TOR-mediated Ypt1 phosphorylation regulates autophagy initiation complex assembly.

The regulation of autophagy initiation is a key step in autophagosome biogenesis. However, our understanding of the molecular mechanisms underlying the stepwise assembly of ATG proteins during this process remains incomplete. The Rab GTPase Ypt1/Rab1 is recognized as an essential autophagy regulator. Here, we identify Atg23 and Atg17 as binding partners of Ypt1, with their direct interaction proving crucial for the stepwise assembly of autophagy initiation complexes. Disruption of Ypt1-Atg23 binding results in significantly reduced Atg9 interactions with Atg11, Atg13, and Atg17, thus preventing the recruitment of Atg9 vesicles to the phagophore assembly site (PAS). Likewise, Ypt1-Atg17 binding contributes to the PAS recruitment of Ypt1 and Atg1. Importantly, we found that Ypt1 is phosphorylated by TOR at the Ser174 residue. Converting this residue to alanine blocks Ypt1 phosphorylation by TOR and enhances autophagy. Conversely, the Ypt1S174D phosphorylation mimic impairs both PAS recruitment and activation of Atg1, thus inhibiting subsequent autophagy. Thus, we propose TOR-mediated Ypt1 as a multifunctional assembly factor that controls autophagy initiation via its regulation of the stepwise assembly of ATG proteins.

Effects of Kinesio taping on lower limb biomechanical characteristics during unexpected jumping in patients with chronic ankle instability.

PURPOSE: The current biomechanical research on the application of Kinesio taping (KT) to patients with chronic ankle instability (CAI) has focused on testing the expected movements. However, unexpected movements are more common in actual sports. Therefore, the present study aimed to investigate the effects of KT on the biomechanical characteristics of the knee and ankle joints during unexpected jumping movements. METHODS: Twenty-one patients with unilateral CAI were recruited to capture the biomechanical parameters during unexpected jumping movements under different interventions: no taping (NT), placebo taping (PT), and KT. A one-way repeated measures analysis of variance was used to compare the differences in knee and ankle biomechanical characteristics among patients with CAI between the three intervention conditions. RESULTS: At initial contact, the KT group demonstrated a significant decrease in ankle plantarflexion and knee flexion angles compared to the NT group (p < 0.05). At the early landing phase, the KT group had a significant increase in peak ankle dorsiflexion angle, peak ankle eversion angle, peak ankle dorsiflexion moment, and peak ankle eversion moment compared to the NT and PT groups (p < 0.05). Furthermore, the KT group had a significantly reduced peak knee flexion angle, peak knee eversion angle, and peak vertical ground reaction force (p < 0.05) compared to the NT and PT groups. CONCLUSION: KT significantly improves the sprain-prone touchdown posture of patients with CAI. And reducing the risk of ankle sprains during the early landing phase by promoting ankle dorsiflexion and eversion angles and moments.

Realization of an autonomously controllable process for atomic layer deposition and its encapsulation application in flexible organic light-emitting diodes.

Atomic layer deposition (ALD), an emerging method of thin film fabrication, has recently witnessed a surge of applications in the optoelectronics field. However, reliable processes capable of controlling film composition have yet to be developed. In this work, the effect of precursor partial pressure and steric hindrance on the surface activity was presented and analyzed in detail, which led to the development of a component tailoring process for ALD composition control in intralayer for the first time. Further, a homogeneous organic/inorganic hybrid film was successfully grown. The component unit of the hybrid film under the joint action of EG and O plasma could achieve arbitrary ratios by controlling the EG/O plasma surface reaction ratio via varied partial pressures. Film growth parameters (growth rate per cycle and mass gain per cycle) and physical properties (density, refractive index, residual stress, transmission, and surface morphology) could be modulated as desired. Moreover, the hybrid film with low residual stress was effectively used in the encapsulation of flexible organic light-emitting diodes (OLEDs). Such a component tailoring process is an important step forward in ALD technology, and allowing for in-situ control of thin film components at the atomic level in intralayer.

Complete stress release in monolayer ALD-Al2O3 films based on mechanical equilibrium homeostasis to realize a bending radius of 1 mm.

