Self-Terminating Surface Reconstruction Induced by High-Index Facets of Delafossite for Accelerating Ammonia Oxidation Reaction Involving Lattice Oxygen.

Ammonia (NH3 ) is a promising hydrogen (H2 ) carrier for future carbon-free energy systems, due to its high hydrogen content and easiness to be liquefied. Inexpensive and efficient catalysts for ammonia electro-oxidation reaction (AOR) are desired in whole ammonia-based energy systems. In this work, ultrasmall delafossite (CuFeO2 ) polyhedrons with exposed high-index facets are prepared by a one-step NH3 -assisted hydrothermal method, serving as AOR pre-catalysts. The high-index CuFeO2 facet is revealed to facilitate surface reconstruction into active Cu-doped FeOOH nanolayers during AOR processes in ammonia alkaline solutions, which is driven by the favorable Cu leaching and terminates as the 2p levels of internal lattice oxygen change. The reconstructed heterostructures of CuFeO2 and Cu-doped FeOOH effectively activate the dehydrogenation steps of NH3 and exhibit a potential improvement of 260 mV for electrocatalytic AOR at 10 mA cm-2 compared to the pre-restructured phase. Further, density functional theory (DFT) calculations confirm that a lower energy barrier of the rate-determining step (*NH3 to *NH2 ) is presented on high-index CuFeO2 facets covered with Cu-doped FeOOH nanolayers. Innovatively, lattice oxygen atoms in Fe-based oxides and oxyhydroxide are involved in the dehydrogenation steps of AOR as a proton acceptor, broadening the horizons for rational designs of AOR catalysts.

Controllable Exfoliation of MOF-Derived Van Der Waals Superstructure into Ultrathin 2D B/N Co-Doped Porous Carbon Nanosheets: A Superior Catalyst for Ambient Ammonia Electrosynthesis.

The electrocatalytic nitrogen reduction reaction (NRR) to synthesize NH3 under ambient conditions is a promising alternative route to the conventional Haber-Bosch process, but it is still a great challenge to develop electrocatalysts' high Faraday efficiency and ammonia yield. Herein, a facile and efficient exfoliation strategy to synthesize ultrathin 2D boron and nitrogen co-doped porous carbon nanosheets (B/NC NS) via a metal-organic framework (MOF)-derived van der Waals superstructure, is reported. The results of experiments and theoretical calculations show that the doping of boron and nitrogen can modulate the electronic structure of the adjacent carbon atoms; which thus, promotes the competitive adsorption of nitrogen and reduces the energy required for ammonia synthesis. The B/NC NS exhibits excellent catalytic performance and stability in electrocatalytic NRR, with a yield rate of 153.4 µg·h-1 ·mg-1 cat and a Faraday efficiency of 33.1%, which is better than most of the reported NRR electrocatalysts. The ammonia yield of B/NC NS can maintain 92.7% of the initial NRR activity after 48 h stability test. The authors' controllable exfoliation strategy using MOF-derived van der Waals superstructure can provide a new insight for the synthesis of other 2D materials.

Reduced Graphene Oxide Modulated FeSe/C Anode Materials for High-Stable and Long-Life Potassium-Ion Batteries.

Reduced graphene oxide (rGO) has been demonstrated to effectively enhance the potassium storage performance of transition metal selenides due to its robust mechanical properties and high conductivity. However, the impact of rGO on the electrode-electrolyte interface, a crucial factor in the electrochemical performance of potassium-ion batteries (PIBs), requires further exploration. In this study, we synthesized a seamless architecture of rGO on FeSe/C nanocrystals (FeSe/C@rGO). Comparative analysis between FeSe/C and FeSe/C@rGO reveals that the rGO layer exhibits robust adsorption energies towards EC and DEC, inducing the formation of organic-rich solid-electrolyte interphase (SEI) without damage to the structural integrity. Furthermore, incorporating rGO triggers K+ -ions into the double electrode layer (EDL), markedly improving the transport of K+ -ions. As a PIB anode, FeSe/C@rGO exhibits a reversible capacity of 332 mAh g-1 at 200 mA g-1 after 300 cycles, along with excellent long-term cycling stability, showcasing an ultralow decay rate of only 0.086 % per cycle after 1900 cycles at 1000 mA g-1 .

