RESUMEN

Background: The interplay between colon adenocarcinoma (COAD) and branched-chain amino acid (BCAA) metabolism is not fully understood, presenting a crucial area for investigation. Methods: We developed a prognostic model based on BCAA metabolism using the least absolute shrinkage and selection operator (LASSO) regression algorithm. We employed qRT-PCR and Western blot analyses to examine NOTCH3 expression in COAD tissues versus adjacent non-cancerous tissues and various cell lines. We also investigated the impact of NOTCH3 on COAD cell proliferation, invasion, and migration through in vitro and in vivo experiments. Results: Our BCAA metabolism-related signature (BRS) distinguished between different immune features, tumor mutation burdens, responses to immunotherapy, and drug sensitivity among COAD patients. NOTCH3 was found to be overexpressed in COAD, promoting tumor growth as verified through various assays. The model effectively predicted COAD prognosis and patient responses to treatments, underscoring the potential of BCAA pathways as therapeutic targets. Conclusion: The BRS is instrumental in predicting the prognosis and therapeutic response in COAD, with NOTCH3 playing a significant role in the proliferation, invasion and migration of COAD. These findings suggest that targeting BCAA metabolism and NOTCH3 could advance COAD treatment strategies.

Asunto(s)

Asunto(s)

RESUMEN

Denitrification driven by bacteria and fungi is the main source of nitrous oxide （N2O） emissions from paddy soil. It is generally believed that biochar reduces N2O emissions by influencing the bacterial denitrification process, but the relevant mechanism of its impact on fungal denitrification is still unclear. In this study, the long-term straw carbonization returning experimental field in Changshu Agricultural Ecological Experimental Base of the Chinese Academy of Sciences was taken as the object. Through indoor anaerobic culture and molecular biology technology, the relative contributions of bacteria and fungi to denitrifying N2O production in paddy soil and the related microorganism mechanism were studied under different long-term biochar application amounts （blank, 2.25 t·hm-2, and 22.5 t·hm-2, respectively, expressed by BC0, BC1, and BC10）. The results showed that compared with that in BC0, biochar treatment significantly reduced N2O emission rate, denitrification potential, and cumulative N2O emissions, and the contribution of bacterial denitrification was greater than that of fungal denitrification in all three treatments. Among them, the relative contribution rate of bacterial denitrification in BC10 （62.9%） was significantly increased compared to BC0 （50.8%）, whereas the relative contribution rate of fungal denitrification in BC10 （37.1%） was significantly lower than that in BC0 （49.2%）. The application of biochar significantly increased the abundance of bacterial denitrification functional genes （nirK, nirS, and nosZ） but reduced the abundance of fungal nirK genes. The contribution rate of fungal denitrification was significantly positively correlated with the N2O emission rate and negatively correlated with soil pH, TN, SOM, and DOC. Biochar may have inhibited the growth of denitrifying fungi by increasing pH and carbon and nitrogen content, reducing the abundance of related functional genes, thereby weakening the reduction ability of NO to N2O during fungal denitrification process. This significantly reduces the contribution rate of N2O production during the fungal denitrification process and the denitrification N2O emissions from paddy soil. This study helps to broaden our understanding of the denitrification process in paddy soil and provides a theoretical basis for further regulating fungal denitrification N2O emissions.

Asunto(s)

RESUMEN

OBJECTIVE: Lindqvist-type polyoxometalates (POMs) exhibit potential antitumor activities. This study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying mechanism. METHODS: Using different cancer cell lines, the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side strains. Cell colony formation assay, autophagy detection, mitochondrial observation, qRT-PCR, Western blotting, and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related mechanism. RESULTS: MO-4, a Lindqvist-type POM linking a proline at its side strain, was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer cells. It was found that MO-4 induced the apoptosis of multiple types of breast cancer cells. Mechanistically, MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species (ROS) levels and resulting in apoptosis. In vivo, breast tumor growth and distant metastasis were significantly reduced following MO-4 treatment. CONCLUSION: Collectively, the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.

