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1.
Mol Cell ; 79(2): 234-250.e9, 2020 07 16.
Article in English | MEDLINE | ID: mdl-32579944

ABSTRACT

Somatic cell nuclear transfer (SCNT) can reprogram a somatic nucleus to a totipotent state. However, the re-organization of 3D chromatin structure in this process remains poorly understood. Using low-input Hi-C, we revealed that, during SCNT, the transferred nucleus first enters a mitotic-like state (premature chromatin condensation). Unlike fertilized embryos, SCNT embryos show stronger topologically associating domains (TADs) at the 1-cell stage. TADs become weaker at the 2-cell stage, followed by gradual consolidation. Compartments A/B are markedly weak in 1-cell SCNT embryos and become increasingly strengthened afterward. By the 8-cell stage, somatic chromatin architecture is largely reset to embryonic patterns. Unexpectedly, we found cohesin represses minor zygotic genome activation (ZGA) genes (2-cell-specific genes) in pluripotent and differentiated cells, and pre-depleting cohesin in donor cells facilitates minor ZGA and SCNT. These data reveal multi-step reprogramming of 3D chromatin architecture during SCNT and support dual roles of cohesin in TAD formation and minor ZGA repression.


Subject(s)
Cell Cycle Proteins/physiology , Chromatin/physiology , Chromosomal Proteins, Non-Histone/physiology , Nuclear Transfer Techniques , Zygote/physiology , Animals , Cell Line , Cell Nucleus , Chromatin Assembly and Disassembly , Computational Biology/methods , Datasets as Topic , Embryonic Development , Female , Male , Mice , Mice, Inbred C57BL , Cohesins
2.
BMC Genomics ; 25(1): 492, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760719

ABSTRACT

Rapeseed (Brassica napus L.), accounts for nearly 16% of vegetable oil, is the world's second produced oilseed. However, pod shattering has caused significant yield loses in rapeseed production, particularly during mechanical harvesting. The GH28 genes can promote pod shattering by changing the structure of the pod cell wall in Arabidopsis. However, the role of the GH28 gene family in rapeseed was largely unknown. Therefore, a genome-wide comprehensive analysis was conducted to classify the role of GH28 gene family on rapeseed pod shattering. A total of 37 BnaGH28 genes in the rapeseed genome were identified. These BnaGH28s can be divided into five groups (Group A-E), based on phylogenetic and synteny analysis. Protein property, gene structure, conserved motif, cis-acting element, and gene expression profile of BnaGH28 genes in the same group were similar. Specially, the expression level of genes in group A-D was gradually decreased, but increased in group E with the development of silique. Among eleven higher expressed genes in group E, two BnaGH28 genes (BnaA07T0199500ZS and BnaC06T0206500ZS) were significantly regulated by IAA or GA treatment. And the significant effects of BnaA07T0199500ZS variation on pod shattering resistance were also demonstrated in present study. These results could open a new window for insight into the role of BnaGH28 genes on pod shattering resistance in rapeseed.


Subject(s)
Brassica napus , Phylogeny , Plant Proteins , Brassica napus/genetics , Plant Proteins/genetics , Gene Expression Regulation, Plant , Multigene Family , Genome, Plant , Synteny , Gene Expression Profiling
3.
BMC Med ; 22(1): 4, 2024 01 02.
Article in English | MEDLINE | ID: mdl-38166913

