Single-cell RNA sequencing reveals the heterogeneity of epithelial cell and fibroblast cells from non- to metastatic lymph node OTSCC.

Lymph node metastasis (LNM) is one of the common features of oral tongue squamous cell carcinoma (OTSCC). LNM is also taken as a sign of advanced OTSCC and poor survival rate. Recently, single-cell RNA sequencing has been applied in investigating the heterogeneity of tumor microenvironment and discovering the potential biomarkers for helping the diagnosis and prognosticating. Pathogenesis of LNM in OTSCC remains unknown. Specifically, cancer-associated fibroblasts (CAFs) and epithelial tumor cells could foster the progression of tumors. Thus, in this study, we aimed to comprehensively analyze the roles of subpopulations of CAFs and epithelial tumor cells in lymph node metastatic OTSCC using the integration of OTSCC single-cell RNA sequencing datasets. Four distinct subtypes of CAFs, namely vascular CAFs, myofibroblast CAFs, inflammatory CAFs, and growth arrest CAFs were successfully discovered in LNM tumor and confirmed the roles of GAS and PTN pathways in the progression of tumor metastasis. In addition, NKAIN2+ epithelial cells and FN1+ epithelial cells specifically exhibited an upregulation of PTN, NRG, MIF, and SPP1 signaling pathways in the metastatic OTSCC. In doing so, we put forth some potential biomarkers that could be utilized for the purpose of diagnosing and prognosticating OTSCC during its metastatic phase and tried to confirm by immunofluorescence assays.

Two-Dimensional Transition Metal Phosphides As Cathode Additive in Robust Lithium-Sulfur Batteries.

The development of advanced cathode materials able to promote the sluggish redox kinetics of polysulfides is crucial to bringing lithium-sulfur batteries to the market. Herein, two electrode materials: namely, Zr2PS2 and Zr2PTe2, are identified through screening several hundred thousand compositions in the Inorganic Crystal Structure Database. First-principles calculations are performed on these two materials. These structures are similar to that of the classical MXenes. Concurrently, calculations show that Zr2PS2 and Zr2PTe2 possess high electrical conductivity, promote Li ion diffusion, and have excellent electrocatalytic activity for the Li-S reaction and particularly for the Li2S decomposition. Besides, the mechanisms behind the excellent predicted performance of Zr2PS2 and Zr2PTe2 are elucidated through electron localization function, charge density difference, and localized orbital locator. This work not only identifies two candidate sulfur cathode additives but may also serve as a reference for the identification of additional electrode materials in new generations of batteries, particularly in sulfur cathodes.

Revealing the Effect of Electronic Configuration in Cux Species on CO2 Photoreduction Characteristic Products.

As of the present time, the in-depth study of the structure-activity relationship between electronic configuration and CO2 photoreduction performance is often overlooked. Herein, a series of Cux species modified CeO2 nanodots are constructed in situ by flame spray pyrolysis (FSP) to achieve an efficient photocatalytic CO2-to-C2 conversion with an electron utilization of up to 142.5 µmol g-1. Through an in-depth study of the electronic behavior and catalytic pathways, it is found that the Cu0/Cu+ species in the coexistence state of Cu0/Cu+/Cu2+ can optimize the energy band structure, photocurrent stability, and provide a kinetic basis for the active surface catalytic reaction process that requires the conversion of multiple electrons into C2 products, which ultimately enhances the CO2-to-C2H6 photoreduction by 3.8-fold and that for CO2-to-C2H4 photoreduction by 5.2-fold. Besides, the Cu2+ species in the coexistence state of Cu0/Cu+/Cu2+ are able to regulate the electronic behavior and the choice of the catalytic pathway, enabling the transitions between CO2-to-C2H6 and CO2-to-C2H4. This work indicates that electronic configuration optimization is an effective strategy to significantly enhance the CO2 photoreduction performance and provides new ideas for the design and synthesis of high-performance heterostructure photocatalysts.

LY86 facilitates ox-LDL-induced lipid accumulation in macrophages by upregulating SREBP2/HMGCR expression.

