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1.
Infect Genet Evol ; : 105602, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38734397

ABSTRACT

Hepatitis E, caused by the hepatitis E virus (HEV), is a global public health issue. Low similarity between the gene sequences of mouse and human HEV led to the belief that the risk of human infection was low. Recent reports of chronic and acute hepatitis E caused by murine HEV infection in humans in Hong Kong have raised global concerns. Therefore, it is crucial to investigate the epidemiology and prevalence of HEV in China. We comprehensively analyzed different rodent HEV strains to understand rocahepevirus occurrence in Hubei Province, China. The HEV positivity rate for was 6.43% (73/1136). We identified seven near-full-length rocahepevirus strains and detected rat HEV antigens in tissues from different mouse species. HEV has extensive tissue tropism and a high viral load in the liver. We highlight the genetic diversity of HEVs in rodents and underscore the importance of paying attention to their variation and evolution.

2.
Nat Immunol ; 25(5): 834-846, 2024 May.
Article in English | MEDLINE | ID: mdl-38561495

ABSTRACT

Cancer remains one of the leading causes of mortality worldwide, leading to increased interest in utilizing immunotherapy strategies for better cancer treatments. In the past decade, CD103+ T cells have been associated with better clinical prognosis in patients with cancer. However, the specific immune mechanisms contributing toward CD103-mediated protective immunity remain unclear. Here, we show an unexpected and transient CD61 expression, which is paired with CD103 at the synaptic microclusters of T cells. CD61 colocalization with the T cell antigen receptor further modulates downstream T cell antigen receptor signaling, improving antitumor cytotoxicity and promoting physiological control of tumor growth. Clinically, the presence of CD61+ tumor-infiltrating T lymphocytes is associated with improved clinical outcomes, mediated through enhanced effector functions and phenotype with limited evidence of cellular exhaustion. In conclusion, this study identified an unconventional and transient CD61 expression and pairing with CD103 on human immune cells, which potentiates a new target for immune-based cellular therapies.


Subject(s)
Antigens, CD , Apyrase , Integrin alpha Chains , Receptors, Antigen, T-Cell , Signal Transduction , Humans , Antigens, CD/metabolism , Antigens, CD/immunology , Integrin alpha Chains/metabolism , Signal Transduction/immunology , Receptors, Antigen, T-Cell/metabolism , Receptors, Antigen, T-Cell/immunology , Animals , Mice , Cytotoxicity, Immunologic , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Cell Line, Tumor , T-Lymphocytes, Cytotoxic/immunology , Neoplasms/immunology , Neoplasms/therapy
3.
J Integr Plant Biol ; 66(3): 484-509, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38456625

ABSTRACT

Brassica napus, commonly known as rapeseed or canola, is a major oil crop contributing over 13% to the stable supply of edible vegetable oil worldwide. Identification and understanding the gene functions in the B. napus genome is crucial for genomic breeding. A group of genes controlling agronomic traits have been successfully cloned through functional genomics studies in B. napus. In this review, we present an overview of the progress made in the functional genomics of B. napus, including the availability of germplasm resources, omics databases and cloned functional genes. Based on the current progress, we also highlight the main challenges and perspectives in this field. The advances in the functional genomics of B. napus contribute to a better understanding of the genetic basis underlying the complex agronomic traits in B. napus and will expedite the breeding of high quality, high resistance and high yield in B. napus varieties.


Subject(s)
Brassica napus , Brassica napus/genetics , Quantitative Trait Loci/genetics , Plant Breeding , Genomics , Phenotype
4.
Mol Neurobiol ; 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38436832

