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Introduction: Neurological dysfunction induced by fluoride contamination is still one of major concern worldwide. Recently, neuroprotective roles of silent information regulator 1 (SIRT1) focusing on mitochondrial function have been highlighted. However, what roles SIRT1 exerts and the underlying regulative mechanisms, remain largely uncharacterized in such neurotoxic process of fluoride. Objectives: We aimed at evaluating the regulatory roles of SIRT1 in human neuroblastoma SH-SY5Y cells and Sprague-Dawley rats with fluoride treatment, and to further identify potential miRNA directly targeting SIRT1. Methods: Pharmacological suppression of SIRT1 by nicotinamide (NIC) and promotion of SIRT1 by adenovirus (Ad-SIRT1) or resveratrol (RSV) were employed to assess the effects of SIRT1 in mitochondrial dysfunction induced by fluoride. Also, miRNAs profiling and bioinformatic prediction were used to screen the miRNAs which can regulate SIRT1 directly. Further, chemical mimic or inhibitor of chosen miRNA was applied to validate the modulation of chosen miRNA. Results: NIC exacerbated defects in mitochondrial network dynamics and cytochrome c (Cyto C) release-driven apoptosis, contributing to fluoride-induced neuronal death. In contrast, the ameliorative effects were observed when overexpressing SIRT1 by Ad-SIRT1 in vitro or RSV in vivo. More importantly, miR-708-3p targeting SIRT1 directly was identified. And interestingly, moreover, treatment with chemically modified miR-708-3p mimic aggravated, while miR-708-3p inhibitor suppressed fluoride-caused neuronal death. Further confirmedly, overexpressing SIRT1 effectively neutralized miR-708-3p mimic-worsened fluoride neuronal death via correcting mitochondrial network dynamics. On contrary, inhibiting SIRT1 counteracted the promotive effects of miR-708-3p inhibitor against neurotoxic response by fluoride through aggravating abnormal mitochondrial network dynamics. Conclusion: These data underscore the functional importance of SIRT1 to mitochondrial network dynamics in neurotoxic process of fluoride and further screen a novel unreported neuronal function of miR-708-3p as an upstream regulator of targeting SIRT1, which has important theoretical implications for a potential therapeutic and preventative target for treatment of neurotoxic progression by fluoride.

Abstract Liposomal irinotecan has shown promising antitumor activity in patients with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) who have undergone prior gemcitabine-based therapies. This randomized, double-blind, parallel-controlled, multicenter phase 3 study (NCT05074589) assessed the efficacy and safety of liposomal irinotecan HR070803 combined with 5-fluorouracil (5-FU) and leucovorin (LV) in this patient population. Patients with unresectable, locally advanced, or metastatic PDAC who had previously received gemcitabine-based therapies were randomized 1:1 to receive either HR070803 (60 mg/m2 anhydrous irinotecan hydrochloride, equal to 56.5 mg/m2 free base) or placebo, both in combination with 5-FU (2000 mg/m2) and LV (200 mg/m2), all given intravenously every two weeks. The primary endpoint of the study was overall survival (OS). A total of 298 patients were enrolled and received HR070803 plus 5-FU/LV (HR070803 group, n = 149) or placebo plus 5-FU/LV (placebo group, n = 149). Median OS was significantly improved in the HR070803 group compared to the placebo group (7.4 months [95% CI 6.1–8.4] versus 5.0 months [95% CI 4.3–6.0]; HR 0.63 [95% CI 0.48–0.84]; two-sided p = 0.0019). The most common grade ≥ 3 adverse events in the HR070803 group were increased gamma-glutamyltransferase (19.0% versus 11.6% in placebo group) and decreased neutrophil count (12.9% versus 0 in placebo group). No treatment-related deaths occurred in the HR070803 group, while the placebo group reported one treatment-related death (abdominal infection). HR070803 in combination with 5-FU/LV has shown promising efficacy and manageable safety in advanced or metastatic PDAC in the second-line setting, representing a potential option in this patient population.

