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1.
Angew Chem Int Ed Engl ; : e202409004, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38837495

ABSTRACT

Previous N-glycosylation approaches have predominately involved acidic conditions, facing challenges of low stereoselectivity and limited scope. Herein, we introduce a radical activation strategy that enables versatile and stereoselective N-glycosylation using readily accessible glycosyl sulfinate as a donor under basic conditions and exhibits exceptional tolerance towards various N-aglycones containing alkyl, aryl, heteroaryl and nucleobase functionalities. Preliminary mechanistic studies indicate a pivotal role of iodide, which orchestrates the formation of a glycosyl radical from the glycosyl sulfinate and subsequent generation of the key intermediate, a configurationally well-defined glycosyl iodide, which is subsequently attacked by an N-aglycone in a stereospecific SN2 manner to give the desired N-glycosides. An alternative route involving the coupling of a glycosyl radical and a nitrogen-centered radical is also proposed, affording the exclusive 1,2-trans product. This novel approach promises to broaden the synthetic landscape of N-glycosides, offering a powerful tool for the construction of complex glycosidic structures under mild conditions.

2.
Brain Sci ; 14(5)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38790400

ABSTRACT

Attention plays an important role in not only the awareness and perception of tinnitus but also its interactions with external sounds. Recent evidence suggests that attention is heightened in the tinnitus brain, likely as a result of relatively local cortical changes specific to deafferentation sites or global changes that help maintain normal cognitive capabilities in individuals with hearing loss. However, most electrophysiological studies have used passive listening paradigms to probe the tinnitus brain and produced mixed results in terms of finding a distinctive biomarker for tinnitus. Here, we designed a selective attention task, in which human adults attended to one of two interleaved tonal (500 Hz and 5 kHz) sequences. In total, 16 tinnitus (5 females) and 13 age- and hearing-matched control (8 females) subjects participated in the study, with the tinnitus subjects matching the tinnitus pitch to 5.4 kHz (range = 1.9-10.8 kHz). Cortical responses were recorded in both passive and attentive listening conditions, producing no differences in P1, N1, and P2 between the tinnitus and control subjects under any conditions. However, a different pattern of results emerged when the difference was examined between the attended and unattended responses. This attention-modulated cortical response was significantly greater in the tinnitus than control subjects: 3.9-times greater for N1 at 5 kHz (95% CI: 2.9 to 5.0, p = 0.007, ηp2 = 0.24) and 3.0 for P2 at 500 Hz (95% CI: 1.9 to 4.5, p = 0.026, ηp2 = 0.17). We interpreted the greater N1 modulation as local neural changes specific to the tinnitus frequency and the greater P2 as global changes to hearing loss. These two cortical measures were used to differentiate between the tinnitus and control subjects, producing 83.3% sensitivity and 76.9% specificity (AUC = 0.81, p = 0.006). These results suggest that the tinnitus brain is more plastic than that of the matched non-tinnitus controls and that the attention-modulated cortical response can be developed as a clinically meaningful biomarker for tinnitus.

3.
Anal Chem ; 96(22): 9078-9087, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38770734

ABSTRACT

As an important disease biomarker, the development of sensitive detection strategies for miRNA, especially intracellular miRNA imaging strategies, is helpful for early diagnosis of diseases, pathological research, and drug development. Hybridization chain reaction (HCR) is widely used for miRNA imaging analysis because of its high specificity and lack of biological enzymes. However, the classic HCR reaction exhibits linear amplification with low efficiency, limiting its use for the rapid analysis of trace miRNA in living cells. To address this problem, we proposed a toehold-mediated exponential HCR (TEHCR) to achieve highly sensitive and efficient imaging of miRNA in living cells using ß-FeOOH nanoparticles as transfection vectors. The detection limit of TEHCR was as low as 92.7 fM, which was 8.8 × 103 times lower compared to traditional HCR, and it can effectively distinguish single-base mismatch with high specificity. The TEHCR can also effectively distinguish the different expression levels of miRNA in cancer cells and normal cells. Furthermore, TEHCR can be used to construct OR logic gates for dual miRNA analysis without the need for additional probes, demonstrating high flexibility. This method is expected to play an important role in clinical miRNA-related disease diagnosis and drug development as well as to promote the development of logic gates.


