Treating chronic atrophic gastritis: identifying sub-population based on real-world TCM electronic medical records.

Background and Objective: Chronic atrophic gastritis (CAG) is a complex chronic disease caused by multiple factors that frequently occurs disease in the clinic. The worldwide prevalence of CAG is high. Interestingly, clinical CAG patients often present with a variety of symptom phenotypes, which makes it more difficult for clinicians to treat. Therefore, there is an urgent need to improve our understanding of the complexity of the clinical CAG population, obtain more accurate disease subtypes, and explore the relationship between clinical symptoms and medication. Therefore, based on the integrated platform of complex networks and clinical research, we classified the collected patients with CAG according to their different clinical characteristics and conducted correlation analysis on the classification results to identify more accurate disease subtypes to aid in personalized clinical treatment. Method: Traditional Chinese medicine (TCM) offers an empirical understanding of the clinical subtypes of complicated disorders since TCM therapy is tailored to the patient's symptom profile. We gathered 6,253 TCM clinical electronic medical records (EMRs) from CAG patients and manually annotated, extracted, and preprocessed the data. A shared symptom-patient similarity network (PSN) was created. CAG patient subgroups were established, and their clinical features were determined through enrichment analysis employing community identification methods. Different clinical features of relevant subgroups were correlated based on effectiveness to identify symptom-botanical botanical drugs correspondence. Moreover, network pharmacology was employed to identify possible biological relationships between screened symptoms and medications and to identify various clinical and molecular aspects of the key subtypes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: 5,132 patients were included in the study: 2,699 males (52.60%) and 2,433 females (47.41%). The population was divided into 176 modules. We selected the first 3 modules (M29, M3, and M0) to illustrate the characteristic phenotypes and genotypes of CAG disease subtypes. The M29 subgroup was characterized by gastric fullness disease and internal syndrome of turbidity and poison. The M3 subgroup was characterized by epigastric pain and disharmony between the liver and stomach. The M0 subgroup was characterized by epigastric pain and dampness-heat syndrome. In symptom analysis, The top symptoms for symptom improvement in all three subgroups were stomach pain, bloating, insomnia, poor appetite, and heartburn. However, the three groups were different. The M29 subgroup was more likely to have stomach distention, anorexia, and palpitations. Citrus medica, Solanum nigrum, Jiangcan, Shan ci mushrooms, and Dillon were the most popular botanical drugs. The M3 subgroup has a higher incidence of yellow urine, a bitter tongue, and stomachaches. Smilax glabra, Cyperus rotundus, Angelica sinensis, Conioselinum anthriscoides, and Paeonia lactiflora were the botanical drugs used. Vomiting, nausea, stomach pain, and appetite loss are common in the M0 subgroup. The primary medications are Scutellaria baicalensis, Smilax glabra, Picrorhiza kurroa, Lilium lancifolium, and Artemisia scoparia. Through GO and KEGG pathway analysis, We found that in the M29 subgroup, Citrus medica, Solanum nigrum, Jiangcan, Shan ci mushrooms, and Dillon may exert their therapeutic effects on the symptoms of gastric distension, anorexia, and palpitations by modulating apoptosis and NF-κB signaling pathways. In the M3 subgroup, Smilax glabra, Cyperus rotundus, Angelica sinensis, Conioselinum anthriscoides, and Paeonia lactiflora may be treated by NF-κB and JAK-STAT signaling pathway for the treatment of stomach pain, bitter mouth, and yellow urine. In the M0 subgroup, Scutellaria baicalensis, Smilax glabra, Picrorhiza kurroa, Lilium lancifolium, and Artemisia scoparia may exert their therapeutic effects on poor appetite, stomach pain, vomiting, and nausea through the PI3K-Akt signaling pathway. Conclusion: Based on PSN identification and community detection analysis, CAG population division can provide useful recommendations for clinical CAG treatment. This method is useful for CAG illness classification and genotyping investigations and can be used for other complicated chronic diseases.

Red-light-dependent chlorophyll synthesis kindles photosynthetic recovery of chlorotic dormant cyanobacteria using a dark-operative enzyme.