ABSTRACT

Neurofibromatosis type 1 (NF1) is caused by NF1 gene mutations. Patients with NF1 often have complications with tumors, such as neurofibroma. In order to investigate the pathogenesis of human neurofibroma, a systematic comparison of protein expression levels between Schwann cell-like sNF96.2 cells, which originated from malignant peripheral nerve sheath tumors (MPNST), and normal Schwann cells was performed using 4-D label-free proteomic analysis. In addition, the expression levels and localization of dysregulated proteins were confirmed using a Gene Expression Omnibus (GEO) transcriptomic dataset, Western blot analysis, and immunofluorescence labeling. The effects of SRY-box transcription factor 9 (SOX9) in the neurofibroma and surrounding microenvironment were evaluated in vivo using a tumor transplantation model. The present study observed that SOX9 and procollagen C-endopeptidase enhancer (PCOLCE) were significantly altered. NF1 mutation promoted the nuclear translocation and transcriptional activity of SOX9 in neurofibromas. SOX9 increased collagen VI secretions by enhancing the activation of PCOLCE in neurofibroma cells. These findings might provide new perspectives on the pathophysiological significance of SOX9 in neurofibromas and elucidate a novel molecular mechanism underlying neurofibromas.

5.
Virol Sin ; 39(2): 194-204, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38360150

ABSTRACT

Haemaphysalis longicornis ticks, commonly found in East Asia, can transmit various pathogenic viruses, including the severe fever with thrombocytopenia syndrome virus (SFTSV) that has caused febrile diseases among humans in Hubei Province. However, understanding of the viromes of H. longicornis was limited, and the prevalence of viruses among H. longicornis ticks in Hubei was not well clarified. This study investigates the viromes of both engorged (fed) and free (unfed) H. longicornis ticks across three mountainous regions in Hubei Province from 2019 to 2020. RNA-sequencing analysis identified viral sequences that were related to 39 reference viruses belonging to unclassified viruses and seven RNA viral families, namely Chuviridae, Nairoviridae, Orthomyxoviridae, Parvoviridae, Phenuiviridae, Rhabdoviridae, and Totiviridae. Viral abundance and diversity in these ticks were analysed, and phylogenetic characteristics of the Henan tick virus (HNTV), Dabieshan tick virus (DBSTV), Okutama tick virus (OKTV), and Jingmen tick virus (JMTV) were elucidated based on their full genomic sequences. Prevalence analysis demonstrated that DBSTV was the most common virus found in individual H. longicornis ticks (12.59%), followed by HNTV (0.35%), whereas JMTV and OKTV were not detected. These results improve our understanding of H. longicornis tick viromes in central China and highlight the role of tick feeding status and geography in shaping the viral community. The findings of new viral strains and their potential impact on public health raise the need to strengthen surveillance efforts for comprehensively assessing their spillover potentials.


Subject(s)
Ixodidae , Phylogeny , Virome , Animals , Virome/genetics , China , Ixodidae/virology , Genome, Viral , RNA Viruses/genetics , RNA Viruses/isolation & purification , RNA Viruses/classification , Ticks/virology , RNA, Viral/genetics , Sequence Analysis, RNA , Haemaphysalis longicornis
6.
Pharmacol Res ; 202: 107099, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38342327

ABSTRACT

Cancer cells frequently develop resistance to chemotherapeutic therapies and targeted drugs, which has been a significant challenge in cancer management. With the growing advances in technologies in isolation and identification of natural products, the potential of natural products in combating cancer multidrug resistance has received substantial attention. Importantly, natural products can impact multiple targets, which can be valuable in overcoming drug resistance from different perspectives. In the current review, we will describe the well-established mechanisms underlying multidrug resistance, and introduce natural products that could target these multidrug resistant mechanisms. Specifically, we will discuss natural compounds such as curcumin, resveratrol, baicalein, chrysin and more, and their potential roles in combating multidrug resistance. This review article aims to provide a systematic summary of recent advances of natural products in combating cancer drug resistance, and will provide rationales for novel drug discovery.


