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1.
BMC Geriatr ; 23(1): 66, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36732687

RESUMO

BACKGROUND: For elderly adults undergoing hip arthroplasty, fascia iliaca compartment block (FICB) is often used before spinal anesthesia to reduce the pain of posture placement. However, the impact of FICB within 48 h needs further study. METHODS: 89 elderly adults scheduled to undergo arthroplasty for hip fracture were enrolled and randomized into the FICB group (n = 45) and the control group (n = 44). The fascia iliaca on the operated side was located using ultrasound, and a puncture needle was placed under the fascia iliaca. The FICB group was injected with 40 ml of 0.5% ropivacaine, and the control group was injected with 40 ml of normal saline. Spinal anesthesia was performed after 20 min. Our primary outcome measures were: duration of analgesia, muscle strength, and Quality of Recovery (QoR). RESULTS: The duration of analgesia in the FICB group was 403.5 ± 39.6 min, which was longer than that (357.5 ± 35.9 min) of the control group (P = 0.012). There were 19 (42.2%) patients with muscle strength of grade 4 in the FICB group and 36 (81.8%) patients with muscle strength of grade 4 in the control group. FICB group was lower (P < 0.001). QoR-15 at 24 h after surgery was 114.1 ± 8.3 in the FICB group and 104.6 ± 8.4 in the control group (P < 0.001). QoR-15 at 48 h after surgery was 122.7 ± 8.4 in the FICB group and 120.5 ± 9.5 in the control group (P = 0.232). CONCLUSIONS: For elderly adults with hip fractures, FICB provided longer analgesia and improved 24-h QoR, but reduced postoperative muscle strength. TRAIL REGISTRATION: Chinese Clinical Registry Center, ChiCTR2200056937, 23/02/2022.

2.
Artigo em Inglês | MEDLINE | ID: mdl-36722433

RESUMO

Due to the nonspecific strong nano-bio interaction, the nanocarriers with permanent rough surface are difficult to cross the multiple biological barriers to realize the efficient delivery. Herein, a camouflaged virus-like nanocarrier with transformable rough surface is reported, which is composed by inner virus-like mesoporous SiO2 nanoparticle with rough surface (vSiO2) and outer acid responsive camouflage polymer. At normal physiological environment, the spikes on vSiO2 are hidden by outer polymer, which can effectively inhibit the rough surface induced nonspecific strong nano-bio interaction. While in the acidic tumor microenvironment, the rough surface can be re-exposed by shedding the polymer camouflage, thus improving its retention ability and promoting endocytosis of the nanocarrier by tumor cell. Based on its dynamically variable rough surface, the rationally designed smart nanocarrier exhibit extended blood circulation and enhanced tumor accumulation.

3.
Cell Discov ; 9(1): 6, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36646705

RESUMO

Hypertrophic cardiomyopathy (HCM) is the most common cardiac genetic disorder characterized by cardiomyocyte hypertrophy and cardiac fibrosis. Pathological cardiac remodeling in the myocardium of HCM patients may progress to heart failure. An in-depth elucidation of the lineage-specific changes in pathological cardiac remodeling of HCM is pivotal for the development of therapies to mitigate the progression. Here, we performed single-nucleus RNA-seq of the cardiac tissues from HCM patients or healthy donors and conducted spatial transcriptomic assays on tissue sections from patients. Unbiased clustering of 55,122 nuclei from HCM and healthy conditions revealed 9 cell lineages and 28 clusters. Lineage-specific changes in gene expression, subpopulation composition, and intercellular communication in HCM were discovered through comparative analyses. According to the results of pseudotime ordering, differential expression analysis, and differential regulatory network analysis, potential key genes during the transition towards a failing state of cardiomyocytes such as FGF12, IL31RA, and CREB5 were identified. Transcriptomic dynamics underlying cardiac fibroblast activation were also uncovered, and potential key genes involved in cardiac fibrosis were obtained such as AEBP1, RUNX1, MEOX1, LEF1, and NRXN3. Using the spatial transcriptomic data, spatial activity patterns of the candidate genes, pathways, and subpopulations were confirmed on patient tissue sections. Moreover, we showed experimental evidence that in vitro knockdown of AEBP1 could promote the activation of human cardiac fibroblasts, and overexpression of AEBP1 could attenuate the TGFß-induced activation. Our study provided a comprehensive analysis of the lineage-specific regulatory changes in HCM, which laid the foundation for targeted drug development in HCM.