LY86, also known as MD1, has been implicated in various pathophysiological processes including inflammation, obesity, insulin resistance, and immunoregulation. However, the role of LY86 in cholesterol metabolism remains incompletely understood. Several studies have reported significant up-regulation of LY86 mRNA in atherosclerosis; nevertheless, the regulatory mechanism by which LY86 is involved in this disease remains unclear. In this study, we aimed to investigate whether LY86 affects ox-LDL-induced lipid accumulation in macrophages. Firstly, we confirmed that LY86 is indeed involved in the process of atherosclerosis and found high expression levels of LY86 in human atherosclerotic plaque tissue. Furthermore, our findings suggest that LY86 may mediate intracellular lipid accumulation induced by ox-LDL through the SREBP2/HMGCR pathway. This mechanism could be associated with increased cholesterol synthesis resulting from enhanced endoplasmic reticulum stress response.

Streptococcus suis meningoencephalitis diagnosed with metagenomic next-generation sequencing: A case report with literature review.

Streptococcus suis is a pathogen of emerging zoonotic diseases and meningoencephalitis is the most frequent clinical symptom of S. suis infection in humans. Rapid diagnosis of S. suis meningoencephalitis is critical for the treatment of the disease. While the current routine microbiological tests including bacterial culture and gram staining are poorly sensitive, diagnosis of S. suis meningoencephalitis by metagenomic next-generation sequencing (mNGS) has been rarely reported. Here, we report a 52-year-old female pork food producer with a broken finger developed S. suis meningoencephalitis. After her admission, no pathogenic bacteria were detected through bacterial culture and Gram staining microscopy in the cerebrospinal fluid obtained via lumbar puncture. However, mNGS identified the presence of S. suis in the sample. mNGS is a promising diagnostic tool for rapid diagnosis of rare infectious diseases in the central nervous system.

Tablet-based tests of everyday visual function in a diabetic macular oedema (DME) clinic waiting area: A feasibility study.

PURPOSE: (1) To assess the feasibility of conducting tablet-based vision tests in hospital clinic waiting areas; (2) To test the hypothesis that increasing severity of diabetic macular oedema (DME) is associated with the performance of tablet-based surrogates of everyday tasks and self-reported visual function. METHODS: Sixty-one people with mild (n = 28), moderate (n = 24) or severe (n = 9) DME performed two tablet-based tests of 'real-world' visual function (visual search and face recognition) while waiting for appointments in a hospital outpatient clinic. Participants also completed a tablet-based version of a seven-item, visual-functioning (VF-7) patient-reported outcome measure. Test performance was compared to previously published 99% normative limits for normally sighted individuals. RESULTS: Thirty-four participants (56%; 95% confidence interval [CI] 43%-68%) exceeded normative limits for visual search, while eight (13%; 95% CI 65%-24%) exceeded normative limits for face discrimination. Search duration was significantly longer for people with severe DME than those with mild and moderate DME (p = 0.01). Face discrimination performance was not significantly associated with DME severity. VF-7 scores were statistically similar across DME severity groups. Median time to complete all elements (eligibility screening, both tablet-based tasks and the VF-7) was 22 (quartiles 19, 25) min. Further, 98% and 87% of participants, respectively, reported the search task and face discrimination task to be enjoyable, while 25% and 97%, respectively, reported finding the two tasks to be difficult. CONCLUSIONS: Portable tablet-based tests are quick, acceptable to patients and feasible to be performed in a clinic waiting area with minimal supervision. They have the potential to be piloted in patients' homes for self-monitoring.

Effect of botulinum toxin type A on muscular temporomandibular disorder: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Botulinum toxin type A (BTX-A) is increasingly used to manage painful temporomandibular disorders (TMD). However, the effect of BTX-A on muscular TMD remains unclear. OBJECTIVE: To assess the efficacy, safety and optimal dose of BTX-A for treating TMD. METHODS: We conducted systematic literature searches in MEDLINE, Embase, Web of Science, ClinicalTrials.gov and Cochrane Library until March 2023. We extracted data from randomized controlled trials (RCTs) that evaluated the efficacy and safety of BTX-A in treating muscular TMD. We performed a meta-analysis using a random-effects model. RESULTS: Fifteen RCTs involving 504 participants met the inclusion criteria. BTX-A was significantly more effective than placebo in reducing pain intensity, as measured on a 0-10 scale, at 1 month (MD [95% CI] = -1.92 [-2.87, -0.98], p < .0001) and 6 months (MD [95% CI] -2.08, [-3.19 to -0.98]; p = .0002). A higher dosage of BTX-A (60-100 U bilaterally) was associated with a greater reduction in pain at 6 months (MD [95% CI] = -2.98 [-3.52, -2.44]; p < .001). BTX-A also resulted in decreased masseter muscle intensity (µV) (MD [95% CI] = -44.43 [-71.33, -17.53]; p = .001) at 1 month and occlusal force (kg) at 3 months (MD [95% CI] = -30.29 [-48.22 to -12.37]; p = .0009). There was no significant difference in adverse events between BTX-A and placebo. CONCLUSIONS: BTX-A is a safe and effective treatment for reducing pain and improving temporomandibular muscle and joint function in muscular TMD patients. A bilateral dose of 60-100 U might be an optimal choice for treating muscular TMD pain.

