Chromosome-level genome provides insights into environmental adaptability and innate immunity in the common dolphin (delphinus delphis).

The common dolphin (Delphinus delphis) is widely distributed worldwide and well adapted to various habitats. Animal genomes store clues about their pasts, and can reveal the genes underlying their evolutionary success. Here, we report the first high-quality chromosome-level genome of D. delphis. The assembled genome size was 2.56 Gb with a contig N50 of 63.85 Mb. Phylogenetically, D. delphis was close to Tursiops truncatus and T. aduncus. The genome of D. delphis exhibited 428 expanded and 1,885 contracted gene families, and 120 genes were identified as positively selected. The expansion of the HSP70 gene family suggested that D. delphis has a powerful system for buffering stress, which might be associated with its broad adaptability, longevity, and detoxification capacity. The expanded IFN-α and IFN-ω gene families, as well as the positively selected genes encoding tripartite motif-containing protein 25, peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, and p38 MAP kinase, were all involved in pathways for antiviral, anti-inflammatory, and antineoplastic mechanisms. The genome data also revealed dramatic fluctuations in the effective population size during the Pleistocene. Overall, the high-quality genome assembly and annotation represent significant molecular resources for ecological and evolutionary studies of Delphinus and help support their sustainable treatment and conservation.

MixEHR-SurG: A joint proportional hazard and guided topic model for inferring mortality-associated topics from electronic health records.

Survival models can help medical practitioners to evaluate the prognostic importance of clinical variables to patient outcomes such as mortality or hospital readmission and subsequently design personalized treatment regimes. Electronic Health Records (EHRs) hold the promise for large-scale survival analysis based on systematically recorded clinical features for each patient. However, existing survival models either do not scale to high dimensional and multi-modal EHR data or are difficult to interpret. In this study, we present a supervised topic model called MixEHR-SurG to simultaneously integrate heterogeneous EHR data and model survival hazard. Our contributions are three-folds: (1) integrating EHR topic inference with Cox proportional hazards likelihood; (2) integrating patient-specific topic hyperparameters using the PheCode concepts such that each topic can be identified with exactly one PheCode-associated phenotype; (3) multi-modal survival topic inference. This leads to a highly interpretable survival topic model that can infer PheCode-specific phenotype topics associated with patient mortality. We evaluated MixEHR-SurG using a simulated dataset and two real-world EHR datasets: the Quebec Congenital Heart Disease (CHD) data consisting of 8211 subjects with 75,187 outpatient claim records of 1767 unique ICD codes; the MIMIC-III consisting of 1458 subjects with multi-modal EHR records. Compared to the baselines, MixEHR-SurG achieved a superior dynamic AUROC for mortality prediction, with a mean AUROC score of 0.89 in the simulation dataset and a mean AUROC of 0.645 on the CHD dataset. Qualitatively, MixEHR-SurG associates severe cardiac conditions with high mortality risk among the CHD patients after the first heart failure hospitalization and critical brain injuries with increased mortality among the MIMIC-III patients after their ICU discharge. Together, the integration of the Cox proportional hazards model and EHR topic inference in MixEHR-SurG not only leads to competitive mortality prediction but also meaningful phenotype topics for in-depth survival analysis. The software is available at GitHub: https://github.com/li-lab-mcgill/MixEHR-SurG.

The use of amino acids and their derivates to mitigate against pesticide-induced toxicity.

Exposure to pesticides induces oxidative stress and deleterious effects on various tissues in non-target organisms. Numerous models investigating pesticide exposure have demonstrated metabolic disturbances such as imbalances in amino acid levels within the organism. One potentially effective strategy to mitigate pesticide toxicity involves dietary intervention by supplementing exogenous amino acids and their derivates to augment the body's antioxidant capacity and mitigate pesticide-induced oxidative harm, whose mechanism including bolstering glutathione synthesis, regulating arginine-NO metabolism, mitochondria-related oxidative stress, and the open of ion channels, as well as enhancing intestinal microecology. Enhancing glutathione synthesis through supplementation of substrates N-acetylcysteine and glycine is regarded as a potent mechanism to achieve this. Selection of appropriate amino acids or their derivates for supplementation, and determining an appropriate dosage, are of the utmost importance for effective mitigation of pesticide-induced oxidative harm. More experimentation is required that involves large population samples to validate the efficacy of dietary intervention strategies, as well as to determine the effects of amino acids and their derivates on long-term and low-dose pesticide exposure. This review provides insights to guide future research aimed at preventing and alleviating pesticide toxicity through dietary intervention of amino acids and their derivates.

