Clinical application of digital technology in the use of anterolateral thigh lobulated perforator flaps to repair complex soft tissue defects of the limbs.

Background: It is challenging to repair wide or irregular defects with traditional skin flaps, and anterolateral thigh (ALT) lobulated perforator flaps are an ideal choice for such defects. However, there are many variations in perforators, so good preoperative planning is very important. This study attempted to explore the feasibility and clinical effect of digital technology in the use of ALT lobulated perforator flaps for repairing complex soft tissue defects in limbs. Methods: Computed tomography angiography (CTA) was performed on 28 patients with complex soft tissue defects of the limbs, and the CTA data were imported into Mimics 20.0 software in DICOM format. According to the perforation condition of the lateral circumflex femoral artery and the size of the limb defect, one thigh that had two or more perforators from the same source vessel was selected for 3D reconstruction of the ALT lobulated perforator flap model. Mimics 20.0 software was used to visualize the vascular anatomy, virtual design and harvest of the flap before surgery. The intraoperative design and excision of the ALT lobulated perforator flap were guided by the preoperative digital design, and the actual anatomical observations and measurements were recorded. Results: Digital reconstruction was successfully performed in all patients before surgery; this reconstruction dynamically displayed the anatomical structure of the flap vasculature and accurately guided the design and harvest of the flap during surgery. The parameters of the harvested flaps were consistent with the preoperative parameters. Postoperative complications occurred in 7 patients, but all flaps survived uneventfully. All of the donor sites were closed directly. All patients were followed up for 13-27 months (mean, 19.75 months). The color and texture of each flap were satisfactory and each donor site exhibited a linear scar. Conclusions: Digital technology can effectively and precisely assist in the design and harvest of ALT lobulated perforator flaps, provide an effective approach for individualized evaluation and flap design and reduce the risk and difficulty of surgery.

Coping with alpine habitats: genomic insights into the adaptation strategies of Triplostegia glandulifera (Caprifoliaceae).

How plants find a way to thrive in alpine habitats remains largely unknown. Here we present a chromosome-level genome assembly for an alpine medicinal herb, Triplostegia glandulifera (Caprifoliaceae), and 13 transcriptomes from other species of Dipsacales. We detected a whole-genome duplication event in T. glandulifera that occurred prior to the diversification of Dipsacales. Preferential gene retention after whole-genome duplication was found to contribute to increasing cold-related genes in T. glandulifera. A series of genes putatively associated with alpine adaptation (e.g. CBFs, ERF-VIIs, and RAD51C) exhibited higher expression levels in T. glandulifera than in its low-elevation relative, Lonicera japonica. Comparative genomic analysis among five pairs of high- vs low-elevation species, including a comparison of T. glandulifera and L. japonica, indicated that the gene families related to disease resistance experienced a significantly convergent contraction in alpine plants compared with their lowland relatives. The reduction in gene repertory size was largely concentrated in clades of genes for pathogen recognition (e.g. CNLs, prRLPs, and XII RLKs), while the clades for signal transduction and development remained nearly unchanged. This finding reflects an energy-saving strategy for survival in hostile alpine areas, where there is a tradeoff with less challenge from pathogens and limited resources for growth. We also identified candidate genes for alpine adaptation (e.g. RAD1, DMC1, and MSH3) that were under convergent positive selection or that exhibited a convergent acceleration in evolutionary rate in the investigated alpine plants. Overall, our study provides novel insights into the high-elevation adaptation strategies of this and other alpine plants.

Assessing the ecological security of the Three Gorges reservoir complex ecosystem based on the improved three-dimensional emergy ecological footprint model.

