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1.
Int J Psychophysiol ; 202: 112373, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38844053

ABSTRACT

Sleep quality often deteriorates with age, and insomnia among the elderly increases the risks of both physical and psychiatric disorders. To elucidate the mechanisms and identify useful diagnostic biomarkers for insomnia in the elderly, the current study investigated the associations of waking brain activity patterns with susceptibility to stress-induced insomnia (sleep reactivity) and dysfunctional beliefs about sleep, major factors precipitating and maintaining insomnia, respectively. Forty-five participants aged 60 years or older with insomnia completed self-reported measures assessing depression, anxiety, sleep quality, dysfunctional beliefs about sleep, and sleep reactivity. Participants were then examined by quantitative electroencephalography (qEEG) during wakefulness, and spectral analysis was conducted to examine associations of regional frequency band power with these insomnia-precipitating and -maintaining factors. Dysfunctional beliefs about sleep were significantly correlated with higher beta/high-beta frequency band powers, while sleep reactivity was correlated with higher theta and delta frequency band powers. These findings suggest that sleep reactivity of older adults is associated with widespread cortical deactivation leading to poor stress coping, while their dysfunctional beliefs about sleep are associated with hyperactivation which is related to cognitive processes. These associations suggest that cognitive inflexibility and maladaptive stress-coping contribute to insomnia among the elderly.

2.
Front Cell Neurosci ; 18: 1379438, 2024.
Article in English | MEDLINE | ID: mdl-38694537

ABSTRACT

Retinoic acid (RA), derived from vitamin A (retinol), plays a crucial role in modulating neuroplasticity within the adult brain. Perturbations in RA signaling have been associated with memory impairments, underscoring the necessity to elucidate RA's influence on neuronal activity, particularly within the hippocampus. In this study, we investigated the cell type and sub-regional distribution of RA-responsive granule cells (GCs) in the mouse hippocampus and delineated their properties. We discovered that RA-responsive GCs tend to exhibit a muted response to environmental novelty, typically remaining inactive. Interestingly, chronic dietary depletion of RA leads to an abnormal increase in GC activation evoked by a novel environment, an effect that is replicated by the localized application of an RA receptor beta (RARß) antagonist. Furthermore, our study shows that prolonged RA deficiency impairs spatial discrimination-a cognitive function reliant on the hippocampus-with such impairments being reversible with RA replenishment. In summary, our findings significantly contribute to a better understanding of RA's role in regulating adult hippocampal neuroplasticity and cognitive functions.

3.
J Microbiol ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38700775

ABSTRACT

This study aimed to develop synthetic Claudin18.2 (CLDN18.2) chimeric antigen receptor (CAR)-T (CAR-T) cells as a treatment for advanced gastric cancer using lentiviral vector genetic engineering technology that targets the CLDN18.2 antigen and simultaneously overcomes the immunosuppressive environment caused by programmed cell death protein 1 (PD-1). Synthetic CAR T cells are a promising approach in cancer immunotherapy but face many challenges in solid tumors. One of the major problems is immunosuppression caused by PD-1. CLDN18.2, a gastric-specific membrane protein, is considered a potential therapeutic target for gastric and other cancers. In our study, CLDN18.2 CAR was a second-generation CAR with inducible T-cell costimulatory (CD278), and CLDN18.2-PD1/CD28 CAR was a third-generation CAR, wherein the synthetic PD1/CD28 chimeric-switch receptor (CSR) was added to the second-generation CAR. In vitro, we detected the secretion levels of different cytokines and the killing ability of CAR-T cells. We found that the secretion of cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) secreted by three types of CAR-T cells was increased, and the killing ability against CLDN18.2-positive GC cells was enhanced. In vivo, we established a xenograft GC model and observed the antitumor effects and off-target toxicity of CAR-T cells. These results support that synthetic anti-CLDN18.2 CAR-T cells have antitumor effect and anti-CLDN18.2-PD1/CD28 CAR could provide a promising design strategy to improve the efficacy of CAR-T cells in advanced gastric cancer.