Low-temperature-deposited, transparent, high-barrier-performance atomic layer deposition (ALD) Al2O3 films are widely utilized to protect organic optoelectronic devices. However, because the internal compression residual stresses result in poor mechanical properties, these films are unable to realize independent encapsulation. In this work, we propose a pre-bending and substrate thermal expansion process to fabricate low-residual-stress ALD-Al2O3 films by multistep adjustment of mechanical equilibrium homeostasis, compare and analyze the key properties of the films to determine the optimal processing conditions, and adjust the surface area differences between the film and the substrate to acquire a flat-bottom encapsulation substrate. Therefore, fewer cracks form in ALD-Al2O3 deposited at 40 °C, and no significant increase in the water-vapor-transmission rate (WVTR) occurred after multiple bending processes at a 3 mm radius. Furthermore, both the bending radius for the first crack generation and crack saturation density were optimal, resulting in excellent mechanical stability, and a bending radius of 1 mm was achieved. Finally, we confirm the feasibility of the monolayer ALD-Al2O3 prepared by our process for applications in OLEDs. The encapsulated OLED maintained 94% of its initial efficiency after 10 days of bending in a harsh environment at 30 °C and 90% relative humidity.

Comparative analyses of hypothalamus transcriptomes reveal fertility-, growth-, and immune-related genes and signal pathways in different ploidy cyprinid fish.

Triploid crucian carp (TCC) is obtained by hybridization of female diploid red crucian carp (Carassius auratus red var., RCC) and male allotetraploid hybrids. In this study, high-throughput sequencing was used to conduct the transcriptome analysis of the female hypothalamus of diploid RCC, diploid common carp (Cyprinus carpio L., CC) and TCC. The key functional expression genes of the hypothalamus were obtained through functional gene annotation and differential gene expression screening. A total of 71.56 G data and 47,572 genes were obtained through sequencing and genome mapping, respectively. The Fuzzy Analysis Clustering assigned the differentially expressed genes (DEGs) into eight groups, two of which, overdominance expression (6005, 12.62%) and underdominance expression (3849, 8.09%) in TCC were further studied. KEGG enrichment analysis showed that the DEGs in overdominance were mainly enriched in four pathways. The expression of several fertility-related genes was lower levels in TCC, whereas the expression of several growth-related genes and immune-related genes was higher levels in TCC. Besides, 15 DEGs were verified by quantitative real-time PCR (qPCR). The present study can provide a reference for breeding sterility, fast-growth, and disease-resistant varieties by distant hybridization.

Elevated expression of inhibin α gene in sterile allotriploid crucian carp.

Inhibin and Activin, belong to the transforming growth factor ß superfamily (TGF-ß), which associate with the regulation of the reproductive process by the modulation of the hypothalamic-pituitary-gonad (HPG) axis. In this study, we reported the molecular cloning and tissue expression of inhibin α in allotriploid crucian carp and its parent- diploid red crucian carp. The full-length cDNA of inhibin α were respectively 1632 bp and 1642 bp in allotriploids and diploids, which both consisted of a 1044 bp open reading frame (ORF) encoding 347 amino acids. Real-time quantitative PCR (RT-qPCR) showed that allotriploids and diploids had significant expression of inhibin α in testis and ovary, and the expression of inhibin α in the gonads of allotriploids was higher than that of diploids. The immunohistochemistry indicated that the ovarian development of allotriploids was abnormal, and the expression of Inhibin α in the ovary of allotriploids was higher than that of diploids. Results of co-immunoprecitation (co-IP) demonstrated that the Inhibin α and Activin ßA, Inhibin α and Activin ßB can form dimers. These findings suggested that the elevated expression of inhibin α and the competitive binding of Inhibin α subunit with Activin ß subunits in allotriploids may be releted to the sterility of allotriploids. Furthermore, these results will facilitate the investigation of reproduction characteristics in allotriploids and provide theoretical basis for the study of polyploid breeding in the future.

Screening for arrhythmia with the new portable single-lead electrocardiographic device (SnapECG): an application study in community-based elderly population in Nanjing, China.

