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1.
BMC Genomics ; 25(1): 663, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961347

RESUMO

BACKGROUND: The Atlantic cod is a prolific species in the Atlantic, despite its inconsistent specific antibody response. It presents a peculiar case within vertebrate immunology due to its distinct immune system, characterized by the absence of MHCII antigen presentation pathway, required for T cell-dependent antibody responses. Thorough characterisation of immunoglobulin loci and analysis of the antibody repertoire is necessary to further our understanding of the Atlantic cod's immune response on a molecular level. RESULTS: A comprehensive search of the cod genome (gadmor3.0) identified the complete set of IgH genes organized into three sequential translocons on chromosome 2, while IgL genes were located on chromosomes 2 and 5. The Atlantic cod displayed a moderate germline V gene diversity, comprising four V gene families for both IgH and IgL, each with distinct chromosomal locations and organizational structures. 5'RACE sequencing revealed a diverse range of heavy chain CDR3 sequences and relatively limited CDR3 diversity in light chains. The analysis highlighted a differential impact of V-gene germline CDR3 length on receptor CDR3 length between heavy and light chains, underlining different recombination processes. CONCLUSIONS: This study reveals that the Atlantic cod, despite its inconsistent antibody response, maintains a level of immunoglobulin diversity comparable to other fish species. The findings suggest that the extensive recent duplications of kappa light chain genes do not result in increased repertoire diversity. This research provides a comprehensive view of the Atlantic cod's immunoglobulin gene organization and repertoire, necessary for future studies of antibody responses at the molecular level.


Assuntos
Gadus morhua , Sequenciamento de Nucleotídeos em Larga Escala , Animais , Gadus morhua/genética , Cadeias Pesadas de Imunoglobulinas/genética , Imunoglobulinas/genética , Loci Gênicos , Genes de Imunoglobulinas , Região Variável de Imunoglobulina/genética
2.
J Vasc Surg Cases Innov Tech ; 10(2): 101403, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38435787

RESUMO

This study aims to investigate the significance of using the Toumai robotic platform for the resection of inferior vena cava (IVC) hemangiomas. Our objective is to provide information on the potential benefits of this innovative approach in managing these uncommon vascular tumors and to contribute to the growing body of knowledge in the field of surgical oncology and vascular surgery. A 37-year-old female patient with an incidental finding of a right retroperitoneal mass underwent contrast-enhanced magnetic resonance imaging, which confirmed the diagnosis of an IVC hemangioma. Due to the rarity and complexity of this vascular tumor, the medical team opted for a novel approach using the Toumai robotic surgical platform (Shanghai MicroPort MedBot Group Co, Ltd). Under general anesthesia, the patient was placed in the left lateral decubitus position, and the robotic arms were controlled remotely through the Toumai platform. A transperitoneal approach was adopted, and the surgeon meticulously resected the tumor while preserving the integrity of the IVC. The use of the Toumai robotic platform facilitated precise tumor resection, minimizing the risk of damage to surrounding structures. The minimally invasive nature of the robotic surgery contributed to a reduced incidence of postoperative complications and accelerated patient recovery. Furthermore, the remote fifth-generation mobile network surgical capabilities of the Toumai platform allow for expert care to be provided to patients despite geographic barriers. The robotic-assisted surgical approach using the Toumai platform demonstrates its potential benefits in managing rare and complex vascular tumors such as IVC hemangiomas. Robotic technology has the potential to revolutionize the field of surgical oncology and vascular surgery, leading to improved patient outcomes and healthcare delivery. However, more extensive clinical studies and larger case series are needed to validate the long-term safety and efficacy of this innovative surgical approach. Continued research and collaboration between clinicians and robotic technology experts are essential to fully realize the potential of robotic-assisted surgery for the benefit of patients with rare and challenging medical conditions.