ABSTRACT

BACKGROUND: We aimed to determine whether and how the combination of acetazolamide and remote ischemic preconditioning (RIPC) reduced the incidence and severity of acute mountain sickness (AMS). METHODS: This is a prospective, randomized, open-label, blinded endpoint (PROBE) study involving 250 healthy volunteers. Participants were randomized (1:1:1:1:1) to following five groups: Ripc (RIPC twice daily, 6 days), Rapid-Ripc (RIPC four times daily, 3 days), Acetazolamide (twice daily, 2 days), Combined (Acetazolamide plus Rapid-Ripc), and Control group. After interventions, participants entered a normobaric hypoxic chamber (equivalent to 4000 m) and stayed for 6 h. The primary outcomes included the incidence and severity of AMS, and SpO2 after hypoxic exposure. Secondary outcomes included systolic and diastolic blood pressure, and heart rate after hypoxic exposure. The mechanisms of the combined regime were investigated through exploratory outcomes, including analysis of venous blood gas, complete blood count, human cytokine antibody array, ELISA validation for PDGF-AB, and detection of PDGF gene polymorphisms. RESULTS: The combination of acetazolamide and RIPC exhibited powerful efficacy in preventing AMS, reducing the incidence of AMS from 26.0 to 6.0% (Combined vs Control: RR 0.23, 95% CI 0.07-0.70, P = 0.006), without significantly increasing the incidence of adverse reactions. Combined group also showed the lowest AMS score (0.92 ± 1.10). Mechanistically, acetazolamide induced a mild metabolic acidosis (pH 7.30 ~ 7.31; HCO3- 18.1 ~ 20.8 mmol/L) and improved SpO2 (89 ~ 91%) following hypoxic exposure. Additionally, thirty differentially expressed proteins (DEPs) related to immune-inflammatory process were identified after hypoxia, among which PDGF-AB was involved. Further validation of PDGF-AB in all individuals showed that both acetazolamide and RIPC downregulated PDGF-AB before hypoxic exposure, suggesting a possible protective mechanism. Furthermore, genetic analyses demonstrated that individuals carrying the PDGFA rs2070958 C allele, rs9690350 G allele, or rs1800814 G allele did not display a decrease in PDGF-AB levels after interventions, and were associated with a higher risk of AMS. CONCLUSIONS: The combination of acetazolamide and RIPC exerts a powerful anti-hypoxic effect and represents an innovative and promising strategy for rapid ascent to high altitudes. Acetazolamide improves oxygen saturation. RIPC further aids acetazolamide, which synergistically regulates PDGF-AB, potentially involved in the pathogenesis of AMS. TRIAL REGISTRATION: ClinicalTrials.gov NCT05023941.


Subject(s)
Altitude Sickness , Ischemic Preconditioning , Humans , Altitude Sickness/prevention & control , Altitude Sickness/diagnosis , Acetazolamide , Prospective Studies , Acute Disease , Hypoxia/prevention & control
4.
J Neuroinflammation ; 21(1): 243, 2024 Sep 28.
Article in English | MEDLINE | ID: mdl-39342313

ABSTRACT

Demyelination occurs widely in the central nervous system (CNS) neurodegenerative diseases, especially the multiple sclerosis (MS), which with a complex and inflammatory lesion microenvironment inhibiting remyelination. Sirtuin6 (SIRT6), a histone/protein deacetylase is of interest for its promising effect in transcriptional regulation, cell cycling, inflammation, metabolism and longevity. Here we show that SIRT6 participates in the remyelination process in mice subjected to LPC-induced demyelination. Using pharmacological SIRT6 inhibitor or activator, we found that SIRT6 modulated LPC-induced damage in motor or cognitive function. Inhibition of SIRT6 impaired myelin regeneration, exacerbated neurological deficits, and decreased oligodendrocyte precursor cells (OPCs) proliferation and differentiation, whereas activation of SIRT6 reversed behavioral performance in mice, demonstrating a beneficial effect of SIRT6. Importantly, based on RNA sequencing analysis of the corpus callosum tissues, it was further revealed that SIRT6 took charge in regulation of glial activation during remyelination, and significant alterations in CHI3L1 were obtained, a glycoprotein specifically secreted by astrocytes. Impaired proliferation and differentiation of OPCs could be induced in vitro using supernatants from reactive astrocyte, especially when SIRT6 was inhibited. Mechanistically, SIRT6 regulates the secretion of CHI3L1 from reactive astrocytes by histone-H3-lysine-9 acetylation (H3K9Ac). Adeno-associated virus-overexpression of SIRT6 (AAV-SIRT6-OE) in astrocytes improved remyelination and functional recovery after LPC-induced demyelination, whereas together with AAV-CHI3L1-OE inhibits this therapeutic effect. Collectively, our data elucidate the role of SIRT6 in remyelination and further reveal astrocytic SIRT6/CHI3L1 as the key regulator for improving the remyelination environment, which may be a potential target for MS therapy.


Subject(s)
Astrocytes , Demyelinating Diseases , Sirtuins , Animals , Male , Mice , Astrocytes/metabolism , Astrocytes/drug effects , Astrocytes/pathology , Cells, Cultured , Demyelinating Diseases/chemically induced , Demyelinating Diseases/metabolism , Demyelinating Diseases/pathology , Lysophosphatidylcholines/toxicity , Mice, Inbred C57BL , Remyelination/drug effects , Remyelination/physiology , Sirtuins/metabolism , Sirtuins/genetics
5.
Glob Chang Biol ; 30(3): e17234, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38469998

