Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 169
Filter
1.
J Psychosom Obstet Gynaecol ; 45(1): 2356212, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38949115

ABSTRACT

AIM: Comparing the anxiety and depression severity and their impact on subsequent birth outcomes in pregnant women before and during Omicron wave in Shanghai in 2022. METHODS: The depression-anxiety symptoms networks were compared between the pregnant women during the outbreak period (outbreak group; n = 783) and a matched control group of pregnant women before the outbreak (pre-outbreak group; n = 783). The impact of baseline mental state on follow-up pregnancy and neonatal outcomes was also explored by logistic regression. FINDINGS: Levels of depression and anxiety between the two groups were not significant different. Network analysis showed that central symptom "trouble relaxing" and bridge symptom "depressed mood" shared by both groups. Different symptom associations in different periods of the pandemic. Total scores and sub-symptom scores of prenatal depressive and anxious severities increased the odds ratios of maternal and neonatal syndromes. The influence of mental state on gestational and neonatal outcomes differed across different pandemic periods. CONCLUSION: The Omicron wave did not have a significant negative impact on the depressive and anxious mood in pregnant women. Targeting central and bridge symptoms intervention may be effective in reducing their adverse effects on co-occurring of anxious and depressive mood and birth outcomes.


Subject(s)
Anxiety , COVID-19 , Depression , Pregnancy Complications , Pregnancy Outcome , Humans , Female , Pregnancy , COVID-19/psychology , COVID-19/epidemiology , Adult , Case-Control Studies , Depression/epidemiology , Depression/psychology , Anxiety/epidemiology , Anxiety/psychology , Pregnancy Outcome/epidemiology , Prospective Studies , China/epidemiology , Pregnancy Complications/epidemiology , Pregnancy Complications/psychology , SARS-CoV-2 , Severity of Illness Index , Infant, Newborn , Pregnant Women/psychology
2.
Neurosci Lett ; 836: 137871, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38857698

ABSTRACT

Parkinson's disease (PD) entails the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc), leading to movement-related impairments. Accurate assessment of DA neuron health is vital for research applications. Manual analysis, however, is laborious and subjective. To address this, we introduce TrueTH, a user-friendly and robust pipeline for unbiased quantification of DA neurons. Existing deep learning tools for tyrosine hydroxylase-positive (TH+) neuron counting often lack accessibility or require advanced programming skills. TrueTH bridges this gap by offering an open-sourced and user-friendly solution for PD research. We demonstrate TrueTH's performance across various PD rodent models, showcasing its accuracy and ease of use. TrueTH exhibits remarkable resilience to staining variations and extreme conditions, accurately identifying TH+ neurons even in lightly stained images and distinguishing brain section fragments from neurons. Furthermore, the evaluation of our pipeline's performance in segmenting fluorescence images shows strong correlation with ground truth and outperforms existing models in accuracy. In summary, TrueTH offers a user-friendly interface and is pretrained with a diverse range of images, providing a practical solution for DA neuron quantification in Parkinson's disease research.

3.
J Agric Food Chem ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38935872

ABSTRACT

A new fusicoccane diterpenoid, harziaderma A (1), two novel harziane diterpenoids, harzianones G and H (2 and 3), one revised harziane diterpenoid (4), and two known diterpenoids (5 and 6) were isolated from the fungus Trichoderma harzianum and established via NMR, HRESIMS, Mo2(OAc)4-induced circular dichroism (ICD) and electronic circular dichroism (ECD) calculations. It is worth noting that compound 1 represents the first instance of a fusicoccane-type diterpenoid derived from T. harzianum. The structure of furanharzianone B was revised to 4 via careful spectroscopic analyses. Additionally, compounds 2 and 5 could suppress the overall growth of the foodborne bacterial pathogen Bacillus cereus. Compound 4 showed a moderate suppressive impact on NO generation in lipopolysaccharide (LPS)-treated RAW 264.7 cells. The discoveries from the current study not only expanded the structural variety of diterpenoids isolated from T. harzianum but also laid a robust foundation for the development of harziane diterpenoids as anti-foodborne pathogen agents.