4.
Genes Genomics ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38700830

ABSTRACT

BACKGROUND: Insects encounter various environmental stresses, in response to which they generate reactive oxygen species (ROS). Superoxide dismutase (SOD) is an antioxidant metalloenzyme that scavenges superoxide radicals to prevent oxidative damage. OBJECTIVE: To investigate expressions of SODs under oxidative stress in Tenebrio molitor. METHODS: Here, we investigated the transcriptional expression of SODs by pesticide and heavy metals in Tenebrio moltior. First, we searched an RNA-Seq database for T. molitor SOD (TmSOD) genes and identified two SOD isoforms (TmSOD1-iso1 and iso2). We examined their activities under developmental stage, tissue-specific, and various types (pesticide and heavy metal) of oxidative stress by using qPCR. RESULTS: Our results revealed two novel forms of TmSODs. These TmSODs had a copper/zinc superoxide dismutase domain, active site, Cu2+ binding site, Zn2+ binding site, E-class dimer interface, and P-class dimer interface. TmSODs (TmSOD1-iso1 and iso2) were expressed in diverse developmental phases and tissues. Pesticides and heavy metals caused an upregulation of these TmSODs. CONCLUSION: Our findings suggest that the two TmSODs have different functions in T. molitor, providing insights into the detoxification ability of T. molitor.

5.
Food Res Int ; 187: 114349, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38763638

ABSTRACT

Due to the constraints of the COVID-19 pandemic, conducting sensory evaluations requiring direct interactions became challenging. In response, researchers have been motivated to devise non-face-to-face testing methods as alternatives. This study aimed to compare two non-face-to-face home-use tests (HUT) with the traditional face-to-face central location test (CLT). Both HUTs involved online recruitment and sample delivery to participants' homes. One HUT provided a written protocol with no direct interaction (contactless HUT; C-HUT), whereas the other included an online meeting with a researcher for live guidance (online HUT; O-HUT). Four coffee samples were evaluated on the basis of liking and sensory and emotional attributes. The comparison between CLT and O-HUT showed RV coefficients of 0.92, 0.93, and 0.98 (P < 0.05) for liking and sensory and emotional attributes, respectively. In addition, based on the RV coefficient, the CLT results showed a significantly greater similarity to those of O-HUT compared to those of C-HUT. The O-HUT also outperformed the C-HUT in its ability to significantly discriminate between samples. Hence, real-time interactions between researchers and participants, as facilitated by O-HUT, may be more suitable in certain scenarios compared to C-HUT, which relies solely on a written protocol. Overall, these findings suggest that C-HUT and O-HUT are suitable methods for collecting sensory data and overcoming geographic and face-to-face contact limitations, providing greater flexibility, and reducing the time and cost associated with traditional sensory evaluations.


Subject(s)
COVID-19 , Coffee , Consumer Behavior , Humans , Coffee/chemistry , Male , Female , Adult , COVID-19/epidemiology , Young Adult , Taste , Middle Aged , SARS-CoV-2 , Emotions , Food Preferences , Internet
6.
Pract Radiat Oncol ; 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38697347

ABSTRACT

PURPOSE: We aimed to develop and investigate positional reproducibility using a fixation device (Unity Brain tumor Immobilization Device [UBID]) in patients with brain tumor undergoing magnetic resonance (MR)-guided radiation therapy (RT) with a 1.5 Tesla (T) MR-linear accelerator (MR-LINAC) to evaluate its feasibility in clinical practice and report representative cases of patients with central nervous system (CNS) tumor. MATERIALS AND METHODS: Quantitative analysis was performed by comparing images obtained by placing only the MR phantom on the couch with those obtained by placing UBID next to the MR phantom. Twenty patients who underwent RT for CNS tumors using 1.5T MR-LINAC between June and October 2022 were retrospectively analyzed. Among them, 5 did not use UBID, whereas 15 used UBID. The positional reproducibility of UBID was evaluated using the median interfractional and intrafractional errors in the first 10 fractions. RESULTS: Each MR quality factor of the MR phantom with UBID satisfied the criteria presented by Elekta. Median values of median shifts in the mediolateral, anteroposterior, and craniocaudal axes for interfractional errors were 2.98, 2.35, and 1.40 mm, respectively. For intrafractional errors, the median values were 0.05, 0.03, and 0.06 mm, respectively. The median values of the median rotations in pitch, roll, and yaw for both interfractional and intrafractional rotations were 0.00°. One patient diagnosed with an optic nerve sheath meningioma received RT with motion monitoring during irradiation. In 2 patients, changes in the tumor cavity and residual lesions were observed in the MRI obtained using 1.5T MR-LINAC on the day of the first treatment and immediately before the 21st fraction, respectively; therefore, offline/online adaptation was performed. CONCLUSIONS: The reproducible and immobile UBID is clinically feasible in patients with CNS tumors receiving RT with 1.5T MR-LINAC. Based on our initial experience, we developed a workflow for 1.5T MR-LINAC treatment of CNS tumors.

