Humid heat environment causes anxiety-like disorder via impairing gut microbiota and bile acid metabolism in mice.

Climate and environmental changes threaten human mental health, but the impacts of specific environmental conditions on neuropsychiatric disorders remain largely unclear. Here, we show the impact of a humid heat environment on the brain and the gut microbiota using a conditioned housing male mouse model. We demonstrate that a humid heat environment can cause anxiety-like behaviour in male mice. Microbial 16 S rRNA sequencing analysis reveals that a humid heat environment caused gut microbiota dysbiosis (e.g., decreased abundance of Lactobacillus murinus), and metabolomics reveals an increase in serum levels of secondary bile acids (e.g., lithocholic acid). Moreover, increased neuroinflammation is indicated by the elevated expression of proinflammatory cytokines in the serum and cortex, activated PI3K/AKT/NF-κB signalling and a microglial response in the cortex. Strikingly, transplantation of the microbiota from mice reared in a humid heat environment readily recapitulates these abnormalities in germ-free mice, and these abnormalities are markedly reversed by Lactobacillus murinus administration. Human samples collected during the humid heat season also show a decrease in Lactobacillus murinus abundance and an increase in the serum lithocholic acid concentration. In conclusion, gut microbiota dysbiosis induced by a humid heat environment drives the progression of anxiety disorders by impairing bile acid metabolism and enhancing neuroinflammation, and probiotic administration is a potential therapeutic strategy for these disorders.

Indirect photodegradation of typical pyrrolizidine alkaloids in water induced by triplet states of dissolved organic matter.

The occurrence of pyrrolizidine alkaloids (PAs) in the aquatic environment has received growing attention due to their persistent mutagenicity and carcinogenicity. In this study, the photooxidation processes of four representative PAs (senecionine, senecionine N-oxide, europine, and heliotrine) in the presence of dissolved organic matter (DOM) were investigated. The excited triplet DOM (3DOM*) was demonstrated to play a dominant role in the phototransformation of PAs. The observed degradation rates of PAs largely depended on the DOM concentration. Alkaline conditions and the presence of HCO3-/CO32- were conducive to the photodegradation. Based on kinetic modeling, the second-order reaction rate constants of PAs with 3DOM* were predicted to be (1.7∼5.3)×108 M-1 s-1, nearly two orders of magnitude higher than those with singlet oxygen (1O2). The monoester structure and electron-withdrawing substituent (e.g., -O atom) substantially affected the one-electron oxidation potential of PAs, which dictates the reaction rates of PAs with 3DOM*. Finally, a tentative degradation pathway of PAs was proposed, involving the formation of an N-centered radical cation through one-electron transfer, which then likely deprotonated and further oxidized to more persistent and toxic phototransformation products with an added oxygen atom into the pyrrole ring.

A Self-Cascade Penetrating Brain Tumor Immunotherapy Mediated by Near-Infrared II Cell Membrane-Disrupting Nanoflakes via Detained Dendritic Cells.

Immunotherapy can potentially suppress the highly aggressive glioblastoma (GBM) by promoting T lymphocyte infiltration. Nevertheless, the immune privilege phenomenon, coupled with the generally low immunogenicity of vaccines, frequently hampers the presence of lymphocytes within brain tumors, particularly in brain tumors. In this study, the membrane-disrupted polymer-wrapped CuS nanoflakes that can penetrate delivery to deep brain tumors via releasing the cell-cell interactions, facilitating the near-infrared II (NIR II) photothermal therapy, and detaining dendritic cells for a self-cascading immunotherapy are developed. By convection-enhanced delivery, membrane-disrupted amphiphilic polymer micelles (poly(methoxypoly(ethylene glycol)-benzoic imine-octadecane, mPEG-b-C18) with CuS nanoflakes enhances tumor permeability and resides in deep brain tumors. Under low-power NIR II irradiation (0.8 W/cm2), the intense heat generated by well-distributed CuS nanoflakes actuates the thermolytic efficacy, facilitating cell apoptosis and the subsequent antigen release. Then, the positively charged polymer after hydrolysis of the benzoic-imine bond serves as an antigen depot, detaining autologous tumor-associated antigens and presenting them to dendritic cells, ensuring sustained immune stimulation. This self-cascading penetrative immunotherapy amplifies the immune response to postoperative brain tumors but also enhances survival outcomes through effective brain immunotherapy.