5.
Cell ; 187(9): 2236-2249.e17, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38614100

ABSTRACT

Unlike those of double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), and ssRNA viruses, the mechanism of genome packaging of dsRNA viruses is poorly understood. Here, we combined the techniques of high-resolution cryoelectron microscopy (cryo-EM), cellular cryoelectron tomography (cryo-ET), and structure-guided mutagenesis to investigate genome packaging and capsid assembly of bluetongue virus (BTV), a member of the Reoviridae family of dsRNA viruses. A total of eleven assembly states of BTV capsid were captured, with resolutions up to 2.8 Å, with most visualized in the host cytoplasm. ATPase VP6 was found underneath the vertices of capsid shell protein VP3 as an RNA-harboring pentamer, facilitating RNA packaging. RNA packaging expands the VP3 shell, which then engages middle- and outer-layer proteins to generate infectious virions. These revealed "duality" characteristics of the BTV assembly mechanism reconcile previous contradictory co-assembly and core-filling models and provide insights into the mysterious RNA packaging and capsid assembly of Reoviridae members and beyond.


Subject(s)
Bluetongue virus , Capsid Proteins , Capsid , Cryoelectron Microscopy , RNA, Viral , Viral Genome Packaging , Bluetongue virus/genetics , Bluetongue virus/physiology , Bluetongue virus/metabolism , Capsid/metabolism , Capsid/ultrastructure , Capsid Proteins/metabolism , Capsid Proteins/genetics , Capsid Proteins/chemistry , Animals , RNA, Viral/metabolism , RNA, Viral/genetics , Genome, Viral/genetics , Virus Assembly , Electron Microscope Tomography , Virion/metabolism , Virion/genetics , Virion/ultrastructure , Models, Molecular , Cell Line , Cricetinae
6.
Huan Jing Ke Xue ; 45(2): 1222-1232, 2024 Feb 08.
Article in Chinese | MEDLINE | ID: mdl-38471958

ABSTRACT

The analysis of the willingness of individual farmers to cover costs is an important basis for measuring the economic value of agricultural non-point pollution management, and determining the ecological and economic value of rural surface pollution control is a necessary measure to internalize the externalities of agricultural production. Based on the analysis of the hierarchy of factors influencing the cognition of farmers, this study constructed a theoretical framework based on distributed cognition theory to analyze their willingness to pay for agricultural non-point source pollution control from the perspective of individual farmers. On the basis of this framework, we used the Double-Hurdle model to empirically test the overall process of farmers'willingness to pay and their willingness to pay the amount for agricultural non-point source pollution control by combining 531 microscopic research datapoints in Guanzhong, Shaanxi Province. The results showed that: ① the number of farmers with willingness to pay for agricultural non-point source pollution control was 267, accounting for 50.30% of the total sample, and the average value of willingness to pay was 1 469.77 yuan·hm-2; the total economic value of agricultural non-point source pollution control in Shaanxi Province in 2020 was estimated to be 5.791 billion yuan based on the expected value of the willingness to pay level of the research sample. ② Farmers'willingness to pay for agricultural non-point source pollution control was influenced by the combined effects of personal, regional, and cultural forces, and the effects of each dimension were similar; farmers' willingness to pay for agricultural non-point source pollution control was mainly influenced by the cultural force factor, and the effects of personal and regional forces were very limited. ③ The results of the regressions by income level showed that personal and cultural strengths had a significant impact on the willingness to pay among the low-income group but did not contribute to the increase in the willingness to pay.


Subject(s)
Farmers , Non-Point Source Pollution , Humans , Farmers/psychology , Agriculture , Rural Population , Cognition , China
7.
J Agric Food Chem ; 72(7): 3549-3559, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38325810

ABSTRACT

Bipoladiens A-E (1-5), five new ophiobolin-derived sesterterpenoids, and a known compound 6 (bipolaricin R) were isolated from the cultures of the phytopathogenic fungus Bipolaris maydis. Their structures and absolute configurations were elucidated based on comprehensive spectroscopic analyses, HRESIMS, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analyses. Notably, compound 1 has an undescribed tetracyclic 5/8/5/7 fused carbon skeleton, and compound 2 possesses a rare multicyclic caged ring system. The biosynthetic pathway of 1 was proposed starting from 6 via a series of oxidation and cyclization reactions. Compound 6 showed excellent antiproliferation and apoptosis induction effects against A549 cell line. Additionally, compounds 5 and 6 exhibited noticeable antimicrobial ability against Bacillus cereus, Staphylococcus aureus, and Staphylococcus epidermidis. These findings not only developed the chemical and bioactivities diversities of ophiobolin-sesterterpenoid but also provided an idea to boost the application of natural products in the control of food pathogens.


