Identification of Differentially Expressed mRNAs and lncRNAs Contributes to Elucidation of Underlying Pathogenesis and Therapeutic Strategy of Recurrent Implantation Failure.

Recurrent implantation failure (RIF) is a complex and poorly understood clinical disorder characterized by failure to conceive after repeated embryo transfers. Endometrial receptivity (ER) is a prerequisite for implantation, and ER disorders are associated with RIF. However, little is known regarding the molecular mechanisms underlying ER in RIF. In the present study, RNA sequencing data from the mid-secretory endometrium of patients with and without RIF were analyzed to explore the potential long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) involved in RIF. The analysis revealed 213 and 1485 differentially expressed mRNAs and lncRNAs, respectively (fold change ≥ 2 and p < 0.05). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that these genes were mostly involved in processes related to immunity or inflammation. 5 key genes (TTR, ALB, TF, AFP, and CFTR) and a key module including 14 hub genes (AFP, ALB, APOA1, APOA2, APOB, APOH, FABP1, FGA, FGG, GC, ITIH2, SERPIND1, TF and TTR) were identified in the protein-protein interaction (PPI) network. The 5 key genes were used to further explore the lncRNA-miRNA-mRNA regulatory network. Finally, the drug ML-193 based on the 14 hub genes was identifed through the CMap. After ML-193 treatment, endometrial cell proliferation was increased, the hub genes were mostly down-regulated, and the ER marker HOXA10 was up-regulated. These results offer insights into the regulatory mechanisms of lncRNAs and mRNAs and suggest ML-193 as a therapeutic agent for RIF by enhancing ER.

Vertical is Beneficial but volume is Irrelevant: Optimization of urban guide signs based on spatial representation of road networks.

Urban guide signs, a fundamental component of traffic sign systems, convey both directional and locational information. Previous studies mainly focused on the font or volume of information, while little attention was paid to the layout of text-based Chinese guide signs, which is an unregulated area but crucial in practical applications and related to people's travel safety. This study investigates the impact of text layout and information volume on the spatial representation of road networks through two experimental studies, examining the effects of different designs on path determination and global road network knowledge. The results indicate that the text layout of urban road guide signs significantly influences the formation of spatial representation of the road network. Specifically, vertical guide signs displaying road names on both sides proved more effective than horizontal ones. While the volume of road name information does not markedly affect the formation of spatial representation, the arrangement of road names does influence the determination of information volume, with vertical layouts facilitating the presentation of more information. It is anticipated that these design recommendations for road signs can effectively mitigate the incidence of road traffic accidents.

Exogenous ethephon treatment on the biosynthesis and accumulation of astragaloside IV in Astragalus membranaceus Bge. Var. Mongholicus (Bge.) Hsiao.

BACKGROUND: Astragaloside IV is a main medicinal active ingredient in Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao, which is also the key biomarker of A. membranaceus quality. Ethylene has been well-documented to involve in secondary metabolites biosynthesis in plants. Nevertheless, how ethylene regulates astragaloside IV biosynthesis in A. membranaceus is still unclear. Therefore, in the present study different dosages and time-dependent exogenous application of ethephon (Eth) were employed to analyze astragaloside IV accumulation and its biosynthesis genes expression level in hydroponically A. membranaceus. RESULTS: Exogenous 200 µmol·L- 1Eth supply is most significantly increased astragaloside IV contents in A. membranaceus when compared with non-Eth supply. After 12 h 200 µmol·L- 1 Eth treatment, the astragaloside IV contents reaching the highest content at 3 d Eth treatment(P ≤ 0.05). Moreover, After Eth treatment, all detected key genes involved in astragaloside IV synthesis were significant decrease at 3rd day(P ≤ 0.05). However, SE displayed a significant increase at the 3rd day under Eth treatment(P ≤ 0.05). Under Eth treatment, the expression level of FPS, HMGR, IDI, SS, and CYP93E3 exhibited significant negative correlations with astragaloside IV content, while expression level of SE displayed a significant positive correlation. CONCLUSIONS: These findings suggest that exogenous Eth treatment can influence the synthesis of astragaloside IV by regulating the expression of FPS, HMGR, IDI, SS, CYP93E3 and SE. This study provides a theoretical basis for utilizing molecular strategies to enhance the quality of A. membranaceus.