Asunto(s)

RESUMEN

Inflammatory arthritis leads to peripheral nerve sensitization, but the therapeutic effect is often unsatisfactory. Our preliminary studies have found that in mice with inflammatory arthritis, the use of ionotropic glutamate receptor antagonists can produce a good analgesic effect without altering foot swelling, suggesting that pain relief may be related to the improvement of neuropathic pain. However, the underlying mechanisms remain unclear. To further investigate the effects of neuropathic pain medications on inflammatory arthritis and the impact of the ionotropic glutamate receptor NR2B subunit (NR2B) on inflammatory arthritis, this study employed gabapentin (GBP) treatment on the inflammatory arthritis mouse model (the adjuvant induced arthritis, AIA), and we found a significant reduction in pain. Further studies revealed that in AIA, the expression levels of NR2B, TRPV1, pain-related molecules (substance P, PGE2), inflammatory cytokines (IL-1, IL-6, TNF-α, and GM-CSF) and Ca2+ were elevated in the foot and dorsal root ganglia (DRG). GBP treatment was able to influence the downregulation of the expression levels of NR2B, TRPV1, pain-related molecules, inflammatory cytokines and Ca2+. Mechanistic studies have shown that GBP treatment affects the downregulation of NR2B, and the downregulation of NR2B expression leads to the downregulation of TRPV1, pain-related molecules and inflammatory cytokines, thereby alleviating pain. These results suggest that in peripheral sensitization caused by AIA, GBP can play a role in improving pain, and NR2B may be a key target of peripheral nerve sensitization induced by inflammatory arthritis. GBP provides a theoretical basis for the clinical treatment of inflammatory arthritis.

Asunto(s)

RESUMEN

The high operating voltage of conventional nanoelectromechanical switches, typically tens of volts, is much higher than the driving voltage of the complementary metal oxide semiconductor integrated circuit (∼1 V). Though the operating voltage can be reduced by adopting a narrow air gap, down to several nanometers, this leads to formidable manufacturing challenges and occasionally irreversible switch failures due to the surface adhesive force. Here, we demonstrate a new nanowire-morphed nanoelectromechanical (NW-NEM) switch structure with ultralow operation voltages. In contrast to conventional nanoelectromechanical switches actuated by unidirectional electrostatic attraction, the NW-NEM switch is bidirectionally driven by Lorentz force to allow the use of a large air gap for excellent electrical isolation, while achieving a record-low driving voltage of <0.2 V. Furthermore, the introduction of the Lorentz force allows the NW-NEM switch to effectively overcome the adhesion force to recover to the turn-off state.

RESUMEN

Emerging evidence suggests that neurological and other post-acute sequelae of COVID-19 can persist beyond or develop following SARS-CoV-2 infection. However, the long-term trajectories of cognitive change after a COVID-19 infection remain unclear. Here we investigated cognitive changes over a period of 2.5 years among 1,245 individuals aged 60 years or older who survived infection with the original SARS-CoV-2 strain in Wuhan, China, and 358 uninfected spouses. We show that the overall incidence of cognitive impairment among older COVID-19 survivors was 19.1% at 2.5 years after infection and hospitalization, evaluated using the Telephone Interview for Cognitive Status-40. Cognitive decline primarily manifested in individuals with severe COVID-19 during the initial year of infection, after which the rate of decline decelerated. Severe COVID-19, cognitive impairment at 6 months and hypertension were associated with long-term cognitive decline. These findings reveal the long-term cognitive trajectory of the disease and underscore the importance of post-infection cognitive care for COVID-19 survivors.

Asunto(s)

RESUMEN

INTRODUCTION: Alzheimer's disease (AD) is a devastating neurological disease with complex genetic etiology. Yet most known loci have only identified from the late-onset type AD in populations of European ancestry. METHODS: We performed a two-stage genome-wide association study (GWAS) of AD totaling 6878 Chinese and 63,926 European individuals. RESULTS: In addition to the apolipoprotein E (APOE) locus, our GWAS of two independent Chinese samples uncovered three novel AD susceptibility loci (KIAA2013, SLC52A3, and TCN2) and a novel ancestry-specific variant within EGFR (rs1815157). More replicated variants were observed in the Chinese (31%) than in the European samples (15%). In combining genome-wide associations and functional annotations, EGFR and TCN2 were prioritized as two of the most biologically significant genes. Phenome-wide Mendelian randomization suggests that high mean corpuscular hemoglobin concentration might protect against AD. DISCUSSION: The current study reveals novel AD susceptibility loci, emphasizes the importance of diverse populations in AD genetic research, and advances our understanding of disease etiology. HIGHLIGHTS: Loci KIAA2013, SLC52A3, and TCN2 were associated with Alzheimer's disease (AD) in Chinese populations. rs1815157 within the EGFR locus was associated with AD in Chinese populations. The genetic architecture of AD varied between Chinese and European populations. EGFR and TCN2 were prioritized as two of the most biologically significant genes. High mean corpuscular hemoglobin concentrations might have protective effects against AD.

