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Cinnamomum camphora chvar. borneol, a rare camphor tree variant recently identified in China, is distinguished by its high concentration of D-borneol, also known as " plant gold" due to its significant value. The essential oil extracted from this variant,rich in monoterpenes and sesquiterpenes, demonstrates a broad spectrum of pharmacological activities, including analgesic, antiinflammatory, antioxidant, cognition-enhancing, anti-bacterial, and insecticidal effects. These properties, underscored by extensive research, highlight the oil's potential in the biomedical, chemical, and food sectors as a valuable commodity. Nonetheless, the safety profile of this valuable oil remains poorly characterized, with its chemical composition and therapeutic efficacy subject to variations in the factors like geographic origin, harvesting timing, part used for extraction, and processing techniques. Such variability poses challenges to its clinical application and hampers the efficient exploitation of this resource. This review synthesizes current studies on C. camphora chvar. borneol essential oil and provides a detailed examination of its chemical and pharmacological profiles. In this study, we discuss existing research gaps and propose strategies for advancing its clinical use and industrial application, aiming to provide a foundational reference for future investigations and the resolution of its commercial and therapeutic challenges.
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Canfanos , Cinnamomum camphora , Óleos Voláteis , Cinnamomum camphora/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Humanos , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologiaRESUMO
Synthetic aromatic esters, widely employed in agriculture, food, and chemical industries, have become emerging environmental pollutants due to their strong hydrophobicity and poor bioavailability. This study attempted to address this issue by extracellularly expressing the promiscuous aminopeptidase (Aps) from Pseudomonas aeruginosa GF31 in B. subtilis, achieving an impressive enzyme activity of 13.7 U/mg. Notably, we have demonstrated, for the first time, the Aps-mediated degradation of diverse aromatic esters, including but not limited to pyrethroids, phthalates, and parabens. A biochemical characterization of Aps reveals its esterase properties and a broader spectrum of substrate profiles. The degradation rates of p-nitrobenzene esters (p-NB) with different side chain structures vary under the action of Aps, showing a preference for substrates with relatively longer alkyl side chains. The structure-dependent degradability aligns well with the binding energies between Aps and p-NB. Molecular docking and enzyme-substrate interaction elucidate that hydrogen bonding, hydrophobic interactions, and π-π stacking collectively stabilize the enzyme-substrate conformation, promoting substrate hydrolysis. These findings provide new insights into the enzymatic degradation of aromatic ester pollutants, laying a foundation for the further development and modification of promiscuous enzymes.
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Aminopeptidases , Proteínas de Bactérias , Ésteres , Simulação de Acoplamento Molecular , Pseudomonas aeruginosa , Hidrólise , Ésteres/metabolismo , Ésteres/química , Aminopeptidases/metabolismo , Aminopeptidases/química , Aminopeptidases/genética , Especificidade por Substrato , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Pseudomonas aeruginosa/enzimologia , Biodegradação Ambiental , Cinética , Bacillus subtilis/enzimologia , Ácidos Ftálicos/química , Ácidos Ftálicos/metabolismoRESUMO
Purpose: We aimed to explore the effects of percutaneous coronary intervention (PCI) on the ophthalmic artery (OA) hemodynamics in patients with acute coronary syndrome (ACS). Methods: A total of 73 participants (Group0: healthy controls, Group1: Patients with ACS underwent PCI < 3 months, Group2: Patients with ACS underwent PCI ≥ 3 months) were enrolled. Computed tomographic angiography images were used to construct three-dimensional models of participants' OAs. Numerical simulations based on computational fluid dynamics were used to acquire hemodynamic parameters. Results: The angle between the OA and internal carotid artery in Group2 was significantly larger compared with Group0 and Group1 (P = 0.003 and P = 0.044). Hemodynamic simulation showed a significantly slower OA blood velocity in Group1 than in the control (P < 0.001) and Group2 (P = 0.033). Lower wall shear stress was found in Group1 than that in control (P = 0.040). Patients after PCI had a higher wall pressure than healthy controls (P = 0.012 and P = 0.004). Mass flow ratios were decreased in Group1 and Group2 (P = 0.021 and P = 0.002). The hemodynamic parameters of OA were correlated with several clinical indicators. Conclusions: The OA blood flow velocity of patients with ACS after PCI initially slowed down, which increased the risk of plaque formation, and then showed an increasing trend. There was a correlation between OA hemodynamic parameters and clinical indexes related to cardiac stress. Ischemia-reperfusion injury and changes in blood flow status after PCI may affect OA morphology and hemodynamics, leading to ocular lesions. Trial registration: ChiCTR2100050428.