4.
Stem Cells Int ; 2023: 5915988, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36698376

RESUMO

Mesenchymal stem cells (MSCs) can self-renew and differentiate into multiple lineages, making MSC transplantation a promising option for bone regeneration. Both matricellular proteins and growth factors play an important role in regulating stem cell fate. In this study, we investigated the effects of matricellular protein SMOC2 (secreted modular calcium-binding protein 2) on bone morphogenetic protein 9 (BMP9) in mouse embryonic fibroblasts (MEFs) and revealed a possible molecular mechanism underlying this process. We found that SMOC2 was detectable in MEFs and that exogenous SMOC2 expression potentiated BMP9-induced osteogenic markers, matrix mineralization, and ectopic bone formation, whereas SMOC2 knockdown inhibited these effects. BMP9 increased the levels of p-FAK and p-AKT, which were either enhanced or reduced by SMOC2 and FAK silencing, respectively. BMP9-induced osteogenic markers were increased by SMOC2, and this increase was partially abolished by silencing FAK or LY290042. Furthermore, we found that general transcription factor 2I (GTF2I) was enriched at the promoter region of SMOC2 and that integrin ß1 interacted with SMOC2 in BMP9-treated MEFs. Our findings demonstrate that SMOC2 can promote BMP9-induced osteogenic differentiation by enhancing the FAK/PI3K/AKT pathway, which may be triggered by facilitating the interaction between SMOC2 and integrin ß1.

5.
BMC Anesthesiol ; 23(1): 34, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36707777

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) is now widely used in various surgical fields including gynecological laparoscopic surgery, but the advantages of opioid-free anesthesia (OFA) in gynecological laparoscopic surgery under ERAS protocol are inexact. AIMS: This study aims to assess the effectiveness and feasibility of OFA technique versus traditional opioid-based anesthesia (OA) technique in gynecological laparoscopic surgery under ERAS. METHODS: Adult female patients aged 18 ~ 65 years old undergoing gynecological laparoscopic surgery were randomly divided into OFA group (Group OFA, n = 39) with esketamine and dexmedetomidine or OA group (Group OA, n = 38) with sufentanil and remifentanil. All patients adopted ERAS protocol. The primary outcome was the area under the curve (AUC) of Visual Analogue Scale (VAS) scores (AUCVAS) postoperatively. Secondary outcomes included intraoperative hemodynamic variables, awakening and orientation recovery times, number of postoperative rescue analgesia required, incidence of postoperative nausea and vomiting (PONV) and Pittsburgh Sleep Quality Index (PSQI) perioperatively. RESULTS: AUCVAS was (Group OFA, 16.72 ± 2.50) vs (Group OA, 15.99 ± 2.72) (p = 0.223). No difference was found in the number of rescue analgesia required (p = 0.352). There were no between-group differences in mean arterial pressure (MAP) and heart rate (HR) (p = 0.211 and 0.659, respectively) except MAP at time of surgical incision immediately [(Group OFA, 84.38 ± 11.08) vs. (Group OA, 79.00 ± 8.92), p = 0.022]. Times of awakening and orientation recovery in group OFA (14.54 ± 4.22 and 20.69 ± 4.92, respectively) were both longer than which in group OA (12.63 ± 3.59 and 18.45 ± 4.08, respectively) (p = 0.036 and 0.033, respectively). The incidence of PONV in group OFA (10.1%) was lower than that in group OA (28.9%) significantly (p = 0.027). The postoperative PSQI was lower than the preoperative one in group OFA (p = 0.013). CONCLUSION: In gynecological laparoscopic surgery under ERAS protocol, OFA technique is non-inferior to OA technique in analgesic effect and intraoperative anesthesia stability. Although awakening and orientation recovery times were prolonged compared to OA, OFA had lower incidence of PONV and improved postoperative sleep quality. TRIAL REGISTRATION: ChiCTR2100052761, 05/11/2021.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Laparoscopia , Adulto , Idoso , Feminino , Humanos , Analgésicos Opioides , Anestesia Geral , Laparoscopia/métodos , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Náusea e Vômito Pós-Operatórios/epidemiologia , Náusea e Vômito Pós-Operatórios/etiologia , Adolescente , Adulto Jovem , Pessoa de Meia-Idade
6.
Adv Sci (Weinh) ; : e2206176, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36638249