ABSTRACT

Rapid biodiversity losses under global climate change threaten forest ecosystem functions. However, our understanding of the patterns and drivers of multiple ecosystem functions across biodiversity gradients remains equivocal. To address this important knowledge gap, we measured simultaneous responses of multiple ecosystem functions (nutrient cycling, soil carbon stocks, organic matter decomposition, plant productivity) to a tree species richness gradient of 1, 4, 8, 16, and 32 species in a young subtropical forest. We found that tree species richness had negligible effects on nutrient cycling, organic matter decomposition, and plant productivity, but soil carbon stocks and ecosystem multifunctionality significantly increased with tree species richness. Linear mixed-effect models showed that soil organisms, particularly arbuscular mycorrhizal fungi (AMF) and soil nematodes, elicited the greatest relative effects on ecosystem multifunctionality. Structural equation models revealed indirect effects of tree species richness on ecosystem multifunctionality mediated by trophic interactions in soil micro-food webs. Specifically, we found a significant negative effect of gram-positive bacteria on soil nematode abundance (a top-down effect), and a significant positive effect of AMF biomass on soil nematode abundance (a bottom-up effect). Overall, our study emphasizes the significance of a multitrophic perspective in elucidating biodiversity-multifunctionality relationships and highlights the conservation of functioning soil micro-food webs to maintain multiple ecosystem functions.


Subject(s)
Ecosystem , Mycorrhizae , Food Chain , Trees , Soil/chemistry , Biodiversity , Plants , Carbon
6.
Reprod Biol Endocrinol ; 22(1): 86, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39044215

ABSTRACT

Reproductive aging not only affects the fertility and physical and mental health of women but also accelerates the aging process of other organs. There is an urgent need newfor novel mechanisms, targets, and drugs to break the vicious cycle of mitochondrial dysfunction, redox imbalance, and germ cell apoptosis associated with ovarian aging. Autophagy, recognized as a longevity mechanism, has recently become a focal point in anti-aging research. Although mitophagy is a type of autophagy, its role and regulatory mechanisms in ovarian aging, particularly in age-related ovarian function decline, remain unclear. Nerve growth factor inducible gene B (Nur77) is an early response gene that can be stimulated by oxidative stress, DNA damage, metabolism, and inflammation. Recent evidence recommends that decreased expression of Nur77 is associated with age-related myocardial fibrosis, renal dysfunction, and Parkinson's disease; however, its association with ovarian aging has not been studied yet. We herein identified Nur77 as a regulator of germ cell senescence, apoptosis, and mitophagy and found that overexpression of Nur77 can activate mitophagy, improve oxidative stress, reduce apoptosis, and ultimately enhance ovarian reserve in aged mice ovaries. Furthermore, we discovered an association between Nur77 and the AKT pathway through String and molecular docking analyses. Experimental confirmation revealed that the AKT/mTOR signaling pathway is involved in the regulation of Nur77 in ovarian function. In conclusion, our results suggest Nur77 as a promising target for preventing and treating ovarian function decline related to reproductive aging.


Subject(s)
Aging , Apoptosis , Mitophagy , Nuclear Receptor Subfamily 4, Group A, Member 1 , Ovary , Animals , Nuclear Receptor Subfamily 4, Group A, Member 1/genetics , Nuclear Receptor Subfamily 4, Group A, Member 1/metabolism , Female , Mitophagy/physiology , Mice , Apoptosis/physiology , Apoptosis/genetics , Ovary/metabolism , Aging/physiology , Aging/genetics , Oxidative Stress/physiology , Signal Transduction/physiology , Ovarian Reserve/physiology , Reproduction/physiology , Proto-Oncogene Proteins c-akt/metabolism , Mice, Inbred C57BL
7.
Reprod Biol Endocrinol ; 22(1): 37, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38576003

ABSTRACT

Inadequate endometrial receptivity often results in embryo implantation failure and miscarriage. Human chorionic gonadotropin (hCG) is a key signaling molecule secreted during early embryonic development, which regulates embryonic maternal interface signaling and promotes embryo implantation. This study aimed to examine the impact of hCG on endometrial receptivity and its underlying mechanisms. An exploratory study was designed, and endometrial samples were obtained from women diagnosed with simple tubal infertility or male factor infertile (n = 12) and recurrent implantation failure (RIF, n = 10). Using reverse transcription-quantitative PCR and western blotting, luteinizing hormone (LH)/hCG receptor (LHCGR) levels and autophagy were detected in the endometrial tissues. Subsequently, primary endometrial stromal cells (ESCs) were isolated from these control groups and treated with hCG to examine the presence of LHCGR and markers of endometrial receptivity (HOXA10, ITGB3, FOXO1, LIF, and L-selectin ligand) and autophagy-related factors (Beclin1, LC3, and P62). The findings revealed that the expressions of receptivity factors, LHCGR, and LC3 were reduced in the endometrial tissues of women with RIF compared with the control group, whereas the expression of P62 was elevated. The administration of hCG to ESCs specifically activated LHCGR, stimulating an increase in the endometrial production of HOXA10, ITGB3, FOXO1, LIF and L-selectin ligands. Furthermore, when ESCs were exposed to 0.1 IU/mL hCG for 72 h, the autophagy factors Beclin1 and LC3 increased within the cells and P62 decreased. Moreover, the apoptotic factor Bax increased and Bcl-2 declined. However, when small interfering RNA was used to knock down LHCGR, hCG was less capable of controlling endometrial receptivity and autophagy molecules in ESCs. In addition, hCG stimulation enhanced the phosphorylation of ERK1/2 and mTOR proteins. These results suggest that women with RIF exhibit lower levels of LHCGR and compromised autophagy function in their endometrial tissues. Thus, hCG/LHCGR could potentially improve endometrial receptivity by modulating autophagy and apoptosis.


