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1.
PLoS Biol ; 21(12): e3002425, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38079449

ABSTRACT

Ciliopathies are associated with wide spectrum of structural birth defects (SBDs), indicating important roles for cilia in development. Here, we provide novel insights into the temporospatial requirement for cilia in SBDs arising from deficiency in Ift140, an intraflagellar transport (IFT) protein regulating ciliogenesis. Ift140-deficient mice exhibit cilia defects accompanied by wide spectrum of SBDs including macrostomia (craniofacial defects), exencephaly, body wall defects, tracheoesophageal fistula (TEF), randomized heart looping, congenital heart defects (CHDs), lung hypoplasia, renal anomalies, and polydactyly. Tamoxifen inducible CAGGCre-ER deletion of a floxed Ift140 allele between E5.5 to 9.5 revealed early requirement for Ift140 in left-right heart looping regulation, mid to late requirement for cardiac outflow septation and alignment, and late requirement for craniofacial development and body wall closure. Surprisingly, CHD were not observed with 4 Cre drivers targeting different lineages essential for heart development, but craniofacial defects and omphalocele were observed with Wnt1-Cre targeting neural crest and Tbx18-Cre targeting epicardial lineage and rostral sclerotome through which trunk neural crest cells migrate. These findings revealed cell autonomous role of cilia in cranial/trunk neural crest-mediated craniofacial and body wall closure defects, while non-cell autonomous multi-lineage interactions underlie CHD pathogenesis, revealing unexpected developmental complexity for CHD associated with ciliopathies.


Subject(s)
Ciliopathies , Heart Defects, Congenital , Animals , Mice , Cilia/metabolism , Heart Defects, Congenital/genetics , Embryonic Development , Carrier Proteins/metabolism , Skull , Ciliopathies/genetics , Ciliopathies/metabolism , Ciliopathies/pathology
2.
Oncologist ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982653

ABSTRACT

BACKGROUND AND OBJECTIVES: Envafolimab is the first and only globally approved subcutaneously injectable PD-L1 antibody for the treatment of instability-high (MSI-H) or DNA mismatch repair deficient (dMMR) advanced solid tumors in adults, including those with advanced colorectal cancer that has progressed after treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. The aim of this investigation was to examine the pharmacokinetic and exposure-response (E-R) profile of envafolimab in patients with solid tumors to support the approval of fixed and alternative dose regimens. METHODS: In this study, a population pharmacokinetic (PopPK) modeling approach will be employed to quantitatively evaluate intrinsic and extrinsic covariates. Additionally, PopPK-estimated exposure parameters were used to evaluate E-R relationship for safety and efficacy to provide a theoretical basis for recommending optimal treatment regimens. Simulations were performed on the dosing regimens of body weight-based regimen of 2.50 mg/kg QW, fixed dose 150 mg QW, and 300 mg Q2W for the selection of alternative dosing regimens. Data from 4 clinical studies (NCT02827968, NCT03101488, NCT03248843, and NCT03667170) were utilized. RESULTS: The PopPK dataset comprised 182 patients with 1810 evaluable envafolimab concentration records. Finally, a one-compartment model incorporating first-order absorption, first-order linear elimination, and time-dependent elimination according to an Emax function was found to accurately describe the concentration-time data of envafolimab in patients with advanced solid tumors. Creatinine clearance and country were identified as statistically significant factors affecting clearance, but had limited clinical significance. A relative flat exposure-response relationship was observed between early measures of safety and efficacy to verify that no dose adjustment is required. Simulation results indicated that 2.50 mg/kg QW, 150 mg QW, and 300 mg Q2W regimen yield similar steady-state exposure. CONCLUSIONS: No statistically significant difference was observed between weight-based and fixed dose regimens. Model-based simulation supports the adoption of a 150 mg weekly or 300 mg biweekly dosing regimen of envafolimab in the solid tumor population, as these schedules effectively balance survival benefits and safety risks.

