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1.
BMC Ecol Evol ; 24(1): 120, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39277725

ABSTRACT

Mollusca is a morphologically diverse phylum, exhibiting an immense variety of calcium carbonate structures. Proteomic studies of adult shells often report high levels of rapidly-evolving, 'novel' shell matrix proteins (SMPs), which are hypothesized to drive shell diversification. However, relatively little is known about the phylogenetic distribution of SMPs, or about the function of individual SMPs in shell construction. To understand how SMPs contribute to shell diversification a thorough characterization of SMPs is required. Here, we build tools and a foundational understanding of SMPs in the marine gastropod species Crepidula fornicata and Crepidula atrasolea because they are genetically-enabled mollusc model organisms. First, we established a staging system of shell development in C. atrasolea for the first time. Next, we leveraged previous findings in C. fornicata combined with phylogenomic analyses of 95 metazoan species to determine the evolutionary lineage of its adult SMP repertoire. We found that 55% of C. fornicata's SMPs belong to molluscan orthogroups, with 27% restricted to Gastropoda, and only 5% restricted at the species level. The low percentage of species-restricted SMPs underscores the importance of broad-taxon sampling and orthology inference approaches when determining homology of SMPs. From our transcriptome analysis, we found that the majority of C. fornicata SMPs that were found conserved in C. atrasolea were expressed in both larval and adult stages. We then selected a subset of SMPs of varying evolutionary ages for spatial-temporal analysis using in situ hybridization chain reaction (HCR) during larval shell development in C. atrasolea. Out of the 18 SMPs analyzed, 12 were detected in the larval shell field. These results suggest overlapping larval vs. adult SMP repertoires. Using multiplexed HCR, we observed five SMP expression patterns and three distinct cell populations within the shell field. These patterns support the idea that modular expression of SMPs could facilitate divergence of shell morphological characteristics. Collectively, these data establish an evolutionary and developmental framework in Crepidula that enables future comparisons of molluscan biomineralization to reveal mechanisms of shell diversification.


Subject(s)
Animal Shells , Larva , Phylogeny , Snails , Animals , Animal Shells/metabolism , Animal Shells/growth & development , Larva/genetics , Larva/growth & development , Larva/metabolism , Snails/genetics , Snails/metabolism
2.
Rev Sci Instrum ; 95(9)2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39225575

ABSTRACT

The inter-satellite laser ranging interferometer is one of the core components of future gravity missions to achieve high ranging precision. This work builds a preliminary breadboard of the off-axis optical bench design, which integrates the merits of the off-axis optical bench design of GRACE Follow-On mission and other on-axis designs. The study finds that the displacement noise between two optical benches has been reduced to 20nm/Hz at a frequency of 10 mHz, and the differential wavefront sensing noise has been suppressed to 10-5rad/Hz at 1 kHz as well. In addition, the tilt-to-length coupling noise related to the piston effect is restricted within 30 µm/rad, and the relative parallelism error of the transmitting beam and receiving beam is less than 4.5%. The results show that this off-axis optical bench design is an important candidate for China's future gravity missions.

3.
Commun Biol ; 7(1): 1085, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39232040

ABSTRACT

The developmental plasticity of the root system plays an essential role in the adaptation of plants to the environment. Among many other signals, auxin and its directional, intercellular transport are critical in regulating root growth and development. In particular, the PIN-FORMED2 (PIN2) auxin exporter acts as a key regulator of root gravitropic growth. Multiple regulators have been reported to be involved in PIN2-mediated root growth; however, our information remains incomplete. Here, we identified ROWY Bro1-domain proteins as important regulators of PIN2 sorting control. Genetic analysis revealed that Arabidopsis rowy1 single mutants and higher-order rowy1 rowy2 rowy3 triple mutants presented a wavy root growth phenotype. Cell biological experiments revealed that ROWY1 and PIN2 colocalized to the apical side of the plasma membrane in the root epidermis and that ROWYs are required for correct PM targeting of PIN2. In addition, ROWYs also affected PIN3 protein abundance in the stele, suggesting the potential involvement of additional PIN transporters as well as other proteins. A global transcriptome analysis revealed that ROWY genes are involved in the Fe2+ availability perception pathway. This work establishes ROWYs as important novel regulators of root gravitropic growth by connecting micronutrient availability to the proper subcellular targeting of PIN auxin transporters.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Gene Expression Regulation, Plant , Gravitropism , Plant Roots , Arabidopsis/growth & development , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Gravitropism/genetics , Plant Roots/growth & development , Plant Roots/metabolism , Indoleacetic Acids/metabolism , Mutation
4.
bioRxiv ; 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39253514