Subject(s)
MicroRNAs , Nucleic Acid Hybridization , MicroRNAs/analysis , MicroRNAs/metabolism , Humans , Limit of Detection , Nucleic Acid Amplification Techniques/methods , Ferric Compounds/chemistry
4.
Anal Chem ; 96(17): 6774-6783, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38634427

ABSTRACT

The identification of a specific tumor cell is crucial for the early diagnosis and treatment of cancer. However, it remains a challenge due to the limited sensitivity and accuracy, long response time, and low contrast of the recent approaches. In this study, we develop a dual miRNA-triggered DNA walker (DMTDW) assisted by APE1 for the specific recognition of tumor cells. miR-10b and miR-155 were selected as the research models. Without miR-10b and miR-155 presence, the DNA walker remains inactive as its walking strand of W is locked by L1 and L2. After miR-10b and miR-155 are input, the DNA walker is triggered as miR-10b and miR-155 bind to L1 and L2 of W-L1-L2, respectively, unlocking W. The DNA walker is driven by endogenous APE1 that is highly catalytic and is highly expressed in the cytoplasm of tumor cells but barely expressed in normal cells, ensuring high contrast and reaction efficiency for specific recognition of tumor cells. Dual miRNA input is required to trigger the DNA walker, making this strategy with a high accuracy. The DMTDW strategy exhibited high sensitivity for miRNA analysis with a detection limit of 44.05 pM. Living cell-imaging experiments confirmed that the DMTDW could effectively respond to the fluctuation of miRNA and specifically identified MDA-MB-231 cells from different cell lines. The proposed DMTDW is sensitive, rapid, and accurate for specific tumor cell recognition. We believe that the DMTDW strategy can become a powerful diagnostic tool for the specific recognition of tumor cells.


Subject(s)
DNA-(Apurinic or Apyrimidinic Site) Lyase , MicroRNAs , MicroRNAs/analysis , MicroRNAs/metabolism , MicroRNAs/genetics , Humans , DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism , DNA/chemistry , Cell Line, Tumor
5.
Sci Total Environ ; 932: 172760, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38670369

ABSTRACT

Owing to stringent vehicle emission regulations and the shifting automotive landscape towards clean-energy vehicles, the emission of non-exhaust tire-wear particles and its implications for microplastic contamination have garnered substantial attention, emerging as a focal point of research interest. Unlike traditional source apportionment methods involving direct environmental sampling, this study focuses on the physical and chemical attributes of tire treads, the tread temperature changes, and the tire-wear particle emissions of three light-duty vehicles manufactured between 2011 and 2021. This study advances the understanding of the effects of tire properties on particle emissions, which provides preliminary information on low-wear tires. The results show that tire-wear particle emissions, mainly composed of ultrafine particles in terms of number, heavily depend on the elevated tread temperatures. The change in tread temperature is influenced not only by the initial tread temperature but also by tread pyrolysis characteristics. Ca, Mg, and Zn are abundantly contained in the tire tread and tire-wear particles.

6.
Int J Nanomedicine ; 19: 3441-3459, 2024.
Article in English | MEDLINE | ID: mdl-38617798

ABSTRACT

Immune cells are pivotal in the dynamic interplay between hypoxia and inflammation. During hypoxic conditions, HIF-1α, a crucial transcription factor, facilitates the adaptation of immune cells to the hypoxic micro-environment. This adaptation includes regulating immune cell metabolism, significantly impacting inflammation development. Strategies for anti-inflammatory and hypoxic relief have been proposed, aiming to disrupt the hypoxia-inflammation nexus. Research extensively focuses on anti-inflammatory agents and materials that target immune cells. These primarily mitigate hypoxic inflammation by encouraging M2-macrophage polarization, restraining neutrophil proliferation and infiltration, and maintaining Treg/TH17 balance. Additionally, oxygen-releasing nano-materials play a significant role. By alleviating hypoxia and clearing reactive oxygen species (ROS), these nano-materials indirectly influence immune cell functions. This paper delves into the response of immune cells under hypoxic conditions and the resultant effects on inflammation. It provides a comprehensive overview of various therapies targeting specific immune cells for anti-inflammatory purposes and explores nano-materials that either carry or generate oxygen to alleviate anoxic micro-environments.


