Search

We synthesized Ca1−xSrxFeO3 containing tetravalent iron Fe4+ with high valence by low temperature heat treatment along with ozone oxidization. We investigated the magnetic properties of perovskite Ca1−xSrxFeO3. The charge disproportionation transition temperature (TCD) of Ca1−xSrxFeO3 was observed from x = 0.0 to 0.6 in the magnetic susceptibility measurements. The decrease in TCD occurs is attributed to deformation of the crystal structure. The metamagnetic transitions with hysteresis were observed in the magnetization curves of all the compositions. The metamagnetic behavior is due to helical magnetism, which means that there are intermediate stable states before magnetization is saturated. In the Sr-rich region with x = 0.8 and 1.0, the saturation magnetization shows forced ferromagnetic order with a value of ∼3.2 μB at high magnetic field, H ∼ 60 T.

Angiosarcoma (AS) is a malignant vascular neoplasm comprising neoplastic endothelial cells accounting for 1%-4% of soft tissue sarcomas. While lymphedema-associated and post-irradiation ASs are almost always driven by a high-level amplification of MYC (8q24), sporadic ASs, including those of breast parenchymal origin, typically lack MYC amplification. Here, we report a case of sporadic breast MYC-amplified AS in a 19-year-old female with no history of lymphedema or irradiation, who was referred to our hospital for an enlarging right breast mass. After needle biopsy, the patient underwent right mastectomy and axillary lymphadenectomy. Microscopically, atypical endothelial cells proliferated and formed well-defined or slit-like vascular channels that invaded and dissected the breast parenchymal fat, ducts, and lobules. In a limited area, the tumor cells showed solid sheet-like proliferation with increased mitotic figures of 40 per 2 mm 2 with a small area of necrosis. Immunohistochemical analysis revealed strong positivity for c-Myc. Fluorescence in situ hybridization (FISH) with MYC break-apart probes showed a high-level 5' single signal amplification. The patient was disease-free 16 months post-surgery. Nanopore sequencing successfully detected not only a high-level amplification of the 8q24 region, including MYC, but also multiple structural variants of the 8q24 region. In-depth analysis revealed extrachromosomal circular DNA amplification including the MYC protein-coding region and upstream region but not the downstream region. We also performed methylation classification using nanopore-based methylation data to successfully categorize the tumor as AS. This case report highlights the potential utility of nanopore sequencing in the diagnosis of sarcomas., (© 2024 Wiley Periodicals LLC.)

Myxoid liposarcoma (MLPS) is a rare sarcoma, typically arising in deep soft tissues during the fourth to fifth decades of life. Histologically, MLPS is composed of uniform oval cells within a background of myxoid stroma and chicken-wire capillaries. Genetically, MLPS is characterized by the FUS/EWSR1::DDIT3 fusion gene, which generally results from balanced interchromosomal translocation and is detectable via DDIT3 break-apart fluorescence in situ hybridization (FISH). Here, we report an unusual intra-articular MLPS case, negative for DDIT3 break-apart FISH but positive for EWSR1::DDIT3. An 18-year-old female was referred to our hospital complaining of an intra-articular mass in the right knee joint. Histologically, the tumor was mainly composed of mature adipocytes, brown fat-like cells, and lipoblasts. Nanopore sequencing detected DNA rearrangements between EWSR1 and DDIT3 and clustered complex rearrangements involving multiple chromosomes, suggesting chromoplexy. Methylation classification using random forest, t-distributed stochastic neighbor embedding, and unsupervised hierarchical clustering correctly classified the tumor as MLPS. The copy number was almost flat. The TERT promoter C-124T was also detected. This report highlights, for the first time, the potential value of a fast and low-cost nanopore sequencer for diagnosing sarcomas., (© 2024 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Functional mass spectrometry imaging (fMSI) is a potent tool for elucidating the spatial distribution of enzyme activities in tissues at high resolution. In this study, we applied fMSI to probe the intricate biosynthesis of phospholipids, which exist as thousands of molecular species in tissues and exhibit a unique distribution specific to cell type. By using deuterium- and 13 C-labeled substrates, we visualized the activities of key enzymes involved in phospholipid synthesis, including glycerol 3-phosphate acyltransferase (GPAT), lysophosphatidic acid acyltransferases (LPAAT), lysophospholipid acyltransferases (LPLAT), and long-chain acyl-CoA synthetase (ACSL). Additionally, we were able to visualize a two-step sequential enzyme reaction involving ACSL and LPLAT. This novel approach unveiled significant variations in enzyme activity distribution depending on the type of fatty acids used as substrates. It will also help to reveal the mechanisms underlying the formation of numerous phospholipid species.