BACKGROUND: SnapECG is a new handheld single-lead electrocardiograph (ECG) device used for arrhythmia screening, it is widely used in clinical practice but not in primary care. AIMS: To evaluate the arrhythmia screening value of SnapECG among a community-based population. METHODS: A cross-sectional community-based study of multistage stratified cluster sampling was conducted from March 1st to April 30th 2019. The sensitivities, specificities and the area under the receiver operating characteristic (AUCROC) curves of the SnapECG and reference 12-lead ECG on arrhythmia were calculated in three age-groups [50-64 years, 65-74 years, and over-75 years]. RESULTS: A total of 2263 participants took part in the arrhythmia screening, these included 1479 aged 50-64 years, 602 aged 65-74 years and 182 aged over-75 years. The SnapECG categorized 1828 (80.8%) as sinus rhythm, 161 (7.1%) as premature atrial/ventricular contractions (PAVs/PCVs), 32 (1.4%) as possible atrial fibrillation (AF), 56 (2.5%) as supraventricular tachycardias or sinus bradycardia (SVT/SB) and 186 (8.2%) as unreadable. SnapECG had 89% sensitivity (95% CI 0.52-1.00) and 99% specificity (95% CI 0.97-0.99) of detecting AF in the 65-74 years age-group. The AUCROC to detect AF was 0.94 for the 65-74 years age-group, 0.77 for over-75 years, 0.62 for the 50-64 years. DISCUSSION: This study is the first community screening application of SnapECG. Main limitation is the SnapECG and the 12-lead ECG were not done simultaneously. CONCLUSIONS: In the people aged 65-74 years, AF can be detected accurately by the SnapECG with high sensitivity, specificity and large area under the ROC curve, which might have the highest screening predictive accuracy.

CO2 laser-based side-polishing of silica optical fibers.

In this Letter, an optical fiber side-polishing process is proposed that is non-contact, versatile, and scalable. A CO2 laser, with carefully selected pulse parameters, is used to remove cladding material from the side of an optical fiber in a controlled manner. The resulting side-polished optical fiber has adiabatic polishing transitions and a flat uniform polished region. The technique provides a pristine polishing surface with an RMS surface roughness of less than 2 nm. Furthermore, in contrast to traditional side-polishing methods, the wear of hard tooling, the associated surface flaws, and issues with residual abrasive particulates are all negated. It is anticipated that this technique will provide a robust platform for the next generation of optical fiber devices that are based on in-fiber light-matter interaction with exotic materials, such as low-dimensional semi-conductors and topological insulators.

Mediating effects of lipids on the association between smoking and coronary artery disease risk among Chinese.

OBJECTIVE: The mechanism between smoking and coronary artery disease (CAD) remains unclear. It is likely that lipid (including triglycerides (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C)) have been functioning as one of the mediators between smoking and the CAD occurrence. The study aimed to investigate the mediating effect of lipid on the relationship between smoking and CAD risk. METHODS: The case-control study included 2048 subjects. General linear regression analysis was used to corroborate the association between smoking and lipid levels. Univariate and multivariate logistic regression analysis were performed to reveal the relationship between smoking, lipid and the risk of CAD. Mediation analysis was used to investigate whether the association between smoking and CAD risk was mediated by lipid. RESULTS: Smoking was found to be associated with the risk of CAD (odds ratio (OR) = 1.34, 95% confidence interval (CI): 1.05-1.71, P = 0.019). Regression analysis showed that TG, TC and HDL-C were associated with CAD (OR = 2.69, 95%CI: 2.12-3.40, P < 0.001; OR = 0.34, 95%CI: 0.29-0.43, P < 0.001; OR = 0.37, 95%CI: 0.30-0.47, P < 0.001). Moreover, the ratio of TG to HDL-C (TG/HDL-C) was also related to CAD (OR = 4.45, 95%CI: 3.52-5.64, P < 0.001). Mediation analysis showed that among the effects of smoking on CAD, 17.52% was mediated by lipid, in which HDL-C accounted for 11.16% and TG accounted for 6.36%. Further analysis showed that the effect was also partially mediated by TG/HDL-C, which was accounted for 28%. CONCLUSIONS: Lipid plays a partial mediation on the association between smoking and CAD risk. The study provides a clue on the mediation effect of lipids on the relationship between smoking and CAD risks, which is a novel insight to the progression of CAD.