Correlation between patient satisfaction and color changes after tooth bleaching.

OBJECTIVE: This study aimed to investigate the relationship between patient satisfaction of outcomes and tooth color changes during and after tooth bleaching. METHODS: In this clinical trial, 63 volunteers participated in an in-office bleaching procedure using a 40% hydrogen peroxide gel. The treatment consisted of two sessions, each comprising two 30-min applications of the bleaching gel. The L*, a*, and b* values of six maxillary anterior teeth were measured at baseline (T1), after the first bleaching session (T2), after the second bleaching session (T3), 1 week after the second in-office bleaching session (T4), and 3 weeks after the second in-office bleaching session (T5). The color differences (ΔE00 ) were calculated using CIEDE2000. A satisfaction scale with a score ranging from 0 to 3 was used to record participants' level of satisfaction with their tooth color at each time point. The data were statistically analyzed using repeated measures analysis of variance and logistic regression (α = 0.05). RESULTS: Significant correlations were observed between ΔL*, Δb*, and ΔE00 values at T3 and patient satisfaction (all p < 0.05). The regression model indicated a more pronounced impact of Δb* on patient satisfaction compared to ΔL*. The established regression models were as follows: Logit (PL*b* ) = -4.354 + 0.271ΔL* - 0.585Δb* and Logit (PΔE00 ) = -2.552 + 0.521ΔE00 . The findings suggested a minimum ΔE00 value of 4.90 for satisfactory results. A minimum ΔE00 value of 3.9, 5.0, and 6.8 was necessary for central incisors, lateral incisors, and canines, respectively, to achieve a satisfactory result. CONCLUSIONS: The ΔL*, Δb*, and ΔE00 values were found to be significantly correlated with patient satisfaction after bleaching. Δb* was identified as having a greater influence on patient satisfaction than ΔL* values in the regression model. Furthermore, attaining a minimum ΔE00 value of 4.90 is necessary to achieve satisfactory outcomes. A greater ΔE00 value is needed for canines than for incisors to achieve equivalent patient satisfaction. CLINICAL SIGNIFICANCE: This study emphasizes the importance of considering the extent of color change needed to achieve patient satisfaction after tooth bleaching procedures.

PSMC5 regulates microglial polarization and activation in LPS-induced cognitive deficits and motor impairments by interacting with TLR4.

Luteolin is a flavonoid found in high concentrations in celery and green pepper, and acts as a neuroprotectant. PSMC5 (proteasome 26S subunit, ATPase 5) protein levels were reduced after luteolin stimulation in activated microglia. We aimed to determine whether regulating PSMC5 expression could inhibit neuroinflammation, and investigate the underlying mechanisms.BV2 microglia were transfected with siRNA PSMC5 before the addition of LPS (lipopolysaccharide, 1.0 µg/ml) for 24 h in serum free DMEM. A mouse model of LPS-induced cognitive and motor impairment was established to evaluate the neuroprotective effects of shRNA PSMC5. Intracerebroventricular administration of shRNA PSMC5 was commenced 7 days prior to i.p. injection of LPS (750 µg/kg). Treatments and behavioral experiments were performed once daily for 7 consecutive days. Behavioral tests and pathological/biochemical assays were performed to evaluate LPS-induced hippocampal damage. Molecular dynamics simulation was used to confirm the interaction between PSMC5 and TLR4 (Toll-like receptor 4) in LPS-stimulated BV2 microglia. SiRNA PSMC5 inhibited BV2 microglial activation, and suppressed the release of inflammatory factors (IL-1ß, COX-2, PGE2, TNF-α, and iNOS) upon after LPS stimulation in BV2 microglia. LPS increased IκB-α and p65 phosphorylation, which was attenuated by siRNA PSMC5. Behavioral tests and pathological/biochemical assays showed that shRNA PSMC5 attenuated LPS-induced cognitive and motor impairments, and restored synaptic ultrastructure and protein levels in mice. ShRNA PSMC5 reduced pro-inflammatory cytokine (TNF-α, IL-1ß, PGE2, and NO) levels in the serum and brain, and relevant protein factors (iNOS and COX-2) in the brain. Furthermore, shRNA PSMC5 upregulated the anti-inflammatory mediators interleukin IL-4 and IL-10 in the serum and brain, and promoted a pro-inflammation-to-anti-inflammation phenotype shift in microglial polarization. Mechanistically, shRNA PSMC5 significantly alleviated LPS-induced TLR4 expression. The polarization of LPS-induced microglial pro-inflammation phenotype was abolished by TLR4 inhibitor and in the TLR-4-/- mouse, as in shRNA PSMC5 treatment. PSMC5 interacted with TLR4 via the amino sites Glu284, Met139, Leu127, and Phe283. PSMC5 site mutations attenuated neuroinflammation and reduced pro-inflammatory factors by reducing TLR4-related effects, thereby reducing TLR4-mediated MyD88 (myeloid differentiation factor 88)-dependent activation of NF-κB. PSMC5 could be an important therapeutic target for treatment of neurodegenerative diseases involving neuroinflammation-associated cognitive deficits and motor impairments induced by microglial activation.

