Orosomucoid proteins limit endoplasmic reticulum stress in plants.

Sphingolipids are cell membrane components and signaling molecules that induce endoplasmic reticulum (ER) stress responses, but the underlying mechanism is unknown. Orosomucoid proteins (ORMs) negatively regulate serine palmitoyltransferase activity, thus helping maintain proper sphingolipid levels in humans, yeast, and plants. In this report, we explored the roles of ORMs in regulating ER stress in Arabidopsis thaliana. Loss of ORM1 and ORM2 function caused constitutive activation of the unfolded protein response (UPR), as did treatment with the ceramide synthase inhibitor Fumonisin B1 (FB1) or ceramides. FB1 treatment induced the transcription factor bZIP28 to relocate from the ER membrane to the nucleus. The transcription factor WRKY75 positively regulates the UPR and physically interacted with bZIP28. We also found that the orm mutants showed impaired ER-associated degradation (ERAD), blocking the degradation of misfolded MILDEW RESISTANCE LOCUS-O 12 (MLO-12). ORM1 and ORM2 bind to EMS-MUTAGENIZED BRI1 SUPPRESSOR 7 (EBS7), a plant-specific component of the Arabidopsis ERAD complex, and regulate its stability. These data strongly suggest that ORMs in the ER membrane play vital roles in the UPR and ERAD pathways to prevent ER stress in Arabidopsis. Our results reveal that ORMs coordinate sphingolipid homeostasis with ER quality control and play a role in stress responses.

Metformin promotes the osseointegration of titanium implants under osteoporotic conditions by regulating BMSCs autophagy, and osteogenic differentiation.

Osteoporosis is a common bone disorder with adverse effects on oral osseointegration, and the effects of metformin on bone metabolism have received increasing attention. The aim of the present study was to test the hypothesis that metformin promoted osteogenesis of bone mesenchymal stem cells (BMSCs) and osseointegration of titanium implants. BMSCs were treated with metformin to assess autophagic capacity, reactive oxygen species (ROS) production, anti-aging ability, and osteogenic differentiation. To determine its potential application in peri-implant of the maxilla, metformin was injected around the implant each day, immediately after the implant was embedded into the tooth socket. The results showed that metformin increased the autophagic capacity and decreased ROS production of osteoporotic BMSCs under hypoxia and serum deprivation (H/SD) culturing conditions. Metformin treatment significantly enhanced stemness properties and mineralized nodule formation, and increased the expression of osteogenic markers, including runt related transcription factor 2 (Runx2), osteocalcin (OCN), and alkaline phosphatase (ALP). Moreover, metformin substantially accelerated the formation of new bone, ameliorated the bone microarchitecture and promoted osseointegration of the dental implant. Collectively, metformin induces an osteogenic effect around the implant. Considering the widespread use of metformin, the results of the present study might promote a novel understanding of the positive effects of local metformin delivery on alveolar ridge defect, and have potential clinical application for the acceleration of osseointegration.

The transalveolar approach with the small segmentation method for inclined maxillary sinus floor elevation: A retrospective study.

OBJECTIVE: To evaluate the clinical outcome of the transalveolar approach with the small segmentation method for inclined maxillary sinus floor elevation. METHODS: Sixty-one patients with an inclined maxillary sinus floor (tilt angle ≥ 10°) and insufficient residual bone height in the posterior maxilla were included and grouped according to the tilt angle of the sinus floor, with group A having patients with the tilt angle ≥ 10° and ≤ 30° and group B having patients with the tilt angle > 30°. After completing sinus membrane elevation and bone augmentation using bone substitute materials, the implants were inserted at the same appointment, and the restoration was completed after 5-6 months of osseointegration. The preoperative sinus floor level and sinus floor elevation achieved postoperatively were assessed and recorded. At pre- and post-operative timepoints, the sagittal plane of the cone beam computed tomography was used to evaluate the bone height changes at the peak, middle and valley points in the slope segment intended for implant implantation. RESULTS: Osseointegration was evident in all 61 patients, and the final restoration was completed with functional loading. After assessing the normality and homogeneity of variance, two-sample t-test or nonparametric tests were employed to estimate the differences in the bone height changes. The degrees of freedom (df) for this analysis were 59. The elevation attained at the middle point in groups A and B were 6.71 ± 1.38 and 5.75 ± 1.56 mm, respectively, demonstrating a significant difference (p < 0.05). Furthermore, at the peak and valley points, group A exhibited bone height changes of 5.79 ± 1.74 and 6.06 ± 1.45 mm, respectively, compared to group B with changes measuring 4.63 ± 2.18 and 5.58 ± 2.39 mm, respectively, with no significant difference in the two groups (p ≥ 0.05). The prevalence of intraoperative sinus membrane perforation was assessed using the chi-square test. It was found that four cases in group A and five cases in group B experienced sinus membrane perforation, with no significant difference in the two groups (p ≥ 0.05, df = 1). CONCLUSION: The transalveolar approach using the small segmentation method suggests a promising approach for elevating the inclined maxillary sinus floor.