3.
Angew Chem Int Ed Engl ; 63(18): e202401949, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38437064

RESUMO

X-ray scintillators have gained significant attention in medical diagnostics and industrial applications. Despite their widespread utility, scintillator development faces a significant hurdle when exposed to elevated temperatures, as it usually results in reduced scintillation efficiency and diminished luminescence output. Here we report a molecular design strategy based on a hybrid perovskite (TpyBiCl5) that overcomes thermal quenching through multi-excited state switching. The structure of perovskite provides a platform to modulate the luminescence centers. The rigid framework constructed by this perovskite structure stabilized its triplet states, resulting in TpyBiCl5 exhibiting an approximately 12 times higher (45 % vs. 3.8 %) photoluminescence quantum yield of room temperature phosphorescence than that of its organic ligand (Tpy). Most importantly, the interactions between the components of this perovskite enable the mixing of different excited states, which has been revealed by experimental and theoretical investigations. The TpyBiCl5 scintillator exhibits a detection limit of 38.92 nGy s-1 at 213 K and a detection limit of 196.31 nGy s-1 at 353 K through scintillation mode switching between thermally activated delayed fluorescence and phosphorescence. This work opens up the possibility of solving the thermal quenching in X-ray scintillators by tuning different excited states.

4.
Gastroenterology ; 167(2): 250-263, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38552723

RESUMO

BACKGROUND & AIMS: The treatment of celiac disease (CeD) with gluten-free diet (GFD) normalizes gut inflammation and disease-specific antibodies. CeD patients have HLA-restricted, gluten-specific T cells persisting in the blood and gut even after decades of GFD, which are reactivated and disease driving upon gluten exposure. Our aim was to examine the transition of activated gluten-specific T cells into a pool of persisting memory T cells concurrent with normalization of clinically relevant biomarkers during the first year of treatment. METHODS: We followed 17 CeD patients during their initial GFD year, leading to disease remission. We assessed activation and frequency of gluten-specific CD4+ blood and gut T cells with HLA-DQ2.5:gluten tetramers and flow cytometry, disease-specific serology, histology, and symptom scores. We assessed gluten-specific blood T cells within the first 3 weeks of GFD in 6 patients and serology in an additional 9 patients. RESULTS: Gluten-specific CD4+ T cells peaked in blood at day 14 while up-regulating Bcl-2 and down-regulating Ki-67 and then decreased in frequency within 10 weeks of GFD. CD38, ICOS, HLA-DR, and Ki-67 decreased in gluten-specific cells within 3 days. PD-1, CD39, and OX40 expression persisted even after 12 months. IgA-transglutaminase 2 decreased significantly within 4 weeks. CONCLUSIONS: GFD induces rapid changes in the phenotype and number of gluten-specific CD4+ blood T cells, including a peak of nonproliferating, nonapoptotic cells at day 14. Subsequent alterations in T-cell phenotype associate with the quiescent but chronic nature of treated CeD. The rapid changes affecting gluten-specific T cells and disease-specific antibodies offer opportunities for clinical trials aiming at developing nondietary treatments for patients with newly diagnosed CeD.


Assuntos
Linfócitos T CD4-Positivos , Doença Celíaca , Dieta Livre de Glúten , Glutens , Fenótipo , Proteína 2 Glutamina gama-Glutamiltransferase , Humanos , Doença Celíaca/dietoterapia , Doença Celíaca/imunologia , Glutens/imunologia , Glutens/administração & dosagem , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Antígenos HLA-DQ/imunologia , Proteínas de Ligação ao GTP/imunologia , Proteínas de Ligação ao GTP/metabolismo , Ativação Linfocitária , Transglutaminases/imunologia , Biomarcadores/sangue , Biomarcadores/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Células T de Memória/imunologia , Células T de Memória/metabolismo , Fatores de Tempo , Adulto Jovem , Resultado do Tratamento , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo
5.
PLoS One ; 19(3): e0300865, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38517905

