A rescue diet raises the plasma calcium concentration and ameliorates rheumatoid arthritis in mice: Role of CaSR-mediated inhibition of osteoclastogenesis.

Calcium modulates bone cell recruitment, differentiation, and function by binding to the calcium-sensing receptor (CaSR). However, the function of CaSR induced by high extracellular calcium (Ca2+ e ) in the regulation of osteoclast formation in rheumatoid arthritis (RA) remains unknown. Here, we used TNFα-transgenic (TNFTG ) RA mice and their wildtype (WT) littermates fed a normal or a rescue diet (high calcium, high phosphorus, and high lactose diet, termed rescue diet) to compare their joint bone phenotypes. In comparison to TNFTG mice fed the normal diet, articular bone volume and cartilage area are increased, whereas inflamed area, eroded surface, TRAP+ surface, and osteoclast-related genes expression are decreased in TNFTG mice fed the rescue diet. Besides, TNFTG mice fed the rescue diet were found to exhibit more CaSR+ area and less NFATc1+ /TRAP+ area. Furthermore, at normal Ca2+ e concentrations, osteoclast precursors (OCPs) from TNFTG mice formed more osteoclasts than OCPs from WT mice, but the number of osteoclasts gradually decreased when the Ca2+ e concentration increased. Meanwhile, the expression of CaSR increased responding to a high level of Ca2+ e , whereas the expression of NF-κB/NFATc1 signaling molecules decreased. At last, the knockdown of CaSR blocked the inhibition of osteoclast differentiation attributed to high Ca2+ e . Taken together, our findings indicate that high Ca2+ e inhibits osteoclast differentiation in RA mice partially through the CaSR/NF-κB/NFATc1 pathway.

Mirror training device improves dental students' performance on virtual simulation dental training system.

INTRODUCTION: Clinical practice of dentistry entails the use of indirect vision using a dental mirror. The Mirrosistant is a device that helps dental students become proficient with use of indirect vision mirror operation. This study aimed to explore the role of the Mirrosistant on students' performance with the virtual simulation dental training system. MATERIALS AND METHODS: A total of 72 dental students were equally assigned to the Control group and the Experimental group. Subsequently, Mirrosistant was used to conduct a series of mirror training exercises in the Experimental group. The training consisted of tracing the edge and filling in the blank of the prescribed shape, as well as preparing the specified figure on raw eggs using indirect vision via Mirrosistant. Next, both groups were examined using the SIMODONT system, a virtual reality dental trainer, for mirror operation. In addition, a five-point Likert scale questionnaire was used to assess student feedback by using Mirrosistant. RESULTS: The mirror operation examination conducted by the SIMODONT system revealed that mirror training using Mirrosistant had statistically improved students' performances (score: 80.42 ± 6.43 vs. 69.89 ± 15.98, P = 0.0005) and shorten their performance time of mirror operation (time of seconds: 243.28 ± 132.83 vs. 328.53 ± 111.89, P = 0.0013). Furthermore, the questionnaire survey indicated that the participants had positive attitudes toward the mirror training using Mirrosistant. Most students believed that the mirror training device could improve their perceptions of direction and distance, as well as their sensations of dental operation and dental fulcrum. CONCLUSION: Mirror training using Mirrosistant can enhance dental students' mirror perceptual and operational skills on virtual simulation dental training system.

Glucocorticoid Regulates the Synthesis of Porcine Muscle Protein through m6A Modified Amino Acid Transporter SLC7A7.