Arabidopsis Leaf Chloroplasts Have a Specific Sphingolipidome.

Sphingolipids are ubiquitous in eukaryotes and certain prokaryotes, where they serve as vital components of biological membranes and bioactive molecules. Chloroplasts have complex membrane structures that play crucial roles in photosynthesis, but their specific sphingolipidome remains unreported. In this study, we used liquid chromatography-mass spectrometry (LC-MS/MS) to analyze the sphingolipidome of purified Arabidopsis thaliana chloroplasts. We detected 92 chloroplast sphingolipids. The chloroplast sphingolipidome differed from total leaf (TL) samples, with a higher content of free long-chain bases and hydroxyceramides and a greater proportion of complex sphingolipids with 16C fatty acid (FA) forms. Notably, chloroplast glucosylceramides were predominantly the d18:1 h16:0 and t18:1 h16:0 forms rather than the 24C FA form found in TL and other cellular structures. Comparing the sphingolipidomes of different cellular structures underscores the inhomogeneity of the intracellular distribution of sphingolipids. This provides a robust reference for further elucidating the function of sphingolipids in plant cells.

Response of Human Gingival Fibroblasts and Porphyromonas gingivalis to UVC-Activated Titanium Surfaces.

Ultraviolet (UV) photofunctionalization has been demonstrated to synergistically improve the osteoblast response and reduce biofilm formation on titanium (Ti) surfaces. However, it remains obscure how photofunctionalization affects soft tissue integration and microbial adhesion on the transmucosal part of a dental implant. This study aimed to investigate the effect of UVC (100-280 nm) pretreatment on the response of human gingival fibroblasts (HGFs) and Porphyromonas gingivalis (P. g.) to Ti-based implant surfaces. The smooth and anodized nano-engineered Ti-based surfaces were triggered by UVC irradiation, respectively. The results showed that both smooth and nano-surfaces acquired super hydrophilicity without structural alteration after UVC photofunctionalization. UVC-activated smooth surfaces enhanced the adhesion and proliferation of HGFs compared to the untreated smooth ones. Regarding the anodized nano-engineered surfaces, UVC pretreatment weakened the fibroblast attachment but had no adverse effects on proliferation and the related gene expression. Additionally, both Ti-based surfaces could effectively inhibit P. g. adhesion after UVC irradiation. Therefore, the UVC photofunctionalization could be more potentially favorable to synergistically improve the fibroblast response and inhibit P. g. adhesion on the smooth Ti-based surfaces.

Cytotoxicity Induced by Black Phosphorus Nanosheets in Vascular Endothelial Cells via Oxidative Stress and Apoptosis Activation.

Black phosphorus (BP), an emerging two-dimensional material with unique optical, thermoelectric, and mechanical properties, has been proposed as bioactive material for tissue engineering. However, its toxic effects on physiological systems remain obscure. The present study investigated the cytotoxicity of BP to vascular endothelial cells. BP nanosheets (BPNSs) with a diameter of 230 nm were fabricated via a classical liquid-phase exfoliation method. Human umbilical vein endothelial cells (HUVECs) were used to determine the cytotoxicity induced by BPNSs (0.31-80 µg/mL). When the concentrations were over 2.5 µg/mL, BPNSs adversely affected the cytoskeleton and cell migration. Furthermore, BPNSs caused mitochondrial dysfunction and generated excessive intercellular reactive oxygen species (ROS) at tested concentrations after 24 h. BPNSs could influence the expression of apoptosis-related genes, including the P53 and BCL-2 family, resulting in the apoptosis of HUVECs. Therefore, the viability and function of HUVECs were adversely influenced by the concentration of BPNSs over 2.5 µg/mL. These findings provide significant information for the potential applications of BP in tissue engineering.

NAMPT/SIRT1 Expression Levels in White Blood Cells Differentiate the Different Rheumatoid Arthritis Subsets: An Inspiration from Traditional Chinese Medicine.

Background: Rheumatoid arthritis (RA) patients are prone to developing different metabolic complications. Traditional Chinese Medicine attributes this uncertainty to varied syndrome types. Methods and Results: We retrospectively analyzed some serological indicators of active RA patients and healthy individuals. Randomly selected RA patients were divided into three groups according to NAMPT and SIRT1 expression levels in white blood cells (WBCs). Their disease severity and metabolic status were compared. Representative blood samples were subjected to a UPLC-MS/MS-based metabolomics analysis. Different human WBCs were treated with oleic acid and palmitic acid in vitro. The results indicated that blood glucose and lipid levels were decreased in RA patients, but their decrease was not in accordance with disease severity. Nutrients in the patients highly expressing SIRT1 were well preserved, with the lowest levels of RF and ß-CTX and the highest levels of adiponectin and resistin. Most of them exhibited cold symptoms. When SIRT1 deficiency was obvious, lipid depletion became evident, irrespective of expression levels of NAMPT. Simultaneous high-expression of SIRT1 and NAMPT coincided with the increase in production of lactic acid and the prevalence of hot symptoms. Despite the low levels of IL-6, joint injuries were severe. The corresponding WBCs were especially sensitive to fatty acids anti-inflammatory treatments. The levels of CCL27, CCL11, CCL5, AKP, CRP and ESR were similar among all the groups. Conclusion: NAMPT overexpression is a risk factor for joint injuries and nutrient depletion in RA. Supplementation with lipids would exert beneficial effects on these RA patients. Its aftermath would cause even severe inflammation. Contrarily, SIRT1 up-regulation restrains inflammation and lipid depletion.

