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Journal of Colloid and Interface Science Jun 2024Rational design of coordination environment of Fe-based metal-organic frameworks (Fe-MOFs) is still a challenge in achieving enhanced catalytic activity for Fenten-like...
Rational design of coordination environment of Fe-based metal-organic frameworks (Fe-MOFs) is still a challenge in achieving enhanced catalytic activity for Fenten-like advanced oxidation process. Here in, novel porous Fe-MOFs with modulated O-Fe-N coordination was developed by configurating amino terephthalic acid (HATA) and pyrazine-dicarboxylic acid (PzDC) (Fe-ATA/PzDC-7:3). PzDC ligands introduce pyridine-N sites to form O-Fe-N coordination with lower binding energy, which affect the local electronic environment of Fe-clusters in Fe-ATA, thus decreased its interfacial HO activation barrier. O-Fe-N coordination also accelerate Fe(II)/Fe(III) cycling of Fe-clusters by triggering the reactive oxidant species mediated Fe(III) reduction. As such, Fe-ATA/PzDC-7:3/HO system exhibited excellent degradation performance for typical antibiotic sulfamethoxazole (SMX), in which the steady-state concentration of hydroxyl radical (OH) was 1.6 times higher than that of unregulated Fe-ATA. Overall, this study highlights the role of O-Fe-N coordination and the electronic environment of Fe-clusters on regulating Fenton-like catalytic performance, and provides a platform for precise engineering of Fe-MOFs.
PubMed: 38936084
DOI: 10.1016/j.jcis.2024.06.155 -
Journal of the American Chemical Society Jun 2024Bridged bicyclic scaffolds are emerging bioisosteres of planar aromatic rings under the concept of "escape from flatland". However, adopting this concept into the...
Bridged bicyclic scaffolds are emerging bioisosteres of planar aromatic rings under the concept of "escape from flatland". However, adopting this concept into the exploration of bioisosteres of pyridines remains elusive due to the challenge of incorporating a N atom into such bridged bicyclic structures. Herein, we report practical routes for the divergent synthesis of 2- and 3-azabicyclo[3.1.1]heptenes (aza-BCHepes) as potential bioisosteres of pyridines from the readily accessible vinyl azides and bicyclo[1.1.0]butanes (BCBs) via two distinct catalytic annulations. The reactivity of vinyl azides tailored with BCBs is the key to achieving divergent transformations. Ti-catalyzed single-electron reductive generation of C-radicals from BCBs allows a concise (3 + 3) annulation with vinyl azides, affording novel 2-aza-BCHepe scaffolds. In contrast, scandium catalysis enables an efficient dipolar (3 + 2) annulation with vinyl azides to generate 2-azidobicyclo[2.1.1]hexanes, which subsequently undergo a chemoselective rearrangement to construct 3-aza-BCHepes. Both approaches efficiently deliver unique azabicyclo[3.1.1]heptene scaffolds with a high functional group tolerance. The synthetic utility has been further demonstrated by scale-up reactions and diverse postcatalytic transformations, providing valuable azabicyclics including 2- and 3-azabicyclo[3.1.1]heptanes and rigid bicyclic amino esters. In addition, the related sp-hybridized nitrogen atom and the similar geometric property between pyridines and corresponding aza-BCHepes indicate that they are promising bioisosteres of pyridines.
PubMed: 38935924
DOI: 10.1021/jacs.4c04485 -
JCO Precision Oncology Jun 2024The National Cancer Institute-Children's Oncology Group (NCI-COG) Pediatric MATCH trial assigns patients age 1-21 years with refractory malignancies to phase II...
Phase II Study of Ulixertinib in Children and Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Alterations: APEC1621J of the National Cancer Institute-Children's Oncology Group Pediatric MATCH Trial.
PURPOSE
The National Cancer Institute-Children's Oncology Group (NCI-COG) Pediatric MATCH trial assigns patients age 1-21 years with refractory malignancies to phase II treatment arms of molecularly targeted therapies on the basis of genetic alterations detected in their tumor. Patients with activating alterations in the mitogen-activated protein kinase pathway were treated with ulixertinib, an extracellular signal-regulated kinase (ERK)1/2 inhibitor.