Chlorosis dormancy resulting from nitrogen starvation and its resuscitation upon available nitrogen contributes greatly to the fitness of cyanobacterial population under nitrogen-fluctuating environments. The reinstallation of the photosynthetic machinery is a key process for resuscitation from a chlorotic dormant state; however, the underlying regulatory mechanism is still elusive. Here, we reported that red light is essential for re-greening chlorotic Synechocystis sp. PCC 6803 (a non-diazotrophic cyanobacterium) after nitrogen supplement under weak light conditions. The expression of dark-operative protochlorophyllide reductase (DPOR) governed by the transcriptional factor RpaB was strikingly induced by red light in chlorotic cells, and its deficient mutant lost the capability of resuscitation from a dormant state, indicating DPOR catalyzing chlorophyll synthesis is a key step in the photosynthetic recovery of dormant cyanobacteria. Although light-dependent protochlorophyllide reductase is widely considered as a master switch in photomorphogenesis, this study unravels the primitive DPOR as a spark to activate the photosynthetic recovery of chlorotic dormant cyanobacteria. These findings provide new insight into the biological significance of DPOR in cyanobacteria and even some plants thriving in extreme environments.

Nitric oxide mediates positive regulation of Nostoc flagelliforme polysaccharide yield via potential S-nitrosylation of G6PDH and UGDH.

Based on our previous findings that salicylic acid and jasmonic acid increased Nostoc flagelliforme polysaccharide yield by regulating intracellular nitric oxide (NO) levels, the mechanism through which NO affects polysaccharide biosynthesis in Nostoc flagelliforme was explored from the perspective of S-nitrosylation (SNO). The addition of NO donor and scavenger showed that intracellular NO had a significant positive effect on the polysaccharide yield of N. flagelliforme. To explore the mechanism, we investigated the relationship between NO levels and the activity of several key enzymes involved in polysaccharide biosynthesis, including fructose 1,6-bisphosphate aldolase (FBA), glucokinase (GK), glucose 6-phosphate dehydrogenase (G6PDH), mitochondrial isocitrate dehydrogenase (ICDH), and UDP-glucose dehydrogenase (UGDH). The enzymatic activities of G6PDH, ICDH, and UGDH were shown to be significantly correlated with the shifts in intracellular NO levels. For further validation, G6PDH, ICDH, and UGDH were heterologously expressed in Escherichia coli and purified via Ni+-NAT affinity chromatography, and subjected to a biotin switch assay and western blot analysis, which revealed that UGDH and G6PDH were susceptible to SNO. Furthermore, mass spectrometry analysis of proteins treated with S-nitrosoglutathione (GSNO) identified the SNO modification sites for UGDH and G6PDH as cysteine 423 and cysteine 249, respectively. These findings suggest that NO modulates polysaccharide biosynthesis in N. flagelliforme through SNO of UGDH and G6PDH. This reveals a potential mechanism through which NO promotes polysaccharide synthesis in N. flagelliforme, while also providing a new strategy for improving the industrial production of polysaccharides.

Chemical Isotope Labeling and Dual-Filtering Strategy for Comprehensive Profiling of Urinary Glucuronide Conjugates.

Glucuronidation, a crucial process in phase II metabolism, plays a vital role in the detoxification and elimination of endogenous substances and xenobiotics. A comprehensive and confident profiling of glucuronate-conjugated metabolites is imperative to understanding their roles in physiological and pathological processes. In this study, a chemical isotope labeling and dual-filtering strategy was developed for global profiling of glucuronide metabolites in biological samples. N,N-Dimethyl ethylenediamine (DMED-d0) and its deuterated counterpart DMED-d6 were used to label carboxylic acids through an amidation reaction. First, carboxyl-containing compounds were extracted based on a characteristic mass difference (Δm/z, 6.037 Da) observed in MS between light- and heavy-labeled metabolites (filter I). Subsequently, within the pool of carboxyl-containing compounds, glucuronides were identified using two pairs of diagnostic ions (m/z 247.1294/253.1665 and 229.1188/235.1559 for DMED-d0/DMED-d6-labeled glucuronides) originating from the fragmentation of the derivatized glucuronic acid group in MS/MS (filter II). Compared with non-derivatization, DEMD labeling significantly enhanced the detection sensitivity of glucuronides, as evidenced by a 3- to 55-fold decrease in limits of detection for representative standards. The strategy was applied to profiling glucuronide metabolites in urine samples from colorectal cancer (CRC) patients. A total of 685 features were screened as potential glucuronides, among which 181 were annotated, mainly including glucuronides derived from lipids, organic oxygen, and phenylpropanoids. Enzymatic biosynthesis was employed to accurately identify unknown glucuronides without standards, demonstrating the reliability of the dual-filtering strategy. Our strategy exhibits great potential for profiling the glucuronide metabolome with high coverage and confidence to reveal changes in CRC and other diseases.