Subject(s)
Anti-Infective Agents , Sesterterpenes , Sesterterpenes/pharmacology , Sesterterpenes/chemistry , Bipolaris , Molecular Structure
8.
Eur Geriatr Med ; 15(2): 553-559, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38227111

ABSTRACT

PURPOSE: Nutrition intake is one of the modifiable risk factors for cognitive decline. Whether energy and protein intakes alter the association between pulmonary function (PF) and cognition has not been studied. METHODS: We made use of information from the U.S. National Health and Nutrition Examination Survey (NHANES) 2011-2012. PF measures, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF), were calculated, whereas cognitive function was assessed through four tests: the Immediate Recall test (IRT), the Delayed Recall test (DRT), the Animal Fluency test (AFT) and the Digit Symbol Substitution test (DSST). Energy and protein intakes were measured using the 24-h dietary recall method. Weighted generalized linear regression was performed upon adjustment for covariates. Further interaction analyses were conducted to investigate the effect of energy and protein intakes on the association between PF and cognition. RESULTS: We finally included 803 participants aged ≥ 60 years (54.4% female, weighted value). After adjusting for covariates, multiple measures (including FEV1, FVC, PEF, and composite PF) were all positively associated with better global cognition and the DSST score (P < 0.05). A stronger positive association between the DSST score and FEV1 (P for interaction = 0.001), FVC (P for interaction = 0.004), PEF (P for interaction = 0.003), and composite PF (P for interaction = 0.001) in lower energy intake. Similar results were observed in lower protein intake (all P for interaction < 0.05). CONCLUSION: Higher PF was independently associated with improved specific components of cognitive function (i.e., the DSST score). The positive association between PF and the DSST score was stronger in individuals with lower energy and protein intakes.


Subject(s)
Cognition , Lung , Aged , Animals , Humans , Female , United States/epidemiology , Male , Nutrition Surveys , Vital Capacity , Forced Expiratory Volume
9.
Food Funct ; 15(1): 196-207, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38047408

ABSTRACT

Ovomucoid is the immune-dominant allergen in the egg white of hens. Due to its structure based on nine disulfide bonds as well as its resistance to heat and enzymatic hydrolysis, the allergenicity of this food protein is difficult to decrease by technological processes. We sought to reduce its allergenicity through the Maillard reaction. The unfolding of ovomucoid with L-cysteine-mediated reduction was used to increase accessibility to conformational and linear epitopes by modifying the secondary and tertiary structures of the allergen. Glycation with different saccharides revealed the beneficial effect of maltose glycation on the IgG-binding capacity reduction. By determining the better glycation conditions of unfolded ovomucoid, we produced ovomucoid with reduced IgE binding capacity due to the glycation sites (K17, K112, K129, and K164) on epitopes. Moreover, after simulated infant and adult gastrointestinal digestion, the unfolded plus glycated ovomucoid showed higher ABTS˙+ scavenging activity, O2˙- scavenging activity, ˙OH scavenging activity, Fe2+ chelating activity, and a FRAP value; in particular, for ˙OH scavenging activity, there was a sharp increase of more than 100%.


Subject(s)
Maillard Reaction , Ovomucin , Humans , Infant , Adult , Animals , Female , Ovomucin/chemistry , Ovomucin/metabolism , Antioxidants , Chickens/metabolism , Epitopes/chemistry , Allergens/chemistry , Immunoglobulin E/chemistry , Immunoglobulin G/chemistry
10.
Microorganisms ; 11(12)2023 Nov 26.
Article in English | MEDLINE | ID: mdl-38138004