Extracellular vesicles (EVs) are crucial for transferring bioactive materials between cells and play vital roles in both health and diseases. Cellular protrusions, including filopodia and microvilli, are generated by the bending of the plasma membrane and are considered to be rigid structures facilitating various cellular functions, such as cell migration, adhesion, and environment sensing. Compelling evidence suggests that these protrusions are dynamic and flexible structures that can serve as sources of a new class of EVs, highlighting the unique role they play in intercellular material transfer. Cytonemes are specialized filopodia protrusions that make direct contact with neighboring cells, mediating the transfer of bioactive materials between cells through their tips. In some cases, these tips fuse with the plasma membrane of neighboring cells, creating tunneling nanotubes that directly connect the cytosols of the adjacent cells. Additionally, virus particles can be released from infected cells through small bud-like of plasma membrane protrusions. These different types of protrusions, which can transfer bioactive materials, share common protein components, including I-BAR domain-containing proteins, actin cytoskeleton, and their regulatory proteins. The dynamic and flexible nature of these protrusions highlights their importance in cellular communication and material transfer within the body, including development, cancer progression, and other diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Hu, Nishimura, Kawana, Dante, D’Angelo and Suetsugu.)

An aneurysmal bone cyst (ABC) is a benign bone neoplasm that typically occurs during the first and second decades of life. ABC usually presents as a rapidly growing intramedullary expansile mass with multiple blood-filled cysts in the metaphysis of the long tubular bones. Here, we report a case of a periosteal solid ABC that was initially diagnosed as a high-grade surface osteosarcoma. A 10-year-old male was referred to our hospital for swelling and tenderness of the left upper arm. Radiography revealed periosteal mass without fluid-fluid levels. On performing open biopsy, the tumor showed hypercellular proliferation of uniform spindle to epithelioid cells with brisk mitotic activity (up to 12/2 mm 2 ) and lace-like osteoid formation, which was diagnosed as a high-grade surface osteosarcoma. After one course of chemotherapy using adriamycin and cisplatin, peripheral sclerosis was conspicuous, which led to pathological review and revision of diagnosis as "possibly osteoblastoma." The patient was disease-free for 4 years after marginal resection and curettage. Retrospective nanopore DNA sequencing unexpectedly detected a PAFAH1B1::USP6 rearrangement. The fusion gene was further validated using reverse transcription-polymerase chain reaction and the diagnosis was revised to ABC. Chromothripsis involving chromosome 17 has also been identified. Methylation analysis classified the present tumor as an ABC or non-ossifying fibroma using t-distributed stochastic neighbor embedding and unsupervised hierarchical clustering. This case report highlights the utility of nanopore DNA sequencing for soft tissue and bone tumor diagnosis., (© 2024 Wiley Periodicals LLC.)

Background: Dynamic navigation for implant placement is becoming popular under the concept of top-down treatment. The purpose of this study is to verify the accuracy of a dynamic navigation system for implant placement., Methods: Implant placement was performed on 38 patients using 50 implant fixtures. Patients in group C were treated using a conventional method, in which thermoplastic clips were fixed to the teeth, and patients in group M were treated using thermoplastic clips fixed to a mouthpiece attached to the teeth. The groups were compared to verify whether an accuracy difference existed. A treatment planning support program for dental implants was used to superimpose the postoperative computed tomography data on the preoperative implant design data to measure the entry point, apex point, and angular deviation., Results: The accuracy of group C was 1.36 ± 0.51 mm for entry point, 1.30 ± 0.59 mm for apex point, and 3.20 ± 0.74° for angular deviation. The accuracy of group M was 1.06 ± 0.31 mm for the entry point, 1.02 ± 0.30 mm for the apex point, and 2.91 ± 0.97° for angular deviation. Significant differences were observed in the entry and apex points between the two groups., Conclusions: The results indicate that group M exhibited better accuracy than group C, indicating that the stability of the thermoplastic clip is important for ensuring the accuracy of the dynamic navigation system. No previous studies have verified the accuracy of this system using the mouthpiece method, and additional data is required to confirm its accuracy for dental implant placement. The mouthpiece method improves the accuracy of implant placement and provides a safer implant treatment than the conventional method., Trial Registration: University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), Registration Number: UMIN000051949, URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view_his.cgi on August 21, 2023., (© 2024. The Author(s).)

