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1.
Small ; : e2400952, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39011941

RESUMEN

Pickering water-in-water (W/W) emulsions stabilized by biobased colloids are pertinent to engineering biomaterials with hierarchical and confined architectures. In this study, stable W/W emulsions are developed through membranization utilizing biopolymer structures formed by the adsorption of cellulose II nanospheres and a globular protein, bovine serum albumin (BSA), at droplet surfaces. The produced cellulose II nanospheres (NPcat, 63 nm diameter) bearing a soft and highly accessible shell, endow rapid and significant binding (16 mg cm- 2) with BSA. NPcat and BSA formed complexes that spontaneously stabilized liquid droplets, resulting in stable W/W emulsions. It is proposed that such a system is a versatile all-aqueous platform for encapsulation, (bio)catalysis, delivery, and synthetic cell mimetics.

2.
Front Pharmacol ; 15: 1348688, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38948474

RESUMEN

Purpose: To evaluate the cost-effectiveness of sotorasib versus docetaxel in non-small cell lung cancer (NSCLC) patients with KRASG12C mutation from the China and United States'social perspective. Materials and Methods: A Markov model that included three states (progression-free survival, post-progression survival, and death) was developed. Incremental cost-effectiveness ratio (ICER), quality-adjusted life-year (QALY), and incremental QALY were calculated for the two treatment strategies. One-way sensitivity analysis was used to investigate the factors that had a greater impact on the model results, and tornado diagrams were used to present the results. Probabilistic sensitivity analysis was performed with 1,000 Monte Carlo simulations. Assume distributions based on parameter types and randomly sample all parameter distributions each time., The results were presented as cost-effectiveness acceptable curves. Results: This economic evaluation of data from the CodeBreak 200 randomized clinical trial. In China, sotorasib generated 0.44 QAYL with a total cost of $84372.59. Compared with docetaxel, the ICER value of sotorasib was $102701.84/QALY, which was higher than willingness to pay (WTP), so sotorasib had no economic advantage. In the US, sotorasib obtained 0.35 QALY more than docetaxel, ICER was $15,976.50/QALY, which was more than 1 WTP but less than 3 WTP, indicating that the increased cost of sotorasib was acceptable. One-way sensitivity analysis showed that the probability of sotorasib having economic benefits gradually increased when the cost of follow-up examination was reduced in China. And there was no influence on the conclusions within the range of changes in China. When the willingness to pay (WTP) exceeds $102,500, the probability of sotorasib having cost effect increases from 0% to 49%. Conclusion: Sotorasib had a cost effect from the perspective in the United States. However, sotorasib had no cost effect from the perspective in China, and only when the WTP exceeds $102,500, the probability of sotorasib having cost effect increases from 0% to 49%.

3.
Anaesthesia ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39037325

RESUMEN

BACKGROUND: Postoperative nausea and vomiting occur frequently following thyroid and parathyroid surgery and are associated with worse patient outcomes. We hypothesised that opioid-free propofol anaesthesia would reduce the incidence of postoperative nausea and vomiting compared with opioid-inclusive propofol anaesthesia in patients undergoing these procedures. METHODS: We conducted a randomised, double-blinded controlled trial in adult patients scheduled to undergo thyroid and parathyroid surgery at two medical centres in mainland China. Patients were allocated randomly (1:1, stratified by sex and trial site) to an opioid-free anaesthesia group (esketamine, lidocaine, dexmedetomidine and propofol) or an opioid-inclusive group (sufentanil and propofol). Propofol infusions were titrated to bispectral index 45-55. Patients received prophylaxis for nausea and vomiting using dexamethasone and ondansetron and multimodal analgesia with paracetamol and flurbiprofen axetil. The primary outcome was the incidence of postoperative nausea and vomiting in the first 48 h after surgery. RESULTS: We assessed 557 patients for eligibility and 394 completed this trial. The incidence of postoperative nausea and vomiting in the first postoperative 48 h was lower in the opioid-free anaesthesia group (10/197, 5%) compared with opioid-inclusive group (47/197, 24%) (OR (95%CI) 0.17 (0.08-0.35), p < 0.001), yielding a number needed to treat of 5.3. Additionally, opioid-free propofol anaesthesia was associated with a reduced need for rescue anti-emetics, lower rates of hypotension and desaturation after tracheal extubation, and higher patient satisfaction. Time to tracheal extubation was prolonged slightly in the opioid-free group. The two groups had similar postoperative pain scores and 30-day outcomes. DISCUSSION: Opioid-free propofol anaesthesia reduced postoperative nausea and vomiting in patients undergoing thyroid and parathyroid surgery. An opioid-free anaesthetic regimen can optimise anaesthetic care during thyroid and parathyroid surgery.