Iron-Doped Metal-Zinc-Centered Organic Framework Mesoporous Carbon Derivatives for Single-Wavelength NIR-Activated Photothermal/Photodynamic Synergistic Therapy.

Recently, single-wavelength synergetic photothermal/photodynamic (PTT/PDT) therapy is beginning to make its mark in cancer treatment, and the key to it is a photosensitizer. In this work, an iron-doped metal-zinc-centered organic framework mesoporous carbon derivative (denoted as Fex-Zn-NCT) with a similar porphyrin property was successfully synthesized by a mild, simple, and green aqueous reaction. The effects of different Fe contents and pyrolysis temperatures on the morphology, structure, and PTT/PDT of Fex-Zn-NCT were investigated. Most importantly, we found that Fe50-Zn-NC900 exhibited excellent PTT/PDT performance under single-wavelength near-infrared (808 nm) light irradiation in a hydrophilic environment. The photothermal conversion efficiency (η) was counted as ∼81.3%, and the singlet oxygen (1O2) quantum yield (Φ) was compared with indocyanine green (ICG) as ∼0.0041. Furthermore, Fe50-Zn-NC900 is provided with a clear ability for generating 1O2 in living tumor cells and inducted massive necrosis/apoptosis of tumor cells with single-wavelength near-infrared laser irradiation. All of these are clear to consider that Fe50-Zn-NC900 displays great potential as an excellent photosensitizer for single-wavelength dual-mode PTT/PDT therapy.

Identification of Heterophilic Epitopes of H1N1 Influenza Virus Hemagglutinin.

Our previous studies found that the H1-50 monoclonal antibody (mAb) of influenza A virus hemagglutinin (HA) cross-reacted with pancreatic tissue and islet ß-cells, and further studies showed that H1-50 mAb binds to prohibitin (PHB) protein of islet ß-cells. These suggest that there are heterophilic epitopes between influenza virus HA and pancreatic tissue, which may be involved in the pathogenesis of type 1 diabetes. To further investigate these heterophilic epitopes, we screened binding epitopes of H1-50 mAb using a phage 12-peptide library. DNA sequencing and comparative analysis were performed on specific positive phage clones, and the sequence of 12-peptide binding to H1-50 mAb was obtained. The binding epitopes of H1-50 mAb in influenza virus HA were determined by sequence analysis and experimental verification, and their distribution within the three-dimensional structure was assessed by PyMOL. The results showed that H1-50 mAb specifically binds to polypeptides (306-SLPFQNIHPITIGK-319) of influenza A virus HA, located in the stem of the HA protein. However, there is no specific binding sequence between H1-50 mAb and the PHB protein of islet ß-cells in the primary structure, and we speculate that the binding of H1-50 mAb to islet ß-cells may depend on the spatial conformation. The identification of the heterophilic epitopes of H1N1 influenza virus hemagglutinin provides a new perspective on type 1 diabetes that may be caused by influenza virus infection, which may contribute to the prevention and control of influenza.

Metal-Organic Framework Derived Ni2P/FeP@NPC Heterojunction as Stability Bifunctional Electrocatalysts for Large Current Density Water Splitting.

The construction of heterojunction has been widely accepted as a prospective strategy for the exploration of non-precious metal-based catalysts that possess high-performance to achieve electrochemical water splitting. Herein, we design and prepare a metal-organic framework derived N, P-doped-carbon-encapsulated Ni2P/FeP nanorod with heterojunction (Ni2P/FeP@NPC) for accelerating the water splitting and working stably at industrially relevant high current densities. Electrochemical results confirmed that Ni2P/FeP@NPC could both accelerate the hydrogen and oxygen evolution reactions. It could substantially expedite the overall water splitting (1.94 V for 100 mA cm-2) which is close to the performance of RuO2 and the Pt/C couple (1.92 V for 100 mA cm-2). In particular, the durability test exhibited that Ni2P/FeP@NPC delivers 500 mA cm-2 without decay after 200 h, demonstrating the great potential for large-scale applications. Furthermore, the density functional theory simulations demonstrated that the heterojunction interface could give rise to the redistribution of electrons, which could not only optimize the adsorption energy of H-containing intermediates to achieve the optimal ΔGH* in a hydrogen evolution reaction, but also reduce the ΔG value in the rate-determining step of an oxygen evolution reaction, thus improving the HER/OER performance.