Subject(s)
Antineoplastic Agents , Biological Products , Neoplasms , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Biological Products/pharmacology , Biological Products/therapeutic use , Neoplasms/drug therapy , Drug Resistance, Multiple , Drug Resistance, Neoplasm
7.
Int J Biol Macromol ; 262(Pt 1): 129973, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38325697

ABSTRACT

The formation of the egg white precipitate (EWP) during dilution poses challenges in food processing. In this paper, the effects of 90 W and 360 W ultrasonic intensities on the inhibition of EWP formation were investigated. The findings revealed that 360 W sonication effectively disrupted protein aggregates, decreasing the dry matter of EWP by 5.24 %, particle size by 57.86 %, and viscosity by 82.28 %. Furthermore, the ultrasonic pretreatment unfolded protein structures and increased the content of ß-sheet structures. Combined with quantitative proteomics and intermolecular forces analysis, the mechanism by which ultrasonic pretreatment inhibited water-diluted EWP formation by altering protein interactions was proposed: ultrasonic pretreatment disrupted electrostatic interactions centered on lysozyme, as well as hydrogen-bonding interactions between ovomucin and water. In conclusion, our research provides valuable insights into the application of ultrasonic pretreatment as a means to control and improve the quality of egg white-based products.


Subject(s)
Egg Proteins , Egg White , Egg Proteins/chemistry , Egg White/chemistry , Water , Ultrasonics , Proteomics
8.
Nanomicro Lett ; 16(1): 123, 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38372847

ABSTRACT

Conformable and wireless charging energy storage devices play important roles in enabling the fast development of wearable, non-contact soft electronics. However, current wireless charging power sources are still restricted by limited flexural angles and fragile connection of components, resulting in the failure expression of performance and constraining their further applications in health monitoring wearables and moveable artificial limbs. Herein, we present an ultracompatible skin-like integrated wireless charging micro-supercapacitor, which building blocks (including electrolyte, electrode and substrate) are all evaporated by liquid precursor. Owing to the infiltration and permeation of the liquid, each part of the integrated device attached firmly with each other, forming a compact and all-in-one configuration. In addition, benefitting from the controllable volume of electrode solution precursor, the electrode thickness is easily regulated varying from 11.7 to 112.5 µm. This prepared thin IWC-MSC skin can fit well with curving human body, and could be wireless charged to store electricity into high capacitive micro-supercapacitors (11.39 F cm-3) of the integrated device. We believe this work will shed light on the construction of skin-attachable electronics and irregular sensing microrobots.

9.
Proc Natl Acad Sci U S A ; 121(5): e2320237121, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38252821

ABSTRACT

Dynamic 3D covalent organic frameworks (COFs) have shown concerted structural transformation and adaptive gas adsorption due to the conformational diversity of organic linkers. However, the isolation and observation of COF rotamers constitute undergoing challenges due to their comparable free energy and subtle rotational energy barrier. Here, we report the atomic-level observation and structural evolution of COF rotamers by cryo-3D electron diffraction and synchrotron powder X-ray diffraction. Specifically, we optimize the crystallinity and morphology of COF-320 to manifest its coherent dynamic responses upon adaptive inclusion of guest molecules. We observe a significant crystal expansion of 29 vol% upon hydration and a giant swelling with volume change up to 78 vol% upon solvation. We record the structural evolution from a non-porous contracted phase to two narrow-pore intermediate phases and the fully opened expanded phase using n-butane as a stabilizing probe at ambient conditions. We uncover the rotational freedom of biphenylene giving rise to significant conformational changes on the diimine motifs from synclinal to syn-periplanar and anticlinal rotamers. We illustrate the 10-fold increment of pore volumes and 100% enhancement of methane uptake capacity of COF-320 at 100 bar and 298 K. The present findings shed light on the design of smarter organic porous materials to maximize host-guest interaction and boost gas uptake capacity through progressive structural transformation.