Gßγ dimers mediate low K+ stress-inhibited root growth via modulating auxin redistribution in Arabidopsis.

In the investigation of heterotrimeric G protein-mediated signal transduction in planta, their roles in the transmittance of low K+ stimuli remain to be elucidated. Here, we found that the primary root growth of wild-type Arabidopsis was gradually inhibited with the decrease of external K+ concentrations, while the primary root of the mutants for G protein ß subunit AGB1 and γ subunits AGG1, AGG2 and AGG3 could still grow under low K+ conditions (LK). Exogenous NAA application attenuated primary root elongation in agb1 and agg1/2/3 but promoted the growth in wild-type seedlings under LK stress. Using ProDR5:GFP, ProPIN1:PIN1-GFP and ProPIN2:PIN2-GFP reporter lines, a diminishment in auxin concentration at the radicle apex and a reduction in PIN1and PIN2 efflux carrier abundance were observed in wild-type roots under LK, a phenomenon not recorded in the agb1 and agg1/2/3. Further proteolytic and transcriptional assessments revealed an enhanced degradation of PIN1 and a suppressed expression of PIN2 in the wild-type background under LK, contrasting with the stability observed in the agb1 and agg1/2/3 mutants. Our results indicate that the G protein ß and γ subunits play pivotal roles in suppressing of Arabidopsis root growth under LK by modulating auxin redistribution via alterations in PIN1 degradation and PIN2 biosynthesis.

Rescue and characterization of PCV4 infectious clones: pathogenesis and immune response in piglets.

Porcine circovirus 4 (PCV4) was first identified in 2019, categorized within the genus Circovirus in the family Circoviridae. To date, the virus has not been isolated from clinical samples. Meanwhile, many aspects of the biology and pathogenic mechanisms of PCV4 infection remain unknown. In this study, PCV4 was successfully rescued from an infectious clone. We utilized a PCV4 virus stock derived from this infectious clone to intranasally inoculate 4-week-old specific-pathogen-free piglets to evaluate PCV4 pathogenesis. The rescued PCV4 was capable of replicating in both PK-15 cells and piglets, with the virus detectable in nearly all collected samples from the challenge groups. Pathological lesions and PCV4-specific antigens were observed in various tissues and organs, including the lungs, kidneys, lymph nodes, spleen, and liver, in the inoculated piglets. Additionally, the levels of pro-inflammatory cytokines in the serum of the PCV4-inoculated group were significantly elevated compared to the control group, indicating that the induced inflammatory response may contribute to tissue damage associated with PCV4 infection. These findings offer new insights into the pathogenesis and inflammatory responses associated with PCV4-related diseases.

Association between PER and CRY gene polymorphisms and the response to caffeine citrate treatment in infants with apnea of prematurity.

