Integrated physiological, transcriptomics and metabolomics analysis revealed the molecular mechanism of Bupleurum chinense seedlings to drought stress.

Drought stress is a prominent abiotic factor that adversely influences the growth and development of Bupleurum chinense during its seedling stage, negatively impacting biomass and secondary metabolite production, thus affecting yield and quality. To investigate the molecular mechanism underlying the response of B. chinense seedlings under drought stress, this study employed comprehensive physiological, transcriptomic, and metabolomic analyses. The results revealed that under drought stress, the root soluble sugar and free proline content in B. chinense seedlings significantly increased, while the activities of SOD, POD, and CAT increased in the leaves. These findings indicate the presence of distinct response mechanisms in B. chinense to cope with drought stress. Integrated analysis further identified significant correlations between genes and metabolites related to amino acid biosynthesis in the leaves, as well as genes and metabolites associated with acetaldehyde and dicarboxylic acid metabolism. In the roots, genes and metabolites related to plant hormone signaling and the tricarboxylic acid (TCA) cycle showed significant correlations. These findings provide vital views into the molecular-level response mechanisms of B. chinense under drought stress. Moreover, this study establishes the groundwork for identifying drought-tolerant genes and breeding drought-resistant varieties, which could improve the drought tolerance of medicinal plants and have broader implications for agriculture and crop production in water-scarce areas.

Multi-medium residues and ecological risk of herbicides in a typical agricultural watershed of the Mollisols region, Northeast China.

The widespread use of herbicides impacts non-target organisms, promotes weed resistance, posing a serious threat to the global goal of green production in agriculture. Although the herbicide residues have been widely reported in individual environmental medium, their presence across different media has received scant attention, particularly in Mollisols regions with intensive agricultural application of herbicides. A systematic investigation was conducted in this study to clarify the occurrence of herbicide residues in soil, surface water, sediments, and grains from a typical agricultural watershed in the Mollisols region of Northeast China. Concentrations of studied herbicides ranged from 0.30 to 463.49 µg/kg in soil, 0.31-29.73 µg/kg in sediments, 0.006-1.157 µg/L in water, and 0.32-2.83 µg/kg in grains. Among these, Clomazone was the most priority herbicide detected in soil, sediments, and water, and Pendimethalin in grains. Crop types significantly affected the residue levels of herbicides in grains. Clomazone posed high ecological risks in soil and water, with 86.4 % of water samples showing high risks from herbicide mixtures (RQ > 1). These findings aid in enhancing our comprehension of the pervasive occurrence and potential ecological risks of herbicides in different media within typical agricultural watersheds, providing detailed data to inform the development of targeted mitigation strategies.

Streamlined Synthesis of Varied Heteroarene-Condensed Benzofuran Derivatives via [4 + 2] Annulation of Benzofuran-Derived Azadienes and N-Alkyl Quinolinium Salts.

Herein we have pioneered an innovative synthetic strategy for the efficient assembly of various heteroarene-condensed benzofuran derivatives, utilizing benzofuran-derived azadienes (BDAs) and quinolines as the starting materials. This method functions with transition-metal catalysis and uses cost-effective formic acid as the reducing agent. Mechanistic investigations indicate that this transformation would involve a [4 + 2] annulation cascade process. This approach demonstrates a high tolerance to various functional groups and yields excellent results.

Interfacial Spinel Local Interlocking Strategy Toward Structural Integrity in P3 Oxide Cathodes.

P3-layered transition oxide cathodes have garnered considerable attention owing to their high initial capacity, rapid Na+ kinetics, and less energy consumption during the synthesis process. Despite these merits, their practical application is hindered by the substantial capacity degradation resulting from unfavorable structural transformations, Mn dissolution and migration. In this study, we systematically investigated the failure mechanisms of P3 cathodes, encompassing Mn dissolution, migration, and the irreversible P3-O3' phase transition, culminating in severe structural collapse. To address these challenges, we proposed an interfacial spinel local interlocking strategy utilizing P3/spinel intergrowth oxide as a proof-of-concept material. As a result, P3/spinel intergrowth oxide cathodes demonstrated enhanced cycling performance. The effectiveness of suppressing Mn migration and maintaining local structure of interfacial spinel local interlocking strategy was validated through depth-etching X-ray photoelectron spectroscopy, X-ray absorption spectroscopy, and in situ synchrotron-based X-ray diffraction. This interfacial spinel local interlocking engineering strategy presents a promising avenue for the development of advanced cathode materials for sodium-ion batteries.