METHODS
As there were no previous pediatric data, ulixertinib was initially tested in a dose escalation cohort to establish the recommended phase II dose (RP2D) before proceeding to the phase II cohort. Ulixertinib was administered at 260 mg/m/dose orally twice a day (dose level 1 [DL1], n = 15) or 350 mg/m/dose orally twice a day (DL2, n = 5). The primary end point was objective response rate; secondary end points included safety/tolerability and progression-free survival (PFS).
RESULTS
Twenty patients (median 12 years; range, 5-20) were treated, all evaluable for response. CNS tumors comprised 55% (11/20) of diagnoses, with high-grade glioma and low-grade glioma most common (n = 5 each). All CNS tumors except one harbored fusions or V600E mutations. Rhabdomyosarcoma (n = 5) was the most frequent non-CNS diagnosis. DL1 was declared the RP2D in the dose escalation cohort after dose-limiting toxicities in Cycle 1 occurred in 1/6 patients at DL1 and 2/5 patients at DL2, including fatigue, anorexia, rash, nausea, vomiting, diarrhea, dehydration, hypoalbuminemia, and hypernatremia. No objective responses were observed. Six-month PFS was 37% (95% CI, 17 to 58). Three patients with -altered CNS tumors achieved stable disease >6 months.
CONCLUSION
Ulixertinib, a novel targeted agent with no previous pediatric data, was successfully evaluated in a national precision medicine basket trial. The pediatric RP2D of ulixertinib is 260 mg/m/dose orally twice a day. Limited single-agent efficacy was observed in a biomarker-selected cohort of refractory pediatric tumors.
Topics: Humans; Adolescent; Child; Female; Male; Young Adult; Child, Preschool; Neoplasms; Infant; United States; Mitogen-Activated Protein Kinases; National Cancer Institute (U.S.); MAP Kinase Signaling System; Aminopyridines; Pyrroles
PubMed: 38935895
DOI: 10.1200/PO.24.00103 -
ACS Applied Materials & Interfaces Jun 2024An alarming increase in the use of pesticides and organoarsenic compounds and their toxic impacts on the environment have inspired us to develop a selective and highly...
Reusable MOF-Coated Chitosan@Paper Strip Composite for Real-Time Monitoring of Pesticide Pendimethalin and Organoarsenic Feed Additive Roxarsone Levels in Environmental Water, Food, and Vegetable Samples.
An alarming increase in the use of pesticides and organoarsenic compounds and their toxic impacts on the environment have inspired us to develop a selective and highly sensitive sensor for the detection of these pollutants. Herein, a bio-friendly, low-cost Al-based luminescent metal-organic framework ()-based fluorescent material is demonstrated that helps in sustaining water quality by rapid monitoring and quantification of a long-established pesticide (pendimethalin) and a widely employed organoarsenic feed additive (roxarsone). A pyridine-functionalized porous aluminum-based metal-organic framework (Al-MOF) was solvothermally synthesized. After activation, it was used for fast (<10 s) and selective turn-off detection of roxarsone and pendimethalin over other competitive analytes. This is the first MOF-based recyclable sensor for pendimethalin with a remarkably low limit of detection (LOD, 14.4 nM). Real-time effectiveness in detection of pendimethalin in various vegetable and food extracts was successfully verified. Moreover, the aqueous-phase recyclable detection of roxarsone with an ultralow detection limit (13.1 nM) makes it a potential candidate for real-time application. The detection limits for roxarsone and pendimethalin are lower than the existing luminescent material based sensors. Furthermore, the detection of roxarsone in different environmental water and a wide pH range with a good recovery percentage was demonstrated. In addition, a cheap and bio-friendly strip composite was prepared and successfully employed for the hands-on detection of pendimethalin and roxarsone. The turn-off behavior of in the presence of pendimethalin and roxarsone was examined systematically, and plausible mechanistic pathways were proposed with the help of multiple experimental evidences.
PubMed: 38935865
DOI: 10.1021/acsami.4c08083 -
Journal of the American Chemical Society Jun 2024The incorporation of three-dimensional structures into drug molecules has demonstrated significant improvements in clinical success. Late-stage saturation of drug...
