variety of pathogens, including S. japonicum. However, the contribution of the Z chromosome to evolution and adaptation is often neglected. METHODS: We obtained 1,077,526 high-quality SNPs on the Z chromosome in 72 S. japonicum using re-sequencing data publicly. To examine the faster Z effect, we compared the sequence divergence of S. japonicum with two closely related species, Schistosoma haematobium and S. mansoni. Genetic diversity was compared between the Z chromosome and autosomes in S. japonicum by calculating the nucleotide diversity (π) and Dxy values. Population structure was also assessed based on PCA and structure analysis. Besides, we employed multiple methods including Tajima's D, FST, iHS, XP-EHH, and CMS to detect positive selection signals on the Z chromosome. Further RNAi knockdown experiments were performed to investigate the potential biological functions of the candidate genes. RESULTS: Our study found that the Z chromosome of S. japonicum showed faster evolution and more pronounced genetic divergence than autosomes, although the effect may be smaller than the variation among genes. Compared with autosomes, the Z chromosome in S. japonicum had a more pronounced genetic divergence of sub-populations. Notably, we identified a set of candidate genes associated with host-parasite co-evolution. In particular, LCAT exhibited significant selection signals within the Taiwan population. Further RNA interference experiments suggested that LCAT is necessary for S. japonicum survival and propagation in the definitive host. In addition, we identified several genes related to the specificity of the intermediate host in the C-M population, including Rab6 and VCP, which are involved in adaptive immune evasion to the host. CONCLUSIONS: Our study provides valuable insights into the adaptive evolution of the Z chromosome in S. japonicum and further advances our understanding of the co-evolution of this medically important parasite and its hosts.

Prediction of ovarian cancer prognosis using statistical radiomic features of ultrasound images.

Ovarian cancer is the deadliest gynecologic malignancy worldwide. Ultrasound is the most useful non-invasive test for preoperative diagnosis of ovarian cancer. In this study, by leveraging multiple ultrasound images from the same patient to generate personalized, informative statistical radiomic features, we aimed to develop improved ultrasound image-based prognostic models for ovarian cancer. A total of 2,057 ultrasound images from 514 ovarian cancer patients, including 355 patients with epithelial ovarian cancer, from two hospitals in China were collected for this study. The models were constructed using our recently developed Frequency Appearance in Multiple Univariate pre-Screening (FAMUS) feature selection algorithm and Cox proportional hazards model. The models showed high predictive performance for overall survival (OS) and recurrence-free survival (RFS) in both epithelial and nonepithelial ovarian cancer, with concordance indices (C-index) ranging from 0.773 to 0.794. Radiomic scores predicted 2-year OS and RFS risk groups with significant survival differences (log-rank test, P<1.0e-4 for both validation cohorts). OS and RFS hazard ratios between low- and high-risk groups were 15.994 and 30.692 (internal cohort) and 19.339 and 19.760 (external cohort), respectively. The improved performance of these newly developed prognostic models was mainly attributed to the use of multiple preoperative ultrasound images from the same patient to generate statistical radiomic features, rather than simply using the largest tumor ROI among them. The models also revealed that the roundness of tumor lesion shape was positively correlated with prognosis for ovarian cancer. In summary, the newly developed prognostic models based on statistical radiomic features from ultrasound images were highly predictive of the risk of cancer-related death and possible recurrence not only for patients with epithelial ovarian cancer but also for those with nonepithelial ovarian cancer. They thereby provide reliable, non-invasive markers for individualized prognosis evaluation and clinical decision-making for patients with ovarian cancer.

Post-marketing risk analysis of bendamustine: a real-world approach based on the FAERS database.