Subject(s)
Hypoxia , Inflammation , Humans , Inflammation/drug therapy , Oxygen , Macrophage Activation , Anti-Inflammatory Agents/pharmacology
7.
Chemistry ; 30(20): e202303852, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38299784

ABSTRACT

Recently, extensive works have focused on increasing the dissymmetry factors (glum) of various circularly polarized luminescence (CPL) materials, which is one of the most important factors for future applications of CPL. Herein, we designed a chiral co-assembled liquid crystal polymer (LCP) PTZ@R/S-PB2, which was prepared by chiral binary co-polymer (R/S-PB2) doped with achiral phenothiazine derivation dye (PTZ). For comparison, ternary co-polymerized LCP (R/S-PT) was synthesized by co-polymerizing with mesogenic monomer, chiral monomer and emissive monomer. Both PTZ@R/S-PB2 and R/S-PT showed aggregation-induced emission (AIE) properties. Interestingly, the CPL signals of both PTZ@R/S-PB2 and R/S-PT were reversed and amplified after thermal annealing treatment. The |glum| values of the co-assembled PTZ@R/S-PB2 were up to 0.13 at a 32 nm thickness, which was 5.4 times that of R/S-PT (|glum|=0.024). This is due to PTZ@R/S-PB2 could form more orderly chiral co-assembly structures. Noticeably, increasing the LCP film thickness could further improve the glum value, and the maximum glum of PTZ@R/S-PB2 could be enhanced to +0.91/-0.82 at a 220 nm thickness.

8.
Ecol Evol ; 14(2): e10893, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38314313

ABSTRACT

The Guizhou golden monkey (Rhinopithecus brelichi) is a critically endangered wildlife species, and understanding its diet composition may be useful for assessing its feeding strategies. DNA metabarcoding was used to determine the dietary diversity of R. brelichi. DNA was extracted from 31 faecal samples and amplified chloroplast rbcL and mitochondrial COI DNA was sequenced using the Illumina NovaSeq platform. A comparative analysis of the sequences revealed that the five most abundant plant genera were Magnolia, Morinda, Viburnum, Tetradium and Eurya. In winter, R. brelichi mostly consumed shrubs, herbs and shrubs/trees according to the habit of plant genera with higher abundances comparatively. The five most abundant families in animal diet were Psychodidae, Trichinellidae, Staphylinidae, Scarabaeidae and Trichoceridae. This study is the first to show the composition of the winter animal diets of R. brelichi based on DNA metabarcoding. These results provide an important basis for understanding the diet of wild R. brelichi, which inhabits only the Fanjingshan National Nature Reserve, China.

9.
NPJ Syst Biol Appl ; 10(1): 15, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38346982

ABSTRACT

With the increasing availability of large-scale biology data in crop plants, there is an urgent demand for a versatile platform that fully mines and utilizes the data for modern molecular breeding. We present Crop-GPA ( https://crop-gpa.aielab.net ), a comprehensive and functional open-source platform for crop gene-phenotype association data. The current Crop-GPA provides well-curated information on genes, phenotypes, and their associations (GPAs) to researchers through an intuitive interface, dynamic graphical visualizations, and efficient online tools. Two computational tools, GPA-BERT and GPA-GCN, are specifically developed and integrated into Crop-GPA, facilitating the automatic extraction of gene-phenotype associations from bio-crop literature and predicting unknown relations based on known associations. Through usage examples, we demonstrate how our platform enables the exploration of complex correlations between genes and phenotypes in crop plants. In summary, Crop-GPA serves as a valuable multi-functional resource, empowering the crop research community to gain deeper insights into the biological mechanisms of interest.