The ecological security (ES) of the reservoir complex ecosystem (RCE) is one of the critical components of watershed water security and sustainable development. Hence, accurately assessing the ES of the RCE is of utmost importance. This study proposed a novel ecological security assessment model based on the improved three-dimensional emergy ecological footprint (ESM-IEEF3D), which integrated various emergy flows during the RCE's construction and operation into a three-dimensional emergy ecological footprint (EEF3D) calculation account. The Three Gorges Project (TGP) is selected as a case study to evaluate the ES from 1993 to 2022 comprehensively. The results showed that the Three Gorges RCE mainly showed an ecological remainder state, and the inflow runoff enormously promoted the TGP's sustainability. The EEF3D indicated a fluctuation decrease trend with a mean value of 7.18 × 102 ha, illustrating that TGP's ecological security and sustainability levels are gradually improving. Regarding the ES evaluation indicators, the TGP's resource dependency and ecological pressure on the natural ecosystem and the external socio-economic system are steadily relieved. Furthermore, the Three Gorges RCE's resource utilization condition is safe, the structural characteristics are healthy, and the eco-economic coordination degree is continuously enlightening. Finally, applicable policy implications for improving the ecological security of Three Gorges RCE were provided. This study helps to understand the complex relationship between humans and ecosystems. It provides a novel framework to be used as an evaluation index and policy insights for hydropower ecological security and sustainable development.

NbC Nanoparticles Decorated Carbon Nanofibers as Highly Active and Robust Heterostructural Electrocatalysts for Ammonia Synthesis.

Transition-metal carbides with metallic properties have been extensively used as electrocatalysts due to their excellent conductivity and unique electronic structures. Herein, NbC nanoparticles decorated carbon nanofibers (NbC@CNFs) are proposed as an efficient and robust catalyst for electrochemical synthesis of ammonia from nitrate/nitrite reduction, which achieves a high Faradaic efficiency (FE) of 94.4% and a large ammonia yield of 30.9 mg h-1 mg-1cat.. In situ electrochemical tests reveal the nitrite reduction at the catalyst surface follows the *NO pathway and theoretical calculations reveal the formation of NbC@CNFs heterostructure significantly broadens density of states nearby the Fermi energy. Finite element simulations unveil that the current and electric field converge on the NbC nanoparticles along the fiber, suggesting the dispersed carbides are highly active for nitrite reduction.

Utility of paired plasma and drainage fluid mNGS in diagnosing acute intra-abdominal infections with sepsis.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) has been increasingly applied in sepsis. We aimed to evaluate the diagnostic and therapeutic utility of mNGS of paired plasma and peritoneal drainage (PD) fluid samples in comparison to culture-based microbiological tests (CMTs) among critically ill patients with suspected acute intra-abdominal infections (IAIs). METHODS: We conducted a prospective study from October 2021 to December 2022 enrolling septic patients with suspected IAIs (n = 111). Pairwise CMTs and mNGS of plasma and PD fluid were sent for pathogen detection. The mNGS group underwent therapeutic regimen adjustment based on mNGS results for better treatment. The microbial community structure, clinical features, antibiotic use and prognoses of the patients were analyzed. RESULTS: Higher positivity rates were observed with mNGS versus CMTs for both PD fluid (90.0% vs. 48.3%, p < 0.005) and plasma (76.7% vs. 1.6%, p < 0.005). 90% of enrolled patients had clues of suspected pathogens combining mNGS and CMT methods. Gram-negative pathogens consist of most intra-abdominal pathogens, including a great variety of anaerobes represented by Bacteroides and Clostridium. Patients with matched plasma- and PD-mNGS results had higher mortality and sepsis severity. Reduced usage of carbapenem (30.0% vs. 49.4%, p < 0.05) and duration of anti-MRSA treatment (5.1 ± 3.3 vs. 7.0 ± 8.4 days, p < 0.05) was shown in the mNGS group in our study. CONCLUSIONS: Pairwise plasma and PD fluid mNGS improves microbiological diagnosis compared to CMTs for acute IAI. Combining plasma and PD mNGS could predict poor prognosis. mNGS may enable optimize empirical antibiotic use.

Protective Effect of Silibinin on Lipopolysaccharide-Induced Endotoxemia by Inhibiting Caspase-11-Dependent Cell Pyroptosis.