The occurrence of stress is unavoidable in the process of livestock production, and prolonged stress will cause the decrease of livestock productivity. The stress response is mainly regulated by the hypothalamic-pituitary-adrenal axis (HPA axis), which produces a large amount of stress hormones, namely glucocorticoids (GCs), and generates a severe impact on the energy metabolism of the animal body. It is reported that m6A modification plays an important role in the regulation of stress response and also participates in the process of muscle growth and development. In this study, we explored the effect of GCs on the protein synthesis procession of porcine skeletal muscle cells (PSCs). We prove that dexamethasone affects the expression of SLC7A7, a main amino acid transporter for protein synthesis by affecting the level of m6A modification in PSCs. In addition, we find that SLC7A7 affects the level of PSC protein synthesis by regulating the conduction of the mTOR signaling pathway, which indicates that the reduction of SLC7A7 expression may alleviate the level of protein synthesis under stress conditions.

Expression and distribution of epithelial sodium channel in nasal polyp and nasal mucosa.

To evaluate the expression and location of epithelial sodium channels (ENaCs) in human nasal polyp and normal nasal mucosa, and to characterize the relevance of ENaCs to the development of NPs. Nasal polyp tissue from 17 patients and nasal mucosa from ten patients were obtained through endoscopic sinus surgery. The mRNA concentrations of ENaC-α, ß, and γ were detected by real-time polymerase chain reaction. The expression of ENaC-α was detected using western blot and immunofluorescence techniques. The distribution of ENaC-α in mucosal tissue was observed using a laser scanning confocal microscope. The transcriptional expression of three subunits of ENaC was in the following order: α > ß > γ, in both groups. The transcriptional expression of α, ß, and γ subunits of ENaC was elevated in nasal polyp compared to nasal mucosa (p < 0.01). ENaC-α expression was higher in nasal polyp than in nasal mucosa (p < 0.05). Immunofluorescent staining indicated that ENaC-α protein was distributed in the epithelial cell apical membrane. The expression of ENaC is upregulated in human nasal polyp, which might in turn facilitate the formation and development of nasal polyp.

Surgical treatment of MRI-negative temporal lobe epilepsy based on PET: a retrospective cohort study.

INTRODUCTION: Using retrospective and comparative methods, we aim to discuss the surgical treatment of magnetic resonance imaging (MRI)-negative temporal lobe epilepsy (TLE) presented with positive positron emission tomography (PET) results. METHODS: From the viewpoint of semiology, demography, surgical treatment and prognosis evaluation, we compared 19 MRI-negative, PET-positive TLE patients to 41 TLE with hippocampal sclerosis patients, and then statistically analyzed the differences between these 2 cohorts. RESULTS: Under intraoperative electrocorticography monitoring, all patients underwent successful standard anterior temporal lobectomy. It appears that there is no significant difference between the surgical outcome of MRI-negative/PET-positive TLE (Engle class I: 68.4%, Engle class I + II: 84.2%) and TLE with hippocampal sclerosis (Engle class I: 68.3%, Engle class I + II: 80.5%). The analysis also shows that to some extent MRI-negative, PET-positive TLE might be distinct from TLE with hippocampal sclerosis as a clinical entity, i.e. the former is not a subtype of the latter. History of febrile convulsion and occurrence of secondary generalized tonic-clonic seizure may possibly differentiate them from each other. CONCLUSION: Successful resective surgery of MRI-negative TLE based on PET can yield similar favorable results to TLE with hippocampal sclerosis. This study demonstrates that with reasonable presurgical workup, such TLE subtypes can be surgically treated without invasive intracranial electrode implantation.

Biostable hydrogels consisting of hybrid ß-sheet fibrils assembled by a pair of enantiomeric peptides.

