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1.
Proc Natl Acad Sci U S A ; 121(17): e2320713121, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38621119

RESUMO

As the SARS-CoV-2 virus continues to spread and mutate, it remains important to focus not only on preventing spread through vaccination but also on treating infection with direct-acting antivirals (DAA). The approval of Paxlovid, a SARS-CoV-2 main protease (Mpro) DAA, has been significant for treatment of patients. A limitation of this DAA, however, is that the antiviral component, nirmatrelvir, is rapidly metabolized and requires inclusion of a CYP450 3A4 metabolic inhibitor, ritonavir, to boost levels of the active drug. Serious drug-drug interactions can occur with Paxlovid for patients who are also taking other medications metabolized by CYP4503A4, particularly transplant or otherwise immunocompromised patients who are most at risk for SARS-CoV-2 infection and the development of severe symptoms. Developing an alternative antiviral with improved pharmacological properties is critical for treatment of these patients. By using a computational and structure-guided approach, we were able to optimize a 100 to 250 µM screening hit to a potent nanomolar inhibitor and lead compound, Mpro61. In this study, we further evaluate Mpro61 as a lead compound, starting with examination of its mode of binding to SARS-CoV-2 Mpro. In vitro pharmacological profiling established a lack of off-target effects, particularly CYP450 3A4 inhibition, as well as potential for synergy with the currently approved alternate antiviral, molnupiravir. Development and subsequent testing of a capsule formulation for oral dosing of Mpro61 in B6-K18-hACE2 mice demonstrated favorable pharmacological properties, efficacy, and synergy with molnupiravir, and complete recovery from subsequent challenge by SARS-CoV-2, establishing Mpro61 as a promising potential preclinical candidate.


Assuntos
Antivirais , Citidina/análogos & derivados , Hepatite C Crônica , Hidroxilaminas , Lactamas , Leucina , Nitrilas , Prolina , Ritonavir , Humanos , Animais , Camundongos , Antivirais/farmacologia , Protocolos Clínicos , Combinação de Medicamentos
2.
Nano Lett ; 24(6): 1959-1966, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38294858

RESUMO

Overall water splitting, as a critical approach to producing green hydrogen, is greatly impeded by the mass transfer of gaseous bubbles and dissolved gas molecules. Herein, a bifunctional superaerophilic/superaerophobic (SAL/SAB) NiFe layered-double-hydroxides (LDHs) electrode has been developed, which can drive H2 and O2 bubbles out of the reaction system by asymmetric Laplace pressure and accelerate dissolved gases diffusion through reducing their diffusion distance. Consequently, the SAL/SAB NiFe-LDHs electrode exhibits excellent HER activity with an overpotential of -76 mV at -10 mA cm-2 and outstanding oxygen evolution reaction activity with an overpotential of 253 mV at 100 mA cm-2. The bifunctional SAL/SAB NiFe-LDHs electrode is further utilized in overall water splitting, which can achieve 10 mA cm-2 with a cell voltage of 1.54 V. This work provides an efficient strategy to improve the efficiency of overall water splitting and can stimulate new electrode design in various gas-involved processes.

3.
J Am Chem Soc ; 146(15): 10599-10607, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38567740

RESUMO

The success of electrochemical CO2 reduction at high current densities hinges on precise interfacial transportation and the local concentration of gaseous CO2. However, the creation of efficient CO2 transportation channels remains an unexplored frontier. In this study, we design and synthesize hydrophobic porous Cu2O spheres with varying pore sizes to unveil the nanoporous channel's impact on gas transfer and triple-phase interfaces. The hydrophobic channels not only facilitate rapid CO2 transportation but also trap compressed CO2 bubbles to form abundant and stable triple-phase interfaces, which are crucial for high-current-density electrocatalysis. In CO2 electrolysis, in situ spectroscopy and density functional theory results reveal that atomic edges of concave surfaces promote C-C coupling via an energetically favorable OC-COH pathway, leading to overwhelming CO2-to-C2+ conversion. Leveraging optimal gas transportation and active site exposure, the hydrophobic porous Cu2O with a 240 nm pore size (P-Cu2O-240) stands out among all the samples and exhibits the best CO2-to-C2+ productivity with remarkable Faradaic efficiency and formation rate up to 75.3 ± 3.1% and 2518.2 ± 8.1 µmol h-1 cm-2, respectively. This study introduces a novel paradigm for efficient electrocatalysts that concurrently addresses active site design and gas-transfer challenges.