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Tumor recurrence and chronic bacterial infection constitute two major criteria in postsurgical intervention for malignant melanoma. One plausible strategy is the equipment of consolidation therapy after surgery, which relies on adjuvants to eliminate the residual tumor cells and inhibit bacterial growth. Until now, a number of proof-of-concept hybrid nanoadjuvants have been proposed to combat tumor recurrence and postsurgical bacterial infection, which may suffer from the potential bio-unsafety or involve complex design and synthesis. The batch-to-batch inconsistencies in drug composition further delay the clinical trials. To circumvent these issues, herein we develop a programmable strategy to generate lipopeptide nanotherapeutics with identical constitution for tandem intervention of postsurgical bacterial infection and cancer recurrence of melanoma. Increasing the number of hydrophobic linoleic acid within lipopeptides has been found to be a simple and practical strategy to improve the therapeutic outcomes for both tumor cells and bacteria. Self-assembled lipopeptide nanotherapeutics with two linoleic acid molecules possesses excellent antitumor activity and antimicrobial function toward both susceptible strains and drug-resistant bacteria. Arising from the incorporation of unsaturated linoleic acid, the unavoidable hemolysis of cationic peptide drugs was effectively alleviated. In vivo therapeutic abilities of postsurgical infection and tumor recurrence were investigated in BALB/c nude mice bearing a B16-F10 tumor model, with an incomplete surgical resection and in situ infection by methicillin-resistant Staphylococcus aureus (MRSA). Self-assembled lipopeptide nanotherapeutics could effectively inhibit cancer cell growth and bacterial infection, as well as promote wound healing. The easily scalable large-scale production, broad-spectrum antitumor and antibacterial bioactivities as well as fixed component endows lipopeptide nanotherapeutics as promising adjuvants for clinically postsurgical therapy of melanoma.
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Temozolomide (TMZ) is an oral DNA-alkylating drug used in colorectal cancer (CRC) chemotherapy. In this work, we proposed a safe and biomimetic platform for macrophages-targeted delivery of TMZ and O6-benzylguanine (O6-BG). TMZ was loaded in poly (D, l-lactide-coglycolide) (PLGA) nanoparticles, followed by sequential coating with O6-BG-grafted chitosan (BG-CS) layers and yeast shell walls (YSW) via layer-by-layer assembly (LBL) process, forming TMZ@P-BG/YSW biohybrids. Due to the yeast cell membrane-camouflage, TMZ@P-BG/YSW particles exhibited significantly enhanced colloidal stability as well as low premature drug leakage in simulated gastrointestinal conditions. In vitro drug release profiles of TMZ@P-BG/YSW particles revealed noticeable higher TMZ release in simulated tumor acidic environment within 72 h. Meanwhile, O6-BG could down-regulate MGMT expression in CT26 colon carcinoma cells, ultimately facilitating TMZ-induced tumor cell death. After oral delivery of yeast cell membrane-camouflaged particles containing fluorescent tracer (Cy5), TMZ@P-BG/YSW and bare YSW displayed high retention time of 12 h in the colon and small intestine (ileum). Correspondingly, oral gavage administration of TMZ@P-BG/YSW particles afforded favorable tumor-specific retention and superior tumor growth inhibition. Overall, TMZ@P-BG/YSW is validated to be a safe, targetable and effective formulation, paving a new avenue towards highly effective and precise treatment of malignancies.
