Sex differences in the impact of frailty on patients with heart failure: A retrospective cohort study.

AIMS: Limited literature shows the existence of sex differences in the long-term prognosis of heart failure (HF) patients with frailty. In this study, whether sex differences exist in the impact of frailty on death from cardiovascular causes in patients with HF was investigated by conducting a retrospective cohort study. METHODS AND RESULTS: Data from the National Health and Nutrition Examination Survey (NHANES) study (2009-2018) were used to conduct a retrospective cohort study of 958 participants with HF. Patients were grouped based on sex and frailty index (FI). The relationship between death from cardiovascular causes and baseline frailty was assessed by Cox proportional hazard analysis and the Kaplan-Meier (K-M) plot. The study population had an age of 67.3 ± 12.3. Among them, around 54.5% were male. A median follow-up of 3.6 years was performed. After that, females who died from cardiovascular causes exhibited higher baseline FI values, while males did not show this trend (P < 0.05; P = 0.1253). Cox regression analysis demonstrated a significant association between FI and cardiovascular mortality in females (most frail: hazard ratio (HR) = 3.65, 95% confidence interval (CI): 1.07 ~ 12.39, P < 0.05; per 1-unit increase in FI: HR = 1.78, 95% CI: 1.33 ~ 2.39, P < 0.001). A dose-response association between FI and cardiovascular mortality was presented by restricted cubic splines. CONCLUSIONS: Frailty is related to an increased risk of cardiovascular mortality in HF patients, particularly female patients.

An enantioselective fluorescent probe for detecting arginine and glutamic acids.

Amino acids are important chiral compounds in the human body, and are important basic components that make up the human body and play an important role in the human body. Among them, different enantiomers of an amino acid may have different roles, and different types of amino acids can be interconverted. However, the content of D-amino acids is much lower than that of L-amino acids, which is difficult to be detected. At present, many of the potential roles of D-amino acids, such as the conversion of D-amino acids to each other, have not yet been fully revealed. Hence, we synthesized fluorescent probe (R)-5 by condensation of 1,1'-Bi-2-naphthol (BINOL) and 2-(Aminomethyl)pyridine with Schiff base, which can recognize both D-arginine and D-glutamic acid at low concentrations. Meanwhile, (R)-5 can be applied to paper-based sensors for the detection of arginine and glutamate in living cells and for food amino acid detection.

Different emotional states engage distinct descending pathways from the prefrontal cortex.

Emotion regulation, essential for adaptive behavior, depends on the brain's capacity to process a range of emotions. Current research has largely focused on individual emotional circuits without fully exploring how their interaction influences physiological responses or understanding the neural mechanisms that differentiate emotional valence. Using in vivo calcium imaging, electrophysiology, and optogenetics, we examined neural circuit dynamics in the medial prefrontal cortex (mPFC), targeting two key areas: the basal lateral amygdala (BLA) and nucleus accumbens (NAc). Our results demonstrate distinct activation patterns in the mPFC→BLA and mPFC→NAc pathways in response to social stimuli, indicating a mechanism for discriminating emotions: increased mPFC→BLA activity signals anxiety, while heightened mPFC→NAc responses are linked to exploration. Additionally, chronic emotional states amplify activity in these pathways-positivity enhances mPFC→NAc, while negativity boosts mPFC→BLA. This study sheds light on the nuanced neural circuitry involved in emotion regulation, revealing the pivotal roles of mPFC projections in emotional processing. Identifying these specific circuits engaged by varied emotional states advances our understanding of emotional regulation's biological underpinnings and highlights potential targets for addressing emotional dysregulation in psychiatric conditions. Significance statement: While existing circuitry studies have underscored the significance of emotional circuits, the majority of research has concentrated on individual circuits. The assessment of whether and how the balance among multiple circuits influences overall physiological outcomes is often overlooked. This study delves into the neural underpinnings of emotion regulation, focusing on how positive and negative valences are discriminated and managed. By examining the specific pathways from the medial prefrontal cortex (mPFC) to key emotional centers-the basal lateral amygdala (BLA) for negative valence and the nucleus accumbens (NAc) for positive one-we uncovered a novel dual-balanced neural circuit mechanism that enables this essential aspect of human cognition.