RESUMO

Entomological sampling and storage conditions often prioritise efficiency, practicality and conservation of morphological characteristics, and may therefore be suboptimal for DNA preservation. This practice can impact downstream molecular applications, such as the generation of high-throughput genomic libraries, which often requires substantial DNA input amounts. Here, we use a practical Tn5 transposase tagmentation-based library preparation method optimised for 96-well plates and low yield DNA extracts from insect legs that were stored under sub-optimal conditions for DNA preservation. The samples were kept in field vehicles for extended periods of time, before long-term storage in ethanol in the freezer, or dry at room temperature. By reducing DNA input to 6ng, more samples with sub-optimal DNA yields could be processed. We matched this low DNA input with a 6-fold dilution of a commercially available tagmentation enzyme, significantly reducing library preparation costs. Costs and workload were further suppressed by direct post-amplification pooling of individual libraries. We generated medium coverage (>3-fold) genomes for 88 out of 90 specimens, with an average of approximately 10-fold coverage. While samples stored in ethanol yielded significantly less DNA compared to those which were stored dry, these samples had superior sequencing statistics, with longer sequencing reads and higher rates of endogenous DNA. Furthermore, we find that the efficiency of tagmentation-based library preparation can be improved by a thorough post-amplification bead clean-up which selects against both short and large DNA fragments. By opening opportunities for the use of sub-optimally preserved, low yield DNA extracts, we broaden the scope of whole genome studies of insect specimens. We therefore expect these results and this protocol to be valuable for a range of applications in the field of entomology.


Assuntos
DNA , Sequenciamento de Nucleotídeos em Larga Escala , Transposases , DNA/genética , Biblioteca Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Etanol , Análise de Sequência de DNA/métodos
6.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013573

RESUMO

Objective To analyze the echinococcosis surveillance results in Bayingolin Mongol Autonomous Prefecture, Xinjiang Uygur Autonomous Region from 2017 to 2022, so as to provide insights into formulation of echinococcosis control measures in the prefecture. Methods Villagers were randomly sampled using a multistage sampling method from class I and II echinococcosis endemic counties in Bayingolin Mongolian Autonomous Prefecture from 2017 to 2022 for detection of human echinococcosis, while all patients undergoing ultrasound examinations in medical institutions in class III endemic counties received active echinococcosis screening. In addition, livestock in centralized slaughterhouses or slaughtering sites were screened for echinococcosis using the palpation and necropsy method, and fresh domestic dog feces samples were collected from randomly selected dog owners in each administrative village for detection of Echinococcus copro-antigen in domestic dogs. The trends in detection of human and livestock echinococcosis, detection of newly diagnosed human echinococcosis cases and detection of Echinococcus coproantigen in domestic dogs were analyzed in Bayingolin Mongol Autonomous Prefecture from 2017 to 2022. Results The mean detection rate of human echinococcosis was 0.13% (540/407 803) in Bayingolin Mongol Autonomous Prefecture from 2017 to 2022, which appeared a tendency towards a decline over years (χ2trend = 1 217.21, P < 0.001), and the highest detection of newly diagnosed echinococcosis cases was seen in Hejing County (0.28%, 191/67 865). The detection of livestock echinococcosis appeared a tendency towards a decline over years from 2017 to 2022 (χ2trend = 147.02, P < 0.001), with the highest detection rate seen in Hejing County (3.44%, 86/2 500), and the detection of Echinococcus copro-antigen in domestic dogs appeared a tendency towards a decline over years from 2017 to 2022 (χ2trend = 302.46, P < 0.001), with the highest detection rate in Qiemo County (2.74%, 118/4 313). Conclusions The detection of human and livestock echinococcosis and dog feces antigens Echinococcus copro-antigen in domestic dogs all appeared a tendency towards a decline in Bayingolin Mongol Autonomous Prefecture, Xinjiang Uygur Autonomous Region from 2017 to 2022; however, there is still a high echinococcosis transmission risk in local areas. Sustainable integrated echinococcosis control is required in Bayingolin Mongol Autonomous Prefecture.