The assembly of chiral peptides facilitates the formation of diverse supramolecular structures with unique physicochemical and biological properties. However, the effects of chirality on peptide assembly and resulting hydrogel properties remain underexplored. In this study, we systematically investigated the assembly propensity, morphology, and biostability of mixture of a pair of enantiomeric peptides LELCLALFLF (ECF-5) and DEDCDADFDF (ecf-5) at various ratios. Results indicate the development of ß-sheet fibrils, ultimately leading to the formation of self-supporting hybrid hydrogels. The hydrogel formed at a ratio of 1:1 exhibits a significantly lower storage modulus (G') than of the ratios of 0:1, 1:3, 3:1 and 1:0 (nD/nL; same below). Kink-separated fragments of approximately 100 nm in length predominate at ratios of 1:3 and 3:1, compared with the smooth fibrils at other ratios, probably attributed to an alternating arrangement of the co-assembled and self-assembled peptide fragments. The introduction of ecf-5 to the hybrid hydrogels improves resistance to proteolytic digestion and maintains commendable biocompatibility in both MIN6 and HUVECs cells. These findings provide valuable insights into the development of hydrogels with tailored properties, positing them potential scaffolds for 3D cell culture and tissue engineering.

Effect of graphene oxide on sodium alginate hydrogel as a carrier triggering release of ibuprofen.

The design and preparation of safe wound dressings with antibacterial and controlled drug release abilities is valuable in medicine. This research focuses on the fabrication of a hydrogel carrier with graphene oxide (GO)-triggered ibuprofen (IBU) release to control inflammation. The hydrogel was prepared by cross-linking the base polymer sodium alginate (SA) and functionalized GO. The morphology of the gel was observed by a scanning electron microscope (SEM), and its structure was analyzed through X-ray diffraction (XRD) and Fourier transform infrared reflection (FTIR) spectroscopy. The effects of GO on swelling capacity, IBU release behavior and antibacterial activity were investigated by using the prepared GO/SA hydrogel as a drug carrier and IBU as a drug model. In vitro studies confirmed that the GO/SA hydrogel had good antimicrobial activity and excellent cytotoxicity. The analysis of cumulative IBU release rates revealed that the addition of GO could promote the release of IBU, and the change in GO content did not have a prominent effect on IBU release. At the same time, the rate of IBU release from the GO/SA hydrogel was affected by near-infrared light. Under a light source, the release rate of IBU increased, and the release amount of IBU showed a clear stepwise increase under light on-off conditions. These results suggest that the GO/SA hydrogel could be a potential antibacterial and anti-inflammatory wound dressing.

Peptide-Based Double-Network Hydrogels for Melanoma Treatment and Wound Healing Promotion.

Although surgery is the primary method to treat malignant melanoma, it has drawbacks such as residual tumor that could trigger cancer recurrence and wound infections that are especially difficult to heal in diabetics. In this research, we have constructed anti-cancer peptides/polyvinyl alcohol (PVA) double-network (DN) hydrogels for the treatment of melanoma. The maximum stress of the DN hydrogels is found to be larger than 2 MPa, which endows the DN hydrogels with ideal mechanical performance for therapeutic wound dressing. The peptides naphthalene-FIIIKKK (IK1) and phloretic acid-FIIIKKK (IK3) that were previously developed as effective antibacterial peptides, as well as the peptide/PVA DN hydrogels, are found to have good anti-cancer efficacy and target mouse melanoma cells B16-F10 while being nontoxic to normal cells. Further studies have revealed that IK1 and IK3 damage the tumor cell membrane and mitochondrial membrane and eventually trigger apoptosis. In the mouse melanoma model and the diabetic bacterial infection model, the DN hydrogels exhibit great anti-tumor, anti-bacterial, and wound healing promotion abilities in vivo. Because of their excellent mechanical properties, the DN hydrogels are promising soft materials for directly treating malignant melanomas as well as for preventing recurrence and bacterial infection after melanoma surgery that promote wound healing.

Loss of SENP3 mediated the formation of nasal polyps in nasal mucosal inflammation by increasing alternative activated macrophage.