4.
Med Phys ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38873848

RESUMEN

BACKGROUND: Although the FLASH radiotherapy (FLASH) can improve the sparing of organs-at-risk (OAR) via the FLASH effect, it is generally a tradeoff between the physical dose coverage and the biological FLASH coverage, for which the concept of FLASH effective dose (FED) is needed to quantify the net improvement of FLASH, compared to the conventional radiotherapy (CONV). PURPOSE: This work will develop the first-of-its-kind treatment planning method called simultaneous dose and dose rate optimization via dose modifying factor modeling (SDDRO-DMF) for proton FLASH that directly optimizes FED. METHODS: SDDRO-DMF models and optimizes FED using FLASH dose modifying factor (DMF) models, which can be classified into two categories: (1) the phenomenological model of the FLASH effect, such as the FLASH effectiveness model (FEM); (2) the mechanistic model of the FLASH radiobiology, such as the radiolytic oxygen depletion (ROD) model. The general framework of SDDRO-DMF will be developed, with specific DMF models using FEM and ROD, as a demonstration of general applicability of SDDRO-DMF for proton FLASH via transmission beams (TB) or Bragg peaks (BP) with single-field or multi-field irradiation. The FLASH dose rate is modeled as pencil beam scanning dose rate. The solution algorithm for solving the inverse optimization problem of SDDRO-DMF is based on iterative convex relaxation method. RESULTS: SDDRO-DMF is validated in comparison with IMPT and a state-of-the-art method called SDDRO, with demonstrated efficacy and improvement for reducing the high dose and the high-dose volume for OAR in terms of FED. For example, in a SBRT lung case of the dose-limiting factor that the max dose of brachial plexus should be no more than 26 Gy, only SDDRO-DMF met this max dose constraint; moreover, SDDRO-DMF completely eliminated the high-dose (V70%) volume to zero for CTV10mm (a high-dose region as a 10 mm ring expansion of CTV). CONCLUSION: We have proposed a new proton FLASH optimization method called SDDRO-DMF that directly optimizes FED using phenomenological or mechanistic models of DMF, and have demonstrated the efficacy of SDDO-DMF in reducing the high-dose volume or/and the high-dose value for OAR, compared to IMPT and a state-of-the-art method SDDRO.

5.
J Phys Chem Lett ; 15(23): 6108-6114, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38829304

RESUMEN

Two-dimensional metal-organic networks (2D MONs) having heterogeneous coordination nodes (HCNs) could exhibit excellent performance in catalysis and optoelectronics because of the unbalanced electron distribution of the coordinating metals. Therefore, the design and construction of 2D MONs with HCNs are highly desirable but remain challenging. Here, we report the construction of 2D organometallic coordination networks with an organic Kagome lattice and a semiregular metal lattice on Au(111) via the in situ formation of HCNs. Using a bifunctional precursor 1,4-dibromo-2,5-diisocyanobenzene, the coordination of isocyano with Au adatom on a room-temperature Au(111) yielded metal-organic coordination chains with isocyano-Au-isocyano nodes. In contrast, on a high-temperature Au(111), a selective debromination/coordination cascade reaction occurred, affording 2D organometallic coordination networks with phenyl-Au-isocyano nodes. By combining scanning tunneling microscopy and density functional theory calculations, we determined the structures of coordination products and the nature of coordination nodes, demonstrating a thermodynamically favorable pathway for forming the phenyl-Au-isocyano nodes.