Objective: Bendamustine was approved for treating chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma. Despite its therapeutic benefits, the long-term safety of bendamustine in a large population remains inadequately understood. This study evaluates the adverse events (AEs) associated with bendamustine, using a real-world pharmacovigilance database to support its clinical application. Methods: We conducted a post-marketing risk analysis to assess the association between bendamustine and its AEs. Data were extracted from the US FDA's Adverse Event Reporting System (FAERS), covering the period from January 2017 to September 2023. The characteristics of bendamustine-associated AEs and the onset time were further analyzed. Statistical analysis was performed using MYSQL 8.0, Navicat Premium 15, Microsoft EXCEL 2016, and Minitab 21.0. Results: 9,461,874 reports were collected from the FAERS database, 9,131 identified bendamustine as the "primary suspected" drug. We identified 331 significant disproportionality preferred terms (PTs). Common AEs included pyrexia, neutropenia, infusion site reaction, progressive multifocal leukoencephalopathy (PML), injection site vasculitis, and pneumonia-all documented on bendamustine's label. Notably, 16 unexpected and significant AEs were discovered, including hypogammaglobulinemia, which is concerning due to its potential to increase infection susceptibility following bendamustine treatment. Other significant findings were anaphylactic reactions, PML, and cutaneous malignancies, suggesting updates to the drug's label may be necessary. Physicians should monitor for neurological and skin changes in patients and discontinue treatment if PML is suspected. Moreover, the median onset time for bendamustine-associated AEs was 13 days, with an interquartile range [IQR] of 0-59 days, predominantly occurring on the first day post-initiation. The ß of bendamustine-related AEs suggested risk reduction over time. Conclusion: Our study uncovered some potential pharmacovigilance signals for bendamustine, providing important insights for its safe and effective clinical use.

Changes in subset distribution and impaired function of circulating natural killer cells in patients with colorectal cancer.

Natural killer (NK) cells are closely associated with malignant tumor progression and metastasis. However, studies on their relevance in colorectal cancer (CRC) are limited. We aimed to comprehensively analyze the absolute counts, phenotypes, and function of circulating NK cells in patients with CRC using multiparametric flow cytometry. The distribution of NK cell subsets in the peripheral circulation of patients with CRC was significantly altered relative to the control group. This is shown by the decreased frequency and absolute count of CD56dimCD16+ NK cells with antitumor effects, contrary to the increased frequency of CD56bright NK and CD56dimCD16- NK cells with poor or ineffective antitumor effects. NK cells in patients with CRC were functionally impaired, with decreased intracellular interferon (IFN)-γ secretion and a significantly lower percentage of cell surface granzyme B and perforin expression. In addition, IFN-γ expression decreased significantly with the tumor stage progression. Based on a comprehensive analysis of the absolute counts, phenotypes, and functional markers of NK cells, we found an altered subset distribution and impaired function of circulating NK cells in patients with CRC.

Optically Readable, Physically Unclonable Subwavelength Pixel via Multicolor Quantum Dot Printing for Anticounterfeiting.

We present a secure and user-friendly ultraminiaturized anticounterfeiting labeling technique─the color-encoded physical unclonable nanotag. These nanotags consist of subwavelength spots formed by random combinations of multicolor quantum dots, which are fabricated using a cost-efficient printing method developed in this study. The nanotags support over 170,000 different colors and are inherently resistant to cloning. Moreover, their high brightness and color purity, owing to the quantum dots, ensure an ease of readability. Additionally, these nanotags can function as color-encrypted pixels, enabling the incorporation of labels (such as QR codes) into ultrasmall physically unclonable hidden tags with a resolution exceeding 100,000 DPI. The unique blend of compactness, flexibility, and security positions the color-encoded nanotag as a potent and versatile solution for next-generation anticounterfeiting applications.

Discovery of potent CSK inhibitors through integrated virtual screening and molecular dynamic simulation.

Oncogenic overexpression or activation of C-terminal Src kinase (CSK) has been shown to play an important role in triple-negative breast cancer (TNBC) progression, including tumor initiation, growth, metastasis, drug resistance. This revelation has pivoted the focus toward CSK as a potential target for novel treatments. However, until now, there are few inhibitors designed to target the CSK protein. Responding to this, our research has implemented a comprehensive virtual screening protocol. By integrating energy-based screening methods with AI-driven scoring functions, such as Attentive FP, and employing rigorous rescoring methods like Glide docking and molecular mechanics generalized Born surface area (MM/GBSA), we have systematically sought out inhibitors of CSK. This approach led to the discovery of a compound with a potent CSK inhibitory activity, reflected by an IC50 value of 1.6 nM under a homogeneous time-resolved fluorescence (HTRF) bioassay. Subsequently, molecule 2 exhibits strong growth inhibition of MD anderson - metastatic breast (MDA-MB) -231, Hs578T, and SUM159 cells, showing a level of growth inhibition comparable to that observed with dasatinib. Treatment with molecule 2 also induced significant G1 phase accumulation and cell apoptosis. Furthermore, we have explored the explicit binding interactions of the compound with CSK using molecular dynamics simulations, providing valuable insights into its mechanism of action.