LASSO-derived nomogram for early identification of pediatric monogenic lupus.

BACKGROUND: Monogenic lupus is defined as systemic lupus erythematosus (SLE)/SLE-like patients with either dominantly or recessively inherited pathogenic variants in a single gene with high penetrance. However, because the clinical phenotype of monogenic SLE is extensive and overlaps with that of classical SLE, it causes a delay in diagnosis and treatment. Currently, there is a lack of early identification models for clinical practitioners to provide early clues for recognition. Our goal was to create a clinical model for the early identification of pediatric monogenic lupus, thereby facilitating early and precise diagnosis and treatment for patients. METHODS: This retrospective cohort study consisted of 41 cases of monogenic lupus treated at the Department of Pediatrics at Peking Union Medical College Hospital from June 2012 to December 2022. The control group consisted of classical SLE patients recruited at a 1:2 ratio. Patients were randomly divided into a training group and a validation group at a 7:3 ratio. A logistic regression model was established based on the least absolute shrinkage and selection operator to generate the coefficient plot. The predictive ability of the model was evaluated using receiver operator characteristic curves and the area under the curve (AUC) index. RESULTS: A total of 41 cases of monogenic lupus patients and 82 cases of classical SLE patients were included. Among the monogenic lupus cases (with a male-to-female ratio of 1:1.05 and ages of onset ranging from birth to 15 years), a total of 18 gene mutations were identified. The variables included in the coefficient plot were age of onset, recurrent infections, intracranial calcifications, growth and developmental delay, abnormal muscle tone, lymphadenopathy/hepatosplenomegaly, and chilblain-like skin rash. Our model demonstrated satisfactory diagnostic performance through internal validation, with an AUC value of 0.97 (95% confidence interval = 0.92-0.97). CONCLUSIONS: We summarized and analyzed the clinical characteristics of pediatric monogenic lupus and developed a predictive model for early identification by clinicians. Clinicians should exercise high vigilance for monogenic lupus when the score exceeds - 9.032299.

Quality of lymph node dissection and early recurrence in robotic versus thoracoscopic lobectomy for stage N1-2 non-small cell lung cancer: Eleven-year real-world data from a high-volume center.

BACKGROUND: The efficacy of lymph node dissection (LND) and oncological outcomes of robot-assisted (RL) versus video-assisted thoracoscopic lobectomy (VL) for non-small cell lung cancer (NSCLC) with nodal involvement remains controversial. This study aims to compare LND quality and early recurrence (ER) rate between RL and VL for stage N1-2 NSCLC patients based on eleven-year real-world data from a high-volume center. METHODS: Pathologic stage IIB-IIIB (T1-3N1-2) NSCLC patients undergoing RL or VL in Shanghai Chest Hospital from 2010 to 2021 were retrospectively reviewed from a prospectively maintained database. Propensity-score matching (PSM, 1:4 RL versus VL) was performed to mitigate baseline differences. LND quality was evaluated by adequate (≥16) LND and nodal upstaging rates. ER was defined as recurrence occurring within 24 months post-surgery. RESULTS: Out of 1578 cases reviewed, PSM yielded 200 RL and 800 VL cases. Without compromising perioperative outcomes, RL assessed more N1 and N2 LNs and N1 stations, and led to higher incidences of adequate LND (58.5 % vs. 42.0 %, p < 0.001) and nodal upstaging (p = 0.026), compared to VL. Notably, RL improved perioperative outcomes for patients undergoing adequate LND than VL. Finally, RL notably reduced ER rate (22.0 % vs. 29.6 %, p = 0.032), especially LN ER rate (15.0 % vs. 21.5 %, p = 0.041), and prolonged disease-free survival (DFS; hazard ratio = 0.837, p = 0.040) compared with VL. Further subgroup analysis of ER and DFS within the cN1-2-stage cohort verified this survival benefit. CONCLUSIONS: RL surpasses VL in enhancing LND quality, reducing ER rates, and improving perioperative outcomes when adequate LND is performed for stage N1-2 NSCLC patients.