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Nanopartículas , Neoplasias , Dacarbazina/farmacologia , Saccharomyces cerevisiae , O(6)-Metilguanina-DNA Metiltransferase , Temozolomida , Membrana Celular/metabolismo , Antineoplásicos Alquilantes/farmacologia , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológicoRESUMO
Two haloargentate hybrids, [Me-dabco]Ag2X3 (Me-dabco = 1-methyl-1,4-diazabicyclo-[2.2.2]octan-1-ium, X = I (1) or Br (2)), with the same formula but different structures have been synthesized by a slow evaporation method and characterized by microanalysis, infrared spectroscopy, thermogravimetric, and powder X-ray diffraction techniques. Hybrid 1 consists of completely isolated [Ag4I6]2- clusters, while hybrid 2 exhibits a complicated one-dimensional (1D) chain structure formed by four different configurations of neutral chains and two dissimilar configurations of anionic chains. Hybrid 2 undergoes two reversible order-disorder phase transitions, while hybrid 1 displays one reversible and one irreversible structural phase transition. Both 1 and 2 displayed step-like dielectric anomalies in the vicinity of the phase transition temperature. The corresponding dielectric constants in the high dielectric states are approximately 13 and 6 times higher than those in the low dielectric states for 1 and 2, respectively. Interestingly, the subtle change of halides from I- to Br- significantly affects the aggregated structure of haloargentate, the phase transition, and dielectric behaviors, revealing the typical 'butterfly effect' with the ion radii of halides in these two haloargentate hybrids.
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Three novel actinomycete strains, designated TRM66264-DLMT, TRM88002T and TRM88003T, were isolated by using polyaspartic acid as a water-retaining agent for the enrichment in situ. The 16S rRNA gene sequence and phylogenetic analyses of three strains indicated that they belonged to the genus Actinoplanes. The phylogenetically closest strains of TRM66264-DLMT, TRM88002T and TRM88003T were Actinoplanes bogorensis LIPI11-2-Ac043T (98.4â%), Actinoplanes abujensis A4029T (98.0â%) and Actinoplanes ferrugineus IFO15555T (98.1â%), respectively. The major polar lipids of strains TRM66264-DLMT and TRM88002T were phosphatidylethanolamine and disphosphatidylglycerol, while strain TRM88003T only had phosphatidylethanolamine. The predominant menaquinones of strain TRM66264-DLMT were identified as MK-9(H4) and MK-9 (H6). Strains TRM88002T and TRM88003T had MK-9(H4). The cell-wall peptidoglycan of three strains contained meso-diaminopimelic acid. The whole-cell sugars of strain TRM66264-DLMT were identified as arabinose, glucose, galactose and xylose. Strains TRM88002T and TRM88003T mainly had arabinose and glucose. The DNA G+C content of strains TRM66264-DLMT, TRM88002T and TRM88003T were 70.48, 70.46 and 70.64âmol%, respectively. Genotypic and phenotypic analysis confirmed that all three strains sre new members of the genus Acinoplanes. Therefore, it is proposed that strains TRM66264-DLMT, TRM88002T and TRM88003T represent three novel species of the genus Actinoplanes, for which the names Actinoplanes polyasparticus sp. nov. (type strain TRM66264-DLMT=CCTCC AA 2021015T=LMG 32389T), Actinoplanes hotanensis sp. nov. (type strain TRM88002T=CCTCC AA 2021036T=LMG 32621T) and Actinoplanes aksuensis sp. nov. (type strain TRM88003T=CCTCC AA 2021037 T=LMG 32622T) are proposed.
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Actinoplanes , Ácidos Graxos , Ácidos Graxos/química , Fosfatidiletanolaminas , Água , Filogenia , RNA Ribossômico 16S/genética , Arabinose , Análise de Sequência de DNA , DNA Bacteriano/genética , Composição de Bases , Técnicas de Tipagem Bacteriana , Glucose , Vitamina K 2 , Fosfolipídeos/análiseRESUMO
Developing new high-performance electrode materials for improving the energy density of supercapacitors is an important task. Herein, a new three-dimensional (3D) metal-orgainc framework (MOF) [Mn(BGPD)(H2O)2] (Mn-BGPD; BGPD = N,N'-bis(glycinyl)pyromellitic diimide) was synthesized. When Mn-BGPD is used as the electrode material of supercapacitors, in a three-electrode setup, it shows an outstanding specific capacitance of 832.6 F g-1 at a current density of 1 A g-1. The asymmetrical supercapacitor of Mn-BGPD shows an attractive specific capacitance of 100 F g-1 at 1 A g-1, which corresponds to an excellent energy density of 35.5 W h kg-1. Moreover, better cycling stability with a capacitance retention of 46.7% is also shown. The high electrochemical performance makes Mn-BGPD a very promising electrode material for supercapacitors.
