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1.
Neural Regen Res ; 20(4): 1124-1134, 2025 Apr 01.
Article in English | MEDLINE | ID: mdl-38989951

ABSTRACT

JOURNAL/nrgr/04.03/01300535-202504000-00028/figure1/v/2024-07-06T104127Z/r/image-tiff The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration. However, it remains largely unclear how PINK1 and Parkin are expressed in mammalian brains. This has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small animals. Understanding this issue is critical for elucidating the in vivo roles of PINK1 and Parkin. Recently, we showed that the PINK1 kinase is selectively expressed as a truncated form (PINK1-55) in the primate brain. In the present study, we used multiple antibodies, including our recently developed monoclonal anti-PINK1, to validate the selective expression of PINK1 in the primate brain. We found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages, which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey brains. PINK1 was enriched in the membrane-bound fractionations, whereas Parkin was soluble with a distinguishable distribution. Immunofluorescent double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes, though they did colocalize on mitochondria when the cells were exposed to mitochondrial stress. These findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

2.
J Colloid Interface Sci ; 675: 560-568, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38986329

ABSTRACT

Artificial photosynthesis of hydrogen peroxide (H2O2) is a hopeful alternative to the industrial anthraquinone process. However, rational fabrication of the photocatalysts for the production of H2O2 without any sacrificial agents is still a formidable challenge. Herein, two kinds of linear conjugated polymers (LCPs) including pyridinic N functionalized polymer (DEB-N2) and pyridinic N non-contained polymer (DEB-N0) were successfully synthesized. DEB-N2 displays enhanced light capturing ability and good dispersion in water, leading to a substantial initial H2O2 generation rate of 3492µmol g-1h-1 as well as remarkable photocatalytic stability in pure water. Furthermore, the temperature programmed desorption (TPD) and density functional theory (DFT) analysis reveal that highly electronegative pyridine-N atoms in DEB-N2 boost the adsorption affinity of oxygen molecules, which facilitates the occurrence of the oxygen reduction reaction, therefore enhancing the performance of photocatalytic H2O2 production. This study unveils that the presence of pyridinic N in DEB-N2 has a significant impact on photocatalytic H2O2 production, suggesting the precise manipulation of the chemical structure of polymer photocatalysts is essential to achieve efficient solar-to-chemical energy conversion.

3.
Infection ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38995550

ABSTRACT

BACKGROUND: Carbapenem-resistant gram-negative bacteria (CRGNB) present a considerable global threat due to their challenging treatment and increased mortality rates, with bloodstream infection (BSI) having the highest mortality rate. Patients with end-stage renal disease (ESRD) undergoing renal replacement therapy (RRT) face an increased risk of BSI. Limited data are available regarding the prognosis and treatment outcomes of CRGNB-BSI in patients with ESRD in intensive care units (ICUs). METHODS: This multi-center retrospective observational study included a total of 149 ICU patients with ESRD and CRGNB-BSI in Taiwan from January 2015 to December 2019. Clinical and microbiological outcomes were assessed, and multivariable regression analysis was used to evaluate the independent risk factors for day-28 mortality and the impact of antimicrobial therapy regimen on treatment outcomes. RESULTS: Among the 149 patients, a total of 127 patients (85.2%) acquired BSI in the ICU, with catheter-related infections (47.7%) and pneumonia (32.2%) being the most common etiologies. Acinetobacter baumannii (49.0%) and Klebsiella pneumoniae (31.5%) were the most frequently isolated pathogens. The day-28 mortality rate from BSI onset was 52.3%, and in-hospital mortality was 73.2%, with survivors experiencing prolonged hospital stays. A higher Sequential Organ Failure Assessment (SOFA) score (adjusted hazards ratio [aHR], 1.25; 95% confidence interval [CI] 1.17-1.35) and shock status (aHR, 2.12; 95% CI 1.14-3.94) independently predicted day-28 mortality. Colistin-based therapy reduced day-28 mortality in patients with shock, a SOFA score of ≥ 13, and Acinetobacter baumannii-related BSI. CONCLUSIONS: CRGNB-BSI led to high mortality in critically ill patients with ESRD. Day-28 mortality was independently predicted by a higher SOFA score and shock status. In patients with higher disease severity and Acinetobacter baumannii-related BSI, colistin-based therapy improved treatment outcomes.