3.
Small ; : e2403775, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949055

ABSTRACT

Despite the challenges associated with the synthesis of flexible metal-covalent organic frameworks (MCOFs), these offer the unique advantage of maximizing the atomic utilization efficiency. However, the construction of flexible MCOFs with flexible building units or linkages has rarely been reported. In this study, novel flexible MCOFs are constructed using flexible building blocks and copper clusters with hydrazone linkages. The heterometallic frameworks (Cu, Co) are prepared through the hydrazone linkage coordination method and evaluated as catalysts for the oxygen evolution reaction (OER). Owing to the spatial separation and functional cooperation of the heterometallic MCOF catalysts, the as-synthesized MCOFs exhibited outstanding catalytic activities with an overpotential of 268.8 mV at 10 mA cm-2 for the OER in 1 M KOH, which is superior to those of the reported covalent organic frameworks (COFs)-based OER catalysts. Theoretical calculations further elucidated the synergistic effect of heterometallic active sites within the linkages and frameworks, contributing to the enhanced OER activity. This study thus introduces a novel approach to the fundamental design of flexible MCOF catalysts for the OER, emphasizing their enhanced atomic utilization efficiency.

4.
Chemistry ; : e202402572, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39167364

ABSTRACT

Encapsulation of transition metals represents a crucial method for modifying the electronic structure and regulating the reactivity of fullerene, thereby expanding its applications. Herein, we present calculations with density functional theory methods to investigate the mechanisms of the Diels-Alder (DA) reactions of cyclopentadiene and La@C60 or Gd@C60 as well as their tricationic derivatives. Our findings indicate that the encapsulation of La and Gd into the C60 cage is thermodynamically favorable. The DA reactions are favored by the presence of La and Gd, with lower barriers, though the regioselectivity, favoring 6-6 bonds in the fullerene, is not affected. The effect of external electric fields has been also considered.

5.
Langmuir ; 40(31): 16113-16120, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39051840

ABSTRACT

The field of artificial photosynthesis, which focuses on harnessing solar light for the conversion of CO2 to economically valuable chemical products, remains a captivating area of research. In this study, we developed a series of photocatalysts based on Earth abundant elements (Fe, Co, Ni, Cu, and Zn) incorporated into 2D metalloporphyrin-conjugated organic polymers known as MTBPP-BEPA-COPs. These photocatalysts were utilized for the photoreduction of CO2 employing only H2O as the electron donor, without the need for any sacrificial agents or precious-metal cocatalysts. Remarkably, all of the synthesized MTBPP-BEPA-COPs exhibited an exceptional CO2 photoreduction performance only irradiated by visible light. Particularly, upon optimizing the metal ion coordinated with porphyrin units, ZnTBPP-BEPA-COP outperformed the other MTBPP-BEPA-COPs in terms of photocatalytic activity, achieving an impressive CO reduction yield of 152.18 µmol g-1 after just 4 h of irradiation. The electrostatic potential surfaces calculated by density functional theory suggest the potential involvement of metal centers as binding and catalytic sites for the binding of CO2. The calculated adsorption energy of CO2 with ZnTBPP-BEPA-COP exhibited one of the two smallest values. This may be the reason for the excellent catalytic effect of ZnTBPP-BEPA-COP. Thus, the present study not only demonstrates the potential of porphyrin-based conjugated polymers as highly efficient photocatalysts for CO2 reduction but also offers valuable insights into the rational design of such materials in the future.

6.
Diabetes Obes Metab ; 26(2): 592-601, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37953687

ABSTRACT

AIM: To employ a model-informed drug development approach in facilitating decision making and expediting the clinical progress of cofrogliptin (HSK7653), a novel ultralong-acting dipeptidyl peptidase-4 (DPP-4) inhibitor, for the treatment of type 2 diabetes (T2D) via a biweekly dosing regimen. METHODS: Firstly, a population pharmacokinetics and pharmacodynamics (PopPKPD) model was developed using PK and PD data from a single ascending dose study to simulate the PK and PD time profiles of HSK7653 after multiple doses. Secondly, model-based meta-analysis (MBMA) was performed on published clinical studies of Eastern Asian subjects for all DPP-4 inhibitors. We hypothesized a consistent relationship between PK and DPP-4 inhibition in both healthy individuals and in those with T2D, establishing a quantitative correlation between DPP-4 inhibition and HbA1c. Finally, the predicted PK/DPP-4 inhibition/HbA1c profiles were validated by T2D patients in late clinical trials. RESULTS: The PK/DPP-4 inhibition/HbA1c profiles of T2D patients treated with HSK7653 matched the modelled data. Our PopPKPD and MBMA models predict multiple ascending dosing PK and PD characteristics from single ascending dosing data, as well as the long-term efficacy in T2D patients, based on healthy subjects. CONCLUSIONS: Successful waiver approval for the phase 2b dose-finding study was achieved through model-informed recommendations, facilitating the clinical development of HSK7653 and other DPP-4 inhibitors.