RESUMO

The currently available materials cannot meet the requirements of human thermal comfort against the hot and cold seasonal temperature fluctuations. In this study, a dual-mode Janus film with a bonded interface to gain dual-mode functions of both highly efficient radiative cooling and solar heating for year-round thermal management is designed and prepared. The cooling side is achieved by embedding NaH2 PO2 particles with high infrared radiation (IR) emittance into a porous polymethyl methacrylate (PMMA) film during pore formation process, which is reported for the first time to the knowledge. A synergistic enhancement of NaH2 PO2 and 3D porous structure leads to efficient radiant cooling with high solar reflectance (R̅solar ≈ 92.6%) and high IR emittance (ε̅IR ≈ 97.2%), especially the ε̅IR value is much greater than that of the reported best porous polymer films. In outdoor environments under 750 mW cm-2 solar radiation, the dual-mode Janus film shows subambient cooling temperature of ≈8.8 °C and heating temperature reaching ≈39.3 °C, indicating excellent thermal management capacity. A wide temperature range is obtained only by flipping the dual-mode Janus film for thermal management. This work provides an advanced zero-energy-consumption human thermal management technique based on the high-performance dual-mode integrated Janus film material.

7.
ACS Appl Mater Interfaces ; 15(1): 378-390, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36594213

RESUMO

Most enzyme catalysts are unable to achieve effective oxidation resistance because of the monotonous mimicking function or production of secondary reactive oxygen species (ROS). Herein, the Au@Cu2O heterostructure with multienzyme-like activities is deigned, which has significantly improved antioxidant capacity compared with pure Cu2O for the scavenging of highly cell-damaging secondary ROS, i.e.,·OH. Experiments and theoretical calculations show that the heterostructure exhibits a built-in electric field and lattice mismatch at the metal-semiconductor interface, which facilitate to generate abundant oxygen vacancies, redox couples, and surface electron deficiency. On the one hand, the presence of rich oxygen vacancies and redox couple can enhance the adsorption and activation of oxygen-containing ROS (including O2·- and H2O2). On the other hand, the electron transfer between the electron-deficient Au@Cu2O surface and electron donor would promote peroxide-like activity and avoid producing ·OH. Importantly, endogenous ·OH could be eliminated in both acidic and neutral conditions, which is no longer limited by the volatile physiological environment. Therefore, Au@Cu2O can simulate superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and glutathione peroxidase (GPx) to form a complete antioxidant system. The deigned nanoenzyme is explored in the real sample world such as A549 cells and zebrafish. This work provides theoretical and practical strategies for the construction of a complete antioxidant enzyme system.


Assuntos
Antioxidantes , Peróxido de Hidrogênio , Animais , Espécies Reativas de Oxigênio , Peixe-Zebra , Oxigênio , Superóxido Dismutase/química , Catalase/química
8.
FASEB J ; 37(2): e22758, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36607288