Spontaneous spheroids from alveolar bone-derived mesenchymal stromal cells maintain pluripotency of stem cells by regulating hypoxia-inducible factors.

BACKGROUND: Spontaneous spheroid culture is a novel three-dimensional (3D) culture strategy for the rapid and efficient selection of progenitor cells. The objectives of this study are to investigate the pluripotency and differentiation capability of spontaneous spheroids from alveolar bone-derived mesenchymal stromal cells (AB-MSCs); compare the advantages of spontaneous spheroids to those of mechanical spheroids; and explore the mechanisms of stemness enhancement during spheroid formation from two-dimensional (2D) cultured cells. METHODS: AB-MSCs were isolated from the alveolar bones of C57BL/6 J mice. Spontaneous spheroids formed in low-adherence specific culture plates. The stemness, proliferation, and multi-differentiation capacities of spheroids and monolayer cultures were investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, alkaline phosphatase (ALP) activity, and oil-red O staining. The pluripotency difference between the spontaneous and mechanical spheroids was analyzed using RT-qPCR. Hypoxia-inducible factor (HIFs) inhibition experiments were performed to explore the mechanisms of stemness maintenance in AB-MSC spheroids. RESULTS: AB-MSCs successfully formed spontaneous spheroids after 24 h. AB-MSC spheroids were positive for MSC markers and pluripotency markers (Oct4, KLF4, Sox2, and cMyc). Spheroids showed higher Ki67 expression and lower Caspase3 expression at 24 h. Under the corresponding conditions, the spheroids were successfully differentiated into osteogenic and adipogenic lineages. AB-MSC spheroids can induce neural-like cells after neurogenic differentiation. Higher expression of osteogenic markers, adipogenic markers, and neurogenic markers (NF-M, NeuN, and GFAP) was found in spheroids than in the monolayer. Spontaneous spheroids exhibited higher stemness than mechanical spheroids did. HIF-1α and HIF-2α were remarkably upregulated in spheroids. After HIF-1/2α-specific inhibition, spheroid formation was significantly reduced. Moreover, the expression of the pluripotency genes was suppressed. CONCLUSIONS: Spontaneous spheroids from AB-MSCs enhance stemness and pluripotency. HIF-1/2α plays an important role in the stemness regulation of spheroids. AB-MSC spheroids exhibit excellent multi-differentiation capability, which may be a potent therapy for craniomaxillofacial tissue regeneration.

The current status of photoperiod adaptability in soybean.

Flowering represents the transition from vegetative stage to reproductive stage. As a photoperiod- sensitive crop, soybean can perceive changes in photoperiod to regulate flowering and reproductive periods, thereby influencing soybean yield and other agronomic traits, and determining the photoperiodic adaptability. Therefore, understanding the regulatory mechanisms of photoperiod on flowering and reproductive periods in soybean is one of the hotspots in soybean research. In this review, we introduce the molecular mechanisms of early flowering and early maturation during soybean domestication, and the molecular regulatory pathways of cultivated soybean expansion from the origin to high and low latitudes, respectively. At last, we summarize the research progress on photoperiod adaptability in wild soybean. Analyzing the regulatory mechanisms of photoperiod on soybean life history and domestication will provide valuable insights for the breeding of superior soybean varieties.