Subject(s)
Endometrium , L-Selectin , Pregnancy , Humans , Male , Female , Beclin-1 , L-Selectin/metabolism , Endometrium/metabolism , Chorionic Gonadotropin/pharmacology , Chorionic Gonadotropin/metabolism , Embryo Implantation/physiology , Autophagy , Stromal Cells/metabolism , Apoptosis
8.
Protein Expr Purif ; 222: 106522, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38851552

ABSTRACT

OBJECTIVE: To screen and obtain specific anti-lymphocyte activation gene-3 (LAG3) nanobody sequences, purify and express recombinant anti-LAG3 nanobody, and verify its effect on promoting T cells to kill tumor cells. METHODS: Based on the camel derived natural nanobody phage display library constructed by the research group, the biotinylated LAG3 antigen was used as the target, and the anti-LAG3 nanobody sequences were screened by biotin-streptavidin liquid phase screening, phage-ELISA and sequencing. The sequence-conjµgated human IgG1 Fc fragment was obtained, the recombinant anti-LAG3 nanobody expression vector was constructed, the expression of the recombinant anti-LAG3 nanobody was induced by IPTG and purified, and the characteristics and functions of the recombinant anti-LAG3 nanobody were verified by SDS-PAGE, Western blot, cytotoxicity assay, etc. RESULTS: One anti-LAG3 nanobody sequence was successfully screened, and the corresponding recombinant anti-LAG3 nanobody-expressing bacteria were constructed. The results of SDS-PAGE, Western blot and cytotoxicity assay showed that the recombinant anti-LAG3 nanobody was successfully expressed, which was specific, and it could promote the killing ability of T cells against tumor cells, and the optimal concentration was 200 µg/mL. CONCLUSION: The recombinant anti-LAG3 nanobody screened and expressed has specific and auxiliary anti-tumor cell effects, which lays a foundation for its subsequent application.


Subject(s)
Lymphocyte Activation Gene 3 Protein , Single-Domain Antibodies , Single-Domain Antibodies/genetics , Single-Domain Antibodies/immunology , Single-Domain Antibodies/chemistry , Single-Domain Antibodies/biosynthesis , Single-Domain Antibodies/pharmacology , Humans , Antigens, CD/genetics , Antigens, CD/immunology , Antigens, CD/metabolism , Antigens, CD/biosynthesis , Recombinant Proteins/genetics , Recombinant Proteins/biosynthesis , Recombinant Proteins/immunology , Recombinant Proteins/chemistry , Animals , Peptide Library , Camelus/immunology , Camelus/genetics , Cell Line, Tumor , Escherichia coli/genetics , T-Lymphocytes/immunology , Gene Expression
9.
Cancer Control ; 31: 10732748241287011, 2024.
Article in English | MEDLINE | ID: mdl-39334516

ABSTRACT

OBJECTIVE: This study ascertained current status and influencing factors of readiness for hospital discharge (RHD) of lung cancer (LC) patients with enhanced recovery after surgery (ERAS) concept-guided postoperative management. METHODS: This study prospectively and consecutively included 217 LC patients who underwent whole-course ERAS concept-guided postoperative management at the Department of Thoracic Surgery of Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University from November 2023 to April 2024. RHD, quality of discharge teaching (QDT), and social support (SS) were evaluated using RHDS, QDTS, and SSRS, followed by correlation analyses of RHD with the other 2 factors. The clinical baseline and pathological data were compared between the high and low RHD groups, and the characteristics showing statistical significance were assigned as independent variables for regression analysis with RHD as the dependent variable. RESULTS: RHD, QDT, and SS were above average among LC patients with ERAS concept-guided postoperative management, and RHD was positively correlated with both QDT and SS. Age, education level, self-care ability, number of admissions, and presence of drainage tubes were independent influence factors for RHD of LC patients with ERAS concept-guided postoperative management. CONCLUSION: In LC patients with ERAS concept-guided postoperative management, RHD may be improved by increasing QDT and SS and intervened by factors such as age, education level, self-care ability, number of admissions, and presence of drainage tubes.