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OBJECTIVE: To investigate the preparation of novel nanoliposomes (Borneol Angelica Polysaccharide Liposomes, BAPL) for anti-cerebral ischaemia and verify its curative effects and mechanism. METHODS: By applying a uniform experiment design to investigate the fitting combination of BAPL. Encapsulation Efficiency Evaluation of BAPL Preparation; Particle Size and Surface Potential Evaluation of BAPL Biological activity; Cerebral ischaemia models of rats Evaluation of BAPL curative effects and mechanism. RESULTS: (1) The fitting combination of lecithin, Cholesterol, AP mass and the borneol mass was 60 mg, 60 mg, 45 mg and 5 mg. the highest encapsulation efficiency was 80.4%, the particle size was 179.1 nm, and the surface zeta potential was -17.2 mV. It conforms to the nano-material standards. (2) The results of animal experiments show that: In the BAPL group, the infarct volume of TTC staining was significantly decreased, and the expression levels of NF-κBp65, TLR-4, IL-8, IL-6, IL-1ß in brain tissue were significantly decreased, while the expression levels of ZO-1, ZO-2, IL-10 were significantly increased after cerebral ischaemia-reperfusion. CONCLUSION: BAPL is a novel nano and effective material for anti-cerebral ischaemia.
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Isquemia Encefálica , Lipossomos , Ratos , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia , Polissacarídeos/farmacologiaRESUMO
Water-saving is one of the most important problems in agricultural development, especially in arid and semi-arid areas. The effects of polyaspartic acid (PASP) on soil water storage, soil microbial community, soil physiochemical properties, cotton yield and fiber quality were studied to find water-saving material utilized in cotton field. The experiment was divided into two parts, the first part concerned the direct application of three different amounts of PASP under field conditions. In the second part, PASP was mixed with soil in different proportions and the mixtures were put into bottles, which were then buried in the cotton field. The application of PASP improved the water-holding capacity and thus increased water content available to the cotton root system in the cotton field for a long time, and significantly (p < 0.05) increased the content of soil organic matter, available P and ammonium-N. Relative abundances of Methylophaga, Sphingomonas, Cupriavidus, Pseudeurotium, Fusarium and Nectria were significantly affected by applying PASP. Compared to the control group, 15, 75 and 150 kg ha-1 of PASP increased seed cotton yield by 3.94, 8.31 and 7.71%, respectively. The application of PASP also increased the reflectance degree, Micronaire and short fiber index of cotton. These results suggested that 75 kg ha-1 of PASP can be appropriate to alleviate drought stress in arid and semi-arid areas.
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Solo , Água , Solo/química , Microbiologia do Solo , AgriculturaRESUMO
The nonselective membrane disruption of antimicrobial peptides (AMPs) helps in combating the antibacterial resistance. But their overall positive charges lead to undesirable hemolysis and toxicity toward normal living cells, as well as the rapid clearance from blood circulation. In consequence, developing smart AMPs to optimize the antimicrobial outcomes is highly urgent. Relying on the local acidity of microbial infection sites, in this work, we designed an acidity-triggered charge reversal nanotherapeutics with adaptable geometrical morphology for bacterial targeting and optimized therapy. C16-A3K4-CONH2 was proposed and the ε-amino groups in lysine residues were acylated by dimethylmaleic amide (DMA), enabling the generated C16-A3K4(DMA)-CONH2 to self-assemble into negatively charged spherical nanostructure, which relieved the protein adsorption and prolonged blood circulation in vivo. After the access of C16-A3K4(DMA)-CONH2 into the microbial infection sites, acid-sensitive ß-carboxylic amide would hydrolyze to regenerate the positive C16-A3K4-CONH2 to destabilize the negatively charged bacterial membrane. In the meanwhile, attractively, the self-assembled spherical nanoparticle transformed to rod-like nanostructure, which was in favor of the efficient binding with bacterial membranes due to the larger contact area. Our results showed that the acid-activated AMP nanotherapeutics exhibited strong and broad-spectrum antimicrobial activities against Yeast, Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and methicillin-resistant Staphylococcus aureus (MRSA). Moreover, the biocompatible lipopeptide nanotherapeutics dramatically improved the dermapostasis caused by bacterial infection. The strategy of merging pathology-activated therapeutic function and morphological adaptation to augment therapeutic outcomes shows the great potential for bacterial inhibition. STATEMENT OF SIGNIFICANCE: The overall positive charges of antimicrobial peptides (AMPs) lead to undesirable hemolysis and nonselective toxicity, as well as the rapid clearance from blood circulation. Infection-activated lipopeptide nanotherapeutics with adaptable geometrical morphology were developed to address these issues. The self-assembled lipopeptide was pre-decorated to reverse the positive charge to reduce the hemolysis and nonselective cytotoxicity. After accessing the acidic infection sites, the nanotherapeutics recovered the positive charge to destabilize negatively charged bacterial membranes. Meanwhile, the morphology of self-assembled nanotherapeutics transformed from spherical nanoparticles to rod-like nanostructures in the lesion site, facilitating the improved association with bacterial membranes to boost the therapeutic efficiency. These results provide new design rationale for AMPs developed for bacterial inhibition.