6.
Angew Chem Int Ed Engl ; : e202408670, 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38943429

RESUMEN

Peptide folding is a dynamic process driven by non-covalent cross-linking leading to functional nanostructures for essential biochemical activities. However, replicating this process in synthetic systems is challenging due to the difficulty in mimicking nature's real-time regulation of non-covalent crosslinking for single-chain polymer folding. Here, we address this by employing anionic dithiol building blocks to create macrocyclic disulfides as non-covalent crosslinkers that adapted to the folding process. Initially, small macrocycles facilitated a low degree folding of a polycation. Then, this preorganized structure catalysed the production of larger macrocycles that enhanced the folding conversely. The self-adaptive synthesis was verified through the encapsulation of an anticancer drug, showing an updated production distribution of non-covalent crosslinkers and maximizing drug-loading efficiency against drug-resistant cancer in vitro. Our research advances the understanding of molecular systems by exploring species evolution via the structural dynamics of polymer folding. Additionally, adaptive synthesis enables controlled, sequential folding of synthetic polymers, with the potential to mimic protein functions.

7.
Bioorg Chem ; 150: 107536, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38878751

RESUMEN

Carboxylesterase 1 (CES1), a member of the serine hydrolase superfamily, is involved in a wide range of xenobiotic and endogenous substances metabolic reactions in mammals. The inhibition of CES1 could not only alter the metabolism and disposition of related drugs, but also be benefit for treatment of metabolic disorders, such as obesity and fatty liver disease. In the present study, we aim to develop potential inhibitors of CES1 and reveal the preferred inhibitor structure from a series of synthetic pyrazolones (compounds 1-27). By in vitro high-throughput screening method, we found compounds 25 and 27 had non-competitive inhibition on CES1-mediated N-alkylated d-luciferin methyl ester (NLMe) hydrolysis, while compound 26 competitively inhibited CES1-mediated NLMe hydrolysis. Additionally, Compounds 25, 26 and 27 can inhibit CES1-mediated fluorescent probe hydrolysis in live HepG2 cells with effect. Besides, compounds 25, 26 and 27 could effectively inhibit the accumulation of lipid droplets in mouse adipocytes cells. These data not only provided study basis for the design of newly CES1 inhibitors. The present study not only provided the basis for the development of lead compounds for novel CES1 inhibitors with better performance, but also offered a new direction for the explore of candidate compounds for the treatment of hyperlipidemia and related diseases.


Asunto(s)
Adipocitos , Hidrolasas de Éster Carboxílico , Inhibidores Enzimáticos , Pirazolonas , Humanos , Hidrolasas de Éster Carboxílico/metabolismo , Hidrolasas de Éster Carboxílico/antagonistas & inhibidores , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipocitos/citología , Animales , Ratones , Pirazolonas/farmacología , Pirazolonas/química , Pirazolonas/síntesis química , Relación Estructura-Actividad , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Estructura Molecular , Células Hep G2 , Diferenciación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células 3T3-L1
8.
Nat Commun ; 15(1): 5147, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886343

RESUMEN

Bacteria-mediated cancer therapeutic strategies have attracted increasing interest due to their intrinsic tumor tropism. However, bacteria-based drugs face several challenges including the large size of bacteria and dense extracellular matrix, limiting their intratumoral delivery efficiency. In this study, we find that hyperbaric oxygen (HBO), a noninvasive therapeutic method, can effectively deplete the dense extracellular matrix and thus enhance the bacterial accumulation within tumors. Inspired by this finding, we modify Escherichia coli Nissle 1917 (EcN) with cypate molecules to yield EcN-cypate for photothermal therapy, which can subsequently induce immunogenic cell death (ICD). Importantly, HBO treatment significantly increases the intratumoral accumulation of EcN-cypate and facilitates the intratumoral infiltration of immune cells to realize desirable tumor eradication through photothermal therapy and ICD-induced immunotherapy. Our work provides a facile and noninvasive strategy to enhance the intratumoral delivery efficiency of natural/engineered bacteria, and may promote the clinical translation of bacteria-mediated synergistic cancer therapy.