Clypeasterol, a novel aromatic ergosterol skeleton from the mushroom Entoloma clypeatum.

Chemical investigation of the wild mushroom Entoloma clypeatum led to the isolation of one new A-nor B-aromatic C28 steroid (1), along with eight known compounds (2-9) from this mushroom. As far as we know, compound 1 represents an unprecedented type of natural product. The structure of the new compound was elucidated based on extensive spectroscopic data analysis of HR-ESI-MS, 1D, and 2D NMR, while the relative configuration was confirmed by NOESY correlations. In addition, the anti-inflammatory activity of compound 1 was evaluated against LPS induced NO production in RAW 264.7 macrophages. Compound 1 exhibited a moderate anti-inflammatory activity with an IC50 value of 24.56 ± 1.72 µM.

Fouling behavior of BTEX in petrochemical wastewater treated by nanofiltration (NF).

Membrane fouling generated by small molecular-weight aromatic compounds with poor biodegradability is a major barrier to advanced petrochemical wastewater treatment using nanofiltration (NF) technology. In this study, the fouling behavior of ten BTEX with different substituent existing in petrochemical wastewater on the NF membrane was systematically investigated. By examining the effect of the number, position, and type of substituents on the permeability of NF membranes and membrane resistance analysis, combined with XDLVO theory and correlation analysis, we found that stronger dipole-dipole interactions of BTEX with higher polarity and hydrogen bonding effects between substituents and the membrane surface were verified to be the main forces driving the attachment to the surface of membranes. Furthermore, by analyzing the effect of common inorganic ions in petrochemical wastewater on membrane fouling, it was found that electron-donating substituents (-CH3, -C2H5, and -NH2) enhanced the electron cloud density of the benzene ring, a process that exacerbated membrane fouling by strengthening electrostatic interactions between the benzene ring and Ca2+ ions. The fouling potential of electron-withdrawing substituted (-NO2, -OH) BTEX exhibited the opposite trend. Overall, this study provides a theoretical basis for developing effective membrane fouling control strategies in NF advanced treatment of petrochemical wastewater. ENVIRONMENTAL IMPLICATION: Aromatic chemicals in petrochemical effluent are difficult to degrade, and their accumulation will cause significant harm to humans and ecological systems. Determine the composition of small molecule BTEX in petrochemical wastewater, gain an in-depth comprehension of the membrane fouling behavior of nanofiltration membrane filtration, identify the primary forces causing irreversible membrane surface fouling using experimental data and model fitting, and propose viable anti-fouling membrane modification strategies. Establish a technical foundation for membrane fouling management in the long-term operation of petrochemical wastewater membrane treatment.

Comparison of dual-energy computed tomography (DECT) polychromatic and monochromatic images with and without iterative metal artifact reduction algorithm in patients with dental implants.

Background: Dual-energy computed tomography (DECT) and iterative metal artifact reduction (iMAR) algorithms are valuable tools for reducing metal artifacts. Different parameters of these technologies and their combination can achieve different performance. This study compared various polychromatic and monochromatic images obtained via DECT with and without using iMAR algorithm to reduce artifacts in patients with dental implants. Methods: This study included 30 patients with dental implants who underwent DECT for head and neck imaging. The computed tomography (CT) image sets comprised DECT polychromatic image sets [dual-energy (DE) polychromatic] that linearly blended 100 kV and tin-filtered 140 kV images using composition ratios of -1, -0.6, -0.3, 0, and 0.6, and virtual monochromatic images (DE monochromatic) at 90, 110, 130, 150, and 170 keV. These image sets were obtained with and without using iMAR, resulting in a total of 20 image sets. For subjective analysis, metal artifacts and image quality were assessed using a 5-point Likert scale. For objective analysis, CT attenuation, standard deviation (SD), contrast-to-noise ratio (CNR) and artifact index (AI) were evaluated. In addition, subgroup analysis was performed based on implant size. Results: In the subjective evaluation, iMAR + DE polychromatic (-0.3) images exhibited the lowest metal artifact scores [median (interquartile range): 2 (2-3)]. iMAR + DE monochromatic (110 keV) images demonstrated optimal image quality scores [median (interquartile range): 2 (2-3)]. In the objective evaluation, none of the images demonstrated a significant difference in the CNR, except polychromatic images with a composition of -1 and 0.6. iMAR + DE polychromatic (0) exhibited the lowest AI [median (interquartile range): 8.7 (5.9-14.5)]. There was no significant difference between the two groups with different implant sizes for the techniques combined with iMAR (all P>0.05). Conclusion: iMAR + DE polychromatic (-0.3 and 0) and iMAR + DE monochromatic (110 keV) images exhibited better image quality and substantial metal artifact reduction (MAR) compared with the other image sets. The performance of the techniques combined with iMAR was not affected by the size of the implant.