OBJECTIVE: To explore the protective effect and the underlying mechanism of silibinin (SIB), one of the active compounds from Silybum marianum (L.) Gaertn in endotoxemia. METHODS: Mouse peritoneal macrophage were isolated via intraperitoneally injection of BALB/c mice with thioglycolate medium. Cell viability was assessed using the cell counting kit-8, while cytotoxicity was determined through lactate dehydrogenase cytotoxicity assay. The protein expressions of interleukin (IL)-1 α, IL-1 ß, and IL-18 were determined by enzyme-linked immunosorbent assay. Intracellular lipopolysaccharide (LPS) levels were measured by employing both the limulus amoebocyte lysate assay and flow cytometry. Additionally, proximity ligation assay was employed for the LPS and caspase-11 interaction. Mice were divided into 4 groups: the control, LPS, high-dose-SIB (100 mg/kg), and low-dose-SIB (100 mg/kg) groups (n=8). Zebrafish were divided into 4 groups: the control, LPS, high-dose-SIB (200 εmol/L), and low-dose-SIB (100 εmol/L) groups (n=30 for survival experiment and n=10 for gene expression analysis). The expression of caspase-11, gasdermin D (GSDMD), and N-GSDMD was determined by Western blot and the expressions of caspy2, gsdmeb, and IL-1 ß were detected using quantitative real-time PCR. Histopathological observation was performed through hematoxylineosin staining, and protein levels in bronchoalveolar lavage fluid were quantified using the bicinchoninicacid protein assay. RESULTS: SIB noticeably decreased caspase-11 and GSDMD-mediated pyroptosis and suppressed the secretion of IL-1 α, IL-1 ß, and IL-18 induced by LPS (P<0.05). Moreover, SIB inhibited the translocation of LPS into the cytoplasm and the binding of caspase-11 and intracellular LPS (P<0.05). SIB also attenuated the expression of caspase-11 and N-terminal fragments of GSDMD, inhibited the relative cytokines, prolonged the survival time, and up-regulated the survival rate in the endotoxemia models (P<0.05). CONCLUSIONS: SIB can inhibit pyroptosis in the LPS-mediated endotoxemia model, at least in part, by inhibiting the caspase-11-mediated cleavage of GSDMD. Additionally, SIB inhibits the interaction of LPS and caspase-11 and inhibits the LPS-mediated up-regulation of caspase-11 expression, which relieves caspase-11-dependent cell pyroptosis and consequently attenuates LPS-mediated lethality.

Tumor acidification and GSH depletion by bimetallic composite nanoparticles for enhanced chemodynamic therapy of TNBC.

Chemodynamic therapy (CDT) based on intracellular Fenton reaction to produce highly cytotoxic reactive oxygen species (ROS) has played an essential role in tumor therapy. However, this therapy still needs to be improved by weakly acidic pH and over-expression of glutathione (GSH) in tumor microenvironment (TEM), which hinders its future application. Herein, we reported a multifunctional bimetallic composite nanoparticle MnO2@GA-Fe@CAI based on a metal polyphenol network (MPN) structure, which could reduce intracellular pH and endogenous GSH by remodeling tumor microenvironment to improve Fenton activity. MnO2 nanoparticles were prepared first and MnO2@GA-Fe nanoparticles with Fe3+ as central ion and gallic acid (GA) as surface ligands were prepared by the chelation reaction. Then, carbonic anhydrase inhibitor (CAI) was coupled with GA to form MnO2@GA-Fe@CAI. The properties of the bimetallic composite nanoparticles were studied, and the results showed that CAI could reduce intracellular pH. At the same time, MnO2 could deplete intracellular GSH and produce Mn2+ via redox reactions, which re-established the TME with low pH and GSH. In addition, GA reduced Fe3+ to Fe2+. Mn2+ and Fe2+ catalyzed the endogenous H2O2 to produce high-lever ROS to kill tumor cells. Compared with MnO2, MnO2@GA-Fe@CAI could reduce the tumor weight and volume for the xenograft MDA-MB-231 tumor-bearing mice and the final tumor inhibition rate of 58.09 ± 5.77%, showing the improved therapeutic effect as well as the biological safety. Therefore, this study achieved the high-efficiency CDT effect catalyzed by bimetallic through reshaping the tumor microenvironment.

Arming Amorphous NiMoO4 on Nickel Phosphide Enables Highly Stable Alkaline Seawater Oxidation.