Observation of Chiral Channels in Helical Covalent Organic Frameworks.

Unraveling the mechanism of chirality transfer across length scales is crucial to the rational development of functional materials with hierarchical chirality. The key obstacle is the lack of structural information, especially at the mesoscopic level. We report herein the structural identification of helical covalent organic frameworks (heliCOFs) with hierarchical chirality, which integrate molecular chirality, channel chirality, and morphology chirality into one crystalline entity. Specifically, benefiting from the highly ordered structure of heliCOFs, the existence of chiral channels at the mesoscopic level has been confirmed by electron crystallography, and the handedness of these chiral channels has been directly determined through the stereopair imaging technique. Accordingly, the chirality transfer in heliCOFs from microscopic to macroscopic levels could be rationalized with a layer-rotating model that has been supported by both crystal structure analysis and theoretical calculations. Observation of chiral channels in heliCOFs not only provides unprecedented data for the understanding of the chirality transfer process but also sheds new light on the rational construction of highly ordered polymeric materials with hierarchical chirality.

Transcriptome analysis of Kluyveromyces marxianus under succinic acid stress and development of robust strains.

Kluyveromyces marxianus has become an attractive non-conventional yeast cell factory due to its advantageous properties such as high thermal tolerance and rapid growth. Succinic acid (SA) is an important platform molecule that has been applied in various industries such as food, material, cosmetics, and pharmaceuticals. SA bioproduction may be compromised by its toxicity. Besides, metabolite-responsive promoters are known to be important for dynamic control of gene transcription. Therefore, studies on global gene transcription under various SA concentrations are of great importance. Here, comparative transcriptome changes of K. marxianus exposed to various concentrations of SA were analyzed. Enrichment and analysis of gene clusters revealed repression of the tricarboxylic acid cycle and glyoxylate cycle, also activation of the glycolysis pathway and genes related to ergosterol synthesis. Based on the analyses, potential SA-responsive promoters were investigated, among which the promoter strength of IMTCP2 and KLMA_50231 increased 43.4% and 154.7% in response to 15 g/L SA. In addition, overexpression of the transcription factors Gcr1, Upc2, and Ndt80 significantly increased growth under SA stress. Our results benefit understanding SA toxicity mechanisms and the development of robust yeast for organic acid production. KEY POINTS: • Global gene transcription of K. marxianus is changed by succinic acid (SA) • Promoter activities of IMTCP2 and KLMA_50123 are regulated by SA • Overexpression of Gcr1, Upc2, and Ndt80 enhanced SA tolerance.

Biomedical Applications of Sulfonylcalix[4]arene-Based Metal-Organic Supercontainers.

Coordination cages sustained by metal-ligand interactions feature polyhedral architectures and well-defined hollow structures, which have attracted significant attention in recent years due to a variety of structure-guided promising applications. Sulfonylcalix[4]arenes-based coordination cages, termed metal-organic supercontainers (MOSCs), that possess unique multi-pore architectures containing an endo cavity and multiple exo cavities, are emerging as a new family of coordination cages. The well-defined built-in multiple binding domains of MOSCs allow the efficient encapsulation of guest molecules, especially for drug delivery. Here, we critically discuss the design strategy, and, most importantly, the recent advances in research surrounding cavity-specified host-guest chemistry and biomedical applications of MOSCs.

Photocleavable DNA Nanotube-Based Dual-Amplified Resonance Rayleigh Scattering System for MicroRNA Detection Incorporating Molecular Computing-Cascaded Keypad Lock Functionality.

