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1.
J Am Chem Soc ; 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36896677

RESUMO

The development of stimuli-responsive materials with afterglow emission is highly desirable but remains a formidable challenge in a single-component material system. Herein, we propose a strategy to achieve photoactivated afterglow emission in a variety of amorphous copolymers through self-doping, endowed by the synergetic effect of self-host-induced guest sensitization and thermal-processed polymer rigidification for boosting the generation and stabilization of triplet excitons. Upon continuous ultraviolet illumination for regulating the oxygen concentration, a photoactivated afterglow showing increased lifetimes from 0.34 to 867.4 ms is realized. These afterglow emissions can be naturally or quickly deactivated to the pristine state under ambient conditions or heating treatment. Interestingly, programmable and reusable afterglow patterns, conceptual pulse-width indicators, and "excitation-time lock" Morse code are successfully established using stimuli-responsive afterglow polymers as recorded media. These findings offer an avenue to construct a single-component polymeric system with photoactivated organic afterglow features and demonstrate the superiority of stimuli-responsive materials for remarkable applications.

2.
EMBO J ; : e113033, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36896912

RESUMO

Mitophagy is a fundamental quality control mechanism of mitochondria. Its regulatory mechanisms and pathological implications remain poorly understood. Here, via a mitochondria-targeted genetic screen, we found that knockout (KO) of FBXL4, a mitochondrial disease gene, hyperactivates mitophagy at basal conditions. Subsequent counter screen revealed that FBXL4-KO hyperactivates mitophagy via two mitophagy receptors BNIP3 and NIX. We determined that FBXL4 functions as an integral outer-membrane protein that forms an SCF-FBXL4 ubiquitin E3 ligase complex. SCF-FBXL4 ubiquitinates BNIP3 and NIX to target them for degradation. Pathogenic FBXL4 mutations disrupt SCF-FBXL4 assembly and impair substrate degradation. Fbxl4-/- mice exhibit elevated BNIP3 and NIX proteins, hyperactive mitophagy, and perinatal lethality. Importantly, knockout of either Bnip3 or Nix rescues metabolic derangements and viability of the Fbxl4-/- mice. Together, beyond identifying SCF-FBXL4 as a novel mitochondrial ubiquitin E3 ligase restraining basal mitophagy, our results reveal hyperactivated mitophagy as a cause of mitochondrial disease and suggest therapeutic strategies.

3.
Small ; : e2208105, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36897001

RESUMO

Polymer-based dielectrics are essential components in electrical and power electronic systems for high power density storage and conversion. A mounting challenge for polymer dielectrics is how to maintain their electrical insulation at not only high electric fields but also elevated temperatures, in order to meet the growing needs for renewable energies and grand electrifications. Here, a sandwiched barium titanate/polyamideimide nanocomposite with reinforced interfaces via two-dimensional nanocoatings is presented. It is demonstrated that boron nitride and montmorillonite nanocoatings can block and dissipate injected charges, respectively, to present a synergetic effect on the suppression of conduction loss and the enhancement of breakdown strength. Ultrahigh energy densities of 2.6, 1.8, and 1.0 J cm-3 are obtained at 150 °C, 200 °C, and 250 °C, respectively, with a charge-discharge efficiency >90%, far outperforming the state-of-the-art high-temperature polymer dielectrics. Cyclic charge-discharge tests up to 10 000 times verify the excellent lifetime of the interface-reinforced sandwiched polymer nanocomposite. This work provides a new pathway to design high-performance polymer dielectrics for high-temperature energy storage via interfacial engineering.

4.
Angew Chem Int Ed Engl ; : e202217623, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36897277

RESUMO

The development and mechanistic investigation of a nickel-catalyzed sulfonylation of aryl bromides is disclosed. The reaction proceeds in good yields for a variety of substrates and utilizes an inexpensive, stench-free, inorganic sulfur salt (K2S2O5) as a uniquely effective SO2 surrogate. The active oxidative addition complex was synthesized, isolated, and fully characterized by a combination of NMR spectroscopy and X-ray crystallography analysis. The use of the isolated oxidative addition complex in both stoichiometric and catalytic reactions revealed that SO2 insertion occurs via dissolved SO2, likely released upon thermal decomposition of K2S2O5. Key to the success of the reaction is the role of K2S2O5 as a reservoir of SO2 that is slowly released, thus preventing catalyst poisoning.