Organizational display rules in nursing: Impacts on caring behaviors and emotional exhaustion through emotional labor.

AIM: To examine the impact of display rules on nurses' caring behaviors and emotional exhaustion and the mediating role of emotional labor (surface/deep acting). BACKGROUND: Hospitals often implement emotional display rules for nurses with the expectation of performance benefits. However, these rules may have an impact on nurses' caring behaviors and emotional exhaustion. METHODS: This cross-sectional correlational study included a sample of 746 nurses from five hospitals and used the STROBE checklist. Relationships between display rules, emotional labor, caring behaviors, and emotional exhaustion were analyzed using structural equation modeling. RESULTS: Display rules did not directly affect caring behaviors or emotional exhaustion. Emotional labor mediated the relationships. Display rules were associated more with surface acting. Deep acting increased caring behaviors and reduced emotional exhaustion; surface acting had the opposite effect. CONCLUSIONS: Findings challenge the assumption that display rules effectively promote caring behaviors. Display rules lead to emotional labor and emotional exhaustion. Reducing display rules, emotional labor, and surface acting while supporting deep acting may alleviate emotional exhaustion. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nurse managers should review the nature and implementation of emotional display rules and explore ways to reduce emotional labor, encourage deep acting, mitigate the negative impact of surface acting, and ultimately improve nursing caring behaviors.

Drug resistance profiles and influencing factors among HIV-infected children and adolescents receiving long-term ART: a multicentre observational study in China.

OBJECTIVES: To analyse the characteristics and determinants of drug resistance mutations (DRMs) in HIV-infected children and adolescents on long-term ART in China. METHODS: An observational cohort study was conducted in five centres. All participants younger than 15 years at ART initiation were screened, and those identified as having virological failure (VF) with viral load (VL) ≥ 400 copies/mL were included for genotypic resistance testing. Logistic regression analysis was performed and the accumulation of major mutations was analysed in a subgroup of resistant individuals with complete VL results since HIV diagnosis. RESULTS: Among 562 eligible participants, protease and RT regions were successfully amplified for 93 who failed treatment with a median of 10.0 years ART. Sixty-eight (73.1%) harboured ≥1 major mutations. NRTI, NNRTI and dual-class resistance accounted for 48.4%, 63.4% and 38.7%, respectively. Only 3.2% were resistant to PIs. Age at ART initiation [adjusted OR (aOR) = 0.813, 95% CI 0.690-0.957], subtype B (aOR = 4.378, 95% CI 1.414-13.560) and an initial NNRTI-based regimen (aOR = 3.331, 95% CI 1.180-9.402) were independently associated with DRMs. Among 40 resistant participants with additional VL data, 55.0% had continued VF on a suboptimal regimen and the estimated duration of VF was positively correlated with the total number of major mutations (r = 0.504, P = 0.001). CONCLUSIONS: The development of DRMs was common in children and adolescents receiving long-term treatment, and continued VF was prevalent in those with resistance. Timely genotypic testing and new child-friendly formulations are therefore urgently required.

Prevalence of doravirine cross-resistance in HIV-infected adults who failed first-line ART in China, 2014-18.

OBJECTIVES: To evaluate the prevalence and characteristics of doravirine resistance and cross-resistance in patients who failed first-line ART in China. METHODS: From 2014 to 2108, 4132 patients from five provinces were tested for drug resistance by genotypic resistance testing. Drug resistance mutations were assessed using the Stanford HIVdb algorithm Version 9.0. Sequences classified as having low-level, intermediate and high-level resistance were defined as having drug resistance. RESULTS: Overall, the prevalence of doravirine and other NNRTIs cross-resistance was 69.5%, with intermediate and high-level resistance accounting for 56.4%. Doravirine resistance highly correlated with efavirenz (r = 0.720) and nevirapine (r = 0.721) resistance and moderately correlated with etravirine (r = 0.637) and rilpivirine (r = 0.692) resistance. The most frequent doravirine-associated resistance mutations were V106M (8.7%), K101E (6.8%) and P225H (5.1%). High-level resistance was mainly due to Y188L (3.2%) and M230L (2.7%). There were significant differences between genotypes and provinces. Compared with CRF01_AE, CRF07_BC (OR = 0.595, 95% CI = 0.546-0.648) and CRF08_BC (OR = 0.467, 95% CI = 0.407-0.536) were associated with lower risks of doravirine resistance. Conversely, genotype A (OR = 3.003, 95% CI = 1.806-4.991) and genotype B (OR = 1.250, 95% CI = 1.021-1.531) were associated with higher risks of doravirine resistance. The risk of doravirine resistance was significantly lower in Xinjiang compared with other provinces. CONCLUSIONS: In China, the prevalence of doravirine cross-resistance among patients who have failed first-line ART is high. Therefore, doravirine should not be used blindly without genotypic resistance testing and is not recommended for people who have failed first-line NNRTI-based ART.