RESUMO

Stress in the endoplasmic reticulum (ER) may perturb proteostasis and activates the unfolded protein response (UPR). UPR activation is frequently observed in cancer cells and is believed to fuel cancer progression. Here, we report that one of the three UPR sensors, ATF6α, was associated with prostate cancer (PCa) development, while both genetic and pharmacological inhibition of ATF6α impaired the survival of castration-resistance PCa (CRPC) cells. Transcriptomic analyses identified the molecular pathways deregulated upon ATF6α depletion, and also discovered considerable disparity in global gene expression between ATF6α knockdown and Ceapin-A7 treatment. In addition, combined analyses of human CRPC bulk RNA-seq and single-cell RNA-seq (scRNA-seq) public datasets confirmed that CRPC tumors with higher ATF6α activity displayed higher androgen receptor (AR) activity, proliferative and neuroendocrine (NE) like phenotypes, as well as immunosuppressive features. Lastly, we identified a 14-gene set as ATF6α NE gene signature with encouraging prognostic power. In conclusion, our results indicate that ATF6α is correlated with PCa progression and is functionally relevant to CRPC cell survival. Both specificity and efficacy of ATF6α inhibitors require further refinement and evaluation.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Resposta a Proteínas não Dobradas , Retículo Endoplasmático/metabolismo , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Linhagem Celular Tumoral , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo
9.
Anim Nutr ; 12: 263-275, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36712404

RESUMO

This study was to investigate time-course effects of different types of dietary fiber on the energy values, fecal microbiota and short-chain fatty acid (SCFA) concentration in growing pigs. A total of 24 barrows (initial body weight, 19.8 ± 0.5 kg) were assigned to 4 dietary treatments based on body weight (BW) in a completely randomized design, including a basal diet (CON) and 3 fiber-rich diets replacing corn, soybean meal and soybean oil in the CON diet with 20% sugar beet pulp (SBP), defatted rice bran (DFRB) or soybean hull (SBH), respectively. Fresh feces were sampled on d 7, 14 and 21, followed by 5 d total feces and urine collections. The results showed that there were no differences in DE and ME between any of the fiber ingredients on d 7, 14 or 21. However, fiber inclusion decreased the DE and ME of the diet (P < 0.05) regardless of the time effect. Principal coordinate analysis (PCoA) revealed distinctly different microbial communities on the DFRB diet and SBH diet across different times (P < 0.05) and the fecal microbiota of the 4 diet groups demonstrated notably distinct clusters at each time point (P < 0.05). With adaptation time increased from 7 to 21 d, cellulose-degrading bacteria and SCFA-producing bacteria (e.g., Ruminococcaceae _UCG-014, Rikenellaceae _RC9_gut_group and Bifidobacterium) increased in the fiber inclusion diets, and pathogenic genera (e.g., Streptococcus and Selenomonas) were increased in the basal diet (P < 0.05). Furthermore, the gut microbiota of growing pigs adapted more easily and quickly to the SBP diet compared to the DFRB diet, as reflected by the concentration of propionate, butyrate, isovalerate and total SCFA which increased with time for growing pigs fed the DFRB diet (P < 0.05). Collectively, our results indicated at least 7 d adaptation was required to evaluate the energy values of fiber-rich ingredients, as the hindgut microbiota of growing pigs may need more time to adapt to a high fiber diet, especially for insoluble dietary fiber.

10.
Front Pharmacol ; 14: 1085765, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36713829

RESUMO

Background: Cancer precision medicine is an effective strategy to fight cancers by bridging genomics and drug discovery to provide specific treatment for patients with different genetic characteristics. Although some public databases and modelling frameworks have been developed through studies on drug response, most of them only considered the ramifications of the drug on the cell line and the effects on the patient still require a huge amount of work to integrate data from various databases and calculations, especially concerning precision treatment. Furthermore, not only efficacy but also the adverse effects of drugs on patients should be taken into account during cancer treatment. However, the adverse effects as essential indicators of drug safety assessment are always neglected. Method: A holistic estimation explores various drugs' efficacy levels by calculating their potency both in reversing and enhancing cancer-associated gene expression change. And a method for bridging the gap between cell culture and living tissue estimates the effectiveness of a drug on individual patients through the mappings of various cell lines to each person according to their genetic mutation similarities. Result: We predicted the efficacy of FDA-recommended drugs, taking into account both efficacy and toxicity, and obtained consistent results. We also provided an intuitive and easy-to-use web server called DBPOM (http://www.dbpom.net/, a comprehensive database of pharmaco-omics for cancer precision medicine), which not only integrates the above methods but also provides calculation results on more than 10,000 small molecule compounds and drugs. As a one-stop web server, clinicians and drug researchers can also analyze the overall effect of a drug or a drug combination on cancer patients as well as the biological functions that they target. DBPOM is now public, free to use with no login requirement, and contains all the data and code. Conclusion: Both the positive and negative effects of drugs during precision treatment are essential for practical application of drugs. DBPOM based on the two effects will become a vital resource and analysis platform for drug development, drug mechanism studies and the discovery of new therapies.