5.
J Exp Med ; 220(5)2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36880999

RESUMO

The small intestine plays a key role in immunity and mediates inflammatory responses to high fat diets. We have used single-cell RNA-sequencing (scRNA-seq) and statistical modeling to examine gaps in our understanding of the dynamic properties of intestinal cells and underlying cellular mechanisms. Our scRNA-seq and flow cytometry studies of different layers of intestinal cells revealed new cell subsets and modeled developmental trajectories of intestinal intraepithelial lymphocytes, lamina propria lymphocytes, conventional dendritic cells, and enterocytes. As compared to chow-fed mice, a high-fat high-sucrose (HFHS) "Western" diet resulted in the accumulation of specific immune cell populations and marked changes to enterocytes nutrient absorption function. Utilizing ligand-receptor analysis, we profiled high-resolution intestine interaction networks across all immune cell and epithelial structural cell types in mice fed chow or HFHS diets. These results revealed novel interactions and communication hubs among intestinal cells, and their potential roles in local as well as systemic inflammation.


Assuntos
Dieta Ocidental , Intestinos , Animais , Camundongos , Homeostase , Enterócitos , Comunicação Celular
6.
Front Endocrinol (Lausanne) ; 14: 1125829, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36923221

RESUMO

Background: Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) are closely related to immune and inflammatory pathways. This study aimed to explore the diagnostic markers for CKD patients with NAFLD. Methods: CKD and NAFLD microarray data sets were screened from the GEO database and analyzed the differentially expressed genes (DEGs) in GSE10495 of CKD date set. Weighted Gene Co-Expression Network Analysis (WGCNA) method was used to construct gene coexpression networks and identify functional modules of NAFLD in GSE89632 date set. Then obtaining NAFLD-related share genes by intersecting DEGs of CKD and modular genes of NAFLD. Then functional enrichment analysis of NAFLD-related share genes was performed. The NAFLD-related hub genes come from intersection of cytoscape software and machine learning. ROC curves were used to examine the diagnostic value of NAFLD related hub genes in the CKD data sets and GSE89632 date set of NAFLD. CIBERSORTx was also used to explore the immune landscape in GSE104954, and the correlation between immune infiltration and hub genes expression was investigated. Results: A total of 45 NAFLD-related share genes were obtained, and 4 were NAFLD-related hub genes. Enrichment analysis showed that the NAFLD-related share genes were significantly enriched in immune-related pathways, programmed cell death, and inflammatory response. ROC curve confirmed 4 NAFLD-related hub genes in CKD training set GSE104954 and other validation sets. Then they were used as diagnostic markers for CKD. Interestingly, these 4 diagnostic markers of CKD also showed good diagnostic value in the NAFLD date set GSE89632, so these genes may be important targets of NAFLD in the development of CKD. The expression levels of the 4 diagnostic markers for CKD were significantly correlated with the infiltration of immune cells. Conclusion: 4 NAFLD-related genes (DUSP1, NR4A1, FOSB, ZFP36) were identified as diagnostic markers in CKD patients with NAFLD. Our study may provide diagnostic markers and therapeutic targets for CKD patients with NAFLD.