ABSTRACT

The interplay between transcription factors and chromatin accessibility regulates cell type diversification during vertebrate embryogenesis. To systematically decipher the gene regulatory logic guiding this process, we generated a single-cell multi-omics atlas of RNA expression and chromatin accessibility during early zebrafish embryogenesis. We developed a deep learning model to predict chromatin accessibility based on DNA sequence and found that a small number of transcription factors underlie cell-type-specific chromatin landscapes. While Nanog is well-established in promoting pluripotency, we discovered a new function in priming the enhancer accessibility of mesendodermal genes. In addition to the classical stepwise mode of differentiation, we describe instant differentiation, where pluripotent cells skip intermediate fate transitions and terminally differentiate. Reconstruction of gene regulatory interactions reveals that this process is driven by a shallow network in which maternally deposited regulators activate a small set of transcription factors that co-regulate hundreds of differentiation genes. Notably, misexpression of these transcription factors in pluripotent cells is sufficient to ectopically activate their targets. This study provides a rich resource for analyzing embryonic gene regulation and reveals the regulatory logic of instant differentiation.

5.
Int J Biol Macromol ; 277(Pt 1): 134145, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39059542

ABSTRACT

Bacterial defense-associated sirtuin 2 (DSR2) proteins harbor an N-terminal sirtuin (SIR2) domain degrading NAD+. DSR2 from Bacillus subtilis 29R is autoinhibited and unable to hydrolyze NAD+ in the absence of phage infection. A tail tube protein (TTP) of phage SPR activates the DSR2 while a DSR2-inhibiting protein of phage SPbeta, known as DSAD1 (DSR anti-defense 1), inactivates the DSR2. Although DSR2 structures in complexed with TTP and DSAD1, respectively, have been reported recently, the autoinhibition and activation mechanisms remain incompletely understood. Here, we present cryo-electron microscopy structures of the DSR2-NAD+ complex in autoinhibited state and the in vitro assembled DSR2-TFD (TTP tube-forming domain) complex in activated state. The DSR2-NAD+ complex reveals that the autoinhibited DSR2 assembles into an inactive tetramer, binding NAD+ through a distinct pocket situated outside active site. Binding of TFD into cavities within the sensor domains of DSR2 triggers a conformational change in SIR2 regions, activating its NADase activity, whereas the TTP ß-sandwich domain (BSD) is flexible and does not contribute to the activation process. The activated form of DSR2 exists as tetramers and dimers, with the tetramers exhibiting more NADase activity. Overall, our results extend the current understanding of autoinhibition and activation of DSR2 immune proteins.


Subject(s)
Bacillus subtilis , Models, Molecular , NAD , NAD/metabolism , NAD/chemistry , Protein Binding , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Sirtuins/chemistry , Sirtuins/metabolism , Sirtuin 2/chemistry , Sirtuin 2/metabolism , Protein Multimerization , Cryoelectron Microscopy , Protein Domains , Protein Conformation
6.
J Bone Miner Res ; 39(8): 1147-1161, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-38896028