4.
Bioorg Med Chem ; 110: 117828, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38981219

ABSTRACT

The approval of Trodelvy® validates TROP2 as a druggable but challenging target for antibody-drug conjugates (ADCs) to treat metastatic triple-negative breast cancer (mTNBC). Here, based on the TROP2-targeted antibody sacituzumab, we designed and developed several site-specific ADC candidates, which employ MMAE (monomethyl auristatin E) as the toxin, via IgG glycoengineering or affinity-directed traceless conjugation. Systematic evaluation of these site-specific ADCs in homogeneity, hydrophilicity, stability, and antitumor efficiency was conducted. The results indicate that the site-specific ADCs gsADC 3b made from one-step glycoengineering exhibit good aggregation stability and in vivo efficacy, providing a new format of ADCs that target TROP2.

5.
Life Sci ; : 122914, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39004275

ABSTRACT

AIMS: Colorectal cancer (CRC) remains a major global health issue, with metastatic cases presenting poor prognosis despite advances in chemotherapy and targeted therapy. Irinotecan, a key drug for advanced CRC treatment, faces challenges owing to the development of resistance. This study aimed to understand the mechanisms underlying irinotecan resistance in colorectal cancer. MAIN METHODS: We created a cell line resistant to irinotecan using HT29 cells. These resistant cells were utilized to investigate the role of the CDK7-MDK axis. We employed bulk RNA sequencing, conducted in vivo experiments with mice, and analyzed patient tissues to examine the effects of the CDK7-MDK axis on the cellular response to irinotecan. KEY FINDINGS: Our findings revealed that HT29 cells resistant to irinotecan, a crucial colorectal cancer medication, exhibited significant phenotypic and molecular alterations compared to their parental counterparts, including elevated stem cell characteristics and increased levels of cytokines and drug resistance proteins. Notably, CDK7 expression was substantially higher in these resistant cells, and targeting CDK7 effectively decreased their survival and tumor growth, enhancing irinotecan sensitivity. RNA-seq analysis indicated that suppression of CDK7 in irinotecan-resistant HT29 cells significantly reduced Midkine (MDK) expression. Decreased CDK7 and MDK levels, achieved through siRNA and the CDK7 inhibitor THZ1, enhanced the sensitivity of resistant HT29 cells to irinotecan. SIGNIFICANCE: Our study sheds light on how CDK7 and MDK influence irinotecan resistance in colorectal and highlights the potential of MDK-targeted therapies. We hypothesized that irinotecan sensitivity and overall treatment efficacy would improve by inhibiting MDK. This finding encourages a careful yet proactive investigation of MDK as a therapeutic target to enhance outcomes in colorectal cancer patients.

6.
Inorg Chem ; 63(26): 12073-12080, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38946340

ABSTRACT

Luminescent materials typically emit their fluorescence or phosphorescence at a specific wavelength with different excitation energies via the so-called Kasha's rule. If fluorescence or phosphorescence emission via anti-Kasha's rule could be achieved, it will hold great promise for applications in many fields. In this work, we report the synthesis and characterization of new metal-organic halide materials with dual emission of efficient room-temperature phosphorescence and fluorescence, which obey anti-Kasha's rule. Here, three emitting metal-organic halides with formula [ZnX2(bidpe)] (X = Cl for 1, X = Br for 2, X = I for 3, bidpe = 4,4'-bis(imidazol-1-yl)diphenyl ether) were prepared and their photophysical properties were investigated. The complexes exhibit dual emission of fluorescence and phosphorescence via anti-Kasha's rule, and their RTP properties of resultant products are modulated by halide substitution synthesis. DFT calculations indicate that the singlet states exhibit a halide-ligand charge transfer (XLCT) character while the triplet states are dominated by the intraligand π-π* transitions. Furthermore, the multilevel information encryption and anticounterfeiting applications are developed by virtue of anti-Kasha's rule emission.

7.
Orthop Surg ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38946660

ABSTRACT

BACKGROUND: Mobile bearing fracture is a rare long-term complication of unicompartmental knee arthroplasty (UKA), and relevant reports are sparse. Hence, its treatment options need further exploration. CASE PRESENTATION: This study presents the case of fracture of a polyethylene insert that occurred 12 years after mobile bearing medial UKA in a 75-year-old overweight woman who then underwent surgical intervention at our institution. However, we encountered significant challenges in removing the fragments from the broken bearing, resulting in retention of the remaining one-third of the fragment. We solved this problem by replacing the fractured insert with thicker mobile bearing. During the 1-month postoperative follow-up, the patient achieved good range of motion and excellent satisfaction, with no reported complications and a Knee Society Score of 90. Additionally, we reviewed the literature on the treatment for mobile bearing fractures after UKA. CONCLUSIONS: Bearing fracture is a rare cause of failure of mobile bearing UKA. This case highlights the challenges of UKA fracture bearing retrieval and underscores that mobile bearing replacement can be an effective intervention. The case we report shows that when removal of a residual meniscal bearing in a posterior dislocation is difficult to achieve, compromise may be an appropriate option because it does not cause additional complaints to the patient. This case emphasizes the importance of the surgeon having a thorough preoperative understanding of the location and potential pitfalls of fracture fragments in such situations.