Cascade molecular events in complex systems are of vital importance for enhancing molecular diagnosis and information processing. However, the conversion of a cascaded biosensing system into a multilayer encrypted molecular keypad lock remains a significant challenge in the development of molecular logic devices. In this study, we present a photocleavable DNA nanotube-based dual-amplified resonance Rayleigh scattering (RRS) system for detecting microRNA-126 (miR-126). The cascading dual-amplification biosensing system provides a multilayer-encrypted prototype with the functionality of a molecular computing cascade keypad lock. RRS signals were greatly amplified by using photocleavable DNA nanotubes and enzyme-assisted strand displacement amplification (SDA). In the presence of miR-126, enzyme-assisted SDA produced numerous identical nucleotide fragments as the target, which were then specifically attached to magnetic beads through the DNA nanotube by using a Y-shaped DNA scaffold. Upon ultraviolet irradiation, the DNA nanotube was released into the solution, resulting in an increase in the intensity of the RRS signal. This strategy demonstrated a low limit of detection (0.16 fM) and a wide dynamic range (1 fM to 1 nM) for miR-126. Impressively, the enzyme-assisted SDA offers a molecular computing model for generating the target pool, which serves as the input element for unlocking the system. By cascading the molecular computing process, we successfully constructed a molecular keypad lock with a multilevel authentication technique. The proposed system holds great potential for applications in molecular diagnosis and information security, indicating significant value in integrating molecular circuits for intelligent sensing.

Associated factors of depression in primiparas with hypothyroidism during pregnancy.

This cross-sectional study aimed to explore the associated factors of depression in primiparas with hypothyroidism during pregnancy. The research subjects were 200 primiparas with hypothyroidism during pregnancy who were admitted to our hospital between December 2016 and December 2019. Self-rating depression scale scores were used to evaluate the depression, and the incidence of depression were examined. The data from all the subjects were collected to compare the differences between primiparas with hypothyroidism during pregnancy with and without depression. A logistic regression equation was used to analyze the influencing factors of depression in these patients. Of the 200 primiparas who took part in this study, 27 suffered from depression, accounting for 13.50%. There were differences in age, education level, economic income, sleep quality, and conjugal relations between the depressed and the nondepressed participants. When the above factors were included in the logistic regression equation, it was found that the odds ratio values for these factors were all >1, which indicated that they had an influence on maternal depression in primiparas with hypothyroidism during pregnancy. This study demonstrated that pregnancy-associated hypothyroidism in primiparas is affected by age, education level, economic income, sleep quality, and conjugal relations, all of which increase the incidence of depression. Relevant preventive measures should be provided in clinical practice to avoid the occurrence of depression.

Development and External Validation of Clinical Features-based Machine Learning Models for Predicting COVID-19 in the Emergency Department.

Introduction: Timely diagnosis of patients affected by an emerging infectious disease plays a crucial role in treating patients and avoiding disease spread. In prior research, we developed an approach by using machine learning (ML) algorithms to predict serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on clinical features of patients visiting an emergency department (ED) during the early coronavirus 2019 (COVID-19) pandemic. In this study, we aimed to externally validate this approach within a distinct ED population. Methods: To create our training/validation cohort (model development) we collected data retrospectively from suspected COVID-19 patients at a US ED from February 23-May 12, 2020. Another dataset was collected as an external validation (testing) cohort from an ED in another country from May 12-June 15, 2021. Clinical features including patient demographics and triage information were used to train and test the models. The primary outcome was the confirmed diagnosis of COVID-19, defined as a positive reverse transcription polymerase chain reaction test result for SARS-CoV-2. We employed three different ML algorithms, including gradient boosting, random forest, and extra trees classifiers, to construct the predictive model. The predictive performances were evaluated with the area under the receiver operating characteristic curve (AUC) in the testing cohort. Results: In total, 580 and 946 ED patients were included in the training and testing cohorts, respectively. Of them, 98 (16.9%) and 180 (19.0%) were diagnosed with COVID-19. All the constructed ML models showed acceptable discrimination, as indicated by the AUC. Among them, random forest (0.785, 95% confidence interval [CI] 0.747-0.822) performed better than gradient boosting (0.774, 95% CI 0.739-0.811) and extra trees classifier (0.72, 95% CI 0.677-0.762). There was no significant difference between the constructed models. Conclusion: Our study validates the use of ML for predicting COVID-19 in the ED and demonstrates its potential for predicting emerging infectious diseases based on models built by clinical features with temporal and spatial heterogeneity. This approach holds promise for scenarios where effective diagnostic tools for an emerging infectious disease may be lacking in the future.

