The OsMYC2-JA feedback loop regulates diurnal flower-opening time via cell wall loosening in rice.

Diurnal flower-opening time (DFOT), the time of spikelet opening during the day, is an important trait for hybrid rice (Oryza sativa L.) seed production. Hybrids between indica and japonica rice varieties have strong heterosis, but the parental lines usually have different, nonoverlapping DFOTs. This reduces the success of hybrid seed production in crosses between indica and japonica subspecies, thus hindering the utilization of indica and japonica inter-subspecies heterosis. However, little is known about the molecular mechanisms regulating DFOT in rice. Here, we obtained japonica rice lines with a DFOT 1.5 h earlier than the wild type by overexpressing OsMYC2, a gene encoding a key transcription factor in the jasmonate (JA) signaling pathway. OsMYC2 is activated by JA signaling and directly regulates the transcription of genes related to JA biosynthesis and cell wall metabolism. Overexpressing OsMYC2 led to significantly increased JA contents and decreased cellulose and hemicellulose contents in lodicule cells, as well as the softening of lodicule cell walls. This may facilitate the swelling of lodicules, resulting in early diurnal flower-opening. These results suggest that the OsMYC2-JA feedback loop regulates DFOT in rice via cell wall remodeling. These findings shed light on the understanding of regulatory mechanism of the DFOT of plants, which should promote the development of indica and japonica varieties suitable for hybrid rice breeding.

Controlling diurnal flower-opening time by manipulating the jasmonate pathway accelerates development of indica-japonica hybrid rice breeding.

Inter-subspecific indica-japonica hybrid rice (Oryza sativa) has the potential for increased yields over traditional indica intra-subspecies hybrid rice, but limited yield of F1 hybrid seed production (FHSP) hinders the development of indica-japonica hybrid rice breeding. Diurnal flower-opening time (DFOT) divergence between indica and japonica rice has been a major contributing factor to this issue, but few DFOT genes have been cloned. Here, we found that manipulating the expression of jasmonate (JA) pathway genes can effectively modulate DFOT to improve the yield of FHSP in rice. Treating japonica cultivar Zhonghua 11 (ZH11) with methyl jasmonate (MeJA) substantially advanced DFOT. Furthermore, overexpressing the JA biosynthesis gene OPDA REDUCTASE 7 (OsOPR7) and knocking out the JA inactivation gene CHILLING TOLERANCE 1 (OsHAN1) in ZH11 advanced DFOT by 1- and 2-h respectively; and knockout of the JA signal suppressor genes JASMONATE ZIM-DOMAIN PROTEIN 7 (OsJAZ7) and OsJAZ9 resulted in 50-min and 1.5-h earlier DFOT respectively. The yields of FHSP using japonica male-sterile lines GAZS with manipulated JA pathway genes were significantly higher than that of GAZS wildtype. Transcriptome analysis, cytological observations, measurements of elastic modulus and determination of cell wall components indicated that the JA pathway could affect the loosening of the lodicule cell walls by regulating their composition through controlling sugar metabolism, which in turn influences DFOT. This research has vital implications for breeding japonica rice cultivars with early DFOT to facilitate indica-japonica hybrid rice breeding.

Acutalibacter caecimuris sp. nov., Acutalibacter intestini sp. nov. and Neglectibacter caecimuris sp. nov., three novel species of the family Oscillospiraceae isolated from caecal contents of C57BL/6J mice.

The intestines of mice are colonized by diverse, as-yet-uncultivated bacteria. In this report, we describe the isolation, culture, genotypic and phenotypic characterization, as well as taxonomic classification of three novel anaerobic bacterial strains derived from the caecal contents of C57BL/6J male mice. According to the phenotypic and genotype-based polyphasic taxonomy, we propose three novel species within the family Oscillospiraceae. They are Acutalibacter caecimuris sp. nov. (type strain M00118T=CGMCC 1.18042T=KCTC 25739T), Acutalibacter intestini sp. nov. (type strain M00204T=CGMCC 1.18044T=KCTC 25741T) and Neglectibacter caecimuris sp. nov. (type strain M00184T=CGMCC 1.18043T=KCTC 25740T).