8.
Environ Pollut ; 358: 124507, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38968984

ABSTRACT

Nitrate and Cr(VI) are the typical and prevalent co-contaminants in the groundwater, how to synchronously and effectively diminish them has received growing attention. The most problem that currently limits the nitrate and Cr(VI) reduction technology for groundwater remediation is with emphasis on exploring the optimal electron donors. This study investigated the feasibility of utilizing the synergistical effect of inorganic electron donors (pyrite, sulfur) and inherently limited organics to promote synchronous nitrate and Cr(VI) removal, which meets the requirement of naturally low-carbon and eco-friendly technologies. The NO3--N and Cr(VI) removal efficiencies in the pyrite and sulfur involved mixotrophic biofilter (PS-BF: approximately 90.8 ± 0.6% and 99.1 ± 2.1%) were substantially higher than that in a volcanic rock supported biofilter (V-BF: about 49.6% ± 2.8% and 50.0% ± 9.3%), which was consistent with the spatial variations of their concentrations. Abiotic and biotic batch tests directly confirmed the decisive role of pyrite and sulfur for NO3--N and Cr(VI) removal via chemical and microbial pathways. A server decline in sulfate production correlated with decreasing COD consumption revealed that there was sulfur disproportionation induced by limited organics. Metagenomic analysis suggested that chemoautotrophic microbes like Sulfuritalea and Thiobacillus were key players responsible for sulfur oxidation, nitrate and Cr(VI) reduction. The metabolic pathway analysis suggested that genes encoding functional enzymes related to complete denitrification, S oxidation, and dissimilatory sulfate reduction were upregulated, however, genes encoding Cr(VI) reduction enzymes (e.g. chrA, chrR, nemA, and azoR) were downregulated in PS-BF, which further explained the synergistical effect of multiple electron donors. These findings provide insights into their potential cooperative interaction of multiple electron donors on greatly promoting nitrate and Cr(VI) removal and have implications for the remediation technology of nitrate and Cr(VI) co-contaminated groundwater.

9.
World J Gastrointest Surg ; 16(6): 1803-1824, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38983344

ABSTRACT

BACKGROUND: Stomach adenocarcinoma (STAD) is one of the main reasons for cancer-related deaths worldwide. This investigation aimed to define the connection between STAD and Cuproptosis-related genes (CRGs). Cuproptosis is a newly identified form of mitochondrial cell death triggered by copper. AIM: To explore the identification of potential biomarkers for STAD disease based on cuproptosis. METHODS: A predictive model using Gene Ontology (GO), Least Absolute Shrinkage and Selection Operator (LASSO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Variation Analysis (GSVA), and Gene Set Enrichment Analysis analyzed gene interconnections, focusing on 3 copper-related genes and their expression in The Cancer Genome Atlas-STAD. Networks for mRNA-miRNA and mRNA-transcription factor interactions were constructed. The prognostic significance of CRG scores was evaluated using time-receiver operating characteristic, Kaplan-Meier curves, and COX regression analysis. Validation was conducted with datasets GSE26942, GSE54129, and GSE66229. Expression of copper-related differentially expressed genes was also analyzed in various human tissues and gastric cancer subpopulations using the human protein atlas. RESULTS: Three significant genes (FDX1, LIAS, MTF1) were identified and selected via LASSO analysis to predict and classify individuals with STAD into high and low CRG score subgroups. These genes were down-regulated in both risk categories. GO and KEGG analyses highlighted their involvement mainly in the electron transport chain. After validating their differential expression, FDX1 emerged as the most accurate diagnostic marker for gastric cancer. Additionally, the RCircos package localized FDX1 on chromosome 11. CONCLUSION: Our study revealed that FDX1 could be a potential biomarker and treatment target for gastric malignancy, providing new ideas for further scientific research.