Subject(s)
Enhanced Recovery After Surgery , Lung Neoplasms , Patient Discharge , Humans , Female , Male , Lung Neoplasms/surgery , Middle Aged , Aged , Prospective Studies , Postoperative Care/methods , Adult , Postoperative Period
10.
Inorg Chem ; 63(15): 6743-6751, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38573011

ABSTRACT

The development of a solid-state electrolyte (SSE) is crucial for overcoming the side reactions of metal potassium anodes and advancing the progress of K-ion batteries (KIBs). Exploring the diffusion mechanism of the K ion in SSE is important for deepening our understanding and promoting its development. In this study, we conducted static calculations and utilized deep potential molecular dynamics (DeepMD) to investigate the behavior of cubic K3SbS4. The original K3SbS4 exhibited poor ionic conductivity, but we discovered that introducing heterovalent tungsten doping created vacancies, which significantly reduced the activation energy to 0.12 eV and enhanced the ionic conductivity to 1.80 × 10-2 S/cm. The diffusion of K-ions in K3SbS4 primarily occurs through the exchange of positions with K vacancies. This research provides insights into the design of SSE with high ionic conductivity. Furthermore, it highlights the effectiveness of DeepMD as a powerful tool for studying the SSE.

11.
Bioorg Med Chem ; 108: 117776, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38852257

ABSTRACT

Myocardial ischemia/reperfusion (MI/R) is a common cardiovascular disease that seriously affects the quality of life and prognosis of patients. In recent years, matrine has attracted widespread attention in the treatment of cardiovascular diseases. This study designed, synthesized, and characterized 20 new matrine derivatives and studied their protective effects on ischemia-reperfusion injury through in vivo and in vitro experiments. Based on cellular assays, most newly synthesized derivatives have a certain protective effect on Hypoxia/Reoxygenation (H/R) induced H9C2 cell damage, with compound 22 having the best activity and effectively reducing cell apoptosis and necrosis. In vitro experimental data shows that compound 22 can significantly reduce the infarct size of rat myocardium and improve cardiac function after MI/R injury. In summary, compound 22 is a new potential cardioprotective agent that can promote angiogenesis and enhance antioxidant activity by activating ADCY5, CREB3l4, and VEGFA, thereby protecting myocardial cell apoptosis and necrosis induced by MI/R.


Subject(s)
Alkaloids , Apoptosis , Drug Design , Matrines , Myocardial Reperfusion Injury , Quinolizines , Rats, Sprague-Dawley , Alkaloids/pharmacology , Alkaloids/chemistry , Alkaloids/chemical synthesis , Animals , Quinolizines/pharmacology , Quinolizines/chemical synthesis , Quinolizines/chemistry , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/pathology , Rats , Apoptosis/drug effects , Male , Structure-Activity Relationship , Molecular Structure , Cardiotonic Agents/pharmacology , Cardiotonic Agents/chemical synthesis , Cardiotonic Agents/chemistry , Dose-Response Relationship, Drug , Cell Line , Neovascularization, Physiologic/drug effects , Angiogenesis
12.
Phys Chem Chem Phys ; 26(35): 23277-23287, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39196348

ABSTRACT

In response to the pressing need for more efficient and targeted cancer therapies, this study presents the development of biodegradable hydroxyapatite/polyaniline (HAp/PANI) nanocomposite drug carriers for near-infrared (NIR)-induced drug delivery. The synthesis involved loading polyaniline onto mesoporous hydroxyapatite spheres, resulting in high drug loading capacity and tunable NIR responsiveness. The HAp/PANI spheres exhibited superior photothermal properties compared to pristine HAp under NIR irradiation, along with excellent biocompatibility. Importantly, the drug release behavior could be precisely controlled by adjusting NIR power and irradiation time, leading to enhanced anticancer efficacy against HCT-116 colorectal cancer cells. These findings highlight the potential of HAp/PANI mesoporous spheres as promising drug carriers for NIR-responsive cancer therapy.