A new index for cervical curvature evaluation - relative cervical curvature area.

OBJECTIVE: To put forward a new index of cervical curvature evaluation - relative cervical curvature area,and a new classification of cervical spine was proposed according to the relative cervical curvature area. METHODS: A total of 167 subjects with cervical spondylosis were included in the study. Firstly, 119 subjects were selected to measure C2-C7 lordosis angle by Cobb angle method, Harrison posterior tangent method and Jackson physiological stress line method, and then their relative cervical curvature area, C1-C7 Cobb angle, C7 slope and T1 slope were measured.The correlation between relative cervical curvature area and three measurement methods and common sagittal parameters was analyzed.According to the angle classification method, we calculated the diagnostic boundary value of the relative cervical curvature area classification, and selected 48 subjects to evaluate its diagnostic efficacy.Finally, 119 subjects were re-evaluated according to the diagnostic threshold and the number of intersections to verify the feasibility of the new classification. RESULTS: The results showed that the relative cervical curvature area index had good intra-observer and inter-observer repeatability. Relative cervical curvature area was correlated with Harrison posterior tangent method ( r = 0.930 ), Cobb angle method ( r = 0.886 ) and Jackson physiological stress line method ( r = 0.920 ), and correlated with C1-C7 Cobb angle, C7 slope and T1 slope.The relative cervical curvature area has a good diagnostic performance for distinguishing patients with lordosis, straightening and kyphosis.According to the new classification of cervical spine, 119 subjects were divided into 57 simple lordosis, 11 simple straightening, 4 simple kyphosis, 26 S-type and 21 RS-type. CONCLUSION: The relative cervical curvature area uses the area parameter instead of the original angle parameter and distance parameter to incorporate the change of segmental curvature, which makes up for the shortcomings of the Cobb angle method that only evaluates the curvature of two vertebrae, and better reflects the cervical curvature.Studies have shown that relative cervical curvature area has good repeatability and diagnostic value, and found that it has a good correlation with common cervical sagittal parameters.The new classification of cervical spine makes up for the disadvantage that the angle classification method cannot distinguish between S-type and RS-type, and initially proposes to use the number of intersections and the relative absolute value area to reflect the severity of S-type.

Identification of DNase I hypersensitive sites in the human genome by multiple sequence descriptors.

DNase I hypersensitive sites (DHSs) are chromatin regions highly sensitive to DNase I enzymes. Studying DHSs is crucial for understanding complex transcriptional regulation mechanisms and localizing cis-regulatory elements (CREs). Numerous studies have indicated that disease-related loci are often enriched in DHSs regions, underscoring the importance of identifying DHSs. Although wet experiments exist for DHSs identification, they are often labor-intensive. Therefore, there is a strong need to develop computational methods for this purpose. In this study, we used experimental data to construct a benchmark dataset. Seven feature extraction methods were employed to capture information about human DHSs. The F-score was applied to filter the features. By comparing the prediction performance of various classification algorithms through five-fold cross-validation, random forest was proposed to perform the final model construction. The model could produce an overall prediction accuracy of 0.859 with an AUC value of 0.837. We hope that this model can assist scholars conducting DNase research in identifying these sites.

Effects of carrier surface hydrophilic modification on sludge granulation: From sludge characteristics, extracellular polymeric substances, and microbial community.