Subject(s)
Phenotype , Crops, Agricultural/genetics , Genes, Plant
10.
Adv Mater ; 36(16): e2312331, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38217293

ABSTRACT

Stimuli-responsive circularly polarized luminescence (CPL) materials show great promise in applying information encryption and anticounterfeiting. Herein, light-driven CPL sign inversion is achieved by combining a photoresponsive achiral negative dichroic dye (KG) and a static achiral positive dichroic dye (NR) as dopants at the 0.5:0.5 weight ratio into the cholesteric liquid crystal (CLC) host. The side chains of KG undergo trans/cis isomerization after 365 nm UV light irradiation, leading to the dichroism (SF) decrease. The |glum| value of CLC doping with KG (CLC-KG) weakens from 0.67 to 0.28 in response to the order degree change. Taking advantage of its unique CPL response property, the light-driven CPL sign inversion is achieved (from -0.20/0.14 to 0.02/-0.04) by incorporating NR (0.5:0.5) into the CLC-KG with helical superstructure static. Based on the synergistic use of circular polarization and responsiveness state as cryptographic primitives, the multidimensional information encryption CLC system can be realized.

11.
Int J Biol Macromol ; 260(Pt 2): 129454, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38237836

ABSTRACT

Persistent bleeding and the absence of alveolar bone stress following tooth loss can hinder socket healing, complicating future dental implant procedures, and potentially leading to neighboring tooth instability. Therefore, developing materials that promote alveolar bone regeneration and possess both hemostatic and osteogenic properties is crucial for preserving the extraction sites. This study introduces a silk-based laponite composite scaffold material with proficient hemostatic and osteogenic functions, and excellent shape-memory properties for efficient extraction- site filling. In vitro studies research demonstrated that the scaffold's inherent negative charge of the scaffold significantly enhanced blood coagulation and thrombin generation. Moreover, its porous structure and slightly rough inner surface promoted blood cell adhesion and, improved the hemostatic performance. Furthermore, the scaffold facilitated stem cell osteogenic differentiation by activating the TRPM7 channel through the released of magnesium ions. In vivo tests using rat models confirmed its effectiveness in promoting coagulation and mandibular regeneration. Thus, this study proposes a promising approach for post-extraction alveolar bone regenerative repair. The composite scaffold material, with its hemostatic and osteogenic capabilities and shape-memory features, can potentially enhance dental implant success and overall oral health.


Subject(s)
Dental Implants , Hemostatics , Silicates , Rats , Animals , Osteogenesis , Silk/pharmacology , Hemostatics/pharmacology , Bone Regeneration , Tooth Extraction
12.
Adv Sci (Weinh) ; 11(7): e2306298, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38064101

ABSTRACT

Pancreatic cancer (PCa) is one of the most fatal human malignancies. The enhanced infiltration of stromal tissue into the PCa tumor microenvironment limits the identification of key tumor-specific transcription factors and epigenomic abnormalities in malignant epithelial cells. Integrated transcriptome and epigenetic multiomics analyses of the paired PCa organoids indicate that the basic helix-loop-helix transcription factor 40 (BHLHE40) is significantly upregulated in tumor samples. Increased chromatin accessibility at the promoter region and enhanced mTOR pathway activity contribute to the elevated expression of BHLHE40. Integrated analysis of chromatin immunoprecipitation-seq, RNA-seq, and high-throughput chromosome conformation capture data, together with chromosome conformation capture assays, indicate that BHLHE40 not only regulates sterol regulatory element-binding factor 1 (SREBF1) transcription as a classic transcription factor but also links the enhancer and promoter regions of SREBF1. It is found that the BHLHE40-SREBF1-stearoyl-CoA desaturase axis protects PCa cells from ferroptosis, resulting in the reduced accumulation of lipid peroxidation. Moreover, fatostatin, an SREBF1 inhibitor, significantly suppresses the growth of PCa tumors with high expressions of BHLHE40. This study highlights the important roles of BHLHE40-mediated lipid peroxidation in inducing ferroptosis in PCa cells and provides a novel mechanism underlying SREBF1 overexpression in PCa.