4.
J Am Chem Soc ; 146(33): 23121-23137, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-38980064

RESUMO

Addressing the global challenge of bacterial resistance demands innovative approaches, among which multitargeting is a widely used strategy. Current strategies of multitargeting, typically achieved through drug combinations or single agents inherently aiming at multiple targets, face challenges such as stringent pharmacokinetic and pharmacodynamic requirements and cytotoxicity concerns. In this report, we propose a bacterial-specific global disruption approach as a vastly expanded multitargeting strategy that effectively disrupts bacterial subcellular organization. This effect is achieved through a pioneering chemical design of ligand-receptor interaction-induced aggregation of small molecules, i.e., DNA-induced aggregation of a diarginine peptidomimetic within bacterial cells. These intracellular aggregates display affinity toward various proteins and thus substantially interfere with essential bacterial functions and rupture bacterial cell membranes in an "inside-out" manner, leading to robust antibacterial activities and suppression of drug resistance. Additionally, biochemical analysis of macromolecule binding affinity, cytoplasmic localization patterns, and bacterial stress responses suggests that this bacterial-specific intracellular aggregation mechanism is fundamentally different from nonselective classic DNA or membrane binding mechanisms. These mechanistic distinctions, along with the peptidomimetic's selective permeation of bacterial membranes, contribute to its favorable biocompatibility and pharmacokinetic properties, enabling its in vivo antimicrobial efficacy in several animal models, including mice-based superficial wound models, subcutaneous abscess models, and septicemia infection models. These results highlight the great promise of ligand-receptor interaction-induced intracellular aggregation in achieving a globally disruptive multitargeting effect, thereby offering potential applications in the treatment of malignant cells, including pathogens, tumor cells, and infected tissues.


Assuntos
Antibacterianos , Ligantes , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Camundongos , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana/efeitos dos fármacos , Peptidomiméticos/farmacologia , Peptidomiméticos/química , Separação de Fases
5.
Oncologist ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39226089

RESUMO

BACKGROUND: Alternating sequential administration of drugs may be a promising approach to overcome chemotherapy resistance in advanced pancreatic ductal adenocarcinoma (PDAC). METHODS: This study was an open-label, single-arm, and prospective trial included patients with untreated advanced PDAC. They received 2 cycles of NS regimen (nab-paclitaxel:125 mg/m2, intravenously injected on days 1 and 8, plus S-1:40-60 mg, orally twice per day for 1-14 days) followed by 2 cycles of GemOx regimen (gemcitabine, intravenously injected on days 1 and 8, and oxaliplatin: 130 mg/m2, intravenously injected on day 1). The primary efficacy endpoint was a progression-free survival rate at 6 months (PFSR-6m). The secondary efficacy endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Specific mRNA transcripts were used to explore survival associated genes. RESULTS: Forty-two patients received a minimum of one treatment cycle, and of these, 30 patients completed one alternating treatment consisting of 4 cycles. The PFSR-6m was 71% (95% CI = 58%-87%). The median PFS and OS were 6.53 months (95% CI = 6.03-8.43) and 11.4 months (95% CI = 9.8-14.4), respectively. Common grades 3-4 hematological AEs included neutropenia 30.9%, leukopenia 26.2%, anemia 2.4%, and thrombocytopenia in 11.9%. Patients with OS > 10 months showed high expression of HLA-DQA2 while melanoma-associated antigen genes (MAGE) were notably upregulated in patients with OS < 10 months. CONCLUSION: The alternating sequential administration of the NS and GemOx regimens may be a novel approach for first-line chemotherapy in patients with advanced PDAC requiring further study (ClinicalTrials.gov Identifier: ChiCTR1900024867).