7.
Tob Induc Dis ; 21: 38, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36923486

RESUMO

INTRODUCTION: The home is the primary source of children's exposure to secondhand smoke. This study investigated the status and influencing factors of child exposure to secondhand smoke at home when people smoke in the household. METHODS: Participants with at least one child living in their household from 10 communities in Chongqing were recruited and provided a self-administered questionnaire using a multistage proportional random sampling design from June to August 2021. The chi-squared test and binary logistic regression analyses were used to identify influencing factors. RESULTS: The questionnaire completed by 1345 families showed that 631 (46.9%) families lived with smokers in their household, and 509 (80.7%) of those families reported that smoking occurred within the home while the children were present. Binary logistic regression analyses demonstrated that the time between waking up and household smokers having the first cigarette of the day (OR=0.44; 95% CI: 0.22-0.85), changes to smoking habits and behaviors within the last six months (OR=1.76; 95% CI: 1.06-2.90), attitudes towards tobacco control in the household (OR=2.91; 95% CI: 1.72-4.92), self-efficacy in maintaining a smoke-free home (OR=2.27; 95% CI: 1.36-3.79), having rules to maintain a smoke-free home (OR=3.25; 95% CI: 1.68-6.29), and the status of providing cigarettes to guests at home (OR=11.0; 95% CI: 1.33-90.8) were associated with exposure to SHS. CONCLUSIONS: Education focusing on the impact of smoking on children's health should be encouraged. Smoke-free homes should be established, and smoking restrictions in the household should be enacted. Therefore, information about the available tobacco-control services should be given to family members and be used properly. It is an effective way to decrease the risk of at-home exposure to SHS for children, to overcome any obstacles in tobacco control.

8.
Am J Med Genet A ; 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36924216

RESUMO

Arteriovenous malformations (AVMs) are vascular lesions in which an overgrowth of blood vessels of varying sizes develops with one or more direct connections between the arterial and venous circulation. We performed a retrospective review of a cohort of 54 patients with AVMs referred to our clinical genomic laboratory for high-depth next-generation sequencing (NGS) panel of Disorders of Somatic Mosaicism (DoSM). Thirty-seven of 54 patients were female (68.5%). Among the 54 cases, 37 (68.5%) cases had pathogenic and/or likely pathogenic (P/LP) variants identified, two cases (3.7%) had variants of uncertain clinical significance, and the remaining 15 cases (27.8%) had negative results. MAP2K1 variants were found in 12 cases, followed by eight cases with KRAS variants and seven with TEK variants, and the remainder being identified in several other genes on the panel. Among the 37 positive cases, 32 cases had somatic alterations only; the remaining five cases had at least one germline P/LP variant, including four cases with PTEN and one with RASA1. Of note, two cases had the unexpected co-existence of two P/LP variants. In summary, this study illustrated the molecular diagnostic yield (68.5%) of this cohort of patients with a clinical indication of AVMs by our high-depth DoSM NGS panel.

9.
Front Mol Neurosci ; 16: 1097553, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36910266

RESUMO

Objective: This study aims to prove that the de novo variants in MAST4 gene are associated with neurodevelopmental disorders (NDD) with developmental delay (DD) and infantile spasm (IS) and to determine the genotype-phenotype correlations. Methods: Trio-based exome sequencing (ES) was performed on the four families enrolled in this study. We collected and systematically reviewed the four probands' clinical data, magnetic resonance images (MRI), and electroencephalography (EEG). We also carried out bioinformatics analysis by integrating published exome/genome sequencing data and human brain transcriptomic data. Results: We described four patients whose median age of seizure onset was 5 months. The primary manifestation was infantile spasms with typical hypsarrhythmia on EEG. Developmental delays or intellectual disabilities varied among the four individuals. Three de novo missense variants in MAST4 gene were identified from four families, including chr5:66438324 (c.2693T > C: p.Ile898Thr) z, chr5:66459419 (c.4412C > T: p.Thr1471Ile), and chr5:66462662 (c.7655C > G:p.Ser2552Trp). The missense variant p.Ile898Thr is mapped to the AGC-kinase C-terminal with phosphatase activity. The other variant p.Ser2552Trp is located in a phosphoserine-modified residue which may affect cell membrane stability and signal transduction. Besides, the variant p.Thr1471Ile is a recurrent site screened out in two unrelated patients. Compared to private mutations (found only in a single family or a small population) of MAST4 in the gnomAD non-neuro subset, all de novo variants were predicted to be damaging or probably damaging through different bioinformatic analyses. Significantly higher CADD scores of the variant p.Thr1471Ile indicate more deleteriousness of the recurrent site. And the affected amino acids are highly conserved across multiple species. According to the Brainspan Atlas database, MAST4 is expressed primarily in the mediodorsal nucleus of the thalamus and medial prefrontal cortex during the prenatal period, potentially contributing to embryonic brain development. Conclusion: Our results revealed that the variants of MAST4 gene might lead to neurodevelopmental disorders with developmental delay and infantile spasm. Thus, MAST4 variants should be considered the potential candidate gene in patients with neurodevelopmental disorders clinically marked by infantile spasms.