Examining multidimensional health poverty and determining factors among rural women of childbearing age in ningxia, china.

BACKGROUND: The multidimensional health poverty afflicting rural women of reproductive age bears profound implications for the sustainable development of families, societies, and healthy villages. Elucidating vulnerable groups at risk of multidimensional health poverty and delineating its determinants can inform refinements and implementation of health-poverty alleviation policies. METHODS: Based on the 2022 "Health Status and Health Service Utilization" survey data in rural Ningxia, China, this study analyzes the dimension of health status, capacity for health service utilization, health expenditure and security using the A-F dual-threshold method, logit model, and probit model. It comprehensively evaluates multidimensional health poverty and analyzes its determining factors among rural women of childbearing age. RESULTS: With k set at 0.3, the health multidimensional poverty index, incidence, and intensity among rural women of reproductive age were 0.021, 0.053, and 0.392, respectively. Chronic illness, capacity for free gynecological examination utilization, health examination utilization, and borrowing due to illness contributed significantly to multidimensional health poverty. Risk factors for multidimensional health poverty among rural women of childbearing age include age, unemployment, family size, and lack of sanitary toilets. Protective factors include being married, educational level, non-farm or student occupation, receiving government support, separate housing and kitchen, owning a television and computer. CONCLUSIONS: Even with the elimination of absolute poverty, the multidimensional health poverty situation among rural women remains important from a gender perspective. It is recommended to strengthen economic assistance and health service support for these groups, improve the level of rural health services from a gender perspective, and enhance housing structure and sanitation toilet usage in rural areas. Efforts should be made to narrow the digital divide in rural areas and promote digital health education. Pre-interventions on multidimensional health poverty can provide new pathways for the development, empowerment, and well-being of rural women of childbearing age.

Multiple aortic root pseudoaneurysms with dissecting aneurysm of the interventricular septum diagnosed by multimodal imaging.

Aortic root pseudoaneurysm is a devastating complication post aortic valve replacement with a high mortality rate. And dissecting aneurysm into the interventricular septum is a rare variant of aortic root pseudoaneurysm, which is scarcely reported. Multimodal imaging is of great value in its diagnosis and differential diagnosis.

Association between cooking with solid fuels and depressive symptoms among middle-aged and older adults in China: The mediating effect of the residential environment.

BACKGROUND: Depression is a common issue among elderly people in both developing and developed countries. Existing research indicates that cooking with solid fuels has a negative impact on the mental health of middle-aged and elderly people (aged 45 and older). However, the potential role of the residential environment in this process is not yet clear. Clarifying this issue may help identify effective interventions to improve public health for elderly people. This study aimed to explore the association between cooking with solid fuels and depressive symptoms, as well as the potential mediating role of the residential environment in this relationship. METHOD: This study utilized cross-sectional data from the China Health and Retirement Longitudinal Study (CHARLS) for 2020, involving approximately 19,000 respondents aged 45 years and older. Propensity score matching (PSM) was used to explore the association between cooking with solid fuels and depressive symptoms. Additionally, a range of potential covariates were adjusted, and the Sobel test was applied to assess the potential mediating effect of the residential environment on this relationship. RESULTS: According to the fully adjusted model, cooking with solid fuels was significantly associated with an increased risk of depressive symptoms in middle-aged and older adults (ß = 0.315, P < 0.001), and this finding was confirmed through robustness tests using different propensity score matching methods. Heterogeneity analysis revealed that this association was particularly significant among men (ß = 0.318, P < 0.001), those aged 60-74 (ß = 0.347, P < 0.001), and individuals with a middle school education (ß = 0.353, P < 0.001). Mediation effect analysis revealed that indoor cleanliness (ß = 0.0090, P < 0.001), indoor broadband coverage (ß = 0.0077, P < 0.001), and the installation of indoor air purifiers (ß = 0.0010, P < 0.1) mediated the relationships between cooking with solid fuels and depressive symptoms. CONCLUSION: Given the growing attention given to improving indoor environments and enhancing mental health, the findings of this paper highlight that improving indoor cleanliness, increasing broadband coverage indoors, and installing air purifiers can effectively intervene in and prevent depressive symptoms caused by cooking with solid fuels.