A PEGylated water-soluble fluorescent and colorimetric probe for carbon monoxide detection.

A CO probe with PEGylation is synthesized, achieving the detection of CO in pure water solution with high intensity color change and fluorescence enhancement. Importantly, this probe with high affinity to paper strips and low toxicity to living cells is successfully used for sensing CO in air and in living cells.

Adsorption in Reversed Order of C2 Hydrocarbons on an Ultramicroporous Fluorinated Metal-Organic Framework.

Metal-organic frameworks have been widely studied in the separation of C2 hydrocarbons, which usually preferentially bind unsaturated hydrocarbons with the order of acetylene (C2 H2 )>ethylene (C2 H4 )>ethane (C2 H6 ). Herein, we report an ultramicroporous fluorinated metal-organic framework Zn-FBA (H2 FBA=4,4'-(hexafluoroisopropylidene)bis(benzoic acid)), shows a reversed adsorption order characteristic for C2 hydrocarbons, that the uptake for C2 hydrocarbons of the framework and the binding affinity between the guest molecule and the framework follows the order C2 H6 >C2 H4 >C2 H2 . Density-functional theory calculations confirm that the completely reversed adsorption order behavior is attributed to the close van der Waals interactions and multiple cooperative C-H⋅⋅⋅F hydrogen bonds between the framework and C2 H6 . Moreover, Zn-FBA exhibits a high selectivity of about 2.9 for C2 H6 over C2 H4 at 298 K and 1 bar. The experimental breakthrough studies show that the high-purity C2 H4 can be obtained from C2 H6 and C2 H4 mixtures in one step.

Neutralizing antibody PR8-23 targets the footprint of the sialoglycan receptor binding site of H1N1 hemagglutinin.

Influenza virus cause seasonal influenza epidemic and seriously sporadic influenza pandemic outbreaks. Hemagglutinin (HA) is an important target in the therapeutic treatment and diagnostic detection of the influenza virus. Variation in the sialic acid receptor binding site leads to strain-specific binding and results in different binding modes to the host receptors. Here, we evaluated the neutralizing activity and hemagglutination inhibition activity of a prepared murine anti-H1N1 monoclonal antibody PR8-23. Then we identified the epitope peptide of antibody PR8-23 by phage display technique from phage display peptide libraries. The identified epitope, 63-IAPLQLGKCNIA-74, containing two α-helix and two ß-fold located at the footprint of the sialoglycan receptor on the RBS in the globular head domain of HA. It broads the growing arsenal of motifs for the amino acids on the globular head domain of HA in sialic acid receptor binding site and neutralizing antibody production.

Monoclonal Antibody Targeting the HA191/199 Region of H1N1 Influenza Virus Mediates the Damage of Neural Cells.

Vaccination is the most effective mean of preventing influenza virus infections. However, vaccination-induced adverse reactions of the nervous system, the causes of which are unknown, lead to concerns on the safety of influenza A vaccine. In this study, we used flow cytometry, cell ELISA, and immunofluorescence to find that H1-84 monoclonal antibody (mAb) against the191/199 region of the H1N1 influenza virus hemagglutinin (HA) protein binds to neural cells and mediates cell damage. Using molecular simulation software, such as PyMOL and PDB viewer, we demonstrated that the HA191/199 region maintains the overall structure of the HA head. Since the HA191/199 region cannot be removed from the HA structure, it has to be altered via introducing point mutations by site-directed mutagenesis. This will provide an innovative theoretical support for the subsequent modification the influenza A vaccine for increasing its safety.