7.
Article in English | MEDLINE | ID: mdl-38683636

ABSTRACT

Dimensional confinement has shown to be an effective strategy to tune competing degrees of freedom in complex oxides. Here, we achieved atomic layered growth of trigonal vanadium sesquioxide (V2O3) by means of oxygen-assisted molecular beam epitaxy. This led to a series of high-quality epitaxial ultrathin V2O3 films down to unit cell thickness, enabling the study of the intrinsic electron correlations upon confinement. By electrical and optical measurements, we demonstrate a dimensional confinement-induced metal-insulator transition in these ultrathin films. We shed light on the Mott-Hubbard nature of this transition, revealing a vanishing quasiparticle weight as demonstrated by photoemission spectroscopy. Furthermore, we prove that dimensional confinement acts as an effective out-of-plane stress. This highlights the structural component of correlated oxides in a confined architecture, while opening an avenue to control both in-plane and out-of-plane lattice components by epitaxial strain and confinement, respectively.

8.
BMC Biol ; 22(1): 93, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38654335

ABSTRACT

BACKGROUND: The human upper respiratory tract (URT) microbiome, like the gut microbiome, varies across individuals and between health and disease states. However, study-to-study heterogeneity in reported case-control results has made the identification of consistent and generalizable URT-disease associations difficult. RESULTS: In order to address this issue, we assembled 26 independent 16S rRNA gene amplicon sequencing data sets from case-control URT studies, with approximately 2-3 studies per respiratory condition and ten distinct conditions covering common chronic and acute respiratory diseases. We leveraged the healthy control data across studies to investigate URT associations with age, sex, and geographic location, in order to isolate these associations from health and disease states. CONCLUSIONS: We found several robust genus-level associations, across multiple independent studies, with either health or disease status. We identified disease associations specific to a particular respiratory condition and associations general to all conditions. Ultimately, we reveal robust associations between the URT microbiome, health, and disease, which hold across multiple studies and can help guide follow-up work on potential URT microbiome diagnostics and therapeutics.


Subject(s)
Microbiota , RNA, Ribosomal, 16S , Respiratory System , Humans , Microbiota/genetics , RNA, Ribosomal, 16S/genetics , Respiratory System/microbiology , Respiratory Tract Diseases/microbiology , Case-Control Studies , Male , Bacteria/genetics , Bacteria/classification , Bacteria/isolation & purification , Female
9.
Cell Rep ; 43(4): 114000, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38527063

ABSTRACT

Fear overgeneralization is a maladaptive response to traumatic stress that is associated with the inability to discriminate between threat and safety contexts, a hallmark feature of post-traumatic stress disorder (PTSD). However, the neural mechanisms underlying this deficit remain unclear. Here, we show that traumatic stress exposure impairs contextual discrimination between threat and safety contexts in the learned helplessness (LH) model. Mossy cells (MCs) in the dorsal hippocampus are suppressed in response to traumatic stress. Bidirectional manipulation of MC activity in the LH model reveals that MC inhibition is causally linked to impaired contextual discrimination. Mechanistically, MC inhibition increases the number of active granule cells in a given context, significantly overlapping context-specific ensembles. Our study demonstrates that maladaptive inhibition of MCs after traumatic stress is a substantial mechanism underlying fear overgeneralization with contextual discrimination deficit, suggesting a potential therapeutic target for cognitive symptoms of PTSD.