In-situ synthesized MgIn2S4/CdWO4 type-II heterojunction as a light-driven photoelectrochemical sensor for ultrasensitive detection of catechol in environmental water samples.

As an essential chemical intermediate, catechol (CC) residues may have adverse effects on human health. Herein, an effective and facile photoelectrochemical sensor platform based on MgIn2S4/CdWO4 composite is constructed for monitoring CC. MgIn2S4 increases light absorption range and activity, while CdWO4 enhances photoelectronic stability, and the type-II heterojunction formed can significantly enhance photocurrent response. Due to the autoxidation process, CC is converted into oligomeric products, which increase the spatial site resistance and attenuate the overall photocurrent response. It is worth noting that the cauliflower-like structure of MgIn2S4 can provide a large specific surface area, and the presence of Mg2+ promotes autoxidation, thus providing a suitable condition for detecting CC. Under optimal conditions, the MgIn2S4/CdWO4/GCE photoelectrochemical sensor has a prominent linear relationship in the range of CC concentration from 2 nM to 7 µM, with a limit of detection of 0.27 nM. With satisfactory selectivity, excellent stability, and remarkable reproducibility, this sensor provides a crucial reference value for effectively and rapidly detecting pollutants in environmental water samples.

Neferine Pretreatment Attenuates Isoproterenol-Induced Cardiac Injury Through Modulation of Oxidative Stress, Inflammation, and Apoptosis in Rats.

Heart attacks, also known as myocardial infarctions (MIs), are one of the main reasons people die from cardiovascular diseases (CVDs) worldwide. Neferine, an alkaloid derived from Nelumbo nucifera seeds, has garnered interest due to its purported medicinal effects. In the current research, we induced MI in rats using the ß-adrenergic agonist isoproterenol to investigate whether neferine can improve cardiac dysfunction. The rats were separated into four groups: control, isoproterenol (ISO), and two treatment groups received neferine at doses of 10 or 20 mg/kg once daily for 28 days. On days 27 and 28, the groups undergoing treatment were administered with an ISO injection. Results showed that pretreatment with neferine strongly protected against changes in lipid profiles and cardiac functional markers in ISO-administered rats. Neferine attenuated histopathologic changes, collagen deposition, and myocardial fibrosis in rats administered ISO. Neferine pretreatment significantly inhibited the oxidative stress, inflammatory, and apoptotic markers in the heart of ISO-injected rats. This was achieved through Nrf2/Keap1/ARE signaling stimulation, TLR4/NF-κB/MAPK-mediated signaling inhibition, and activation of the intrinsic apoptotic pathway. Using CB-Dock-2, researchers determined that neferine has a high binding affinity with protein receptors that are pivotal in several biological processes. In conclusion, the study provides strong evidence that pretreatment with neferine protects rats from ISO-induced heart damage.

Advances in fluorescent probe development for bioimaging of potential Parkinson's biomarkers.

Parkinson's disease (PD) is a common neurodegenerative disease. The clinical symptoms of PD are usually related to motor symptoms, including postural instability, rigidity, bradykinesia, and resting tremors. At present, the pathology of PD is not yet clear. Therefore, revealing the underlying pathological mechanism of PD is of great significance. A variety of bioactive molecules are produced during the onset of Parkinson's, and these bioactive molecules may be a key factor in the development of Parkinson's. The emerging fluorescence imaging technology has good sensitivity and high signal-to-noise ratio, making it possible to deeply understand the pathogenesis of PD through these bioactive molecules. Currently, fluorescent probes targeting PD biomarkers are widely developed and applied. This article categorizes and summarizes fluorescent probes based on different PD biomarkers, systematically introduces their applications in the pathological process of PD, and finally briefly elaborates on the challenges and prospects of these probes. We hope that this review will provide in-depth reference insights for designing fluorescent probes, and contribute to study of the pathogenesis and clinical treatment of PD.

Small peptide signaling via OsCIF1/2 mediates Casparian strip formation at the root endodermal and nonendodermal cell layers in rice.