Marein, a novel natural product for restoring chemo-sensitivity to cancer cells through competitive inhibition of ABCG2 function.

The pivotal roles of ATP-binding cassette (ABC) transporters in drug resistance have been widely appreciated. Here we report that marein, a natural product from Coreopsis tinctoria Nutt, is a potent chemo-sensitizer in drug resistant cancer cells overexpressing ABCG2 transporter. We demonstrate that marein can competitively inhibit efflux activity of ABCG2 protein and increase the intracellular accumulation of the chemotherapeutic drugs that belong to substrate of this transporter. We further show that marein can bind to the conserved amino acid residue F439 of ABCG2, a critical site for drug-substrate interaction. Moreover, marein can significantly sensitize the ABCG2-expressing tumor cells to chemotherapeutic drugs such as topotecan, mitoxantrone, and Olaparib. This study reveals a novel role and mechanism of marein in modulating drug resistance, and may have important implications in treatment of cancers that are resistant to chemotherapeutic drugs that belong to the substrates of ABCG2 transporters.

A paper-based dual functional biosensor for safe and user-friendly point-of-care urine analysis.

Safe, accurate, and reliable analysis of urinary biomarkers is clinically important for early detection and monitoring of the progression of chronic kidney disease (CKD), as it has become one of the world's most prevalent non-communicable diseases. However, current technologies for measuring urinary biomarkers are either time-consuming and limited to well-equipped hospitals or lack the necessary sensitivity for quantitative analysis and post a health risk to frontline practitioners. Here we report a robust paper-based dual functional biosensor, which is integrated with the clinical urine sampling vial, for the simultaneous and quantitative analysis of pH and glucose in urine. The pH sensor was fabricated by electrochemically depositing IrOx onto a paper substrate using optimised parameters, which enabled an ultrahigh sensitivity of 71.58 mV pH-1. Glucose oxidase (GOx) was used in combination with an electrochemically deposited Prussian blue layer for the detection of glucose, and its performance was enhanced by gold nanoparticles (AuNPs), chitosan, and graphite composites, achieving a sensitivity of 1.5 µA mM-1. This dual function biosensor was validated using clinical urine samples, where a correlation coefficient of 0.96 for pH and 0.98 for glucose detection was achieved with commercial methods as references. More importantly, the urine sampling vial was kept sealed throughout the sample-to-result process, which minimised the health risk to frontline practitioners and simplified the diagnostic procedures. This diagnostic platform, therefore, holds high promise as a rapid, accurate, safe, and user-friendly point-of-care (POC) technology for the analysis of urinary biomarkers in frontline clinical settings.

Structure, Biological Functions, Separation, Properties, and Potential Applications of Milk Fat Globule Membrane (MFGM): A Review.

BACKGROUND: The milk fat globule membrane (MFGM) is a thin film that exists within the milk emulsion, suspended on the surface of milk fat globules, and comprises a diverse array of bioactive components. Recent advancements in MFGM research have sparked a growing interest in its biological characteristics and health-related functions. Thorough exploration and utilization of MFGM as a significant bioactive constituent in milk emulsion can profoundly impact human health in a positive manner. Scope and approach: This review comprehensively examines the current progress in understanding the structure, composition, physicochemical properties, methods of separation and purification, and biological activity of MFGM. Additionally, it underscores the vast potential of MFGM in the development of additives and drug delivery systems, with a particular focus on harnessing the surface activity and stability of proteins and phospholipids present on the MFGM for the production of natural emulsifiers and drug encapsulation materials. KEY FINDINGS AND CONCLUSIONS: MFGM harbors numerous active substances that possess diverse physiological functions, including the promotion of digestion, maintenance of the intestinal mucosal barrier, and facilitation of nerve development. Typically employed as a dietary supplement in infant formula, MFGM's exceptional surface activity has propelled its advancement toward becoming a natural emulsifier or encapsulation material. This surface activity is primarily derived from the amphiphilicity of polar lipids and the stability exhibited by highly glycosylated proteins.

