Integrated multi-omics analysis reveals molecular changes associated with chronic lipid accumulation following contusive spinal cord injury.

Functional and pathological recovery after spinal cord injury (SCI) is often incomplete due to the limited regenerative capacity of the central nervous system (CNS), which is further impaired by several mechanisms that sustain tissue damage. Among these, the chronic activation of immune cells can cause a persistent state of local CNS inflammation and damage. However, the mechanisms that sustain this persistent maladaptive immune response in SCI have not been fully clarified yet. In this study, we integrated histological analyses with proteomic, lipidomic, transcriptomic, and epitranscriptomic approaches to study the pathological and molecular alterations that develop in a mouse model of cervical spinal cord hemicontusion. We found significant pathological alterations of the lesion rim with myelin damage and axonal loss that persisted throughout the late chronic phase of SCI. This was coupled by a progressive lipid accumulation in myeloid cells, including resident microglia and infiltrating monocyte-derived macrophages. At tissue level, we found significant changes of proteins indicative of glycolytic, tricarboxylic acid cycle (TCA), and fatty acid metabolic pathways with an accumulation of triacylglycerides with C16:0 fatty acyl chains in chronic SCI. Following transcriptomic, proteomic, and epitranscriptomic studies identified an increase of cholesterol and m6A methylation in lipid-droplet-accumulating myeloid cells as a core feature of chronic SCI. By characterizing the multiple metabolic pathways altered in SCI, our work highlights a key role of lipid metabolism in the chronic response of the immune and central nervous system to damage.

Correction: Qi et al. Melatonin Alleviates High Temperature-Induced Pollen Abortion in Solanum lycopersicum. Molecules 2018, 23, 386.

In the original publication [...].

A CRISPR/RfxCas13d-mediated strategy for efficient RNA knockdown in mouse embryonic development.

The growing variety of RNA classes, such as mRNAs, lncRNAs, and circRNAs, plays pivotal roles in both developmental processes and various pathophysiological conditions. Nonetheless, our comprehension of RNA functions in live organisms remains limited due to the absence of durable and effective strategies for directly influencing RNA levels. In this study, we combined the CRISPR-RfxCas13d system with sperm-like stem cell-mediated semi-cloning techniques, which enabled the suppressed expression of different RNA species. This approach was employed to interfere with the expression of three types of RNA molecules: Sfmbt2 mRNA, Fendrr lncRNA, and circMan1a2(2,3,4,5,6). The results confirmed the critical roles of these RNAs in embryonic development, as their loss led to observable phenotypes, including embryonic lethality, delayed embryonic development, and embryo resorption. In summary, our methodology offers a potent toolkit for silencing specific RNA targets in living organisms without introducing genetic alterations.

Prevalence of subthreshold depression and its related factors in Chinese college students: A cross-sectional study.

Objective: To investigate the prevalence of subthreshold depression among Chinese college students and to explore the related factors. Methods: The research subjects were Chinese college students participating in the "2022 Psychology and Behavior Investigation of Chinese Residents (PBICR-2022)". Data on respondents' general characteristics, quality of life, perceived pressure, family communication, perceived social support, self-efficacy, and depression status were gathered. To investigate the association between each variable and the risk of subthreshold depression, statistical analyses, including chi-square tests and rank sum tests were conducted. Furthermore, a binary stepwise logistic regression was employed to establish the regression model of the factors related to subthreshold depression among Chinese college students. Results: A prevalence of subthreshold depression of about 39.7 % was found among the 8934 respondents. Logistic regression analysis revealed that respondents who are female, have chronic diseases, are in debt, experience significant impacts from epidemic control policies, have lower self-assessed quality of life, experience challenges in family communication, perceive lower social support, have lower self-efficacy, and feel higher perceived pressure are more likely to develop subthreshold depression compared to the control group. (P < 0.05). Conclusion: The prevalence rate of subthreshold depression among Chinese college students was found to be approximately 40 %. Female college students suffering from chronic diseases, with households in debt, greatly impacted by epidemic control policies, and experiencing high perceived stress, may be at risk for subthreshold depression among Chinese college students. On the other hand, strong family communication, perceived social support, and self-efficacy were identified as potential protective factors. In order to facilitate timely screening, diagnosis, and treatment of subthreshold depression in Chinese college students, it is crucial for the government, local communities, colleges, and families to prioritize the mental health of college students and implement targeted measures accordingly.