Waste rubber - Black pollution reframed as a global issue: Ecological challenges and sustainability initiatives.

In contrast to "white pollution" originating from waste plastics, waste rubber is often referred to as "black pollution." The quantity and variety of waste rubber are increasing at an alarming rate, with a considerable fraction entering the global ecosystem via various pathways. This study presents the first critical review of waste rubber research with a focus on the risks associated with toxicant discharge and existing problems in waste rubber disposal, management, and recycling practices. We aim to obtain a comprehensive understanding of current research, particularly regarding the ecological impacts of these wastes, highlight major gaps, and propose the most significant research directions. A total of 192 studies published in journals were critically analysed. The importance of conducting long-term and large-scale experiments and developing efficient waste rubber recycling systems is also emphasised. This study highlights the need to address the challenges posed by waste rubber pollution and offers insights and references for undertaking ecological risk assessments and understanding the mechanisms underlying toxicant behaviour. Suggestions and countermeasures are proposed with ecosystem sustainability as the ultimate goal. Further long-term, comprehensive, and systematic research in this area is required.

[Effects of Different Forms of Nitrogen Addition on Soil Physical and Chemical Properties and Microbial Community Structure of Perennial Alpine Cultivated Grassland].

This study aimed to investigate the impact of different nitrogen forms on soil physicochemical properties and microbial community structure in perennial alpine cultivated grasslands, in order to provide scientific basis for developing nitrogen addition strategies for perennial alpine cultivated grasslands. In June 2022, a 4-year-old Qinghai grassland mixed with Poa pratensis Qinghai and Festuca sinensis Qinghai was established at the Bakatai Farm in Gonghe County, Hainan Tibetan Autonomous Prefecture, Qinghai Province. The study was conducted without fertilization as a control (CK), and three different forms of nitrogen treatments were set up, namely, U:urea (amide nitrogen), A:ammonium sulfate (ammonium nitrogen), and N:calcium nitrate (nitrate nitrogen); the nitrogen application rate for each treatment was 67.5 kg·(hm2·a)-1, and the composition and diversity of soil nutrients and microbial communities under different treatments were analyzed. The results showed that the input of exogenous ammonium nitrogen significantly increased NH4+-N content, AP content, and EC; amide nitrogen input significantly increased SOC content and TN content; and nitrate nitrogen input significantly increased NO3--N content, AN content, and TC content. Exogenous nitrogen input changed the structure of soil bacterial and fungal communities, as well as the relative abundance of dominant phyla and genera, but it did not significantly affect the alpha diversity of bacterial and fungal communities. Principal coordinate analysis (PCoA) showed that different forms of nitrogen addition had a significant impact on the Beta diversity of bacterial communities, whereas the impact on fungal communities was not significant. Redundancy analysis (RDA) indicated that nitrogen addition mainly changed the composition and structure of microbial communities through soil ammonium nitrogen. Overall, ammonium nitrogen fertilizer should be given priority in the soil remediation process of perennial cultivated grasslands in the Qinghai Tibet Plateau.

Discovery of Novel 1-Phenylpiperidine Urea-Containing Derivatives Inhibiting ß-Catenin/BCL9 Interaction and Exerting Antitumor Efficacy through the Activation of Antigen Presentation of cDC1 Cells.