6.
Opt Express ; 32(10): 18366-18378, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858994

RESUMO

Mode-pairing quantum key distribution (MP-QKD) holds great promise for the practical implementation of QKD in the near future. It combines the security advantages of measurement device independence while still being capable of breaking the Pirandola-Laurenza-Ottaviani-Banchi bound without the need for highly demanding phase-locking and phase-tracking technologies for deployment. In this work, we explore optimization strategies for MP-QKD in a wavelength-division multiplexing scenario. The simulation results reveal that incorporation of multiple wavelengths not only leads to a direct increase in key rate but also enhances the pairing efficiency by employing our novel pairing strategies among different wavelengths. As a result, our work provides a new avenue for the future application and development of MP-QKD.

7.
Glob Chang Biol ; 30(4): e17264, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38556774

RESUMO

Nutrient enrichment often alters the biomass and species composition of plant communities, but the extent to which these changes are reversible after the cessation of nutrient addition is not well-understood. Our 22-year experiment (15 years for nutrient addition and 7 years for recovery), conducted in an alpine meadow, showed that soil nitrogen concentration and pH recovered rapidly after cessation of nutrient addition. However, this was not accompanied by a full recovery of plant community composition. An incomplete recovery in plant diversity and a directional shift in species composition from grass dominance to forb dominance were observed 7 years after the nutrient addition ended. Strikingy, the historically dominant sedges with low germination rate and slow growth rate and nitrogen-fixing legumes with low germination rate were unable to re-establish after nutrient addition ceased. By contrast, rapid recovery of aboveground biomass was observed after nutrient cessation as the increase in forb biomass only partially compensated for the decline in grass biomass. These results indicate that anthropogenic nutrient input can have long-lasting effects on the structure, but not the soil chemistry and plant biomass, of grassland communities, and that the recovery of soil chemical properties and plant biomass does not necessarily guarantee the restoration of plant community structure. These findings have important implications for the management and recovery of grassland communities, many of which are experiencing alterations in resource input.


Assuntos
Pradaria , Plantas , Biomassa , Poaceae , Solo/química , Nitrogênio/análise , Nutrientes
8.
Bioorg Chem ; 144: 107163, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38306825

RESUMO

The development of effective antibacterial drugs to combat bacterial infections, particularly the biofilm-related infections, remains a challenge. There are two important features of bacterial biofilms, which are well-known critical factors causing biofilms hard-to-treat in clinical, including the dense and impermeable extracellular polymeric substances (EPS) and the metabolically repressed dormant and persistent bacterial population embedded. These characteristics largely increase the difficulty for regular antibiotic treatment due to insufficient penetration into EPS. In addition, the dormant bacteria are insensitive to the growth-inhibiting mechanism of traditional antibiotics. Herein, we explore the potential of a series of new oligopyridinium-based oligomers bearing a multi-biomacromolecule targeting function as the potent bacterial biofilm eradication agent. These oligomers were rationally designed to be "charge-on-backbone" that can offer a special alternating amphiphilicity. This novel and unique feature endows high affinity to bacterial membrane lipids, DNAs as well as proteins. Such a broad multi-targeting nature of molecules not only enables its penetration into EPS, but also plays vital roles in the bactericidal mechanism of action that is highly effective against dormant and persistent bacteria. Our in vitro, ex vivo, and in vivo studies demonstrated that OPc3, one of the most effective derivatives, was able to offer excellent antibacterial potency against a variety of bacteria and effectively eliminate biofilms in zebrafish models and mouse wound biofilm infection models.