ABSTRACT

Arsenic (As) is a highly toxic metalloid, and its widespread contamination of water is a serious threat to human health. This study explored As removal using Fe(II)-oxidizing bacteria. The strain Fe7 isolated from iron mine soil was classified as the genus Pseudarthrobacter based on 16S rRNA gene sequence similarities and phylogenetic analyses. The strain Fe7 was identified as a strain of Gram-positive, rod-shaped, aerobic bacteria that can oxidize Fe(II) and produce iron mineral precipitates. X-ray diffraction, X-ray photoelectron spectroscopy, and energy-dispersive X-ray spectroscopy patterns showed that the iron mineral precipitates with poor crystallinity consisted of Fe(III) and numerous biological impurities. In the co-cultivation of the strain Fe7 with arsenite (As(III)), 100% of the total Fe and 99.9% of the total As were removed after 72 h. During the co-cultivation of the strain Fe7 with arsenate (As(V)), 98.4% of the total Fe and 96.9% of the total As were removed after 72 h. Additionally, the iron precipitates produced by the strain Fe7 removed 100% of the total As after 3 h in both the As(III) and As(V) pollution systems. Furthermore, enzyme activity experiments revealed that the strain Fe7 oxidized Fe(II) by producing extracellular enzymes. When 2% (v/v) extracellular enzyme liquid of the strain Fe7 was added to the As(III) or As(V) pollution system, the total As removal rates were 98.6% and 99.4%, respectively, after 2 h, which increased to 100% when 5% (v/v) and 10% (v/v) extracellular enzyme liquid of the strain Fe7 were, respectively, added to the As(III) and As(V) pollution systems. Therefore, iron biomineralized using a co-culture of the strain Fe7 and As, iron precipitates produced by the strain Fe7, and the extracellular enzymes of the strain Fe7 could remove As(III) and As(V) efficiently. This study provides new insights and strategies for the efficient remediation of arsenic pollution in aquatic environments.

11.
BMC Prim Care ; 24(1): 230, 2023 11 03.
Article in English | MEDLINE | ID: mdl-37919671

ABSTRACT

BACKGROUND: The majority of patients with perinatal depression (PND) in China do not receive adequate treatment. As forming a therapeutic alliance with patients is crucial for depression treatment, shared decision-making (SDM) shows promise in promoting patients' uptake of evidence-based mental health services, but its impact on patient outcomes and implementation in real-world maternal care remain uncertain. Therefore, this study aims to develop and evaluate an interprofessional shared decision-making (IP-SDM) model for PND to enhance maternal mental health services. METHODS: This study contains four research phases: feasibility testing (Phase 1), toolkit development (Phase 2), usability evaluation (Phase 3), and effectiveness evaluation (Phase 4). During the development stage, focus group interviews will be conducted with expectant and new mothers, as well as maternal care providers for feasibility testing. A toolkit, including a patient decision aid along with its user guide and training materials, will be developed based on the findings of Phase 1 and syntheses of up-to-date evidence and appraised by the Delphi method. Additionally, a cognitive task analysis will be used for assessing the usability of the toolkit. During the evaluation stage, a prospective randomized controlled trial embedded in a mixed methods design will be used to evaluate the effectiveness and cost-effectiveness of the IP-SDM care model. The study targets to recruit 410 expectant and new mothers who screen positive for depression. They will be randomly assigned to either an intervention group or a control group in a 1:1 ratio. Participants in the intervention group will receive decision aid, decision coaching, and clinical consultation, in addition to usual services, while the control group will receive usual services. The primary outcome is the quality of decision-making process, and the secondary outcomes include SDM, mental health service utilization and costs, depressive symptoms, and health-related quality of life. In-depth interviews will be used to explore the facilitating and hindering factors of SDM. DISCUSSION: This study will develop an IP-SDM care model for PND that can be implemented in maternal care settings in China. This study will contribute to the understanding of how SDM impacts mental health outcomes and facilitate the integration of mental health services into maternal care. TRIAL REGISTRATION: ChiCTR2300072559. Registered on 16 June 2023.