Temporal change in multimorbidity prevalence, clustering patterns, and the association with mortality: findings from the China Kadoorie Biobank study in Jiangsu Province.

Objectives: The characteristics of multimorbidity in the Chinese population are currently unclear. We aimed to determine the temporal change in multimorbidity prevalence, clustering patterns, and the association of multimorbidity with mortality from all causes and four major chronic diseases. Methods: This study analyzed data from the China Kadoorie Biobank study performed in Wuzhong District, Jiangsu Province. A total of 53,269 participants aged 30-79 years were recruited between 2004 and 2008. New diagnoses of 15 chronic diseases and death events were collected during the mean follow-up of 10.9 years. Yule's Q cluster analysis method was used to determine the clustering patterns of multimorbidity. A Cox proportional hazards model was used to estimate the associations of multimorbidity with mortalities. Results: The overall multimorbidity prevalence rate was 21.1% at baseline and 27.7% at the end of follow-up. Multimorbidity increased more rapidly during the follow-up in individuals who had a higher risk at baseline. Three main multimorbidity patterns were identified: (i) cardiometabolic multimorbidity (diabetes, coronary heart disease, stroke, and hypertension), (ii) respiratory multimorbidity (tuberculosis, asthma, and chronic obstructive pulmonary disease), and (iii) mental, kidney and arthritis multimorbidity (neurasthenia, psychiatric disorders, chronic kidney disease, and rheumatoid arthritis). There were 3,433 deaths during the follow-up. The mortality risk increased by 24% with each additional disease [hazard ratio (HR) = 1.24, 95% confidence interval (CI) = 1.20-1.29]. Compared with those without multimorbidity at baseline, both cardiometabolic multimorbidity and respiratory multimorbidity were associated with increased mortality from all causes and four major chronic diseases. Cardiometabolic multimorbidity was additionally associated with mortality from cardiovascular diseases and diabetes, with HRs of 2.64 (95% CI = 2.19-3.19) and 28.19 (95% CI = 14.85-53.51), respectively. Respiratory multimorbidity was associated with respiratory disease mortality, with an HR of 9.76 (95% CI = 6.22-15.31). Conclusion: The prevalence of multimorbidity has increased substantially over the past decade. This study has revealed that cardiometabolic multimorbidity and respiratory multimorbidity have significantly increased mortality rates. These findings indicate the need to consider high-risk populations and to provide local evidence for intervention strategies and health management in economically developed regions.

Ketamine administration causes cognitive impairment by destroying the circulation function of the glymphatic system.

BACKGROUND: Ketamine, as a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, was originally used in general anesthesia. Epidemiological data show that ketamine has become one of the most commonly abused drugs in China. Ketamine administration might cause cognitive impairment; however, its molecular mechanism remains unclear. The glymphatic system is a lymphoid system that plays a key role in metabolic waste removal and cognitive regulation in the central nervous system. METHODS: Focusing on the glymphatic system, this study evaluated the behavioral performance and circulatory function of the glymphatic system by building a short-term ketamine administration model in mice, and detected the expression levels of the 5-HT2c receptor, ΔFosb, Pten, Akt, and Aqp4 in the hippocampus. Primary astrocytes were cultured to verify the regulatory relationships among related indexes using a 5-HT2c receptor antagonist, a 5-HT2c receptor short interfering RNA (siRNA), and a ΔFosb siRNA. RESULTS: Ketamine administration induced ΔFosb accumulation by increasing 5-HT2c receptor expression in mouse hippocampal astrocytes and primary astrocytes. ΔFosb acted as a transcription factor to recognize the AATGATTAAT bases in the 5' regulatory region of the Aqp4 gene (-1096 bp to -1087 bp), which inhibited Aqp4 expression, thus causing the circulatory dysfunction of the glymphatic system, leading to cognitive impairment. CONCLUSIONS: Although this regulatory mechanism does not involve the Pten/Akt pathway, this study revealed a new mechanism of ketamine-induced cognitive impairment in non-neuronal systems, and provided a theoretical basis for the safety of clinical treatment and the effectiveness of withdrawal.