BACKGROUND AND AIM: Small ubiquitin-like modifier (SUMO)-specific protease (SENP)3 is a protease molecule that responds to reactive oxygen species (ROS) with high sensitivity. However, the role of ROS and SENP3 in the formation of nasal polyps (NPs) remains unclear. This study aimed to explore how SENP3 influenced the outcome of chronic rhinosinusitis (CRS) by altering macrophage function, that is, the formation of NPs. METHODS: The alternative activation of macrophage (M2) was detected with CD68+ CD206+ in humans and CD206+ in mice. The nasal mucosa of patients with CRS was tested using flow cytometry (CD68, CD80, and CD206) and triple-color immunofluorescence staining (CD68, CD206, and SENP3). The bone marrow-derived macrophages from SENP3 knockout and control mice were stimulated with interleukin (IL)-4 and IL-13 to analyze alternative macrophage polarization in vitro. An animal model of allergic rhinitis was constructed using SENP3 knockout mice. CD206 was detected by immunofluorescence staining. The thickening of eosinophil-infiltrated mucosa was detected by Luna staining. RESULTS: The number of CD68+ CD206+ M2 increased in the nasal mucosa of patients with CRS with NP (CRSwNP) compared with patients with CRS without NP (CRSsNP), but with no significant difference between the groups. SENP3 knockout increased the polarization of F4/80+ CD206+ M2. Meanwhile, the number of CD206+ M2 significantly increased in the allergic rhinitis model constructed using SENP3 knockout mice and controls, with a more obvious proliferation of the nasal mucosa. CONCLUSION: Downregulation of SENP3 promotes the formation of nasal polyps mediated by increasing alternative activated macrophage in nasal mucosal inflammation.

Exacerbation of allergic rhinitis by the commensal bacterium Streptococcus salivarius.

Allergic rhinitis (AR)-commonly called hay fever-is a widespread condition that affects the quality of life of millions of people. The pathophysiology of AR remains incompletely understood. In particular, it is unclear whether members of the colonizing nasal microbiota contribute to AR. Here, using 16S ribosomal RNA sequencing, we show that the nasal microbiome of patients with AR (n = 55) shows distinct differences compared with that from healthy individuals (n = 105), including decreased heterogeneity and the increased abundance of one species, Streptococcus salivarius. Using ex vivo and in vivo models of AR, we demonstrate that this commensal bacterium contributes to AR development, promoting inflammatory cytokine release and morphological changes in the nasal epithelium that are characteristic of AR. Our data indicate that this is due to the ability of S. salivarius to adhere to the nasal epithelium under AR conditions. Our study indicates the potential of targeted antibacterial approaches for AR therapy.

NaCl Pretreatment Enhances the Low Temperature Tolerance of Tomato Through Photosynthetic Acclimation.

Plants often need to withstand multiple types of environmental stresses (e.g., salt and low temperature stress) because of their sessile nature. Although the physiological responses of plants to single stressor have been well-characterized, few studies have evaluated the extent to which pretreatment with non-lethal stressors can maintain the photosynthetic performance of plants in adverse environments (i.e., acclimation-induced cross-tolerance). Here, we studied the effects of sodium chloride (NaCl) pretreatment on the photosynthetic performance of tomato plants exposed to low temperature stress by measuring photosynthetic and chlorophyll fluorescence parameters, stomatal aperture, chloroplast quality, and the expression of stress signaling pathway-related genes. NaCl pretreatment significantly reduced the carbon dioxide assimilation rate, transpiration rate, and stomatal aperture of tomato leaves, but these physiological acclimations could mitigate the adverse effects of subsequent low temperatures compared with non-pretreated tomato plants. The content of photosynthetic pigments decreased and the ultra-microstructure of chloroplasts was damaged under low temperature stress, and the magnitude of these adverse effects was alleviated by NaCl pretreatment. The quantum yield of photosystem I (PSI) and photosystem II (PSII), the quantum yield of regulatory energy dissipation, and non-photochemical energy dissipation owing to donor-side limitation decreased following NaCl treatment; however, the opposite patterns were observed when NaCl-pretreated plants were exposed to low temperature stress. Similar results were obtained for the electron transfer rate of PSI, the electron transfer rate of PSII, and the estimated cyclic electron flow value (CEF). The production of reactive oxygen species induced by low temperature stress was also significantly alleviated by NaCl pretreatment. The expression of ion channel and tubulin-related genes affecting stomatal aperture, chlorophyll synthesis genes, antioxidant enzyme-related genes, and abscisic acid (ABA) and low temperature signaling-related genes was up-regulated in NaCl-pretreated plants under low temperature stress. Our findings indicated that CEF-mediated photoprotection, stomatal movement, the maintenance of chloroplast quality, and ABA and low temperature signaling pathways all play key roles in maintaining the photosynthetic capacity of NaCl-treated tomato plants under low temperature stress.