10.
Ecol Evol ; 14(7): e11692, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38983706

ABSTRACT

Water availability strongly influences the survival, growth, and reproduction of most terrestrial plant species. Experimental evidence has well documented the effect of changes in total amount of water availability on non-native vs. native plants. However, little is known about how fluctuations in water availability affect these two groups, although more extreme fluctuations in water availability increasingly occur with prolonged drought and extreme precipitation events. Here, we grew seven non-native and seven native plant species individually in the greenhouse. Then, we exposed them to four watering treatments, each treatment with the same total amount of water, but with different divisions: W1 (added water 16 times with 125 mL per time), W2 (8 times, 250 mL per time), W3 (4 times, 500 mL per time), and W4 (2 times, 1000 mL per time). We found that both non-native and native plants produced the most biomass under medium frequency/magnitude watering treatments (W2 and W3). Interestingly, non-native plants produced 34% more biomass with the infrequent, substantial watering treatment (W4) than with frequent, minor watering treatment (W1), whereas native plants showed opposite patterns, producing 26% more biomass with W1 than with W4. Differences in the ratio of root to shoot under few/large and many/small watering treatments of non-native vs. native species probably contributed to their different responses in biomass production. Our results advance the current understanding of the effect of water availability on non-native plants, which are affected not only by changes in amount of water availability but also by fluctuations in water availability. Furthermore, our results indicate that an increased few/large precipitation pattern expected under climate change conditions might further promote non-native plant invasions. Future field experiments with multiple phylogenetically controlled pairs of non-native and native species will be required to enhance our understanding of how water availability fluctuations impact on non-native invasions.

11.
Proc Natl Acad Sci U S A ; 121(29): e2404958121, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38985767

ABSTRACT

Hydrogen production through water splitting is a vital strategy for renewable and sustainable clean energy. In this study, we developed an approach integrating nanomaterial engineering and synthetic biology to establish a bionanoreactor system for efficient hydrogen production. The periplasmic space (20 to 30 nm) of an electroactive bacterium, Shewanella oneidensis MR-1, was engineered to serve as a bionanoreactor to enhance the interaction between electrons and protons, catalyzed by hydrogenases for hydrogen generation. To optimize electron transfer, we used the microbially reduced graphene oxide (rGO) to coat the electrode, which improved the electron transfer from the electrode to the cells. Native MtrCAB protein complex on S. oneidensis and self-assembled iron sulfide (FeS) nanoparticles acted in tandem to facilitate electron transfer from an electrode to the periplasm. To enhance proton transport, S. oneidensis MR-1 was engineered to express Gloeobacter rhodopsin (GR) and the light-harvesting antenna canthaxanthin. This led to efficient proton pumping when exposed to light, resulting in a 35.6% increase in the rate of hydrogen production. The overexpression of native [FeFe]-hydrogenase further improved the hydrogen production rate by 56.8%. The bionanoreactor engineered in S. oneidensis MR-1 achieved a hydrogen yield of 80.4 µmol/mg protein/day with a Faraday efficiency of 80% at a potential of -0.75 V. This periplasmic bionanoreactor combines the strengths of both nanomaterial and biological components, providing an efficient approach for microbial electrosynthesis.


Subject(s)
Graphite , Hydrogen , Shewanella , Hydrogen/metabolism , Shewanella/metabolism , Shewanella/genetics , Graphite/metabolism , Hydrogenase/metabolism , Hydrogenase/genetics , Electron Transport , Bioreactors , Synthetic Biology/methods , Electrodes , Rhodopsins, Microbial/metabolism , Rhodopsins, Microbial/genetics , Periplasm/metabolism , Bioelectric Energy Sources/microbiology
12.
J Asian Nat Prod Res ; : 1-13, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958642

ABSTRACT

Fuzheng Huayu recipe (FZHYR) is a Chinese patent medicine for the treatment of fibrosis. The effects of FZHYR on pulmonary fibrosis and macrophage polarization were investigated in vitro. FZHYR inhibited pulmonary inflammation and fibrosis and M2 polarization of macrophages in bleomycin-induced pulmonary fibrosis (BPF) of rat model. Differentially expressed genes were screened by high-throughput mRNA sequencing and GSEA showed that oxidative phosphorylation (OXPHOS) was correlated with BPF. FZHYR inhibited expressions of Ndufa2 and Ndufa6 in lung tissues of BPF rats. These findings suggest that OXPHOS pathway serves as a possible target for pulmonary fibrosis therapy by FZHYR.