Subject(s)
Dentate Gyrus , Stress Disorders, Post-Traumatic , Animals , Male , Stress Disorders, Post-Traumatic/physiopathology , Mice , Mice, Inbred C57BL , Fear/physiology , Mossy Fibers, Hippocampal/pathology , Helplessness, Learned
10.
Microorganisms ; 12(3)2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38543560

ABSTRACT

BACKGROUND: Understanding the immune response to evolving viral strains is crucial for evidence-informed public health strategies. The main objective of this study is to assess the influence of vaccination on the neutralizing activity of SARS-CoV-2 delta and omicron infection against various SARS-CoV-2 variants. METHODS: A total of 97 laboratory-confirmed COVID-19 cases were included. To assess the influence of vaccination on neutralizing activity, we measured the neutralizing activity of SARS-CoV-2 delta or omicron (BA.1 or BA.2) infection against wild-type (WT), delta, BA.1, and BA.2, with the results stratified based on vaccination status. RESULTS: The neutralizing activity against the WT, delta, and omicron variants (BA.1 and BA.2) was significantly higher in the vaccinated patients than those in the unvaccinated patients. In the unvaccinated individuals infected with the delta variant, the decrease in binding to BA.1 and BA.2 was statistically significant (3.9- and 2.7-fold, respectively) compared to the binding to delta. In contrast, vaccination followed by delta breakthrough infection improved the cross-neutralizing activity against omicron variants, with only 1.3- and 1.2-fold decreases in BA.1 and BA.2, respectively. Vaccination followed by infection improved cross-neutralizing activity against WT, delta, and BA.2 variants in patients infected with the BA.1 variant, compared to that in unvaccinated patients. CONCLUSIONS: Vaccination followed by delta or BA.1 infection is associated with improved cross-neutralizing activity against different SARS-CoV-2 variants. The enhanced protection provided by breakthrough infections could have practical implications for optimizing vaccination strategies.

11.
Med Image Anal ; 93: 103096, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38301347

ABSTRACT

We present a fully automated method of integrating intraoral scan (IOS) and dental cone-beam computerized tomography (CBCT) images into one image by complementing each image's weaknesses. Dental CBCT alone may not be able to delineate precise details of the tooth surface due to limited image resolution and various CBCT artifacts, including metal-induced artifacts. IOS is very accurate for the scanning of narrow areas, but it produces cumulative stitching errors during full-arch scanning. The proposed method is intended not only to compensate the low-quality of CBCT-derived tooth surfaces with IOS, but also to correct the cumulative stitching errors of IOS across the entire dental arch. Moreover, the integration provides both gingival structure of IOS and tooth roots of CBCT in one image. The proposed fully automated method consists of four parts; (i) individual tooth segmentation and identification module for IOS data (TSIM-IOS); (ii) individual tooth segmentation and identification module for CBCT data (TSIM-CBCT); (iii) global-to-local tooth registration between IOS and CBCT; and (iv) stitching error correction for full-arch IOS. The experimental results show that the proposed method achieved landmark and surface distance errors of 112.4µm and 301.7µm, respectively.


Subject(s)
Spiral Cone-Beam Computed Tomography , Trimethylsilyl Compounds , Humans , Artifacts , Cone-Beam Computed Tomography , Imidazoles
12.
Brain Sci ; 14(1)2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38248291

ABSTRACT

The widespread use of mobile devices and laptops has replaced traditional paper-based learning and the question of how the brain efficiency of digital tablet-based learning differs from that of paper-based learning remains unclear. The purpose of this study was to investigate the difference in brain efficiency for learning between paper-based and digital tablet-based learning by measuring activity in the prefrontal cortex (PFC) using functional near-infrared spectroscopy. Thirty-two subjects were randomly assigned to the paper-based learning or the digital tablet-based learning group. Subjects in each group performed a memory task that required memorizing a three-minute novel (encoding phase) on a paper or digital tablet, followed by a test in which they answered four multiple-choice questions based on the novel's content. To compare both groups, behavioral performance on the test (retrieval phase) and activity in the PFC were measured. As a result, no significant difference in behavioral performance between both groups was observed (p > 0.05). However, the paper-based learning group showed significantly lower activity in the PFC in the encoding phase than the digital tablet-based learning group (p < 0.05) but not in the retrieval phase. The current study demonstrated that brain efficiency in encoding is higher in subjects with paper-based learning than those with digital tablet-based learning. This finding has important implications for education, particularly in terms of the pros and cons of electronic document-based learning.