Integrated Physiological, Transcriptomic, and Proteomic Analyses Reveal the Regulatory Role of Melatonin in Tomato Plants' Response to Low Night Temperature.

Melatonin is a direct free radical scavenger that has been demonstrated to increase plants' resistance to a variety of stressors. Here, we sought to examine the effect of melatonin on tomato seedlings subjected to low night temperatures using an integrated physiological, transcriptomic, and proteomic approach. We found that a pretreatment with 100 µM melatonin increased photosynthetic and transpiration rates, stomatal apertures, and peroxidase activity, and reduced chloroplast damage of the tomato plant under a low night temperature. The melatonin pretreatment reduced the photoinhibition of photosystem I by regulating the balance of both donor- and acceptor-side restriction of PSI and by increasing electron transport. Furthermore, the melatonin pretreatment improved the photosynthetic performance of proton gradient regulation 5 (SlPGR5) and SlPGR5-like photosynthetic phenotype 1 (SlPGRL1)-suppressed transformants under a low night temperature stress. Transcriptomic and proteomic analyses found that the melatonin pretreatment resulted in the upregulation of genes and proteins related to transcription factors, signal transduction, environmental adaptation, and chloroplast integrity maintenance in low night temperature-stressed tomato plants. Collectively, our results suggest that melatonin can effectively improve the photosynthetic efficiency of tomato plants under a low night temperature and provide novel insights into the molecular mechanism of melatonin-mediated abiotic stress resistance.

Atractylon inhibits the tumorigenesis of glioblastoma through SIRT3 signaling.

Glioblastoma (GBM) is the most common primary malignant brain tumor. Although there are various treatments for glioblastoma including surgery, radiotherapy, systemic therapy (chemotherapy and targeted therapy) and supportive therapy, the overall prognosis remains poor and the long-term survival rate is very low. Atractylon, a bioactive compound extracted from the Chinese herb Atractylodes lancea (Thunb.) DC. or Atractylodes chinensis (DC.) Koidz., has been reported to induce apoptosis and suppress metastasis in hepatic cancer cells. However, the roles and mechanisms of atractylon in GBM cells remain unknown. In the present study, we aimed to evaluate the effects of atractylon on the anti-tumorigenesis properties of GBM. Firstly, results of CCK8, colony formation, cell proliferation, and flow cytometry assays showed that atractylon inhibited the proliferation of GBM cells by arresting cells at the G1 phase of cell cycle. In addition, atractylon suppressed the migration and induced apoptosis of GBM cells. Mechanistically, atractylon treatment caused a significant up-regulation of sirtuin 3 (SIRT3, a tumor suppressor) mRNA and protein in GBM cells. Furthermore, inhibition of SIRT3 by the selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP) partially restored the anti-proliferation and migration effects of atractylon in GBM cells. Finally, atractylon treatment also inhibited the in vivo growth of GBM cells in xenograft models through SIRT3 activation. Taken together, these results reveal a previously unknown role of atractylon in inhibiting GBM in vitro and in vivo through up-regulating SIRT3, which suggests novel strategies for the treatment of GBM.

Fraxinellone inhibits progression of glioblastoma via regulating the SIRT3 signaling pathway.