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Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Humanos , Lipopeptídeos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Testes de Sensibilidade Microbiana , Anti-Infecciosos/farmacologia , Bactérias , Hemólise , Amidas , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
Objective: To compare and analyze the pass rate and screening strategy of hearing rescreening for newborns with high risk factors. Methods: Retrospective chart review of high-risk newborns who failed their initial newborn hearing screen and subsequently underwent secondary hearing tests from June 2011 to June 2018 in Guangzhou Women and Children's Medical Center were performed. Results: Eight hundred and sixty-eight newborns with high risk factors were included in the study. The 57-70 days (83.5%) and 71-84 days (83.4%) group had the highest pass rate compared with 42-56 days (75.8%) and < 42 days (68.3%) group. As for different screening strategies, the pass rate of OAE(otoacoustic emissions), AABR (auto auditory brainstem response) and OAE + AABR was the highest in 57-70 days group and 71-84 days group, respectively. The OAE + AABR had the lowest pass rate compared to the other two modalities. When the pass rate was compared as different risk factors, the 57-70 days and 71-84 days group also had the highest pass rate compared with 42-56 days and < 42 days group and the pass rate had no significant differences among various risk factors group. Conclusion: Our results showed that all the pass rate of OAE, AABR and OAE + AABR was the highest in 57-70 days group and 71-84 days group with significant difference, suggesting that the delayed screening time (>57 days) may increase the re-screening pass rate and reduce anxiety of parents, which is of great significance for clinical work.
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OBJECTIVE: To evaluate the feasibility and efficacy of computed tomography (CT)-guided radiofrequency ablation (RFA) of cervical intervertebral discs for the treatment of discogenic cervicogenic headache (CEH). BACKGROUND: Some patients with CEH experience no obvious therapeutic effect after conventional therapy, particularly patients with refractory CEH originating from abnormal cervical intervertebral discs. Treatment for this type of CEH remains poorly characterized. METHODS: Using a single intervention arm, pretest/posttest design, we retrospectively analyzed the data of patients who underwent CT-guided RFA of cervical intervertebral discs for CEH at the Pain Medicine Center of Zhejiang Provincial People's Hospital from January 2017 to April 2021. If conservative treatment failed in patients with discogenic CEH, we classified the patients as having refractory CEH and performed RFA of cervical intervertebral discs. We used a numeric rating scale (NRS) to assess pain intensity for 6 months. We also compared therapeutic outcome of patients with different characteristics. RESULTS: A total of 44 patients who underwent CT-guided RFA of cervical intervertebral discs were enrolled and 41 of them were analyzed in the present study. The preoperative median (25th, 75th) NRS score was 4 (4, 5), and it was significantly reduced to 1 (0, 4) 6 months after RFA (p < 0.001). The number of patients with ≥50% of their pain relieved after 6 months was 28 of 41 (68%). No serious treatment-related complications occurred in this study. Compared with single-level RFA, multi-level RFA shows greater effects on pain intensity reduction (p = 0.032) and pain relief rate (p = 0.047) of patients. CONCLUSION: In patients who have discogenic CEH, CT-guided RFA of the cervical intervertebral discs appears to be a promising treatment with no serious complications.