People often change their evaluations upon learning about their peers' evaluations, i.e., social learning. Given sleep's vital role in consolidating daytime experiences, sleep may facilitate social learning, thereby further changing people's evaluations. Combining a social learning task and the sleep-based targeted memory reactivation technique, we asked whether social learning-induced evaluation updating can be modulated during sleep. After participants had indicated their initial evaluation of snacks, they learned about their peers' evaluations while hearing the snacks' spoken names. During the post-learning non-rapid-eye-movement sleep, we re-played half of the snack names (i.e., cued snack) to reactivate the associated peers' evaluations. Upon waking up, we found that the social learning-induced evaluation updating further enlarged for both cued and uncued snacks. Examining sleep electroencephalogram (EEG) activity revealed that cue-elicited delta-theta EEG power and the overnight N2 sleep spindle density predicted post-sleep evaluation updating for cued but not for uncued snacks. These findings underscore the role of sleep-mediated memory reactivation and the associated neural activity in supporting social learning-induced evaluation updating.

Indiscriminate drug administration may lead to drug therapy results with varying effects on patients, and the proposal of personalized medication can help patients to receive effective drug therapy. Conventional ways of personalized medication, such as pharmacogenomics and therapeutic drug monitoring (TDM), can only be implemented from a single perspective. The development of pharmacometabolomics provides a research method for the realization of precise drug administration, which integrates the environmental and genetic factors, and applies metabolomics technology to study how to predict different drug therapeutic responses of organisms based on baseline metabolic levels. The published research on pharmacometabolomics has achieved satisfactory results in predicting the pharmacokinetics, pharmacodynamics, and the discovery of biomarkers of drugs. Among them, the pharmacokinetics related to pharmacometabolomics are used to explore individual variability in drug metabolism from the level of metabolism of the drugs in vivo and the level of endogenous metabolite changes. By searching for relevant literature with the keyword pharmacometabolomics on the two major literature retrieval websites, PubMed and Web of Science, from 2006 to 2023, we reviewed articles in the field of pharmacometabolomics that incorporated pharmacokinetics into their research. This review explains the therapeutic effects of drugs on the body from the perspective of endogenous metabolites and pharmacokinetic principles, and reports the latest advances in pharmacometabolomics related to pharmacokinetics to provide research ideas and methods for advancing the implementation of personalized medication.

The flow field structure for aero-engine combustor is one of the most important factors for combustion performance. To investigate how the rotating direction of dual-axial swirlers affects the flow field and combustion characteristics, particle image velocimetry (PIV) experiments were conducted in the primary combustion and intermediate zones. Additionally, planar laser induced fluorescence (PLIF) was used to map the distribution of kerosene and OH in the primary combustion zone. The results show that the swirling jets in co-swirl exhibit greater jet momentum, resulting in a longer primary recirculation zone and a larger deflection angle of the primary jets. This ultimately leads to a higher recirculation rate compared to counter-swirl. The primary jets define the boundary of the flow field structure. The rotating direction primarily affects the flow field structure upstream of the primary jets, exerts a relatively weaker influence on the intermediate zone, which is mainly affected by the deflection direction of the primary jets, and essentially has no impact on the dilution jets. Co-swirl has a relatively stable flow field than counter-swirl, whereas the flow field in counter-swirl is more chaotic, featuring a greater number of vortex cores in the primary recirculation zone. The coupling between the primary and swirling jets affects the mass transfer direction in the intermediate zone, which is reflected in the fact that the mass transfer is from top-left to bottom-right in co-swirl, while it is in the opposite direction in counter-swirl. OH is predominantly found in the swirling shear layers, the primary and secondary combustion zones, whereas kerosene is mainly concentrated in the shear layers of swirling jets. The kerosene distribution in co-swirl shows a larger and more concentrated expansion angle compared to counter-swirl. In contrast, the OH distribution downstream of counter-swirl is broader, with more intense combustion due to enhanced kerosene decomposition and fuel-air mixing. The smaller primary recirculation zone in counter-swirl forces the primary combustion zone to extend downstream, leading to a more intense reaction in the secondary recirculation zone.

Under the goal of “carbon peaking and carbon neutrality”, the penetration rate of renewable energy continues to rise, whose volatility, intermittency, and uncertainty pose significant challenges to the safe and stable operation of the power system. As a typical application of the sharing economy in the field of energy storage, shared energy storage (SES) can maximize the utilization of resources by separating the “ownership” and “usage” of energy storage resources, which provides a new solution to the problem of imbalance between supply and demand caused by the large-scale integration of renewable energy into the grid, and has broad development prospects. The business model of SES is explored based on value positioning, cost modeling, and profitability strategies, and a detailed summary of SES trading varieties, operational structure, and engineering applications is discussed. Finally, the future trend of shared energy storage is discussed and envisioned.