Stereoselective Bioconcentration and Neurotoxicity of Perfluoroethylcyclohexane Sulfonate in Marine Medaka.

Perfluoroethylcyclohexane sulfonate (PFECHS) is an emerging per- and polyfluoroalkyl substance used to replace perfluorooctane sulfonate (PFOS), mainly in aircraft hydraulic fluids. However, previous research indicates the potential neurotoxicity of this replacement chemical. In this study, marine medaka (Oryzias melastigma) was exposed to environmentally relevant concentrations of PFECHS (concentrations: 0, 0.08, 0.26, and 0.91 µg/L) from the embryonic stage for 90 days. After exposure, the brain and eyes of the medaka were collected to investigate the bioconcentration potential of PFECHS stereoisomers and their effects on the nervous systems. The determined bioconcentration factors (BCFs) of PFECHS ranged from 324 ± 97 to 435 ± 89 L/kg and from 454 ± 60 to 576 ± 86 L/kg in the brain and eyes of medaka, respectively. The BCFs of trans-PFECHS were higher than those of cis-PFECHS. PFECHS exposure significantly altered γ-aminobutyric acid (GABA) levels in the medaka brain and disrupted the GABAergic system, as revealed by proteomics, implying that PFECHS can disturb neural signal transduction like PFOS. PFECHS exposure resulted in significant alterations in multiple proteins associated with eye function in medaka. Abnormal locomotion was observed in PFECHS-exposed medaka larvae, which was rescued by adding exogenous GABA, suggesting the involvement of disrupted GABA signaling pathways in PFECHS neurotoxicity.

Natural Antioxidant Vitamin C Improves Photovoltaic Performance of Tin-Lead Mixed Perovskite Solar Cells.

The oxidation of Sn2+ can occur even after the completion of the perovskite crystallization in a low oxygen environment. Concerning this, the natural antioxidant vitamin C (VC) is introduced to the surface of Sn-Pb mixed perovskite using a postprocessing method to achieve the purpose of inhibiting Sn2+ oxidation and enhancing perovskite solar cells performance. The results indicate that the VC could effectively inhibit Sn2+ oxidation and heal the vacancy defects of the annealed perovskite film. Meanwhile, the introduction of VC significantly improves the morphology and crystalline quality of the perovskite films. After optimization, the highest power conversion efficiency of the VC-treated Sn-Pb mixed device increased to 20.44%. Moreover, the VC-treated unencapsulated device shows excellent long-term stability, retaining 75.3% of its initial efficiency after 800 h of aging in a N2 atmosphere, which is much higher than the 20.1% of the control device.

Macrophage Membrane-Encapsulated Dopamine-Modified Poly Cyclodextrin Multifunctional Biomimetic Nanoparticles for Atherosclerosis Therapy.