Seawater electrolysis holds tremendous promise for the generation of green hydrogen (H2 ). However, the system of seawater-to-H2 faces significant hurdles, primarily due to the corrosive effects of chlorine compounds, which can cause severe anodic deterioration. Here, a nickel phosphide nanosheet array with amorphous NiMoO4 layer on Ni foam (Ni2 P@NiMoO4 /NF) is reported as a highly efficient and stable electrocatalyst for oxygen evolution reaction (OER) in alkaline seawater. Such Ni2 P@NiMoO4 /NF requires overpotentials of just 343 and 370 mV to achieve industrial-level current densities of 500 and 1000 mA cm-2 , respectively, surpassing that of Ni2 P/NF (470 and 555 mV). Furthermore, it maintains consistent electrolysis for over 500 h, a significant improvement compared to that of Ni2 P/NF (120 h) and Ni(OH)2 /NF (65 h). Electrochemical in situ Raman spectroscopy, stability testing, and chloride extraction analysis reveal that is situ formed MoO4 2- /PO4 3- from Ni2 P@NiMoO4 during the OER test to the electrode surface, thus effectively repelling Cl- and hindering the formation of harmful ClO- .

Tungstate Intercalated NiFe Layered Double Hydroxide Enables Long-Term Alkaline Seawater Oxidation.

Renewable electricity-driven seawater splitting presents a green, effective, and promising strategy for building hydrogen (H2 )-based energy systems (e.g., storing wind power as H2 ), especially in many coastal cities. The abundance of Cl- in seawater, however, will cause severe corrosion of anode catalyst during the seawater electrolysis, and thus affect the long-term stability of the catalyst. Herein, seawater oxidation performances of NiFe layered double hydroxides (LDH), a classic oxygen (O2 ) evolution material, can be boosted by employing tungstate (WO4 2- ) as the intercalated guest. Notably, insertion of WO4 2- to LDH layers upgrades the reaction kinetics and selectivity, attaining higher current densities with ≈100% O2 generation efficiency in alkaline seawater. Moreover, after a 350 h test at 1000 mA cm-2 , only trace active chlorine can be detected in the electrolyte. Additionally, O2 evolution follows lattice oxygen mechanism on NiFe LDH with intercalated WO4 2- .

Construction and evaluation of a nanosystem that combines acidification promoted chemodynamic therapy and intracellular drug release monitoring.

Triple-negative breast cancer (TNBC) is a highly invasive subtype of breast cancer that seriously affects women's physical and mental health. Chemodynamic therapy (CDT) induces cell death by specifically generating Fenton/Fenton-like reactions within tumor cells. However, the weak acidity of the tumor microenvironment (TME) greatly weakens the effectiveness of CDT. This work constructed a kind of P-CAIDF/PT nanoparticles (NPs), composed of two Pluronic F127 (PF127) based polymers: one was PF127-CAI (P-CAI), composed by connecting PF127 with the carbonic anhydrase IX (CA IX) inhibitor (CAI); the other was PF127-SS-TPE (PT), composed of PF127 and the aggregation-induced emission molecule, tetraphenylethylene (TPE), via the linkage of disulfide bonds. The two polymers were employed to construct the doxorubicin (DOX) and ferrocene (Fc) co-loaded P-CAIDF/PT NPs through the film dispersion method. After being administrated via i.v., P-CAIDF/PT could be accumulated in the TME by the enhanced permeability and retention (EPR) effect and engulfed by tumor cells. P-CAI induced intracellular acidification by inhibiting the overexpressed CA IX, thus promoting CDT by enhancing the Fc-mediated Fenton reaction. The acidification-enhanced CDT combined with the DOX-mediated chemotherapy could improve the therapeutic effect on TNBC. Moreover, P-CAIDF/PT also monitored the intracellular drug release processes through the fluorescence resonance energy transfer (FRET) effect depending on the inherent DOX/TPE pair. In conclusion, the P-CAIDF/PT nanosystem can achieve the combination therapy of acidification-enhanced CDT and chemotherapy as well as therapy monitoring, thus providing new ideas for the design and development of TNBC therapeutic agents.

Application of three-dimensional material CZIF-8/CS-MS as adsorbents for the determination of plant growth regulators in Schisandra chinensis.