Background: Circadian rhythms impact metabolism and the therapeutic effects of drugs. The purpose of this study was to determine the association between PER and CRY polymorphisms and caffeine citrate treatment response in infants with apnea of prematurity. Methods: A total of 221 preterm infants of gestational age <34 weeks were included in this study (160 in the response group and 61 in the non-response group). The propensity score matching method was used to perform a 1:1 matching for all premature infants, and the general characteristics and clinical outcomes of the two groups were compared. The association between polymorphisms of the circadian transcription repressors PER and CRY and caffeine citrate treatment response in infants with apnea of prematurity was analyzed with co-dominant, dominant, recessive, and over-dominant models, as well as analysis of alleles. Generalized multifactor dimensionality reduction (GMDR) analysis was used to analyze the interaction between the PER and CRY genes. Results: After propensity score matching, 45 preterm infants were included in each of the response and non-response groups, and there were no statistically significant differences in general characteristics between the two groups (P > 0.05). Infants in the non-response groups had a higher incidence of moderate and severe bronchopulmonary dysplasia (BPD) (P = 0.043), retinopathy of prematurity (ROP) (P = 0.035), and invasive ventilation (P = 0.027), and their duration of oxygen use (P = 0.041) was longer. When corrected for false discovery rate, the PER3 rs228669 recessive model (P FDR = 0.045) and the over-dominant model (P FDR = 0.045) were both associated with caffeine citrate treatment response. Preterm infants with the rs228669 CC genotype had a significantly lower rate of caffeine citrate non-response in the recessive model (OR = 0.28, 95% CI = 0.12-0.66), which was significantly higher in preterm infants with the CT genotype in the over-dominant model (OR = 4.18, 95% CI = 1.64-10.66). GMDR analysis revealed an interaction between the PER and CRY genes (P < 0.05). Conclusions: Circadian rhythms may play a role in the response of premature infants to caffeine citrate, and polymorphisms of the PER and CRY genes may influence the effectiveness of caffeine citrate treatment for apnea of prematurity.

The Connection between Sleep Patterns and Mental Health: Insights from Rural Chinese Students.

BACKGROUND: The association between sleep patterns and young students' mental health, which is crucial for their development, remains understudied in rural China. Therefore, the relationship between sleep patterns and mental health among primary and junior high school students in rural China was examined. METHOD: A total of 1592 primary and junior high school students from rural areas of Gansu Province were surveyed, and the Depression Anxiety and Stress Scale (DASS) was utilized to assess mental health, alongside self-reported data on their daily sleep patterns. RESULTS: Significant sleep inadequacies were identified: 28% of students received less than 8 h of sleep on weekdays, and 19% went to bed later than recommended. On weekends, 38% of students had delayed bedtimes, though only 7.2% received less than 8 h of sleep. Notably, a "U-shaped" relationship was uncovered between sleep duration and mental health for students on weekends, with optimal mental health correlated with receiving 10-11 h of sleep, while both shorter and longer sleep durations on weekends worsened outcomes. This pattern is absent on weekdays. Additionally, adequate sleep and an earlier bedtime was linked to a 6-8% decrease in mental health risks. CONCLUSIONS: These findings provide valuable insights for policymakers seeking to enhance student mental well-being in rural settings, emphasizing the importance of implementing measures that promote balanced sleep habits among young students.

Para-Hydroxycinnamic Acid Mitigates Senescence and Inflammaging in Human Skin Models.

Para-hydroxycinnamic acid (pHCA) is one of the most abundant naturally occurring hydroxycinnamic acids, a class of chemistries known for their antioxidant properties. In this study, we evaluated the impact of pHCA on different parameters of skin aging in in vitro skin models after H2O2 and UV exposure. These parameters include keratinocyte senescence and differentiation, inflammation, and energy metabolism, as well as the underlying molecular mechanisms. Here we demonstrate that pHCA prevents oxidative stress-induced premature senescence of human primary keratinocytes in both 2D and 3D skin models, while improving clonogenicity in 2D. As aging is linked to inflammation, referred to as inflammaging, we analyzed the release of IL-6, IL-8, and PGE2, known to be associated with senescence. All of them were downregulated by pHCA in both normal and oxidative stress conditions. Mechanistically, DNA damage induced by oxidative stress is prevented by pHCA, while pHCA also exerts a positive effect on the mitochondrial and glycolytic functions under stress. Altogether, these results highlight the protective effects of pHCA against inflammaging, and importantly, help to elucidate its potential mechanisms of action.

Seroreactivity against Leptospira spp. differs between community cats and privately-owned cats in Hong Kong.