11.
Artigo em Inglês | MEDLINE | ID: mdl-36719253

RESUMO

Transition-metal catalyzed intermolecular 1,2-diarylation of electronically unactivated alkenes has emerged as an extensive research topic in organic synthesis. However, most examples are mainly limited to terminal alkenes. Furthermore, transition-metal catalyzed asymmetric 1,2-diarylation of unactivated alkenes still remains unsolved and is a formidable challenge. Herein, we describe a highly efficient directed nickel-catalyzed reductive 1,2-diarylation of unactivated internal alkenes with high diastereoselectivities. More importantly, our further effort towards enantioselective 1,2-diarylation of the unactivated terminal and challenging internal alkenes is achieved, furnishing various polyarylalkanes featuring benzylic stereocenters in high yields and with good to high enantioselectivities and high diastereoselectivities. Interestingly, the generation of cationic Ni-catalyst by adding alkali metal fluoride is the key to increased efficiency of this enantioselective reaction.

12.
J Mol Histol ; 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36719565

RESUMO

Extracellular matrix (ECM) production and nucleus pulposus (NP) cell migration increase under periodic mechanical stress (PMS), but the underpinning regulatory mechanism remains unclear. This work aimed to examine the regulatory effects of cytoskeleton-lipid raft-integrin α1 signaling in NP cells exposed to PMS. Briefly, In NP cells, cytoskeleton rearrangement, lipid raft aggregation and integrin α1 expression in the stress and control groups were assessed by immunofluorescent staining and immunoblot. In addition, cell migration and ECM gene expression were detected by a scratch test and quantitative reverse transcription polymerase chain reaction (qRT­PCR), respectively. As a result, PMS up-regulated ECM gene expression and enhanced NP cell migration (both P < 0.05), accompanied by increased integrin α1, lipid raft, caveolin-3, F-actin and ß-tubulin amounts. Pretreatment with the lipid raft inhibitor methyl-ß-cyclodextrin (MßCD) or small interfering RNA (siRNA) targeting caveolin-3 resulted in decreased ECM mRNA synthesis and cell migration induced by PMS (both P < 0.05); meanwhile, integrin α1 expression was also reduced. F-actin and ß-tubulin inhibition by cytochalasin D and colchicine, respectively, not only reduced ECM mRNA synthesis and cell migration (both P < 0.05), but also disrupted lipid raft and caveolin-3 amount increases induced by PMS in NP cells. In conclusion, PMS promotes ECM mRNA up-regulation and cell migration through the cytoskeleton-lipid raft-integrin α1 signaling pathway, inhibiting cytoskeleton and lipid rafts could block the cellular effects.

13.
J Agric Food Chem ; 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36719855

RESUMO

Type 2 diabetic osteoporosis (T2DOP) is a chronic bone metabolic disease. Compared with traditional menopausal osteoporosis, the long-term high glucose (HG) microenvironment increases patients' risk of fracture and osteonecrosis. We were accumulating evidence that implicated ferroptosis as a pivotal mechanism of glucolipotoxicity-mediated death of osteocytes and osteoblast, a novel form of programmed cell death resulting from uncontrolled lipid peroxidation depending on iron. Vitamin K2 (VK2), a fat-soluble vitamin, is clinically applied to prevent osteoporosis and improve coagulation. This study aimed to clarify the role and mechanism of VK2 in HG-mediated ferroptosis. We established the mouse T2DOP model by intraperitoneal injection of streptozotocin solution and a high-fat and high-sugar diet. We also cultured bone marrow mesenchymal stem cells (BMSCs) in HG to simulate the diabetic environment in vitro. Based on our data, VK2 inhibited HG-mediated bone loss and ferroptosis, the latter manifested by decreased levels of mitochondrial reactive oxygen species, lipid peroxidation, and malondialdehyde and increased glutathione in vitro. In addition, VK2 treatment was capable of restoring bone mass and strengthening the expression of SIRT1, GPX4, and osteogenic markers in the distal femurs. As for further mechanism exploration, we found that VK2 could activate AMPK/SIRT1 signaling, and knockdown of SIRT1 by siRNA prevented the VK2-mediated positive effect in HG-cultured BMSCs. Summarily, VK2 could ameliorate T2DOP through the activation of the AMPK/SIRT1 signaling pathway to inhibit ferroptosis.