Introduction: Vitexin is a natural flavonoid compound extracted from Vitex leaves or seeds, exhibiting various pharmacological activities including anticancer, antihypertensive, anti-inflammatory, and spasmolytic effects. However, its protective effects on hypertensive nephropathy (HN) and the underlying mechanisms remain unclear. Methods: Spontaneous hypertension rats were fed a high-sugar and high-fat diet for 8 weeks to induce the disease HN model. From the 5th week, the rats were administered vitexin via gavage. Blood pressure was measured bi-weekly using the tail-cuff method. Histopathological changes were assessed using HE staining, and biochemical analyses were performed to evaluate the effects of vitexin on HN rats. The underlying mechanisms of vitexin treatment were investigated through western blotting. Results: The data demonstrated that vitexin significantly lowered systolic, diastolic, and mean arterial pressures, and ameliorated histopathological changes in HN rats. Biochemical analyses revealed that vitexin reduced the levels of creatinine (Cr), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), total protein (TP), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and advanced glycation end products (AGEs), while increasing the levels of albumin (ALB) and superoxide dismutase (SOD). Western blotting results indicated that vitexin treatment decreased the expression of TNF-α, IL-6, and nuclear factor kappa-B (NF-κB), while increasing the expression of SOD. Conclusion: The findings of this study suggest that vitexin exerts protective effects against HN, providing pharmacological evidence for its potential use in HN treatment.

Subgroup 4 (Sg4) members of the R2R3-MYB are generally known as negative regulators of the phenylpropanoid pathway in plants. Our previous research showed that a R2R3-MYB Sg4 member from Camellia sinensis (CsMYB4a) inhibits expression of some genes in the phenylpropanoid pathway, but its physiological function in the tea plant remained unknown. Here, CsMYB4a was found to be highly expressed in anther and filaments, and participated in regulating filament growth. Transcriptome analysis and exogenous auxin treatment showed that the target of CsMYB4a might be the auxin signal pathway. Auxin/indole-3-acetic acid 4 (AUX/IAA4), a repressor in auxin signal transduction, was detected from a yeast two-hybrid screen using CsMYB4a as bait. Gene silencing assays showed that both CsIAA4 and CsMYB4a regulate filament growth. Tobacco plants overexpressing CsIAA4 were insensitive to exogenous α-NAA, consistent with overexpression of CsMYB4a. Protein-protein interaction experiments revealed that CsMYB4a interacts with N-terminal of CsIAA4 to prevent CsIAA4 degradation. Knock out of the endogenous NtIAA4 gene, a CsIAA4 homolog, in tobacco alleviated filament growth inhibition and α-NAA insensitivity in plants overexpressing CsMYB4a. All results strongly suggest that CsMYB4a works synergistically with CsIAA4 and participates in regulation of the auxin pathway in stamen.

ObjectiveTo investigate the molecular and biological characteristics of Vibrio vulnificus （V. vulnificus）isolated from Guangzhou.MethodsThirty-eight strains of V. vulnificus were collected from Guangzhou， and whole-genome sequences were obtained. The population structure of V. vulnificus was inferred by utilizing 50 publicly available genome sequences obtained from NCBI. FineSTRUCTURE software was employed for this analysis. Antibiotic resistance and virulence factors were identified using CARD， ResFinder， and VFDB databases.ResultsFour well-supported phylogenetic groups or lineages （L1-L4） were identified， and all genomes of the strains in Guangzhou were classified into L1 （47%） and L2 （53%）. The predominant ST were ST357， ST157， ST136， ST139， ST345， ST303， and so on， which showed regional aggregation. Multiple genome identification of V. vulnificus revealed 11 drug resistance genes： acrF， CRP， catB9， rpoC， ugd， and others. MCR genes related to polymyxin resistance were identified in V. vulnificus for the first time. The species also carries 23 virulence genes in five classes encoding flagellin， type Ⅱ secretory system protein， capsular polysaccharide， RtxA toxin， iron overload， and other virulence-related genes.ConclusionVibrio vulnificus in Guangzhou undergoes highly homologous recombination and carries a variety of antimicrobial resistance genes and virulence-related genes. Therefore， monitoring and management of Vibrio vulnificus should be strengthened.