Atherosclerotic plaques exhibit high cholesterol deposition and oxidative stress resulting from high reactive oxygen species (ROS). These are the major components in plaques and the main pro-inflammatory factor. Therefore, it is crucial to develop an effective therapeutic strategy that can simultaneously address the multiple pro-inflammatory factors via removing cholesterol and inhibiting the overaccumulated ROS. In this study, we constructed macrophage membrane-encapsulated biomimetic nanoparticles (MM@DA-pCD@MTX), which not only alleviate cholesterol deposition at the plaque lesion via reverse cholesterol transport but also scavenge the overaccumulated ROS. ß-Cyclodextrin (ß-CD) and the loaded methotrexate (MTX) act synergistically to induce cholesterol efflux for inhibiting the formation of foam cells. Among them, MTX up-regulated the expression of ABCA1, CYP27A1, and SR-B1. ß-CD increased the solubility of cholesterol crystals. In addition, the ROS scavenging property of dopamine (DA) was perfectly preserved in MM@DA-pCD@MTX, which could scavenge the overaccumulated ROS to alleviate the oxidative stress at the plaque lesion. Last but not least, MM-functionalized "homing" targeting of atherosclerotic plaques not only enables the targeted drug delivery but also prolongs in vivo circulation time and drug half-life. In summary, MM@DA-pCD@MTX emerges as a potent, multifunctional therapeutic platform for AS treatment, offering a high degree of biosafety and efficacy in addressing the complex pathophysiology of atherosclerosis.

Defluorination of monofluorinated alkane by Rhodococcus sp. NJF-7 isolated from soil.

Microbial degradation of fluorinated compounds raised significant attention because of their widespread distribution and potential environmental impacts. Here, we report a bacterial isolate, Rhodococcus sp. NJF-7 capable of defluorinating monofluorinated medium-chain length alkanes. This isolate consumed 2.29 ± 0.13 mmol L- 1 of 1-fluorodecane (FD) during a 52 h incubation period, resulting in a significant release of inorganic fluoride amounting to 2.16 ± 0.03 mmol L- 1. The defluorination process was strongly affected by the initial FD concentration and pH conditions, with lower pH increasing fluoride toxicity to bacterial cells and inhibiting enzymatic defluorination activity. Stoichiometric conversion of FD to fluoride was observed at neutral pH with resting cells, while defluorination was significantly lower at reduced pH (6.5). The discovery of the metabolites decanoic acid and methyl decanoate suggests that the initial attack by monooxygenases may be responsible for the biological defluorination of FD. The findings here provide new insights into microbial defluorination processes, specifically aiding in understanding the environmental fate of organic semi-fluorinated alkane chemicals.

Receive wireless sensor data through IoT gateway using web client based on border gateway protocol.

One of the significant topics in the field of the Internet of Things (IoT) pertains to the interaction and information sharing among people. The utilization of the Border Gateway Protocol (BGP) stack enhances the integration of web protocols and sensor networks, leading to greater accessibility. However, the BGP protocol stack introduces substantial overhead to messages transmitted at each layer, resulting in increased data overhead and energy consumption in networks by several orders of magnitude. This paper proposes a method to reduce the overhead on small and medium-sized packets. In multi-temporal networks utilizing BGP, scheduling and aggregating BGP packets at sensor nodes help achieve specific objectives. Various research methodologies and measures are employed to facilitate this, including request classification, BGP response prioritization within the network, determination of maximum acceptable delay, and overall network management. Synchronization and temporal integration of received messages at sensor nodes are performed, considering the maximum allowable delay for each message and the availability of the destination to process the accumulated messages. The evaluation results of the proposed method demonstrate a significant reduction in energy consumption and network traffic, particularly in monitoring applications within multi-stage networks. The protocol stack used is derived from the BGP standard.

Microplastics in Hong Kong's marine waters: Impact of rainfall and Pearl River discharge.

This study provided a systematic investigation of microplastics in Hong Kong's surface marine waters during the pandemic from 2019 to 2021. Microplastics (2.07 ± 4.00 particles/m3) exhibited significant temporal variations with higher abundance in the wet season, without a consistent trend after the mandatory mask-wearing requirement was announced. The impact of pandemic restrictions on microplastic distribution was found to be relatively minor. However, significant correlations between microplastic abundances and rainfall highlighted the substantial contribution of local emissions through surface runoff. Notably, sites in closer proximity to the Pearl River Delta exhibited higher microplastic abundances, indicating their association with emission sources. The influence of rainfall and adverse weather on marine microplastic loads demonstrated different sensitivities among various locations but can generally last for one month. These results revealed the impact of seasonal rainfall on coastal microplastics and emphasized the need for efforts to reduce microplastic discharge from land-based sources.