Background: Proprioceptive impairment contributes to gait and balance impairments in patients with stroke. Diagnosis functional impairments and evaluation treatment efficacy require quantitative proprioception assessment. However, proprioception assessment has remained limited to ordinal scale measurement, with a lack of ratio scale measurements., Purpose: This case report describes a physiotherapy management program focusing on proprioceptive impairment in patients with stroke using quantitative tests such as Threshold to Detect Passive Motion (TDPM) and Joint Position Sense (JPS)., Case Description: A63-year-old male patient with an acute pontine lacunar infarction was admitted to our hospital. His muscle strength, selective movement, and trunk activity were preserved. However, the Berg Balance Scale (BBS) and Gait Assessment andIntervention Tool (GAIT) score were 42 and 9 points, observing balance impairment and the buckling knee pattern with hip ataxia during gait. Based on these, TDPM and JPS using image capture were performed. In physiotherapeuticdiagnosis, proprioceptive impairments in the hip and knee joints were the primary functional impairments related to balance and gait. To address these proprioceptive impairments, a 13-day treatment protocol incorporating transcutaneous electrical nerve stimulation (intensity: sensory threshold, frequency: 100 Hz) targeting the quadriceps femoris was performed., Outcomes: The patient was discharged after achieving independent ambulation and improvement in BBS (56 points) and GAIT (2 points) scores, exceeding the minimum clinically important difference. Recovery of proprioceptive impairment corresponded withimproved balance and gait ability., Conclusion: Quantitatively evaluating proprioceptive impairments may provide novel rehabilitation for patients with stroke who have proprioceptive impairments and contribute to clinical decision-making.

EWSR1::NFATC2 sarcoma, a rare round cell sarcoma constituting the majority of EWSR1::non-ETS sarcomas, has recently been defined in the latest WHO classification. To date, the cytological findings of EWSR1::NFATC2 sarcoma remain undocumented. We present the case of a 25-year-old man with a history of polyostotic fibrous dysplasia in the right leg, referred to our hospital with left thigh pain. Cytological findings included metachromasia, minimally pleomorphic round cells, and eosinophilic infiltration. There was no precursor fibrous dysplasia and the initial diagnosis was undifferentiated pleomorphic sarcoma. Following histologic review, we successfully performed immunocytochemistry and fluorescence in situ hybridization (FISH) on archival cytology specimens. The tumor cells were positive for NKX2-2, NKX3-1, and PAX7 and showed amplified 5' single signals of EWSR1 gene. Reverse transcriptase-polymerase chain reaction revealed an in-frame fusion of EWSR1 and NFATC2. This report describes the cytological features of EWSR1::NFATC2 sarcoma and highlights the diagnostic utility of archival cytology specimens., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Maxillary molars have low alveolar bone height diameter due to the presence of the maxillary sinus; thus, a sinus lift may be required in some cases. Changes in the volume of bone substitutes can affect the success of implant therapy. Therefore, this study aimed to compare the changes in the volume of two different bone substitutes-one based on carbonate apatite and the other on octacalcium phosphate-used in maxillary sinus floor elevation., Methods: Nineteen patients and 20 sites requiring maxillary sinus floor elevation were included in the study. Digital Imaging and Communications in Medicine data for each patient obtained preoperatively and immediately and 6 months postoperatively were used to measure the volume of the bone grafting material using a three-dimensional image analysis software. The immediate postoperative volume of octacalcium phosphate was 95.3775 mm 3 per piece of grafting material used. It was multiplied by the number of pieces used and converted to mL to determine the immediate postoperative volume., Results: The mean resorption values of carbonate apatite and octacalcium phosphate were 12.7 ± 3.6% and 17.3 ± 3.9%, respectively. A significant difference in the amount of resorption of the two bone replacement materials was observed (P = 0.04)., Conclusions: The results of this study indicate that both bone substitute materials tend to resorb. The two bone grafting materials that are currently medically approved in Japan have not been in the market for a long time, and their long-term prognosis has not yet been reported. Further clinical data are warranted., (© 2024. The Author(s).)