7.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013443

RESUMO

Arsenic, a naturally occurring metal-like chemical element, is one of the 10 chemicals of major public concerns listed by the World Health Organization as harmful to the environment and human health. It can enter the human body through breathing, intaking food, drinking water, skin exposure, and other ways, and long-term exposure to arsenic can cause cancer of multiple organs and impaired function of multiple systems. Epigenetic mechanisms play an important role in arsenic-induced health effects, and research suggested that the carcinogenicity of arsenic may be associated with epigenetic changes. Previous studies focused on the effects of arsenic on DNA methylation modification. In recent years, research showed that 5-hydroxymethylcytosine (5-hmC), an intermediate of active demethylation of DNA, can act as a sensitive epigenetic mark and play a crucial role as a "bridge" between arsenic exposure and health effects. Based on the latest research progress on the role of DNA hydroxymethylation in the health effects associated with arsenic exposure, this article briefly described the relationship between the health effects of arsenic exposure and DNA hydroxymethylation, summarized the possible mechanisms of DNA hydroxymethylation in the health effects associated with arsenic exposure, and provided a scientific basis for preventing and treating the health effects associated with arsenic exposure.

8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1006455

RESUMO

Background Long-term exposure to noise during sleep may has adverse effects on metabolic system, and liver lipid metabolism is closely related to circadian clock genes. Objective To investigate the effects of long-term noise exposure during sleep on liver circadian clock and lipid metabolism in mice and its related mechanism. Methods Twenty C57BL/6J male mice were randomly divided into two groups: a noise exposure group and a control group with 10 mice in each group. The mice in the noise exposure group were exposed to white noise at 90 dB sound pressure level (SPL) for 30 consecutive days, 8 h a day, from 9:00 to 17:00. The mice in the control group were exposed to background noise ≤40 dB SPL. After noise exposure, the animals were neutralized at 14:00 (ZT6) and 2:00 (ZT18), 5 animals at each time spot, and the liver tissues were collected. Total cholesterol and triglyceride in liver were determined by cholesterol oxidase method and glycerol phosphate oxidase method respectively. The expressions of circadian clock genes (Clock, Bmal1, Rev-erbα, and Rev-erbβ) and lipid metabolism genes (Srebp1c, Hmgcr, Fasn, Lxrα, Acc1, and Chrebp) in liver were detected by quantitative real-time PCR. Results Compared with the control group, the content of total cholesterol in liver in the noise exposure group increased by 48% (P<0.05) and the content of liver triglyceride increased by 61% (P<0.05) at ZT18. The mRNA expression levels of circadian clock genes Clock and Bmal1 in the noise exposure group was significantly increased at ZT18 and decreased at ZT6 (P<0.05). The mRNA expression level of Rev-erbα decreased at both ZT6 and ZT18 (P<0.05). The mRNA expression level of Rev-erbβ had no significant change at ZT6 and ZT18. The mRNA expression levels of liver lipid metabolism related genes Srebp1c, Hmgcr, Chrebp, and Lxrα in the noise exposure group were higher than those in the control group at ZT18 (P<0.05). The mRNA expression levels of Acc1 and Fasn showed no significant change at ZT6, then an upward trend at ZT18, but no significant difference between the two time spots (P>0.05). Conclusion Long-term noise exposure during sleep can cause circadian clock and lipid metabolism disorders in mice. Among them, suppression of key circadian clock genes may be associated with Rev-erbα-mediated upregulation of the nuclear receptors Srebp1c and Chrebp for lipid synthesis and deposition in the liver, resulting in lipid metabolism disorder.