Dual Biosignal-Functional Injectable Microspheres for Remodeling Osteogenic Microenvironment.

Bone defect regeneration depends on the population and lifespan of M2 macrophages, which are regulated by dual signals generated by the "physical" spatial configuration of biological tissues and "molecular" chemokines. Herein, inspired by the reprogramming of macrophages, immunoengineered porous microspheres are constructed to accelerate bone repair through the regulation of both "physical" and "molecular" signals. The porous structure of injectable poly (l-lactic acid) (PLLA) microspheres prepared by the microfluidic technique provides a "physical signal" for osteogenic differentiation. Additionally, interleukin (IL)-4-loaded liposomes (Ls) are modified on PLLA microspheres through amide bonds to produce IL-4/Ls/PLLA microspheres, providing a "molecular signal" in stimulating the differentiation of macrophages to M2 type. It is confirmed that IL-4/Ls/PLLA microspheres could induce M2-macrophages polarization and potentiate osteoblast proliferation and differentiation while coculturing with macrophages and osteoblasts in vitro. Besides, IL-4/Ls/PLLA microspheres are proved to promote bone defect regeneration by inducing the conversion of M1 macrophages to M2 through dual biosignal-functional regulation in both the calvaria defect and maxillary sinus defect models. Overall, the immuno-reprogrammed IL-4/Ls/PLLA microspheres achieve the precise immuno-reprogramming of macrophages by dual biosignal-functional regulation. This immune reengineering strategy paves a way for clinical bone defect treatment.

Downregulation of LAPTM4B Contributes to the Impairment of the Autophagic Flux via Unopposed Activation of mTORC1 Signaling During Myocardial Ischemia/Reperfusion Injury.

RATIONALE: Impaired autophagic flux contributes to ischemia/reperfusion (I/R)-induced cardiomyocyte death, but the underlying molecular mechanisms remain largely unexplored. OBJECTIVE: To determine the role of LAPTM4B (lysosomal-associated transmembrane protein 4B) in the regulation of autophagic flux and myocardial I/R injury. METHODS AND RESULTS: LAPTM4B was expressed in murine hearts but downregulated in hearts with I/R (30 minutes/2 hours) injury and neonatal rat cardiomyocytes with hypoxia/reoxygenation (6 hours/2 hours) injury. During myocardial reperfusion, LAPTM4B-knockout (LAPTM4B-/-) mice had a significantly increased infarct size and lactate dehydrogenase release, whereas adenovirus-mediated LAPTM4B-overexpression was cardioprotective. Concomitantly, LAPTM4B-/- mice showed higher accumulation of the autophagy markers LC3-II (microtubule-associated protein 1A/1B-light chain 3), but not P62, in the I/R heart, whereas they did not alter chloroquine-induced further increases of LC3-II and P62 in both sham and I/R hearts. Conversely, LAPTM4B-overexpression had opposite effects. The hypoxia/reoxygenation-reduced viability of neonatal rat cardiomyocytes, ratio of autolysosomes/autophagosomes, and function of lysosomes were further decreased by LAPTM4B-knockdown but reversed by LAPTM4B-overexpression. Moreover, the LAPTM4B-overexpression-mediated benefits were abolished by knockdown of lysosome-associated membrane protein-2 (an autophagosome-lysosome fusion protein) in vivo and by the autophagy inhibitor bafilomycin A1 in vivo. In contrast, rapamycin (Rapa) successfully restored the impaired autophagic flux in LAPTM4B-/- mice and the subsequent myocardial I/R injury. Mechanistically, LAPTM4B regulated the activity of mTORC1 (mammalian target of rapamycin complex 1) via interacting with mTOR through its EC3 (extracelluar) domain. Thus, mTORC1 was overactivated in LAPTM4B-/- mice, leading to the repression of TFEB (transcription factor EB), a master regulator of lysosomal and autophagic genes, during myocardial I/R. The mTORC1 inhibition or TFEB-overexpression rescued the LAPTM4B-/--induced impairment in autophagic flux and I/R injury, whereas TFEB-knockdown abolished the LAPTM4B-overexpression-mediated recovery of autophagic flux and cardioprotection. CONCLUSIONS: The downregulation of LAPTM4B contributes to myocardial I/R-induced impairment of autophagic flux via modulation of the mTORC1/TFEB pathway. Graphic Abstract: A graphic abstract is available for this article.