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Ablação por Cateter , Transtornos da Cefaleia , Disco Intervertebral , Cefaleia Pós-Traumática , Transtornos da Cefaleia/complicações , Humanos , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/cirurgia , Dor/complicações , Cefaleia Pós-Traumática/diagnóstico por imagem , Cefaleia Pós-Traumática/etiologia , Cefaleia Pós-Traumática/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
The preparation of clean fuel or CO2 adsorbents using industrial and domestic garbage is an alternative way of meeting global energy needs and alleviating environmental problems. Herein, H2-mixed CH4 fuel and CaO-based CO2 sorbent were first prepared in one pot by the mechanochemical reaction of pretreated clamshell or eggshell wastes (carbon and calcium source) with calcium hydride (hydrogen source) at room temperature. In the above reactions, CH4 was the sole hydrocarbon product, and its yield reached 78.23%. The H2/CH4 ratio of the produced H2-mixed CH4 fuel was tunable according to the need by changing the reaction conditions. It is inspiring that the simultaneously formed solid CaO/carbon products were efficient CaO-based sorbents, which possessed a higher CO2 adsorption capacity (49.81-58.74 wt.%) at 650 °C and could maintain good adsorption stability in 30 carbonation/calcination cycles (average activity loss per cycle of only 1.6%). The three achievements of the idea are that it can simultaneously eliminate clamshell or eggshell wastes, obtain valuable clean fuel, and acquire efficient CaO-based sorbents.
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Compostos de Cálcio , Óxidos , Adsorção , Animais , Cálcio , Carbono , Dióxido de Carbono , Casca de Ovo , Hidrogenação , TemperaturaRESUMO
The short lifetime of singlet oxygen reduces its accumulation in the endoplasmic reticulum, which limits the output of photodynamic therapy. A nanodevice with functions of singlet oxygen production, storage and release can improve the lifetime of singlet oxygen for enhancing phototherapeutic efficacy.
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Fotoquimioterapia , Oxigênio Singlete , Fármacos Fotossensibilizantes/farmacologiaRESUMO
Low-dimensional organic-inorganic metal halides, especially lead-free perovskites, are attracting increasing attention because of their environmentally friendly processing, flexible structures, chemical stability, and promising nonlinear optical properties. Herein, we report a new stable polar 0D lead-free hybrid bismuth chloride to enable the second-harmonic generation (SHG) active material (BTA)3Bi2Cl9 (BTA = benzyltriethylammonium, C6H5CH2N(C2H5)3+) that was obtained by the antisolvent vapor diffusion method and crystallized in the polar Cc space group. Its structure features organic cations surrounded by face-sharing [Bi2Cl9]3- dimers. (BTA)3Bi2Cl9 exhibits a wide direct bandgap (3.21 eV) and a strong phase-matchable SHG conversion efficiency (1.39 × KDP). Theoretical calculation reveals that the SHG response is owing to the synergistic effect of distorted inorganic [Bi2Cl9]3- anions and polar organic BTA+ cations. This work not only enriches the family of organic-inorganic A3M2X9 (A = monovalent cations; M = trivalent metal ions; and X = halide ions) NLO crystals but also provides the possibilities for further designing novel lead-free semiconducting piezoelectric, pyroelectric and ferroelectric materials.
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An "antibiotic-free strategy" provides a viable option to address bacterial infections, especially for the "superbug" challenge. However, the undesirable antibacterial activity of antibiotic-free agents hinders their practical applications. In this study, we developed a combination antibacterial strategy of coupling peptide-drug therapy with chemodynamic therapy (CDT) to achieve the effective bacterial inhibition. An amphiphilic oligopeptide (LAOOH-OPA) containing a therapeutic unit of D(KLAK)2 peptide and a hydrophobic linoleic acid hydroperoxide (LAHP) was designed. The positively charged D(KLAK)2 peptide with an α-helical conformation enabled rapid binding with microbial cells via electrostatic interaction and subsequent membrane insertion to deactivate the bacterial membrane. When triggered by Fe2+, moreover, LAHP could generate singlet oxygen (1O2) to elicit lipid bilayer leakage for enhanced bacteria inhibition. In vitro assays demonstrated that the combination strategy possessed excellent antimicrobial activity not only merely toward susceptible strains (Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli) but also toward methicillin-resistant Staphylococcus aureus (MRSA). On the mouse skin abscess model induced by S. aureus, self-assembled LAOOH-OPA exhibited a more significant bacteria reduction (1.4 log10 reduction) in the bioburden compared to that of the standard vancomycin (0.9 log10 reduction) without apparent systemic side effects. This combination antibacterial strategy shows great potential for effective bacterial inhibition.