Valuation of the cultural adaptation and psychometric properties of the Chinese version of the hidden curriculum evaluation scale in nursing education.

BACKGROUND: The hidden curriculum in baccalaureate nursing programs is a means of moral education. Evaluation of the curriculum by students and faculty can increase awareness of its characteristics, which could be useful for planning and further development. OBJECTIVES: This study's aim was to translate the Hidden Curriculum Evaluation Scale in Nursing Education (HCES-N) to Chinese, adapt the scale to the Chinese culture and evaluate its validity and reliability in a sample of undergraduate nursing students. DESIGN: Psychometric assessment of a tool using two cross-sectional surveys. SETTINGS: University-based schools of nursing in seven provinces and cities of China. PARTICIPANTS: Undergraduate nursing students in a baccalaureate program. METHODS: The English version of the HCES-N was translated to Chinese using the Brislin translation model. The test-retest, internal consistency and split-half reliabilities of the HCES-N were examined in a sample of 1016 undergraduate nursing students. Exploratory factor analysis and confirmatory factor analysis were conducted to examine the scale's content validity. RESULTS: The exploratory factor analysis of the final 44-item HCES-N revealed three common factors and a cumulative variance contribution rate of 73.535%. The results of the confirmatory factor analysis showed that the final 44-item, 3-factor model was adequate for the s cale's structure (Chi-square/df = 6.59, RMSEA = 0.074, SRMR = 0.040, CFI = 0.911 and TLI = 0.905). The results confirmed that the Chinese version of HCES-N had good internal consistency (Cronbach α = 0.945); the scale's split-half-reliability was 0.794 and its test-retest reliability after two weeks was 0.894. CONCLUSION: The Chinese version of the HCES-N has good reliability and validity and it can be used to assess the hidden curriculum in baccalaureate nursing programs.

Effects of straw return with potassium fertilizer on the stem lodging resistance, grain quality and yield of spring maize (Zea mays L.).

This experiment aimed to study the effects of straw return combined with potassium fertilizer on stem lodging resistance, grain quality, and yield of spring maize. The objective was to provide a scientific basis for the rational utilization of Inner Mongolia spring maize straw and potassium fertilizer resources. The test material used was 'Xianyu 335', and the study was conducted in three ecological regions from east to west of Inner Mongolia (Tumochuan Plain Irrigation Area, Hetao Plain Irrigation Area, and Lingnan Warm Dry Zone). A split-plot design was employed, with the straw return method as the main plot and potassium fertilizer dosage as the secondary plot. We determined the stem resistance index, grain quality, and yield. The results showed that both straw return and potassium application improved stem lodging resistance, grain quality, and maize yield. Combining straw return with the reasonable application of potassium fertilizer enhanced the effectiveness of potassium fertilizer, increased lodging resistance, maize yield, and improved grain quality and yield stability. Under the straw return treatment, with potassium application compared to no potassium application, significant increases were observed in maize plant height, stem diameter, dry weight of stems, stem compressive strength, stem bending strength, grain protein content, yield, straw potassium accumulation content, and soil available potassium content. These increases were up to 30.79 cm, 2.63 mm, 15.40 g, 74.93 N/mm2, 99.65 N/mm2, 13.68%, 3142.43 kg/hm2, 57.97 kg/hm2, and 19.80 mg/kg, respectively. Therefore, the interaction of straw return and potassium fertilizer was found to be the most effective measure for maintaining high-yield and stress-resistant cultivation, improving grain quality, and optimizing the management of straw and potassium fertilizer resources. This approach is suitable for promotion and application in the spring maize growing areas of Inner Mongolia.

Photocontrollable DNA Walker-Based Molecular Circuit for the Tunable Detection of MicroRNA-21 Using Metal-Organic Frameworks as Label-Free Fluorescence Tags.