13.
Food Sci Anim Resour ; 44(1): 87-102, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38229854

ABSTRACT

This study aims to compare the chemical composition, quality, and muscle fiber characteristics of cull sows and commercial pigs, investigating the effect of changes in muscle fiber characteristics on pork quality. The proximate composition, color, pH, water-holding capacity (drip loss and cooking loss), protein solubility, total collagen content, and muscle fiber characteristics of cull sows (n=20) and commercial pigs (n=20) pork were compared. No significant differences were found between cull sows and commercial pigs in terms of proximate composition, drip loss, protein solubility, or total collagen content of their meat (p<0.05). However, cull sow pork exhibited a red color and a higher pH (p<0.05). This appears to be the result of changes in muscle fiber number and area composition (p<0.05). Cull sow meat also displayed better water-holding capacity as evident in a smaller cooking loss (p<0.05), which may be related to an increase in muscle fiber cross-sectional area (p<0.05). In conclusion, muscle fiber composition influences the pork quality; cull sow pork retains more moisture when cooked, resulting in minimal physical loss during processing and can offer more processing suitability.

14.
Food Sci Anim Resour ; 44(1): 103-118, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38229866

ABSTRACT

The aim of this study is to compare the quality characteristics of dry-cured loins with different levels of proteolysis and lipid oxidation and to investigate the relationship between these factors on quality characteristics. The dry-cured loins were divided into four groups [proteolytic index (PI) and 2-thiobarbituric acid reactive substances (TBARS) of high levels (HH), PI of high level and TBARS of low level (HL), PI of low level and TBARS of high level (LH), and PI and TBARS of low levels (LL)] based on the proteolysis index and TBARS. Moisture, protein, and fat content were all significantly influenced by proteolysis and lipid oxidation (p<0.05). The total fatty acid content in the high proteolysis groups (HH and HL) was significantly lower than that in the low proteolysis groups (LH and LL; p<0.05). For total free amino acid content, HH was the highest, and LL was the lowest (p<0.05). On the other hand, there was no significant difference between HL and LH (p>0.05). In the amount of total volatile compounds, there was no significant difference between HH and HL (p>0.05), but LH and LL significantly differed (p<0.05). In conclusion, proteolysis and lipid oxidation can influence the quality characteristics of dry-cured loin. Additionally, proteolysis might be as influential in generating volatile compounds as lipid oxidation.

15.
Redox Biol ; 69: 103023, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38181706

ABSTRACT

The oral colonization of periodontal pathogens onto gingival tissues establishes hypoxic microenvironment, often disrupting periodontal homeostasis in conjunction with oxidative stress. The association between reactive oxygen species (ROS) and osteolytic periodontitis have been suggested by recent studies. PTEN-induced kinase 1 (PINK1), a mitochondrial serine/threonine kinase, is an essential protein for mitochondrial quality control as it protects cells from oxidative stress by promoting degradation of damaged mitochondria through mitophagy. However, the pathophysiological roles of PINK1 in osteoclast-mediated bone loss have not been explored. Here we aimed to determine whether PINK1 plays a role in the regulation of osteoclastogenesis and alveolar bone resorption associated with periodontitis. C57BL/6 wild type (WT) and Pink1 knockout (KO) mice were subjected to ligature-induced periodontitis (LIP), and alveolar bones were evaluated by µCT-analysis and tartrate-resistant acid phosphatase (TRAP) staining. The µCT-analysis showed that bone volume fraction and travecular thickness were lower in Pink1 KO compared to WT mice. The number of TRAP-positive osteoclasts was markedly increased in the periodontal tissues of Pink1 KO mice with LIP. The genetic silencing or deletion of Pink1 promoted excessive osteoclast differentiation and bone resorption in vitro, as respectively indicated by TRAP staining and resorption pits on dentin slices. PINK1 deficiency led to mitochondrial instabilities as indicated by confocal microscopy of mitochondrial ROS, mitochondrial oxygen consumption rate (OCR) analysis, and transmission electron microscopy (TEM). Consequently, a significant increase in Ca2+-nuclear factor of activated T cells 1 (NFATc1) signaling was also found. On the other hand, restoration of mitophagy and autophagy by spermidine (SPD) treatment and the resolution of oxidative stress by N-acetyl-l-cysteine (NAC) treatment protected PINK1 deficiency-induced excessive generation of osteoclasts. Taken together, our findings demonstrate that PINK1 is essential for maintaining mitochondrial homeostasis during osteoclast differentiation. Therefore, targeting PINK1 may provide a novel therapeutic strategy for severe periodontitis with fulminant osteolysis.