Leptospirosis is a bacterial zoonotic disease of major One Health significance and public health impact globally, with a wide host range including mammals, cetaceans and herpetofauna. This study aimed to determine Leptospira seroprevalence, risk factors for seroreactivity and prevalence of urinary Leptospira shedding among domestic cats in Hong Kong. Microagglutination testing of 22 Leptospira serovars from 20 serogroups was performed on 738 sera from outdoor free-roaming "community" cats (n = 391) and privately-owned (n = 347) cats. Urine from 268 community cats was tested for pathogenic Leptospira DNA by qPCR targeting lipL32. Potential risk factors associated with exposure were assessed using logistic regression. Overall Leptospira seroprevalence was 9.35%. Of 14 serogroups detected, Javanica (4.3%), Djasiman (2.3%) and Australis (1.5%) were most common. Seroreactivity was significantly higher among community (13.3%) than privately-owned cats (4.9%; OR 2.98 [95% CI 1.68-5.25], P < 0.001), especially to Javanica (7.65% of community cats versus 0.58% of privately-owned cats (P < 0.001). Antibody titres to all serogroups ranged from 1:100 to 1:6400 (median 1:200) and were highest for Javanica (median 1:800). Leptospira DNA was detected in urine from 12/268 community cats (4.48%; median load 6.42 × 102 copies/mL urine; range 1.40 × 101-9.63 × 104). One in three seroreactive community cats with paired urine and blood samples had leptospiruria. After adjusting for source, none of breed, sex, neuter status, age, district rodent infestation rate, serum alanine transaminase or creatinine values were associated with seroreactivity. Cats in Hong Kong are exposed to a diversity of Leptospira serogroups and can shed Leptospira silently in urine. The higher seroprevalence among outdoor free-roaming community cats highlights the importance of environmental drivers in leptospirosis transmission and risks of exposure for sympatric human populations. Gloves should be worn when handling feline urine to minimise the risk of zoonotic transmission from subclinically infected cats.

[Effect of total saponins from Panacis Majoris Rhizoma on proliferation, apoptosis and autophagy of human cervical carcinoma HeLa cells].

This paper investigated the effect of total saponins from Rhizoma Panacis Majoris on the proliferation, apoptosis, and autophagy of human cervical carcinoma HeLa cells. The saponin content was detected by ultraviolet-visible spectrophotometry. Cell coun-ting kit-8(CCK-8) assay, 4,6-diamidino-2-phenylindole(DAPI) staining, and flow cytometry were used to detect the effects of total saponins of Panacis Majoris Rhizoma on cell viability, morphology, cell cycle and apoptosis of HeLa cells. Western blot was used to detect the expression of apoptosis-related proteins B cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cleaved caspase-9, and cleaved caspase-3, autophagy-related proteins Beclin-1 and SQSTM1(p62), and the proteins related to the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR) and mitogen-activated protein kinase(MAPK) signaling pathways. It was found that the yield and saponin content of total saponins from Rhizoma Panacis Majoris were 6.3% and 78.3%, respectively. Total saponins from Rhizoma Panacis Majoris could significantly inhibit the proliferation(P<0.001), effect the nuclear morphology, block the G_0/G_1 cycle, and induce cell apoptosis in HeLa cells with a concentration-dependent manner. In addition, total saponins from Rhizoma Panacis Majoris up-regulated the expression of pro-apoptotic proteins Bax, cleaved caspase-9, and cleaved caspase-3, and autophagy-related protein p62(P<0.05), while down-regulated the expression of anti-apoptotic protein Bcl-2 and autophagy-related protein Beclin-1(P<0.01). Total saponins from Rhizoma Panacis Majoris could promote the expression of p-p38/p38, p-Jun N-terminal kinase(JNK)/JNK, p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR proteins in PI3K/Akt/mTOR and MAPK signaling pathways(P<0.05). In contrast, the effect on p-ERK/ERK expression was not obvious. Therefore, total saponins from Rhizoma Panacis Majoris may inhibit autophagy and promote apoptosis of HeLa cells through the activation of the PI3K/Akt/mTOR, c-JNK, and p38 MAPK signaling pathways, which indicates that total saponins from Rhizoma Panacis Majoris may have a potential role in cervical cancer treatment.

Identification of anoikis-related gene signatures and construction of the prognosis model in prostate cancer.