Adsorption Site Selective Occupation Strategy within a Metal-Organic Framework for Highly Efficient Sieving Acetylene from Carbon Dioxide.

The separation of acetylene and carbon dioxide is an essential but challenging process owing to the similar molecular sizes and physical properties of the two gas molecules. Notably, these molecules usually exhibit different orientations in the pore channel. We report an adsorption site selective occupation strategy by taking advantage of differences in orientation to sieve the C2 H2 from CO2 in a judiciously designed amine-functionalized metal-organic framework, termed CPL-1-NH2 . In this material, the incorporation of amino groups not only occupies the adsorption sites of CO2 molecules and shields the interaction of uncoordinated oxygen atom and CO2 molecules resulting in a negligible adsorption amount and a decrease in enthalpy of adsorption but also strengthened the binding affinity toward C2 H2 molecules. This material thus shows an extremely high amount of C2 H2 at low pressure and a remarkably high C2 H2 /CO2 IAST selectivity (119) at 1 bar and 298 K.

Quantitative Detection and Viral Load Analysis of SARS-CoV-2 in Infected Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a public health emergency. The widely used reverse transcription-polymerase chain reaction (RT-PCR) method has limitations for clinical diagnosis and treatment. METHODS: A total of 323 samples from 76 COVID-19-confirmed patients were analyzed by droplet digital PCR (ddPCR) and RT-PCR based 2 target genes (ORF1ab and N). Nasal swabs, throat swabs, sputum, blood, and urine were collected. Clinical and imaging data were obtained for clinical staging. RESULTS: In 95 samples that tested positive by both methods, the cycle threshold (Ct) of RT-PCR was highly correlated with the copy number of ddPCR (ORF1ab gene, R2 = 0.83; N gene, R2 = 0.87). Four (4/161) negative and 41 (41/67) single-gene positive samples tested by RT-PCR were positive according to ddPCR with viral loads ranging from 11.1 to 123.2 copies/test. The viral load of respiratory samples was then compared and the average viral load in sputum (17 429 ±â€…6920 copies/test) was found to be significantly higher than in throat swabs (2552 ±â€…1965 copies/test, P < .001) and nasal swabs (651 ±â€…501 copies/test, P < .001). Furthermore, the viral loads in the early and progressive stages were significantly higher than that in the recovery stage (46 800 ±â€…17 272 vs 1252 ±â€…1027, P < .001) analyzed by sputum samples. CONCLUSIONS: Quantitative monitoring of viral load in lower respiratory tract samples helps to evaluate disease progression, especially in cases of low viral load.

Serum Total Bile Acid is Closely Related to the Significant Liver Injury in Patients with Non-Cholestatic Chronic Hepatitis B Virus Infection: a Cross-Sectional Study.

BACKGROUND: The relationship between non-cholestatic liver disease and total bile acid (TBA) remains obscure. The present study aimed to verify this relationship in patients with non-cholestatic chronic hepatitis B virus (HBV) infection. METHODS: A total of 922 consecutive chronic HBV infected patients with alkaline phosphatase (ALP) ≤ 1.5 upper limit of normal (ULN) and gamma-glutamyl transferase (GGT) ≤ 3 ULN were rigorously included in this cross-sectional study. Liver biopsy was performed in 53 patients and Scheuer scoring system was used to evaluate inflammation grade. G3/G4 or Child-Pugh B/C were considered to be significant liver injury. RESULTS: Compared to Child-Pugh A, TBA, total bilirubin (TBIL), ALP, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and AST to ALT ratio (AST/ALT) were significantly higher in Child-Pugh B/C, while TBIL to TBA ratio (TBIL/TBA) was significantly lower (all p < 0.001). In multivariate analysis, TBA and AST/ALT were independently correlated with Child-Pugh B/C [odds ratio (OR) = 1.04, p < 0.001; OR = 1.79, p < 0.001, respectively]. The area under the curve (AUC) of TBA (0.82) was significantly higher than that of AST (0.73, p < 0.001) and ALT (0.63, p < 0.001). Furthermore, in patients with liver biopsy, TBA was also significantly higher in G3/G4 while TBIL/TBA was significantly lower (p < 0.05). After adjusting the factors related to bile excretion, TBIL/TBA was independently associated with G3/G4 (OR = 0.89, p = 0.037). CONCLUSIONS: Serum TBA shows a close relationship with significant liver injury in chronic HBV infected patients without cholestasis. Assessment of TBA, especially in combination with TBIL/TBA, may serve as a non-invasive marker for the diagnosis of non-cholestatic hepatic damage.