Aerobic granular sludge (AGS) is a powerful biotechnological tool capable of treating multiple pollutants simultaneously. However, the granulation process and pollutant removal efficiency still need to be further improved. In this study, Fe2O3- and MnO2-surface-modified straw foam-based AGS (Fe2O3@SF-AGS and MnO2@SF-AGS), with an average particle size of 3 mm, were developed and evaluated. The results showed that surface modification reduced the hydrophobic groups of carriers, facilitating the attachment and proliferation of microorganisms. Notably, MnO2@SF-AGS showed excellent granulation performance, reaching a stable state about one week earlier than the unmodified SF-AGS. The polymeric substance content of MnO2@SF-AGS was found to be 1.28 times higher than that of the control group. Furthermore, the removal rates for NH4+-N, TN, and TP were enhanced by 27.28%, 12.8%, and 32.14%, respectively. The bacterial communities exhibited significant variations in response to different surface modifications of AGS, with genera such as Saprospiraceae, Terrimonas, and Ferruginibacter playing a crucial role in the formation of AGS and the removal of pollutants specifically in MnO2@SF-AGS. The charge transfer of metal ions of MnO2@SF promotes the granulation process and pollutant removal. These results highlight that MnO2@SF-AGS is an effective strategy for improving nitrogen and phosphorus removal efficiency from wastewater.

Carnosol suppresses cardiomyocyte hypertrophy via promoting the activation of AMPK pathway.

Pathological cardiac hypertrophy is associated with adverse cardiovascular events and can gradually lead to heart failure, arrhythmia, and even sudden death. However, the current development of treatment strategies has been unsatisfactory. Therefore, it is of great significance to find new and effective drugs for the treatment of myocardial hypertrophy. We found that carnosol can inhibit myocardial hypertrophy induced by PE stimulation, and the effect is very significant at 5 µM. Moreover, we demonstrated that 50 mg/kg of carnosol protect against cardiac hypertrophy and fibrosis induced by TAC surgery in mice. Mechanically, we proved that the inhibitory effect of carnosol on cardiac hypertrophy depends on its regulation on the phosphorylation activation of AMPK. In conclusion, our study suggested that carnosol may be a novel drug component for the treatment of pathological cardiac hypertrophy.

Metal-polyphenol self-assembled nanodots for NIR-II fluorescence imaging-guided chemodynamic/photodynamic therapy-amplified ferroptosis.

The effectiveness of tumor treatment using reactive oxygen species as the primary therapeutic medium is hindered by limitations of tumor microenvironment (TME), such as intrinsic hypoxia in photodynamic therapy (PDT) and overproduction of reducing glutathione (GSH) in chemodynamic therapy (CDT). Herein, we fabricate metal-polyphenol self-assembled nanodots (Fe@BDP NDs) guided by second near-infrared (NIR-II) fluorescence imaging. The Fe@BDP NDs are designed for synergistic combination of type-I PDT and CDT-amplified ferroptosis. In a mildly acidic TME, Fe@BDP NDs demonstrate great Fenton activity, leading to the generation of highly toxic hydroxyl radicals from overproduced hydrogen peroxide in tumor cells. Furthermore, Fe@BDP NDs show favorable efficacy in type-I PDT, even in tolerating tumor hypoxia, generating active superoxide anion upon exposure to 808 nm laser irradiation. The significant efficiency in reactive oxygen species (ROS) products results in the oxidation of sensitive polyunsaturated fatty acids, accelerating lethal lipid peroxidation (LPO) bioprocess. Additionally, Fe@BDP NDs illustrate an outstanding capability for GSH depletion, causing the inactivation of glutathione peroxidase 4 and further promoting lethal LPO. The synergistic type-I photodynamic and chemodynamic cytotoxicity effectively trigger irreversible ferroptosis by disrupting the intracellular redox homeostasis. Moreover, Fe@BDP NDs demonstrate charming NIR-II fluorescence imaging capability and effectively accumulated at the tumor site, visualizing the distribution of Fe@BDP NDs and the treatment process. The chemo/photo-dynamic-amplified ferroptotic efficacy of Fe@BDP NDs was evidenced both in vitro and in vivo. This study presents a compelling approach to intensify ferroptosis via visualized CDT and PDT. STATEMENT OF SIGNIFICANCE: In this study, we detailed the fabrication of metal-polyphenol self-assembled nanodots (Fe@BDP NDs) guided by second near-infrared (NIR-II) fluorescence imaging, aiming to intensify ferroptosis via the synergistic combination of type-I PDT and CDT. In a mildly acidic TME, Fe@BDP NDs exhibited significant Fenton activity, resulting in the generation of highly toxic •OH from overproduced H2O2 in tumor cells. Fe@BDP NDs possessed a remarkable capability for GSH depletion, resulting in the inactivation of glutathione peroxidase 4 (GPX4) and further accelerating lethal LPO. This study presented a compelling approach to intensify ferroptosis via visualized CDT and PDT.