10.
Anal Chem ; 95(10): 4644-4652, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36855862

RESUMO

Most fluorescence-based bioanalytical applications need labeling of analytes. Conventional labeling requires washing to remove the excess fluorescent labels and reduce the noise signals. These pretreatments are labor intensive and need specialized equipment, hindering portable applications in resource-limited areas. Herein, we use the aqueous two-phase system (ATPS) to realize the partitioning-induced isolation of labeled analytes from background signals without extra processing steps. ATPS is formed by mixing two polymers at sufficiently high concentrations. ATPS-based isolation is driven by intrinsic affinity differences between analytes and excess labels. To demonstrate the partitioning-induced isolation and analysis, fluorescein isothiocyanate (FITC) is selected as the interfering fluorophore, and a monoclonal antibody (IgG) is used as the analyte. To optimize ATPS compositions, different molecular weights and mass fractions of polyethylene glycol (PEG) and dextran and different phosphate-buffered saline (PBS) concentrations are investigated. Various operational scales of our approach are demonstrated, suggesting its compatibility with various bioanalytical applications. In centimeter-scale ATPS, the optimized distribution ratios of IgG and FITC are 91.682 and 0.998 using PEG 6000 Da and dextran 10,000 Da in 10 mM PBS. In millimeter-scale ATPS, the analyte is enriched to 6.067 fold using 15 wt % PEG 35,000 Da and 5 wt % dextran 500,000 Da in 10 mM PBS. In microscale ATPS, analyte dilutions are isolated into picoliter droplets, and the measured fluorescence intensities linearly correlated with the analyte concentrations (R2 = 0.982).


Assuntos
Dextranos , Água , Fluoresceína-5-Isotiocianato , Polietilenoglicóis , Polímeros , Imunoglobulina G
11.
J Mater Chem B ; 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36916313

RESUMO

Convenient and low-cost dressings can reduce the difficulty of wound treatment. Alginate gel dressings have the advantages of low cost and safe usage, and they have obvious potential for development in biomedical materials. Alginate gel dressings are currently a research area of great interest owing to their versatility, intelligent, and their application attempts in treating complex wounds. We present a detailed summary of the preparation of alginate hydrogels and a study of their performance improvement. Herein, we summarize the various applications of alginate hydrogels. The research focuses in this area mainly include designing multifunctional dressings for the treatment of various wounds and fabricating specialized dressings to assist physicians in the treatment of complex wounds (TOC). This review gives an outlook for future directions in the field of alginate hydrogel dressings. We hope to attract more research interest and studies in alginate hydrogel dressings, thus contributing to the creation of low-cost and highly effective wound treatment materials.

12.
Nano Lett ; 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36880306

RESUMO

Vortex beams, which intrinsically possess optical orbital angular momentum (OAM), are considered as one of the promising chiral light waves for classical optical communications and quantum information processing. For a long time, it has been an expectation to utilize artificial three-dimensional (3D) chiral metamaterials to manipulate the transmission of vortex beams for practical optical display applications. Here, we demonstrate the concept of selective transmission management of vortex beams with opposite OAM modes assisted by the designed 3D chiral metahelices. Utilizing the integrated array of the metahelices, a series of optical operations, including display, hiding, and even encryption, can be realized by the parallel processing of multiple vortex beams. The results open up an intriguing route for metamaterial-dominated optical OAM processing, which fosters the development of photonic angular momentum engineering and high-security optical encryption.