Background: One of the primary reasons for tumor invasion and metastasis is anoikis resistance. Biochemical recurrence (BCR) of prostate cancer (PCa) serves as a harbinger of its distant metastasis. However, the role of anoikis in PCa biochemical recurrence has not been fully elucidated. Methods: Differential expression analysis was used to identify anoikis-related genes based on the TCGA and GeneCards databases. Prognostic models were constructed utilizing LASSO regression, univariate and multivariate Cox regression analyses. Moreover, Gene Expression Omnibus datasets (GSE70770 and GSE46602) were applied as validation cohorts. Gene Ontology, KEGG and GSVA were utilized to explore biological pathways and molecular mechanisms. Further, immune profiles were assessed using CIBERSORT, ssGSEA, and TIDE, while anti-cancer drugs sensitivity was analyzed by GDSC database. In addition, gene expressions in the model were examined using online databases (Human Protein Atlas and Tumor Immune Single-Cell Hub). Results: 113 differentially expressed anoikis-related genes were found. Four genes (EEF1A2, RET, FOSL1, PCA3) were selected for constructing a prognostic model. Using the findings from the Cox regression analysis, we grouped patients into groups of high and low risk. The high-risk group exhibited a poorer prognosis, with a maximum AUC of 0.897. Moreover, larger percentage of immune infiltration of memory B cells, CD8 Tcells, neutrophils, and M1 macrophages were observed in the high-risk group than those in the low-risk group, whereas the percentage of activated mast cells and dendritic cells in the high-risk group were lower. An increased TIDE score was founded in the high-risk group, suggesting reduced effectiveness of ICI therapy. Additionally, the IC50 results for chemotherapy drugs indicated that the low-risk group was more sensitive to most of the drugs. Finally, the genes EEF1A2, RET, and FOSL1 were expressed in PCa cases based on HPA website. The TISCH database suggested that these four ARGs might contribute to the tumor microenvironment of PCa. Conclusion: We created a risk model utilizing four ARGs that effectively predicts the risk of BCR in PCa patients. This study lays the groundwork for risk stratification and predicting survival outcomes in PCa patients with BCR.

Study on factors influencing carbon dioxide emissions and carbon peak heterogenous pathways in Chinese provinces.

Implementing a Carbon Peak Action Plan at the regional level requires comprehensive consideration of the developmental heterogeneity among different provinces, which is an effective pathway for China to realize the goal of carbon peak by 2030. However, there is currently no clear provincial roadmap for carbon peak, and existing studies on carbon peak pathways inadequately address provincial heterogeneity. Therefore, this paper employs the Stochastic Impacts by Regression on Population, Affluence, and Technology (STIRPAT) model to decompose assess 8 factors influencing carbon emissions of 30 provinces. According to scenario analysis, the paper explores the differentiated pathways for provincial carbon peaks based on policy expectation indicators (including population, economy, and urbanization rate) and comprises policy control indicators (including the energy structure, energy efficiency, industrial structure, transportation structure, and innovation input). The results indicate that population, per capita GDP, urbanization rate, and innovation input are the primary factors for influencing (negatively) the growth of carbon emissions. In contrast, the optimization and upgrading of the industrial structure, energy intensity, energy structure, and transportation structure have mitigating effects on carbon emissions, especially for the first two factors. The forecasting results reveal that robust regulations of the energy and industry can effectively accelerate carbon peak at a reduced magnitude. If developed at BAU, China cannot achieve carbon peak by 2030, continuing an upward trend. However, by maximizing the adjustment strength of energy and industrial transformation within the scope of provincial capabilities, China could achieve carbon peak as early as 2025, with a peak of 12.069 billion tons. In this scenario, 24 provinces could achieve carbon peak before 2030. Overall, this study suggests the feasibility of differentiated pathway to achieve carbon peaks in China, exploring the carbon peak potential and paths of 30 provinces, and identifying provinces where carbon peak is more challenging. It also provides a reference for the design of carbon peak roadmaps at both provincial and national levels and offers targeted recommendations for the implementation of differentiated policy strategies for the government.

Superlarge, Rigidified DNA Tetrahedron with a Y-Shaped Backbone for Organizing Biomolecules Spatially and Maintaining Their Full Bioactivity.