Paternal high-fat diet altered H3K36me3 pattern of pre-implantation embryos.

The global transition towards diets high in calories has contributed to 2.1 billion people becoming overweight, or obese, which damages male reproduction and harms offspring. Recently, more and more studies have shown that paternal exposure to stress closely affects the health of offspring in an intergenerational and transgenerational way. SET Domain Containing 2 (SETD2), a key epigenetic gene, is highly conserved among species, is a crucial methyltransferase for converting histone 3 lysine 36 dimethylation (H3K36me2) into histone 3 lysine 36 trimethylation (H3K36me3), and plays an important regulator in the response to stress. In this study, we compared patterns of SETD2 expression and the H3K36me3 pattern in pre-implantation embryos derived from normal or obese mice induced by high diet. The results showed that SETD2 mRNA was significantly higher in the high-fat diet (HFD) group than the control diet (CD) group at the 2-cell, 4-cell, 8-cell, and 16-cell stages, and at the morula and blastocyst stages. The relative levels of H3K36me3 in the HFD group at the 2-cell, 4-cell, 8-cell, 16-cell, morula stage, and blastocyst stage were significantly higher than in the CD group. These results indicated that dietary changes in parental generation (F0) male mice fed a HFD were traceable in SETD2/H3K36me3 in embryos, and that a paternal high-fat diet brings about adverse effects for offspring that might be related to SETD2/H3K36me3, which throws new light on the effect of paternal obesity on offspring from an epigenetic perspective.

Increased iron deposition in nucleus accumbens associated with disease progression and chronicity in migraine.

BACKGROUND: Migraine is one of the world's most prevalent and disabling diseases. Despite huge advances in neuroimaging research, more valuable neuroimaging markers are still urgently needed to provide important insights into the brain mechanisms that underlie migraine symptoms. We therefore aim to investigate the regional iron deposition in subcortical nuclei of migraineurs as compared to controls and its association with migraine-related pathophysiological assessments. METHODS: A total of 200 migraineurs (56 chronic migraine [CM], 144 episodic migraine [EM]) and 41 matched controls were recruited. All subjects underwent MRI and clinical variables including frequency/duration of migraine, intensity of migraine, 6-item Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS), and Pittsburgh Sleep Quality Index (PSQI) were recorded. Quantitative susceptibility mapping was employed to quantify the regional iron content in subcortical regions. Associations between clinical variables and regional iron deposition were studied as well. RESULTS: Increased iron deposition in the putamen, caudate, and nucleus accumbens (NAC) was observed in migraineurs more than controls. Meanwhile, patients with CM had a significantly higher volume of iron deposits compared to EM in multiple subcortical nuclei, especially in NAC. Volume of iron in NAC can be used to distinguish patients with CM from EM with a sensitivity of 85.45% and specificity of 71.53%. As the most valuable neuroimaging markers in all of the subcortical nuclei, higher iron deposition in NAC was significantly associated with disease progression, and higher HIT-6, MIDAS, and PSQI. CONCLUSIONS: These findings provide evidence that iron deposition in NAC may be a biomarker for migraine chronicity and migraine-related dysfunctions, thus may help to understand the underlying vascular and neural mechanisms of migraine. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT04939922.

Potential molecular targets and drugs for basement membranes-related intervertebral disk degeneration through bioinformatics analysis and molecular docking.