Dihydroartemisinin alleviates AngII-induced vascular smooth muscle cell proliferation and inflammatory response by blocking the FTO/NR4A3 axis.

OBJECTIVE: Inflammation and proliferation of vascular smooth muscle cells (VSMCs), induced by angiotensin II (AngII) and other growth factors, play important roles in the pathogenesis of hypertension, restenosis, and atherosclerosis. Dihydroartemisinin (DHA) exhibits broad protective effects. However, the effects of DHA on AngII-induced inflammation and proliferation of VSMCs remain unknown. MATERIALS AND METHODS: AngII was used to construct VSMCs and vascular inflammation model in vitro and in vivo. The protective roles of DHA in inflammatory response and proliferation were evaluated through CCK-8, BrdU assay and immunofluorescence staining. The level of mRNA N6-methyladenosine was measured by m6A-RNA immunoprecipitation (MeRIP) assay. Western blot and quantitative real-time PCR were used to investigate the relationship between FTO and its potential downstream signaling molecules. RESULTS: In the present study, we found that DHA significantly suppressed AngII-induced proliferation of VSMCs and the expression of IL-6 and Ccl2 in a dose-dependent manner. Additionally, we confirmed that fat mass and obesity-associated (FTO) plays a critical role in AngII-induced VSMC proliferation and inflammation. FTO knockdown increased the methylation level of NR4A3 mRNA, whereas FTO, but not mutated FTO overexpression, reduced the methylation level of NR4A3 mRNA. These results suggest that DHA plays a protective role in AngII-induced VSMC proliferation and the associated inflammation by inhibiting the FTO/NR4A3 axis. CONCLUSION: Our findings provide new insight into the mechanisms of DHA and its critical role in the pathogenesis of hypertension-related vascular complications.

Palladium-Catalyzed Preparation of N-Substituted Benz[c,d]indol-2-imines and N-Substituted Amino-1-naphthylamides.

Here, we report a novel and facile protocol for the synthesis of benz[c,d]indol-2-imines via palladium-catalyzed C-C and C-N coupling of 8-halo-1-naphthylamines with isocyanides in a single step. The reaction features broad substrate scopes and mild conditions, providing an efficient alternative for the construction of antiproliferative agents and BET bromodomain inhibitors. If 0.1 mL of H2O was added to this reaction, the N-substituted amino-1-naphthylamides could be obtained easily.

A novel adiponectin receptor agonist (AdipoAI) ameliorates type 2 diabetes-associated periodontitis by enhancing autophagy in osteoclasts.

BACKGROUND AND OBJECTIVE: Type 2 diabetes (T2D)-associated periodontitis is severe and refractory in many cases. Considered an inflammatory disease, T2D predisposes to periodontitis by increasing whole-body inflammation. One mechanism of increased inflammation is thatT2D is mediated by loss of production or function of the anti-inflammatory hormone adiponectin. In our previous report, AdipoRon, an adiponectin receptor agonist, and AdipoAI, a newly discovered, more specific agonist, attenuated T2D-associated inflammation by inhibiting osteoclastogenesis and LPS-induced endotoxemia. Autophagy plays an important role during osteoclast differentiation and function. The impact of AdipoAI on osteoclast function and autophagy involved in osteoclastogenesis is not known. Here, we compare AdipoRon and AdipoAI potency, side effects and mechanism of action in T2D-associated periodontitis. METHODS: The RAW 264.7 cell line was used for in vitro studies. We analyzed the potential cytotoxicity of AdipoAI using the CCK-8 assay. The anti-osteoclastogenic potential of AdipoAI was studied by real-time qPCR and tartrate-resistant acid phosphatase staining. The actions of AdipoAI involved in autophagy were tested by real-time qPCR, western blot and immunofluorescence staining. In the diet-induced obesity model of T2D, we investigated the impact of AdipoAI on fasting blood glucose, alveolar bone loss, and gingival inflammation in mice with experimental periodontitis. RESULTS: AdipoRon inhibited osteoclastogenesis and AdipoAI inhibited osteoclastogenesis at lower doses than AdipoRon without any cytotoxicity. In DIO mice with experimental periodontitis, AdipoAI reduced mouse body weight in 14 days, reducing fasting glucose levels, alveolar bone destruction, osteoclast number along the alveolar bone surface, and decreased the expression of pro-inflammatory factors in periodontal tissues. AdipoAI and AdipoRon also enhanced LC3A/B expression when cultured with RANKL.3-Methyladenine, a known autophagy inhibitor, decreased LC3A/B expression and reversed the inhibition of osteoclastogenesis during AdipoAI treatment. CONCLUSIONS: Our results demonstrate that AdipoAI ameliorates the severity of T2D-associated periodontitis by enhancing autophagy in osteoclasts at lower doses than AdipoRon without demonstrable side effects. Thus, AdipoAI has pharmaceutical potential for treating diabetes-associated periodontal disease.