A major impediment to the clinical translation of DNA tiling nanostructures is a technical bottleneck for the programmable assembly of DNA architectures with well-defined local geometry due to the inability to achieve both sufficient structural rigidity and a large framework. In this work, a Y-backbone was inserted into each face to construct a superlarge, sufficiently rigidified tetrahedral DNA nanostructure (called RDT) with extremely high efficiency. In RDT, the spatial size increased by 6.86-fold, and the structural rigidity was enhanced at least 4-fold, contributing to an ∼350-fold improvement in the resistance to nucleolytic degradation even without a protective coating. RDT can be mounted onto an artificial lipid-bilayer membrane with molecular-level precision and well-defined spatial orientation that can be validated using the fluorescence resonance energy transfer (FRET) assay. The spatial orientation of Y-shaped backbone-rigidified RDT is unachievable for conventional DNA polyhedrons and ensures a high level of precision in the geometric positioning of diverse biomolecules with an approximately homogeneous environment. In tests of RDT, surface-confined horseradish peroxidase (HRP) exhibited nearly 100% catalytic activity and targeting aptamer-immobilized gold nanoparticles showed 5.3-fold enhanced cellular internalization. Significantly, RDT exhibited a 27.5-fold enhanced structural stability in a bodily environment and did not induce detectable systemic toxicity.

Application of Weak-Beam Dark-Field STEM for Dislocation Loop Analysis†.

Nanoscale dislocation loops formed by irradiation can significantly contribute to both irradiation hardening and embrittlement of materials when subjected to extreme nuclear reactor environments. This study explores the application of weak-beam dark-field (WBDF) scanning transmission electron microscopy (STEM) methods for quantitative irradiation-induced defect analysis in crystalline materials, with a specific focus on dislocation loop imaging and analysis. A high-purity Fe-5 wt% Cr model alloy was irradiated with 8 MeV Fe2+ ions at 450°C to a fluence of 8.8 × 1019 m-2, inducing dislocation loops for analysis. While transmission electron microscopy (TEM) has traditionally been the primary tool for dislocation imaging, recent advancements in STEM technology have reignited interest in using STEM for defect imaging. This study introduces and compares three WBDF STEM methods, demonstrating their effectiveness in suppressing background contrasts, isolating defect information for dislocation loop type classification, providing finer dislocation line images for small loop analysis, and presenting inside-outside contrast for identifying loop nature. Experimental findings indicate that WBDF STEM methods surpass traditional TEM approaches, yielding clearer and more detailed images of dislocation loops. The study concludes by discussing the potential applications of WBDF STEM techniques in defect analysis, emphasizing their adaptability across various material systems beyond nuclear materials.

Droplet Impact on Superhydrophobic Mesh Surfaces.

Reducing the contact time of droplet impacts on surfaces is crucial for various applications including corrosion prevention and anti-icing. This study aims to explore a novel strategy that greatly reduces contact time using a superhydrophobic mesh surface with multiple sets of mutually perpendicular ridges while minimizing the influence of the impacting location. The effects of the impact Weber numbers and ridge spacing on the characteristics of the impact dynamics and contact time are studied experimentally. The experimental results reveal that, for the droplet impact on mesh surfaces, ridges can segment the liquid film into independently multiple-retracting liquid subunits. The retracted subunits provide the upward driving force, which may promote the splashing or pancake bouncing of droplets. At this point, the contact time has a negligible sensitivity for the impacting position and is significantly reduced by up to 68%. Furthermore, the time, dynamic pressure, and energy criteria for triggering splashing and pancake bouncing are proposed theoretically. This work provides an understanding of the mechanism and the design guidelines for effectively reducing the contact time of the impacting droplet on superhydrophobic surfaces.

Rapid, sensitive, and visual detection of pseudorabies virus with an RPA-CRISPR/EsCas13d-based dual-readout portable platform.