An epitope on the stem region of hemagglutinin of H1N1 influenza A virus recognized by neutralizing monoclonal antibody.

Influenza A viruses are a major threat to human health and inflict a significant public health challenge worldwide. Hemagglutinin (HA) is the main contributor to the infectivity of the virus and is a potential target for the development of antiviral therapeutic agents. The stem region of HA, which has been shown to be conserved, is the primary target in the development of antibody-based therapeutic strategies and preventive tools. Here, we confirmed the neutralizing activity and prophylactic efficacy of murine monoclonal antibody PR8-25 as well as Western blot analysis of different influenza virus strains. Then, we identified the epitope of PR8-25, 328-LRMVTGLRNIPS-339, by phage-displayed 12-mer random peptide library. The identified epitope targeted in the stem region of HA, specifically at the C-terminal of the HA1 fragment. This result suggest that the identified epitope may be a potential basis for antiviral drugs and stem-based universal influenza vaccines.

Type 1 diabetes mellitus and non-alcoholic fatty liver disease: a two-sample Mendelian randomization study.

Background: NAFLD (Nonalcoholic fatty liver disease) is becoming an increasingly common cause of chronic liver disease. Metabolic dysfunction, overweight/obesity, and diabetes are thought to be closely associated with increased NAFLD risk. However, few studies have focused on the mechanisms of NAFLD occurrence in T1DM. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal association between T1DM and NAFLD with/without complications, such as coma, renal complications, ketoacidosis, neurological complications, and ophthalmic complications. Multiple Mendelian randomization methods, such as the inverse variance weighted (IVW) method, weighted median method, and MR-Egger test were performed to evaluate the causal association of T1DM and NAFLD using genome-wide association study summary data from different consortia, such as Finngen and UK biobank. Results: We selected 37 SNPs strongly associated with NAFLD/LFC (at a significance level of p < 5 × 10-8) as instrumental variables from the Finnish database based on the T1DM phenotype (8,967 cases and 308,373 controls). We also selected 14/16 SNPs based on with or without complications. The results suggest that the genetic susceptibility of T1DM does not increase the risk of NAFLD (OR=1.005 [0.99, 1.02], IVW p=0.516, MR Egger p=0.344, Weighted median p=0.959, Weighted mode p=0.791), regardless of whether complications are present. A slight causal effect of T1DM without complications on LFC was observed (OR=1.025 [1.00, 1.03], MR Egger p=0.045). However, none of the causal relationships were significant in the IVW (p=0.317), Weighted median (p=0.076), and Weighted mode (p=0.163) methods. Conclusion: Our study did not find conclusive evidence for a causal association between T1DM and NAFLD, although clinical observations indicate increasing abnormal transaminase prevalence and NAFLD progression in T1DM patients.

Identification of Piperazinyl-Difluoro-indene Derivatives Containing Pyridyl Groups as Potent FGFR Inhibitors against FGFR Mutant Tumor: Design, Synthesis, and Biological Evaluation.

The fibroblast growth factor receptor (FGFR) signaling pathway plays important roles in cellular processes such as proliferation, differentiation, and migration. In this study, we highlighted the potential of FGFR inhibitors bearing the (S)-3,3-difluoro-1-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-indene scaffold containing a crucial 3-pyridyl group for the treatment of FGFR mutant cancers. The representative compound (S)-23, which was identified through comprehensive evaluation, exhibited potent antiproliferative activity with GI50 in the range of 6.4-10.4 nM against FGFR1 fusion protein-carrying, FGFR2-amplified, and FGFR2 mutant cancer cell lines and good antiproliferative activity against FGFR3 translocation and mutant FGFR4 cancer cell lines, as well as potency assessment against FGFR1-4 kinases. Moreover, compound (S)-23 exhibited favorable pharmacokinetic properties, low potential for drug-drug interactions, and very potent antitumor activity in MFE-296 xenograft mouse models with a TGI of 99.1% at the dose of 10 mg/kg. These findings demonstrate that compound (S)-23 is a potential therapeutic agent for FGFR mutant tumors.