Subject(s)
Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Humans , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/chemically induced , Glycated Hemoglobin , Dose-Response Relationship, Drug , Hypoglycemic Agents/pharmacology , Dipeptidyl Peptidase 4
7.
BMC Endocr Disord ; 24(1): 152, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39138447

ABSTRACT

BACKGROUND: Previous studies examined the association of Helicobacter pylori infection (H. pylori) with complications of diabetes, but the results have been inconsistent. The aim of this study of patients with type-2 diabetes (T2D) was to determine the association of H. pylori infection with the major complications of diabetes. METHODS: This single-center retrospective study examined patients with T2D who received H. pylori testing between January 2016 and December 2021. Logistic regression analyses were used to evaluate the association of H. pylori infection with four major complications of diabetes. RESULTS: We examined 960 patients with T2D, and 481 of them (50.1%) were positive for H. pylori. H. pylori infection was significantly associated with diabetic nephropathy (odds ratio [OR] = 1.462; 95% confidence interval [CI]: 1.006,2.126; P = 0.046). In addition, the co-occurrence of H. pylori positivity with hypertension (OR = 4.451; 95% CI: 2.351,8.427; P < 0.001), with glycated hemoglobin A1c (HbA1c) of at least 8% (OR = 2.925; 95% CI: 1.544,5.541; P = 0.001), and with diabetes duration of at least 9 years (OR = 3.305; 95% CI:1.823,5.993; P < 0.001) further increased the risk of diabetic nephropathy. There was no evidence of an association of H. pylori infection with retinopathy, neuropathy, or peripheral vascular disease. CONCLUSIONS: Our study of T2D patients indicated that those with H. pylori infections had an increased risk of nephropathy, and this risk was greater in patients who also had hypertension, an HbA1c level of 8% or more, and diabetes duration of 9 years or more.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Helicobacter Infections , Helicobacter pylori , Humans , Helicobacter Infections/complications , Retrospective Studies , Male , Female , Middle Aged , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Helicobacter pylori/isolation & purification , Diabetic Nephropathies/epidemiology , Diabetic Nephropathies/etiology , Diabetic Nephropathies/complications , Aged , Diabetes Complications/microbiology , Diabetes Complications/epidemiology , Glycated Hemoglobin/analysis , Glycated Hemoglobin/metabolism , Follow-Up Studies , Prognosis , Adult
8.
Molecules ; 29(10)2024 May 11.
Article in English | MEDLINE | ID: mdl-38792130

ABSTRACT

Lycium ruthenicum Murray possesses significant applications in both food and medicine, including antioxidative, anti-tumor, anti-fatigue, anti-inflammatory, and various other effects. Consequently, there has been a surge in research endeavors dedicated to exploring its potential benefits, necessitating the organization and synthesis of these findings. This article systematically reviews the extraction and content determination methods of active substances such as polysaccharides, anthocyanins, flavonoids, and polyphenols in LRM in the past five years, as well as some active ingredient composition determination methods, biological activities, and product development. This review is divided into three main parts: extraction and determination methods, their bioactivity, and product development. Building upon prior research, we also delve into the economic and medicinal value of Lycium ruthenicum Murray, thereby contributing significantly to its further exploration and development. It is anticipated that this comprehensive review will serve as a valuable resource for advancing research on Lycium ruthenicum Murray.