Versatile function of NF-ĸB in inflammation and cancer.

Nuclear factor-kappaB (NF-ĸB) plays a crucial role in both innate and adaptive immune systems, significantly influencing various physiological processes such as cell proliferation, migration, differentiation, survival, and stemness. The function of NF-ĸB in cancer progression and response to chemotherapy has gained increasing attention. This review highlights the role of NF-ĸB in inflammation control, biological mechanisms, and therapeutic implications in cancer treatment. NF-ĸB is instrumental in altering the release of inflammatory factors such as TNF-α, IL-6, and IL-1ß, which are key in the regulation of carcinogenesis. Specifically, in conditions including colitis, NF-ĸB upregulation can intensify inflammation, potentially leading to the development of colorectal cancer. Its pivotal role extends to regulating the tumor microenvironment, impacting components such as macrophages, fibroblasts, T cells, and natural killer cells. This regulation influences tumorigenesis and can dampen anti-tumor immune responses. Additionally, NF-ĸB modulates cell death mechanisms, notably by inhibiting apoptosis and ferroptosis. It also has a dual role in stimulating or suppressing autophagy in various cancers. Beyond these functions, NF-ĸB plays a role in controlling cancer stem cells, fostering angiogenesis, increasing metastatic potential through EMT induction, and reducing tumor cell sensitivity to chemotherapy and radiotherapy. Given its oncogenic capabilities, research has focused on natural products and small molecule compounds that can suppress NF-ĸB, offering promising avenues for cancer therapy.

Black carp A20 inhibits interferon signaling through de-ubiquitinating IKKß.

IkappaB kinase beta (IKKß) is a key member of IκB kinases and functions importantly in interferon (IFN) signaling. Phosphorylation and ubiquitination are involved in the activation of IKKß. A20 is a de-ubiquitin enzyme and functions as a suppressor in inflammation signaling, which has been reported to be phosphorylated and activated by IKKß. However, the role and relationship of IKKß and A20 in teleost remains unclear. In this study, IKKß (bcIKKß) and A20 (bcA20) of black carp (Mylopharyngodon piceus) have been cloned and characterized. Overexpressed bcIKKß in EPC cells showed strong anti-viral ability by activating both NF-κB and IFN signaling. EPC cells stable expressing bcIKKß presented improved anti-viral activity as well. The interaction between bcA20 and bcIKKß was identified, and overexpression of bcA20 was able to suppress bcIKKß-mediated activation of NF-κB and IFN signaling. Meanwhile, knock-down of A20 increased host the antiviral ability of host cells. Importantly, it has been identified that bcA20 was able to remove K27-linked ubiquitination and decrease the phosphorylation of bcIKKß. Thus, our data conclude that bcA20 suppresses the anti-viral activity of bcIKKß and removes its K27-linked ubiquitination, which presents a new mechanism of IKKß regulation.

Electronic Health Record-Oriented Knowledge Graph System for Collaborative Clinical Decision Support Using Multicenter Fragmented Medical Data: Design and Application Study.