No association between interleukin-18 levels and risk of cardiovascular disease: A Mendelian randomization study.

OBJECTIVE: In this study, Mendelian randomization method was used to determine whether there was a causal association between inflammatory cytokine IL-18 and cardiovascular disease risk. METHODS: We performed a meta-analysis to evaluate the association between IL-18-137G/C and -607C/A polymorphisms and phenotype of IL-18 levels, and also the risks of CVD. All the literatures were searched before September 30, 2019. The logistic regression and linear regression were used to evaluate between IL-18 level and the risk of CVDs. RESULT: Twelve eligible articles of the association between IL-18-137G/C and CVD risks and 8 eligible literatures related to IL-18-607C/A and CVD risks; 2 qualified literatures of the association between IL-18 SNPs and IL-18 levels and 4 eligible literatures related to IL-18 levels and CVD risks. Data of 4 literatures on the correlation between IL-18 level and CVD were summarized. Compared with patients with CVD, the mean of IL-18 level in the normal group was significantly decreased by 50.844 pg/ml (P < 0.05). But the association between IL-18-137G/C, IL-18-607C/A and CVD were not significant (P > 0.05), and the association between IL-18-607C/A and IL-18 level was also not significant (P > 0.05), Mendelian randomization study was failed to prove the association between IL-18 level and CVD risk. CONCLUSION: This study does not support a causal association between IL-18 level and the risks of CVD.

Energy deprivation-induced autophagy and aggrephagy: insights from yeast and mammals. / ä»Žé µæ¯å’Œå“ºä¹³åŠ¨ç‰©ç»†èƒžè§£æžèšé›†ä½“è‡ªå™¬å’Œèƒ½é‡åŒ®ä¹è¯±å¯¼çš„è‡ªå™¬.

Autophagy plays a crucial role in maintaining cellular homeostasis in response to various stimuli. Compared to research on nutrient deprivation-induced autophagy, the understanding of the molecular mechanisms and physiological/pathological significance of autophagy triggered by energy deprivation remains limited. A primary focus of our lab is to elucidate how cells sense energy deprivation and initiate autophagy. Using the model organisms Saccharomyces cerevisiae and mammalian cells, we found that cellular reactive oxygen species (ROS), DNA damage sensor Mec1, and mitochondrial aerobic respiration play essential roles in the autophagy induced by energy deprivation. This review aims to provide a concise overview of these research findings.

Quantum Sensing of Free Radical Generation in Mitochondria of Human Keratinocytes during UVB Exposure.

Ultraviolet (UV) radiation is known to cause skin issues, such as dryness, aging, and even cancer. Among UV rays, UVB stands out for its ability to trigger problems within cells, including mitochondrial dysfunction, oxidative stress, and DNA damage. Free radicals are implicated in these cellular responses, but they are challenging to measure due to their short lifetime and limited diffusion range. In our study, we used a quantum sensing technique (T1 relaxometry) involving fluorescent nanodiamonds (FNDs) that change their optical properties in response to magnetic noise. This allowed us to monitor the free radical presence in real time. To measure radicals near mitochondria, we coated FNDs with antibodies, targeting mitochondrial protein voltage-dependent anion channel 2 (anti-VDAC2). Our findings revealed a dynamic rise in radical levels on the mitochondrial membrane as cells were exposed to UVB (3 J/cm2), with a significant increase observed after 17 min.

Quantum Sensing of Free Radical Generation in Mitochondria of Single Heart Muscle Cells during Hypoxia and Reoxygenation.

Cells are damaged during hypoxia (blood supply deprivation) and reoxygenation (oxygen return). This damage occurs in conditions such as cardiovascular diseases, cancer, and organ transplantation, potentially harming the tissue and organs. The role of free radicals in cellular metabolic reprogramming under hypoxia is under debate, but their measurement is challenging due to their short lifespan and limited diffusion range. In this study, we employed a quantum sensing technique to measure the real-time production of free radicals at the subcellular level. We utilize fluorescent nanodiamonds (FNDs) that exhibit changes in their optical properties based on the surrounding magnetic noise. This way, we were able to detect the presence of free radicals. To specifically monitor radical generation near mitochondria, we coated the FNDs with an antibody targeting voltage-dependent anion channel 2 (anti-VDAC2), which is located in the outer membrane of mitochondria. We observed a significant increase in the radical load on the mitochondrial membrane when cells were exposed to hypoxia. Subsequently, during reoxygenation, the levels of radicals gradually decreased back to the normoxia state. Overall, by applying a quantum sensing technique, the connections among hypoxia, free radicals, and the cellular redox status has been revealed.