Phenylboronic acid functionalized dextran loading curcumin as nano-therapeutics for promoting the bacteria-infected diabetic wound healing.

Chronic bacterial infections, excessive inflammation, and oxidative stress significantly hinder diabetic wound healing by prolonging the inflammatory phase and complicating the healing process. In this study, phenylboronic acid functionalized dextran (PODP) was developed to encapsulate curcumin, referred to as PODP@Cur. Experimental results indicate that PODP significantly improves the water solubility of curcumin and exhibits synergistic biological activity both in vitro and in vivo. PODP@Cur is capable of accelerating drug release under the pathological microenvironment with ROS accumulation. Furthermore, phenylboronic acid (PBA) has demonstrated potential for targeted bacterial drug delivery, enhancing antibacterial efficacy and trapping free LPS/PGN from dead bacteria to reduce undesirable inflammation. In a diabetic mouse model, PODP@Cur exhibits an excellent antibacterial, anti-inflammatory and antioxidant activities to ultimately promote the efficient and safe wound healing. Due to the specific interaction between PBA and LPS, PODP@Cur could enhance antibacterial activity against bacteria, reduce toxic side effects on normal cells, and alleviate the LPS-mediated pro-inflammatory pathological microenvironment. Therefore, PODP@Cur is capable of being exploited as an efficient and safe candidate for promoting the bacteria-infected diabetic wound healing.

Self-Assembled PD-L1 Downregulator to Boost Photodynamic Activated Tumor Immunotherapy Through CDK5 Inhibition.

The immunosuppressive characteristics and acquired immune resistance can restrain the therapy-initiated anti-tumor immunity. In this work, an antibody free programmed death receptor ligand 1 (PD-L1) downregulator (designated as CeSe) is fabricated to boost photodynamic activated immunotherapy through cyclin-dependent kinase 5 (CDK5) inhibition. Among which, FDA approved photosensitizer of chlorin e6 (Ce6) and preclinical available CDK5 inhibitor of seliciclib (Se) are utilized to prepare the nanomedicine of CeSe through self-assembly technique without drug excipient. Nanoscale CeSe exhibits an increased stability and drug delivery efficiency, contributing to intracellular production of reactive oxygen species (ROS) for robust photodynamic therapy (PDT). The PDT of CeSe can not only suppress the primary tumor growth, but also induce the immunogenic cell death (ICD) to release tumor associated antigens. More importantly, the CDK5 inhibition by CeSe can downregulate PD-L1 to re-activate the systemic anti-tumor immunity by decreasing the tumor immune escape and therapy-induced acquired immune resistance. This work provides an antibody free strategy to activate systemic immune response for metastatic tumor treatment, which may accelerate the development of translational nanomedicine with sophisticated mechanism.

Obeticholic acid attenuates the intestinal barrier disruption in a rat model of short bowel syndrome.

BACKGROUND: Short bowel syndrome (SBS) features nutrients malabsorption and impaired intestinal barrier. Patients with SBS are prone to sepsis, intestinal flora dysbiosis and intestinal failure associated liver disease. Protecting intestinal barrier and preventing complications are potential strategies for SBS treatment. This study aims to investigate the effects of farnesoid X receptor (FXR) agonist, obeticholic acid (OCA), have on intestinal barrier and ecological environment in SBS. METHODS AND RESULTS: Through testing the small intestine and serum samples of patients with SBS, impaired intestinal barrier was verified, as evidenced by reduced expressions of intestinal tight junction proteins (TJPs), increased levels of apoptosis and epithelial cell damage. The intestinal expressions of FXR and related downstream molecules were decreased in SBS patients. Then, global FXR activator OCA was used to further dissect the potential role of the FXR in a rat model of SBS. Low expressions of FXR-related molecules were observed on the small intestine of SBS rats, along with increased proinflammatory factors and damaged barrier function. Furthermore, SBS rats possessed significantly decreased body weight and elevated death rate. Supplementation with OCA mitigated the damaged intestinal barrier and increased proinflammatory factors in SBS rats, accompanied by activated FXR-related molecules. Using 16S rDNA sequencing, the regulatory role of OCA on gut microbiota in SBS rats was witnessed. LPS stimulation to Caco-2 cells induced apoptosis and overexpression of proinflammatory factors in vitro. OCA incubation of LPS-pretreated Caco-2 cells activated FXR-related molecules, increased the expressions of TJPs, ameliorated apoptosis and inhibited overexpression of proinflammatory factors. CONCLUSIONS: OCA supplementation could effectively ameliorate the intestinal barrier disruption and inhibit overexpression of proinflammatory factors in a rat model of SBS and LPS-pretreated Caco-2 cells. As a selective activator of FXR, OCA might realize its protective function through FXR activation.