In this study, we employed a melamine sponge (MS) as the skeleton material and utilized carbonized ZIF-8 (CZIF-8) and chitosan (CS) as the raw materials to prepare CZIF-8/CS-MS, a novel material featuring a three-dimensional interconnected porous network. The resulting CZIF-8/CS-MS material possesses a unique porous structure, significant specific surface area and abundant active sites. These characteristics make CZIF-8/CS-MS a promising absorbent for selective purification of plant growth regulators (PGRs) including 1-naphthlcetic acid (NAA), naphthoxyacetic acid (NOA), 4-chlorophenoxyacetic acid (4-CPA), 2,4-dichlorophenoxyacetic acid (2,4-D). After optimizing the extraction conditions, excellent linearity (r > 0.9994) was observed within a wide linear range of 1-100 ng/mL using ultra high performance liquid chromatography-tandem quadrupole mass spectrometry. The detection limits (LODs) and limits of quantification (LOQs) were found to be in the range of 0.013-0.154 ng/mL and 0.044-0.515 ng/mL, respectively. Additionally, the relative recovery of Schisandra chinensis fruit samples was determined to be 89.7-99.4 %, with a relative standard deviation (RSDs) of ≤ 8.4 % (n = 3). Compared to other methods, this approach offers a multitude of benefits, which include but are not limited to exceptional sensitivity, reduced sample volume requirements, low LODs, a comparable linear range, and high reproducibility. The findings of this study pave the way for exploring novel functionalized sponge columns, which leverage the integration of nano-sorbent materials and coating agents, for the purpose of analyzing PGRs within intricate matrix samples.

Dexamethasone-Loaded Lipid Calcium Phosphate Nanoparticles Treat Experimental Colitis by Regulating Macrophage Polarization in Inflammatory Sites.

Background: The M1/M2 polarization of intestinal macrophages exerts an essential function in the pathogenesis of ulcerative colitis (UC), which can be adjusted to alleviate the UC symptoms. Purpose: A kind of pH-sensitive lipid calcium phosphate core-shell nanoparticles (NPs), co-loading with dexamethasone (Dex) and its water-soluble salts, dexamethasone sodium phosphate (Dsp), was constructed to comprehensively regulate macrophages in different states towards the M2 phenotype to promote anti-inflammatory effects. Methods: Dex and Dsp were loaded in the outer lipid shell and inner lipid calcium phosphate (Cap) core of the LdCaPd NPs, respectively. Then, the morphology of NPs and methods for determining drug concentration were investigated, followed by in vitro protein adsorption, stability, and release tests. Cell experiments evaluated the cytotoxicity, cellular uptake, and macrophage polarization induction ability of NPs. The in vivo distribution and anti-inflammatory effect of NPs were evaluated through a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced BALB/c mice ulcerative colitis model. Results: The LdCaPd NPs showed a particle size of about 200 nm and achieved considerable loading amounts of Dex and Dsp. The in vitro and in vivo studies revealed that in the acidic UC microenvironment, the cationic lipid shell of LdCaPd underwent protonated dissociation to release Dex first for creating a microenvironment conducive to M2 polarization. Then, the exposed CaP core was further engulfed by M1 macrophages to release Dsp to restrict the pro-inflammatory cytokines production by inhibiting the activation and function of the nuclear factor kappa-B (NF-κB) through activating the GC receptor and the NF kappa B inhibitor α (I-κBα), respectively, ultimately reversing the M1 polarization to promote the anti-inflammatory therapy. Conclusion: The LdCaPd NPs accomplished the sequential release of Dex and Dsp to the UC site and the inflammatory M1 macrophages at this site, promoting the regulation of macrophage polarization to accelerate the remission of UC symptoms.

Pharmacologically significant constituents collectively responsible for anti-sepsis action of XueBiJing, a Chinese herb-based intravenous formulation.

Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing's anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing's pharmacologically significant constituents supports the medicine's anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

Metabolomics and pharmacodynamic analysis unveil the therapeutic role of icaritin on osteoporosis rats.