Glioblastoma (GBM) is the most prevalent type of adult primary brain tumor and chemotherapy of GBM was limited by drug-resistance. Fraxinellone is a tetrahydro-benzofuranone derivative with various pharmacological activities. However, the pharmacological effects of fraxinellone on GBM remains largely unknown. Here, we found that fraxinellone inhibited the proliferation and growth of GBM cells in a dose-dependent manner in vitro. Subsequently, we found that fraxinellone suppressed the migration and induced apoptosis of GBM cells in vitro. Using western blot and immunostaining, we further found that fraxinellone downregulated the expressions of sirtuin 3 (SIRT3), and superoxide dismutase 2 (SOD2), a downstream of SIRT3 in GBM cells. Meanwhile, reactive oxygen species (ROS) were increased in these fraxinellone-treated GBM cells. Interestingly, overexpression of SIRT3 (SIRT3-OE) indeed partially restored the inhibition of both cell proliferation and migration of GBM cells induced by fraxinellone. Finally, we found that fraxinellone could inhibit the growth of GBM in xenograft model through the inactivation of SIRT3 signaling pathway. Taken together, these results suggest that fraxinellone suppressed the growth and migration of GBM cells by downregulating SIRT3 signaling in vitro, and inhibited the tumorigenesis of GBMs in vivo.

A study on differences about the influencing factors of depressive symptoms between medical staff and residents during 2022 city-wide temporary static management period to fighting against COVID-19 pandemic in Shanghai.

Objectives: Our study aimed to identify the latent class of depressive symptoms in the Shanghai population during the city-wide temporary static management period and compare differences in the factors influencing depressive symptoms between medical staff and residents. Methods: An online cross-sectional survey was conducted with 840 participants using questionnaires, including Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Pittsburgh Sleep Quality Index (PSQI), and self-compiled questionnaire (demographic characteristics and internet usage time). Latent class analysis (LCA) was performed based on participants' depressive symptoms. The latent class subgroups were compared using the chi-square test and t-test. Logistic regression was used in our study to analyze the factors influencing depressive symptoms within the medical staff group and residents group and then compare their differences. Results: Two distinct subgroups were identified based on the LCA: the group with low-depressive symptoms and the group with high-depressive symptoms. There were significant differences between the two groups (P < 0.05) on age, education level, marital status, internet usage time, identity characteristics (medical staff or residents), family income level, living style, overall quality of sleep, and anxiety levels. Furthermore, logistic regression analysis results showed that compared with the residents group, the participants in the group of medical staff with "increasing internet usage time" and the "daytime dysfunction" would have nearly two times the possibility of getting serious depressive symptoms. Conclusions: There are differences in the factors influencing depression symptoms between medical staff and residents during the 2022 city-wide temporary static management period to fighting against the COVID-19 pandemic in Shanghai. We should pay special attention to those with increasing internet usage time and daytime dysfunction in medical staff working in a special environment such as the COVID-19 pandemic.

A study on the correlation between family dynamic factors and depression in adolescents.

Objectives: To evaluate the relationship between systemic family dynamics and adolescent depression. Methods: An offline survey was distributed to 4,109 students in grades 6-12, with the final analysis including 3,014 students (1,524 boys and 1,490 girls) aged 10-18 years. The questionnaire included the Self-Rating Scale of Systemic Family Dynamics (SSFD), the Self-Rating Depression Scale (SDS), and demographic characteristics. Results: Family dynamics were negatively correlated with depressive symptoms, with better family dynamics (high scores) associated with lower levels of depression based on the SDS score. After adjusting for sociodemographic characteristics, an ordinal multiclass logistic regression analysis identified family atmosphere (OR = 0.952, 95% CI: 0.948-0.956, p < 0.001) as the most important protective family dynamic against depression, followed by individuality (OR = 0.964, 95% CI: 0.960-0.968, p < 0.001). Latent class analysis (LCA) created the low family dynamic and high family dynamic groups. There were significant differences in the mean SDS scores between the two groups (45.52 ± 10.57 vs. 53.78 ± 11.88; p < 0.001) that persisted after propensity matching. Family atmosphere and individuation had a favorable diagnostic value for depression, with AUCs of 0.778 (95% CI: 0.760-0.796) and 0.710 (95% CI: 0.690-0.730), respectively. The diagnostic models for depression performed well. Conclusion: Poor family dynamics may be responsible for adolescent depression. A variety of early intervention strategies focused on the family may potentially avoid adolescent depression.