Tunable detection of microRNA is crucial to meet the desired demand for sample species with varying concentrations in clinical settings. Herein, we present a DNA walker-based molecular circuit for the detection of miRNA-21 (miR-21) with tunable dynamic ranges and sensitivity levels ranging from fM to pM. The phosphate-activated fluorescence of UiO-66-NH2 metal-organic framework nanoparticles was used as label-free fluorescence tags due to their competitive coordination effect with the Zr atom, which significantly inhibited the ligand-to-metal charge transfer. To achieve a tunable detection performance for miR-21, the ultraviolet sensitive o-nitrobenzyl was induced as a photocleavable linker, which was inserted at various sites between the loop and the stem of the hairpin probe to regulate the DNA strand displacement reaction. The dynamic range can be precisely regulated from 700- to 67,000-fold with tunable limits of detection ranging from 2.5 fM to 36.7 pM. Impressively, a Boolean logic tree and complex molecular circuit were constructed for logic computation and cancer diagnosis in clinical blood samples. This intelligent biosensing method presents a powerful solution for converting complex biosensing systems into actionable healthcare decisions and will facilitate early disease diagnosis.

Automated marker-free longitudinal infrared breast image registration by GA-PSO.

The automated marker-free longitudinal Infrared (IR) breast image registration overcomes several challenges like no anatomic fiducial markers on the body surface, blurry boundaries, heat pattern variation by environmental and physiological factors, nonrigid deformation, etc, has the ability of quantitative pixel-wise analysis with the heat energy and patterns change in a time course study. To achieve the goal, scale-invariant feature transform, Harris corner, and Hessian matrix were employed to generate the feature points as anatomic fiducial markers, and hybrid genetic algorithm and particle swarm optimization minimizing the matching errors was used to find the appropriate corresponding pairs between the 1st IR image and thenth IR image. Moreover, the mechanism of the IR spectrogram hardware system has a high level of reproducibility. The performance of the proposed longitudinal image registration system was evaluated by the simulated experiments and the clinical trial. In the simulated experiments, the mean difference of our system is 1.64 mm, which increases 57.58% accuracy than manual determination and makes a 17.4% improvement than the previous study. In the clinical trial, 80 patients were captured several times of IR breast images during chemotherapy. Most of them were well aligned in the spatiotemporal domain. In the few cases with evident heat pattern dissipation and spatial deviation, it still provided a reliable comparison of vascular variation. Therefore, the proposed system is accurate and robust, which could be considered as a reliable tool for longitudinal approaches to breast cancer diagnosis.

The effect of exercise on the risk of metabolic syndrome associated with sleep insufficiency: a cross-sectional study.

Introduction: Sleep disturbance and insufficient sleep have been linked to metabolic syndrome, increasing cardiovascular disease and mortality risk. However, few studies investigate the joint effect of sleep and exercise on metabolic syndrome. We hypothesized that regular exercise can mitigate the exacerbation of metabolic syndrome by sleep insufficiency. Objective: The aim of this study was to investigate whether exercise can attenuate or eliminate the relationship between sleep insufficiency and metabolic syndrome. Method: A total of 6,289 adults (mean age = 33.96 years; women: 74.81%) were included in the study, a cross-sectional study conducted based on the results of employee health screening questionnaires and databases from a large healthcare system in central Taiwan. Participants reported sleep insufficiency or not. Self-reported exercise habits were classified into 3 levels: no exercise, exercise <150 min/week, and exercise ≧150 min/week. Multiple logistic regression and sensitivity analyses were conducted to understand the joint associations of sleep patterns and exercise with metabolic syndrome with exposure variables combining sleep duration/disturbances and PA. Results: Compared with the reference group (sufficient sleep), individuals with sleep insufficiency had a higher risk for metabolic syndrome [adjusted odds ratio (AOR) = 1.40, 95% confidence interval (95% CI): 1.01-1.94, p < 0.05] in females aged 40-64 years, but not in other populations. Sleep insufficiency was not associated with the risk of metabolic syndrome among individuals achieving an exercise level of <150 min/week, and in particular among those achieving ≧150 min/week in all populations in our study. Conclusion: Sleep insufficiency was related to a higher risk of metabolic syndrome in female healthcare staff aged 40-64 years. Being physically active with exercise habits in these individuals, the risk of metabolic syndrome was no longer significant.