Subject(s)
Ferroptosis , Pancreatic Neoplasms , Humans , Homeodomain Proteins/genetics , Ferroptosis/genetics , Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Pancreatic Neoplasms/genetics , Tumor Microenvironment , Sterol Regulatory Element Binding Protein 1/genetics , Sterol Regulatory Element Binding Protein 1/metabolism
13.
J Food Sci ; 89(1): 684-700, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38010752

ABSTRACT

Date palm (Phoenix dactylifera L.) is an important commercial crop extensively consumed as a staple food and has been applied in many ethnomedical systems. Fruit vinegar is a preservative, condiment, and beverage with a spectrum of health benefits. Studies about the preparation, chemical profiles, and bioactivities of date fruit vinegar (DFV) are fundamental requirements for industrialization production. This study focused on the lab-scaled producing conditions, chemical profiles of DFV, and its bioactivities in vitro. According to the results, a date wine containing 9.75% methanol was obtained by yeast fermenting the enzyme-hydrolyzed date juice with 23.11% ± 0.39% of total sugar content. The optimized acidic fermentation conditions were an inoculation amount of 0.02%, a fermentation temperature of 31.14°C, and an initial alcohol content of 7.78%. Total acidity and total phenolic contents of the DFV were 7.74% ± 0.29% and 1.44 mg gallic acid equivalent/mL, respectively. In total, 32 organic acids were quantitated in the unaged DFV, with acetic, L-malic, and oxoglutaric acids as the predominant compounds. A total of 930 volatiles were identified in the DFV, including 186 esters, 177 terpenoids, and 148 heterocyclic compounds. There are 18 phenolic acids presented in the DFV. In addition, 42 flavonoids were quantitated in the DFV, including catechin, taxifolin, and cynaroside. The results of free radical scavenging activities and reducing power demonstrated that the DFV displayed good antioxidant properties. The DFV also acted well on angiotensin-converting enzyme 2 inhibition. These results suggest that the DFV can be industrially developed as a dietary supplement.


Subject(s)
Antioxidants , Phoeniceae , Antioxidants/chemistry , Acetic Acid/analysis , Angiotensin-Converting Enzyme 2/analysis , Flavonoids/analysis , Fruit/chemistry
14.
Front Endocrinol (Lausanne) ; 14: 1251718, 2023.
Article in English | MEDLINE | ID: mdl-38116308

ABSTRACT

A Chinese family was identified to have two patients with rickets, an adult female and a male child (proband), both exhibiting signs related to X-linked hypophosphatemic rickets (XLH). Gene sequencing analysis revealed a deletion of adenine at position 1985 (c.1985delA) in the PHEX-encoding gene. To investigate the relationship between this mutation and the pathogenicity of XLH, as well as analyze the effects of different dosages of PHEX gene mutations on clinical phenotypes, we developed a rat model carrying the PHEX deletion mutation. The CRISPR/Cas9 gene editing technology was employed to construct the rat model with the PHEX gene mutation (c.1985delA). Through reproductive procedures, five genotypes of rats were obtained: female wild type (X/X), female heterozygous (-/X), female homozygous wild type (-/-), male wild type (X/Y), and male hemizygous (-/Y). The rats with different genotypes underwent analysis of growth, serum biochemical parameters, and bone microstructure. The results demonstrated the successful generation of a stable rat model inheriting the PHEX gene mutation. Compared to the wild-type rats, the mutant rats displayed delayed growth, shorter femurs, and significantly reduced bone mass. Among the female rats, the homozygous individuals exhibited the smallest body size, decreased bone mass, shortest femur length, and severe deformities. Moreover, the mutant rats showed significantly lower blood phosphorus concentration, elevated levels of FGF23 and alkaline phosphatase, and increased expression of phosphorus regulators. In conclusion, the XLH rat model with the PHEX gene mutation dosage demonstrated its impact on growth and development, serum biochemical parameters, and femoral morphology.


Subject(s)
Familial Hypophosphatemic Rickets , Animals , Female , Male , Rats , Familial Hypophosphatemic Rickets/genetics , Familial Hypophosphatemic Rickets/diagnosis , Genotype , Mutation , Pedigree , PHEX Phosphate Regulating Neutral Endopeptidase/genetics , Phosphorus
15.
Genome Res ; 33(10): 1788-1805, 2023 10.
Article in English | MEDLINE | ID: mdl-37827697