Single-cell RNA landscape of the osteoimmunology microenvironment in periodontitis.

Single-cell RNA sequencing (scRNA-seq) enables specific profiling of cell populations at single-cell resolution. The osteoimmunology microenvironment in the occurrence and development of periodontitis remains poorly understood at the single-cell level. In this study, we used single-cell transcriptomics to comprehensively reveal the complexities of the molecular components and differences with counterparts residing in periodontal tissues. Methods: We performed scRNA-seq to identify 51248 single cells from healthy controls (n=4), patients with severe chronic periodontitis (n=5), and patients with severe chronic periodontitis after initial periodontal therapy within 1 month (n=3). Uniform manifold approximation and projection (UMAP) were further conducted to explore the cellular composition of periodontal tissues. Pseudotime cell trajectory and RNA velocity analysis, combined with gene enrichment analysis were used to reveal the molecular pathways underlying cell fate decisions. CellPhoneDB were performed to identify ligand-receptor pairs among the major cell types in the osteoimmunology microenvironment of periodontal tissues. Results: A cell atlas of the osteoimmunology microenvironment in periodontal tissues was characterized and included ten major cell types, such as fibroblasts, monocytic cells, endothelial cells, and T and B cells. The enrichment of TNFRSF21+ fibroblasts with high expression of CXCL1, CXCL2, CXCL5, CXCL6, CXCL13, and IL24 was detected in patients with periodontitis compared to healthy individuals. The fractions of CD55+ mesenchymal stem cells (MSCs), APOE+ pre-osteoblasts (pre-OBs), and IBSP+ osteoblasts decreased significantly in response to initial periodontal therapy. In addition, CXCL12+ MSC-like pericytes could convert their identity into a pre-OB state during inflammatory responses even after initial periodontal therapy confirmed by single-cell trajectory. Moreover, we portrayed the distinct subtypes of monocytic cells and abundant endothelial cells significantly involved in the immune response. The heterogeneity of T and B cells in periodontal tissues was characterized. Finally, we mapped osteoblast/osteoclast differentiation mediators to their source cell populations by identifying ligand-receptor pairs and highlighted the effects of Ephrin-Eph signaling on bone regeneration after initial periodontal therapy. Conclusions: Our analyses uncovered striking spatiotemporal dynamics in gene expression, population composition, and cell-cell interactions during periodontitis progression. These findings provide insights into the cellular and molecular underpinning of periodontal bone regeneration.

Discriminative Feature Network Based on a Hierarchical Attention Mechanism for Semantic Hippocampus Segmentation.

The morphological analysis of hippocampus is vital to various neurological studies including brain disorders and brain anatomy. To assist doctors in analyzing the shape and volume of the hippocampus, an accurate and automatic hippocampus segmentation method is highly demanded in the clinical practice. Given that fully convolutional networks (FCNs) have made significant contributions in biomedical image segmentation applications, we propose a notably discriminative feature network based on a hierarchical attention mechanism in hippocampal segmentation. First, considering the problem that the hippocampus is a rather small part in MR images, we design a context-aware high-level feature extraction module (CHFEM) to extract high-level features of scale invariance in the encoder stage. Further, we introduce a hierarchical attention mechanism into our segmentation framework. The mechanism is divided into three parts: a low-level feature spatial attention module (LFSAM) is developed to learn the spatial relationship between different pixels on each channel in the low-level stage of the encoder, a high-level feature channel attention module (HFCAM) is to model the semantic information relationship on different channel images in the high-level stage of the encoder, and a cross-connected attention module (CCAM) is designed in the decoder part to further suppress the noisy boundaries of hippocampus and simultaneously utilize the attentional low-level features from the encoder to better guide the high-level hippocampus edge segmentation in the decoder phase. The proposed approach achieves outstanding performance on the ADNI dataset and the Decathlon dataset compared with other semantic segmentation models and existing hippocampal segmentation approaches. Source code is available at https://github.com/LannyShi/Hippocampal-segmentation.