A tree peony RING-H2 finger protein, PsATL33, plays an essential role in cold-induced bud dormancy release by regulating gibberellin content.

Bud dormancy is crucial for woody perennial plants to resist low-temperature stress in winter. However, the molecular regulatory mechanisms underlying bud dormancy release are largely unclear. Here, a tree peony (Paeonia suffruticosa) transcript ARABIDOPSIS TOXICOS EN LEVADURA 33 (PsATL33), encoding a RING-H2 finger protein, was selected from previously generated RNA sequencing data of chilling-treated buds. The objective of this study is to investigate the role of PsATL33 in the regulation of cold-induced bud dormancy release. Subcellular localization assay revealed that PsATL33 was localized to the nucleus and plasma membrane. Reverse transcription-quantitative PCR analysis showed that PsATL33 was dramatically upregulated during cold-triggered bud dormancy release. Exogenous treatments with gibberellin (GA3) increased, but abscisic acid (ABA) inhibited the transcription of PsATL33. Ectopic transformation assay indicated that overexpression of PsATL33 in petunia promoted seed germination, plant growth, and axillary bud break. Silencing of PsATL33 in tree peony through virus-induced gene silencing assay delayed bud dormancy release. tobacco rattle virus (TRV)-PsATL33-infected buds exhibited reduced expression levels of dormancy break-related genes EARLY BUD-BREAK 1 (PsEBB1) and CARBOXYLESTERASE 15 (PsCXE15). Silencing of PsATL33 decreased the accumulation of bioactive GAs, GA1 and GA3, rather than ABA. Transcript levels of several genes involved in GA biosynthesis and signaling, including GA20-OXIDASE 1 (PsGA20ox1), GA3-OXIDASE 1 (PsGA3ox1), PsGA3ox3, GA2-OXIDASE 1 (PsGA2ox1), and GA-INSENSITIVE 1A (PsGAI1A), were changed by PsATL33 silencing. Taken together, our data suggest that PsATL33 functions as a positive regulator of cold-induced bud dormancy release by modulating GA production.

Influence of 3D printed surface micro-structures on molding performance and dental bonding properties of zirconia.

OBJECTIVES: To investigate the influence of the 3D printed micro-structured surfaces on the bond strength of zirconia to resin cement. METHODS: Zirconia specimens were divided into five groups based on manufacturing technique and surface preparation: (1) milled zirconia (M group); (2) milled zirconia airborne abraded (MA group); (3) printed zirconia (M group); (4) printed zirconia airborne abraded (PA group); and (5) printed zirconia with micro-structured surface (PM group). The surface morphology, cross-sectional morphology, and elemental composition were observed using a scanning electron microscope (SEM). Surface roughness was measured using a laser scanning confocal microscope (SLCM). Shear bond strength (SBS) was measured using a universal testing machine after bonding resin cement (n = 10). The failure modes of the bonded fracture interfaces were observed and counted using a stereomicroscope and a SEM. In addition, boundary dimensional accuracy (n = 10) and micro-structural dimensional accuracy (n = 20) of printed zirconia specimens with micro-structured surfaces were measured using digital calipers and Fiji software. The crystalline phase changes before and after surface treatment were investigated using X-ray diffractometry. Data was analysed using one-way ANOVA and Tukey HSD post-hoc tests (α = 0.05). RESULT: The surface micro-structures of the PM group had regular morphology and no obvious defects. The surface roughness results showed that the PM group had higher Sa (42.21±1.38 um) and Ra (21.25±1.80 um) values than the other four groups (p < 0.001). The SBS test showed that the bond strength of the PM group reached 11.23 ± 0.66 MPa, which was 55.97% (p < 0.001) higher than that of the P group (7.20 ± 1.14 MPa). The boundary dimensional accuracy of the PM group was proficient (diameter: 99.63 ± 0.31%, thickness: 98.05 ± 1.12%), and the actual fabrication dimensions of the hexagonal micro-structures reached 77.45%-80.01% of the original design. The micro-structured surface did not affect the crystalline phase of zirconia. CONCLUSIONS: The current study illustrates that 3D-printed microstructured surfaces effectively improve the bond strength of zirconia to resin cements. CLINICAL SIGNIFICANCE: With the advantage of 3D printing, this study provides a new idea for improving the bonding properties of zirconia.