13.
Int J Biol Sci ; 20(9): 3257-3268, 2024.
Article in English | MEDLINE | ID: mdl-38993553

ABSTRACT

Lung cancer stands as a major contributor to cancer-related fatalities globally, with cigarette smoke playing a pivotal role in its development and metastasis. Cigarette smoke is also recognized as a risk factor for bone loss disorders like osteoporosis. However, the association between cigarette smoke and another bone loss disorder, lung cancer osteolytic bone metastasis, remains largely uncertain. Our Gene Set Enrichment Analysis (GSEA) indicated that smokers among lung cancer patients exhibited higher expression levels of bone turnover gene sets. Both The Cancer Genome Atlas (TCGA) database and our clinic samples demonstrated elevated expression of the osteolytic factor IL-6 in ever-smokers with bone metastasis among lung cancer patients. Our cellular experiments revealed that benzo[α]pyrene (B[α]P) and cigarette smoke extract (CSE) promoted IL-6 production and cell migration in lung cancer. Activation of the PI3K, Akt, and NF-κB signaling pathways was involved in cigarette smoke-augmented IL-6-dependent migration. Additionally, cigarette smoke lung cancer-secreted IL-6 promoted osteoclast formation. Importantly, blocking IL-6 abolished cigarette smoke-facilitated lung cancer osteolytic bone metastasis in vivo. Our findings provide evidence that cigarette smoke is a risk factor for osteolytic bone metastasis. Thus, inhibiting IL-6 may be a valuable therapeutic strategy for managing osteolytic bone metastasis in lung cancer patients who smoke.


Subject(s)
Bone Neoplasms , Cell Movement , Interleukin-6 , Lung Neoplasms , Interleukin-6/metabolism , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Humans , Bone Neoplasms/secondary , Bone Neoplasms/metabolism , Animals , Mice , Signal Transduction , Cell Line, Tumor , Osteolysis/metabolism , Smoke/adverse effects , Smoking/adverse effects
14.
Nat Commun ; 15(1): 5899, 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39003324

ABSTRACT

Challenges in direct catalytic oxidation of biomass-derived aldehyde and alcohol into acid with high activity and selectivity hinder the widespread biomass application. Herein, we demonstrate that a Pd/Ni(OH)2 catalyst with abundant Ni2+-O-Pd interfaces allows electrooxidation of 5-hydroxymethylfurfural to 2, 5-furandicarboxylic acid with a selectivity near 100 % and 2, 5-furandicarboxylic acid yield of 97.3% at 0.6 volts (versus a reversible hydrogen electrode) in 1 M KOH electrolyte under ambient conditions. The rate-determining step of the intermediate oxidation of 5-hydroxymethyl-2-furancarboxylic acid is promoted by the increased OH species and low C-H activation energy barrier at Ni2+-O-Pd interfaces. Further, the Ni2+-O-Pd interfaces prevent the agglomeration of Pd nanoparticles during the reaction, greatly improving the stability of the catalyst. In this work, Pd/Ni(OH)2 catalyst can achieve 100% 5-hydroxymethylfurfural conversion and >90% 2, 5-furandicarboxylic acid selectivity in a flow-cell and work stably over 200 h under a fixed cell voltage of 0.85 V.

15.
Nat Commun ; 15(1): 5879, 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-38997253

ABSTRACT

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.


Subject(s)
Anti-Bacterial Agents , Methicillin-Resistant Staphylococcus aureus , Xanthenes , Methicillin-Resistant Staphylococcus aureus/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Xanthenes/chemical synthesis , Xanthenes/pharmacology , Xanthenes/chemistry , Microbial Sensitivity Tests , Stereoisomerism , Polycyclic Compounds/chemical synthesis , Polycyclic Compounds/pharmacology , Polycyclic Compounds/chemistry , Drug Discovery , Molecular Structure
16.
Materials (Basel) ; 17(13)2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38998458

ABSTRACT

In this paper, we demonstrate that the absorption frequencies of the bimodal absorber shift with the coupling strength of the bright and dark modes. The coupling between the bright mode and the dark mode can acquire electromagnetically induced transparency, we obtain the analytical relationship between the absorbing frequencies, the resonant frequencies, losses of the bright mode and dark mode, and the coupling strength between two modes by combining the coupled mode theory with the interference theory. As the coupling strength between the bright mode and the dark mode decreases, the two absorption peaks gradually move closer to each other, inversely, they will move away from each other. The simulation employs three distinct metasurface structures with coupling of the bright and dark modes, thereby verifying the generality of the theoretical findings.