14.
Psychol Res Behav Manag ; 16: 169-177, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36699988

RESUMO

Objective: Based on the motivated cognition account, this study aimed to explore the relationship between mental health education competency and interpersonal trust among college counselors, as well as the mediating effect of neuroticism. Materials and Methods: A total of 483 college counselors were selected, including 155 men and 328 women. The youngest college counselor was 22 years old and the oldest was 56 years old (M = 31.69, SD = 6.12). The college counselors were asked to fill out the Mental Health Education Competency Scale for College Counselors, a 10-item short version of the Big Five Inventory, and an Interpersonal Trust Scale. Results: (1) This study found a significantly positive correlation between mental health education competency and interpersonal trust. (2) Mental health education competency and interpersonal trust were negatively correlated with neuroticism. (3) The mediating role of neuroticism in the association between mental health education competency and interpersonal trust was significant. Conclusion: Mental health education competency partly affected interpersonal trust via the mediating effect of neuroticism.

15.
Food Chem ; 411: 135527, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36701915

RESUMO

Albino tea has been receiving growing attention on the tea market due to its attractive appearance and fresh taste, mainly caused by high amino acid contents. Here, variations in the contents of five free amino acids in relation to pigment contents and tree age in two hybrid populations'Longjin 43'(♀) × 'Baijiguan'(♂) and 'Longjin 43'(♀) ×'Huangjinya'(♂) with 334 first filial generation individuals including chlorophyll-deficient and normal tea plants were investigated. The data showed that the contents of main amino acids in all filial generation gradually decreased as plant age increased. Principal component analysis indicated that the amino acid content of individual plant tended to be stable with the growth of plants. Correlation analysis clarified that several main amino acids were significantly negatively correlated with chlorophyll a, chlorophyll b and carotenoid contents. Our results showed that the accumulation of amino acids in tea plant was closely related to leaf color variation and the tree age during growing period.

16.
Nat Med ; 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36702948

RESUMO

Early detection of visual impairment is crucial but is frequently missed in young children, who are capable of only limited cooperation with standard vision tests. Although certain features of visually impaired children, such as facial appearance and ocular movements, can assist ophthalmic practice, applying these features to real-world screening remains challenging. Here, we present a mobile health (mHealth) system, the smartphone-based Apollo Infant Sight (AIS), which identifies visually impaired children with any of 16 ophthalmic disorders by recording and analyzing their gazing behaviors and facial features under visual stimuli. Videos from 3,652 children (≤48 months in age; 54.5% boys) were prospectively collected to develop and validate this system. For detecting visual impairment, AIS achieved an area under the receiver operating curve (AUC) of 0.940 in an internal validation set and an AUC of 0.843 in an external validation set collected in multiple ophthalmology clinics across China. In a further test of AIS for at-home implementation by untrained parents or caregivers using their smartphones, the system was able to adapt to different testing conditions and achieved an AUC of 0.859. This mHealth system has the potential to be used by healthcare professionals, parents and caregivers for identifying young children with visual impairment across a wide range of ophthalmic disorders.