Electroconvulsive therapy enhances degree centrality in the orbitofrontal cortex in depressive rumination.

Depressive rumination has been implicated in the onset, duration, and treatment response of refractory depression. Electroconvulsive therapy (ECT) is remarkably effective in treatment of refractory depression by modulating the functional coordination between brain hubs. However, the mechanisms by which ECT regulates depressive rumination remain unsolved. We investigated degree centrality (DC) in 32 pre- and post-ECT depression patients as well as 38 matched healthy controls. An identified brain region was defined as the seed to calculate functional connectivity (FC) in whole brains. Rumination was measured by the Ruminative Response Scale (RRS) and its relationships with identified DC and FC alterations were examined. We found a significant negative correlation between DC of the right orbitofrontal cortex (rOFC) before ECT and brooding level before and after treatment. Moreover, rOFC DC increased after ECT. DC of the left superior temporal gyrus (lSTG) was positively correlated with reflective level before intervention, while lSTG DC decreased after ECT. Patients showed elevated FC in the rOFC with default mode network. No significant association was found between decreased RRS scores and changes in DC and FC. Our findings suggest that functional changes in rOFC and lSTG may be associated with the beneficial effects of ECT on depressive rumination.

Changed brain entropy and functional connectivity patterns induced by electroconvulsive therapy in majoy depression disorder.

OBJECTIVE: Our objective is to innovatively integrate both linear and nonlinear characteristics of brain signals in Electroconvulsive Therapy (ECT) research, with the goal of uncovering deeper insights into the pathogenesis of Major Depressive Disorder (MDD) and identifying novel targets for other physical intervention therapies. METHODS: We measured brain entropy (BEN) in 42 MDD patients and 42 matched healthy controls (HC) using rs-fMRI data. Brain regions that differed significantly in patients with MDD before and after ECT were extracted. Then, we use these brain regions as seed points to investigate the differences in whole-brain resting-state functional connectivity (RSFC) patterns before and after ECT. RESULTS: Compared to HCs, patients had higher BEN levels in the right precuneus (PCUN.R) and right angular gyrus (ANG.R). After ECT, patients had lower BEN levels in the PCUN.R and ANG.R. Compared with before ECT, patients showed significantly increased RSFC after ECT between the PCUN.R and right middle temporal gyrus and ANG.R. Significantly increased RSFC was observed between the ANG.R and right middle frontal gyrus and right supramarginal gyrus after ECT. CONCLUSION: Combining the linear and nonlinear characteristics of brain signals can effectively explore the pathogenesis of depression and provide new targets for ECT.

Psychological Responses of Chinese Medical Students to the COVID-19 Pandemic: Empirical Research Qualitative.

Aim: This study aims to explore the psychological reactions of medical students during the pandemic. Design: A qualitative study. Methods: A purposive sampling technique was employed, and a qualitative approach was adopted. Semi-structured questionnaires were utilized, and online interviews were conducted. Forty medical students were selected as participants for the interviews. The interview data were analyzed using Colaizzi's seven-step analysis method. Results: The study identified five themes related to the psychological reactions of medical students during the pandemic. Firstly, COVID-19's influence on medical careers was characterized by increased interest and determination in pursuing medical professions, heightened admiration for frontline workers, reinforced commitment to a medical career due to the pandemic, and recognition of the significance of medical education. Secondly, challenges and concerns in medical career pursuit were identified, including negative sentiments towards medical careers during COVID-19 and hesitations and concerns about entering the medical field amidst the pandemic. Thirdly, the impact on mental well-being encompassed diverse anxieties expressed by participants regarding control, transmission, treatment, and intentional spreading of the virus. Participants experienced an emotional progression from calmness to fear and anxiety, with heightened anxiety when relatives or acquaintances contracted COVID-19. Academic delays also contributed to anxiety among medical students. Fourthly, changes in behaviors and mindset were observed, including altered behaviors and mindset in response to the pandemic, as well as increased attention to personal hygiene and disease prevention measures. Lastly, expectations of medical students from government, public, and parents were explored. Conclusion: Understanding the psychological reactions of medical students during public health emergencies is crucial for their well-being and professional development. The findings have implications for medical education and the development of strategies to enhance the psychological well-being of medical students during similar crises.