9.
J Food Sci ; 89(1): 581-595, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38126106

RESUMO

Cronobacter sakazakii, an important Gram-negative foodborne pathogen, can cause neonatal meningitis and sepsis with high rates of infection and death. Gene ESA_RS15745 encodes a sugar transporter protein, which is not only essential for osmotic pressure maintenance during bacterial growth and reproduction but also associated with their desiccation tolerance, motility, and biofilm formation. Here, a mutant strain of ESA_RS15745 (ΔESA_RS15745) and the complementation strain (cpESA_RS15745) were constructed using a suicide vector knockout and gene complementation. ΔESA_RS15745 was found to have a decrease in its ability to transport maltose and trehalose and resist desiccation, whereas an increase in the ability of motility and biofilm formation, implying that ESA_RS15745 may positively regulate sugar transport and desiccation tolerance and negatively regulate motility and biofilm formation. To further investigate the molecular mechanisms underlying the function of related genes, RNA-seq was performed to explore the differentially expressed genes in the mutants. RNA-seq results showed the upregulation of 114 genes (mainly including those regulating chemotaxis and flagellar motility) and the downregulation of 22 genes (mainly including those regulating sugar transport). qRT-PCR analysis supported the RNA-seq results and showed that ESA_RS15745 may influence the dehydration tolerance though decreasing the intracellular trehalose content and negatively regulate the motility though the chemotactic signaling pathway. In addition, the biofilm formation of C. sakazakii should also be speculated to negatively regulate by ESA_RS15745 by consuming the extracellular carbohydrates concentration and then downregulating the intracellular cyclic diguanosine monophosphate. This study offers a reference for comprehending the molecular mechanism of gene ESA_RS15745 in C. sakazakii.


Assuntos
Cronobacter sakazakii , Cronobacter , Humanos , Recém-Nascido , Cronobacter sakazakii/genética , Dessecação , Trealose , Regulação para Baixo , Biofilmes
10.
Sci Adv ; 9(44): eadj0101, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-37910624

RESUMO

The constant exposure of the fish branchial cavity to aquatic pathogens causes local mucosal immune responses to be extremely important for their survival. Here, we used a marker for T lymphocytes/natural killer (NK) cells (ZAP70) and advanced imaging techniques to investigate the lymphoid architecture of the zebrafish branchial cavity. We identified a sub-pharyngeal lymphoid organ, which we tentatively named "Nemausean lymphoid organ" (NELO). NELO is enriched in T/NK cells, plasma/B cells, and antigen-presenting cells embedded in a network of reticulated epithelial cells. The presence of activated T cells and lymphocyte proliferation, but not V(D)J recombination or hematopoiesis, suggests that NELO is a secondary lymphoid organ. In response to infection, NELO displays structural changes including the formation of T/NK cell clusters. NELO and gill lymphoid tissues form a cohesive unit within a large mucosal lymphoid network. Collectively, we reveal an unreported mucosal lymphoid organ reminiscent of mammalian tonsils that evolved in multiple teleost fish families.


Assuntos
Tonsila Palatina , Peixe-Zebra , Humanos , Animais , Tecido Linfoide , Faringe , Linfócitos T , Mamíferos
11.
Heliyon ; 9(9): e20244, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809410

RESUMO

Emissions from transportation fuel vehicles are polluting the environment more than ever before. Currently, autonomous delivery vehicles (ADVs) are welcomed by logistics service providers and lots of consumers in general for their significant contribution in reducing environmental pollution and increasing delivery efficiency. However, there is a lack of in-depth research on consumers' willingness to adopt ADVs, despite the fact that ADVs are innovative delivery method in the field of last-mile delivery. The purpose of the study is to expand the existing knowledge of consumers' adoption behaviors by developing and testing the extended Value-Belief-Norm (VBN) theory in autonomous delivery literature. In particular, the study adds subjective norms and COVID-19 risk into the original VBN model as a theoretical framework to gain a comprehensive understanding of the consumer decision-making processes with respect to their intentions to use ADVs. Structural equation modeling is conducted using data from a web-based survey of 561 consumers through an online sample platform. The results of the study demonstrated that both subjective norms and COVID-19 risk are all related with consumers' intention to use ADVs. The casual chain hypotheses of the extend VBN theory mentioned in our study are all supported. The results of the study make significant theoretical and managerial contributions to the field of last-mile delivery and the adoption behaviors of emerging technologies.