Subject(s)
Lycium , Plant Extracts , Lycium/chemistry , Plant Extracts/chemistry , Anthocyanins/chemistry , Humans , Flavonoids/chemistry , Antioxidants/chemistry , Antioxidants/pharmacology , Polyphenols/chemistry , Phytochemicals/chemistry , Phytochemicals/pharmacology , Polysaccharides/chemistry
9.
Angew Chem Int Ed Engl ; 63(20): e202401750, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38407379

ABSTRACT

The catalytic performance for electrocatalytic CO2 reduction reaction (CO2RR) depends on the binding strength of the reactants and intermediates. Covalent organic frameworks (COFs) have been adopted to catalyze CO2RR, and their binding abilities are tuned via constructing donor-acceptor (DA) systems. However, most DA COFs have single donor and acceptor units, which caused wide-range but lacking accuracy in modulating the binding strength of intermediates. More elaborate regulation of the interactions with intermediates are necessary and challenge to construct high-efficiency catalysts. Herein, the three-component COF with D-A-A units was first constructed by introducing electron-rich diarylamine unit, electron-deficient benzothiazole and Co-porphyrin units. Compared with two-component COFs, the designed COF exhibit elevated electronic conductivity, enhanced reducibility, high efficiency charge transfer, further improving the electrocatalytic CO2RR performance with the faradic efficiency of 97.2 % at -0.8 V and high activity with the partial current density of 27.85 mA cm-2 at -1.0 V which exceed other two-component COFs. Theoretical calculations demonstrate that catalytic sites in three-component COF have suitable binding ability of the intermediates, which are benefit for formation of *COOH and desorption of *CO. This work offers valuable insights for the advancement of multi-component COFs, enabling modulated charge transfer to improve the CO2RR activity.

10.
Angew Chem Int Ed Engl ; 63(27): e202404637, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38644436

ABSTRACT

Application of silicon-based anodes is significantly challenged by low initial Coulombic efficiency (ICE) and poor cyclability. Traditional pre-lithiation reagents often pose safety concerns due to their unstable chemical nature. Achieving a balance between water-stability and high ICE in prelithiated silicon is a critical issue. Here, we present a lithium-enriched silicon/graphite material with an ultra-high ICE of ≥110 % through a high-stable lithium pre-storage methodology. Lithium pre-storage prepared a nano-drilled graphite material with surficial lithium functional groups, which can form chemical bonds with adjacent silicon during high-temperature sintering. This results in an unexpected O-Li-Si interaction, leading to in situ pre-lithiation of silicon nanoparticles and providing high stability in air and water. Additionally, the lithium-enriched silicon/graphite materials impart a combination of high ICE, high specific capacity (620 mAh g-1), and long cycling stability (>400 cycles). This study opens up a promising avenue for highly air- and water-stable silicon anode prelithiation methods.

11.
Angew Chem Int Ed Engl ; 63(21): e202315802, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38453646

ABSTRACT

The development of nonpyrolytic catalysts featuring precisely defined active sites represents an effective strategy for investigating the fundamental relationship between the catalytic activity of oxygen reduction reaction (ORR) catalysts and their local coordination environments. In this study, we have synthesized a series of model electrocatalysts with well-defined CoN4 centers and nonplanar symmetric coordination structures. These catalysts were prepared by a sequential process involving the chelation of cobalt salts and 1,10-phenanthroline-based ligands with various substituent groups (phen(X), where X=OH, CH3, H, Br, Cl) onto covalent triazine frameworks (CTFs). By modulating the electron-donating or electron-withdrawing properties of the substituent groups on the phen-based ligands, the electron density surrounding the CoN4 centers was effectively controlled. Our results demonstrated a direct correlation between the catalytic activity of the CoN4 centers and the electron-donating ability of the substituent group on the phenanthroline ligands. Notably, the catalyst denoted as BCTF-Co-phen(OH), featuring the electron-donating OH group, exhibited the highest ORR catalytic activity. This custom-crafted catalyst achieved a remarkable half-wave potential of up to 0.80 V vs. RHE and an impressive turnover frequency (TOF) value of 47.4×10-3 Hz at 0.80 V vs. RHE in an alkaline environment.