ABSTRACT

In previous studies, we have demonstrated that stress response-induced high glucocorticoid levels could be the underlying cause of traumatic heterotopic ossification (HO), and we have developed a glucocorticoid-induced ectopic mineralization (EM) mouse model by systemic administration of a high dose of dexamethasone (DEX) to animals with muscle injury induced by cardiotoxin injection. In this model, dystrophic calcification (DC) developed into HO in a cell autonomous manner. However, it is not clear how DC is formed after DEX treatment. Therefore, in this study, we aimed to explore how glucocorticoids initiate muscle EM at a cellular and molecular level. We showed that DEX treatment inhibited inflammatory cell infiltration into injured muscle but inflammatory cytokine production in the muscle was significantly increased, suggesting that other non-inflammatory muscle cell types may regulate the inflammatory response and the muscle repair process. Accompanying this phenotype, transforming growth factor ß1 (TGF-ß1) expression in fibro-adipogenic progenitors (FAPs) was greatly downregulated. Since TGF-ß1 is a strong immune suppressor and FAP's regulatory role has a large impact on muscle repair, we hypothesized that downregulation of TGF-ß1 in FAPs after DEX treatment resulted in this hyperinflammatory state and subsequent failed muscle repair and EM formation. To test our hypothesis, we utilized a transgenic mouse model to specifically knockout Tgfb1 gene in PDGFRα-positive FAPs to investigate if the transgenic mice could recapitulate the phenotype that was induced by DEX treatment. Our results showed that the transgenic mice completely phenocopied this hyperinflammatory state and spontaneously developed EM following muscle injury. On the contrary, therapeutics that enhanced TGF-ß1 signaling in FAPs inhibited the inflammatory response and attenuated muscle EM. In summary, these results indicate that FAPs-derived TGF-ß1 is a key molecule in regulating muscle inflammatory response and subsequent EM, and that glucocorticoids exert their effect via downregulating TGF-ß1 in FAPs.


Heterotopic ossification (HO) is abnormal bone formation in soft tissue. Glucocorticoids, which have strong anti-inflammatory properties, have usually been used as HO therapeutics. However, our findings suggest that glucocorticoids can also promote HO formation. In this study, we tried to explain the underlying reason for these seemingly contradictory observations. We showed that glucocorticoids, in addition to exerting an anti-inflammatory effect on inflammatory cells, can also target another type of muscle cell to exert a proinflammatory effect. These cells are called fibro-adipogenic progenitors (FAPs), and we demonstrated that FAPs played a master regulatory role in the muscle inflammatory response by modulating the expression of transforming growth factor ß1 (TGF-ß1), a well-known immune suppressor. In summary, our findings highlighted the importance of FAP TGF-ß1 levels in affecting the progression and regression of muscle HO and provided new treatment options for HO based on their ability to elevate TGF-ß1 levels in FAPs.


Subject(s)
Dexamethasone , Down-Regulation , Stem Cells , Transforming Growth Factor beta1 , Animals , Transforming Growth Factor beta1/metabolism , Down-Regulation/drug effects , Mice , Dexamethasone/pharmacology , Stem Cells/metabolism , Stem Cells/drug effects , Adipogenesis/drug effects , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Muscle, Skeletal/drug effects
7.
Sex Med ; 12(3): qfae034, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38846267

ABSTRACT

Background: Pelvic floor muscle training (PFMT) has emerged as a potential intervention to improve post-total hysterectomy (TH) sexual function. Electromyographic (EMG) biofeedback is an adjunct that may improve outcomes. Aim: In this study we aimed to compare the EMG biofeedback-assisted PFMT and PFMT alone for improving sexual function in women after TH. Methods: For this prospective study we enrolled women undergoing TH in our hospital between January 2022 and April 2023. Participants were divided according to the treatment they selected: EMG biofeedback-assisted PFMT or PFMT alone. Outcomes: The primary study outcome was change in patient sexual function evaluated by use of the Female Sexual Function Index. Secondary outcomes were changes in anxiety and depression evaluated with the Hospital Anxiety and Depression Scale score and pelvic floor muscle strength was evaluated with the Glazer assessment performed from before to after treatment. Results: A total of 73 patients were included, with 38 patients treated with Electromyographic biofeedback-assisted pelvic floor muscle training. After treatment, sexual function was significantly improved compared to baseline in all patients (all P < .001). Compared to patients with pelvic floor muscle training, the changes in total Female Sexual Function Index scores from before to after treatment in patients with Electromyographic biofeedback-assisted pelvic floor muscle training were significantly higher (all P < .05). There were no significant differences between the 2 groups in the changes in the Glazer score and Hospital Anxiety and Depression Scale scores from before to after treatment (both P > .05). Clinical Translation: The results demonstrate that Electromyographic biofeedback-assisted pelvic floor muscle training may be used to improve the sexual function of patients following TH. Strengths and Limitations: This study is limited by its single-center design, small sample size, lack of randomization, and absence of estrogen monitoring in enrolled participants. Conclusions: Electromyographic biofeedback-assisted pelvic floor muscle training appears to be more effective than pelvic floor muscle training alone in improving sexual function among patients after total hysterectomy.