A fast Fourier transform based method to estimate frequency response mismatches in time interleaved systems.

Time interleaving (TI) technique is widely used in acquisition systems to improve the sampling rate. However, as a parallel sampling structure, it inevitably brings in channel mismatches, such as the offset mismatch, gain mismatch, and time mismatch. Moreover, the gain mismatch and time mismatch are frequency-dependent, which means that the gain mismatch and time mismatch will be different when the signal frequency changes. This is because the gain and time mismatches are the special circumstances of frequency response mismatches. In this paper, a frequency response mismatch estimation method in TI acquisition systems is proposed and analyzed. First, the two kinds of mismatch models are compared to find the relationship between frequency response mismatches and the gain and time mismatches. Then, a mismatch estimation method that can estimate mismatches when the analog bandwidth exceeds the sampling rate of a single channel in a time interleaving analog to digital converter is proposed. Sinusoids with different frequencies are utilized to convert the question of estimating frequency response mismatches to acquiring the mismatch coefficients at a series of frequency points. Furthermore, a semi-automatic estimation technique is proposed to reduce the operation time, and a 10 GSPS eight-channel TI system is introduced. Simulations show the accuracy and effectiveness of the proposed method. At last, the frequency response mismatches are calibrated by using the estimated parameters. The calibration improves the performance of an eight-channel TI system from the original spurious free dynamic range of 27.6639 to 56.7029 dB and signal-to-noise ratio of 25.5468 to 32.7667 dB. The calibration result demonstrates the usefulness of the proposed method.

Abscisic acid and putrescine synergistically regulate the cold tolerance of melon seedlings.

Low temperature in early spring severely endangers the growth and development of melon seedlings. Abscisic acid (ABA) and polyamines (PAs) are important signal molecules in plant response to stress. However, the issue of whether they interact to regulate melon cold tolerance remains largely uncharacterized. Here, we identified a total of 14 key genes related to ABA and PAs biosynthesis, including four CmNCEDs, and ten genes in PA pathway (one CmADC, one CmODC, four CmSAMDCs, two CmSPDSs, and two CmSPAMs). Two oriental melon cultivars (IVF571, cold-tolerant; IVF004, cold-sensitive) were selected to explore the difference of ABA and PAs biosynthesis under cold stress (15 °C/6 °C, day/night). Results showed that the expressions of CmNCED3, CmNCED3-2, CmADC, CmSAMDCs, CmSPDS2 and CmSPMS1 were significantly up-regulated. ABA and putrescine levels were significantly increased in IVF571 under cold stress. Inhibiting the biosynthesis of endogenous ABA with nordihydroguaiaretic acid (NDGA) or Put with D-Arginine (D-Arg) dramatically decreased the levels of each other and aggravated the cold injury of melon seedlings. In addition, spraying with exogenous 75 µM ABA or 1 mM Put improved the activities of superoxide dismutase, catalase and ascorbate peroxidase, and reduced the membrane lipid peroxidation damage of melon seedlings under cold stress. In all, the higher cold tolerance of IVF571 seedlings than that of IVF004 seedlings might be related to the increase in ABA and Put levels triggered by cold stress. ABA and Put could regulate the biosynthesis of each other and might act as signals to trigger the antioxidant system, thereby increasing melon cold tolerance.