Asunto(s)
Escherichia coli , Oxigenoterapia Hiperbárica , Inmunoterapia , Terapia Fototérmica , Oxigenoterapia Hiperbárica/métodos , Animales , Inmunoterapia/métodos , Ratones , Terapia Fototérmica/métodos , Línea Celular Tumoral , Humanos , Muerte Celular Inmunogénica/efectos de los fármacos , Neoplasias/terapia , Neoplasias/inmunología , Femenino , Ratones Endogámicos BALB C , Matriz Extracelular/metabolismo
9.
Exploration (Beijing) ; 4(2): 20230105, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38855612

RESUMEN

The tumour-targeting efficiency of systemically delivered chemodrugs largely dictates the therapeutic outcome of anticancer treatment. Major challenges lie in the complexity of diverse biological barriers that drug delivery systems must hierarchically overcome to reach their cellular/subcellular targets. Herein, an "all-in-one" red blood cell (RBC)-derived microrobot that can hierarchically adapt to five critical stages during systemic drug delivery, that is, circulation, accumulation, release, extravasation, and penetration, is developed. The microrobots behave like natural RBCs in blood circulation, due to their almost identical surface properties, but can be magnetically manipulated to accumulate at regions of interest such as tumours. Next, the microrobots are "immolated" under laser irradiation to release their therapeutic cargoes and, by generating heat, to enhance drug extravasation through vascular barriers. As a coloaded agent, pirfenidone (PFD) can inhibit the formation of extracellular matrix and increase the penetration depth of chemodrugs in the solid tumour. It is demonstrated that this system effectively suppresses both primary and metastatic tumours in mouse models without evident side effects, and may represent a new class of intelligent biomimicking robots for biomedical applications.

10.
J Affect Disord ; 362: 45-53, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38942204

RESUMEN

BACKGROUND: Insomnia has been identified as a potential risk factor for suicidality. However, to date, few studies using the longitudinal-design have examined the underlying mechanism of this relationship. Based on a resilience perspective, this study aimed to investigate the dynamic longitudinal relationships between insomnia, resilience, and suicidality. METHODS: A total of 5785 freshmen were sampled from a large-scale health-related cohort among Chinese college students. This study spanned six waves, covering the period from 2020 to 2022. Data from T1 to T4 were used because resilience was not measured at baseline (T0) and T5. The cross-lagged panel models and the latent growth curve mediation model were used to examine the longitudinal dynamic relationships between insomnia, resilience, and suicidality. RESULTS: The results showed that insomnia symptoms and suicidality mutually predicted each other, and resilience played a longitudinal mediating role in linking insomnia symptoms and suicidality. CONCLUSIONS: Given that resilience served as a mediator in the relation between insomnia symptoms and suicidality, some resilience-oriented prevention and intervention programs will be helpful in reducing the risk of suicide among university students.

11.
Biodivers Data J ; 12: e121451, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38827584

RESUMEN

Background: The family Nemouridae, belonging to Plecoptera, comprises 21 genera and over 700 species found globally, with the greatest diversity observed in temperate regions. Nemoura Latreille, 1796 and Amphinemura Ris, 1902 are two largest genera of the family with the highest diversity in China. New information: Two new species of Nemoura Latreille, 1796 of the family Nemouridae, Nemouraexterclava Zhu, Rehman & Du sp. nov. and Nemouracerciserrata Zhu, Du & Rehman sp. nov., are described and illustrated from the Nanling Mountains Region in Guangdong Province, southern China. The morphological characteristics of the new species are compared with related taxa. Additionally, the status of Indonemouravoluta Li & Yang, 2008, originally from Maoershan National Natural Reserve in Guangxi Zhuang Autonomous Region, was addressed and moved to the genus Amphinemura Ris, 1902 on the basis of newly-caught topotypes.