8.
J Microbiol ; 62(7): 525-533, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38819759

ABSTRACT

Vulvovaginal candidiasis (VVC) is a prevalent condition affecting a significant portion of women worldwide. Licochalcone A (LA), a natural compound with diverse biological activities, holds promise as a protective agent against Candida albicans (C. albicans) infection. This study aims to investigate the potential of LA to safeguard vaginal epithelial cells (VECs) from C. albicans infection and elucidate the underlying molecular mechanisms. To simulate VVC in vitro, VK2-E6E7 cells were infected with C. albicans. Candida albicans biofilm formation, C. albicans adhesion to VK2-E6E7 cells, and C. albicans-induced cell damage and inflammatory responses were assessed by XTT reduction assay, fluorescence assay, LDH assay, and ELISA. CCK-8 assay was performed to evaluate the cytotoxic effects of LA on VK2-E6E7 cells. Western blotting assay was performed to detect protein expression. LA dose-dependently hindered C. albicans biofilm formation and adhesion to VK2-E6E7 cells. Furthermore, LA mitigated cell damage, inhibited the Bax/Bcl-2 ratio, and attenuated the secretion of pro-inflammatory cytokines in C. albicans-induced VK2-E6E7 cells. The investigation into LA's impact on the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway revealed that LA downregulated TLR4 expression and inhibited NF-κB activation in C. albicans-infected VK2-E6E7 cells. Furthermore, TLR4 overexpression partially abated LA-mediated protection, further highlighting the role of the TLR4/NF-κB pathway. LA holds the potential to safeguard VECs against C. albicans infection, potentially offering therapeutic avenues for VVC management.


Subject(s)
Biofilms , Candida albicans , Candidiasis, Vulvovaginal , Chalcones , Epithelial Cells , NF-kappa B , Signal Transduction , Toll-Like Receptor 4 , Vagina , Epithelial Cells/microbiology , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Humans , NF-kappa B/metabolism , Toll-Like Receptor 4/metabolism , Candida albicans/drug effects , Candida albicans/physiology , Signal Transduction/drug effects , Vagina/microbiology , Biofilms/drug effects , Chalcones/pharmacology , Female , Candidiasis, Vulvovaginal/microbiology , Cell Line , Antifungal Agents/pharmacology
9.
Biochem Biophys Res Commun ; 718: 150037, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38735135

ABSTRACT

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for more than 80 % of lung cancer (LC) cases, making it the primary cause of cancer-related mortality worldwide. T-box transcription factor 5 (TBX5) is an important regulator of embryonic and organ development and plays a key role in cancer development. Here, our objective was to investigate the involvement of TBX5 in ferroptosis within LC cells and the underlying mechanisms. METHODS: First, TBX5 expression was examined in human LC cells. Next, overexpression of TBX5 and Yes1-associated transcriptional regulator (YAP1) and knockdown of TEA domain 1 (TEAD1) were performed in A549 and NCI-H1703 cells. The proliferation ability of A549 and NCI-H1703 cells, GSH, MDA, ROS, and Fe2+ levels were measured. Co-immunoprecipitation (Co-IP) was performed to verify whether TBX5 protein could bind YAP1. Then TBX5, YAP1, TEAD1, GPX4, p53, FTH1, SLC7A11 and PTGS2 protein levels were assessed. Finally, we verified the effect of TBX5 on ferroptosis in LC cells in vivo. RESULTS: TBX5 expression was down-regulated in LC cells, especially in A549 and NCI-H1703 cells. Overexpression of TBX5 significantly decreased proliferation ability of A549 and NCI-H1703 cells, downregulated GPX4 and GSH levels, and upregulated MDA, ROS, and Fe2+ levels. Co-IP verified that TBX5 protein could bind YAP1. Moreover, oe-YAP1 promoted proliferation ability of A549 and NCI-H1703 cells transfected with Lv-TBX5, upregulated GPX4 and GSH levels and downregulated MDA, ROS, and Fe2+ levels. Additionally, oe-YAP1 promoted FTH1 and SLC7A11 levels and inhibited p53 and PTGS2 levels in A549 and NCI-H1703 cells transfected with Lv-TBX5. However, transfection with si-TEAD1 further reversed these effects. In vivo experiments further validated that TBX5 promoted ferroptosis in LC cells. CONCLUSIONS: TBX5 inhibited the activation of YAP1-TEAD1 pathway to promote ferroptosis in LC cells.