Assuntos
Infecções Bacterianas , Peixe-Zebra , Animais , Camundongos , Biofilmes , Bactérias , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-39256293

RESUMO

PURPOSE: In clinical practice, the success of preimplantation genetic testing for monogenic diseases (PGT-M) for thalassemia was hindered by the absence of probands, incomplete family members, or failure in detecting embryonic gene mutation sites. This study aimed to address these issues. METHODS: This retrospective study included 342 couples undergoing PGT-M for α- or ß-thalassemia at three reproductive medicine centers from 2019 to 2022. Various methods were used to construct parental haplotypes. A total of 1778 embryos were analyzed and selected for transfer based on chromosomal ploidy and PGT-M results. Follow-up involved amniocentesis results and clinical outcomes. RESULTS: Haplotypes were established using DNA samples from probands or parents, as well as sibling blood samples, single sperm, and affected embryos, achieving an overall success rate was 99.4% (340/342). For α-thalassemia and ß-thalassemia, the concordance between embryo single nucleotide polymorphism (SNP) haplotype analysis results and mutation loci detection results was 93.8% (1011/1078) and 98.2% (538/548), respectively. Multiple annealing and looping-based amplification cycles (MALBAC) showed a higher whole genome amplification success rate than multiple displacement amplification (MDA) (98.8% (1031/1044) vs. 96.2% (703/731), p < 0.001). Amniocentesis confirmed PGT-M outcomes in 100% of cases followed up (99/99). CONCLUSION: This study summarizes feasible solutions to various challenging scenarios encountered in PGT-M for thalassemia, providing valuable insights to enhance success rate of PGT-M in clinical practice.

10.
BMC Biol ; 21(1): 231, 2023 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-37867192

RESUMO

BACKGROUND: RNA splicing plays significant roles in fundamental biological activities. However, our knowledge about the roles of alternative splicing and underlying mechanisms during spermatogenesis is limited. RESULTS: Here, we report that Serine/arginine-rich splicing factor 2 (SRSF2), also known as SC35, plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf2 by Stra8-Cre caused complete infertility and defective spermatogenesis. Further analyses revealed that deletion of Srsf2 disrupted differentiation and meiosis initiation of spermatogonia. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF2 regulatory networks play critical roles in several major events including reproductive development, spermatogenesis, meiotic cell cycle, synapse organization, DNA recombination, chromosome segregation, and male sex differentiation. Furthermore, SRSF2 affected expression and alternative splicing of Stra8, Stag3 and Atr encoding critical factors for spermatogenesis in a direct manner. CONCLUSIONS: Taken together, our results demonstrate that SRSF2 has important functions in spermatogenesis and male fertility by regulating alternative splicing.


Assuntos
Splicing de RNA , Espermatogênese , Masculino , Humanos , Espermatogênese/genética , Proteínas de Ligação a RNA/genética , Processamento Alternativo , Meiose/genética , RNA Mensageiro
11.
Environ Toxicol ; 39(3): 1874-1888, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38189626

RESUMO

Paraquat (PQ), is characterized by neurotoxicity, which increases the potential risk of Parkinson's disease (PD) exposure in the long-term and low doses. Triggering microglia activation and neuroinflammation is deemed an early event resulting in PD. However, the underlying pathogenesis of PD by PQ is not clear yet. In this article, C57BL/6J mice treated with PQ could successfully act out Parkinson-like. In addition, we observed the fluorescence intensity enhancement of Iba-1 activated microglia with released pro-inflammatory, all ahead of both the damage of dopaminergic neurons in the substantia nigra and corpus striatum of the brain. Surprisingly, the injection of minocycline before PQ for many hours not only can effectively improve the neurobehavioral symptoms of mice but inhibit the activation of microglia and the release of pro-inflammatory substances, even controlling the gradual damage and loss of neurons. A further mechanism of minocycline hampered the expression levels of key signaling proteins PI3K, PDK1, p-AKT, and CD11b (the receptor of microglia membrane recognition), while a large number of inflammatory factors. Our results suggested that the CD11b/PI3K/NOX2 pathway may be a clue that microglia-mediated inflammatory responses and neuronal damage in a PQ-induced abnormal behavior Parkinson-like mouse.