BACKGROUND: The medical knowledge graph provides explainable decision support, helping clinicians with prompt diagnosis and treatment suggestions. However, in real-world clinical practice, patients visit different hospitals seeking various medical services, resulting in fragmented patient data across hospitals. With data security issues, data fragmentation limits the application of knowledge graphs because single-hospital data cannot provide complete evidence for generating precise decision support and comprehensive explanations. It is important to study new methods for knowledge graph systems to integrate into multicenter, information-sensitive medical environments, using fragmented patient records for decision support while maintaining data privacy and security. OBJECTIVE: This study aims to propose an electronic health record (EHR)-oriented knowledge graph system for collaborative reasoning with multicenter fragmented patient medical data, all the while preserving data privacy. METHODS: The study introduced an EHR knowledge graph framework and a novel collaborative reasoning process for utilizing multicenter fragmented information. The system was deployed in each hospital and used a unified semantic structure and Observational Medical Outcomes Partnership (OMOP) vocabulary to standardize the local EHR data set. The system transforms local EHR data into semantic formats and performs semantic reasoning to generate intermediate reasoning findings. The generated intermediate findings used hypernym concepts to isolate original medical data. The intermediate findings and hash-encrypted patient identities were synchronized through a blockchain network. The multicenter intermediate findings were collaborated for final reasoning and clinical decision support without gathering original EHR data. RESULTS: The system underwent evaluation through an application study involving the utilization of multicenter fragmented EHR data to alert non-nephrology clinicians about overlooked patients with chronic kidney disease (CKD). The study covered 1185 patients in nonnephrology departments from 3 hospitals. The patients visited at least two of the hospitals. Of these, 124 patients were identified as meeting CKD diagnosis criteria through collaborative reasoning using multicenter EHR data, whereas the data from individual hospitals alone could not facilitate the identification of CKD in these patients. The assessment by clinicians indicated that 78/91 (86%) patients were CKD positive. CONCLUSIONS: The proposed system was able to effectively utilize multicenter fragmented EHR data for clinical application. The application study showed the clinical benefits of the system with prompt and comprehensive decision support.

Analysis of the causal relationship between gut microbiota and bone remodeling growth factor from the gene association.

BACKGROUND: A growing body of evidence indicates a close association between the gut microbiota (GM) and the bone remodeling (BR) process, raising suspicions that the GM may actively participate in BR by modulating the levels of growth factors. However, the precise causal relationship between them remains unclear. Due to many confounding factors, many microorganisms related to BR growth factors have not been identified. We aimed to elucidate the causal relationship between the GM and BR growth factors. METHODS: We evaluated the genome-wide association study (GWAS) summary statistics for GM and five common growth factors associated with BR: namely, bone morphogenetic proteins (BMP), transforming growth factors(TGF), insulin growth factors (IGFs), epidermal growth factors (EGFs), and fibroblast growth factors (FGF). The causal relationship between the GM and BR growth factors was studied by double-sample Mendelian randomized analysis. We used five Mendelian randomization (MR) methods, including inverse variance-weighted (IVW), MR-Egger, simple mode, weighted median, and weighted model methods. RESULTS: Through MR analysis, a total of 56 bacterial genera were co-identified as associated with BMP, TGF, IGF, EGF, and FGF. Among them, eight genera were found to have a causal relationship with multiple growth factors: Marvinbryantia was causally associated with BMP-6 (P = 0.018, OR = 1.355) and TGF-ß2 (P = 0.002, OR = 1.475); Lachnoclostridium, BMP-7 (P = 0.021, OR = 0.73) and IGF-1 (P = 0.046, OR = 0.804); Terrisporobacter, TGF-ß (P = 0.02, OR = 1.726) and FGF-23 levels (P = 0.016, OR = 1.76); Ruminiclostridium5, TGF-ß levels (P = 0.024, OR = 0.525) and FGFR-2 (P = 0.003, OR = 0.681); Erysipelatoclostridium, TGF-ß2 (P = 0.001, OR = 0.739) and EGF and its receptor (EGFR) (P = 0.012, OR = 0.795); Eubacterium_brachy_group, FGFR-2 (P = 0.045, OR = 1.153) and EGF (P = 0.013, OR = 0.7); Prevotella9 with EGFR (P = 0.022, OR = 0.818) and FGFR-2 (P = 0.011, OR = 1.233) and Faecalibacterium with FGF-23 (P = 0.02, OR = 2.053) and IGF-1 (P = 0.005, OR = 0.843). CONCLUSION: We confirmed the causal relationship between the GM and growth factors related to BR, which provides a new perspective for the study of BR, through targeted regulation of specific bacteria to prevent and treat diseases and growth factor-mediated BR disorders.

Full-chain analysis on emerging contaminants in soil: Source, migration and remediation.