13.
Obes Facts ; 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36882014

RESUMO

Introduction Obesity is a risk factor for both the development of and mortality from breast cancer in postmenopausal but not in premenopausal women. However, which part of the fat mass is associated with risk remains unclear, and whether the difference in the risk for breast cancer is associated with discrepancy in the distribution of fat with menstrual status requires further study. Methods A dataset from the UK Biobank, which included 245,009 female participants, and 5402 females who developed breast cancer during a mean follow-up of 6.6 years was analyzed. Body fat mass was measured according to bioelectrical impedance at baseline by trained technicians. Age- and multivariable-adjusted hazard ratios and corresponding 95% confidence intervals for associations between body fat distribution and the risk for breast cancer were estimated using Cox proportional hazards regression. Height, age, education level, ethnicity, index of multiple deprivation, alcohol intake, smoking, physical activity, fruit consumption, age at menarche, age at first birth, number of births, hormone replacement therapy, family history of breast cancer, hysterectomy, and ovariotomy were adjusted for potential confounders. Results Fat distribution differed between pre- and postmenopausal women. After menopause, there was an increase in fat mass in different body segments (arms, legs, and trunk). After age- and multivariable-adjustment, fat mass in different segments, BMI, and waist circumference were significantly associated with the risk for breast cancer among postmenopausal but not premenopausal women. Conclusion Postmenopausal women exhibited more fat in different body segments, which are associated with increased risk for breast cancer, compared to premenopausal women. Fat mass control throughout the body may be beneficial in mitigating the risk for breast cancer and was not limited to abdominal fat alone among postmenopausal women.

14.
Nutrients ; 15(4)2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36839246

RESUMO

Magnesium (Mg) is an essential nutrient that participates in various enzymatic reactions and regulates important biological functions. The distribution and reference ranges in China have not been reported in populations more than 45 years old. This study aimed to assess the magnesium status and determine the reference values of plasma Mg, Ca, and Ca/Mg ratios for China's population more than 45 years old. A total of 2101 people were randomly selected from the China Nutrition and Health surveillance (CNHS) (2015-2017), considering the regional types and monitoring points. Then, 337 healthy individuals were further selected by a series of strict inclusion criteria to explore the reference range. The plasma magnesium and calcium were tested by inductively coupled plasma mass spectrometry (ICP-MS). The suggested reference values for plasma Mg, Ca, and Ca/Mg ratios were 0.75-1.14 mmol/L, 2.17-3.64 mmol/L, and 2.36-3.66, respectively. Taking 0.75 mmol/L as the lower cut-off limit, the prevalence of Mg deficiency was 6.66%, and the average level of plasma magnesium was 0.88 mmol/L for populations older than 45 years in China. In conclusion, this study provides the magnesium status and reference ranges for plasma Mg, Ca, and Ca/Mg ratio for Chinese people over 45 years old. The results of the recommended reference ranges in this study were very similar to our published results in women of reproductive age. Thus, the reference range of plasma magnesium in different populations in China was further improved.


Assuntos
Cálcio , Magnésio , Humanos , Adulto , Feminino , Pessoa de Meia-Idade , Valores de Referência , População do Leste Asiático , Cálcio da Dieta
15.
Bioact Mater ; 25: 347-359, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36852104

RESUMO

Periodontitis is admittedly a microbe-driven intractable infectious disease, in which Porphyromonas gingivalis (Pg) plays a keystone role. Pg can selectively impair the antimicrobial responses of periodontal resident macrophages including their phagocytic and bactericidal activity without interfering their proinflammatory activity, which leads to microflora disturbance, destructive periodontal inflammation and alveolar bone loss eventually. Here, an injectable ROS-sensitive hydrogel is developed for releasing active bone marrow-derived macrophages (named ex-situ macrophages hereafter) and a complement C5a receptor antagonist (C5A) to the gingival crevice. Through appropriately tuning the hydrogel stiffness, the phagocytic activity of these macrophages is greatly enhanced, reaching an optimal performance at the elastic modulus of 106 kPa. Meanwhile, C5A avoids undesired C5a receptor activation by Pg to ensure the bacterial killing activity of both the ex-situ and in-situ macrophages. Besides, the ROS-sensitive hydrogels show another distinct feature of decreasing the ROS level in periodontal niche, which contributes to the alleviated periodontal inflammation and attenuated bone loss as well. This study highlights the potential of utilizing hydrogels with tailored biomechanical properties to remodel the functions of therapeutic cells, which is expected to find wide applications even beyond periodontitis treatment.