The Casparian strip (CS) is a ring-like lignin structure deposited between endodermal cells that forms an apoplastic barrier to control the selective uptake of nutrients in vascular plants. However, the molecular mechanism of CS formation in rice (Oryza sativa), which possesses one CS each in the endodermis and exodermis, is relatively unknown. Here, we functionally characterized CS INTEGRITY FACTOR1 (OsCIF1a, OsCIF1b), OsCIF2, and SCHENGEN3 (OsSGN3a, OsSGN3b) in rice. OsCIF1s and OsCIF2 were mainly expressed in the stele, while OsSGN3s localized around the CS at the endodermis. Knockout of all three OsCIFs or both OsSGN3s resulted in a discontinuous CS and a dramatic reduction in compensatory (less localized) lignification and suberization at the endodermis. By contrast, ectopic overexpression of OsCIF1 or OsCIF2 induced CS formation as well as overlignification and oversuberization at single or double cortical cell layers adjacent to the endodermis. Ectopic co-overexpression of OsCIF1 and SHORTROOT1 (OsSHR1) induced the formation of more CS-like structures at multiple cortical cell layers. Transcriptome analysis identified 112 downstream genes modulated by the OsCIF1/2-OsSGN3 signaling pathway, which is involved in CS formation and activation of the compensatory machinery in native endodermis and nonnative endodermis-like cell layers. Our results provide important insights into the molecular mechanism of CIF-mediated CS formation at the root endodermal and nonendodermal cell layers.

Transcriptomic Responses to Nitrite Degradation by Limosilactobacillus fermentum RC4 and Effect of ndh Gene Overexpression on Nitrite Degradation.

The excessive nitrite residue may increase cell damage and cancer risk. Limosilactobacillu fermentum RC4 exhibited excellent nitrite degradation ability. Herein, the molecular mechanism of nitrite degradation by L. fermentum RC4 was studied by integrating scanning electron microscopy analysis, transcriptomics, and gene overexpression. The results demonstrated that the gene profile of RC4 cultured in MRS broth with 0, 100, and 300 mg/L NaNO2 varied considerably; RC4 responded to nitrite degradation by regulating pyruvate metabolism, energy synthesis, nitrite metabolism, redox equilibrium, protein protection, and signaling. High nitrite concentrations affected the morphology of RC4 with a longer phenotype, rough and wrinkle cell and reduced cell surface hydrophobicity. Moreover, an up-regulated expression of gene ndh encoding NADH dehydrogenase, which provides electrons for nitrite reduction by catalyzing NADH, was identified when RC4 was exposed to nitrite. Overexpression of ndh in RC4 increased the nitrite degradation rate by 2-9.5% in MRS broth with 100 mg/L NaNO2. Thus, the findings of this study could be helpful for the application of L. fermentum to reduce nitrite residues and improve food safety in fermented food products.

Comprehensive bioinformatics analysis and experimental validation: An anoikis-related gene prognostic model for targeted drug development in head and neck squamous cell carcinoma.

We analyzed RNA-sequencing (RNA-seq) and clinical data from head and neck squamous cell carcinoma (HNSCC) patients in The Cancer Genome Atlas (TCGA) Genomic Data Commons (GDC) portal to investigate the prognostic value of anoikis-related genes (ARGs) in HNSCC and develop new targeted drugs. Differentially expressed ARGs were screened using bioinformatics methods; subsequently, a prognostic model including three ARGs (CDKN2A, BIRC5, and PLAU) was constructed. Our results showed that the model-based risk score was a good prognostic indicator, and the potential of the three ARGs in HNSCC prognosis was validated by the TISCH database, the model's accuracy was validated in two independent cohorts of the Gene Expression Omnibus database. Immune correlation analysis and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno- and chemo-therapeutic responses. Potential small-molecule drugs for HNSCC were subsequently predicted using the L1000FWD database. Finally, in vitro experiments were used to verify the database findings. The relative ARG mRNA expression levels in HNSCC and surrounding normal tissues remained consistent with the model results. BIRC5 knockdown inhibited anoikis resistance in WSU-HN6 and CAL-27 cells. Molecular docking, real-time PCR, cell counting kit-8 (CCK-8), plate clone, and flow cytometry analyses showed that small-molecule drugs predicted by the database may target the ARGs in the prognostic model, inhibit HNSCC cells survival rate, and promote anoikis in vitro. Therefore, we constructed a new ARG model for HNSCC patients that can predict prognosis and immune activity and identify a potential small-molecule drug for HNSCC, paving the way for clinically targeting anoikis in HNSCC.