12.
J Am Chem Soc ; 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36917067

RESUMO

Two-dimensional covalent-organic frameworks (2D COFs) have recently emerged as great prospects for their applications as new photocatalytic platforms in solar-to-hydrogen conversion; nevertheless, their inefficient solar energy capture and fast charge recombination hinder the improvement of photocatalytic hydrogen production performance. Herein, two photoactive three-component donor-π-acceptor (TCDA) materials were constructed using a multicomponent synthesis strategy by introducing electron-deficient triazine and electron-rich benzotrithiophene moieties into frameworks through sp2 carbon and imine linkages, respectively. Compared with two-component COFs, the novel TCDA-COFs are more convenient in regulating the inherent photophysical properties, thereby realizing outstanding photocatalytic activity for hydrogen evolution from water. Remarkably, the first sp2 carbon-linked TCDA-COF displays an impressive hydrogen evolution rate of 70.8 ± 1.9 mmol g-1 h-1 with excellent reusability in the presence of 1 wt % Pt under visible-light illumination (420-780 nm). Utilizing the combination of diversified spectroscopy and theoretical prediction, we show that the full π-conjugated linkage not only effectively broadens the visible-light harvesting of COFs but also enhances charge transfer and separation efficiency.

13.
BMC Public Health ; 23(1): 126, 2023 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-36653837

RESUMO

BACKGROUND: Allergic diseases are highly prevalent in the women of childbearing age. As we know, the immune system could change when pregnancy, which may affect the course of allergic diseases. Meanwhile, they also can affect the course and outcome of pregnancy. The data on incidence of allergies during pregnancy is lacking and conducting clinical trials in pregnant women was limited, therefore, we observed a prebirth cohort to supplement the relevant data and strengthen concerned research conductions. OBJECTIVE: We aim to obtain the incidence of allergies in urban pregnancy and explore the relevant factors of allergic diseases in urban pregnancy. METHODS: We design a multicenter and prospective cohort in 20 institutions above municipal level which were eligible according to the study design from 14 provinces covering all-side of China. This cohort was conducted from 13+6 weeks of gestation to 12 months postpartum and in our study, we chose the prenatal part to analyze. The outcome was developing allergies during pregnancy, which were diagnosed by clinicians according to the uniform criterion from National Health Commission. All the data was collected by electronic questionnaires through tablet computers. RESULTS: The incidence of allergic diseases in urban pregnant women was 21.0% (95%CI 20.0% ~ 22.0%). From social demography data, the history of allergies of pregnant women and their parents had statistical significance(p < 0.01); For exposure to living or working environment, house decoration for less than half a year, exposure to plush toys, disinfectants, insecticides, antihistamines, glucocorticoids, antipyretic analgesics, tocolytic agent and probiotics had statistical significance (all p < 0.05); For psychological status, self-rated depression and anxiety had statistical significance (p = 0.026;p = 0.006). CONCLUSION: The incidence of allergic diseases in urban pregnant women was similar to the former study and kept a medium-high level. The history of allergies of pregnant women and their parents, house decoration time, exposure to plush toys, disinfectants, insecticides, antihistamines, glucocorticoids, antipyretic analgesics, tocolytic agents, probiotics, self-rated depression, and anxiety were relevant factors of allergic diseases during pregnancy.


Assuntos
Antipiréticos , Hipersensibilidade , Inseticidas , Feminino , Gravidez , Humanos , Gestantes/psicologia , Estudos de Coortes , Estudos Prospectivos , Incidência , Glucocorticoides , Hipersensibilidade/epidemiologia , China/epidemiologia
14.
Small Methods ; 7(1): e2201166, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36543365

RESUMO

Graphene-like 2D coordination polymers (GCPs) have been of central research interest in recent decades with significant impact in many fields. According to classical coordination chemistry, Cu(II) can adopt the dsp2 hybridization to form square planar coordination geometry, but not Cu(I); this is why so far, there has been few 2D layered structures synthesized from Cu(I) precursors. Herein a pair of isostructural GCPs synthesized by the coordination of benzenehexathiol (BHT) ligands with Cu(I) and Cu(II) ions, respectively, is reported. Spectroscopic characterizations indicate that Cu(I) and Cu(II) coexist with a near 1:1 ratio in both GCPs but remain indistinguishable with a fractional oxidation state of +1.5 on average, making these two GCPs a unique pair of Creutz-Taube mixed-valence 2D structures. Based on density functional theory calculations, an intramolecular pseudo-redox mechanism is further uncovered whereby the radicals on BHT ligands can oxidize Cu(I) or reduce Cu(II) ions upon coordination, thus producing isostructures with distinct electron configurations. For the first time, it is demonstrated that using Cu(I) or Cu(II), one can achieve 2D isostructures, indicating an unusual fact that a neutral periodic structure can host a different number of total electrons as ground states, which may open a new chapter for 2D materials.