BACKGROUND: Through bioinformatics analysis to identify the hub genes of Intervertebral disc degeneration (IVDD) associated with basement membranes (BMs) and find out the potential molecular targets and drugs for BMs-related annulus fibrosus (AF) degeneration based on bioinformatic analysis and molecular approach. METHODS: Intervertebral disc degeneration (IVDD) related targets were obtained from GeneCards, DisGenet and OMIM databases. BMs related genes were obtained from Basement membraneBASE database. The intersection targets were identified and subjected to protein-to-protein interaction (PPI) construction via STRING. Hub genes were identified and conducted Gene ontology (GO) and pathway enrichment analysis through MCODE and Clue GO in Cytospace respectively. DSigDB database was retrieved to predict therapeutic drugs and molecular docking was performed through PyMOL, AutoDock 1.5.6 to verify the binding energy between the drug and the different expressed hub genes. Finally, GSE70362 from GEO database was obtained to verify the different expression and correlation of each hub gene for AF degeneration. RESULTS: We identified 41 intersection genes between 3 disease targets databases and Basement membraneBASE database. PPI network revealed 25 hub genes and they were mainly enriched in GO terms relating to glycosaminoglycan catabolic process, the TGF-ß signaling pathway. 4 core targets were found to be significant via comparison of microarray samples and they showed strong correlation. The molecular docking results showed that the core targets have strong binding energy with predicting drugs including chitosamine and retinoic acid. CONCLUSIONS: In this study, we identified hub genes, pathways, potential targets, and drugs for treatment in BMs-related AF degeneration and IVDD.

Implantable Electronic Medicine Enabled by Bioresorbable Microneedles for Wireless Electrotherapy and Drug Delivery.

A combined treatment using medication and electrostimulation increases its effectiveness in comparison with one treatment alone. However, the organic integration of two strategies in one miniaturized system for practical usage has seldom been reported. This article reports an implantable electronic medicine based on bioresorbable microneedle devices that is activated wirelessly for electrostimulation and sustainable delivery of anti-inflammatory drugs. The electronic medicine is composed of a radio frequency wireless power transmission system and a drug-loaded microneedle structure, all fabricated with bioresorbable materials. In a rat skeletal muscle injury model, periodic electrostimulation regulates cell behaviors and tissue regeneration while the anti-inflammatory drugs prevent inflammation, which ultimately enhance the skeletal muscle regeneration. Finally, the electronic medicine is fully bioresorbable, excluding the second surgery for device removal.

Deterministic factors modulating assembly of groundwater microbial community in a nitrogen-contaminated and hydraulically-connected river-lake-floodplain ecosystem.

The river-lake-floodplain system (RLFS) undergoes intensive surface-groundwater mass and energy exchanges. Some freshwater lakes are groundwater flow-through systems, serving as sinks for nitrogen (N) entering the lake. Despite the threat of cross-nitrogen contamination, the assembly of the microbial communities in the RLFS was poorly understood. Herein, the distribution, co-occurrence, and assembly pattern of microbial community were investigated in a nitrogen-contaminated and hydraulically-connected RLFS. The results showed that nitrate was widely distributed with greater accumulation on the south than on the north side, and ammonia was accumulated in the groundwater discharge area (estuary and lakeshore). The heterotrophic nitrifying bacteria and aerobic denitrifying bacteria were distributed across the entire area. In estuary and lakeshore with low levels of oxidation-reduction potential (ORP) and high levels of total organic carbon (TOC) and ammonia, dissimilatory nitrate reduction to ammonium (DNRA) bacteria were enriched. The bacterial community had close cooperative relationships, and keystone taxa harbored nitrate reduction potentials. Combined with multivariable statistics and self-organizing map (SOM) results, ammonia, TOC, and ORP acted as drivers in the spatial evolution of the bacterial community, coincidence with the predominant deterministic processes and unique niche breadth for microbial assembly. This study provides novel insight into the traits and assembly of bacterial communities and potential nitrogen cycling capacities in RLFS groundwater.

FGF-21 and GDF-15 are increased in migraine and associated with the severity of migraine-related disability.