Osteoporosis is a systemic metabolic bone disease characterized by a reduction in bone mass resulting from multifactorial causes. Icaritin (ICT), a flavonoid glycoside, exhibits a multitude of effects on bone tissue. To examine the influence of ICT on bone trabecular loss in vivo, ovariectomized (OVX) rats were utilized. The ability of ICT to mitigate bone trabecular loss and the underlying anti-osteoporotic pathways were assessed using ovariectomy-induced osteoporosis rats. Furthermore, we gain insights into the osteoprotective mechanisms of ICT on osteoporosis by conducting UPLC-Orbitrap-MS-based metabolomics of rat urine. The results of experiments demonstrated a significant attenuation of bone trabecular loss, as well as improvements in biochemical indices, biomechanical parameters, and microstructure in the ICT administered group compared to the OVX group. Moreover, metabolomics results suggested that the ICT treatment adjusted 33 different metabolites, which associated with the metabolism of amino acids, lipids, and energy. The findings suggest that the anti-osteoporosis effect of ICT may be related to the activation of PI3K/AKT signal and the inhibition of TLR4 pathway regulated by metabonomics. These results contribute to a better understanding of the therapeutic potential of ICT in the treatment of osteoporosis.

Near-infrared light-actuated on-demand botanicals release and hyperthermia by an antibiotic-free polysaccharide-based hydrogel dressing for the synergistic treatment of wound infections.

Bacterial infection is a key factor affecting wound healing. Conventional treatments might lead to the widespread emergence of drug-resistant bacteria due to the long-term and excessive use of antibiotics. It is necessary to develop an antibiotic-free method for effective treatment of bacterial wound infections. In this work, we constructed an antibiotic-free polysaccharide-based hydrogel dressing (ATB) with near-infrared light-actuated on-demand botanicals release and hyperthermia for the synergistic treatment of wound infections. The ATB hydrogel dressing was made up of agarose as a support matrix, berberine hydrochloride as the active botanicals and TA-Fe(III) nanoparticles as NIR laser-activated photothermal reagents. The ATB hydrogel dressing showed spatiotemporal botanicals release and excellent photothermal properties with NIR irradiation. With the results of in vitro and in vivo antibacterial experiments, the antibiotic-free ATB hydrogel could synergistically eliminate bacteria and accelerate wound healing. Overall, the near-infrared light-responsive ATB hydrogel could provide a promising antibiotic-free strategy for the treatment of bacterial wound infections.

Metabolomics-derived biomarkers for biosafety assessment of Gd-based nanoparticle magnetic resonance imaging contrast agents.

With the rapid development of nanotechnology and biomedicine, numerous gadolinium (Gd)-based nanoparticle MRI contrast agents have been widely investigated. Due to the unique physicochemical properties of nanoparticles and the complexity of biological systems, the biosafety of Gd-based nanoparticle MRI contrast agents has been paid more and more attention. Herein, for the first time, we employed an ultra-high performance liquid chromatography-electrospray ionization quadrupole time-of-flight/mass spectrometry (UPLC-ESI-QTOF/MS)-based metabolomics approach to investigate the potential toxicity of Gd-based nanoparticle MRI contrast agents. In this work, NaGdF4 and PEG-NaGdF4 nanoparticles were successfully constructed and selected as the representative Gd-based nanoparticle MRI contrast agents for the metabolomics analysis. Based on the results of metabolomics, more metabolic biomarkers and pathways were identified in the NaGdF4 group than those in the PEG-NaGdF4 group. Careful analysis of these metabolic biomarkers and pathways suggested that NaGdF4 nanoparticles induced disturbance of pyrimidine and purine metabolism, inflammatory response, and kidney injury to a certain extent compared with PEG-NaGdF4 nanoparticles. These results indicated that Gd-based nanoparticle contrast agents modified with PEG had better biosafety. Additionally, it was demonstrated that the discovery of characteristic metabolomics biomarkers induced by nanoparticles would provide a new approach for biosafety assessment and stimulate the development of nanomedicine.

Boosting Alkaline Seawater Oxidation of CoFe-layered Double Hydroxide Nanosheet Array by Cr Doping.

The pursuit of stable and efficient electrocatalysts toward seawater oxidation is of great interest, yet it poses considerable challenges. Herein, the utilization of Cr-doped CoFe-layered double hydroxide nanosheet array is reported on nickel-foam (Cr-CoFe-LDH/NF) as an efficient electrocatalyst for oxygen evolution reaction in alkaline seawater. The Cr-CoFe-LDH/NF catalyst can achieve current densities of 500 and 1000 mA cm -2 with remarkably low overpotentials of only 334 and 369 mV, respectively. Furthermore, it maintains at least 100 h stability when operated at 500 mA cm-2.