Cellular communication network factor 1 promotes retinal leakage in diabetic retinopathy via inducing neutrophil stasis and neutrophil extracellular traps extrusion.

BACKGROUND: Diabetic retinopathy (DR) is a major cause of blindness and is characterized by dysfunction of the retinal microvasculature. Neutrophil stasis, resulting in retinal inflammation and the occlusion of retinal microvessels, is a key mechanism driving DR. These plugging neutrophils subsequently release neutrophil extracellular traps (NETs), which further disrupts the retinal vasculature. Nevertheless, the primary catalyst for NETs extrusion in the retinal microenvironment under diabetic conditions remains unidentified. In recent studies, cellular communication network factor 1 (CCN1) has emerged as a central molecule modulating inflammation in pathological settings. Additionally, our previous research has shed light on the pathogenic role of CCN1 in maintaining endothelial integrity. However, the precise role of CCN1 in microvascular occlusion and its potential interaction with neutrophils in diabetic retinopathy have not yet been investigated. METHODS: We first examined the circulating level of CCN1 and NETs in our study cohort and analyzed related clinical parameters. To further evaluate the effects of CCN1 in vivo, we used recombinant CCN1 protein and CCN1 overexpression for gain-of-function, and CCN1 knockdown for loss-of-function by intravitreal injection in diabetic mice. The underlying mechanisms were further validated on human and mouse primary neutrophils and dHL60 cells. RESULTS: We detected increases in CCN1 and neutrophil elastase in the plasma of DR patients and the retinas of diabetic mice. CCN1 gain-of-function in the retina resulted in neutrophil stasis, NETs extrusion, capillary degeneration, and retinal leakage. Pre-treatment with DNase I to reduce NETs effectively eliminated CCN1-induced retinal leakage. Notably, both CCN1 knockdown and DNase I treatment rescued the retinal leakage in the context of diabetes. In vitro, CCN1 promoted adherence, migration, and NETs extrusion of neutrophils. CONCLUSION: In this study, we uncover that CCN1 contributed to retinal inflammation, vessel occlusion and leakage by recruiting neutrophils and triggering NETs extrusion under diabetic conditions. Notably, manipulating CCN1 was able to hold therapeutic promise for the treatment of diabetic retinopathy.

Curcumin Inhibits α-Synuclein Aggregation by Acting on Liquid-Liquid Phase Transition.

Parkinson's disease (PD), the second most common neurodegenerative disorder, is linked to α-synuclein (α-Syn) aggregation. Despite no specific drug being available for its treatment, curcumin, from the spice turmeric, shows promise. However, its application in PD is limited by a lack of understanding of its anti-amyloidogenic mechanisms. In this study, we first reconstructed the liquid-liquid phase separation (LLPS) of α-Syn in vitro under different conditions, which may be an initial step in entraining the pathogenic aggregation. Subsequently, we evaluated the effects of curcumin on the formation of droplets, oligomers, and aggregated fibers during the LLPS of α-synuclein, as well as its impact on the toxicity of aggregated α-synuclein to cultured cells. Importantly, we found that curcumin can inhibit amyloid formation by inhibiting the occurrence of LLPS and the subsequent formation of oligomers of α-Syn in the early stages of aggregation. Finally, the molecular dynamic simulations of interactions between α-Syn decamer fibrils and curcumin showed that van der Waal's interactions make the largest contribution to the anti-aggregation effect of curcumin. These results may help to clarify the mechanism by which curcumin inhibits the formation of α-Syn aggregates during the development of PD.

Age-adjusted Charlson comorbidity index is associated with the risk of osteoporosis in older fall-prone men: a retrospective cohort study.