BACKGROUND: Migraine is a prevalent disorder with significant socioeconomic impact. The impairment of metabolic homeostasis in migraine warrants further investigation. Changes in serum levels of Fibroblast-growth-factor 21 (FGF-21) and Growth-differentiation-factor 15 (GDF-15) are characteristic of some metabolic and mitochondrial diseases. This study aimed to assess whether the presence of migraine affects serum levels of FGF-21 and GDF-15, and taking metabolic disorders into account as potential confounding factors. METHODS: We collected serum samples from 221 migraine patients (153 episodic migraineurs and 68 chronic migraineurs) and 124 healthy controls. The serum concentrations of FGF-21 and GDF-15 were measured using an enzyme-linked immunosorbent assay (ELISA) based approach. Clinical variables, including monthly headache days, peak headache pain intensity, the 6-item Headache Impact Test (HIT-6), and the Migraine Disability Assessment (MIDAS), were also addressed. The associations between the clinical variables of migraine patients and serum levels of FGF-21 and GDF-15 were studied. RESULTS: In the multiple regression that corrected for age, we found that the serum levels of FGF-21 and GDF-15 were significantly higher in migraine sufferers than in healthy controls. A significant elevation in serum concentration of FGF-21, but not GDF-15, was observed in patients with chronic migraine (CM) compared to those with episodic migraine (EM). Regarding migraine-related disability, higher scores on the HIT-6 and MIDAS were associated with higher levels of FGF-21 and GDF-15. For the receiver operating characteristic (ROC) analysis, the diagnosis of migraine using GDF-15 showed that the area under the ROC curve (AUC) was 0.801 and the AUC of chronic migraine was 0.880. CONCLUSION: Serum GDF-15 and FGF-21 levels are increased in patients with migraine and associated with the severity of migraine-related disability.

Chromium-Doped Nickel Oxide and Nickel Nitride Mediate Selective Electrocatalytic Oxidation of Sterol Intermediates Coupled with H2 Evolution.

Replacing the oxygen evolution reaction (OER) with the thermodynamically favorable electrooxidation of organics is considered a promising approach for the simultaneous production of hydrogen (H2 ) and high-value chemicals. However, exploring and optimizing efficient electrocatalysts remains a challenge for large-scale production of value-added steroid carbonyl and H2 . Herein, Cr-NiO/GF and Cr-Ni3 N/GF (GF: graphite felt) electrocatalysts were designed as anode and cathode for the production of steroid carbonyls and H2 , respectively. The cooperative Cr-NiO and ACT (4-acetamido-2,2,6,6-tetramethyl-1-piperidine-N-oxyl) electrocatalyst can be extended to the electrooxidation of a series of steroid alcohols to the corresponding aldehydes. Additionally, Cr-Ni3 N displays superior electrocatalytic activity for hydrogen evolution reaction (HER), with a low overpotential of 35 mV to deliver 10 mA cm-2 . Furthermore, the system coupled with anodic electrooxidation of sterol and cathodic HER exhibited excellent performance with high space-time yield of 48.85 kg m-3 h-1 for steroid carbonyl and 1.82 L h-1 for H2 generation in a two-layer stacked flow cell. Density Functional Theory (DFT) calculations indicated that Cr doping effectively stabilizes ACTH on the NiO surface, and ACTH molecule could be captured via the ketonic oxygen interaction with Cr, resulting in excellent electrocatalytic activity. This work develops a novel approach to the rational design of efficient electrocatalysts for the simultaneous production of H2 and large-scale value-added pharmaceutical carbonyl intermediates.

Spatiotemporal Activation of Protein O-GlcNAcylation in Living Cells.

O-linked N-acetylglucosamine (O-GlcNAc) is a prevalent protein modification that plays fundamental roles in both cell physiology and pathology. O-GlcNAc is catalyzed solely by O-GlcNAc transferase (OGT). The study of protein O-GlcNAc function is limited by the lack of tools to control OGT activity with spatiotemporal resolution in cells. Here, we report light control of OGT activity in cells by replacing a catalytically essential lysine residue with a genetically encoded photocaged lysine. This enables the expression of a transiently inactivated form of OGT, which can be rapidly reactivated by photo-decaging. We demonstrate the activation of OGT activity by monitoring the time-dependent increase of cellular O-GlcNAc and profile glycoproteins using mass-spectrometry-based quantitative proteomics. We further apply this activation strategy to control the morphological contraction of fibroblasts. Furthermore, we achieved spatial activation of OGT activity predominantly in the cytosol. Thus, our approach provides a valuable chemical tool to control cellular O-GlcNAc with much needed spatiotemporal precision, which aids in a better understanding of O-GlcNAc function.