10.
Chin J Integr Med ; 30(2): 107-114, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37222827

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of Huashi Baidu Granules (HSBD) in treating patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. METHODS: A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd, 2022. All COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group (HSBD users) and the control group (non-HSBD users). After propensity score matching in a 1:1 ratio, 496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD users. Patients in the treatment group were administrated HSBD (5 g/bag) orally for 1 bag twice a day for 7 consecutive days. Patients in the control group received standard care and routine treatment. The primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day 7. Secondary outcomes included the hospitalized days, the time of the first nucleic acid negative conversion, and new-onset symptoms in asymptomatic patients. Adverse events (AEs) that occurred during the study were recorded. Further subgroup analysis was conducted in vaccinated (378 HSBD users and 390 non-HSBD users) and unvaccinated patients (118 HSBD users and 106 non-HSBD users). RESULTS: The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The negative conversion rate of nucleic acid in the treatment group were significantly higher than those in the control group at day 7 (91.73% vs. 86.90%, P=0.014). Compared with the control group, the hospitalized days in the treatment group were significantly reduced [10 days (IQR: 8-11 days) vs. 11 days (IQR: 10.25-12 days); P<0.01]. The time of the first nucleic acid negative conversion had significant differences between the treatment and control groups [3 days (IQR: 2-4 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The incidence of new-onset symptoms including cough, pharyngalgia, expectoration and fever in the treatment group were lower than the control group (P<0.05 or P<0.01). In the vaccinated patients, the median negative conversion time and hospitalized days were significantly shorter than the control group after HSDB treatment [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days), P<0.01; 10 days (IQR: 8-11 days) vs. 11 days (IQR: 10-12 days), P<0.01]. In the unvaccinated patients, HSBD treatment efficiently shorten the median negative conversion time and hospitalized days [4 days (IQR: 2-6 days) vs. 5 days (IQR: 4-7 days), P<0.01; 10.5 days (IQR: 8.75-11 days) vs. 11.0 days (IQR: 10.75-13 days); P<0.01]. No serious AEs were reported during the study. CONCLUSION: HSBD treatment significantly shortened the negative conversion time of nuclear acid, the length of hospitalization, and the time of the first nucleic acid negative conversion in patients infected with SARS-COV-2 Omicron variant (Trial registry No. ChiCTR2200060472).


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Nucleic Acids , Humans , SARS-CoV-2 , Retrospective Studies , China
11.
Adv Mater ; 36(9): e2307582, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37781979

ABSTRACT

Learning about the strain/stress distribution in a material is essential to achieve its mechanical stability and proper functionality. Conventional techniques such as universal testing machines only apply to static samples with standardized geometry in laboratory environment. Soft mechanical sensors based on stretchable conductors, carbon-filled composites, or conductive gels possess better adaptability, but still face challenges from complicated fabrication process, dependence on extra readout device, and limited strain/stress mapping ability. Inspired by the camouflage mechanism of cuttlefish and chameleons, here an innovative responsive hydrogel containing light-scattering "mechano-iridophores" is developed. Force induced reversible phase separation manipulates the dynamic generation of mechano-iridophores, serving as optical indicators of local deformation. Patch-shaped mechanical sensors made from the responsive hydrogel feature fast response time (<0.4 s), high spatial resolution (≈100 µm), and wide dynamic ranges (e.g., 10-150% strain). The intrinsic adhesiveness and self-healing material capability of sensing patches also ensure their excellent applicability and robustness. This combination of chemical and optical properties allows strain/stress distributions in target samples to be directly identified by naked eyes or smartphone apps, which is not yet achieved. The great advantages above are ideal for developing the next-generation mechanical sensors toward material studies, damage diagnosis, risk prediction, and smart devices.