Subject(s)
Alveolar Bone Loss , Periodontitis , Animals , Mice , Alveolar Bone Loss/complications , Alveolar Bone Loss/drug therapy , Mice, Inbred C57BL , Mitophagy/genetics , Osteoclasts/metabolism , Periodontitis/genetics , Protein Kinases/genetics , Protein Kinases/metabolism , Reactive Oxygen Species/metabolism
16.
Head Neck ; 46(3): 708-712, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38221740

ABSTRACT

Locally advanced laryngeal cancers treatment often involves total laryngectomy, which some patients are unwilling to undergo, even if this choice reduces their survival probability. Therefore, the objective of laryngeal oncologic surgery is not only to remove the tumor, but also to preserve the organ and its functions. To overcome these concerns, several partial laryngectomy techniques have been developed. This article describes the surgical technique and a case study of a 64-year-old male patient with locally advanced laryngeal squamous cell carcinoma who underwent vertical partial laryngectomy extending to the subglottis and hypopharynx using transoral robotic surgery (TORS) with a da Vinci Single Port surgical robot. The video and article provide a detailed description of the surgical technique, which resulted in successful tumor removal with excellent oncological and functional outcomes.


Subject(s)
Head and Neck Neoplasms , Laryngeal Neoplasms , Robotic Surgical Procedures , Robotics , Male , Humans , Middle Aged , Robotic Surgical Procedures/methods , Laryngectomy/methods , Hypopharynx/surgery , Hypopharynx/pathology , Laryngeal Neoplasms/surgery , Laryngeal Neoplasms/pathology , Head and Neck Neoplasms/surgery , Treatment Outcome
17.
J Immigr Minor Health ; 26(1): 91-100, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37676448

ABSTRACT

After the onset of the COVID-19 pandemic in 2020, Asian Americans in the United States have experienced a surge in anti-Asian crimes, leading to heightened psychological distress among this community. Consequently, the mental well-being of Asian Americans demands greater attention than ever. Regrettably, Asians tend to underutilize or delayed mental health care treatments. This study examines the conventional and alternative mental health service utilization among Asians in the United States according to their English proficiency. From the 2015-2018 National Survey on Drug Use and Health, this study examined 3,424 self-identified non-Hispanic Asians aged 18-64 with Kessler score of at least 5. Stratified bivariate analysis and multivariable logistic regression analysis were conducted. Regardless of English proficiency, Asians did not utilize alternative mental health service more than conventional mental health service. However, those with limited English proficiency consistently utilize care less than those with English proficiency. Need factors, such as mental distress severity and self-rated health status, were significant factors associated with their mental health service utilization. English proficiency remains a structural factor in preventing Asians from utilizing mental health services regardless of the nature of services. Due to the COVID-19 pandemic, more Asians have been experiencing mental distress. This study demonstrates a particular need for mental health services that are culturally specific and Asian language friendly.