Assuntos
Paraquat , Doença de Parkinson , Animais , Camundongos , Paraquat/toxicidade , Microglia , Minociclina/metabolismo , Minociclina/farmacologia , Camundongos Endogâmicos C57BL , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Fosfatidilinositol 3-Quinases/metabolismo
12.
J Am Chem Soc ; 145(42): 23372-23384, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37838963

RESUMO

Intracellular bacterial pathogens, such as Staphylococcus aureus, that may hide in intracellular vacuoles represent the most significant manifestation of bacterial persistence. They are critically associated with chronic infections and antibiotic resistance, as conventional antibiotics are ineffective against such intracellular persisters due to permeability issues and mechanistic reasons. Direct subcellular targeting of S. aureus vacuoles suggests an explicit opportunity for the eradication of these persisters, but a comprehensive understanding of the chemical biology nature and significance of precise S. aureus vacuole targeting remains limited. Here, we report an oligoguanidine-based peptidomimetic that effectively targets and eradicates intracellular S. aureus persisters in the phagolysosome lumen, and this oligomer was utilized to reveal the mechanistic insights linking precise targeting to intracellular antimicrobial efficacy. The oligomer has high cellular uptake via a receptor-mediated endocytosis pathway and colocalizes with S. aureus persisters in phagolysosomes as a result of endosome-lysosome interconversion and lysosome-phagosome fusion. Moreover, the observation of a bacterium's altered susceptibility to the oligomer following a modification in its intracellular localization offers direct evidence of the critical importance of precise intracellular targeting. In addition, eradication of intracellular S. aureus persisters was achieved by the oligomer's membrane/DNA dual-targeting mechanism of action; therefore, its effectiveness is not hampered by the hibernation state of the persisters. Such precise subcellular targeting of S. aureus vacuoles also increases the agent's biocompatibility by minimizing its interaction with other organelles, endowing excellent in vivo bacterial targeting and therapeutic efficacy in animal models.


Assuntos
Infecções Estafilocócicas , Staphylococcus aureus , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Bactérias , Biologia , Testes de Sensibilidade Microbiana
13.
Small ; 19(25): e2301063, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36932893

RESUMO

As an important noncovalent interaction, cation-π interaction plays an essential role in a broad area of biology and chemistry. Despite extensive studies in protein stability and molecular recognition, the utilization of cation-π interaction as a major driving force to construct supramolecular hydrogel remains uncharted. Here, a series of peptide amphiphiles are designed with cation-π interaction pairs that can self-assemble into supramolecular hydrogel under physiological condition. The influence of cation-π interaction is thoroughly investigated on peptide folding propensity, morphology, and rigidity of the resultant hydrogel. Computational and experimental results confirm that cation-π interaction could serve as a major driving force to trigger peptide folding, resultant ß-hairpin peptide self-assembled into fibril-rich hydrogel. Furthermore, the designed peptides exhibit high efficacy on cytosolic protein delivery. As the first case of using cation-π interactions to trigger peptide self-assembly and hydrogelation, this work provides a novel strategy to generate supramolecular biomaterials.


Assuntos
Hidrogéis , Peptídeos , Humanos , Hidrogéis/química , Peptídeos/química
14.
IUBMB Life ; 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38009728

RESUMO

Vincristine (VCR) is a microtubule-destabilizing chemotherapeutic agent commonly administered for the treatment of cancers in patients, which can induce severe side effects including neurotoxicity. In context of the effects on female fertility, ovarian toxicity has been found in patients and mice model after VCR exposure. However, the influence of VCR exposure on oocyte quality has not been elucidated. We established VCR exposure in vitro and in vivo model. The results indicated in vitro VCR exposure contributed to failure of oocyte maturation through inducing defects in spindle assembly, activation of SAC, oxidative stress, mitochondrial dysfunction, and early apoptosis, which were confirmed by using in vivo exposure model. Moreover, in vivo VCR exposure caused aneuploidy, reduced oocyte-sperm binding ability, and the number of cortical granules in mouse oocyte cortex. Taken together, this study demonstrated that VCR could cause meiotic arrest and poor quality of mouse oocyte.