Effects of Dietary Colostrum Basic Protein on Bone Growth and Calcium Absorption in Mice.

Colostrum basic protein (CBP) is a trace protein extracted from bovine colostrum. Previous studies have shown that CBP can promote bone cell differentiation and increase bone density. However, the mechanism by which CBP promotes bone activity remains unclear. This study investigated the mechanism of the effect of CBP on bone growth in mice following dietary supplementation of CBP at doses that included 0.015%, 0.15%, 1.5%, and 5%. Compared with mice fed a normal diet, feeding 5% CBP significantly enhanced bone rigidity and improved the microstructure of bone trabeculae. Five-percent CBP intake triggered significant positive regulation of calcium metabolism in the direction of bone calcium accumulation. The expression levels of paracellular calcium transport proteins CLDN2 and CLDN12 were upregulated nearly 1.5-fold by 5% CBP. We conclude that CBP promotes calcium absorption in mice by upregulating the expression of the calcium-transporting paracellular proteins CLND2 and CLND12, thereby increasing bone density and promoting bone growth. Overall, CBP contributes to bone growth by affecting calcium metabolism.

Engineered MgO nanoparticles for cartilage-bone synergistic therapy.

The emerging therapeutic strategies for osteoarthritis (OA) are shifting toward comprehensive approaches that target periarticular tissues, involving both cartilage and subchondral bone. This shift drives the development of single-component therapeutics capable of acting on multiple tissues and cells. Magnesium, an element essential for maintaining skeletal health, shows promise in treating OA. However, the precise effects of magnesium on cartilage and subchondral bone are not yet clear. Here, we investigated the therapeutic effect of Mg2+ on OA, unveiling its protective effects on both cartilage and bone at the cellular and animal levels. The beneficial effect on the cartilage-bone interaction is primarily mediated by the PI3K/AKT pathway. In addition, we developed poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with nano-magnesium oxide modified with stearic acid (SA), MgO&SA@PLGA, for intra-articular injection. These microspheres demonstrated remarkable efficacy in alleviating OA in rat models, highlighting their translational potential in clinical applications.

Effectiveness of novel ß-lactams for Pseudomonas aeruginosa infection: A systematic review and meta-analysis.

BACKGROUND: Novel ß-lactams have in vitro activity against Pseudomonas aeruginosa (PA), but their clinical performances and the selection criteria for practical use are still not clear. We aimed to evaluate the efficacy of novel ß-lactams for PA infection in various sites and to compare the efficacy of each agent. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science for randomized controlled trials that used novel ß-lactams to treat PA infection. The primary outcomes were clinical cure and favorable microbiological response. Subgroup analyses were performed based on drug type, drug resistance of pathogens, and site of infection. Network meta-analysis was carried out within a Bayesian framework. RESULTS: In all studies combined (16 randomized controlled trials), novel ß-lactams indicated comparable performance to other treatment regimens in both outcome measures (relative risk = 1.04; 95% confidence interval 0.94-1.15; P = .43) (relative risk = 0.97; 95% confidence interval 0.81-1.17; P = .76). Subgroup analyses showed that the efficacy of ceftolozane-tazobactam (TOL-TAZ), ceftazidime-avibactam (CAZ-AVI), imipenem-cilastatin-relebactam, and cefiderocol had no apparent differences compared to control groups among different infection sites, drug types and drug resistance of PA. In network meta-analysis, the results showed no statistically significant differences between TOL-TAZ, CAZ-AVI, and cefiderocol. CONCLUSIONS: TOL-TAZ, CAZ-AVI, imipenem-cilastatin-relebactam, and cefiderocol are not inferior to other agents in the treatment of PA infection. Their efficacy is also comparable between TOL-TAZ, CAZ-AVI, and cefiderocol.

Causal relationships between Sjögren's syndrome and Parkinson's disease: A Mendelian randomization study.