12.
Aliment Pharmacol Ther ; 59(3): 393-408, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38010661

ABSTRACT

BACKGROUND: Upadacitinib is an oral, selective Janus kinase inhibitor. AIM: To assess the efficacy and safety of upadacitinib in patients with moderate-to-severe ulcerative colitis following 16-week extended induction therapy, and 52-week maintenance therapy in patients achieving clinical response after 16-week extended induction therapy METHODS: Patients without clinical response to 8 weeks' upadacitinib 45 mg once daily induction therapy in two induction trials were eligible for an additional 8 weeks of therapy. Patients achieving clinical response at Week 16 were subsequently re-randomised (1:1) to upadacitinib 15 or 30 mg once daily for 52-week maintenance therapy. Efficacy was assessed at induction Week 16 (integrated) and maintenance Week 52; safety was assessed throughout. RESULTS: Overall, 127/663 (19.2%) patients did not achieve clinical response to upadacitinib 45 mg at Week 8 and received an additional 8 weeks of therapy; 75/127 (59.1%) subsequently achieved clinical response at Week 16 and entered the maintenance trial. At Week 52, 26.5% of patients receiving upadacitinib 15 mg, and 43.6% receiving 30 mg, achieved clinical remission; efficacy was observed across all other endpoints with both doses. Herpes zoster rates increased with longer duration (16 weeks) of exposure to upadacitinib 45 mg during induction compared with the same population during the first 8 weeks. No other new safety signals were observed, and results are otherwise consistent with the known safety profile of upadacitinib. CONCLUSIONS: Patients without clinical response after 8 weeks' upadacitinib 45 mg induction therapy, may benefit from an additional 8 weeks of therapy. CLINICAL TRIAL REGISTRATION: NCT02819635; NCT03653026.


Subject(s)
Colitis, Ulcerative , Janus Kinase Inhibitors , Humans , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/chemically induced , Heterocyclic Compounds, 3-Ring/adverse effects , Induction Chemotherapy/methods , Janus Kinase Inhibitors/adverse effects , Double-Blind Method , Treatment Outcome
13.
Anal Biochem ; 687: 115453, 2024 04.
Article in English | MEDLINE | ID: mdl-38158108

ABSTRACT

Analysis of mecA gene in Staphylococcus aureus (S. aureus) is essential for controlling infections in intensive care units (ICU) and preventing the use of ineffectual empirical treatments. However, quantitative determination of the mecA gene remains difficult. Herein, we propose a simple and sensitive colorimetric approach by integrating exonuclease-III (Exo-III) assisted signal cascade and G-quadruplex/hemin DNAzymes (G4 DNAzymes) catalyzed 2,2'-azino-bis (3-ethylben-zothiazoline-6-sulfonic acid) (ABTS) based color reaction. In this method, signal amplification does not necessitate the use of complex experimental components, such as multiple enzymes and primer design, while still maintaining a high signal amplifying efficiency. Therefore, the method has a broad mecA gene detection range from 10 fM to 1 nM and a low limit of detection down to 3.4 fM level. Taking the merit of simplicity and high sensitivity, the approach is promising in analyzing mecA gene in S. aureus and diagnosing infections.


Subject(s)
Biosensing Techniques , DNA, Catalytic , G-Quadruplexes , DNA, Catalytic/metabolism , Colorimetry/methods , Staphylococcus aureus/genetics , Staphylococcus aureus/metabolism , Catalysis , Biosensing Techniques/methods , Limit of Detection , Hemin
15.
Mater Today Bio ; 23: 100864, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38024839

ABSTRACT

Reactive oxygen burst in articular chondrocytes is a major contributor to osteoarthritis progression. Although selenium is indispensable role in the antioxidant process, the narrow therapeutic window, delicate toxicity margins, and lack of an efficient delivery system have hindered its translation to clinical applications. Herein, transcriptomic and biochemical analyses revealed that osteoarthritis was associated with selenium metabolic abnormality. A novel injectable hydrogel to deliver selenium nanoparticles (SeNPs) was proposed to intervene selenoprotein expression for osteoarthritis treatment. The hydrogels based on oxidized hyaluronic acid (OHA) cross-linked with hyaluronic acid-adipic acid dihydrazide (HA-ADH) was formulated to load SeNPs through a Schiff base reaction. The hydrogels were further incorporated with SeNPs, which exhibited minimal toxicity, mechanical properties, self-healing capability, and sustained drug release. Encapsulated with SeNPs, the hydrogels facilitated cartilage repair through synergetic effects of scavenging reactive oxygen species (ROS) and depressing apoptosis. Mechanistically, the hydrogel restored redox homeostasis by targeting glutathione peroxidase-1 (GPX1). Therapeutic outcomes of the SeNPs-laden hydrogel were demonstrated in an osteoarthritis rat model created by destabilization of the medial meniscus, including cartilage protection, subchondral bone sclerosis improvement, inflammation attenuation, and pain relief were demonstrated. These results highlight therapeutic potential of OHA/HA-ADH@SeNPs hydrogels, providing fundamental insights into remedying selenium imbalance for osteoarthritis biomaterial development.