Establishment of a prognostic nomogram for elderly patients with limited-stage small cell lung cancer receiving radiotherapy.

The present study explored the risk factors associated with radiotherapy in seniors diagnosed with limited-stage small cell lung cancer (LS-SCLC) to construct and validate a prognostic nomogram. The study retrospectively included 137 elderly patients with LS-SCLC who previously received radiotherapy. Univariate and multivariate COX analyses were conducted to identify independent risk factors and determine optimal cut-off values. Kaplan-Meier survival curves and nomograms were constructed to predict survival. Calibration and receiver operating characteristic (ROC) curves were used to evaluate the accuracy and consistency of the nomogram. Illness rating scale-geriatric (CIRS-G) score, treatment strategy, lymphocyte-to-monocyte ratio (LMR), white blood cell-to-monocyte ratio (WMR), and prognostic nutritional index (PNI) were discovered to be independent prognostic factors. Based on the findings of our multivariate analysis, a risk nomogram was developed to assess patient prognosis. Internal bootstrap resampling was utilized to validate the model, and while the accuracy of the AUC curve at 1 year was modest at 0.657 (95% CI 0.458-0.856), good results were achieved in predicting 3- and 5 year survival with AUCs of 0.757 (95% CI 0.670-0.843) and 0.768 (95% CI 0.643-0.893), respectively. Calibration curves for 1-, 3-, and 5 year overall survival probabilities demonstrated good cocsistency between expected and actual outcomes. Patients with concurrent chemoradiotherapy, CIRS-G score > 5 points and low PNI, WMR and LMR correlated with poor prognosis. The nomogram model developed based on these factors demonstrated good predictive performance and provides a simple, accessible, and practical tool for clinicians to guide clinical decision-making and study design.

Multiple non-covalent-interaction-directed supramolecular double helices: the orthogonality of hydrogen, halogen and chalcogen bonding.

In this study, a benzoselenadiazole- and pyridine-bifunctionalized hydrogen-bonded arylamide foldamer was synthesized. A co-crystallization experiment with 1,4-diiodotetrafluorobenzene showed that a new type of supramolecular double helices, which were induced by three orthogonal interactions, namely, three-center hydrogen bonding (O⋯H⋯O), I⋯N halogen bonding and Se⋯N chalcogen bonding, have been constructed in the solid state. This work presents a novel instance of multiple non-covalent interactions that work together to construct supramolecular architectures.

PQSDC: a parallel lossless compressor for quality scores data via sequences partition and run-length prediction mapping.