Subject(s)
Decision Making , Quality of Life , Humans , Depression/diagnosis , Depression/therapy , Prospective Studies , Decision Making, Shared , Randomized Controlled Trials as Topic
12.
Nat Neurosci ; 26(12): 2081-2089, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37996529

ABSTRACT

It is generally thought that under basal conditions, neurons produce ATP mainly through mitochondrial oxidative phosphorylation (OXPHOS), and glycolytic activity only predominates when neurons are activated and need to meet higher energy demands. However, it remains unknown whether there are differences in glucose metabolism between neuronal somata and axon terminals. Here, we demonstrated that neuronal somata perform higher levels of aerobic glycolysis and lower levels of OXPHOS than terminals, both during basal and activated states. We found that the glycolytic enzyme pyruvate kinase 2 (PKM2) is localized predominantly in the somata rather than in the terminals. Deletion of Pkm2 in mice results in a switch from aerobic glycolysis to OXPHOS in neuronal somata, leading to oxidative damage and progressive loss of dopaminergic neurons. Our findings update the conventional view that neurons uniformly use OXPHOS under basal conditions and highlight the important role of somatic aerobic glycolysis in maintaining antioxidant capacity.


Subject(s)
Glycolysis , Oxidative Phosphorylation , Animals , Mice , Phosphotransferases/metabolism , Oxidative Stress , Glucose/metabolism
13.
World J Microbiol Biotechnol ; 39(10): 262, 2023 Jul 29.
Article in English | MEDLINE | ID: mdl-37507604

ABSTRACT

Tellurium is a super-trace metalloid on Earth. Owing to its excellent physical and chemical properties, it is used in industries such as metallurgy and manufacturing, particularly of semiconductors and - more recently - solar panels. As the global demand for tellurium rises, environmental issues surrounding tellurium have recently aroused concern due to its high toxicity. The amount of tellurium released to the environment is increasing, and microorganisms play an important role in the biogeochemical cycling of environmental tellurium. This review focuses on novel developments on tellurium transformations driven by microbes and includes the following sections: (1) history and applications of tellurium; (2) toxicity of tellurium; (3) microbial detoxification mechanisms against soluble tellurium anions including uptake, efflux and methods of reduction, and reduced ability to cope with oxidation stress or repair damaged DNA; and (4) the characteristics and applications of tellurium nanoparticles (TeNPs) produced by microbes. This review raises the awareness of microorganisms in tellurium biogeochemical cycling and the growing applications for microbial tellurium nanoparticles.


Subject(s)
Nanoparticles , Trace Elements , Tellurium/chemistry
14.
Front Microbiol ; 14: 1229838, 2023.
Article in English | MEDLINE | ID: mdl-37520346

ABSTRACT

Effective control of foodborne pathogen contamination is a significant challenge to the food industry, but the development of new antibacterial nanotechnologies offers new opportunities. Notably, selenium nanoparticles have been extensively studied and successfully applied in various food fields. Selenium nanoparticles act as food antibacterial agents with a number of benefits, including selenium as an essential trace element in food, prevention of drug resistance induction in foodborne pathogens, and improvement of shelf life and food storage conditions. Compared to physical and chemical methods, biogenic selenium nanoparticles (Bio-SeNPs) are safer and more multifunctional due to the bioactive molecules in Bio-SeNPs. This review includes a summarization of (1) biosynthesized of Bio-SeNPs from different sources (plant extracts, fungi and bacteria) and their antibacterial activity against various foodborne bacteria; (2) the antibacterial mechanisms of Bio-SeNPs, including penetration of cell wall, damage to cell membrane and contents leakage, inhibition of biofilm formation, and induction of oxidative stress; (3) the potential antibacterial applications of Bio-SeNPs as food packaging materials, food additives and fertilizers/feeds for crops and animals in the food industry; and (4) the cytotoxicity and animal toxicity of Bio-SeNPs. The related knowledge contributes to enhancing our understanding of Bio-SeNP applications and makes a valuable contribution to ensuring food safety.

15.
Proteins ; 91(12): 1571-1599, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37493353

ABSTRACT

We present an in-depth analysis of selected CASP15 targets, focusing on their biological and functional significance. The authors of the structures identify and discuss key protein features and evaluate how effectively these aspects were captured in the submitted predictions. While the overall ability to predict three-dimensional protein structures continues to impress, reproducing uncommon features not previously observed in experimental structures is still a challenge. Furthermore, instances with conformational flexibility and large multimeric complexes highlight the need for novel scoring strategies to better emphasize biologically relevant structural regions. Looking ahead, closer integration of computational and experimental techniques will play a key role in determining the next challenges to be unraveled in the field of structural molecular biology.