BACKGROUND: Epidemiological and observational studies have indicated an association between Sjögren's syndrome (SS) and Parkinson's disease (PD). However, consistent conclusions have not been reached due to various limitations. In order to determine whether SS and PD are causally related, we conducted a Mendelian randomization study (MR) with two samples. METHODS: Data for SS derived from the FinnGen consortium's R9 release (2495 cases and 365 533 controls). Moreover, data for PD were acquired from the publicly available GWAS of European ancestry, which involved 33 674 cases and 449 056 controls. The inverse variance weighted, along with four other effective methodologies, were employed to comprehensively infer the causal relationships between SS and PD. To assess the estimation's robustness, a number of sensitivity studies were performed. To determine the probability of reverse causality, we performed a reverse MR analysis. RESULTS: There was no evidence of a significant causal effect of SS on PD risks based on the MR [odds ratio (OR) = 1.03; 95% confidence interval (CI) = 0.95-1.11; p = .45]. Similarly, no evidence supported the causal effects of PD on SS (OR = 0.92; 95% CI = 0.81-1.04; p = .20). These findings held up under rigorous sensitivity analysis. CONCLUSIONS: MR bidirectional analysis did not reveal any cause-and-effect relationship between SS and PD, or vice versa. Further study of the mechanisms that may underlie the probable causal association between SS and PD is needed.

The application of autofluorescence system contributes to the preservation of parathyroid function during thyroid surgery.

PURPOSE: The purpose of this study was to investigate the impact of autofluorescence technology on postoperative parathyroid function and short-term outcomes in patients undergoing thyroid surgery. METHODS: A total of 546 patients were included in the study, with 287 in the conventional treatment group and 259 in the autofluorescence group. Both groups underwent central lymph node dissection, which is known to affect parathyroid function. Short-term outcomes, including rates of postoperative hypocalcemia and parathyroid dysfunction, serum calcium and PTH levels on the first postoperative day, as well as the need for calcium supplementation, were analyzed. A multivariable analysis was also conducted to assess the impact of autofluorescence on postoperative parathyroid dysfunction, considering factors such as age, BMI, and preoperative calcium levels. RESULTS: The autofluorescence group demonstrated significantly lower rates of postoperative hypocalcemia and parathyroid dysfunction compared to the conventional treatment group. The autofluorescence group also had better serum calcium and PTH levels on the first postoperative day, and a reduced need for calcium supplementation. Surprisingly, the use of autofluorescence technology did not prolong surgical time; instead, it led to a shorter hospitalization duration. The multivariable analysis showed that autofluorescence significantly reduced the risk of postoperative parathyroid dysfunction, while factors such as age, BMI, and preoperative calcium levels did not show a significant correlation. CONCLUSION: This study provides evidence that autofluorescence technology can improve the preservation of parathyroid function during thyroid surgery, leading to better short-term outcomes and reduced postoperative complications. The findings highlight the potential of autofluorescence as a valuable tool in the management of parathyroid hypofunction. Further research and validation are needed to establish the routine use of autofluorescence technology in the thyroid.

l-Cysteine-Tuned the Hierarchical Structure Based on Benzimidazole: Synthesis, Characterization, and Application in Ratiometric Electrochemiluminescence Immunoassay.

Efficient and robust electrochemiluminescence (ECL) emitters are crucial for enhancing the ECL immunosensor sensitivity. This study introduces a novel ECL emitter, CoBIM/Cys, featuring a hierarchical core-shell structure. The core of the structure is created through the swift coordination between the sulfhydryl and carboxyl groups of l-cysteine (l-Cys) and cobalt ions (Co2+), while the shell is constructed by sequentially coordinating benzimidazole (BIM) with Co2+. This design yields a greater specific surface area and a more intricate porous structure compared to CoBIM, markedly enhancing mass transfer and luminophore accessibility. Moreover, the l-Cys and Co2+ core introduces Co-S and Co-O catalytic sites, which improve the catalytic decomposition of H2O2, leading to an increased production of hydroperoxyl radicals (OOH•). This mechanism substantially amplifies the ECL performance. Leveraging the competitive interaction between isoluminol and BIM for OOH• during ECL emission, we developed a ratiometric immunosensor for cardiac troponin I (cTnI) detection. This immunosensor demonstrates a remarkably broad detection range (1 pg mL-1 to 10 ng mL-1), a low detection limit (0.4 pg mL-1), and exceptional reproducibility and specificity.

Sparse Action Tube Detection.