BACKGROUND: There is growing evidence linking the age-adjusted Charlson comorbidity index (aCCI), an assessment tool for multimorbidity, to fragility fracture and fracture-related postoperative complications. However, the role of multimorbidity in osteoporosis has not yet been thoroughly evaluated. We aimed to investigate the association between aCCI and the risk of osteoporosis in older adults at moderate to high risk of falling. METHODS: A total of 947 men were included from January 2015 to August 2022 in a hospital in Beijing, China. The aCCI was calculated by counting age and each comorbidity according to their weighted scores, and the participants were stratified into two groups by aCCI: low (aCCI < 5), and high (aCCI ≥5). The Kaplan Meier method was used to assess the cumulative incidence of osteoporosis by different levels of aCCI. The Cox proportional hazards regression model was used to estimate the association of aCCI with the risk of osteoporosis. Receiver operating characteristic (ROC) curve was adapted to assess the performance for aCCI in osteoporosis screening. RESULTS: At baseline, the mean age of all patients was 75.7 years, the mean BMI was 24.8 kg/m2, and 531 (56.1%) patients had high aCCI while 416 (43.9%) were having low aCCI. During a median follow-up of 6.6 years, 296 participants developed osteoporosis. Kaplan-Meier survival curves showed that participants with high aCCI had significantly higher cumulative incidence of osteoporosis compared with those had low aCCI (log-rank test: P < 0.001). When aCCI was examined as a continuous variable, the multivariable-adjusted model showed that the osteoporosis risk increased by 12.1% (HR = 1.121, 95% CI 1.041-1.206, P = 0.002) as aCCI increased by one unit. When aCCI was changed to a categorical variable, the multivariable-adjusted hazard ratios associated with different levels of aCCI [low (reference group) and high] were 1.00 and 1.557 (95% CI 1.223-1.983) for osteoporosis (P <  0.001), respectively. The aCCI (cutoff ≥5) revealed an area under ROC curve (AUC) of 0.566 (95%CI 0.527-0.605, P = 0.001) in identifying osteoporosis in older fall-prone men, with sensitivity of 64.9% and specificity of 47.9%. CONCLUSIONS: The current study indicated an association of higher aCCI with an increased risk of osteoporosis among older fall-prone men, supporting the possibility of aCCI as a marker of long-term skeletal-related adverse clinical outcomes.

Dimension-Confined Growth of a Crack-Free PbS Microplate Array for Infrared Image Sensing.

Epitaxy of semiconductors is a necessary step toward the development of electronic devices such as lasers, detectors, transistors, and solar cells. However, the lattice ordering of semiconductor functional films is inevitably disrupted by excessive concentrated stress due to the mismatch of the thermal expansion coefficient. Herein, combined with the first-principles calculation, we find that a rigid film/substrate bilayer heterostructure with a large thermal expansion mismatch upon cooling to room temperature from growth is free of surface cracks when the rigid film exhibits a dimension smaller than the critical condition for the breaking energy. The principle has been verified in a PbS/SrTiO3 bilayer system that is crack free on PbS single-crystalline microplate arrays through the designing of a dimension-confined growth (DCG) method. Interestingly, this crack-free, large-scale PbS microplate array exhibits exceptional uniformity in morphology, dimensions, thickness, and photodetection properties, enabling a broad-band infrared image sensing. This work provides a new perspective to design materials and arrays that demand smooth and continuous surfaces, which are not limited only to semiconductor electronics but also include mechanical structures, optical materials, biomedical materials, and others.

Multifunctional Nanocomposite Yield-Stress Fluids for Printable and Stretchable Electronics.

Compliant materials are crucial for stretchable electronics. Stretchable solids and gels have limitations in deformability and durability, whereas active liquids struggle to create complex devices. This study presents multifunctional yield-stress fluids as printable ink materials to construct stretchable electronic devices. Ionic nanocomposites comprise silica nanoparticles and ion liquids, while electrical nanocomposites use the natural oxidation of liquid metals to produce gallium oxide nanoflake additives. These nanocomposite inks can be printed on an elastomer substrate and stay in a solid state for easy encapsulation. However, their transition into a liquid state during stretching allows ultrahigh deformability up to the fracture strain of the elastomer. The ionic inks produce strain sensors with high stretchability and temperature sensors with high sensitivity of 7% °C-1. Smart gloves are further created by integrating these sensors with printed electrical interconnects, demonstrating bimodal detection of temperatures and hand gestures. The nanocomposite yield-stress fluids combine the desirable qualities of solids and liquids for stretchable devices and systems.

Pangenome characterization and analysis of the NAC gene family reveals genes for Sclerotinia sclerotiorum resistance in sunflower (Helianthus annuus).