Subject(s)
Computational Biology , Proteins , Protein Conformation , Models, Molecular , Computational Biology/methods , Proteins/chemistry
16.
Front Pediatr ; 11: 1043442, 2023.
Article in English | MEDLINE | ID: mdl-36846165

ABSTRACT

Carpal tunnel syndrome (CTS) is an upper extremity median nerve entrapment disorder that is rare in children and adolescents. Anatomical variations of the wrist, such as anomalous muscles, persistent median artery (PMA), and bifid median nerves (BMN), are rare etiology of CTS. Coexistence of all three variants combined with CTS in adolescents has been rarely reported. Case description: A 16-year-old right-hand dominant male presented to our clinic with several years of bilateral thenar muscle atrophy and weakness but no paresthesia or pain in his both hands. Ultrasonography showed that the right median nerve become significantly thinner, and the left median nerve was split into two branches by PMA. Magnetic resonance imaging (MRI) revealed that anomalous muscles in the bilateral wrist extending to the carpal tunnel, causing compression of the median nerve. Considering the possibility of CTS clinically, the patient underwent bilateral open carpal tunnel release without resection of anomalous muscles and PMA. The patient has no discomfort after 2 years. This suggests that anatomical variations of the carpal tunnel may contribute to CTS, which can be confirmed by preoperative ultrasonography and MRI, and the possibility of carpal tunnel anatomical variations should be considered when CTS occurs in adolescents. Open carpal tunnel release is an effective treatment for juvenile CTS without the need to resect abnormal muscle and PMA during the operation.

17.
Cell Rep ; 42(2): 112075, 2023 02 28.
Article in English | MEDLINE | ID: mdl-36774551

ABSTRACT

Booster immunizations and breakthrough infections can elicit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant neutralizing activity. However, the durability of the neutralization response is unknown. We characterize the sensitivity of BA.1, BA.2, BA.2.75, BA.4/BA.5, BF.7, BQ.1.1, and XBB against neutralizing antibodies from vaccination, hybrid immunity, and breakthrough infections 4-6 months after vaccination and infection. We show that a two-dose CoronaVac or a third-dose ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity as well as Delta, BA.1, and BA.2 breakthrough infections induce long-term persistence of the antibody response, and over 70% of sera neutralize BA.1, BA.2, BA.4/BA.5, and BF.7. However, BQ.1.1 and XBB, followed by BA.2.75, are more resistant to neutralization, with neutralizing titer reductions of ∼9- to 41-fold, ∼16- to 63-fold, and ∼4- to 25-fold, respectively. These data highlight additional vaccination in CoronaVac- or ZF2001-vaccinated individuals and provide insight into the durability of neutralization against Omicron subvariants.


Subject(s)
Breakthrough Infections , COVID-19 , Humans , COVID-19/prevention & control , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral
18.
Nat Commun ; 14(1): 899, 2023 02 17.
Article in English | MEDLINE | ID: mdl-36797290

ABSTRACT

Female mosquitoes inject saliva into vertebrate hosts during blood feeding. This process transmits mosquito-borne human pathogens that collectively cause ~1,000,000 deaths/year. Among the most abundant and conserved proteins secreted by female salivary glands is a high-molecular weight protein called salivary gland surface protein 1 (SGS1) that facilitates pathogen transmission, but its mechanism remains elusive. Here, we determine the native structure of SGS1 by the cryoID approach, showing that the 3364 amino-acid protein has a Tc toxin-like Rhs/YD shell, four receptor domains, and a set of C-terminal daisy-chained helices. These helices are partially shielded inside the Rhs/YD shell and poised to transform into predicted transmembrane helices. This transformation, and the numerous receptor domains on the surface of SGS1, are likely key in facilitating sporozoite/arbovirus invasion into the salivary glands and manipulating the host's immune response.