17.
Adv Healthc Mater ; : e2202658, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36652529

RESUMO

The inflammatory cascade after spinal cord injury (SCI) causes necrotizing apoptosis of local stem cells, which limits nerve regeneration. Therefore, coordinating the inflammatory immune response and neural stem cell (NSC) functions is key to promoting the recovery of central nervous system function. In this study, a hydrogel "perfusion" system and electrospinning technology are integrated, and a "concrete" composite support for the repair of nerve injuries is built. The hydrogel's hydrophilic properties activate macrophage integrin receptors to mediate polarization into anti-inflammatory subtypes and cause a 10% increase in polarized M2 macrophages, thus reprogramming the SCI immune microenvironment. Programmed stromal cell-derived factor-1α and brain-derived neurotrophic factor released from the composite increase recruitment and neuronal differentiation of NSCs by approximately four- and twofold, respectively. The fiber system regulates the SCI immune inflammatory microenvironment, recruits endogenous NSCs, promotes local blood vessel germination and maturation, and improves nerve function recovery in a rat SCI model. In conclusion, the engineering fiber composite improves the local inflammatory response. It promotes nerve regeneration through a hydrophilic programmed cytokine-delivery system, which further improves and supplements the immune response mechanism regulated by the inherent properties of the biomaterial. The new fiber composite may serve as a new treatment approach for SCI.

19.
Chemistry ; 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604309

RESUMO

Photonic disinfection, particularly near-infrared (NIR) light triggered antibacterial, has emerged as a highly promising solution for combating pathogenic microbes due to its spatiotemporal operability, safety, and low cost of apparatus. However, it remains challenging to construct NIR-responsive antibacterial agents with high light-converting efficacy and elucidate synergistic mechanisms. In this work, novel ultrathin two-dimensional (2D) BiOCl-Bi2S3-Cu2S ternary heterostructures that can efficiently kill drug-resistant bacteria were synthesized by doping 0D Bi2S3 and Cu2S nanoparticles in the 2D BiOCl nanosheets via a facile one-pot hydrothermal method. Notably, the incorporation of Cu2S nanoparticles bestows strong NIR light-harvesting capability to the composite nanosheets due to their localized surface plasmon resonance (LSPR). Upon NIR light illumination, the BiOCl-Bi2S3-Cu2S nanosheets can exert both enhanced photonic hyperthermia and reaction oxygen species (ROS) generation, serving as single light-activated bi-functional photothermal and photodynamic therapeutics. Here, high-speed hot electrons and large local electronic fields caused by LSPR might play important roles on thermal vibrations and effective carrier separations respectively. Benefiting from the unique ternary heterostructures, both the photothermal conversion efficacy and ROS generation efficacy of BiOCl-Bi2S3-Cu2S nanosheets are remarkably improved in comparison to the binary BiOCl-Cu2S or BiOCl-Bi2S3 nanosheets. Accordingly, the ternary composite nanosheets can effectively kill bacteria via the NIR-driven photonic disinfection mechanism. This work presents a new type of 2D composite nanosheets with ternary heterostructures for NIR photonic disinfection.

20.
Biomater Sci ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607143

RESUMO

The development of efficient nanomedicines to repress the repolarization of M1 phenotype macrophages and therefore inhibit pro-inflammatory cytokine overexpression for anti-inflammatory therapy is still a challenging task. We report here an original gene delivery nanoplatform based on pyrrolidinium-modified amphiphilic generation 1 phosphorus dendron (C12G1) nanomicelles with a rigid phosphorous dendron structure. The nanomicelles display higher gene delivery efficiency than the counterpart materials of pyrrolidinium-modified G1 phosphorus dendrimers, and meanwhile exhibit excellent cytocompatibility. The C12G1 nanomicelles can be employed to co-deliver the miRNA-146a mimic (miR-146a mimic) and miRNA-429 inhibitor (miR-429i) to inhibit the Toll-like receptor-4 signaling pathway and p38 mitogen-activated protein kinase signaling pathway, respectively, thus causing repression of M1 phenotype alveolar macrophage polarization. The developed C12G1/miR-mixture polyplexes enable efficient therapy of lipopolysaccharide-activated alveolar macrophages in vitro and an acute lung injury mouse model in vivo. The generated cationic phosphorus dendron nanomicelles may hold promising potential for anti-inflammatory gene therapy of other inflammatory diseases.

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