Subject(s)
Aniline Compounds , Colonic Neoplasms , Doxorubicin , Drug Carriers , Durapatite , Infrared Rays , Nanoparticles , Durapatite/chemistry , Humans , Doxorubicin/chemistry , Doxorubicin/pharmacology , Aniline Compounds/chemistry , Colonic Neoplasms/drug therapy , Drug Carriers/chemistry , Porosity , Nanoparticles/chemistry , HCT116 Cells , Drug Liberation , Cell Survival/drug effects , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Drug Delivery Systems
13.
Ear Hear ; 45(5): 1274-1283, 2024.
Article in English | MEDLINE | ID: mdl-38769615

ABSTRACT

OBJECTIVES: Children with cochlear implants (CIs) face challenges in perceiving fundamental frequency (F0) information because CIs do not transmit F0 effectively. In Mandarin, F0 can contrast meanings at the word level, that is, via lexical tones with distinct F0 contours, and signal contrastive relations between words at the utterance-level, that is, via contrastive focus with expanded F0 range and longer duration. Mandarin-speaking children with CIs have been reported to face challenges in producing distinct F0 contours across tones, but early implantation facilitates tonal acquisition. However, it is still unclear if utterance-level prosody, such as contrastive focus, is also challenging for these children, and if early implantation also offers benefits for focus production. Therefore, this study asked how accurately children with CIs can produce contrastive focus, and if early implantation leads to more accurate focus production, with acoustic patterns approaching that of children with typical hearing (TH). DESIGN: Participants included 55 Mandarin-speaking children (3 to 7 years) with CIs and 55 age-matched children with TH. Children produced noun phrases with and without contrastive focus, such as RED-COLORED cat versus red-colored cat . Three adult native listeners perceptually scored the productions as correct or incorrect. The "correct" productions were then acoustically analyzed in terms of F0 range and duration. RESULTS: Based on the perceptual scores, children with CIs produced focus with significantly lower accuracy (38%) than their TH peers (84%). The acoustic analysis on their "correct" productions showed that children with TH used both F0 and duration to mark focus, producing focal syllables with an expanded F0 range and long duration, and postfocal syllables with a reduced F0 range and short duration. However, children with CIs differed from children with TH in that they produced focal syllables with long duration but not an expanded F0 range, although they produced postfocal syllables with a reduced F0 range and short duration like their TH peers. In addition, early implantation correlated with the percept of more accurate focus productions and better use of F0 range in focal marking. CONCLUSIONS: This study finds that Mandarin-speaking children with CIs are still learning to apply appropriate acoustic cues to contrastive focus. The challenge appears to lie in the use of an expanded F0 range to mark focus, probably related to the limited transmission of F0 information through the CI devices. These findings thus have implications for parents and those working with children with CIs, showing that utterance-level prosody also requires speech remediation, and underscores the critical role of identifying problems early in the acquisition of F0 functions in Mandarin, not only at the word level but also at the utterance-level.


Subject(s)
Cochlear Implantation , Cochlear Implants , Speech Perception , Humans , Child, Preschool , Male , Child , Female , Deafness/rehabilitation , Speech Acoustics , Language , Case-Control Studies
14.
Cell Mol Life Sci ; 80(7): 195, 2023 Jul 03.
Article in English | MEDLINE | ID: mdl-37395809

ABSTRACT

Organ fibrosis caused by chronic allograft rejection is a major concern in the field of transplantation. Macrophage-to-myofibroblast transition plays a critical role in chronic allograft fibrosis. Adaptive immune cells (such as B and CD4+ T cells) and innate immune cells (such as neutrophils and innate lymphoid cells) participate in the occurrence of recipient-derived macrophages transformed to myofibroblasts by secreting cytokines, which eventually leads to fibrosis of the transplanted organ. This review provides an update on the latest progress in understanding the plasticity of recipient-derived macrophages in chronic allograft rejection. We discuss here the immune mechanisms of allograft fibrosis and review the reaction of immune cells in allograft. The interactions between immune cells and the process of myofibroblast formulation are being considered for the potential therapeutic targets of chronic allograft fibrosis. Therefore, research on this topic seems to provide novel clues for developing strategies for preventing and treating allograft fibrosis.


Subject(s)
Immunity, Innate , Lymphocytes , Humans , Macrophages , Allografts , Fibrosis
15.
Neurol Sci ; 45(4): 1419-1428, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38102519

ABSTRACT

In recent years, the stroke incidence has been increasing year by year, and the related sequelae after stroke, such as cognitive impairment, motor dysfunction, and post-stroke depression, seriously affect the patient's rehabilitation and daily activities. Repetitive transcranial magnetic stimulation (rTMS), as a safe, non-invasive, and effective new rehabilitation method, has been widely recognized in clinical practice. This article reviews the application and research progress of rTMS in treating different functional impairments (cognitive impairment, motor dysfunction, unilateral spatial neglect, depression) after stroke in recent years, and preliminary summarized the possible mechanisms. It has been found that the key parameters that determine the effectiveness of rTMS in improving post-stroke functional impairments include pulse number, stimulated brain areas, stimulation intensity and frequency, as well as duration. Generally, high-frequency stimulation is used to excite the ipsilateral cerebral cortex, while low-frequency stimulation is used to inhibit the contralateral cerebral cortex, thus achieving a balance of excitability between the two hemispheres. However, the specific mechanisms and the optimal stimulation mode for different functional impairments have not yet reached a consistent conclusion, and more research is needed to explore and clarify the best way to use rTMS. Furthermore, we will identify the issues and challenges in the current research, explore possible mechanisms to deepen understanding of rTMS, propose future research directions, and offer insightful insights for better clinical applications.