12.
Fungal Genet Biol ; 173: 103899, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38802054

RESUMEN

Fusarium head blight is a devastating disease that causes severe yield loses and mycotoxin contamination in wheat grain. Additionally, balancing the trade-off between wheat production and disease resistance has proved challenging. This study aimed to expand the genetic tools of the endophyte Phomopsis liquidambaris against Fusarium graminearum. Specifically, we engineered a UDP-glucosyltransferase-expressing P. liquidambaris strain (PL-UGT) using ADE1 as a selection marker and obtained a deletion mutant using an inducible promoter that drives Cas9 expression. Our PL-UGT strain converted deoxynivalenol (DON) into DON-3-G in vitro at a rate of 71.4 % after 36 h. DON inactivation can be used to confer tolerance in planta. Wheat seedlings inoculated with endophytic strain PL-UGT showed improved growth compared with those inoculated with wildtype P. liquidambaris. Strain PL-UGT inhibited the growth of Fusarium graminearum and reduced infection rate to 15.7 %. Consistent with this finding, DON levels in wheat grains decreased from 14.25 to 0.56 µg/g when the flowers were pre-inoculated with PL-UGT and then infected with F. graminearum. The expression of UGT in P. liquidambaris was nontoxic and did not inhibit plant growth. Endophytes do not enter the seeds nor induce plant disease, thereby representing a novel approach to fungal disease control.

14.
Toxicol Mech Methods ; 34(6): 669-675, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38736312

RESUMEN

Although recent studies increasingly suggest the potential anti-cancer effect of quercetin, the exact underlying mechanism remains poorly demonstrated in oral squamous cell carcinoma (oSCC). Therefore, our research explored the impacts of quercetin on the ferroptosis and mTOR/S6KP70 axis in oSCC cell lines. After treating oSCC cells with quercetin or indicated compounds and transfection with SLC7A11- or S6KP70-overexpressing plasmid, cell viability was detected by CCK-8 assay. The level of ferroptosis in oSCC cells was assessed by measuring ROS and GSH levels. The activation of mTOR/S6KP70 axis was assessed by Western blotting. Quercetin promoted ferroptosis in an mTOR/S6KP70-dependent manner to inhibit tumor growth in oSCC cells. Mechanistically, we revealed that quercetin induced lipid peroxidation and reduced GSH levels by repressing SLC7A11 expression in oSCC cells. Specifically, the effects of quercetin on ferroptosis and mTOR and S6KP70 phosphorylation were partially blocked by both mTOR agonist and S6KP70 overexpression. Moreover, mTOR inhibitor promoted ferroptosis in quercetin-treated oSCC cells. Our findings showed that ferroptosis may be a new anti-tumor mechanism of quercetin. Additionally, we identified that quercetin can target mTOR/S6KP70 cascade to inhibit the growth of oSCC cells.


Asunto(s)
Sistema de Transporte de Aminoácidos y+ , Ferroptosis , Neoplasias de la Boca , Quercetina , Serina-Treonina Quinasas TOR , Animales , Humanos , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ferroptosis/efectos de los fármacos , Ratones Desnudos , Neoplasias de la Boca/patología , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/metabolismo , Quercetina/farmacología , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Transducción de Señal/efectos de los fármacos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Serina-Treonina Quinasas TOR/metabolismo
15.
Colloids Surf B Biointerfaces ; 240: 113966, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38781846