GPR34 is a recently identified G-protein coupled receptor, which has an immunomodulatory role and recognizes lysophosphatidylserine (LysoPS) as a putative ligand. Here, we report cryo-electron microscopy structures of human GPR34-G i complex bound with one of two ligands bound: either the LysoPS analogue S3E-LysoPS, or M1, a derivative of S3E-LysoPS in which oleic acid is substituted with a metabolically stable aromatic fatty acid surrogate. The ligand-binding pocket is laterally open toward the membrane, allowing lateral entry of lipidic agonists into the cavity. The amine and carboxylate groups of the serine moiety are recognized by the charged residue cluster. The acyl chain of S3E-LysoPS is bent and fits into the L-shaped hydrophobic pocket in TM4-5 gap, and the aromatic fatty acid surrogate of M1 fits more appropriately. Molecular dynamics simulations further account for the LysoPS-regioselectivity of GPR34. Thus, using a series of structural and physiological experiments, we provide evidence that chemically unstable 2-acyl LysoPS is the physiological ligand for GPR34. Overall, we anticipate the present structures will pave the way for development of novel anticancer drugs that specifically target GPR34., (© 2024. The Author(s).)

DPP-4 inhibitors are frequently used as first-line agents for the treatment of type 2 diabetes in Japan. This study aimed to examine the effects of vildagliptin on glucose metabolism and arterial stiffness. Twenty treatment-naïve patients with type 2 diabetes (8 males and 12 females) received vildagliptin 50 mg twice daily for 6 months. Self-monitored blood glucose measurements and a 75 g OGTT were performed. Arterial stiffness was assessed using the CAVI. After the vildagliptin treatment, a significant decrease in the median HbA1c (from 8.3 to 6.4%) and fasting HOMA-β (from 26.1 to 34.5%), and a marginally significant decrease in the CAVI (from 8.9 to 8.4, p = 0.087) were observed. The glycemic variability parameters also improved, whereas the insulin sensitivity and oxidative stress remained unchanged. Participants with a lower glycemic variability on the 75 g OGTT after vildagliptin treatment showed a significant decrease in their CAVI. The baseline BMI was significantly higher for the participants with a decreased CAVI than in those with no change in their CAVI (24.5 vs. 20.8 kg/m 2 ). After vildagliptin treatment, a decrease in the CAVI was observed, especially in the individuals with improved glycemic variability on the 75 g OGTT. Vildagliptin may be suitable for vascular protection in individuals with high glycemic variability and/or an elevated BMI.

Objectives: This study aimed to evaluate the prognostic treatment outcome of non-operative management of medication-related osteonecrosis of the jaw (MRONJ), particularly regarding the relationship between image findings and treatment outcomes., Methods: This single-center, retrospective observational study included patients with MRONJ who were conservatively treated between 2010 and 2020. All patients were evaluated in terms of MRONJ treatment outcomes, time to healing, and prognostic factors, including sex, age, underlying disease, antiresorptive drug type, discontinuation of antiresorptive treatment, chemotherapy, corticosteroid treatment, diabetes mellitus, location of MRONJ, clinical stage of MRONJ, and computed tomography image findings., Results: The complete healing rate among the patients was 68.5%. Cox proportional hazards regression analysis revealed that "Sequestrum formation" on the internal texture (hazard ratio = 3.66; 95% confidence interval, 1.30-10.29; P =.014) and chemotherapy (hazard ratio = 0.41; 95% confidence interval, 0.18-0.95; P =.037) were significantly associated with treatment outcome. The median time to healing in patients with "Sequestrum formation" on the internal texture (4.4 months) was significantly shorter than the median time to healing in those marked with "Sclerosis" or "Normal" (35.5 months; P <.001) and "Lytic changes with sclerosis" (14.5 months; P =.015)., Conclusions: The image findings on the internal texture of the lesions at the initial examination and chemotherapy were associated with the treatment outcomes of nonoperative management of MRONJ. The image findings of "Sequestrum formation" were associated with lesions taking a short time to heal and better outcomes, whereas "Sclerosis" and "Normal" were associated with lesions with longer healing times.