12.
BMC Genomics ; 24(1): 103, 2023 Mar 09.
Article in English | MEDLINE | ID: mdl-36894869

ABSTRACT

Yellow seed is one favorite trait for the breeding of Brassica oilseed crops, but the performance of seed coat color is very complicated due to the involvement of various pigments. The change of seed coat color of Brassica crops is related to the specific synthesis and accumulation of anthocyanin, and the expression level of structural genes in anthocyanin synthesis pathway is specifically regulated by transcription factors. Despite some previous reports on the regulations of seed coat color from linkage marker development, gene fine-mapping and multi-omics association analysis, the trait of Brassica crops is affected by the evolutionary events such as genome triploidization, the regulatory mechanism is still largely unknown. In this study, we identified genes related to anthocyanin synthesis in six Brassica crops in U-triangle at the genome-wide level and performed collinearity analysis. A total of 1119 anthocyanin-related genes were identified, the collinear relationship of anthocyanin-related genes on subgenomic chromosomes was the best in B. napus (AACC) and the worst in B. carinata (BBCC). The comparisons of gene expressions for anthocyanin metabolic pathways in seed coats during seed development revealed differences in its metabolism among these species. Interestingly, the R2R3-MYB transcription factors MYB5 and TT2 were differentially expressed at all eight stages of seed coat development, indicating that they might be the key genes that caused the variation of the seed coat color. The expression curve and trend analyses of the seed coat development period showed that the main reason for the unexpressed copies of MYB5 and TT2 was likely gene silencing caused by gene structural variation. These results were valuable for the genetic improvement of Brassica seed coat color, and also provided new insights into gene multicopy evolution in Brassica polyploids.


Subject(s)
Brassica , Brassica/genetics , Anthocyanins/genetics , Anthocyanins/metabolism , Pigmentation/genetics , Plant Breeding , Seeds/genetics , Seeds/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
13.
Planta ; 258(1): 19, 2023 Jun 14.
Article in English | MEDLINE | ID: mdl-37314587

ABSTRACT

MAIN CONCLUSION: BraANS.A3 was the key gene controlling purple leaf color in pak choi, and two short fragments of promoter region in green pak choi might be interfering its normal expression. Pak choi (B. rapa L. ssp. chinensis) is an influential and important vegetable with green, yellow, or purple leaves that is cultivated worldwide. The purple leaves are rich in anthocyanins, but the underlying genetics and evolution have yet to be extensively studied. Free-hand sections of the purple leaves indicated that anthocyanins mainly accumulate throughout the adaxial and abaxial epidermal leaf cells. Segregation analyses of an F2 population of a B. rapa ssp. chinensis L. purple leaf mutant ZBC indicated that the purple trait is controlled by an incompletely dominant nuclear gene. Bulked segregant analysis (BSA) showed that the key genes controlling the trait were between 24.25 and 38.10 Mb on chromosome A03 of B. rapa. From the annotated genes, only BraA03g050560.3C, homologous to Arabidopsis AtANS, was related to the anthocyanin synthesis pathway. Genome annotation results and transcriptional sequencing analyses revealed that the BraANS.A3 gene was involved in the purple leaf trait. qRT-PCR analyses showed that BraANS.A3 was highly upregulated in ZBC but hardly expressed in the leaves of an inbred homozygous line of B. campestris ssp. chinensis L. green leaf mutant WTC, indicating that BraANS.A3 played a key role catalyzing anthocyanin synthesis in ZBC. Full-length sequence alignment of BraANS.A3 in WTC and ZBC showed that it was highly conserved in the gene region, with significant variation in the promoter region. In particular, the insertion of two short fragments of the promoter region in WTC may interfere with its normal expression. The promoter regions of ANS in six Brassica species all had multiple cis-elements involved in responses to abscisic acid, light, and stress, suggesting that ANS may be involved in multiple metabolic pathways or biological processes. Protein-protein interactions predicted that BraANS.A3 interacts with virtually all catalytic proteins in the anthocyanin synthesis pathway and has a strong relationship with Transparent Testa 8 (TT8). These results suggest that BraANS.A3 promotes anthocyanin accumulation in purple pak choi and provide new insights into the functional analysis of anthocyanin-related genes in Chinese cabbage and transcriptional regulatory networks.