Synthetic lethality in human bladder cancer cells by curcumin via concurrent Aurora A inhibition and autophagy induction.

Combination therapies to induce mixed-type cell death and synthetic lethality have the potential to overcome drug resistance in cancer. In this study, we demonstrated that the curcumin-enhanced cytotoxicity of cisplatin/carboplatin in combination with gemcitabine was associated with Aurora A suppression-mediated G2/M arrest, and thus apoptosis, as well as MEK/ERK-mediated autophagy in human bladder cancer cells. Animal study data confirmed that curcumin combined with cisplatin/gemcitabine reduced tumorigenesis of xenograft in mice and this phenomenon was associated with elevated expressions of p-ERK and reduced p-Aurora A in tumors. Gene analyses using data repositories further revealed that reduced Aurora A expression alone did not significantly elevate the sensitivity of human bladder carcinoma cells to these anticancer drugs. Unlike other major cancer types, human bladder urothelial carcinoma tissue coexpressed higher AURKA and lower MAP1LC3B than normal tissue, and reduced Aurora A and induction of autophagy have been clinically associated with a better prognosis in patients with early but not advanced stage bladder cancer. Therefore, our results suggest that treatment strategies can utilize the synthetic lethal pair to concurrently suppress oncogenic Aurora A and induce autophagy by coadministrating curcumin with anticancer drugs for early-stage bladder cancer with high expression of Aurora A.

Progress in nanoparticle-based regulation of immune cells.

Immune cells are indispensable defenders of the human body, clearing exogenous pathogens and toxicities or endogenous malignant and aging cells. Immune cell dysfunction can cause an inability to recognize, react, and remove these hazards, resulting in cancers, inflammatory diseases, autoimmune diseases, and infections. Immune cells regulation has shown great promise in treating disease, and immune agonists are usually used to treat cancers and infections caused by immune suppression. In contrast, immunosuppressants are used to treat inflammatory and autoimmune diseases. However, the key to maintaining health is to restore balance to the immune system, as excessive activation or inhibition of immune cells is a common complication of immunotherapy. Nanoparticles are efficient drug delivery systems widely used to deliver small molecule inhibitors, nucleic acid, and proteins. Using nanoparticles for the targeted delivery of drugs to immune cells provides opportunities to regulate immune cell function. In this review, we summarize the current progress of nanoparticle-based strategies for regulating immune function and discuss the prospects of future nanoparticle design to improve immunotherapy.

DNA Tile and Invading Stacking Primer-Assisted CRISPR-Cas12a Multiple Amplification System for Entropy-Driven Electrochemical Detection of MicroRNA with Tunable Sensitivity.

Conventional electrochemical detection of microRNA (miRNA) encounters issues of poor sensitivity and fixed dynamic range. Here, we report a DNA tile and invading stacking primer-assisted CRISPR-Cas12a multiple amplification strategy to construct an entropy-controlled electrochemical biosensor for the detection of miRNA with tunable sensitivity and dynamic range. To amplify the signal, a cascade amplification of the CRISPR-Cas12a system along with invading stacking primer signal amplification (ISPSA) was designed to detect trace amounts of miRNA-31 (miR-31). The target miR-31 could activate ISPSA and produce numerous DNAs, triggering the cleavage of the single-stranded linker probe (LP) that connects a methylene blue-labeled DNA tile with a DNA tetrahedron to form a Y-shaped DNA scaffold on the electrode. Based on the decrease of current, miR-31 can be accurately and efficiently detected. Impressively, by changing the loop length of the LP, it is possible to finely tune the entropic contribution while keeping the enthalpic contribution constant. This strategy has shown a tunable limit of detection for miRNA from 0.31 fM to 0.56 pM, as well as a dynamic range from ∼2200-fold to ∼270,000-fold. Moreover, it demonstrated satisfactory results in identifying cancer cells with a high expression of miR-31. Our strategy broadens the application of conventional electrochemical biosensing and provides a tunable strategy for detecting miRNAs at varying concentrations.