Skeletal muscle consists of both fast- and slow-twitch fibers. Phospholipids are important structural components of cellular membranes, and the diversity of their fatty acid composition affects membrane characteristics. Although some studies have shown that acyl chain species in phospholipids differ among various muscle fiber types, the mechanisms underlying these differences are unclear. To investigate this, we analyzed phosphatidylcholine (PC) and phosphatidylethanolamine (PE) molecules in the murine extensor digitorum longus (EDL; fast-twitch) and soleus (slow-twitch) muscles. In the EDL muscle, the vast majority (93.6%) of PC molecules was palmitate-containing PC (16:0-PC), whereas in the soleus muscle, in addition to 16:0-PC, 27.9% of PC molecules was stearate-containing PC (18:0-PC). Most palmitate and stearate were bound at the sn-1 position of 16:0- and 18:0-PC, respectively, and 18:0-PC was found in type I and IIa fibers. The amount of 18:0-PE was higher in the soleus than in the EDL muscle. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) increased the amount of 18:0-PC in the EDL. Lysophosphatidylglycerol acyltransferase 1 (LPGAT1) was highly expressed in the soleus compared with that in the EDL muscle and was upregulated by PGC-1α. LPGAT1 knockout decreased the incorporation of stearate into PC and PE in vitro and ex vivo and the amount of 18:0-PC and 18:0-PE in murine skeletal muscle with an increase in the level of 16:0-PC and 16:0-PE. Moreover, knocking out LPGAT1 decreased the amount of stearate-containing phosphatidylserine (18:0-PS), suggesting that LPGAT1 regulated the acyl chain profiles of phospholipids, namely, PC, PE, and PS, in the skeletal muscle., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Polylactic acid (PLA) has gained considerable attention as an alternative to petroleum-based materials due to environmental concerns. We fabricated implant models with fused filament fabrication (FFF) 3D printers using PLA, and the accuracies of these PLA models were compared with those of plaster models made from silicone impressions and resin models made with digital light processing (DLP). A base model was obtained from an impact-training model. The scan body was mounted on the plaster, resin, and PLA models obtained from the base model, and the obtained information was converted to stereolithography (STL) data by the 3D scanner. The base model was then used as a reference, and its data were superimposed onto the STL data of each model using Geomagic control. The horizontal and vertical accuracies of PLA models, as calculated using the Tukey-Kramer method, were 97.2 ± 48.4 and 115.5 ± 15.1 μm, respectively, which suggests that the PLA model is the least accurate among the three models. In both cases, significant differences were found between PLA and gypsum and between the PLA and resin models. However, considering that the misfit of screw-retained implant frames should be ≤150 µm, PLA can be effectively used for fabricating implant models.

Based on the hypothesis that the fabrication of dental models using fused deposition modeling and poly-lactic acid (PLA), followed by recycling and reusing, would reduce industrial waste, we aimed to compare the accuracies of virgin and recycled PLA models. The PLA models were recycled using a crusher and a filament-manufacturing machine. Virgin PLA was labeled R, and the first, second, and third recycles were labeled R1, R2, and R3, respectively. To determine the accuracies of the virgin and reused PLA models, identical provisional crowns were fitted, and marginal fits were obtained using micro-computed tomography. A marginal fit of 120 µm was deemed acceptable based on previous literature. The mesial, distal, buccal, and palatal centers were set at M, D, B, and P, respectively. The mean value of each measurement point was considered as the result. When comparing the accuracies of R and R1, R2, and R3, significant differences were noted between R and R3 at B, R and R2, R3 at P, and R and R3 at D ( p < 0.05). No significant difference was observed at M. This study demonstrates that PLA can be recycled only once owing to accuracy limitations.