Subject(s)
Arabidopsis , Brassica rapa , Brassica , Brassica rapa/genetics , Anthocyanins , Abscisic Acid , Arabidopsis/genetics
14.
Mol Breed ; 43(3): 19, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37313299

ABSTRACT

Purple/red appearance is one of the common phenotypic variations in leaves, stems, and siliques of oilseed rape (Brassica napus L.) but very rare in flowers. In this study, the causal genes for the purple/red traits in stems and flowers in two accessions of oilseed rape (DH_PR and DH_GC001, respectively) derived from the wide hybridization were fine mapped, and candidate genes were determined by methods combined with bulked segregant analysis (BSA) and RNA-seq analysis. Both traits of purple stem and red flowers were mapped to the locus as AtPAP2 homologous genes (BnaPAP2.C6a and BnaPAP2.A7b, respectively) belonging to the R2R3-MYB family. Sequence comparisons of full-length allelic genes revealed several InDels and SNPs in intron 1 as well as exons, and completely different promoter region of BnaPAP2.C6a and a 211 bp insertion was identified in the promoter region of BnaPAP2.A7b of DH_GC001. Our results not only contribute to a better understanding of anthocyanin inheritance in B. napus, but also provide a useful toolbox for future breeding of cultivars with purple/red traits through the combination of different functional alleles and homologs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01365-5.

15.
Article in English | MEDLINE | ID: mdl-37498472

ABSTRACT

PURPOSE: Radial artery occlusion (RAO) is an unresolved complication after transradial artery (TRA) puncture. The aim of this observational study was to assess the feasibility and safety of retrograde recanalization of RAO through distal transradial access (dTRA). METHODS: From June 2021 to March 2022, 28 consecutive patients with successful puncture and intubation through the dTRA in the anatomical snuffbox and RAO confirmed by angiography were enrolled. RESULTS: Among the 28 patients, 27 (96.4%) patients with RAO were successfully retrogradely recanalized through the dTRA and successfully underwent coronary angiography or coronary intervention. After the procedure, only 1 (3.7%) patient developed a forearm hematoma, and there were no other bleeding complications or nerve disorders. CONCLUSIONS: DTRA is a safe and feasible approach for retrograded recanalization of RAO, with a high procedure success rate and few complications.

16.
Phys Chem Chem Phys ; 25(5): 3780-3788, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36644933

ABSTRACT

Hydrogen transfer (HT) is of crucial importance in biochemistry and atmospheric chemistry. Here, HT processes involved in the dissociation reaction of dimethyl disulfide radical cations (DMDS˙+, CH3SSCH3˙+) are investigated using quantum chemical calculations. Four HTs from the C to S atom and one HT from the S to S atom are observed and the most probable paths are proposed in the dissociation channel from DMDS˙+ to CHnS+ (n = 2-4). The mechanisms of all these five HTs are described as hydrogen atom transfer (HAT) and four of them are accompanied by electron transfer (ET). Considering the catalytic effect of water molecules existing in organisms and the atmosphere, five HT processes in the dissociation of the [DMDS + H2O]˙+ complex are further explored, which show lower free energy barriers. With the participation of water molecules acting as a base, two HTs from the C to the S atom, which have the largest decrease in energy barriers, are characterized as concerted proton-coupled electron transfer (cPCET). These results can be extended to understand the mechanism of the HT process during the dissociation of disulfide and help provide a strategy to design a rare cPCET mechanism for the activation of the C-H bond.

17.
Nano Lett ; 22(23): 9441-9449, 2022 12 14.
Article in English | MEDLINE | ID: mdl-36442508

ABSTRACT

Approaches to DNA probe-mediated precision medicine have been extensively explored for the diagnosis and treatment of diverse types of cancer. Despite this, simple nanoscale devices with the required recognition specificity and sensitivity for clinical application have remained elusive until now. Here, we report a pH-driven covalent nanoscale device that integrates pH-responsive, switchable structure and proximity-driven covalent cross-linking. A tumor acidic, pH-driven mechanism eliminates "on-target, off-tumor" nonspecific recognition. By manipulating covalent binding to target molecule on the cell surface, this nanodevice avoids binding-then-shedding to improve the sensitivity of tumor recognition. We envision that this pH-driven covalent nanoscale device will inspire more clinical applications toward specific, long-term tumor imaging in the cancer microenvironment.