15.
Ann Surg Oncol ; 30(8): 4876-4885, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37133569

RESUMO

PURPOSE: This study aimed to explore the association of preoperative magnetic resonance imaging (MRI) tumor morphological classification with early recurrence (ER) and overall survival (OS) after radical surgery of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A retrospective analysis of 296 patients with HCC who underwent radical resection was performed. On the basis of LI-RADS, tumor imaging morphology was classified into three types. The clinical imaging features, ER, and survival rates of three types were compared. Univariate and multivariate Cox regression analyses were conducted to identify prognostic factors associated with OS and ER after hepatectomy for HCC. RESULTS: There were 167 tumors of type 1, 95 of type 2, and 34 of type 3. In patients with type 3 HCC, postoperative mortality and ER were significantly higher than in patients with type 1 and type 2 (55.9% versus 32.6% versus 27.5% and 52.9% versus 33.7% versus 28.7%). In multivariate analysis, the LI-RADS morphological type was a stronger risk factor for predicting poor OS [hazard ratio (HR) 2.77, 95% confidence interval (CI) 1.59-4.85, P < 0.001] and ER (HR 2.14, 95% CI 1.24-3.70, P = 0.007). A subgroup analysis revealed that type 3 was associated with poor OS and ER in > 5 cm cases but not in < 5 cm cases. CONCLUSIONS: ER and OS of patients with HCC undergoing radical surgery can be predicted using the preoperative tumor LI-RADS morphological type, which could help to select personalized treatment plans for patients with HCC in the future.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Prognóstico , Hepatectomia , Imageamento por Ressonância Magnética/métodos
16.
Opt Lett ; 48(11): 2797-2800, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37262213

RESUMO

Measurement-device-independent quantum key distribution can remove all possible detector side channels, and is robust against state preparation flaws when further combined with the loss-tolerant method. However, the secure key rate in this scenario is relatively low, thus hindering its practical application. Here, we first present a four-intensity decoy-state protocol where the signal intensity is modulated only in Z basis for key generation while the decoy intensities are modulated in both Z and X bases for parameter estimation. Moreover, we adopt collective constraint and joint-study strategy in statistical fluctuation analysis. We have also experimentally demonstrated this protocol and the result indicates high performance and good security for practical applications.

17.
Biomacromolecules ; 24(12): 5698-5706, 2023 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-37945526

RESUMO

The development of cell-penetrating polymers with endocytosis-independent cell uptake pathways has emerged as a prominent strategy to enhance the transfection efficiency. Inspired by the rigid α-helical structure that endows polypeptides with cell-penetrating ability, we propose that a rigid backbone can facilitate the corresponding polymer vector's performance in gene delivery by bypassing the difficult endosomal escape process. Meanwhile, the installation of aromatic domains, as a way to promote gene transfection efficiency, is employed through the construction of a poly(benzyl ether) (PBE)-based scaffold in this work. We demonstrate that the direct membrane translocation capability of the synthesized PBE contributes to its enhanced transfection performance and excellent biocompatibility profile, rendering the imidazolium-functionalized PBE scaffold with higher activity and biocompatibility. Molecular details of the PBE-lipid interaction are also revealed in molecular dynamics simulations, indicating the important roles of individual structural elements on the polymeric scaffold in the membrane penetration process.


Assuntos
Técnicas de Transferência de Genes , Polímeros , Terapia Genética , Transfecção , Peptídeos/química
18.
Crit Rev Food Sci Nutr ; : 1-15, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37667834