Subject(s)
Ferroptosis , Lung Neoplasms , T-Box Domain Proteins , TEA Domain Transcription Factors , Transcription Factors , YAP-Signaling Proteins , Ferroptosis/genetics , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/genetics , YAP-Signaling Proteins/metabolism , YAP-Signaling Proteins/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , TEA Domain Transcription Factors/metabolism , T-Box Domain Proteins/metabolism , T-Box Domain Proteins/genetics , Animals , Cell Line, Tumor , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/genetics , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Mice, Nude , Cell Proliferation , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Mice , Gene Expression Regulation, Neoplastic , A549 Cells , Signal Transduction , Reactive Oxygen Species/metabolism
10.
Environ Geochem Health ; 46(5): 163, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38592574

ABSTRACT

Microplastics leaching from aging biodegradable plastics pose potential environmental threats. This study used response surface methodology (RSM) to investigate the impact of temperature, light, and humidity on the aging characteristics of polylactic acid (PLA). Key evaluation metrics included the C/O ratio, functional groups, crystallinity, surface topography, and mechanical properties. Humidity was discovered to have the greatest effect on the ageing of PLA, followed by light and temperature. The interactions between temperature and light, as well as humidity and sunlight, significantly impact the aging of PLA. XPS analysis revealed PLA underwent aging due to the cleavage of the ester bond (O-C=O), resulting in the addition of C=O and C-O. The aging process of PLA was characterized by alterations in surface morphology and augmentation in crystallinity, resulting in a decline in both tensile strength and elongation. These findings might offer insights into the aging behavior of degradable plastics under diverse environmental conditions.


Subject(s)
Esters , Plastics , Polyesters
11.
Chemosphere ; 356: 141917, 2024 May.
Article in English | MEDLINE | ID: mdl-38588900

ABSTRACT

Currently, nanobubbles are widely discussed in environmental research due to their unique properties, including significant specific surface area, transfer efficiency, and free radical generation. In this study, O2 and O3 nanobubbles (diameters ranging from 0 to 500 nm) were combined with conventional surfactant technology to investigate their enhanced efficacy in removing diesel contaminants from soil. The impact of various factors such as surfactant concentration, temperature, and soil aging duration on pollutant removal rates was examined across different experimental approaches (stirring/flushing). Soil samples subjected to different treatments were characterized using TG-DTG and FTIR analysis, while GC/MS was employed to assess the degradation products of diesel constituents in the soil. The results indicated that the elution efficiencies of the three surfactants (SDS, SDBS, and TX-100) for diesel in soil correlated positively with concentration (0.3-1.4 CMC) and temperature (18-60 °C), and inversely with aging time (10-300 days), with the elution capacity was SDS > SDBS > TX-100. Mechanical stirring (500 rpm) and temperature variations (18-60 °C) did not affect the stability of the nanobubbles. Upon the introduction of O3 nanobubbles to the surfactant solution, there was a consistent increase in both the removal (degraded and removed) efficiency and rate of diesel under varying experimental conditions, resulting in an enhancement of removal rates by approximately 8-15%. FTIR spectroscopy showed that surfactants containing O3 nanobubbles mitigated the impact on the primary functional groups of soil organic matter. GC/MS analyses indicated that residual pollutants were predominantly alkanes, with degradation difficulty ranking as: alkanes < alkenes < cycloalkanes < aromatic compounds. TG-DTG coupled with GC/MS analysis demonstrated that O3 nanobubbles contributed to a reduction in surfactant residues. This study significantly advances our understanding of how nanobubbles facilitate and optimize surfactant-assisted remediation of contaminated soil, thereby advancing the precise application of nanobubble technology in soil remediation.