16.
Macromol Rapid Commun ; : e2200928, 2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36786588

RESUMO

In recent years, hydrogels have attracted extensive attention in smart sensing owing to their biocompatibility and high elasticity. However, it is still a challenge to develop hydrogels with excellent multiple responsiveness for smart wearable sensors. In this paper, a facile synthesis of carbon quantum dots (CQDs)-doped cross-linked chitosan quaternary/carboxymethylcellulose hydrogels (CCCDs) is presented. Designing of dual network hydrogels decorated with CQDs provides abundant crosslinking and improves the mechanical properties of the hydrogels. The hydrogel-based strain sensor exhibits excellent sensitivity (gauge factor: 9.88), linearity (R2 : 0.97), stretchable ability (stress: 0.67 MPa; strain: 404%), good cyclicity, and durability. The luminescent properties are endowed by the CQDs further broaden the application of hydrogels for realizing flexible electronics. More interestingly, the strain sensor based on CCCDs hydrogel demonstrates photo responsiveness (ΔR/R0 ≈20%) and pH responsiveness (pH range ≈4-7) performance. CCCDs hydrogels can be used for gesture recognition and light sensing switch. As a proof-of-concept, a smart wearable sensor is designed for monitoring human activities and detecting pH variation in human sweat during exercise. This study reveals new possibilities for further applications in wearable health monitoring.

17.
J Orthop Surg Res ; 18(1): 134, 2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36823648

RESUMO

BACKGROUND: Due to the lack of postoperative reporting outcomes and bio-mechanical studies, an optimal management of scapular fractures has not been well-established in clinical treatment, even though there are many options available. This study aimed to compare the stability of the new titanium anatomic and traditional titanium reconstructive plates for extra-articular scapular fractures through finite element analysis. METHODS: Two models of scapular assembly were constructed, including one anatomic plate (AP model) and one reconstructive plate (RP model). After meshing, material parameter, and boundary condition settings, we applied four loading conditions to simulate forces acting on the scapula and osteosynthesis material. To evaluate the bio-mechanical properties, the equivalent von Mises stress, equivalent elastic strain, and total deformation were investigated. RESULT: The stress and strain distribution of model AP has better performance than model RP, with more uniform and lower values. The maximum stress value of the scapula in model AP is smaller than that of the scapula in model RP (102.83 MPa vs. 166.71 MPa). The maximum stress of the anatomic plate is half that of the reconstructive plate (218.34 MPa vs. 416.01 MPa). The maximum strain of the scapula in model AP is smaller than that of the scapula in model RP (0.0071 vs. 0.0106). The maximum strain of the anatomic plate is half that of the reconstructive plate (0.0019 vs. 0.0037). The maximum displacement of each model is all at the acromion, with a similar value (2.2947 mm vs. 1.8308 mm). CONCLUSIONS: With sufficient bio-mechanical stability, the anatomic plate to support scapular fracture fragments was superior to that of the reconstructive plate.


Assuntos
Fraturas do Ombro , Titânio , Humanos , Análise de Elementos Finitos , Modelos Anatômicos , Estresse Mecânico , Fixação Interna de Fraturas , Acrômio , Placas Ósseas , Fenômenos Biomecânicos
18.
Chin Med J (Engl) ; 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36806264