16.
Mol Ther ; 31(12): 3520-3530, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-37915172

ABSTRACT

Otoferlin (OTOF) gene mutations represent the primary cause of hearing impairment and deafness in auditory neuropathy. The c.2485C>T (p. Q829X) mutation variant is responsible for approximately 3% of recessive prelingual deafness cases within the Spanish population. Previous studies have used two recombinant AAV vectors to overexpress OTOF, albeit with limited efficacy. In this study, we introduce an enhanced mini-dCas13X RNA base editor (emxABE) delivered via an AAV9 variant, achieving nearly 100% transfection efficiency in inner hair cells. This approach is aimed at treating OTOFQ829X, resulting in an approximately 80% adenosine-to-inosine conversion efficiency in humanized OtofQ829X/Q829X mice. Following a single scala media injection of emxABE targeting OTOFQ829X (emxABE-T) administered during the postnatal day 0-3 period in OtofQ829X/Q829X mice, we observed OTOF expression restoration in nearly 100% of inner hair cells. Moreover, auditory function was significantly improved, reaching similar levels as in wild-type mice. This enhancement persisted for at least 7 months. We also investigated P5-P7 and P30 OtofQ829X/Q829X mice, achieving auditory function restoration through round window injection of emxABE-T. These findings not only highlight an effective therapeutic strategy for potentially addressing OTOFQ829X-induced hearing loss but also underscore emxABE as a versatile toolkit for treating other monogenic diseases characterized by premature termination codons.


Subject(s)
Deafness , Hearing Loss, Central , Hearing Loss , Animals , Mice , Gene Editing , Hearing Loss/genetics , Hearing Loss/therapy , Mutation
17.
Front Neurosci ; 17: 1201294, 2023.
Article in English | MEDLINE | ID: mdl-37841690

ABSTRACT

Introduction: This study aimed to investigate pathological changes in the "Glutamate (Glu)-γ-aminobutyric acid (GABA)" loop and apply widely targeted metabolomic analysis technology to comprehensively explore metabolite abnormalities/ in the thalamus of rats with tic disorders (TD). Methods: Wistar rats were randomized into control, TD, and tiapride (Tia) groups. Iminodipropionitrile (IDPN) was used to induce TD in rats. The Tia group was administered tiapride. Neurotransmitter levels in the thalamus of rats in the three groups were measured using UPLC-3Q MS. And, the protein expression levels of Glu decarboxylase (GAD65/67) and GABA transporter protein (GAD-T) were measured using western blotting. The mRNA expression levels of these genes were evaluated using real-time polymerase chain reaction. Lastly, other metabolites in the thalamus were detected by widely targeted metabolomic analysis between TD and Control group rats. Results: The Glu level, Glu/GABA ratio, and Asp level in the TD group were significantly higher (all p < 0.001) than those of the Control group, whereas the GABA and Gly levels were lower (p < 0.001 and p = 0.009, respectively). The Tia group exhibited a significant reduction in the Glu level (p = 0.001) compared with the TD group. The protein expression level of GAD67 in TD group was higher (p = 0.009) and the mRNA expression levels of GAD65, GAD67, and GAT-1 were lower (p < 0.05) than those of the Control group. The Tia group did not display any differences in GAD65, GAD67, or GAT-1 expression. Widely targeted metabolomic analysis revealed that 34 substances were abnornal between the TD and Control groups (9 upregulated and 25 downregulated). Neurosteroids (progesterone, corticosterone) exhibited distinct differences. Metabolite analysis using the Kyoto encyclopedia for genes and genomes indicated that the steroid hormone biosynthesis pathway may be involved in TD pathogenesis. Conclusion: This study revealed metabolic abnormalities in the thalamus of rats with TD. The interaction between neurotransmitters and neurosteroid biosynthesis represents a new direction for future studies.