Subject(s)
Agnosia , Stroke Rehabilitation , Stroke , Humans , Transcranial Magnetic Stimulation , Stroke/complications , Stroke/therapy , Brain , Cerebral Cortex
16.
Dev Psychopathol ; : 1-12, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39328179

ABSTRACT

Moral emotions such as shame, guilt and pride are crucial to young children's social-emotional development. Due to the restrictions caused by hearing loss in accessing the social world, deaf and hard of hearing (DHH) children may encounter extra difficulties in their development of moral emotions. However, little research so far has investigated the development trajectory of moral emotions during preschool years in DHH children. The present study used a longitudinal design to explore the development trajectories of shame, guilt, and pride, in a sample of 259 Chinese DHH and typically hearing (TH) preschoolers aged 2 to 6 years old. The results indicated that according to parent reports, DHH children manifested lower levels of guilt and pride compared to their TH peers, yet the manifested levels of shame, guilt, and pride increased throughout the preschool time at a similar pace in all children. Moreover, whilst guilt and pride contributed to increasing levels of psychosocial functioning over the preschool years, shame contributed to lower social competence and more externalizing behaviors in DHH and TH preschoolers. The outcomes imply that early interventions and adjustment to hearing loss could be useful to safeguard the social development of children with severe hearing loss, and cultural variances shall be taken into consideration when studying moral emotions in a Chinese cultural background.

17.
BMC Musculoskelet Disord ; 25(1): 354, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38704573

ABSTRACT

BACKGROUND: This study aimed to investigate the impact of nursing interventions on the rehabilitation outcomes of patients after lumbar spine surgery and to provide effective references for future postoperative care for patients undergoing lumbar spine surgery. METHODS: The study included two groups: a control group receiving routine care and an observation group receiving additional comprehensive nursing care. The comprehensive care encompassed postoperative rehabilitation, pain, psychological, dietary management, and discharge planning. The Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), Short-Form 36 (SF-36) Health Survey, self-rating depression scale (SDS) and self-rating anxiety scale(SAS) were used to assess physiological and psychological recovery. Blood albumin, haemoglobin, neutrophil counts, white blood cell counts, red blood cell counts, inflammatory markers (IL-6, IL-10, and IFN-γ) were measured, and the incidence of postoperative adverse reactions was also recorded. RESULTS: Patients in the observation group exhibited significantly improved VAS, ODI, SF-36, SDS and SAS scores assessments post-intervention compared to the control group (P < 0.05). Moreover, levels of IL-6, IL-10, and IFN-γ were more favorable in the observation group post-intervention (P < 0.05), indicating a reduction in inflammatory response. There was no significant difference in the incidence of postoperative adverse reactions between the groups (P > 0.05), suggesting that the comprehensive nursing interventions did not increase the risk of adverse effects. CONCLUSION: Comprehensive nursing interventions have a significant impact on the postoperative recovery outcomes of patients with LSS, alleviating pain, reducing inflammation levels, and improving the overall quality of patient recovery without increasing the patient burden. Therefore, in clinical practice, it is important to focus on comprehensive nursing interventions for patients with LSS to improve their recovery outcomes and quality of life.


Subject(s)
Lumbar Vertebrae , Humans , Male , Female , Middle Aged , Lumbar Vertebrae/surgery , Treatment Outcome , Adult , Aged , Pain Measurement , Pain, Postoperative/etiology , Pain, Postoperative/rehabilitation , Disability Evaluation , Postoperative Care/methods
18.
Brain Inj ; 38(11): 918-927, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-38828532