Subject(s)
Environmental Restoration and Remediation , Gasoline , Ozone , Soil Pollutants , Soil , Surface-Active Agents , Soil Pollutants/analysis , Soil Pollutants/chemistry , Environmental Restoration and Remediation/methods , Surface-Active Agents/chemistry , Soil/chemistry , Ozone/chemistry , Temperature
12.
Environ Monit Assess ; 196(5): 445, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38607460

ABSTRACT

Periphyton is a complex community composed of diverse prokaryotes and eukaryotes; understanding the characteristics of microbial communities within periphyton becomes crucial for biogeochemical cycles and energy dynamics of aquatic ecosystems. To further elucidate the community characteristics of periphyton across varied aquatic habitats, including unpolluted ecologically restored lakes, aquaculture ponds, and areas adjacent to domestic and industrial wastewater treatment plant outfalls, we explored the composition and diversity of prokaryotic and eukaryotic communities in periphyton by employing Illumina MiSeq sequencing. Our findings indicated that the prokaryotic communities were predominantly composed of Proteobacteria (40.92%), Bacteroidota (21.01%), and Cyanobacteria (10.12%), whereas the eukaryotic communities were primarily characterized by the dominance of Bacillariophyta (24.09%), Chlorophyta (20.83%), and Annelida (15.31%). Notably, Flavobacterium emerged as a widely distributed genus among the prokaryotic community. Unclassified_Tobrilidae exhibited higher abundance in unpolluted ecologically restored lakes. Chaetogaster and Nais were enriched in aquaculture ponds and domestic wastewater treatment plant outfall area, respectively, while Surirella and Gomphonema dominated industrial sewage treatment plant outfall area. The alpha diversity of eukaryotes was higher in unpolluted ecologically restored lakes. pH and nitrogen content ( NO 2 - - N , NO 3 - - N , and TN) significantly explained the variations for prokaryotic and eukaryotic community structures, respectively. Eukaryotic communities exhibited a more pronounced response to habitat variations compared to prokaryotic communities. Moreover, the association networks revealed an intensive positive correlation between dominant Bacillariophyta and Bacteroidota. This study provided useful data for identifying keystone species and understanding their ecological functions.


Subject(s)
Diatoms , Microbiota , Oligochaeta , Periphyton , Animals , Environmental Monitoring , Aquaculture , Bacteroidetes
13.
Front Neurosci ; 18: 1380171, 2024.
Article in English | MEDLINE | ID: mdl-38650618

ABSTRACT

Periaqueductal gray (PAG), an integration center for neuronal signals, is located in the midbrain and regulates multiple physiological and pathological behaviors, including pain, defensive and aggressive behaviors, anxiety and depression, cardiovascular response, respiration, and sleep-wake behaviors. Due to the different neuroanatomical connections and functional characteristics of the four functional columns of PAG, different subregions of PAG synergistically regulate various instinctual behaviors. In the current review, we summarized the role and possible neurobiological mechanism of different subregions of PAG in the regulation of pain, defensive and aggressive behaviors, anxiety, and depression from the perspective of the up-down neuronal circuits of PAG. Furthermore, we proposed the potential clinical applications of PAG. Knowledge of these aspects will give us a better understanding of the key role of PAG in physiological and pathological behaviors and provide directions for future clinical treatments.

14.
Nat Commun ; 15(1): 3661, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38688901

ABSTRACT

Optochemistry, an emerging pharmacologic approach in which light is used to selectively activate or deactivate molecules, has the potential to alleviate symptoms, cure diseases, and improve quality of life while preventing uncontrolled drug effects. The development of in-vivo applications for optochemistry to render brain cells photoresponsive without relying on genetic engineering has been progressing slowly. The nucleus accumbens (NAc) is a region for the regulation of slow-wave sleep (SWS) through the integration of motivational stimuli. Adenosine emerges as a promising candidate molecule for activating indirect pathway neurons of the NAc expressing adenosine A2A receptors (A2ARs) to induce SWS. Here, we developed a brain-permeable positive allosteric modulator of A2ARs (A2AR PAM) that can be rapidly photoactivated with visible light (λ > 400 nm) and used it optoallosterically to induce SWS in the NAc of freely behaving male mice by increasing the activity of extracellular adenosine derived from astrocytic and neuronal activity.