IntroductionCoastal nations heavily rely on their sea areas to achieve sustainable socioeconomic development. Sea areas offer abundant marine ecosystem products and services that are difficult to substitute with industrial goods. Although considerable research has been performed to evaluate the contribution offrom the marine ecosystems to human well-being, systematic and measurable indices are lacking.MethodsTo address this knowledge gap, ecosystem service theory was used to establish a framework for assessing the gross ecosystem product (GEP) of a sea area, which represents the total monetary value of final ecosystem products directly and indirectly used by people within a specific administrative jurisdiction in one year. To evaluate marine GEP, three primary indices, i.e., material products, regulating products, and cultural products, were employed, and they consist of eight secondary indices. Material products in the sea area include aquatic products and oxygen products; regulating products include carbon sequestration, climate regulation, waste treatment, and coastal protection; and cultural products include leisure and recreation, and seascape-added value. The marine GEP was calculated for the administrative sea areas of Changdao County, which is located in the Yellow Sea-Bohai Sea transitional zone.Results and discussionOur analysis indicated that from 2017 to 2019, the marine GEP in Changdao ranged between 32.59 and 33.35 billion Chinese yuan (CNY). Regulating products contributed two-thirds of this total value. However, over the three-year period, the marine GEP underwent a 5.64% decrease in Changdao. Specifically, the value of material products increased by 38.85% while that of regulating and cultural products decreased by 9.16% and 15.87%, respectively. Notably, the spatial distribution of ecosystem product values in Changdao displayed two prominent trends: (1) higher values along the coastal sea areas of islands and lower values in offshore sea areas; and (2) higher values in coastal areas of southern islands and lower values in coastal areas of northern islands. Marine GEP may serve as a comprehensive indicator for assessing the sustainability of marine ecosystem. Combining the assessment of both marine and terrestrial GEP facilitates an understanding of how marine and terrestrial ecosystems interact in coastal regions. Furthermore, the combined use of marine GEP and GDP helps better evaluate and sort the level of green development of coastal nations and regions.

Abstract Wounds can lead to skin and soft tissue damage and their improper management may lead to the growth of pathogenic bacteria at the site of injury. Identifying better ways to promote wound healing is a major unmet need and biomedical materials with the ability to promote wound healing are urgently needed. Here, we report a thermosensitive black phosphorus hydrogel composed of black phosphorus nano-loaded drug silver sulfadiazine (SSD) and chitosan thermosensitive hydrogel for wound healing. The hydrogel has temperature-sensitive properties and enables the continuous release of SSD under near-infrared irradiation to achieve synergistic photothermal and antibacterial treatment. Additionally, it exerts antibacterial effects on Staphylococcus aureus. In a rat skin injury model, it promotes collagen deposition, boosts neovascularization, and suppresses inflammatory markers. In summary, the excellent thermosensitivity, biocompatibility, and wound-healing-promoting qualities of the reported thermosensitive hydrogel make it suitable as an ideal wound dressing in the clinic.

The utilization of unmanned sailboats as a burgeoning instrument for ocean exploration and monitoring is steadily rising. In this study, a dual sail configuration is put forth to augment the sailboats’ proficiency in its wind-catching ability and adapt to the harsh environment of the sea. This proposition is based on a thorough investigation of sail aerodynamics. The symmetric rigid wing sails NACA 0020 and NACA 0016 are selected for use as the mainsail and trailing wing sail, respectively, after considering the operational environment of unmanned sailboats. The wing sail structure is modeled using SolidWorks, and computational fluid dynamics (CFD) simulations are conducted using ANSYS Fluent 2022R1 software to evaluate the aerodynamic performance of the sails. Key aerodynamic parameters, including lift, drag, lift coefficient, drag coefficient, and thrust coefficient, are obtained under different angles of attack. Furthermore, the effects of mainsail aspect ratios, mainsail taper ratios, and the positional relationship between the mainsail and trailing sail on performance are analyzed to determine the optimal structure. The thrust provided by the sail to the boat is mainly generated by the decomposition of lift, and the lift coefficient is used to measure the efficiency of an object in generating lift in the air. The proposed sail structure demonstrates a 37.1% improvement in the peak lift coefficient compared to traditional flexible sails and exhibits strong propulsion capability, indicating its potential for widespread application in the marine field.