ABSTRACT

BACKGROUND: Cognitive impairment is a severe complication of acute respiratory distress syndrome (ARDS). Emerging studies have revealed the effects of pyrrolidine dithiocarbamate (PDTC) on improving surgery-induced cognitive impairment. The major aim of the study was to investigate whether PDTC protected against ARDS-induced cognitive dysfunction and to identify the underlying mechanisms involved. METHODS: The rat model of ARDS was established by intratracheal instillation of lipopolysaccharide (LPS), followed by treatment with PDTC. The cognitive function of rats was analyzed by the Morris Water Maze, and pro-inflammatory cytokines were assessed by quantitative real-time PCR, enzyme-linked immunosorbent assay, and western blot assays. A dual-luciferase reporter gene assay was performed to identify the relationship between miR-181c and its target gene, TAK1 binding protein 2 (TAB2). RESULTS: The results showed that PDTC improved cognitive impairment and alleviated neuroinflammation in the hippocampus in LPS-induced ARDS model. Furthermore, we demonstrated that miR-181c expression was downregulated in the hippocampus of the ARDS rats, which was restored by PDTC treatment. In vitro studies showed that miR-181c alleviated LPS-induced pro-inflammatory response by inhibiting TAB2, a critical molecule in the nuclear factor (NF)-κB signaling pathway. CONCLUSION: PDTC improves cognitive impairment in LPS-induced ARDS by regulating miR-181c/NF-κB axis-mediated neuroinflammation, providing a potential opportunity for the treatment of this disease.


Subject(s)
Cognitive Dysfunction , Disease Models, Animal , Lipopolysaccharides , MicroRNAs , NF-kappa B , Pyrrolidines , Rats, Sprague-Dawley , Respiratory Distress Syndrome , Thiocarbamates , Animals , MicroRNAs/metabolism , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/drug therapy , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Rats , Thiocarbamates/pharmacology , Thiocarbamates/therapeutic use , NF-kappa B/metabolism , Male , Pyrrolidines/pharmacology , Pyrrolidines/therapeutic use , Neuroinflammatory Diseases/metabolism , Neuroinflammatory Diseases/drug therapy , Signal Transduction/drug effects , Hippocampus/metabolism , Hippocampus/drug effects , Maze Learning/drug effects
19.
Ecotoxicol Environ Saf ; 284: 116941, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39208577

ABSTRACT

BACKGROUND: In recent decades, the quality of male semen has decreased worldwide. Air pollution has been linked to lower semen quality in several studies. However, the effects of atmospheric pollutants on different semen characteristics have not always been consistent. The aim of this study was to investigate the association between the Air Quality Index (AQI) and six atmospheric pollutants (PM2.5, PM10, SO2, NO2, CO, and O3), semen quality, and their key exposure window periods. METHODS: This study included 1711 semen samples collected at the reproductive clinics of the First Affiliated Hospital of Shanxi Medical University in Taiyuan, Shanxi, China, from October 10, 2021, to September 30, 2022. We evaluated the association of AQI and six atmospheric pollutants with semen quality parameters throughout sperm development and three key exposure windows in men using single-pollutant models, double-pollutant models, and subgroup analyses of semen quality-eligible groups. RESULTS: Both the single-pollutant model and subgroup analyses showed that PM, CO, and O3 levels were negatively correlated with total and progressive motility. At 70-90 d before semen collection, CO exposure and semen volume (ß =-1.341, 95 % CI: -1.805, -0.877, P <0.001), total motility (ß =-2.593, 95 % CI: -3.425, -1.761, P <0.001), and progressive motility (ß =-4.658, 95 % CI: -5.556, -3.760, P <0.001) were negatively correlated. At 0-9 days before semen collection, CO was negatively correlated with normal morphology (ß =-3.403, 95 % CI: -5.099, -1.708, P <0.001). Additionally, the AQI was adversely associated with total and progressive motility in subgroup analyses of the semen quality-eligible groups. CONCLUSIONS: During the entire sperm development process, multiple air pollutants were determined to have an adverse correlation with semen quality parameters. AQI was significant marker for the combined effects of various atmospheric pollutants on male reproductive health.


Subject(s)
Air Pollutants , Semen Analysis , Air Pollutants/analysis , Air Pollutants/toxicity , China , Male , Humans , Cross-Sectional Studies , Adult , Air Pollution/adverse effects , Air Pollution/statistics & numerical data , Semen/drug effects , Environmental Exposure , Young Adult , Sperm Motility/drug effects
20.
Vasa ; 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39262231

ABSTRACT

Background: A potential independent association between arterial stiffness (AS) and the development of new-onset chronic kidney disease (CKD) has not been thoroughly examined. Patients and methods: A total of 6929 participants were collected from the Kailuan study. All participants were free of CKD at the baseline. The participants were divided into four groups based on their brachial-ankle pulse wave velocity (baPWV) values. Cox regression models were used to analyze the relationship between baPWV values and the risk of new-onset CKD. Results: Over the course of a 10.06-year follow-up period, a total of 962 cases of new-onset CKD were documented. Cox proportional hazards analyses showed that a higher baPWV quartile was linked to an increased risk of new-onset CKD. Conclusions: Brachial-ankle pulse wave velocity has a strong correlation with the development of new-onset CKD. Therefore, baPWV can be considered an innovative indicator for predicting the occurrence of new-onset CKD.

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