ABSTRACT

Cell-cell communication (CCC) is critical for determining cell fates and functions in multicellular organisms. With the advent of single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (ST), an increasing number of CCC inference methods have been developed. Nevertheless, a thorough comparison of their performances is yet to be conducted. To fill this gap, we developed a systematic benchmark framework called ESICCC to evaluate 18 ligand-receptor (LR) inference methods and five ligand/receptor-target inference methods using a total of 116 data sets, including 15 ST data sets, 15 sets of cell line perturbation data, two sets of cell type-specific expression/proteomics data, and 84 sets of sampled or unsampled scRNA-seq data. We evaluated and compared the agreement, accuracy, robustness, and usability of these methods. Regarding accuracy evaluation, RNAMagnet, CellChat, and scSeqComm emerge as the three best-performing methods for intercellular ligand-receptor inference based on scRNA-seq data, whereas stMLnet and HoloNet are the best methods for predicting ligand/receptor-target regulation using ST data. To facilitate the practical applications, we provide a decision-tree-style guideline for users to easily choose best tools for their specific research concerns in CCC inference, and develop an ensemble pipeline CCCbank that enables versatile combinations of methods and databases. Moreover, our comparative results also uncover several critical influential factors for CCC inference, such as prior interaction information, ligand-receptor scoring algorithm, intracellular signaling complexity, and spatial relationship, which may be considered in the future studies to advance the development of new methodologies.


Subject(s)
Single-Cell Analysis , Software , Ligands , Single-Cell Analysis/methods , Algorithms , Cell Communication/genetics , Sequence Analysis, RNA/methods
16.
Biomolecules ; 13(9)2023 08 24.
Article in English | MEDLINE | ID: mdl-37759690

ABSTRACT

The filler/resin matrix interface interaction plays a vital role in the properties of dental resin composites (DRCs). Porous particles are promising fillers due to their potential in constructing micromechanical interlocking at filler/resin matrix interfaces, therefore improving the properties of the resulting DRCs, where the pore size is significantly important. However, how to control the pore size of porous particles via a simple synthesis method is still a challenge, and how their pore sizes affect the properties of resulting DRCs has not been studied. In this study, porous silica (DPS) with a dendritic structure and an adjustable pore size was synthesized by changing the amounts of catalyst in the initial microemulsion. These synthesized DPS particles were directly used as unimodal fillers and mixed with a resin matrix to formulate DRCs. The results showed that the DPS pore size affects the properties of DRCs, especially the mechanical property. Among various DPS particles with different pore sizes, DPS6 resulted in 19.5% and 31.4% improvement in flexural strength, and 24.4% and 30.7% enhancement in compression strength, respectively, compared to DPS1 and DPS9. These DPS particles could help to design novel dental restorative materials and have promising applications in biomedicine, catalysis, and adsorption.


Subject(s)
Excipients , Silicon Dioxide , Porosity , Adsorption , Catalysis , Resins, Synthetic
18.
ACS Appl Mater Interfaces ; 15(35): 41569-41579, 2023 Sep 06.
Article in English | MEDLINE | ID: mdl-37608739

ABSTRACT

In recent years, various porphyrin dyes have been designed to develop efficient dye-sensitized solar cells (DSSCs). Based on our previously reported porphyrin dye XW43, which contains a phenothiazine donor with two diethylene glycol (DEG)-derived substituents, we herein report a porphyrin dye XW89 by introducing a benzo 12-crown-4 (BCE) unit onto the N atom of the phenothiazine donor. On this basis, XW90 and XW91 have been synthesized by replacing a DEG chain in XW89 with two DEG chains and a 12-crown-4 unit, respectively. For iodine electrolyte-based DSSCs, dyes XW89-XW91 exhibit VOC values of 765-779 mV, higher than that of XW43 (755 mV), which may be related to the strong capability of the BCE group in binding Li+ and thus suppressing the downward shift of the TiO2 conduction band and interfacial charge recombination. Moreover, the smaller size of 12-crown-4 than the DEG unit enables higher adsorption amounts of the dyes than XW43, contributing to an enhanced JSC value. Due to the presence of two BCE units, dye XW91 exhibits the highest dye loading amount and JSC of 1.86 × 10-7 mol cm-2 and 19.79 mA cm-2, respectively, affording a high PCE of 11.1%. To further enhance the light-harvesting ability, a concerted companion (CC) dye XW92 has been constructed by linking the two subdye units corresponding to the porphyrin dye XW91 and an organic dye. As a result, XW92 affords an enhanced JSC and efficiency. Further coadsorption of XW92 with chenodeoxycholic acid achieved the highest efficiency of 12.1%. This work provides an effective approach for fabricating efficient DSSCs sensitized by porphyrin and CC dyes based on the introduction of crown ether units with smaller sizes and stronger Li+ affinities.