Keep numbers in view: red-eared sliders (Trachemys scripta elegans) learn to discriminate relative quantities.

The ability to discriminate relative quantities, one of the numerical competences, is considered an adaptive trait in uncertain environments. Besides humans, previous studies have reported this capacity in several non-human primates and birds. Here, we test whether red-eared sliders (Trachemys scripta elegans) can discriminate different relative quantities. Subjects were first trained to distinguish different stimuli with food reward. Then, they were tested with novel stimulus pairs to demonstrate how they distinguished the stimuli. The results show that most subjects can complete the initial training and use relative quantity rather than absolute quantity to make choices during the testing phase. This study provides behavioural evidence of relative quantity discrimination in a reptile species and suggests that such capacity may be widespread among vertebrates.

Comparisons of Two-dimensional Echocardiographic Aortic Dimensions between Chinese, Japanese, and Europeans.

PURPOSE: We aimed to investigate the impacts of age, gender, and race on aortic dimensions in healthy adults. METHODS: We analyzed data from 3 large population-based sample studies, including Chinese Echocardiographic Measurements in Normal Chinese Adults, Japanese the Normal Values for Echocardiographic Measurements Project, and European Normal Reference Ranges for Echocardiography, to compare the two-dimensional echocardiography-derived aortic diameters at different levels and to explore the effects of age, gender, and race on aortic measurements. We also compared the values corrected by body surface area (BSA) or height. RESULTS: The results are as follows: (1) Aortic diameters showed positive correlations with age (r=0.12-0.42, P<0.05), and there were significant inter-age group differences before and after indexing to BSA (P<0.05); (2) Men had greater measurements of aortic diameters than women, with the differences being the same when indexed to height. However, indexing to BSA reversed the differences; (3) The aortic diameters at annulus (Ao-a) and sinus (Ao-s) levels were very close with minor differences between the Chinese and Japanese regardless of whether BSA was used for correction; and (4) The aortic measurements at Ao-s and proximal ascending aorta (Ao-asc) levels in the Chinese were significantly lower than in the Europeans for both genders, with the differences remaining the same even after indexing to BSA or height (P<0.05). CONCLUSION: Aortic dimensions vary with age and gender, and there are significant differences between races or ethnicities even when stratified by gender and age. The indexation by BSA or height cannot eliminate these differences. Therefore, age-specific, gender-specific, race-specific, and nationality-specific reference values may be more appropriate at present for clinical practice to avoid misdiagnosis and misclassification of aortic dilation.

A distributionally robust optimization approach for airline integrated recovery under in-flight pandemic transmission risks.

The COVID-19 pandemic has hit the airline industry hard, leading to heterogeneous epidemiological situations across markets, irregular flight bans, and increasing operational hurdles. Such a melange of irregularities has presented significant challenges to the airline industry, which typically relies on long-term planning. Given the growing risk of disruptions during epidemic and pandemic outbreaks, the role of airline recovery is becoming increasingly crucial for the aviation industry. This study proposes a novel model for airline integrated recovery problem under the risk of in-flight epidemic transmission risks. This model recovers the schedules of aircraft, crew, and passengers to eliminate possible epidemic dissemination while reducing airline operating costs. To account for the high uncertainty with respect to in-flight transmission rates and to prevent overfitting of the empirical distribution, a Wasserstein distance-based ambiguity set is utilized to formulate a distributionally robust optimization model. Aimed at tackling computation difficulties, a branch-and-cut solution method and a large neighborhood search heuristic are proposed in this study based on an epidemic propagation network. The computation results for real-world flight schedules and a probabilistic infection model suggest that the proposed model is capable of reducing the expected number of infected crew members and passengers by 45% with less than 4% increase in flight cancellation/delay rates. Furthermore, practical insights into the selection of critical parameters as well as their relationship with other common disruptions are provided. The integrated model is expected to enhance airline disruption management against major public health events while minimizing economic loss.