RESUMO

ABSTRACT: Adoptive therapeutic immune cells, such as chimeric antigen receptor (CAR)-T cells and natural killer cells, have established a new generation of precision medicine based on which dramatic breakthroughs have been achieved in intractable lymphoma treatments. Currently, well-explored approaches focus on autologous cells due to their low immunogenicity, but they are highly restricted by the high costs, time consumption of processing, and the insufficiency of primary cells in some patients. Induced pluripotent stem cells (iPSCs) are cell sources that can theoretically produce indefinite well-differentiated immune cells. Based on the above facts, it may be reasonable to combine the iPSC technology and the CAR design to produce a series of highly controllable and economical "live" drugs. Manufacturing hypoimmunogenic iPSCs by inactivation or over-expression at the genetic level and then arming the derived cells with CAR have emerged as a form of "off-the-shelf" strategy to eliminate tumor cells efficiently and safely in a broader range of patients. This review describes the reasonability, feasibility, superiority, and drawbacks of such approaches, summarizes the current practices and relevant research progress, and provides insights into the possible new paths for personalized cell-based therapies.

19.
Int J Ophthalmol ; 16(2): 251-259, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36816210

RESUMO

AIM: To evaluate the trend of glaucoma internal filtration surgeries for inpatients between 2015 and 2021 at the Eye Hospital of Wenzhou Medical University. METHODS: A review of the medical records of inpatients who had been diagnosed with glaucoma and received anti-glaucoma surgery between January 1, 2015 and December 31, 2021 was conducted. The glaucoma diagnosis in this study included primary open angle glaucoma, primary angle-closure glaucoma, secondary glaucoma, and paediatric glaucoma. The types of surgeries were categorised as internal filtration, external filtration, and cyclodestruction surgery based on the pathway of aqueous humor outflow. The trend of these glaucoma surgeries in the sample of patients with different types of glaucoma was then analysed. RESULTS: The number of patients hospitalised for glaucoma surgery increased yearly, from 752 in 2015 to 1373 in 2021, at the Eye Hospital of Wenzhou Medical University. Regarding the patients diagnosed with primary open angle glaucoma, internal filtration surgery increased from 27.40% of the sample to 54.40% of the sample, while external filtration surgery decreased from 71.50% to 44.20% between 2015 and 2021. For paediatric glaucoma, internal filtration surgery increased from 37.50% in 2015 to 88.20% in 2021. Whilst different types of surgeries were performed on the sample of patients with secondary glaucoma, the proportion of internal filtration surgery also showed an increase from 18.20% in 2015 to 40.90% in 2021. Meanwhile, internal filtration surgery in the patient sample with primary angle-closure glaucoma already accounted for over 70.00% in 2015, and showed a small increase by 2021. CONCLUSION: As surgical technology and surgical experience continue to elevate and improve, the range of glaucoma surgeries are correspondingly evolving. This study find that internal filtration surgeries accounted for an increasing proportion of treatments in the surgical management of glaucoma between 2015 and 2021.

20.
Adv Healthc Mater ; : e2202943, 2023 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-36773308

RESUMO

Synergistic photodynamic and photothermal therapy (PDT-PTT) has emerged as an appealing effective antitumor approach. However, clinical utilization of PDT-PTT is plagued by aggregation-caused photobleaching, sequential double irradiations, unsatisfying balance between single oxygen (1 O2 ) quantum yield and photothermal conversion efficiency. Here, an anchored tumor-homing cell-penetrating peptide (PEGA-pVEC) and PANI-ES/HMME loaded FRET nanobullet (AHP-P) are reported. Within nanobullet, HMME (donor) and PANI-ES (acceptor) spontaneously form a förster resonance energy transfer (FRET) pair. Upon 660 nm laser irradiation, HMME convert near-infrared fluorescence (NIRF) to PANI, thus produce FRET-amplified photoacoustic imaging guided PTT. In addition, AHP-P with pH-sensitivity can gradually release HMME within acidic tumor environment, boosts the 1 O2 regeneration alongside with highly efficient photothermal conversion for photoinduced cancer PTT-PDT. Furthermore, the AHP-P nanobullet can home in on the tumor site and penetrate into cytoplasm through PEGA-pVEC, inducing remarkable tumor regression with an ≈80% tumor volume reduction and decreased skin phototoxicity in vivo during FRET-amplified PTT-PDT.

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