Aberrant activation of the Wnt/ß-catenin signaling is associated with tumor development, and blocking ß-catenin/BCL9 is a novel strategy for oncogenic Wnt/ß-catenin signaling. Herein, we presented two novel ß-catenin variations and exposed conformational dynamics in several ß-catenin crystal structures at the BCL9 binding site. Furthermore, we identified a class of novel urea-containing compounds targeting ß-catenin/BCL9 interaction. Notably, the binding modalities of inhibitors were greatly affected by the conformational dynamics of ß-catenin. Among them, 28 had a strong affinity for ß-catenin (Kd = 82 nM), the most potent inhibitor reported. In addition, 13 and 35 not only activate T cells but also promote the antigen presentation of cDC1, showing robust antitumor efficacy in the CT26 model. Collectively, our study demonstrated a series of potent small-molecule inhibitors targeting ß-catenin/BCL9, which can enhance antigen presentation and activate cDC1 cells, delivering a potential strategy for boosting innate and adaptive immunity to overcome immunotherapy resistance.

pH-Responsive ß-Glucans-Complexed mRNA in LNPs as an Oral Vaccine for Enhancing Cancer Immunotherapy.

mRNA vaccines for cancer immunotherapy are commonly delivered using lipid nanoparticles (LNPs), which, when administered intravenously, may accumulate in the liver, potentially limiting their therapeutic efficacy. To overcome this challenge, the study introduces an oral mRNA vaccine formulation tailored for efficient uptake by immune cells in the gastrointestinal (GI) tract, known for its high concentration of immune cells, including dendritic cells (DCs). This formulation comprises mRNA complexed with ß-glucans (ßGlus), a potential adjuvant for vaccines, encapsulated within LNPs (ßGlus/mRNA@LNPs). The ßGlus/mRNA complexes within the small compartments of LNPs demonstrate a distinctive ability to partially dissociate and reassociate, responding to pH changes, effectively shielding mRNA from degradation in the harsh GI environment. Upon oral administration to tumor-bearing mice, ßGlus/mRNA@LNPs are effectively taken up by intestinal DCs and local nonimmune cells, bypassing potential liver accumulation. This initiates antigen-specific immune responses through successful mRNA translation, followed by drainage into the mesenteric lymph nodes to stimulate T cells and trigger specific adaptive immune responses, ultimately enhancing antitumor effects. Importantly, the vaccine demonstrates safety, with no significant inflammatory reactions observed. In conclusion, the potential of oral ßGlus/mRNA@LNPs delivery presents a promising avenue in cancer immunotherapy, offering needle-free and user-friendly administration for widespread adoption and self-administration.

A simple and highly sensitive flexible sensor with extended-gate field-effect transistor for epinephrine detection utilizing InZnSnO sensing films.

This study introduces a straightforward method for depositing InZnSnO films onto flexible polyimide substrates at room temperature, enabling their application in electrochemical pH sensing and the detection of epinephrine. A comprehensive analysis of these sensing films, spanning structural, morphological, compositional, and profiling characteristics, was conducted using diverse techniques, including X-ray diffraction, atomic force microscopy, X-ray photoelectron spectroscopy, and secondary ion mass spectroscopy. The investigation into the influence of oxygen flow rates on the performance of InZnSnO sensitive films revealed a significant correlation between their structural properties and sensing capabilities. Notably, exposure to an oxygen flow rate of 30/2 (Ar/O2) the ratio of resulted in the InZnSnO sensitive film demonstrating outstanding pH sensitivity at 59.58 mV/pH within a broad pH range of 2-12, surpassing the performance observed with other oxygen flow rates. Moreover, under this specific condition, the film exhibited excellent stability, with a minimal drift rate of 0.14 mV/h at pH 7 and a low hysteresis voltage of 1.8 mV during a pH cycle of 7 â†’ 4→7 â†’ 10→7. Given the critical role of epinephrine in mammalian central nervous and hormone systems, monitoring its levels is essential for assessing human health. To facilitate the detection of epinephrine, we utilized the carboxyl group of 4-formylphenylboronic acid to enable a reaction with the amino group of the 3-aminopropyltriethoxysilane-coated InZnSnO film. Through optimization, the resulting InZnSnO-based flexible sensor displayed a broad and well-defined linear relationship within the concentration range of 10-7 to 0.1 µM. In practical applications, this sensor proved effective in analyzing epinephrine in human serum, showcasing notable selectivity, stability, and reproducibility. The promising outcomes of this study underscore the potential for future applications, leveraging the advantages of electrochemical sensors, including affordability, rapid response, and user-friendly operation.