18.
Heliyon ; 9(10): e20076, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37842619

ABSTRACT

Mutations within viral epitopes can result in escape from T cells, but the contribution of mutations in flanking regions of epitopes in SARS-CoV-2 has not been investigated. Focusing on two SARS-CoV-2 nucleoprotein CD8+ epitopes, we investigated the contribution of these flanking mutations to proteasomal processing and T cell activation. We found decreased NP9-17-B*27:05 CD8+ T cell responses to the NP-Q7K mutation, likely due to a lack of efficient epitope production by the proteasome, suggesting immune escape caused by this mutation. In contrast, NP-P6L and NP-D103 N/Y mutations flanking the NP9-17-B*27:05 and NP105-113-B*07:02 epitopes, respectively, increased CD8+ T cell responses associated with enhanced epitope production by the proteasome. Our results provide evidence that SARS-CoV-2 mutations outside the epitope could have a significant impact on proteasomal processing, either contributing to T cell escape or enhancement that may be exploited for future vaccine design.

19.
J Am Chem Soc ; 145(42): 22885-22889, 2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37844128

ABSTRACT

Although reticular chemistry has commonly utilized mutually embracing tetrahedral metal complexes as crossing points to generate three-dimensional molecularly woven structures, weaving in two dimensions remains largely unexplored. We report a new strategy to access 2D woven COFs by controlling the angle of the usually linear linker, resulting in the successful synthesis of a 2D woven pattern based on chain-link fence. The synthesis was accomplished by linking aldehyde-functionalized copper(I) bisphenanthroline complexes with bent 4,4'-oxydianiline building units. This results in the formation of a crystalline solid, termed COF-523-Cu, whose structure was characterized by spectroscopic techniques and electron and X-ray diffraction techniques to reveal a molecularly woven, twofold-interpenetrated chain-link fence. The present work significantly advances the concept of molecular weaving and its practice in the design of complex chemical structures.

20.
BMC Biol ; 21(1): 202, 2023 09 29.
Article in English | MEDLINE | ID: mdl-37775748

ABSTRACT

BACKGROUND: Brassica napus is an important oilseed crop providing high-quality vegetable oils for human consumption and non-food applications. However, the regulation between embryo and seed coat for the synthesis of oil and phenylpropanoid compounds remains largely unclear. RESULTS: Here, we analyzed the transcriptomes in developing seeds at 2-day intervals from 14 days after flowering (DAF) to 64 DAF. The 26 high-resolution time-course transcriptomes are clearly clustered into five distinct groups from stage I to stage V. A total of 2217 genes including 136 transcription factors, are specifically expressed in the seed and show high temporal specificity by being expressed only at certain stages of seed development. Furthermore, we analyzed the co-expression networks during seed development, which mainly included master regulatory transcription factors, lipid, and phenylpropane metabolism genes. The results show that the phenylpropane pathway is prominent during seed development, and the key enzymes in the phenylpropane metabolic pathway, including TT5, BAN, and the transporter TT19, were directly or indirectly related to many key enzymes and transcription factors involved in oil accumulation. We identified candidate genes that may regulate seed oil content based on the co-expression network analysis combined with correlation analysis of the gene expression with seed oil content and seed coat content. CONCLUSIONS: Overall, these results reveal the transcriptional regulation between lipid and phenylpropane accumulation during B. napus seed development. The established co-expression networks and predicted key factors provide important resources for future studies to reveal the genetic control of oil accumulation in B. napus seeds.


Subject(s)
Brassica napus , Transcriptome , Humans , Brassica napus/genetics , Gene Expression Profiling , Plant Oils/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Seeds/genetics , Gene Expression Regulation, Plant
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