Subject(s)
Neoplasms , Humans , Neoplasms/drug therapy , Tumor Microenvironment , Diagnostic Imaging , Hydrogen-Ion Concentration
18.
Molecules ; 28(4)2023 Feb 15.
Article in English | MEDLINE | ID: mdl-36838838

ABSTRACT

The effective detection of environmental pollutants is very important to the sustainable development of human health and the environment. A luminescent Cd(II) coordination complex, {[Cd(dbtdb)(1,2,4-H3btc)]·0.5H2O}n (1) (dbtdb = 1-(2,3,5,6-tetramethyl-4-((2-(thiazol-4-yl)-2H-benzo[d]imidazol-3(3aH)-yl)methyl)benzyl)-2,7a-dihydro-2-(thiazol-4-yl)-1H-benzo[d]imidazole, 1,2,4-H3btc = 1,2,4-benzenetricarboxylic acid), was obtained by hydrothermal reactions. Complex 1 has a chain structure decorated with uncoordinated Lewis basic O and S donors and provides good sensing of Fe3+, Cr2O72-, and p-nitrophenol with fluorescence quenching through an energy transfer process. The calculated binding constants were 3.3 × 103 mol-1 for Fe3+, 2.36 × 104 mol-1 for Cr2O72-, and 9.3 × 103 mol-1 for p-nitrophenol, respectively. These results show that 1 is a rare multiresponsive sensory material for efficient detection of Fe3+, Cr2O72-, and p-nitrophenol.


Subject(s)
Cadmium , Nitrophenols , Humans , Fluorescence , Luminescence
19.
Angew Chem Int Ed Engl ; 62(14): e202218742, 2023 Mar 27.
Article in English | MEDLINE | ID: mdl-36655733

ABSTRACT

Two-dimensional covalent organic frameworks (2D COFs) are often employed for electrocatalytic systems because of their structural diversity. However, the efficiency of atom utilization is still in need of improvement, because the catalytic centers are located in the basal layers and it is difficult for the electrolytes to access them. Herein, we demonstrate the use of 1D COFs for the 2e- oxygen reduction reaction (ORR). The use of different four-connectivity blocks resulted in the prepared 1D COFs displaying good crystallinity, high surface areas, and excellent chemical stability. The more exposed catalytic sites resulted in the 1D COFs showing large electrochemically active surface areas, 4.8-fold of that of a control 2D COF, and thus enabled catalysis of the ORR with a higher H2 O2 selectivity of 85.8 % and activity, with a TOF value of 0.051 s-1 at 0.2 V, than a 2D COF (72.9 % and 0.032 s-1 ). This work paves the way for the development of COFs with low dimensions for electrocatalysis.

20.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(7): 767-773, 2023 Jul 15.
Article in Zh | MEDLINE | ID: mdl-37529961

ABSTRACT

Necrotizing enterocolitis (NEC), with the main manifestations of bloody stool, abdominal distension, and vomiting, is one of the leading causes of death in neonates, and early identification and diagnosis are crucial for the prognosis of NEC. The emergence and development of machine learning has provided the potential for early, rapid, and accurate identification of this disease. This article summarizes the algorithms of machine learning recently used in NEC, analyzes the high-risk predictive factors revealed by these algorithms, evaluates the ability and characteristics of machine learning in the etiology, definition, and diagnosis of NEC, and discusses the challenges and prospects for the future application of machine learning in NEC.


Subject(s)
Enterocolitis, Necrotizing , Infant, Newborn, Diseases , Infant, Newborn , Humans , Enterocolitis, Necrotizing/diagnosis , Enterocolitis, Necrotizing/therapy , Prognosis , Gastrointestinal Hemorrhage/diagnosis , Machine Learning
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