17.
Research (Wash D C) ; 7: 0410, 2024.
Article in English | MEDLINE | ID: mdl-38966747

ABSTRACT

Amino acid bioconjugation technology has emerged as a pivotal tool for linking small-molecule fragments with proteins, antibodies, and even cells. The study in Nature by Chang and Toste introduces a redox-based strategy for tryptophan bioconjugation, employing N-sulfonyloxaziridines as oxidative cyclization reagents, demonstrating high efficiency comparable to traditional click reactions. Meanwhile, this tool provides feasible methods for investigating the mechanisms underlying functional tryptophan-related biochemical processes, paving the way for protein function exploration, activity-based proteomics for functional amino acid identification and characterization, and even the design of covalent inhibitors.

18.
Virology ; 597: 110152, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38968676

ABSTRACT

Cobalt-porphyrin phospholipid displays recombinant protein antigens on liposome surfaces via antigen polyhistidine-tag (His-tag), and when combined with monophosphorylated lipid A and QS-21 yields the "CPQ" vaccine adjuvant system. In this proof of principle study, CPQ was used to generate vaccine prototypes that elicited antibodies for two different alphaviruses (AV). Mice were immunized with computationally designed, His-tagged, physicochemical property consensus (PCPcon) protein antigens representing the variable B-domain of the envelope protein 2 (E2) from the serotype specific Venezuelan Equine Encephalitis Virus (VEEVcon) or a broad-spectrum AV-antigen termed EVCcon. The CPQ adjuvant enhanced the antigenicity of both proteins without eliciting detectable anti-His-tag antibodies. Antibodies elicited from mice immunized with antigens admixed with CPQ showed orders-of-magnitude higher levels of antigen-specific IgG compared to alternative control adjuvants. The ELISA results correlated with antiviral activity against VEEV strain TC83 and more weakly to Chikungunya virus 118/25. Thus, display of E.coli-produced His-tagged E2 protein segments on the surface of immunogenic liposomes elicits high levels of antigen-specific and AV neutralizing antibodies in mice with vaccination, while facilitating vaccine preparation and providing dose-sparing potential.

19.
Biomed Pharmacother ; 177: 117050, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38968794

ABSTRACT

Cardiovascular disease (CVD) is a leading cause of death in chronic kidney disease (CKD). Hemodialysis is one of the main treatments for patients with end-stage kidney disease. Epidemiological data has shown that acute myocardial infarction (AMI) accounts for the main reason for death in patients with CKD under hemodialysis therapy. Immune dysfunction and changes in metabolism (including a high level of inflammatory cytokines, a disorder of lipid and mineral ion homeostasis, accumulation of uremic toxins et al.) during CKD can deteriorate stability of atherosclerotic plaque and promote vascular calcification, which are exactly the pathophysiological mechanisms underlying the occurrence of AMI. Meanwhile, the hemodialysis itself also has adverse effects on lipoprotein, the immune system and hemodynamics, which contribute to the high incidence of AMI in these patients. This review aims to summarize the mechanisms and further promising methods of prevention and treatment of AMI in CKD patients undergoing hemodialysis, which can provide an excellent paradigm for exploring the crosstalk between the kidney and cardiovascular system.

20.
Adv Mater ; : e2405776, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38966888

ABSTRACT

Bionic artificial skin which imitates the features and functions of human skin, has broad applications in wearable human-machine interfaces. However, equipping artificial materials with skin-like mechanical properties, self-healing ability, and high sensitivity remains challenging. Here, inspired by the structure of human skin, an artificial skin based on ionogel composites with tailored mechanical properties and robust interface is prepared. Combining finite element analysis and direct ink writing (DIW) 3D printing technology, an ionogel composite with a rigid skeleton and an ionogel matrix is precisely designed and fabricated, realizing the mechanical anisotropy and nonlinear mechanical response that accurately mimic human skin. Robust interface is created through co-curing of the skeleton and matrix resins, significantly enhancing the stability of the composite. The realization of self-healing ability and resistance to crack growth further ensure the remarkable durability of the artificial skin for sensing application. In summary, the bionic artificial skin mimics the characteristics of human skin, including mechanical anisotropy, nonlinear mechanical response, self-healing capability, durability and high sensitivity when applied as flexible sensors. These strategies provide strong support for the fabrication of tissue-like materials with adaptive mechanical behaviors.

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