Fast Visualized Conformational Transition of Polyphenylacetylenes with Stepwise Tunable Circularly Polarized Luminescence.

Two novel poly(3,5-diamide substituted phenylacetylene)s bearing L- or D-alanine residues with a long alkyl chain were synthesized. In low polar or apolar solvents, the polymers adopted contracted cis-cisoid helix showing strong yellow fluorescence, which was transferred to stretched cis-transoid helix by adding polar solvents or decreasing temperature, accompanied with the disappearance of fluorescence. The critical conformational transition temperature could be readily tuned in a wide range by altering the content of polar solvent, and the conformational variation at molecular level could be directly read out via the change in fluorescent property. The synergistical participation of amide and ester groups in the formation of intramolecular hydrogen bonds accelerated the conformational transition rate, resulting in remarkable reduction of hysteresis. Moreover, the polymers displayed switchable CPL performance and the luminescent dissymmetry factor could be stepwise amplified by forming chiral aggregates or liquid crystalline structure. This study may open a new avenue for the development of controllable helical structure-based smart CPL materials.

Research Progress of Nitrite Metabolism in Fermented Meat Products.

Nitrite is a common color and flavor enhancer in fermented meat products, but its secondary amines may transfer to the carcinogen N-nitrosamines. This review focuses on the sources, degradation, limitations, and alteration techniques of nitrite. The transition among NO3- and NO2-, NH4+, and N2 constitutes the balance of nitrogen. Exogenous addition is the most common source of nitrite in fermented meat products, but it can also be produced by contamination and endogenous microbial synthesis. While nitrite is degraded by acids, enzymes, and other metabolites produced by lactic acid bacteria (LAB), four nitrite reductase enzymes play a leading role. At a deeper level, nitrite metabolism is primarily regulated by the genes found in these bacteria. By incorporating antioxidants, chromogenic agents, bacteriostats, LAB, or non-thermal plasma sterilization, the amount of nitrite supplied can be decreased, or even eliminated. Finally, the aim of producing low-nitrite fermented meat products is expected to be achieved.

Transcriptional regulation of macrophages in heart failure.

Adverse cardiac remodeling after acute myocardial infarction is the most important pathological mechanism of heart failure and remains a major problem in clinical practice. Cardiac macrophages, derived from tissue resident macrophages and circulating monocyte, undergo significant phenotypic and functional changes following cardiac injury and play crucial roles in inflammatory response and tissue repair response. Currently, numerous studies indicate that epigenetic regulatory factors and transcription factors can regulate the transcription of inflammatory and reparative genes and timely conversion of inflammatory macrophages into reparative macrophages and then alleviate cardiac remodeling. Accordingly, targeting transcriptional regulation of macrophages may be a promising option for heart failure treatment. In this review, we not only summarize the origin and function of cardiac macrophages, but more importantly, describe the transcriptional regulation of macrophages in heart failure, aiming to provide a potential therapeutic target for heart failure.

A data-driven analysis of the aviation recovery from the COVID-19 pandemic.

In Summer 2022, after a lean COVID-19 spell of almost three years, many airlines reported profits and some airlines even outperformed their pre-pandemic records. In context of the perceived recovery, it is interesting to understand how different markets have gone through the pandemic challenges. In this study, we perform a spatial and temporal dissection of the recovery process the global aviation system went through since May 2020. At the heart of this study, we investigate the patterns underlying market entry decisions during the recovery phase. We identify a rather heterogeneous type of recovery as well as its underlying drivers. We believe that our work is a timely contribution to the research on COVID-19 and aviation, complementary to the existing studies in the literature.

Abnormalities in intron retention characterize patients with systemic lupus erythematosus.