Transient receptor potential (TRP) channels are activated by various extracellular and intracellular stimuli and are involved in many physiological events. Because compounds that act on TRP channels are potential candidates for therapeutic agents, a simple method for evaluating TRP channel activation is needed. In this study, we demonstrated that a transforming growth factor alpha (TGFα) shedding assay, previously developed for detecting G-protein-coupled receptor (GPCR) activation, can also detect TRP channel activation. This assay is a low-cost, easily accessible method that requires only an absorbance microplate reader. Mechanistically, TRP-channel-triggered TGFα shedding is achieved by both of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and 17 (ADAM17), whereas the GPCR-induced TGFα shedding response depends solely on ADAM17. This difference may be the result of qualitative or quantitative differences in intracellular Ca2+ kinetics between TRP channels and GPCRs. Use of epidermal growth factor (EGF) and betacellulin (BTC), substrates of ADAM10, improved the specificity of the shedding assay by reducing background responses mediated by endogenously expressed GPCRs. This assay for TRP channel measurement will not only facilitate the high-throughput screening of TRP channel ligands but also contribute to understanding the roles played by TRP channels as regulators of membrane protein ectodomain shedding., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tatsumi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose We considered the possibility of reducing industrial waste by fabricating and reusing dental models prepared using a fused deposition modeling (FDM) 3D printer and polylactic acid (PLA) filaments. The purpose of this study was to verify the accuracy of models fabricated using FDM and PLA.Methods The same provisional crown was used to check the marginal fit on PLA models prepared using an intraoral scanner (IOS) and FDM, plaster models made with silicone impression material and plaster, and resin models prepared using an IOS and stereolithography apparatus (SLA) 3D printer. The marginal fit was measured using micro-computed tomography at four points on the tooth: the buccal center (B), palatal center (P), mesial center (M), and distal center (D) points.Results At point B, the marginal gaps were 118 ± 21.7, 62 ± 16.4, and 50 ± 26.5 μm for the PLA, resin, and plaster models, respectively, with a significant difference between the PLA model and the other two. However, the marginal gap at all other measurement points was not significantly different between the models (P > 0.05).Conclusions We compared the accuracy of the models fabricated using the FDM, SLA, and conventional methods. The combination of FDM and PLA filaments showed no significant differences from the other models, except at point B, indicating its usefulness. Therefore, FDM and PLA may become necessary materials for dental treatment in the future.

Our group has reported various derivatives of lysophosphatidylserine (LysoPS) as potent and subtype-selective agonists for G-protein-coupled receptors (GPCRs). However, the ester linkage between the glycerol moiety and fatty acid or fatty acid surrogate is present in all of them. In order to develop these LysoPS analogs as drug candidates, appropriate pharmacokinetic consideration is essential. Here, we found that the ester bond of LysoPS is highly susceptible to metabolic degradation in mouse blood. Accordingly, we examined isosteric replacement of the ester linkage with heteroaromatic rings. The resulting compounds showed excellent retention of potency and receptor subtype selectivity, as well as increased metabolic stability in vitro.

Currently, implants are utilized clinically for bone transplant procedures. However, if infectious osteomyelitis occurs at implant sites, removal of bacteria can be challenging. Moreover, altered blood flow at peri-implant infectious sites can create an anaerobic environment, making it more difficult to treat infection with antibiotics. Thus, it would be beneficial if implants could be modified to exhibit antibacterial activity, even in anaerobic conditions. Here, we show antibacterial activity of silver ions coated on titanium rods, even against the anaerobic bacteria Porphyromonas gingivalis (P. gingivalis), both in vitro and in vivo. Specifically, we implanted silver-coated or control uncoated titanium rods along with P. gingivalis in mouse femoral bone BM cavities and observed significantly inhibited P. gingivalis infection with silver-coated compared with non-coated rods, based on in vivo bio-imaging. Osteonecrosis by infectious osteomyelitis and elevation of the inflammatory factors C-reactive protein and IL-6 promoted by P. gingivalis s were also significantly reduced in the presence of silver-coated rods. Overall, our study indicates that silver ion coating of an implant represents a therapeutic option to prevent associated infection, even in anaerobic conditions or against anaerobic bacteria., (© 2022. The Author(s).)