19.
Naunyn Schmiedebergs Arch Pharmacol ; 396(12): 3503-3528, 2023 12.
Article in English | MEDLINE | ID: mdl-37535076

ABSTRACT

Mitochondria serve as a vital energy source for nerve cells. The mitochondrial network also acts as a defense mechanism against external stressors that can threaten the stability of the nervous system. However, excessive accumulation of damaged mitochondria can lead to neuronal death. Mitophagy is an essential pathway in the mitochondrial quality control system and can protect neurons by selectively removing damaged mitochondria. In most neurological disorders, dysfunctional mitochondria are a common feature, and drugs that target mitophagy can improve symptoms. Here, we reviewed the role of mitophagy in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, stroke, and traumatic brain injuries. We also summarized drug and non-drug approaches to promote mitophagy and described their therapeutic role in neurological disorders in order to provide valuable insight into the potential therapeutic agents available for neurological disease treatment. However, most studies on mitophagy regulation are based on preclinical research using cell and animal models, which may not accurately reflect the effects in humans. This poses a challenge to the clinical application of drugs targeting mitophagy. Additionally, these drugs may carry the risk of intolerable side effects and toxicity. Future research should focus on the development of safer and more targeted drugs for mitophagy.


Subject(s)
Alzheimer Disease , Parkinson Disease , Animals , Humans , Mitophagy/physiology , Mitochondria/metabolism , Parkinson Disease/metabolism , Alzheimer Disease/metabolism
20.
Front Endocrinol (Lausanne) ; 14: 1200932, 2023.
Article in English | MEDLINE | ID: mdl-37534207

ABSTRACT

Background: Sorafenib included in Chinese medical insurance is the earliest targeted drug for radioactive iodine refractory differentiated thyroid cancer (RR-DTC). This study is to further demonstrate the clinical efficacy and safety of sorafenib used in Zhujiang Hospital of Southern Medical University. Methods: RR-DTC patients treated at our Department of Nuclear Medicine in Zhujiang Hospital of Southern Medical University (October 2017-May 2020) were retrospectively analyzed. Treatment effects, progression-free survival (PFS), and adverse effects (AEs) during medication were evaluated. Results: Of the 31 patients included, 26 patients were evaluated for efficacy with a median follow-up time of 17.5 months (4.0-51.0 months). The disease control rate (DCR) was 57.7% (n = 15) and the objective response rate (ORR) was 26.9% (n = 7). Most patients with disease control had thyroglobulin decreases of more than 60% (p = 0.004), ORRs were favorable in patients with lung metastasis and lung-only metastasis (p = 0.010 and 0.001, respectively). The PFS of the 26 patients analyzed was 16.5 months (95%CI: 14.41 -23.90 months). In the subgroup analysis, female, patients with lung-only metastasis, hand-foot skin syndrome (HFS), and thyroglobulin response ≥ 60% observed longer PFS (p = 0.038, 0.045, 0.035, and 0.000, respectively), while patients with bone metastasis had lower PFS (p = 0.035). The most common toxicity profile was HFS (93.5%), followed by diarrhea (83.9%), alopecia (74.2%). All the side effects were mainly grade 1-2. Grade 3-4 adverse reactions were more common in diarrhea and HFS. Conclusions: Sorafenib has promising efficacy in RR-DTC, especially in patients with lung metastasis and lung-only metastasis. The AEs of sorafenib were generally mild, and the main AE was HFS.


Subject(s)
Adenocarcinoma , Antineoplastic Agents , Thyroid Neoplasms , Humans , Female , Sorafenib/adverse effects , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/chemically induced , Thyroglobulin , Iodine Radioisotopes/adverse effects , Antineoplastic Agents/adverse effects , Retrospective Studies , Phenylurea Compounds/adverse effects , Diarrhea , Adenocarcinoma/drug therapy
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