Regulation of intron retention (IR), a form of alternative splicing, is a newly recognized checkpoint in gene expression. Since there are numerous abnormalities in gene expression in the prototypic autoimmune disease systemic lupus erythematosus (SLE), we sought to determine whether IR was intact in patients with this disease. We, therefore, studied global gene expression and IR patterns of lymphocytes in SLE patients. We analyzed RNA-seq data from peripheral blood T cell samples from 14 patients suffering from systemic lupus erythematosus (SLE) and 4 healthy controls and a second, independent data set of RNA-seq data from B cells from16 SLE patients and 4 healthy controls. We identified intron retention levels from 26,372 well annotated genes as well as differential gene expression and tested for differences between cases and controls using unbiased hierarchical clustering and principal component analysis. We followed with gene-disease enrichment analysis and gene-ontology enrichment analysis. Finally, we then tested for significant differences in intron retention between cases and controls both globally and with respect to specific genes. Overall decreased IR was found in T cells from one cohort and B cells from another cohort of patients with SLE and was associated with increased expression of numerous genes, including those encoding spliceosome components. Different introns within the same gene displayed both up- and down-regulated retention profiles indicating a complex regulatory mechanism. These results indicate that decreased IR in immune cells is characteristic of patients with active SLE and may contribute to the abnormal expression of specific genes in this autoimmune disease.

On the contagion leakage via incoming flights during China's aviation policies in the fight against COVID-19.

For nearly three years with the COVID-19 pandemic, China has implemented a set of strict policies to control the flux of potential virus carriers in cross-border flights: The so-called Circuit Breaker mechanism. In this study, we review the evolution of this mechanism - a rather unique experiment in the global aviation system - from a data-driven perspective. Specifically, we perform an investigation on the extent of violations and their potential drivers. In total, 183 events are analyzed covering the period from epidemic outbreak in early 2020 to December 2021. In addition to describing the spatial extent and temporal evolution, we develop a regression model which helps us to better understand the universal patterns. By dissecting an under-investigated phenomenon, we believe that our study contributes to the rich literature on aviation and COVID-19, not only in the specific context of China, but also by assessing some of the challenges and potential of containing a global health threat using strict aviation policies.

A novel resilience analysis methodology for airport networks system from the perspective of different epidemic prevention and control policy responses.

As the COVID-19 pandemic fades, the aviation industry is entering a fast recovery period. To analyze airport networks' post-pandemic resilience during the recovery process, this paper proposes a Comprehensive Resilience Assessment (CRA) model approach using the airport networks of China, Europe, and the U.S.A as case studies. The impact of COVID-19 on the networks is analyzed after populating the models of these networks with real air traffic data. The results suggest that the pandemic has caused damage to all three networks, although the damages to the network structures of Europe and the U.S.A are more severe than the damage in China. The analysis suggests that China, as the airport network with less network performance change, has a more stable level of resilience. The analysis also shows that the different levels of stringency policy in prevention and control measures during the epidemic directly affected the recovery rate of the network. This paper provides new insights into the impact of the pandemic on airport network resilience.

An ESIPT-based ratiometric fluorescent probe for detecting H2O2 in water environment and biosystems.

The outbreak of the COVID-19 has resulted in a great increase in the use of H2O2 disinfectant, which is listed as one of the commonly used disinfectants for COVID-19 by the U.S. Environmental Protection Agency. However, excessive use of H2O2 disinfectant can threaten human health and damage the water environment. Therefore, it's of great importance to detect H2O2 in aquatic environments and biological systems. Herein, we proposed a novel ESIPT ratio fluorescent probe (named probe 1) for detecting H2O2 in water environment and biosystems. Probe 1 emits blue fluorescence as the introduction of the phenylboronic acid disrupts the ESIPT process. After reacting with H2O2, the phenylboronic acid is oxidatively removed, and the ESIPT process is restored, which makes the fluorescence emission wavelength red-shifted. Probe 1 exhibited a short response time, high sensitivity, and a large Stokes shift to H2O2. Importantly, it has been successfully used to detect H2O2 not only in actual water samples, but also endogenous and exogenous H2O2 in living cells. The characteristics of probe 1 have a wide range of applications in environmental and biological systems.