Emerging contaminants (ECs) are gaining attention due to their prevalence and potential negative impacts on the environment and human health. This paper provides a comprehensive review of the status and trends of soil pollution caused by ECs, focusing on their sources, migration pathways, and environmental implications. Significant ECs, including plastics, synthetic polymers, pharmaceuticals, personal care products, plasticizers, and flame retardants, are identified due to their widespread use and toxicity. Their presence in soil is attributed to agricultural activities, urban waste, and wastewater irrigation. The review explores both horizontal and vertical migration pathways, with factors such as soil type, organic matter content, and moisture levels influencing their distribution. Understanding the behavior of ECs in soil is critical to mitigating their long-term risks and developing effective soil remediation strategies. The paper also examines the advantages and disadvantages of in situ and ex situ treatment approaches for ECs, highlighting optimal physical, chemical, and biological treatment conditions. These findings provide a fundamental basis for addressing the challenges and governance of soil pollution induced by ECs.

Enantioselective Surface-Enhanced Raman Scattering by Chiral Au Nanocrystals with Finely Modulated Chiral Fields and Internal Standards.

The chiral discrimination of enantiomers is crucial for drug screening and agricultural production. Surface-enhanced Raman scattering (SERS) is proposed for discriminating enantiomers benefiting from chiral plasmonic materials. However, the mechanism of enantioselective SERS is unclear, and fluctuating SERS intensities may result in errors. Herein, this work demonstrates a reliable SERS substrate using chiral Au nanocrystals with finely modulated chiral fields and internal standards. Chiral electromagnetic fields are enhanced after modulation, which is conducive to increasing the difference in the enantiomeric SERS intensity, as evidenced by the experimental and simulation results. Furthermore, the SERS stability is improved by the corrective effect of the internal standards, and the relative standard deviation is significantly reduced. Using finely modulated chiral fields and internal standards, L- and D-phenylalanine exhibit a stable six times difference in SERS ratio. Theoretical simulations reveal that linearly polarized light can also excite the chiral fields of chiral Au nanocrystals, indicating non-chiral far-field light is converted into chiral near-field sources by chiral Au nanocrystals. Thus, the mechanism of enantioselective SERS can be elucidated by the scattering difference of chiral molecules in chiral near fields. This study will pave the way for the development of enantioselective SERS and related chiroptical technologies.

Multiplex influences on vigilance and biochemical variables induced by sleep deprivation.

Introduction: Sleep loss and sleep deprivation (SD) cause deleterious influences on health, cognition, mood and behaviour. Nevertheless, insufficient sleep and SD are prevalent across many industries and occur in various emergencies. The deleterious consequences of SD have yet to be fully elucidated. This study aimed to assess the extensive influences of SD on physiology, vigilance, and plasma biochemical variables. Methods: Seventeen volunteers were recruited to participate in a 32.5-h SD experiment. Multiple physiological and cognitive variables, including tympanic temperature, blood oxygen saturation (SaO2), and vigilance were recorded. Urinal/salivary samples were collected and subjected to cortisol or cortisone analysis, and plasma samples were subjected to transcriptomic analysis of circular RNA (circRNA) expression using microarray. Plasma neurotransmitters were measured by targeted metabolic analysis, and the levels of inflammatory factors were assessed by antibody microarray. Results: The volunteers showed significantly increased sleepiness and decreased vigilance during SD, and the changes in circadian rhythm and plasma biochemistry were observed. The plasma calcium (p = 0.0007) was induced by SD, while ischaemia-modified albumin (IMA, p = 0.0030) and total bile acid (TBA, p = 0.0157) decreased. Differentially expressed circRNAs in plasma were identified, which are involved in multiple signaling pathways including neuronal regulation and immunity. Accordingly, SD induced a decrease in 3-hydroxybutyric acid (3OBH, p = 0.0002) and an increase in thyroxine (T4, p < 0.0001) in plasma. The plasma anti-inflammatory cytokine IL-10 was downregulated while other ten inflammatory factors were upregulated. Conclusion: This study demonstrates that SD influences biochemical, physiological, cognitive variables, and the significantly changed variables may serve as candidates of SD markers. These findings may further our understanding of the detrimental consequence of sleep disturbance at multiple levels.