Subject(s)
Adenosine , Nucleus Accumbens , Receptor, Adenosine A2A , Sleep, Slow-Wave , Animals , Nucleus Accumbens/metabolism , Nucleus Accumbens/drug effects , Nucleus Accumbens/physiology , Male , Receptor, Adenosine A2A/metabolism , Receptor, Adenosine A2A/genetics , Mice , Adenosine/metabolism , Adenosine/pharmacology , Allosteric Regulation , Sleep, Slow-Wave/physiology , Sleep, Slow-Wave/drug effects , Astrocytes/metabolism , Astrocytes/drug effects , Light , Neurons/metabolism , Neurons/drug effects , Mice, Inbred C57BL , Humans , Adenosine A2 Receptor Agonists/pharmacology
15.
Front Med (Lausanne) ; 11: 1328630, 2024.
Article in English | MEDLINE | ID: mdl-38439900

ABSTRACT

Background: Total hip arthroplasty (THA) is a well-established surgical procedure that has been extensively validated to alleviate pain, enhance joint function, improve the ability to perform daily activities, and enhance overall quality of life. However, this procedure is associated with certain complications, among which skeletal muscle fibrosis is a frequently overlooked but significant complication that can lead to persistent pain. Currently, there is no effective method for diagnosing skeletal muscle fibrosis following total hip arthroplasty. Case report: We report a 75-year-old male patient who complained of left groin pain after revision total hip arthroplasty. Serological examinations, X-rays, and bone scan results were all normal. However, during the 68Ga-FAPI PET/CT examination, we observed significant radiotracer uptake along the iliopsoas muscle. This abnormal uptake pattern suggested potential biological activity in this specific area. Combined with physical examination, the patient was diagnosed with iliopsoas fibrosis. Conclusions: The presented images indicated that the uptake pattern was an important indicator for diagnosis, and the prospect of fibroblast activation protein in the diagnosis of skeletal muscle fibrosis has shown certain application value.

16.
PLoS Biol ; 22(3): e3002528, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38427710

ABSTRACT

Streptomyces antibiotic regulatory proteins (SARPs) are widely distributed activators of antibiotic biosynthesis. Streptomyces coelicolor AfsR is an SARP regulator with an additional nucleotide-binding oligomerization domain (NOD) and a tetratricopeptide repeat (TPR) domain. Here, we present cryo-electron microscopy (cryo-EM) structures and in vitro assays to demonstrate how the SARP domain activates transcription and how it is modulated by NOD and TPR domains. The structures of transcription initiation complexes (TICs) show that the SARP domain forms a side-by-side dimer to simultaneously engage the afs box overlapping the -35 element and the σHrdB region 4 (R4), resembling a sigma adaptation mechanism. The SARP extensively interacts with the subunits of the RNA polymerase (RNAP) core enzyme including the ß-flap tip helix (FTH), the ß' zinc-binding domain (ZBD), and the highly flexible C-terminal domain of the α subunit (αCTD). Transcription assays of full-length AfsR and truncated proteins reveal the inhibitory effect of NOD and TPR on SARP transcription activation, which can be eliminated by ATP binding. In vitro phosphorylation hardly affects transcription activation of AfsR, but counteracts the disinhibition of ATP binding. Overall, our results present a detailed molecular view of how AfsR serves to activate transcription.


Subject(s)
DNA-Binding Proteins , Streptomyces , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Streptomyces/genetics , Streptomyces/metabolism , Cryoelectron Microscopy , Transcription Factors/genetics , Transcription Factors/metabolism , Transcriptional Activation , Anti-Bacterial Agents , Adenosine Triphosphate/metabolism , Bacterial Proteins/metabolism , Gene Expression Regulation, Bacterial
17.
IEEE Trans Image Process ; 33: 2116-2130, 2024.
Article in English | MEDLINE | ID: mdl-38470588

ABSTRACT

3D point cloud registration is a crucial task in a variety of fields, including remote sensing mapping, computer vision, virtual reality, and autonomous driving. However, this task is still challenging due to the challenges of noise, non-uniformity, partial overlap, and repeated local features in large scene point clouds. In this paper, we propose an efficient single correspondence voting method for large scene point cloud registration. Specifically, we first propose an efficient hypothetical transformation prediction method called SCVC, which determines the 5 degrees of freedom of the transformation through one correspondence, and then uses Hough voting to determine the last degree of freedom. This algorithm can significantly improve the accuracy of registration in both indoor and outdoor scenes. On the other hand, we propose a more robust transformation verification function called VDIR, which can obtain the optimal registration result of two raw point clouds. Finally, we conduct a series of experiments that demonstrate that our method achieves state-of-the-art performance on four real-world datasets: 3DMatch, 3DLoMatch, KITTI, and WHU-TLS. Our code is available at https://github.com/xingxuejun1989/SCVC.