RESUMEN

An efficient cyclization for the synthesis of 1,2,4,5-tetra-substituted benzenes via copper catalyzed dimerization of γ,δ-unsaturated ketones has been described. This one-pot procedure employs the γ,δ-unsaturated ketones as the sole substrate with multiple C-C bond formation. This protocol features broad substrate scope and provides a facile and robust method to construct polysubstituted benzene derivatives under mild conditions.

RESUMEN

Cobalt substitution for manganese sites in Na0.44MnO2 initiates a dynamic structural evolution process, yielding a composite cathode material comprising intergrown P2 and P3 phases. The novel P2/P3 composite cathode exhibits a reversible phase transition process during Na+ extraction/insertion, showcasing its attractive battery performance in sodium-ion batteries.

RESUMEN

Devices of nanopore sequencing can be highly portable and of low cost. Thus, nanopore sequencing is promising in in-field forensic applications. Previous investigations have demonstrated that nanopore sequencing is feasible for genotyping forensic short tandem repeats (STRs) by using sequencers of Oxford Nanopore Technologies. Recently, Qitan Technology launched a new portable nanopore sequencer and became the second supplier in the world. Here, for the first time, we assess the QNome (QNome-3841) for its accuracy in nanopore sequencing of STRs and compare with MinION (MinION Mk1B). We profile 54 STRs of 21 unrelated individuals and 2800M standard DNA. The overall accuracy for diploid STRs and haploid STRs were 53.5% (378 of 706) and 82.7% (134 of 162), respectively, by using QNome. The accuracies were remarkably lower than those of MinION (diploid STRs, 84.5%; haploid, 90.7%), with a similar amount of sequencing data and identical bioinformatics analysis. Although it was not reliable for diploid STRs typing by using QNome, the haploid STRs were consistently correctly typed. The majority of errors (58.8%) in QNome-based STR typing were one-repeat deviations of repeat units in the error from true allele, related with homopolymers in repeats of STRs.

RESUMEN

Alzheimer's disease (AD) is a neurodegenerative disease that involves multiple systems in the body. Numerous recent studies have revealed bidirectional crosstalk between the brain and bone, but the interaction between bone and brain in AD remains unclear. In this review, we summarize human studies of the association between bone and brain and provide an overview of their interactions and the underlying mechanisms in AD. We review the effects of AD on bone from the aspects of AD pathogenic proteins, AD risk genes, neurohormones, neuropeptides, neurotransmitters, brain-derived extracellular vesicles (EVs), and the autonomic nervous system. Correspondingly, we elucidate the underlying mechanisms of the involvement of bone in the pathogenesis of AD, including bone-derived hormones, bone marrow-derived cells, bone-derived EVs, and inflammation. On the basis of the crosstalk between bone and the brain, we propose potential strategies for the management of AD with the hope of offering novel perspectives on its prevention and treatment. HIGHLIGHTS: The pathogenesis of AD, along with its consequent changes in the brain, may involve disturbing bone homeostasis. Degenerative bone disorders may influence the progression of AD through a series of pathophysiological mechanisms. Therefore, relevant bone intervention strategies may be beneficial for the comprehensive management of AD.

Asunto(s)

RESUMEN

Immunosenescence contributes to systematic aging and plays a role in the pathogenesis of Alzheimer's disease (AD). Therefore, the objective of this study was to investigate the potential of immune rejuvenation as a therapeutic strategy for AD. To achieve this, the immune systems of aged APP/PS1 mice were rejuvenated through young bone marrow transplantation (BMT). Single-cell RNA sequencing revealed that young BMT restored the expression of aging- and AD-related genes in multiple cell types within blood immune cells. The level of circulating senescence-associated secretory phenotype proteins was decreased following young BMT. Notably, young BMT resulted in a significant reduction in cerebral Aß plaque burden, neuronal degeneration, neuroinflammation, and improvement of behavioral deficits in aged APP/PS1 mice. The ameliorated cerebral amyloidosis was associated with an enhanced Aß clearance of peripheral monocytes. In conclusion, our study provides evidence that immune system rejuvenation represents a promising therapeutic approach for AD.