Primary cardiac composite hemangioendothelioma with calcification mimicking a right atrial myxoma: A rare entity.

Composite hemangioendothelioma (CHE) is a rare vascular tumor which shows varying combination of benign, low-grade, and malignant vascular components on pathology. CHE is usually located on the surface of the dermis and subcutaneous tissue of the extremities. We report an unusual case of CHE in the heart.

Unusual case of a right atrial inflammatory myofibroblastic tumor presenting with an episodic cyanosis in an infant.

Cardiac inflammatory myofibroblastic tumor (IMT) is a rare benign tumor that occurs mainly in infants and children. We report a case of right atrial IMT in a 1-month-old girl with episodic cyanosis. Both echocardiography and cardiac computed tomography revealed a right atrial mass. The patient underwent a complete surgical resection of the mass and the postoperative histological examination confirmed the diagnosis of cardiac IMT. The patient recovered well after the operation and further follow-up evaluation was uneventful.

Anomaly Detection in Satellite Telemetry Data Using a Sparse Feature-Based Method.

Anomaly detection based on telemetry data is a major issue in satellite health monitoring which can identify unusual or unexpected events, helping to avoid serious accidents and ensure the safety and reliability of operations. In recent years, sparse representation techniques have received an increasing amount of interest in anomaly detection, although its applications in satellites are still being explored. In this paper, a novel sparse feature-based anomaly detection method (SFAD) is proposed to identify hybrid anomalies in telemetry. First, a telemetry data dictionary and the corresponding sparse matrix are obtained through K-means Singular Value Decomposition (K-SVD) algorithms, then sparse features are defined from the sparse matrix containing the local dynamics and co-occurrence relations in the multivariate telemetry time series. Finally, lower-dimensional sparse features vectors are input to a one-class support vector machine (OCSVM) to detect anomalies in telemetry. Case analysis based on satellite antenna telemetry data shows that the detection precision, F1-score and FPR of the proposed method are improved compared with other existing multivariate anomaly detection methods, illustrating the good effectiveness of this method.

Influence of margin design and restorative material on the stress distribution of endocrowns: a 3D finite element analysis.

BACKGROUND: This study aimed to evaluate the stress distributions in endocrown restorations as applied to endodontically treated teeth (ETT), according to the factors of "margin design" (four levels) and "restorative material" (six levels). METHODS: Four 3D-finite elements models were constructed for endocrown restored molars considering different margin designs. Model A was prepared with a flat butt joint margin and received an endocrown with a 2.0-mm occlusal thickness. Model B was prepared with a 20° bevel margin and received an endocrown with a 2.0-mm occlusal thickness. Model C was prepared with an axial reduction and 1-mm shoulder margin and received an endocrown with a 2.0-mm occlusal thickness. Model D was prepared with an anatomic margin and received an endocrown with a 2.0-mm occlusal thickness. The following endocrown materials were used: In-Ceram Zirconia (Zr), Vita Suprinity (VS), IPS Empress (IE), Grandio blocs (GR), VisCalor bulk (VS), and CopraPeek Light (CP). The Load application (600 N) was performed at the food bolus and tooth surface during the closing phase of the chewing cycle. The results for the endocrown and tooth remnants were determined according to the von Mises stress. The failure risk of the cement layer was also calculated based on the normal stress criterion. RESULTS: Model D (with an anatomic margin) showed the greatest stress concentrations, especially in the irregular and sharp angles of the restoration and tooth remnants. The stress concentrated on the dentin was significantly lower in Model B with a 20° bevel margin (20.86 MPa), i.e., 1.3 times lower than the other three margin designs (27.80 MPa). Restorative materials with higher elastic moduli present higher stress concentrations inside the endocrown and transmit less stress to the cement layer, resulting in lower bonding failure risks. In contrast, materials with an elastic modulus similar to that of dentin presented with a more homogeneous stress distribution on the whole structure. CONCLUSIONS: An endocrown with a 20° bevel margin design could be a favorable preparation option for ETT. Composite resins (GR and VC) exhibit a more even stress distribution, and seem to be more promising materials for endocrown molars.