RESUMEN

Dental Implants are expected to possess both excellent osteointegration and antibacterial activity because poor osseointegration and infection are two major causes of titanium implant failure. In this study, we constructed layer-by-layer self-assembly films consisting of anionic casein phosphopeptides-amorphous calcium phosphate (CPP-ACP) and cationic poly (L-lysine) (PLL) on sandblasted and acid etched (SLA) titanium surfaces and evaluated their osseointegration and antibacterial performance in vitro and in vivo. The surface properties were examined, including microstructure, elemental composition, wettability, and Ca2+ ion release. The impact the surfaces had on the adhesion, proliferation and differentiation abilities of MC3T3-E1 cells were investigated, as well as the material's antibacterial performance after exposure to the oral microorganisms such as Porphyromonas gingivalis (P. g) and Actinobacillus actinomycetemcomitans (A. a). For the in vivo studies, SLA and Ti (PLL/CA-3.0)10 implants were inserted into the extraction socket immediately after extracting the rabbit mandibular anterior teeth with or without exposure to mixed bacteria solution (P. g & A. a). Three rabbits in each group were sacrificed to collect samples at 2, 4, and 6 weeks of post-implantation, respectively. Radiographic and histomorphometry examinations were performed to evaluate the implant osseointegration. The modified titanium surfaces were successfully prepared and appeared as a compact nano-structure with high hydrophilicity. In particular, the Ti (PLL/CA-3.0)10 surface was able to continuously release Ca2+ ions. From the in vitro and in vivo studies, the modified titanium surfaces expressed enhanced osteogenic and antibacterial properties. Hence, the PLL/CPP-ACP multilayer coating on titanium surfaces was constructed via a layer-by-layer self-assembly technology, possibly improving the biofunctionalization of Ti-based dental implants.


Asunto(s)
Antibacterianos , Oseointegración , Polilisina , Propiedades de Superficie , Titanio , Titanio/química , Titanio/farmacología , Oseointegración/efectos de los fármacos , Animales , Polilisina/química , Polilisina/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Ratones , Implantes Dentales/microbiología , Conejos , Porphyromonas gingivalis/efectos de los fármacos , Caseínas/química , Caseínas/farmacología , Proliferación Celular/efectos de los fármacos , Aggregatibacter actinomycetemcomitans/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Adhesión Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Fosfatos de Calcio
16.
Nat Commun ; 15(1): 4328, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773155

RESUMEN

Parental experiences can affect the phenotypic plasticity of offspring. In locusts, the population density that adults experience regulates the number and hatching synchrony of their eggs, contributing to locust outbreaks. However, the pathway of signal transmission from parents to offspring remains unclear. Here, we find that transcription factor Forkhead box protein N1 (FOXN1) responds to high population density and activates the polypyrimidine tract-binding protein 1 (Ptbp1) in locusts. FOXN1-PTBP1 serves as an upstream regulator of miR-276, a miRNA to control egg-hatching synchrony. PTBP1 boosts the nucleo-cytoplasmic transport of pre-miR-276 in a "CU motif"-dependent manner, by collaborating with the primary exportin protein exportin 5 (XPO5). Enhanced nuclear export of pre-miR-276 elevates miR-276 expression in terminal oocytes, where FOXN1 activates Ptbp1 and leads to egg-hatching synchrony in response to high population density. Additionally, PTBP1-prompted nuclear export of pre-miR-276 is conserved in insects, implying a ubiquitous mechanism to mediate transgenerational effects.


Asunto(s)
Transporte Activo de Núcleo Celular , Saltamontes , MicroARNs , Proteína de Unión al Tracto de Polipirimidina , Animales , MicroARNs/metabolismo , MicroARNs/genética , Proteína de Unión al Tracto de Polipirimidina/metabolismo , Proteína de Unión al Tracto de Polipirimidina/genética , Saltamontes/genética , Saltamontes/metabolismo , Femenino , Factores de Transcripción Forkhead/metabolismo , Factores de Transcripción Forkhead/genética , Óvulo/metabolismo , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Núcleo Celular/metabolismo , Oocitos/metabolismo
17.
Artículo en Inglés | MEDLINE | ID: mdl-38761200