Pseudorabies viruses (PRV) pose a major threat to the global pig industry and public health. Rapid, intuitive, affordable, and accurate diagnostic testing is critical for controlling and eradicating infectious diseases. In this study, a portable detection platform based on RPA-CRISPR/EsCas13d was developed. The platform exhibits high sensitivity (1 copy/µL), good specificity, and no cross-reactivity with common pathogens. The platform uses rapid preamplification technology to provide visualization results (lateral flow assays or visual fluorescence) within 1 h. Fifty pig samples (including tissues, oral fluids, and serum) were tested using this platform and real-time quantitative polymerase chain reaction (qPCR), showing 34.0 % (17 of 50) PRV positivity with the portable CRISPR/EsCas13d dual-readout platform, consistent with the qPCR results. These results highlight the stability, sensitivity, efficiency, and low equipment requirements of the portable platform. Additionally, a novel point-of-care test is being developed for clinical use in remote rural and resource-limited areas, which could be a prospective measure for monitoring the progression of pseudorabies and other infectious diseases worldwide.

MAMs and Mitochondrial Quality Control: Overview and Their Role in Alzheimer's Disease.

Alzheimer's disease (AD) represents the most widespread neurodegenerative disorder, distinguished by a gradual onset and slow progression, presenting a substantial challenge to global public health. The mitochondrial-associated membrane (MAMs) functions as a crucial center for signal transduction and material transport between mitochondria and the endoplasmic reticulum, playing a pivotal role in various pathological mechanisms of AD. The dysregulation of mitochondrial quality control systems is considered a fundamental factor in the development of AD, leading to mitochondrial dysfunction and subsequent neurodegenerative events. Recent studies have emphasized the role of MAMs in regulating mitochondrial quality control. This review will delve into the molecular mechanisms underlying the imbalance in mitochondrial quality control in AD and provide a comprehensive overview of the role of MAMs in regulating mitochondrial quality control.

Exploring the Charge-Transport and Optical Characteristics of Organic Doublet Radicals: A Theoretical and Experimental Study with Photovoltaic Applications.

Herein, we present a series of stable radicals containing a trityl carbon-centered radical moiety exhibiting interesting properties. The radicals demonstrate the most blue-shifted anti-Kasha doublet emission reported so far with high color purity (full width at half-maximum of 46 nm) and relatively high photoluminescence quantum yields of deoxygenated toluene solutions reaching 31%. The stable radicals demonstrate equilibrated bipolar charge transport with charge mobility values reaching 10-4 cm2/V·s at high electric fields. The experimental results in combination with the results of TD-DFT calculations confirm that the blue emission of radicals violates the Kasha rule and originates from higher excited states, whereas the bipolar charge transport properties are found to stem from the particularity of radicals to involve the same molecular orbital(s) in electron and hole transport. The radicals act as the efficient materials for interlayers, passivating interfacial defects and enhancing charge extraction in PSCs. Consequently, this leads to outstanding performance of PSC, with power conversion efficiency surpassing 21%, accompanied by a remarkable increase in open-circuit voltage and exceptional stability.

An Integrated Optogenetic and Bioelectronic Platform for Regulating Cardiomyocyte Function.

Bioelectronic medicine is emerging as a powerful approach for restoring lost endogenous functions and addressing life-altering maladies such as cardiac disorders. Systems that incorporate both modulation of cellular function and recording capabilities can enhance the utility of these approaches and their customization to the needs of each patient. Here is report an integrated optogenetic and bioelectronic platform for stable and long-term stimulation and monitoring of cardiomyocyte function in vitro. Optical inputs are achieved through the expression of a photoactivatable adenylyl cyclase, that when irradiated with blue light causes a dose-dependent and time-limited increase in the secondary messenger cyclic adenosine monophosphate with subsequent rise in autonomous cardiomyocyte beating rate. Bioelectronic readouts are obtained through a multi-electrode array that measures real-time electrophysiological responses at 32 spatially-distinct locations. Irradiation at 27 µW mm-2 results in a 14% elevation of the beating rate within 20-25 min, which remains stable for at least 2 h. The beating rate can be cycled through "on" and "off" light states, and its magnitude is a monotonic function of irradiation intensity. The integrated platform can be extended to stretchable and flexible substrates, and can open new avenues in bioelectronic medicine, including closed-loop systems for cardiac regulation and intervention, for example, in the context of arrythmias.