The fatty acid composition of phosphatidylethanolamine (PE) determines cellular metabolism, oxidative stress, and inflammation. However, our understanding of how cells regulate PE composition is limited. Here, we identify a genetic locus on mouse chromosome 11, containing two poorly characterized genes Tlcd1 and Tlcd2, that strongly influences PE composition. We generated Tlcd1/2 double-knockout (DKO) mice and found that they have reduced levels of hepatic monounsaturated fatty acid (MUFA)-containing PE species. Mechanistically, TLCD1/2 proteins act cell intrinsically to promote the incorporation of MUFAs into PEs. Furthermore, TLCD1/2 interact with the mitochondria in an evolutionarily conserved manner and regulate mitochondrial PE composition. Lastly, we demonstrate the biological relevance of our findings in dietary models of metabolic disease, where Tlcd1/2 DKO mice display attenuated development of non-alcoholic steatohepatitis compared to controls. Overall, we identify TLCD1/2 proteins as key regulators of cellular PE composition, with our findings having broad implications in understanding and treating disease., (© 2022. The Author(s).)

The main fatty acids at the sn-1 position of phospholipids (PLs) are saturated or monounsaturated fatty acids such as palmitic acid (C16:0), stearic acid (C18:0), and oleic acid (C18:1) and are constantly replaced, like unsaturated fatty acids at the sn-2 position. However, little is known about the molecular mechanism underlying the replacement of fatty acids at the sn-1 position, i.e., the sn-1 remodeling. Previously, we established a method to evaluate the incorporation of fatty acids into the sn-1 position of lysophospholipids (lyso-PLs). Here, we used this method to identify the enzymes capable of incorporating fatty acids into the sn-1 position of lyso-PLs (sn-1 lysophospholipid acyltransferase [LPLAT]). Screenings using siRNA knockdown and recombinant proteins for 14 LPLATs identified LPLAT7/lysophosphatidylglycerol acyltransferase 1 (LPGAT1) as a candidate. In vitro, we found LPLAT7 mainly incorporated several fatty acids into the sn-1 position of lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE), with weak activities toward other lyso-PLs. Interestingly, however, only C18:0-containing phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were specifically reduced in the LPLAT7-mutant cells and tissues from knockout mice, with a concomitant increase in the level of C16:0- and C18:1-containing PC and PE. Consistent with this, the incorporation of deuterium-labeled C18:0 into PLs dramatically decreased in the mutant cells, while deuterium-labeled C16:0 and C18:1 showed the opposite dynamic. Identifying LPLAT7 as an sn-1 LPLAT facilitates understanding the biological significance of sn-1 fatty acid remodeling of PLs. We also propose to use the new nomenclature, LPLAT7, for LPGAT1 since the newly assigned enzymatic activities are quite different from the LPGAT1s previously reported., Competing Interests: Conflict of Interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Several devices have been developed to measure implant-bone stability as an indicator of successful implant treatment; these include Osstell®, which measures the implant stability quotient (ISQ), and the more recent AnyCheck®, which relies on percussion for the implant stability test (IST). These devices make it possible to measure implant stability. However, no studies have compared the performance of AnyCheck® and Osstell® (i.e., IST and ISQ values) in clinical practice. Therefore, this study aimed to determine the correlation between primary and secondary implant stability using the Osstell® and AnyCheck® devices., Methods: Ten patients (7 women; age [mean ± standard deviation]: 49.1 ± 13.3 years) with partially edentulous jaws who received a total of 15 implants were included. IST (AnyCheck®) and ISQ (Osstell®) values were measured immediately after implantation and at 1, 2, 3, 4, and 6 weeks post-implantation. Each measurement was performed three times, and the average value was used as the result. The correlation between measurements obtained using the two devices was determined using Spearman's rank correlation coefficient., Results: The IST values ranged from 79.1 ± 2.87 to 82.4 ± 2.65. The ISQ values ranged from 76.0 ± 2.8 to 80.2 ± 2.35. Spearman's rank correlation coefficient was r = 0.64 immediately after implantation, r = 0.29 at 1 week, r = 0.68 at 2 weeks, r = 0.53 at 3 weeks, r = 0.68 at 4 weeks, and r = 0.56 at 6 weeks. A positive correlation was found in all cases, except at week 1 when the correlation was weak; the IST and ISQ values decreased the most during the first postoperative week and increased during the second week. The IST values were also slightly higher at all measurement points., Conclusion: The ability to assess implant stability without removing the abutment during healing is essential for determining the timing of loading without the risk of bone resorption. The results of this study suggest that AnyCheck® is useful for determining primary and secondary implant stability., (© 2022. The Author(s).)