The incorporation of three-dimensional structures into drug molecules has demonstrated significant improvements in clinical success. Late-stage saturation of drug molecules provides a direct pathway for this transformation. However, achieving selective and controllable reduction of aromatic rings remains challenging, particularly when multiple aromatic rings coexist. Herein, we present the switchable and chemoselective hydrogenation of benzene and pyridine rings. The utility of the protocol has been comprehensively investigated in diversified substrates with the assistance of a fragment-screening technique. This approach provides convenient access to a diverse array of cyclohexane and piperidine compounds, prevalent in various bioactive molecules and drugs. Furthermore, it discloses promising avenues for applications in the late-stage switchable saturation of drugs, facilitating an increase in the fraction of sp-carbons which holds the potential to enhance the medicinal properties of drugs.
PubMed: 38934861
DOI: 10.1021/jacs.4c05883 -
Virulence Dec 2024The implementation of pretreatment drug-resistance (PDR) surveillance among people living with HIV-1 (PLWH) is a top priority in countries using efavirenz...
The implementation of pretreatment drug-resistance (PDR) surveillance among people living with HIV-1 (PLWH) is a top priority in countries using efavirenz (EFV)/nevirapine (NVP) for first-line ART. In this study, we assessed the prevalence of PDR among PLWH in Shanghai, China during 2017-2021, and to reveal PDR transmission between Shanghai and other regions of China. A total of 5050 PLWH not on ART during 2017-2021 were included. Partial HIV-1 sequences were amplified, sequenced, and analysed for drug-resistance mutations (DRMs). Besides, transmission network of PDR variants was inferred using HIV-TRACE. The overall prevalence of PDR was 4.8% (242/5050; 95% CI, 4.2-5.4). Prevalence of NNRTI-associated PDR was 3.9% (95% CI, 3.4-4.5), higher than those of NRTI-associated (0.8%; 95% CI, 0.5-1.1) and PI-associated PDR (0.9%; 95% CI, 0.6-1.2). High prevalence of PDR (especially high-level resistance) to EFV (132/5050, 2.6%) and NVP (137/5050, 2.7%) were found. CRF01_AE (46.0%) was the predominant HIV-1 genotype with any DRMs, followed by CRF55_01B (21.0%), and CRF07_BC (15.1%). Two NRTI-associated (S68G/N/R and T215A/N/S/Y), five NNRTI-associated (V179D/E/T/L, K103N/R/S/T, E138A/G/K, V106M/I/A and Y181C/I) and two PI-associated mutations (M46I/L/V and Q58E) were the most common observed DRMs in PDR patients in Shanghai. The vast majority of S68G occurred in CRF01_AE (45%). M46I/L/V and Q58E showed a relatively high prevalence in CRF01_AE (4.1%) and CRF07_BC (12.6%). Transmission network analyses demonstrated cross-regional transmission links of PDR variants between Shanghai and other regions of China, which was mainly driven by the potential low-level DRM V179D/E. These results provide crucial information for clinical decision making of first-line ART in PLWH with PDR.
Topics: Humans; China; HIV-1; HIV Infections; Male; Drug Resistance, Viral; Female; Prevalence; Adult; Middle Aged; Anti-HIV Agents; Mutation; Young Adult; Cyclopropanes; Alkynes; Benzoxazines; Adolescent; Genotype; Nevirapine; Aged
PubMed: 38934465
DOI: 10.1080/21505594.2024.2373105 -
Angewandte Chemie (International Ed. in... Jun 2024We show an unexpected aggregation phenomenon of a long oligoyne (Py[16]) with 16 contiguous triple bonds and endcapped with bulky...
We show an unexpected aggregation phenomenon of a long oligoyne (Py[16]) with 16 contiguous triple bonds and endcapped with bulky 3,5-bi(3,5-bis-tert-butylphenyl)pyridine groups. Aggregation of 1D p-conjugated oligoyne chains is rare, given the minimal p-p intermolecular interactions of the weakly polarizable polyyne chain, as well as its flexibility that works against self assembly. In dilute solutions, the reversible aggregation of Py[16] initiates at low temperature in the range of 140-180 K, and is not observed for shorter oligoynes in this series. Cryogenic UV-Vis electronic absorption spectra and vibrational Raman spectra with different laser wavelength lines tuning from in-resonance to off-resonance conditions have been used to extract the vibrational features characterizing the Monomer and aggregate species. Theoretical calculations complement the spectroscopic findings.
PubMed: 38934233
DOI: 10.1002/anie.202404014 -
Frontiers in Endocrinology 2024Tryptophan's (Trp) metabolites are undervalued markers of human health. Their serum concentrations are modified by physical exercise and other factors, among which...