Action tube detection is a challenging task as it requires not only to locate action instances in each frame, but also link them in time. Existing action tube detection methods often employ multi-stage pipelines with complex designs and time-consuming linking procedure. In this paper, we present a simple end-to-end action tube detection method, termed as Sparse Tube Detector (STDet). Unlike those dense action detectors, our core idea is to use a set of learnable tube queries and directly decode them into action tubes (i.e., a set of tracked boxes with action label) from video content. This sparse detection paradigm shares several advantages. First, the large number of hand-crafted anchor candidates in dense action detectors is greatly reduced to a small number of learnable tubes, which results in a more efficient detection framework. Second, our learnable tube queries directly attend the whole video content, which endows our method with the capacity of capturing long-range information for action detection. Finally, our action detector is an end-to-end tube detection without requiring the linking procedure, which directly and explicitly predicts the action boundary instead of depending on the linking strategy. Extensive experiments shows that our STDet outperforms the previous state-of-the-art methods on two challenging untrimmed video action detection datasets of UCF101-24 and MultiSports. We hope our method will be an simple end-to-end tube detection baseline and can inspire new ideas in this direction.

Predissociation dynamics of D2 revealed by variation in fragment anisotropy parameters along the Fano profile.

We conducted a study on the variations of the fragment anisotropy parameters (ß) along the Fano profiles for the predissociation of the D2 molecule. These variations, known as ß profiles, were measured for the D(2l) fragments from the predissociation of the 4pπD'Πu1υ'=1 and 4pσB″Σu+1υ'=2 states. The measured ß profiles show significant asymmetry and broader linewidths compared to the corresponding Fano profiles. By fitting the ß profiles, we were able to determine the fragment anisotropy parameters associated with the resonance state, continuum state, and the interference effect between them. Additionally, we determined the ratios of the absorption cross sections between the unperturbed and perturbed continuum states interacting with the resonance states although these ratios were found to be very small. Furthermore, we derived approximate formulas to calculate the parameters characterizing the ß profile. Despite the linewidths of the four Fano profiles being narrower than our instrumental resolution, we were still able to determine the product of the linewidth with the Fano q parameters. These findings demonstrate the utility of the ß profile as an effective tool for studying the predissociation dynamics in diatomic molecules.

Age-Dependent Inflammatory Microenvironment Mediates Alveolar Regeneration.

Lung aging triggers the onset of various chronic lung diseases, with alveolar repair being a key focus for alleviating pulmonary conditions. The regeneration of epithelial structures, particularly the differentiation from type II alveolar epithelial (AT2) cells to type I alveolar epithelial (AT1) cells, serves as a prominent indicator of alveolar repair. Nonetheless, the precise role of aging in impeding alveolar regeneration and its underlying mechanism remain to be fully elucidated. Our study employed histological methods to examine lung aging effects on structural integrity and pathology. Lung aging led to alveolar collapse, disrupted epithelial structures, and inflammation. Additionally, a relative quantification analysis revealed age-related decline in AT1 and AT2 cells, along with reduced proliferation and differentiation capacities of AT2 cells. To elucidate the mechanisms underlying AT2 cell functional decline, we employed transcriptomic techniques and revealed a correlation between inflammatory factors and genes regulating proliferation and differentiation. Furthermore, a D-galactose-induced senescence model in A549 cells corroborated our omics experiments and confirmed inflammation-induced cell cycle arrest and a >30% reduction in proliferation/differentiation. Physiological aging-induced chronic inflammation impairs AT2 cell functions, hindering tissue repair and promoting lung disease progression. This study offers novel insights into chronic inflammation's impact on stem cell-mediated alveolar regeneration.

Upcycling of Carbon Fiber/Thermoset Composites into High-Performance Elastomers and Repurposed Carbon Fibers.