Peroxygenases are promising catalysts for use in the oxidation of chemicals as they catalyze the direct oxidation of a variety of compounds under ambient conditions using hydrogen peroxide (H 2 O 2 ) as an oxidant. Although the use of peroxygenases provides a simple method for oxidation of chemicals, the anthraquinone process currently used to produce H 2 O 2 requires significant energy input and generates considerable waste, which negatively affects process sustainability and production costs. Thus, generating H 2 O 2 for peroxygenases on site using an environmentally benign method would be advantageous. Here, we utilized spent coffee grounds (SCGs) and tea leaf residues (TLRs) for the production of H 2 O 2 . These waste biomass products reacted with molecular oxygen and effectively generated H 2 O 2 in sodium phosphate buffer. The resulting H 2 O 2 was utilized by the bacterial P450 peroxygenase, CYP152A1. Both SCG-derived and TLR-derived H 2 O 2 promoted the CYP152A1-catalyzed oxidation of 4-methoxy-1-naphthol to Russig's blue as a model reaction. In addition, when CYP152A1 was incubated with styrene, the SCG and TLR solutions enabled the synthesis of styrene oxide and phenylacetaldehyde. This new approach using waste biomass provides a simple, cost-effective, and sustainable oxidation method that should be readily applicable to other peroxygenases for the synthesis of a variety of valuable chemicals., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Phospholipids in the membrane consist of diverse pairs of fatty acids bound to a glycerol backbone. The biological significance of the diversity, however, remains mostly unclear. Part of this diversity is due to lysophospholipid acyltransferases (LPLATs), which introduce a fatty acid into lysophospholipids. The human genome has 14 LPLATs and most of them are highly conserved in vertebrates. Here, we analyzed the function of one of these enzymes, lysophosphatidylglycerol acyltransferase 1 (Lpgat1), in zebrafish. We found that the reproduction of heterozygous (lpgat1 +/- ) male mutants was abnormal. Crosses between heterozygous males and wild-type females produced many eggs with no obvious cleavage, whereas eggs produced by crosses between heterozygous females and wild-type males cleaved normally. Consistent with this, spermatozoa from heterozygous males had reduced motility and abnormal morphology. We also found that the occurrence of lpgat1 homozygous (lpgat1 -/- ) mutants was far lower than expected. In addition, downregulation of lpgat1 by morpholino antisense oligonucleotides resulted in severe developmental defects. Lipidomic analysis revealed that selective phospholipid species with stearic acid and docosahexaenoic acid were reduced in homozygous larvae and spermatozoa from heterozygotes. These results suggest that the specific phospholipid molecular species produced by Lpgat1 have an essential role in sperm fertilization and in embryonic development., (© 2022. The Author(s).)

Signal transduction initiation by G-protein-coupled receptors (GPCRs) normally begins upon extracellular ligand binding. Some oncogenic GPCR mutants are capable of inducing G-protein signaling without ligand stimulation, thus behaving as constitutively active receptors. Evaluation of disease-causing capacity of constitutively active mutations in animal models requires months of time-consuming experiments, which hampers research progress. Here, using zebrafish embryos transiently expressing with constitutively active mutations via mRNA microinjection, we describe G-protein-subtype-specific phenotypes that can be evaluated over several days. Exogenous expression of the cysteinyl leukotriene receptor type II (CysLT 2 R) with an oncogenic L129 3.43 Q mutation by mRNA injection into a fertilized embryo induced developmental arrest during epiboly and eventual embryonic lethality, which were suppressed by treatment with the Gq inhibitor, YM-254890. Embryos with a constitutively active Gα q mutant exhibited an analogous phenotype. Interestingly, expression of constitutively active Gα s , Gα i , and Gα 13 mutants induced distinct phenotypes. These phenotypes may thus serve as useful indicators for rapid in vivo evaluation of signaling activity of GPCR and G-protein mutants., Competing Interests: Declaration of competing interest None to be declared., (Copyright © 2022 Elsevier Inc. All rights reserved.)