18.
J Orthop Surg (Hong Kong) ; 32(1): 10225536241233473, 2024.
Article in English | MEDLINE | ID: mdl-38411153

ABSTRACT

Orthopedic surgeries are associated with high-risk of thromboembolism which occurs in 40% to 60% of orthopedic patients in the absence of thromboprophylaxis. Conventionally heparin anticoagulants were used for thromboprophylaxis and currently direct oral anticoagulants (DOACs) are widely used due to their minimal complexity. Anticoagulant use carries bleeding risk and requires optimal laboratory monitoring through conventional thrombin-based assays, anti-Xa assay, anti-IIa assay and contemporary ecarin chromogenic assay (ECA) and rotational thromboelastometry. Monitoring requires multiple hospital visits and hence, the development of point-of-care assays is gaining momentum. Also, a thorough risk assessment model (RAM) is necessary for successful anticoagulant therapy since it enables personalized approach for better thromboprophylaxis outcomes. Despite welcoming changes, lack of guideline consensus, population-based thromboprophylaxis, deficiencies in risk stratification and non-adherence are still a concern. Stronger clinical and process support system with uniform guidelines approaches and patient-specific RAM can aid in the successful implementation of anticoagulant therapy.


Subject(s)
Orthopedic Procedures , Venous Thromboembolism , Humans , Anticoagulants/therapeutic use , Venous Thromboembolism/etiology , Heparin/therapeutic use , Orthopedic Procedures/adverse effects , Risk Factors
19.
Nanotechnology ; 35(21)2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38320325

ABSTRACT

Metasurface is a new type of micro-optical element developed in recent years. It can intelligently modulate electromagnetic waves by adjusting the geometrical parameters and arrangement of dielectric structures. In this paper, a bifocal metalens based on modulation of propagation phase was designed for the potential application in displacement measurement. The phase of the bifocal lens is designed by the optical holography-like method, which is verified by the scalar diffraction theory. We designed a square aperture lens with a side length of 200µm to realize two focal spots with focal lengths of 900 and 1100µm. The two focal spots aren't on one optical axis. The polarization insensitive TiO2cylinders are chosen as structure units. Four structures with different radius were selected to achieve the four phase steps. We fabricated the designed bifocal metalens using electron beam lithography and atomic layer deposition techniques, and measured the light intensity in the areas near the two foci in the direction of the longitudinal axis. The differential signal was calculated, from which we obtained a linear interval. It demonstrates the ability of bifocal differential measurement to be applied to displacement measurement. Because the metasurfaces production process is semiconductor compatible, the bifocal lens is easy to integrate and can be used for miniaturized displacement measurements, micro-resonators, acceleration measurements, and so on.

20.
Nat Commun ; 15(1): 157, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38167854

ABSTRACT

Controlling the formation of clathrate hydrates is crucial for advancing hydrate-based technologies. However, the microscopic mechanism underlying clathrate hydrate formation through nucleation remains poorly elucidated. Specifically, the critical nucleus, theorized as a pivotal step in nucleation, lacks empirical validation. Here, we report uniform nanoparticles, e.g., graphene oxide (GO) nanosheets and gold or silver nanocubes with controlled sizes, as nanoprobes to experimentally measure the size of the critical nucleus of tetrahydrofuran (THF) clathrate hydrate formation. The capability of the nanoparticles in facilitating THF clathrate hydrate nucleation displays generally an abrupt change at a nanoparticle-size-determined specific supercooling. It is revealed that the free-energy barrier shows an abrupt change when the nanoparticles have an approximately the same size as that of the critical nucleus. Thus, it is inferred that THF clathrate hydrate nucleation involves the creation of a critical nucleus with its size being inversely proportional to the supercooling. By proving the existence and determining the supercooling-dependent size of the critical nucleus of the THF clathrate hydrates, this work brings insights in the microscopic pictures of the clathrate hydrate nucleation.

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