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Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Ácidos Linoleicos/uso terapêutico , Peróxidos Lipídicos/uso terapêutico , Nanopartículas/uso terapêutico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Animais , Antibacterianos/toxicidade , Peptídeos Catiônicos Antimicrobianos/toxicidade , Desenho de Fármacos , Escherichia coli/efeitos dos fármacos , Feminino , Ácidos Linoleicos/toxicidade , Peróxidos Lipídicos/toxicidade , Camundongos Endogâmicos BALB C , Nanopartículas/toxicidade , Oxigênio Singlete/metabolismo , Staphylococcus aureus/efeitos dos fármacosRESUMO
The hypoxic tumor microenvironment is characterized by disordered vasculature and rapid proliferation of tumors, resulting from tumor invasion, progression and metastasis. The hypoxic conditions restrict efficiency of tumor therapies, such as chemotherapy, radiotherapy, phototherapy and immunotherapy, leading to serious results of tumor recurrence and high mortality. Recently, research has concentrated on developing functional nanomaterials to treat hypoxic tumors. In this review, we categorize such nanomaterials into (i) nanomaterials that elevate oxygen levels in tumors for enhanced oxygen-dependent tumor therapy and (ii) nanomaterials with diminished oxygen dependence for hypoxic tumor therapy. To elevate oxygen levels in tumors, oxygen-carrying nanomaterials, oxygen-generating nanomaterials and oxygen-economizing nanomaterials can be used. To diminish oxygen dependence of nanomaterials for hypoxic tumor therapy, therapeutic gas-generating nanomaterials and radical-generating nanomaterials can be used. The biocompatibility and therapeutic efficacy of these nanomaterials are discussed.
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With the emergence of drug resistance in Western medicine, the repeated administration of clinical first-line drugs becomes more severe. There are many factors leading to multidrug resistance(MDR), so it is very difficult to solve the problem. Since traditional Chinese medicine(TCM) has been used in the field of MDR in recent years, the research on the transporter-associated drug resistance and intervention of TCM has gradually become a hot spot. Therefore, in order to further explore the relationships among drug resistance, transporters, and TCM intervention, we review the relevant research progress in recent years and comb the achievements and limitations of this research at present. In the end, we put forward the research direction of changing body's ADME through the host's transporters and gastrointestinal flora, which provides new ideas for future research.
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Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Resistência a Múltiplos Medicamentos , Proteínas de Membrana Transportadoras/genéticaRESUMO
The eCO2RR activity is correlated to the internal structural character of the catalyst. We employed two types of structural models of porphyrin-based MOFs of PCN-222(Cu) and PCN-224(Cu) into heterogeneous catalysis to illustrate the effect of structural factors on the eCO2RR performance. The composite catalyst PCN-222(Cu)/C displays better activity and selectivity (η = 450 mV, FEHCOOH = 44.3%, j = 3.2 mA cm-2) than PCN-224(Cu)/C (η = 450 mV, FEHCOOH = 34.1%, j = 2.4 mA cm-2) for the CO2 reduction to HCOOH in the range of -0.7--0.9 V (vs. RHE) due to its higher BET surface area, CO2 uptake, and a larger pore diameter. It is interesting that PCN-224(Cu)/C displays better performance in the range of -0.4--0.6 V (vs. RHE) due to its greater heat of adsorption, Qst and a higher affinity for CO2 molecule, which could promote the capture of CO2 onto the exposed active sites. As a result, PCN-224(Cu)/C exhibits better stability for the long-term electrolysis.