Asunto(s)

RESUMEN

Understanding the effects of psychosocial stress on serum cholesterol may offer valuable insights into the relationship between psychological disorders and endocrine diseases. However, these effects and their underlying mechanisms have not been elucidated yet. Here we show that serum corticosterone, total cholesterol and low-density lipoprotein cholesterol (LDL-C) are elevated in a mouse model of psychosocial stress. Furthermore, alterations occur in AdipoR2-mediated AMPK and PPARα signaling pathways in liver, accompanied by a decrease in LDL-C clearance and an increase in cholesterol synthesis. These changes are further verified in wild-type and AdipoR2 overexpression HepG2 cells incubated with cortisol and AdipoR agonist, and are finally confirmed by treating wild-type and hepatic-specific AdipoR2 overexpression mice with corticosterone. We conclude that increased glucocorticoid mediates the effects of psychosocial stress to elevate serum cholesterol by inhibiting AdipoR2-mediated AMPK and PPARα signaling to decrease LDL-C clearance and increase cholesterol synthesis in liver.

Asunto(s)

RESUMEN

Percutaneous insertion is one of the most common minimally invasive procedures. Compared with traditional straight rigid needles, bevel-tipped flexible needle can generate curved trajectories to avoid obstacles and sensitive organs. However, the nonlinear large deflection problem challenges the bending prediction of the needle, which dramatically influences the surgical success rate. This paper analyzed the mechanism of needle-tissue interaction, and established a mechanics-based model of the needle bending during an insertion. And then, a discretization of the bending model was adopted to accurately predict the large bending of the needle in soft tissue. Insertion experiments were conducted to validate the bending prediction model. The results showed that the large needle bending was predicted with the mean/RMSE/maximumu error of 0.42 mm / 0.26 mm / 1.08 mm, which was clinically acceptable. This proved the rationality and accuracy of the proposed model.

Asunto(s)

RESUMEN

Accurate differential diagnosis among various dementias is crucial for effective treatment of Alzheimer's disease (AD). The study began with searching for novel blood-based neuronal extracellular vesicles (EVs) that are more enriched in the brain regions vulnerable to AD development and progression. With extensive proteomic profiling, GABRD and GPR162 were identified as novel brain regionally enriched plasma EVs markers. The performance of GABRD and GPR162, along with the AD molecule pTau217, was tested using the self-developed and optimized nanoflow cytometry-based technology, which not only detected the positive ratio of EVs but also concurrently presented the corresponding particle size of the EVs, in discovery (n = 310) and validation (n = 213) cohorts. Plasma GABRD+- or GPR162+-carrying pTau217-EVs were significantly reduced in AD compared with healthy control (HC). Additionally, the size distribution of GABRD+- and GPR162+-carrying pTau217-EVs were significantly different between AD and non-AD dementia (NAD). An integrative model, combining age, the number and corresponding size of the distribution of GABRD+- or GPR162+-carrying pTau217-EVs, accurately and sensitively discriminated AD from HC [discovery cohort, area under the curve (AUC) = 0.96; validation cohort, AUC = 0.93] and effectively differentiated AD from NAD (discovery cohort, AUC = 0.91; validation cohort, AUC = 0.90). This study showed that brain regionally enriched neuronal EVs carrying pTau217 in plasma may serve as a robust diagnostic and differential diagnostic tool in both clinical practice and trials for AD.