INTRODUCTION
Tryptophan's (Trp) metabolites are undervalued markers of human health. Their serum concentrations are modified by physical exercise and other factors, among which fasting has a well-documented role. Although this mechanism is hardly explored, thus, the study aimed to determine the effect of the 8-day fasting period and the impact of such a procedure on a single bout of an endurance exercise on the concentration of kynurenine pathway (KP) metabolites.
METHODS
10 participants fasted for 8 days, and 10 as a control group participated in the study. The exercise was performed at baseline after an overnight fast and repeated post 8 days.
RESULTS
The 8 days of fasting increased the resting 3-hydroxy-L-kynurenine (3HK), picolinic acid (PA), kynurenic acid (KYNA), and xanthurenic acid (XA) serum concentration. Also elevated phenylalanine (Phe) and tyrosine (Tyr) levels were recorded, suggesting expanded proteolysis of muscle proteins. In turn, physical activity caused a decrease in the concentration of 3-hydroxyanthranilic acid (3HAA) and PA after fasting. The obtained results were not recorded in controls.
CONCLUSION
The results of this study show that the health-promoting effects of fasting are associated with changes in the KYN pathway. The increase in the concentration of PA and XA metabolites following fasting is capable of penetrating the blood-brain barrier, and KYNA, which initiates several beneficial changes, supports this assumption.
Topics: Humans; Male; Fasting; Kynurenine; Exercise; Adult; Young Adult; Rest; Healthy Volunteers; Kynurenic Acid; Tryptophan; Biomarkers; Picolinic Acids
PubMed: 38933822
DOI: 10.3389/fendo.2024.1403491 -
The Pan African Medical Journal 2024tuberculosis (TB) and Human Immunodeficiency Virus (HIV) remain major public health threats globally and worse when they co-exist in susceptible individuals. The study...
INTRODUCTION
tuberculosis (TB) and Human Immunodeficiency Virus (HIV) remain major public health threats globally and worse when they co-exist in susceptible individuals. The study examined TB treatment outcomes and their predictive factors among people living with HIV (PLHIVs).
METHODS
a review of TB/HIV co-infected patients who had TB treatments across comprehensive antiretroviral therapy (ART) sites with ≥500 patients was conducted in seven United States of America President's Emergency Plan for AIDS Relief (PEPFAR)-supported States in Nigeria. Data on patient background, HIV and TB care, and TB treatment outcomes were collected using an Excel abstraction template. The data was analyzed using SPSS and an association was examined using a chi-square test while binary logistic regression was used to determine predictors of TB treatment outcomes (P< 0.05).
RESULTS
two thousand six hundred and fifty-two co-infected patients participated in the study. The mean age of participants was 37 ± 14 years. A majority had TB treatment success (cured = 1059 (39.9%), completed = 1186 (44.7%)). Participants who had pulmonary TB, virally suppressed and commenced isoniazid (INH) before TB diagnosis were more likely to have a favorable TB treatment outcome compared to those who had extrapulmonary TB (AOR = 7.110, 95% CI = 1.506 - 33.565), virally unsuppressed (AOR = 1.677, 95% CI = 1.036 - 2.716) or did not commence INH before TB diagnosis (AOR = 1.486, 95% CI = 1.047 - 2.109).
CONCLUSION
site of infection, immune status, exposure to ART, and INH prophylaxis were found to predict TB treatment outcomes among PLHIVs. Stakeholders should ensure early commencement of ART and INH prophylaxis for PLHIVs.
Topics: Humans; Nigeria; HIV Infections; Adult; Female; Antitubercular Agents; Male; Tuberculosis; Middle Aged; Coinfection; Treatment Outcome; Young Adult; Anti-HIV Agents; Isoniazid; Retrospective Studies; Tuberculosis, Pulmonary
PubMed: 38933432
DOI: 10.11604/pamj.2024.47.149.35719 -
AIDS (London, England) Jul 2024
Topics: Humans; Female; Pregnancy; Pyridones; HIV Infections; Pregnancy Complications, Infectious; Tenofovir; Anti-HIV Agents; Oxazines; Heterocyclic Compounds, 3-Ring; Lamivudine; Piperazines; Treatment Outcome
PubMed: 38932745
DOI: 10.1097/QAD.0000000000003911