Comparison of Outcomes between Stent Retriever Combined with Contact Aspiration and Contact Aspiration Alone in Patients without Hyperdense Artery Sign/Susceptibility Vessel Sign.

PURPOSE: To examine the relationship between hyperdense artery sign (HAS)/susceptibility vessel sign (SVS) and thrombus composition and evaluate the effect of HAS/SVS status on the association between first-line thrombectomy techniques and outcomes in patients with acute anterior circulation large vessel occlusion (LVO). MATERIALS AND METHODS: From January 2018 to June 2021, 103 consecutive patients with acute anterior circulation LVO (75 [63.1%] men; median age, 66 years) who underwent thrombectomy and for whom the removed clot was available for histological analyses were retrospectively reviewed. The presence of HAS and SVS was assessed on unenhanced computed tomography (CT) and susceptibility-weighted imaging, respectively. Association of first-line thrombectomy techniques (stent retriever [SR] combined with contact aspiration [CA] vs CA alone) with outcomes was assessed according to HAS/SVS status. RESULTS: Among the included patients, 55 (53.4%) were HAS/SVS-negative, and 69 (67.0%) underwent first-line SR + CA. Higher relative densities of fibrin/platelets (0.56 vs 0.51; P < .001) and lower relative densities of erythrocytes (0.32 vs 0.42; P < .001) were observed in HAS/SVS-negative patients compared with HAS/SVS-positive patients. First-line SR + CA was associated with reduced odds of distal embolization (adjusted odds ratio, 0.18; 95% CI, 0.04-0.83; P = .027) and a more favorable 90-day functional outcome (adjusted odds ratio, 5.29; 95% CI, 1.06-26.34; P = .042) in HAS/SVS-negative patients and a longer recanalization time (53 vs 25 minutes; P = .025) and higher risk of subarachnoid hemorrhage (24.2% vs 0%; P = .044) in HAS/SVS-positive patients. CONCLUSIONS: Absence of HAS/SVS may indicate a higher density of fibrin/platelets in the thrombus, and first-line SR + CA yielded superior functional outcomes than CA alone in patients with acute LVO without HAS/SVS.

Nicotinamide riboside alleviates brain dysfunction induced by chronic cerebral hypoperfusion via protecting mitochondria.

Chronic cerebral hypoperfusion (CCH) is an enduring inadequate blood flow to the brain, resulting in vascular dementia (VaD). However, the effective treatment strategies are lacking. Supplementing with nicotinamide adenine dinucleotide (NAD+) has shown neuroprotective benefits in other neurodegenerative disorders. Nicotinamide riboside (NR), as a precursor of NAD+, is believed to hold promise in improving mitochondrial health, autophagy, and cognitive function. Meanwhile, NR has unique oral bioavailability, good tolerability, and minimal side effects, and it is the most promising for clinical translation. However, the effectiveness of NR in treating CCH-related VaD is still uncertain. The present study examined the neuroprotective effects of NR supplementation and its underlying mechanisms in a CCH rat model. The rats with CCH were given NR at a daily dosage of 400 mg/kg for 3 months. NR supplementation increased blood and brain NAD+ levels and improved brain function in CCH rats, including cognitive function and oxygenation capacity. It also reduced hippocampal neuronal loss and abnormalities and mitigated the decrease in dendritic spine density. The analysis of RNA sequencing in hippocampal tissue supports these findings. Electron microscopy and protein detection results suggest that NR may maintain mitochondrial structural integrity and exert a protective role by attenuating mitochondrial fission and impaired autophagy flux caused by CCH. In conclusion, these findings offer evidence for the neuroprotective potential of NR supplementation in ameliorating cognitive impairment induced by CCH.

Revealing intact neuronal circuitry in centimeter-sized formalin-fixed paraffin-embedded brain.

Tissue-clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.

Six new polyphenolic metabolites isolated from the Suillus granulatus and their cytotoxicity against HepG2 cells.