Asunto(s)

RESUMEN

OBJECTIVES: To explore the context and hotspot changes of forensic mixed stain research through bibliometric approach. METHODS: The literature of forensic mixed stain included in the core collection of Web of Science database from 2011 to 2022 were collected as the study object, and the annual publication number, countrie (region), institution, journal, keywords, etc. were bibliometrically and visually analyzed using the R-based Bibliometrix 1.1.6 package and VOSviewer 1.6.18 software. RESULTS: A total of 732 articles on forensic mixed stain were included from 2011 to 2022, with the annual number of articles published and the annual citation frequency showing a steady increase year by year. Among the 59 countries (regions) with the most published articles, the United States ranked first with 246 articles, followed by China with 153 articles. The literature came from 104 journals, and the total number of articles published in the top 10 journals was 633. FORENSIC SCI INT GENET ranked first with 307 articles. Visual analysis using VOSviewer software showed that keywords could be divided into four research clusters, namely the genetic marker development group (blue), the mixed stain typing analysis theory group (red), the sequencing analysis group (yellow), and the case sample research group (green). It can be divided into four development stages in terms of different time periods: early development (2011-2013), middle development (2014-2016), rapid development (2017-2020) and latest development (2021-2022). CONCLUSIONS: The number of publications by domestic and foreign scholars in the study of mixed stain in forensic science is showing a relatively stable trend. Machine learning, next generation sequencing and other research have been the hottest topics that have attracted the most attention in recent years, which is expected to further develop the theory of mixed stain typing and sequencing analysis in forensic mixed stain research.

Asunto(s)

RESUMEN

In recent years, with the continuous progress of DNA extraction and detection technology, cell-free DNA(cfDNA)has been widely used in the life science field, and its potential application value in forensic identification is becoming more and more obvious. This paper reviews the concept, formation mechanism, and classification of cfDNA, etc., and describes the latest research progress of cfDNA in personal identification of crime scene touch DNA samples and non-invasive prenatal paternity testing (NIPPT). Meanwhile, this paper summarizes the potential application of cfDNA in injury inference, and discusses the advantages and disadvantages of common cfDNA analysis methods and techniques, and its application prospects, to provide a new idea for the wide application of cfDNA in the field of forensic science.

Asunto(s)

RESUMEN

Soil salinization leads to a reduction in arable land area, which seriously endangers food security. Developing saline-alkali land has become a key measure to address the contradiction between population growth and limited arable land. Rice is the most important global food crop, feeding half of the world's population and making it a suitable choice for planting on saline-alkali lands. The traditional salt-alkali improvement method has several drawbacks. Currently, non-thermal plasma (NTP) technology is being increasingly applied in agriculture. However, there are few reports on the cultivation of salt/alkali-tolerant rice. Under alkaline stress, argon NTP treatment significantly increased the germination rate of Longdao 5 (LD5) rice seeds. In addition, at 15 kV and 120 s, NTP treatment significantly increased the activity of antioxidant enzymes such as catalase and SOD. NTP treatment induced changes in genes related to salt-alkali stress in rice seedlings, such as chitinase and xylanase inhibitor proteins, which increased the tolerance of the seeds to salt-alkali stress. This experiment has expanded the application scope of NTP in agriculture, providing a more cost-effective, less harmful, and faster method for developing salt-alkali-tolerant rice and laying a theoretical foundation for cultivating NTP-enhanced salt-alkali-tolerant rice.

Asunto(s)

RESUMEN

Silicon nanowire field effect (SiNW-FET) biosensors have been successfully used in the detection of nucleic acids, proteins and other molecules owing to their advantages of ultra-high sensitivity, high specificity, and label-free and immediate response. However, the presence of the Debye shielding effect in semiconductor devices severely reduces their detection sensitivity. In this paper, a three-dimensional stacked silicon nanosheet FET (3D-SiNS-FET) biosensor was studied for the high-sensitivity detection of nucleic acids. Based on the mainstream Gate-All-Around (GAA) fenestration process, a three-dimensional stacked structure with an 8 nm cavity spacing was designed and prepared, allowing modification of probe molecules within the stacked cavities. Furthermore, the advantage of the three-dimensional space can realize the upper and lower complementary detection, which can overcome the Debye shielding effect and realize high-sensitivity Point of Care Testing (POCT) at high ionic strength. The experimental results show that the minimum detection limit for 12-base DNA (4 nM) at 1 × PBS is less than 10 zM, and at a high concentration of 1 µM DNA, the sensitivity of the 3D-SiNS-FET is approximately 10 times higher than that of the planar devices. This indicates that our device provides distinct advantages for detection, showing promise for future biosensor applications in clinical settings.

Asunto(s)