Macrophages-bone marrow mesenchymal stem cells crosstalk in bone healing.

Bone healing is associated with many orthopedic conditions, including fractures and osteonecrosis, arthritis, metabolic bone disease, tumors and periprosthetic particle-associated osteolysis. How to effectively promote bone healing has become a keen topic for researchers. The role of macrophages and bone marrow mesenchymal stem cells (BMSCs) in bone healing has gradually come to light with the development of the concept of osteoimmunity. Their interaction regulates the balance between inflammation and regeneration, and when the inflammatory response is over-excited, attenuated, or disturbed, it results in the failure of bone healing. Therefore, an in-depth understanding of the function of macrophages and bone marrow mesenchymal stem cells in bone regeneration and the relationship between the two could provide new directions to promote bone healing. This paper reviews the role of macrophages and bone marrow mesenchymal stem cells in bone healing and the mechanism and significance of their interaction. Several new therapeutic ideas for regulating the inflammatory response in bone healing by targeting macrophages and bone marrow mesenchymal stem cells crosstalk are also discussed.

Cloning, distribution, and effects of growth regulation of MC3R and MC4R in red crucian carp (Carassius auratus red var.).

Background: Melanocortin-3 and -4 receptors (MC3R and MC4R), G protein-coupled receptors, play vital roles in the regulation of energy homeostasis. To understand the functions of mc3r and mc4r in the energy homeostasis of red crucian carp (Carassius auratus red var., RCC), we cloned mc3r and mc4r, analyzed the tissue expression and localization of the genes, and investigated the effects of knockout of mc3r (mc3r +/-) and mc4r (mc4r +/-) in RCC. Results: The full-length cDNAs of RCC mc3r and mc4r were 1459 base pairs (bp) and 1894 bp, respectively. qRT-PCR indicated that mc3r and mc4r were profusely expressed in the brain, but lower expressed in the periphery tissues. ISH revealed that mc3r and mc4r were located in NPP, NPO, NAPv, NSC, NAT, NRL, NLTl, and NLTp of the brain, suggesting that mc3r and mc4r might regulate many physiological and behavioral aspects in RCC. To further verify the roles of mc3r and mc4r in energy homeostasis, the mc3r+/- and mc4r+/- fish were obtained by the CRISPR/Cas9 system. The average body weights, total lengths, body depths, and food intake of mc4r+/- fish were significantly higher than those of mc3r+/- and the normal wild-type (WT) fish, but there was no difference between the mc3r+/- and WT fish, indicating that the RCC phenotype and food intake were mainly influenced by mc4r but not mc3r. Interestingly, mc4r+/- fish displayed more visceral fat mass than mc3r+/- and WT fish, and mc3r+/- fish also exhibited slightly more visceral fat mass compared to WT. RNA-seq of the liver and muscle revealed that a large number of differentially expressed genes (DEGs) differed in WT vs. mc3r+/-, WT vs. mc4r+/-, and mc3r+/- vs. mc4r+/-, mainly related to lipid, glucose, and energy metabolism. The KEGG enrichment analysis revealed that DEGs were mainly enriched in pathways such as steroid biosynthesis, fatty acid metabolism, fatty acid biosynthesis, glycolysis/gluconeogenesis, wnt signaling pathway, PPAR signaling pathway, and MAPK signaling pathway, thereby affecting lipid accumulation and growth. Conclusion: In conclusion, these results will assist in the further investigation of the molecular mechanisms in which MC3R and MC4R were involved in the regulation of energy homeostasis in fish.