Construction and Mechanism of IL-15-Based Coactivated Polymeric Micelles for NK Cell Immunotherapy.

Natural killer (NK) cells are an important contributor to cancer immunotherapy, but their antitumor efficacy remains suboptimal. While cytokine-based priming shows promise in enhancing NK-cell activity, its clinical translation faces many challenges, including coactivation of multiple cytokines, poor pharmacokinetics, and limited mechanistic understanding. Here, this work develops a polymeric micelle-based IL-15/IL-2 codelivery system (IL-15/2-PEG-PTMC) for NK-cell activation. In vivo studies demonstrate that half-life of IL-15 and IL-2 and the recruitment of NK cell within tumor tissue are significantly increased after PEG-PTMC loading. Coupled with the coactivation effect of IL-15 and IL-2 conferred by this system, it noticeably delays the growth of tumors compared to conventional NK-cell activation approach, that is free IL-15 and IL-2. It is also surprisingly found that cholesterol metabolism is highly involved in the NK cell activation by IL-15/2-PEG-PTMC. Following stimulation with IL-15/2-PEG-PTMC or IL-15, NK cells undergo a series of cholesterol metabolism reprogramming, which elevates the cholesterol levels on NK cell membrane. This in turn promotes the formation of lipid rafts and activates immune synapses, effectively contributing to the enhancement of NK cell's antitumor activity. It is believed that it will open a new avenue for improving the efficacy of NK cell immunotherapy by regulating cholesterol metabolism.

Semantic-Preserving Surgical Video Retrieval With Phase and Behavior Coordinated Hashing.

Medical professionals rely on surgical video retrieval to discover relevant content within large numbers of videos for surgical education and knowledge transfer. However, the existing retrieval techniques often fail to obtain user-expected results since they ignore valuable semantics in surgical videos. The incorporation of rich semantics into video retrieval is challenging in terms of the hierarchical relationship modeling and coordination between coarse- and fine-grained semantics. To address these issues, this paper proposes a novel semantic-preserving surgical video retrieval (SPSVR) framework, which incorporates surgical phase and behavior semantics using a dual-level hashing module to capture their hierarchical relationship. This module preserves the semantics in binary hash codes by transforming the phase and behavior similarities into high- and low-level similarities in a shared Hamming space. The binary codes are optimized by performing a reconstruction task, a high-level similarity preservation task, and a low-level similarity preservation task, using a coordinated optimization strategy for efficient learning. A self-supervised learning scheme is adopted to capture behavior semantics from video clips so that the indexing of behaviors is unencumbered by fine-grained annotation and recognition. Experiments on four surgical video datasets for two different disciplines demonstrate the robust performance of the proposed framework. In addition, the results of the clinical validation experiments indicate the ability of the proposed method to retrieve the results expected by surgeons. The code can be found at https://github.com/trigger26/SPSVR.

Follicle-stimulating hormone orchestrates glucose-stimulated insulin secretion of pancreatic islets.

Follicle-stimulating hormone (FSH) is involved in mammalian reproduction via binding to FSH receptor (FSHR). However, several studies have found that FSH and FSHR play important roles in extragonadal tissue. Here, we identified the expression of FSHR in human and mouse pancreatic islet ß-cells. Blocking FSH signaling by Fshr knock-out led to impaired glucose tolerance owing to decreased insulin secretion, while high FSH levels caused insufficient insulin secretion as well. In vitro, we found that FSH orchestrated glucose-stimulated insulin secretion (GSIS) in a bell curve manner. Mechanistically, FSH primarily activates Gαs via FSHR, promoting the cAMP/protein kinase A (PKA) and calcium pathways to stimulate GSIS, whereas high FSH levels could activate Gαi to inhibit the cAMP/PKA pathway and the amplified effect on GSIS. Our results reveal the role of FSH in regulating pancreatic islet insulin secretion and provide avenues for future clinical investigation and therapeutic strategies for postmenopausal diabetes.