Optimal cuspal coverage of ceramic restorations using CAD/CAM: Biomechanical characteristic analysis by 3D finite element analysis and in vitro investigation.

AIM: The present in vitro study aimed to evaluate the stress distribution patterns, resistance to fracture, and failure modes of endodontically treated molars restored with different cuspal coverage options. MATERIALS AND METHODS: Three-dimensional models of mandibular first molars with six kinds of typical cuspal coverage were generated: T1: mesiobuccal cuspal coverage; T2: coverage of all buccal cusps; T3: mesiolingual cuspal coverage; T4: coverage of all lingual cusps; T5: mesiobuccal and mesiolingual cuspal coverage; T6: coverage of all cusps. All restorations were fabricated with zirconia-reinforced lithium silicate ceramic. The stress and its distributions under axial and oblique loading were analyzed by finite element analysis (FEA). Sixty human mandibular molar samples were randomly allocated into six groups (n = 10) to simulate the application of six types of restorations with different cuspal coverage, as in the FEA analysis, and were then subjected to a compressive test. All fractured specimens were subjected to fractography. Data were analyzed by one-way analysis of variance (ANOVA), the Tukey post hoc test, and the Fisher exact test (α = 0.05). RESULTS: The T2 and T6 groups presented superior stress distribution patterns under both axial and oblique loading compared with the other models. The fracture loads in the T2 (1627 ± 358 N) and T6 (1639 ± 355 N) groups were significantly higher than those in the other groups (P < 0.05). The T2 and T6 groups exhibited more restorable failure modes. Fractography showed more cracks below the cementoenamel junction in the T3, T4, and T5 groups. CONCLUSIONS: Onlay restorations with whole functional cuspal coverage provided comparable effects to coverage of all cusps in endodontically treated molars, and both methods exhibited a more even stress distribution and fracture resistance and better mechanical performance in high occlusal areas than other types of cuspal coverage. (Int J Comput Dent 2022;25(3):267-276; doi: 10.3290/j.ijcd.b2599709).

Differential and paradoxical roles of new-generation antidepressants in primary astrocytic inflammation.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are commonly used new-generation drugs for depression. Depressive symptoms are thought to be closely related to neuroinflammation. In this study, we used up-to-date protocols of culture and stimulation and aimed to understand how astrocytes respond to the antidepressants. METHODS: Primary astrocytes were isolated and cultured using neurobasal-based serum-free medium. The cells were treated with a cytokine mixture comprising complement component 1q, tumor necrosis factor α, and interleukin 1α with or without pretreatments of antidepressants. Cell viability, phenotypes, inflammatory responses, and the underlying mechanisms were analyzed. RESULTS: All the SSRIs, including paroxetine, fluoxetine, sertraline, citalopram, and fluvoxamine, show a visible cytotoxicity within the range of applied doses, and a paradoxical effect on astrocytic inflammatory responses as manifested by the promotion of inducible nitric oxide synthase (iNOS) and/or nitric oxide (NO) and the inhibition of interleukin 6 (IL-6) and/or interleukin 1ß (IL-1ß). The SNRI venlafaxine was the least toxic to astrocytes and inhibited the production of IL-6 and IL-1ß but with no impact on iNOS and NO. All the drugs had no regulation on the polarization of astrocytic A1 and A2 types. Mechanisms associated with the antidepressants in astrocytic inflammation route via inhibition of JNK1 activation and STAT3 basal activity. CONCLUSIONS: The study demonstrated that the antidepressants possess differential cytotoxicity to astrocytes and function differently, also paradoxically for the SSRIs, to astrocytic inflammation. Our results provide novel pieces into understanding the differential efficacy and tolerability of the antidepressants in treating patients in the context of astrocytes.