Subject(s)
Mental Health Services , Patient Acceptance of Health Care , Humans , Asian , Language , Pandemics , United States/epidemiology
18.
Biotechnol J ; 19(1): e2300461, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37968827

ABSTRACT

2'-Fucosyllactose (2'-FL) which is well-known human milk oligosaccharide was biotechnologically synthesized using engineered Corynebacterium glutamicum, a GRAS microbial workhorse. By construction of the complete de novo pathway for GDP-L-fucose supply and heterologous expression of Escherichia coli lactose permease and Helicobacter pylori α-1,2-fucosyltransferase, bioengineered C. glutamicum BCGW_TL successfully biosynthesized 0.25 g L-1 2'-FL from glucose. The additional genetic perturbations including the expression of a putative 2'-FL exporter and disruption of the chromosomal pfkA gene allowed C. glutamicum BCGW_cTTLEΔP to produce 2.5 g L-1 2'-FL batchwise. Finally, optimized fed-batch cultivation of the BCGW_cTTLEΔP using glucose, fructose, and lactose resulted in 21.5 g L-1 2'-FL production with a productivity of 0.12 g L-1 •h, which were more than 3.3 times higher value relative to the batch culture of the BCGW_TL. Conclusively, it would be a groundwork to adopt C. glutamicum for biotechnological production of other food additives including human milk oligosaccharides.


Subject(s)
Corynebacterium glutamicum , Humans , Corynebacterium glutamicum/genetics , Corynebacterium glutamicum/metabolism , Trisaccharides/genetics , Trisaccharides/metabolism , Oligosaccharides/metabolism , Escherichia coli/genetics , Guanosine Diphosphate Fucose/genetics , Guanosine Diphosphate Fucose/metabolism , Glucose/metabolism , Metabolic Engineering
19.
Biomater Sci ; 12(2): 479-494, 2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38090986

ABSTRACT

Cartilage defects can be difficult to heal, potentially leading to complications such as osteoarthritis. Recently, a tissue engineering approach that uses scaffolds and growth factors has been proposed to regenerate new cartilage tissues. Herein, we investigated the application of hyaluronic acid (HA) gel loaded with transforming growth factor-beta 3 (TGF-ß3) for enhanced cartilage regeneration. We assessed the clinical conditions required to efficiently enhance the ability of the modified HA gel to repair defective cartilage. Based on our findings, the prepared HA gel exhibited good physicochemical and mechanical properties and was non-toxic and non-inflammatory. Moreover, HA gel-loaded TGF-ß3 (HAT) had improved biocompatibility and promoted the synthesis of cartilage-specific matrix and collagen, further improving its ability to repair defects. The application of HAT resulted in an initial burst release of HA, which degraded slowly in vivo. Finally, HAT combined with microfracture-inducing bone marrow stem cells could significantly improve the cartilage microenvironment and regeneration of cartilage defects. Our results indicate that HA is a suitable material for developing growth factor carriers, whereas HAT is a promising candidate for cartilage regeneration. Furthermore, this differentiated strategy provides a rapid and effective clinical approach for next-generation cartilage regeneration.


Subject(s)
Hyaluronic Acid , Mesenchymal Stem Cells , Hyaluronic Acid/chemistry , Transforming Growth Factor beta3/chemistry , Hydrogels/chemistry , Cartilage/metabolism , Transforming Growth Factors/metabolism , Transforming Growth Factors/pharmacology
20.
Adv Sci (Weinh) ; 11(6): e2307306, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38063838

ABSTRACT

Progress in magnetoelectric materials is hindered by apparently contradictory requirements for time-reversal symmetry broken and polar ferroelectric electronic structure in common ferromagnets and antiferromagnets. Alternative routes can be provided by recent discoveries of a time-reversal symmetry breaking anomalous Hall effect (AHE) in noncollinear magnets and altermagnets, but hitherto reported bulk materials are not polar. Here, the authors report the observation of a spontaneous AHE in doped AgCrSe2 , a layered polar semiconductor with an antiferromagnetic coupling between Cr spins in adjacent layers. The anomalous Hall resistivity 3 µ Ω c m $\mu \Omega \, \textnormal {cm}$ is comparable to the largest observed in compensated magnetic systems to date, and is rapidly switched off when the angle of an applied magnetic field is rotated to ≈80° from the crystalline c-axis. The ionic gating experiments show that the anomalous Hall conductivity magnitude can be enhanced by modulating the p-type carrier density. They also present theoretical results that suggest the AHE is driven by Berry curvature due to noncollinear antiferromagnetic correlations among Cr spins, which are consistent with the previously suggested magnetic ordering in AgCrSe2 . The results open the possibility to study the interplay of magnetic and ferroelectric-like responses in this fascinating class of materials.

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