Recycling of carbon fiber-reinforced polymer composites (CFRCs) based on thermosetting plastics is difficult. In the present study, high-performance CFRCs are fabricated through complexation of aromatic pinacol-cross-linked polyurethane (PU-AP) thermosets with carbon fiber (CF) cloths. PU-AP thermosets exhibit a breaking strength of 95.5 MPa and toughness of 473.6 MJ m-3 and contain abundant hydrogen-bonding groups, which can have strong adhesion with CFs. Because of the high interfacial adhesion between CF cloths and PU-AP thermosets and high toughness of PU-AP thermosets, CF/PU-AP composites possess a high tensile strength of >870 MPa. Upon heating in N,N-dimethylacetamide (DMAc) at 100 °C, the aromatic pinacols in the CF/PU-AP composites can be cleaved, generating non-destructive CF cloths and linear polymers that can be converted to high-performance elastomers. The elastomers are mechanically robust, healable, reprocessable, and damage-resistant with an extremely high tensile strength of 74.2 MPa and fracture energy of 149.6 kJ m-2. As a result, dissociation of CF/PU-AP composites enables the recovery of reusable CF cloths and high-performance elastomers, thus realizing the upcycling of CF/PU-AP composites.

Impacts of digital finance on energy efficiency: does environmental regulation matter?

The paper examines how digital finance affects energy efficiency in China using a dynamic panel model and data from 282 cities between 2011 and 2019. The study is based on the hypothesis which is related with digital finance, environmental regulation, and energy efficiency. The results indicate that: (1) Digital finance significantly improves energy efficiency, and this finding is consistent after several tests; (2) Digital finance has a positive effect on energy efficiency in non-resource-based cities, recession and regeneration resource-based cities, and old industrial base cities, but no significant effect on energy efficiency in growth and maturity resource-based cities and non-old industrial base cities; (3) Environmental regulation positively influences how digital finance affects energy efficiency; (4) The impact of digital finance on energy efficiency depends on the degree and tools of environmental regulation. This research offers valuable insights to local governments in China for promoting financial digitization and enhancing energy efficiency.

Conducting and reporting the Delphi method in traditional Chinese medicine syndrome diagnosis research: A cross-sectional analysis.

Background: The Delphi method has been extensively used to reach a consensus in traditional Chinese medicine (TCM) syndrome diagnosis research when subjective judgment is not uniform and objective evidence is lacking. The conduct and reporting of the Delphi method in TCM syndrome diagnosis research have never been critiqued. Our study aims to explore the consistency of using this technique and assess the reporting quality. Methods: A cross-sectional study was employed to scope articles reporting the conduct of the Delphi method in TCM syndrome diagnosis research. We searched the PubMed, Web of Science, CNKI, VIP, Wanfang and SinoMed databases with the restriction of Chinese and English language from their inception to March 25, 2023. A standardized extraction form was designed to collect demographics and methodological processes reflecting the rigor and transparency in TCM syndrome diagnosis research. Results: A total of 1832 studies were screened, and 50 were included. The median number of panels was 30 (IQR 20-34.5) and only 12 (24.0 %) studies were with a heterogeneous sample of panels. Two rounds was most common (37/50; 74.0 %), followed by three (7/50; 14.0 %), and only 13 (26.0 %) studies determined the number of rounds a priori. The reporting quality varied, with 18.0 % (9/50) reporting anonymity, 30.0 % (15/50) describing the controlled feedback, 20.0 % (10/50) reporting the procedure duration (7.14 ± 3.29 months) and 26.0 % (13/50) predefining the consensus. Conclusion: The Delphi method is inconsistently conducted and nontransparently reported in TCM syndrome diagnosis research. Standardized criteria are urgently needed for best practices in future research.

Phocaeicola vulgatus alleviates diet-induced metabolic dysfunction-associated steatotic liver disease progression by downregulating histone acetylation level via 3-HPAA.

Diet-induced metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder with limited effective interventions available. A novel approach to address this issue is through gut microbiota-based therapy. In our study, we utilized multi-omics analysis to identify Phocaeicola vulgatus (P. vulgatus) as a potential probiotic for the treatment of MASLD. Our findings from murine models clearly illustrate that the supplementation of P. vulgatus mitigates the development of MASLD. This beneficial effect is partly attributed to the metabolite 3-Hydroxyphenylacetic acid (3-HPAA) produced by P. vulgatus, which reduces the acetylation levels of H3K27 and downregulates the transcription of Squalene Epoxidase (SQLE), a rate-limiting enzyme in steroid biosynthesis that promotes lipid accumulation in liver cells. This study underscores the significant role of P. vulgatus in the development of MASLD and the critical importance of its metabolite 3-HPAA in regulating lipid homeostasis. These findings offer a promising avenue for early intervention therapy in the context of MASLD.