MOTIVATION: The quality scores data (QSD) account for 70% in compressed FastQ files obtained from the short and long reads sequencing technologies. Designing effective compressors for QSD that counterbalance compression ratio, time cost, and memory consumption is essential in scenarios such as large-scale genomics data sharing and long-term data backup. This study presents a novel parallel lossless QSD-dedicated compression algorithm named PQSDC, which fulfills the above requirements well. PQSDC is based on two core components: a parallel sequences-partition model designed to reduce peak memory consumption and time cost during compression and decompression processes, as well as a parallel four-level run-length prediction mapping model to enhance compression ratio. Besides, the PQSDC algorithm is also designed to be highly concurrent using multicore CPU clusters. RESULTS: We evaluate PQSDC and four state-of-the-art compression algorithms on 27 real-world datasets, including 61.857 billion QSD characters and 632.908 million QSD sequences. (1) For short reads, compared to baselines, the maximum improvement of PQSDC reaches 7.06% in average compression ratio, and 8.01% in weighted average compression ratio. During compression and decompression, the maximum total time savings of PQSDC are 79.96% and 84.56%, respectively; the maximum average memory savings are 68.34% and 77.63%, respectively. (2) For long reads, the maximum improvement of PQSDC reaches 12.51% and 13.42% in average and weighted average compression ratio, respectively. The maximum total time savings during compression and decompression are 53.51% and 72.53%, respectively; the maximum average memory savings are 19.44% and 17.42%, respectively. (3) Furthermore, PQSDC ranks second in compression robustness among the tested algorithms, indicating that it is less affected by the probability distribution of the QSD collections. Overall, our work provides a promising solution for QSD parallel compression, which balances storage cost, time consumption, and memory occupation primely. AVAILABILITY AND IMPLEMENTATION: The proposed PQSDC compressor can be downloaded from https://github.com/fahaihi/PQSDC.

Phytochemistry of Genus Buxus and Pharmacology of Cyclovirobuxine D.

BACKGROUND: Genus Buxus plants, commonly known as "boxwood", are widely distributed in China. The stems, branches, and leaves of the plant are traditionally used for rheumatism, toothache, chest pain, abdominal gas, and other diseases. However, an overview of the genus Buxus remains to be provided. PURPOSE: To provide a scientific basis for the appropriate use and further research the recent advancements in the traditional usage, phytochemistry, and, pharmacology of Buxus. STUDY DESIGN: Chemical composition and pharmacological correlation studies through a literature review. METHODS: Between 1970 and 2023, the available data concerning Buxus was compiled from online scientific sources, such as Sci-Finder, PubMed, CNKI, Google Scholar, and the Chinese Pharmacopoeia. Plant names were verified from "The Plant List" (http://www.theplantlist.org/). RESULTS: To date, 266 structurally diverse chemicals have been extracted and identified from the genus Buxus. Alkaloids constitute one of its primary bioactive phytochemicals. A summary of the channels of action of Cyclovirobuxine D on the cytotoxicity of a variety of cancers has been provided. CONCLUSION: Numerous findings from contemporary phytochemical and pharmacological studies support the traditional use, facilitating its application. Further research is necessary to address various shortcomings, including the identification of the active ingredients and quality control of the genus Buxus.

Molecular imprinting-based Ru@SiO2-embedded covalent organic frameworks composite for electrochemiluminescence detection of cyanidin-3-O-glucoside.

Cyanidin-3-O-glucoside (C3G), a natural antioxidant, plays multiple physiological or pathological roles in maintaining human health; thereby, designing advanced sensors to achieve specific recognition and high-sensitivity detection of C3G is significant. Herein, an imprinted-type electrochemiluminescence (ECL) sensing platform was developed using core-shell Ru@SiO2-CMIPs, which were prepared by covalent organic framework (COF)-based molecularly imprinted polymers (CMIPs) embedded in luminescent Ru@SiO2 cores. The C3G-imprinted COF shell not only helps generate a steady-enhanced ECL signal, but also enables specific recognition of C3G. When C3G is bound to Ru@SiO2-CMIPs with abundant imprinted cavities, resonance energy transfer (RET) behavior is triggered, resulting in a quenched ECL response. The constructed Ru@SiO2-CMIPs nanoprobes exhibit ultra-high sensitivity, absolute specificity, and an ultra-low detection limit (0.15 pg mL-1) for analyzing C3G in food matrices. This study provides a means to construct an efficient and reliable molecular imprinting-based ECL sensor for food analysis.