Edible mushrooms are an important source of nutraceuticals and for the discovery of bioactive metabolites as pharmaceuticals. In this work, six new polyphenolic metabolites suillusol A-D (1-4), suillusinoic acid (5), ethyl suillusinoate (6), were isolated from the Suillus granulatus. The structures of new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy, nuclear magnetic resonance data, and single-crystal X-ray diffraction analysis. As far as we know, compound 1 represents an unprecedented type of natural product and compound 3 represents a new type of polyphenol fungal pigment, which may be biosynthetically related to thelephoric acid. The cytotoxicity against HepG2 cells of the new compounds were also evaluated. Compound 2 demonstrate significant inhibitory activity against HepG2 cells with IC50 values of 10.85 µM, surpassing that of positive control cisplatin. Moreover, compound 1 and 3 also exhibited moderate cytotoxic activity with their IC50 values measured at 35.60 and 32.62 µM, respectively. Our results indicate that S. granulatus is a rich source of chemical constituents that may provide new lead compounds for the development of anticancer agents.

Anti-Hyperglycemic Effect of the Brown Slime Cap Mushroom Chroogomphus rutilus (Agaricomycetes) Crude Polysaccharide In Vitro and In Vivo.

The prevalence of diabetes is increasing worldwide, and it is very important to study new hypoglycemic active substances. In this study, we investigated the hypoglycemic effect of Chroogomphus rutilus crude polysaccharide (CRCP) in HepG2 cells and streptozotocin-induced diabetic mice. A glucose consumption experiment conducted in HepG2 cells demonstrated the in vitro hypoglycemic activity of CRCP. Furthermore, CRCP exhibited significant hypoglycemic effects and effectively ameliorated insulin resistance in insulin resistant HepG2 cells. In high-fat diet and streptozotocin-induced diabetic mice, after 4 weeks of CRCP administration, fasting blood glucose, fasting serum insulin, triglyceride, total cholesterol, low-density lipoprotein cholesterol, glutamate transaminase, alanine transaminase, and insulin resistance index significantly decreased, while high-density lipoprotein cholesterol and insulin sensitivity index (ISI) were markedly increased. Moreover, hematoxylin-eosin (HE) staining and immunofluorescence labeling of tissue sections indicated that CRCP attenuated the pathological damage of liver and pancreas in diabetic mice. These results indicate that CRCP is a potential hypoglycemic agent.

A self-cleaning photocatalytic membrane loaded with Bi2O2CO3/In(OH)3 S-scheme heterojunction composites for removing tetracycline from aqueous solutions.

Bi2O2CO3/In(OH)3 (BON) photocatalysts were synthesized by a one-pot method and loaded onto polyvinylidene fluoride (PVDF) membranes to obtain a Bi2O2CO3/In(OH)3/PVDF (BON-M) catalytic membrane system. The catalytic membranes demonstrated complete degradation of tetracycline within 40 min under visible light. They demonstrated robust photocatalytic activity across a broad pH range (5-11) and in the presence of coexisting ions. The membranes demonstrated excellent self-cleaning performance. Following exposure to light, the irreversible contamination decreased from 27.1% to 4.7% and the membrane's permeability was almost completely restored. Moreover, the charge transfer mechanism at the S-scheme heterojunction interface of BON was demonstrated by Density functional theory and in-situ X-ray Photoelectron Spectroscopy characterisation, and the active sites involved in tetracycline's degradation were identified. Meanwhile, the mechanism of the "anemone effect" of BON-M was demonstrated in conjunction with Electron paramagnetic resonance, and the intrinsic Some factors enhancing the membranes' photocatalytic activity are specified.

Use of Cefiderocol in the Management of Children With Infection or Colonization With Multi-drug Resistant Gram-negative Bacteria: A Retrospective, Single-center Case Series.

Cefiderocol, a novel siderophore cephalosporin, represents a treatment option for infections with multidrug-resistant Gram-negative bacteria, of which rates are rising worldwide. Clinical data on its use in children is limited. In our pediatric case series, the largest reported to date, cefiderocol seems safe and well tolerated, with more favorable clinical outcomes when compared to the literature reviewing adult cases.