RESUMEN

OBJECTIVE: To compare the clinical efficacy of the minimally invasive locking plate technique (Philos plate) and interlocking intramedullary nailing technique (TRIGEN intramedullary nail) in the treatment of Neer two-part and three-part proximal humeral fractures. METHODS AND MATERIALS: The clinical data of 60 patients with Neer two-part and three-part proximal humerus fractures admitted to the hospital from April 2017 to April 2021 were retrospectively analyzed. Thirty-two patients were treated with the minimally invasive locking plate technique (minimally invasive plate group), and 28 patients were treated with the interlocking intramedullary nailing technique (intramedullary nail group). The operation time, intraoperative blood loss, incision length, fracture healing time, and postoperative complications were compared between the two groups. The ASES score and Constant-Murley score were used to evaluate the shoulder joint function of the two groups one year after surgery. RESULTS: All 60 patients were followed up for 12 to 24 months, with an average of 16 months. There was no significant difference in operation time, intraoperative blood loss, incision length, or fracture healing time between the two groups (P > 0.05). The incidence of postoperative complications in the intramedullary nail group was significantly lower than that in the minimally invasive steel plate group, and the difference between the groups was statistically significant (P < 0.05). There was no significant difference in the ASES score or Constant-Murley score between the two groups one year after surgery (P > 0.05). CONCLUSION: The use of the minimally invasive locking plate technique and interlocking intramedullary nailing technique in the treatment of Neer two-part and three-part proximal humerus fractures has the advantages of a small incision, less blood loss, and a high fracture healing rate, and both can achieve satisfactory clinical effects. The internal nail technique is more convenient than the minimally invasive locking plate technique in controlling postoperative complications.

18.
Adv Mater ; : e2404199, 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38734974

RESUMEN

External stimuli triggering chemical reactions in cancer cells to generate highly reactive chemical species are very appealing for cancer therapy, in which external irradiation activating sensitizers to transfer energy or electrons to surrounding oxygen or other molecules is critical for generating cytotoxic reactive species. However, poor light penetration into tissue, low activity of sensitizers, and reliance on oxygen supply restrict the generation of cytotoxic chemical species in hypoxic tumors, which lowers the therapeutic efficacy. Here, this work presents galvanic cell nanomaterials that can directly release highly reactive electrons in tumors without external irradiation or photosensitizers. The released reactive electrons directly react with surrounding biomolecules such as proteins and DNA within tumors to destroy them or react with other surrounding (bio)molecules to yield cytotoxic chemical species to eliminate tumors independent of oxygen. Administering these nanogalvanic cells to mice results in almost complete remission of subcutaneous solid tumors and deep metastatic tumors. The results demonstrate that this strategy can further arouse an immune response even in a hypoxic environment. This method offers a promising approach to effectively eliminate tumors, similar to photodynamic therapy, but does not require oxygen or irradiation to activate photosensitizers.

19.
Sci Total Environ ; 931: 172795, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38677429

RESUMEN

The ubiquitous presence of micro-and nanoplastics (MNPs) in the environment and everyday products has attracted attention due to their hazardous risks. However, the effects of MNPs on reproduction and the underlying mechanisms remain unclear. The present study investigated the impact of polystyrene (PS) nanoplastics of 80, 200 and 500 nm diameters on zebrafish reproduction at an environmentally relevant concentration of 0.5 mg/L. Exposure to PS delayed spermatogenesis and caused aberrant follicular growth, resulting in dysgenesis in F0 adults and impacting F1 embryo development. Notably, the reproductive toxicity exhibited size-dependency, with the 500 nm PS being the most detrimental. Combined analyses of transcriptomics and metabolomics in ovary tissue revealed that treatment with 500 nm PS affected the peroxisome proliferator-activated receptor (PPAR) signaling pathway, dysregulated lipid transport, binding and activity processes, and led to dysgenesis in zebrafish. Specifically, the ovulatory dysfunction induced by PS exposure resembled clinical manifestations of polycystic ovary syndrome (PCOS) and can be attributed to lipid metabolism disorder involving glycerophospholipid, sphingolipid, arachidonic acid, and alpha-linolenic acid. Collectively, our results provide new evidence revealing the molecular mechanisms of PS-induced reproductive toxicity, highlighting that MNPs may pose a risk to female reproductive health.


Asunto(s)
Trastornos del Metabolismo de los Lípidos , Receptores Activados del Proliferador del Peroxisoma , Poliestirenos , Reproducción , Contaminantes Químicos del Agua , Pez Cebra , Animales , Poliestirenos/toxicidad , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Reproducción/efectos de los fármacos , Trastornos del Metabolismo de los Lípidos/inducido químicamente , Contaminantes Químicos del Agua/toxicidad , Femenino , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Microplásticos/toxicidad
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