Alpha peak activity in resting-state EEG is associated with depressive score.

Introduction: Depression is a serious psychiatric disorder characterized by prolonged sadness, loss of interest or pleasure. The dominant alpha peak activity in resting-state EEG is suggested to be an intrinsic neural marker for diagnosis of mental disorders. Methods: To investigate an association between alpha peak activity and depression severity, the present study recorded resting-state EEG (EGI 128 channels, off-line average reference, source reconstruction by a distributed inverse method with the sLORETA normalization, parcellation of 68 Desikan-Killiany regions) from 155 patients with depression (42 males, mean age 35 years) and acquired patients' scores of Self-Rating Depression Scales. We measured both the alpha peak amplitude that is more related to synchronous neural discharging and the alpha peak frequency that is more associated with brain metabolism. Results: The results showed that over widely distributed brain regions, individual patients' alpha peak amplitudes were negatively correlated with their depressive scores, and individual patients' alpha peak frequencies were positively correlated with their depressive scores. Discussion: These results reveal that alpha peak amplitude and frequency are associated with self-rating depressive score in different manners, and the finding suggests the potential of alpha peak activity in resting-state EEG acting as an important neural factor in evaluation of depression severity in supplement to diagnosis.

Apatite-forming ability of sandblasted and acid-etched titanium surfaces modified by ultraviolet irradiation: An in vitro study.

INTRODUCTION: Contamination of large grit sandblasting and acid-etching (SLA) with hydrocarbons make the surface hydrophobic and influence its bioactivity. Preservation in dH2O (modified SLA, modSLA) and ultraviolet (UV) irradiation were proven to be effective in decreasing hydrocarbon contamination and keeping the SLA surface hydrophilic. AIMS: The aim of this study was to detect the in vitro bioactivity of SLA, modSLA and UV-SLA surfaces. DESIGN: The SBF model was used to compare the bone-like apatite forming ability. SETTING: The experiment was conducted at Southern Medical University. MATERIALS AND METHODS: The quantity of apatite was assessed by SEM and weighed on an electronic balance. The elemental composition and crystal phase were assessed by EDS and XRD analysis, respectively. RESULTS: The sediments that completely covered the modSLA and UV-SLA surfaces after 4 weeks of soaking reached 3.23 ± 0.35 mg and 2.13 ± 0.95 mg, respectively. They were eight- and five-fold than that on the SLA surface (0.43 ± 0.15 mg) with statistical significance (p < 0.05 and p < 0.01, respectively). EDS and XRD tests recognized the sediments on the modSLA and UV-SLA surfaces as apatite with similar elemental compositions, Ca/P ratios and crystal phases. DISCUSSION: Hydrophilicity and abundant hydroxyl groups drive modSLA and UV-SLA surfaces to absorb more Ca2+ to accelerate the formation of apatite. CONCLUSION: SLA preservation in dH2O and UV irradiation were recognized as trustworthy methods to acquire greater bioactivity of the SLA surface.

A chemometric modeling-free near infrared barcode strategy for smart authentication and geographical origin discrimination of Chinese ginseng.

With the growing interest in alternative medicine, handy identification and differentiation of herbal medicines are becoming increasingly important. Here we report a chemometric modeling-free near infrared (NIR) barcode strategy for the smart identification and geographical origin discrimination of Chinese ginseng. The novel strategy demands the transformation of Chinese ginseng (standard and sample) NIR spectra into a barcode representation through assigning zero intensity to every NIR peak except the peaks having intensities greater than average peak intensity. Meanwhile, for Chinese ginseng standard NIR barcode, barcoding condition such as padding size was carefully optimized. It has been demonstrated that the padding size for each bar in the barcode is 8 cm-1. By comparing the percentage of nonzero overlap between Chinese ginseng standard barcode and sample barcodes, eight batches of samples (including Chinese ginseng, American ginseng and counterfeit) were successfully identified with 100% accuracy, respectively. Interestingly, the discrimination of the origin of ginsengs from three provinces (Jilin, Liaoning and Heilongjiang) of Northeastern China was achieved utilizing NIR barcode method. Two characteristic bars at 7750 and 8250 cm-1 were inspected in the ginseng sample from Jilin province, two specific bars at 6780 and 7015 cm-1 were displayed in the ginseng sample from Liaoning province and three distinct bars at 6560, 6910 and 7995 cm-1 were monitored in the ginseng sample from Heilongjiang province. The results indicate that the proposed method will be greatly expanded and applied as an inspecting platform for the on-site analysis and valid identification of Chinese ginseng in herbal markets by a handheld spectrometer or barcode scanner.