BACKGROUND: Sunflower (Helianthus annuus) is one of the most important economic crops in oilseed production worldwide. The different cultivars exhibit variability in their resistance genes. The NAC transcription factor (TF) family plays diverse roles in plant development and stress responses. With the completion of the H. annuus genome sequence, the entire complement of genes coding for NACs has been identified. However, the reference genome of a single individual cannot cover all the genetic information of the species. RESULTS: Considering only a single reference genome to study gene families will miss many meaningful genes. A pangenome-wide survey and characterization of the NAC genes in sunflower species were conducted. In total, 139 HaNAC genes are identified, of which 114 are core and 25 are variable. Phylogenetic analysis of sunflower NAC proteins categorizes these proteins into 16 subgroups. 138 HaNACs are randomly distributed on 17 chromosomes. SNP-based haplotype analysis shows haplotype diversity of the HaNAC genes in wild accessions is richer than in landraces and modern cultivars. Ten HaNAC genes in the basal stalk rot (BSR) resistance quantitative trait loci (QTL) are found. A total of 26 HaNAC genes are differentially expressed in response to Sclerotinia head rot (SHR). A total of 137 HaNAC genes are annotated in Gene Ontology (GO) and are classified into 24 functional groups. GO functional enrichment analysis reveals that HaNAC genes are involved in various functions of the biological process. CONCLUSIONS: We identified NAC genes in H. annuus (HaNAC) on a pangenome-wide scale and analyzed S. sclerotiorum resistance-related NACs. This study provided a theoretical basis for further genomic improvement targeting resistance-related NAC genes in sunflowers.

[Research progress of tumor-associated macrophages in cervical cancer].

Tumor-associated macrophages (TAM) can be differentiated into M1-type and M2-type macrophage phenotypes in the tumor microenvironment (TME), with M2-type macrophages playing a crucial role in malignant tumors. In cervical cancer, TAM exacerbates human papilloma virus (HPV) infection, promotes the proliferation, invasion, and metastasis of tumor cells, stimulates angiogenesis, and induces immune tolerance. TAM targeting strategies have emerged as a hot topic in cervical cancer immunotherapy.

Heterologous expression of frog antimicrobial peptide Odorranain-C1 in Pichia pastoris: Biological characteristics and its application in food preservation.

To reduce food spoilage and deterioration caused by microbial contamination, antimicrobial peptides (AMPs) have gradually gained attention as a biological preservative. Odorranain-C1 is an α-helical cationic antimicrobial peptide extracted from the skin of frogs with broad-spectrum antimicrobial activity. In this study, we achieved the expression of Odorranain-C1 in Pichia pastoris (P. pastoris) (also known as Komagataella phaffii) by employing DNA recombination technology. The recombinant Odorranain-C1 showed broad-spectrum antibacterial activity and displayed a minimum inhibitory concentration within the range of 8-12 µg.mL-1. Meanwhile, Odorranain-C1 exhibited superior stability and lower hemolytic activity. Mechanistically, Odorranain-C1 disrupted the bacterial membrane's integrity, ultimately causing membrane rupture and subsequent cell death. In tilapia fillets preservation, Odorranain-C1 inhibited the total colony growth and pH variations, while also reducing the production of total volatile basic nitrogen (TVB-N) and thiobarbituric acid (TBA). In conclusion, these studies demonstrated the efficient recombinant expression of Odorranain-C1 in P. pastoris, highlighting its promising utilization in food preservation.

Nonclassical crystallization of goethite nanorods in limpet teeth by self-assembly of silica-rich nanoparticles reveals structure-mechanical property relations.

The intricate organization of goethite nanorods within a silica-rich matrix makes limpet teeth the strongest known natural material. However, the mineralization pathway of goethite in organisms under ambient conditions remains elusive. Here, by investigating the multi-level structure of limpet teeth at different growth stages, it is revealed that the growth of goethite crystals proceeds by the attachment of amorphous nanoparticles, a nonclassical crystallization pathway widely observed during the formation of calcium-based biominerals. Importantly, these nanoparticles contain a high amount of silica, which is gradually expelled during the growth of goethite. Moreover, in mature teeth of limpet, the content of silica correlates with the size of goethite crystals, where smaller goethite crystals are densely packed in the leading part with higher content of silica. Correspondingly, the leading part exhibits higher hardness and elastic modulus. Thus, this study not only reveals the nonclassical crystallization pathway of goethite nanorods in limpet teeth, but also highlights the critical roles of silica in controlling the hierarchical structure and the mechanical properties of limpet teeth, thus providing inspirations for fabricating biomimetic materials with excellent properties.