15.
Acta Pharmaceutica Sinica ; (12): 2203-2217, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-999143

RESUMO

To address the continuous emergence of drug-resistant strains of viruses and the outbreaks of novel virus infections, developing new antiviral drugs based on novel strategies has become an important and urgent research topic. In recent years, the rapidly developing multi-specific binding strategy has become a focus and been widely applied in antiviral. This review summarizes the recent progress of the multi-specific binding strategy in the antiviral field from the perspective of medicinal chemistry and discusses existing challenges as well as future opportunities for antiviral drug discovery.

16.
Acta Pharmaceutica Sinica ; (12): 3270-3284, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-999071

RESUMO

Hepatitis B virus infection is a serious threat to human life and health. The approved anti-HBV drugs including interferons and nucleos(t)ide analogues have serious adverse effect, rebound phenomena after drug withdrawal, and drug resistance. And the cccDNA cannot be completely eliminated by both of them, which is the reason why a complete cure for hepatitis B cannot be achieved. Therefore, developing anti-HBV drugs directly targeting protein or nucleic acid of HBV remains a current public health priority. Based on the analysis of representative literature from the last decade, this article reviews recent developments in small molecule inhibitors directly targeting HBV from a medicinal chemistry perspective.

17.
Acta Pharmaceutica Sinica ; (12): 2979-2994, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-999040

RESUMO

Hepatitis B virus (HBV) represents a significant global public health challenge. Despite the availability of several approved drugs for hepatitis B treatment, the persistence of covalently closed circular DNA (cccDNA) renders HBV eradication elusive, thereby leading to disease relapse after drug withdrawal. This paper reviews the regulatory mechanisms of cccDNA formation, transcription and replication, and summarizes the research progress of related small molecule regulators from the perspective of medicinal chemistry.

18.
Acta Physiologica Sinica ; (6): 379-389, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-981014

RESUMO

The present article was aimed to compare the effectiveness of different induction methods for depression models. Kunming mice were randomly divided into chronic unpredictable mild stress (CUMS) group, corticosterone (CORT) group, and CUMS+CORT (CC) group. The CUMS group received CUMS stimulation for 4 weeks, and the CORT group received subcutaneous injection of 20 mg/kg CORT into the groin every day for 3 weeks. The CC group received both CUMS stimulation and CORT administration. Each group was assigned a control group. After modeling, forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT) were used to detect the behavioral changes of mice, and the serum levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT) and CORT were detected with ELISA kits. Attenuated total refraction (ATR) spectra of mouse serum were collected and analyzed. HE staining was used to detect morphological changes in mouse brain tissue. The results showed that the weight of model mice from the CUMS and CC groups decreased significantly. There was no significant change in immobility time of model mice from the three groups in FST and TST, while the glucose preference of model mice from the CUMS and CC groups was significantly reduced (P < 0.05). The serum 5-HT levels of model mice from the CORT and CC groups were significantly reduced, while the serum BDNF and CORT levels of model mice from the CUMS, CORT, and CC groups showed no significant changes. Compared with their respective control groups, the three groups showed no significant difference in the one-dimensional spectrum of serum ATR. The difference spectrum analysis results of the first derivative of the spectrogram showed that the CORT group had the greatest difference from its respective control group, followed by the CUMS group. The structures of hippocampus in the model mice from the three groups were all destroyed. These results suggest that both CORT and CC treatments can successfully construct a depression model, and the CORT model is more effective than the CC model. Therefore, CORT induction can be used to establish a depression model in Kunming mice.