RESUMO

Supercooling can preserve food in its original fresh state below its ice point temperature without freezing. However, the supercooled state is unstable in thermodynamics, state breakdown can occur at any moment, resulting in irregular and larger ice crystals formation, leading to food tissue damage, and loss of quality and nutrients. While the effectiveness of supercooling preservation has been verified in the lab and pilot scale tests, the stability of the supercooled state of food remains an open question, posing a limitation for larger industrial-scale application of supercooling preservation. Based on this background, this review presents the instability mechanisms of supercooling preservation and summarizes the factors such as food properties (e.g., material size, food components, specific surface area, and surface roughness) and preservation circumstances (e.g., cooling rate, temperature variation, and mechanical disturbance) that influence the stability of the supercooled state of food. The review also discusses novel techniques for enhancing the supercooling capacity and their limitations (e.g., precise temperature control and magnetic field). Further studies are necessary to comprehensively evaluate the effects of influence factors and supercooling technologies on supercooling, realizing the true sense of 'no-crystal' food products under subzero temperature preservation conditions in commercial applications.


Supercooling can maximize the potential of low temperature in food preservation.Supercooled state of food is unstable, with many factors affecting its stability.The quality of foodstuffs with supercooled failure is unacceptable.Instability of supercooling limits its large application in food industry.Novel technologies are developed to enhance the state stability of food supercooling.

19.
Crit Rev Food Sci Nutr ; : 1-17, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37819615

RESUMO

Postmortem meat tenderization is a process mediated by a series of biochemical reactions related to muscle cell death. Cell death is considered a sign that muscle has started to transform into meat. Mitochondria play a significant role in regulating and executing cell death, as they are an aggregation point for many cell death signals and are also the primary target organelle damaged by tissue anoxia. Mitochondrial damage is likely to have an expanded role in postmortem meat tenderization. This review presents current findings on mitochondrial damage induced by the accumulation of reactive oxygen species during postmortem anaerobic metabolism and on the impact of mitochondrial damage on proteolysis and discusses how this leads to improved tenderness during aging. The underlying mechanisms of mitochondrial regulation of postmortem muscle tenderization likely focus on the mitochondria's role in postmortem cell death and energy metabolism. The death process of postmortem skeletal muscle cells may exhibit multiple types, possibly involving transformation from autophagy to apoptosis and, ultimately, necroptosis or necrosis. Mitochondrial characteristics, especially membrane integrity and ATP-related compound levels, are closely related to the transformation of multiple types of dead postmortem muscle cells. Finally, a possible biochemical regulatory network in postmortem muscle tenderization is proposed.

20.
Appl Microbiol Biotechnol ; 107(7-8): 2707-2721, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36922440

RESUMO

Biofilm cultivation is considered a promising method to achieve higher microalgae biomass productivity with less water consumption and easier harvest compared to conventional suspended cultivation. However, studies focusing on the selection of substratum material and optimization of the growth of certain microalgae species on specific substratum are limited. This study investigated the selection of membranous and fabric fiber substrata for the attachment of unicellular microalgae Scenedesmus dimorphus and filamentous microalgae Tribonema minus in biofilm cultivation. The results indicated that both algal species preferred hydrophilic membranous substrata and nitrate cellulose/cellulose acetate membrane (CN-CA) was selected as a suitable candidate on which the obtained biomass yields were up to 10.24 and 7.81 g m-2 day-1 for S. dimorphus and T. minus, respectively. Furthermore, high-thread cotton fiber (HCF) and low-thread polyester fiber (LPEF) were verified as the potential fabric fiber substrata for S. dimorphus (5.42 g m-2 day-1) and T. minus (5.49 g m-2 day-1) attachment, respectively. The regrowth of microalgae biofilm cultivation strategy was applied to optimize the algae growth on the fabric fiber substrata, with higher biomass density and shear resistibility achieved for both algal species. The present data highlight the importance to establish the standards for selection the suitable substratum materials in ensuring the high efficiency and sustainability of the attached microalgal biomass production. KEY POINTS: • CN-CA was suitable membranous substratum candidate for algal biofilm cultivation. • HCF and LPEF were potential fabric fiber substrata for S. dimorphus and T. minus. • Regrowth biofilm cultivation was effective in improving algal biomass and attachment.


Assuntos
Microalgas , Scenedesmus , Biofilmes , Biomassa , Interações Hidrofóbicas e Hidrofílicas
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