Subject(s)
Anopheles , Animals , Female , Humans , Anopheles/physiology , Salivary Glands/metabolism , Saliva , Insect Proteins/metabolism , Salivary Proteins and Peptides/metabolism
19.
Cell Discov ; 8(1): 126, 2022 Nov 22.
Article in English | MEDLINE | ID: mdl-36414632

ABSTRACT

The α-keto acid dehydrogenase complex family catalyzes the essential oxidative decarboxylation of α-keto acids to yield acyl-CoA and NADH. Despite performing the same overarching reaction, members of the family have different component structures and structural organization between each other and across phylogenetic species. While native structures of α-keto acid dehydrogenase complexes from bacteria and fungi became available recently, the atomic structure and organization of their mammalian counterparts in native states remain unknown. Here, we report the cryo-electron microscopy structures of the endogenous cubic 2-oxoglutarate dehydrogenase complex (OGDC) and icosahedral pyruvate dehydrogenase complex (PDC) cores from bovine kidney determined at resolutions of 3.5 Å and 3.8 Å, respectively. The structures of multiple proteins were reconstructed from a single lysate sample, allowing direct structural comparison without the concerns of differences arising from sample preparation and structure determination. Although native and recombinant E2 core scaffold structures are similar, the native structures are decorated with their peripheral E1 and E3 subunits. Asymmetric sub-particle reconstructions support heterogeneity in the arrangements of these peripheral subunits. In addition, despite sharing a similar monomeric fold, OGDC and PDC E2 cores have distinct interdomain and intertrimer interactions, which suggests a means of modulating self-assembly to mitigate heterologous binding between mismatched E2 species. The lipoyl moiety lies near a mobile gatekeeper within the interdomain active site of OGDC E2 and PDC E2. Analysis of the twofold related intertrimer interface identified secondary structural differences and chemical interactions between icosahedral and cubic geometries of the core. Taken together, our study provides a direct structural comparison of OGDC and PDC from the same source and offers new insights into determinants of interdomain interactions and of architecture diversity among α-keto acid dehydrogenase complexes.

20.
Sci Rep ; 12(1): 18873, 2022 11 07.
Article in English | MEDLINE | ID: mdl-36344586

ABSTRACT

The study objective was to observe the treatment effect of the farnesoid X receptor (FXR) agonist GW4064 in a rat model of hilar cholangiocarcinoma to explore a new therapeutic target for gene therapy for hilar cholangiocarcinoma. Eighty male Wistar rats were randomly divided into four groups (treatment group, model group, control group and sham operation group, 20 rats in each group). The four groups were fed a standard diet. The treatment group and the model group were injected with a suspension of cholangiocarcinoma QBC939 cells into the hilar bile duct with a microsyringe, the control group was injected with normal saline, and the sham operation group was not injected with anything. A modified tail suspension test (TST) was used to evaluate the vitality of the rats. At 4 weeks, one rat in the treatment group and model group was euthanized, and the changes in the hilar bile duct were recorded. The procedure was repeated at 6 weeks. After 6 weeks, hilar cholangiocarcinoma occurred in the treatment group and model group. Then, the treatment group was injected with GW4064 intraperitoneally at a dose of 50 mg/kg/day. One week after injection, the rats in the four groups were euthanized. Pathological examination confirmed that tumours had formed, and hilar bile duct tissues were taken from the four groups. FXR, Bsep, Ntcp and NF-κB expression in the hilar bile duct was detected by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. After three weeks, the rats in the treatment group and model group ate less, and their weight was significantly reduced. Six weeks later, hilar cholangiocarcinoma was detected in the treatment group and model group. After treatment with GW4064, the ratios of FXR/GAPDH mRNA, Bsep/GAPDH mRNA, Ntcp/GAPDH mRNA and NF-κBp65/GAPDH mRNA were significantly different among the four groups. Under a light microscope, FXR protein reacted with anti-FXR antibody, Bsep protein reacted with anti-Bsep antibody, Ntcp protein reacted with anti-Ntcp antibody and NF-κBp65 protein reacted with anti-NF-κBp65 antibody, and they showed granular expression. Every pathological section included 4,800 cells, and there were different numbers of positive cells in each group. FXR expression in the hilar cholangiocarcinoma of rats was significantly lower than that in normal hilar bile duct tissues. GW4064 increased the expression of FXR in tumour tissues. These findings suggest that FXR may be a new therapeutic target and that GW4064 may be helpful in the treatment of hilar cholangiocarcinoma.


Subject(s)
Bile Duct Neoplasms , Klatskin Tumor , Animals , Male , Rats , Bile Duct Neoplasms/drug therapy , Bile Ducts, Intrahepatic , Rats, Wistar , Receptors, Cytoplasmic and Nuclear , RNA, Messenger
SELECTION OF CITATIONS
SEARCH DETAIL
...