Assuntos
Camundongos , Animais , Depressão/etiologia , Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo , Serotonina
19.
Digital Chinese Medicine ; (4): 317-327, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-997735

RESUMO

@#Objective To investigate the underlying mechanism of the compound Bugansan Decoction (补肝散, BGSD) in intervening learning and memory in D-galactose (D-gal)-induced aging rats. @*Methods@#A total of 40 rats were randomly assigned to four groups: control, model, BGSD [14.06 g/(kg·d)], and piracetam [0.4 g/(kg·d)] groups, with 10 rats in each group. D-gal [400 mg/(kg·d)] was injected intraperitoneally to establish the aging rat model. The rats' body weight, water intake, food intake, and gripping strength were recorded each week. The eightarm maze and step-down test were used to measure the rats' capacity for learning and memory. Liver, thymus, spleen, and brain tissues were weighed to calculate the corresponding organ indices; serum malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured. Hematoxylin and eosin (HE) staining was adopted to observe the pathological changes of the hippocampus; enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the hippocampus. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of receptors for advanced glycation end products (RAGE), nuclear factor-κB (NF-κB), TNF-α, IL-6, and IL-1β mRNA in the hippocampus. Western blot (WB) was employed to detect the expression levels of advanced glycation end products (AGEs), RAGE, and NF-κB protein in the hippocampus. @*Results@#In D-gal-induced aging rats, BGSD significantly increased food intake, water intake, body weight, gripping strength, and organ indices (P < 0.05), and significantly decreased working memory error (WME), reference memory error (RME), and total memory errors (TE) in an eight-arm maze (P < 0.05). In the step-down test, step-down latency was prolonged and the frequency of errors dropped (P < 0.05). Additionally, BGSD could lessen the harm done to hippocampus neurons, increase serum SOD activity, lower MDA levels, and down-regulate the expression levels of the pro-inflammatory molecules TNF-α, IL-6, and IL-1β (P < 0.05). Further findings showed that BGSD significantly decreased hippocampal AGEs, RAGE, and NF-κB expression (P < 0.05). @*Conclusion@#By blocking the AGEs/RAGE/NF-κB signaling pathway, BGSD may regulate the neuroinflammatory damage in D-gal-induced aging rats, and thus improve learning and memory.

20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-995250

RESUMO

Objective:To provide data reference for using Chinese rhesus macaques as research model by studying the immunophenotype and function of peripheral blood lymphocytes in Chinese rhesus macaques.Methods:By optimizing antibody clones and fluorescent colors, the lymphocyte subset assay and T cell function assay panels were determined. Then the panels were used to analyze the proportion of T, B, NK and other cell subsets in peripheral blood mononuclear cells (PBMCs) in 15 healthy Chinese rhesus monkeys, and the ability of T cells to secrete cytokines after non-specific stimulation.Results:Two multi-color flow cytometry analytic panels were established. Panel 1 could simultaneously detect a variety of lymphocyte subsets, including cytotoxic T lymphocytes, follicular helper T cells, regulatory T cells, B cells and NK cells. Panel 2 could detect the functions of multiple T cell subsets and the expression of immune checkpoint moleculars. The mean percentages of T, B, NK, Tfh, Treg, CD16 + NK and CD56 + NK cells in PBMCs of the Chinese rhesus macaques were (75.32±7.73)%, (13.22±7.50)%, (0.88±0.48)%, (0.73±0.27)%, (0.75±0.43)%, (47.87±22.35)% and (10.69±12.41)%. After non-specific stimulation, the proportion of CD4 + T cells secreting IL-2 and TNF-α was higher than that of CD8 + T cells, and the proportion of CD8 + T cells secreting CD107a and IFN-γ was higher than that of CD4 + T cells, while the proportion of CD4 + and CD8 + T cells secreting IL-17A was low. Conclusions:This study established a multi-color flow detection scheme that could simultaneously detect multiple cellular surface molecules and cytokines at the single cell level and could accurately and comprehensively analyze the immune cell subsets, functions and the immune checkpoint molecules in peripheral blood of Chinese rhesus macaques, providing a new experimental method and basic data for the development of vaccines and drugs against infectious diseases.

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