Drug-Coated Balloon Angioplasty Versus Standard Uncoated Balloon Angioplasty for Long Femoropopliteal Lesions: Post Hoc Analysis of the 24-Month Results of the AcoArt I Study.

OBJECTIVE: Restenosis is a common complication after endovascular treatment of peripheral artery disease. Drug-coated balloon (DCB) treatment has been proven safe and effective in reducing the rate of restenosis for simple and short lesions. However, the clinical results of DCBs for long lesions are still very limited. This study aimed to evaluate the efficacy and safety of DCBs in the treatment of long femoropopliteal artery disease. And the results of this study will also complement the existing evidence of DCB treatment of long lesions. METHODS: Patients with lesion length ≥ 15cm according to computed tomography angiography (CTA) or angiography in the AcoArt I Study were included into this study. Based on the balloon catheter used in treatment, patients were divided into the DCB group and the percutaneous transluminal angioplasty (PTA) group. The demographic, lesion, and procedural characteristics and 24-month follow-up results were compared between the 2 groups. The primary efficacy endpoints were angiographic late lumen loss (LLL) at 6 months or at the time of clinically driven target lesion revascularization (CD-TLR), primary patency (PP), freedom from CD-TLR, and changes in the ankle-brachial index (ABI) and Rutherford class during 24 months of follow-up. The safety endpoint was the occurrence of major adverse events. RESULTS: The total number of patients was 87, including 42 in the DCB group and 45 in the PTA group. There were no significant differences between the 2 groups in demographic, lesion,and procedural characteristics. The 6-month follow-up angiography showed that the LLL was significantly smaller in the DCB group than the PTA group (0.27 ± 0.90 mm vs 1.32 ± 0.91 mm; P < 0.001). At 24 months, compared with the PTA group, the DCB group had a significantly higher rate of freedom from CD-TLR (81.58% vs 43.18%; P < 0.001) and a significantly higher PP rate (46.88% vs 15.00%; P = 0.003). The DCB group had a significantly higher ABI than the PTA group at 6, 12, and 24 months (P < 0.001, P = 0.004 and P = 0.018, respectively). The DCB group had a better Rutherford class than the PTA group at 6 and 12 months (P = 0.033 and P = 0.012, respectively); the Rutherford class did not significantly differ between the 2 groups at 24 months (P = 0.127). The incidence of major adverse events did not significantly differ between the 2 groups. CONCLUSION: The effectiveness of the DCB is superior to a standard uncoated balloon in treating long lesions during 24 months of follow-up. Furthermore, the safety of the DCB is equivalent to that of PTA.

Early predictors of brain injury in patients with acute carbon monoxide poisoning and the neuroprotection of mild hypothermia.

INTRODUCTION: Carbon monoxide (CO) poisoning can cause serious neurological sequelae. However, there is neither effective treatment strategy nor reliable indicators to determine the prognosis of patients with CO poisoning. The present study aimed to observe the changes of neurological function score, disease severity score, cerebral oxygen utilization (O2UCc), bispectral (BIS) index and neuron-specific enolase (NSE) concentration, and to elucidate the clinical significance of these potential indicators and the neuroprotective effect of mild hypothermia on brain injury in patients with severe acute CO poisoning. MATERIALS AND METHODS: A total of 277 patients with acute severe CO poisoning from 2013 to 2018 were enrolled in our hospital. Patients were divided into three groups according to their body temperature on the day of admission and their willingness to treat: a fever group (n = 78), a normal temperature group (NT group, n = 113), and a mild hypothermia group (MH group, n = 86). All patients were given hyperbaric oxygen therapy, while those in the MH group received additional mild hypothermia treatment. The severity of the disease, the neurobehavioral status, the incidence of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP), and other indicators including BIS, O2UCc, NSE were further evaluated in all patients at given time-points. RESULTS: Mild hypothermia therapy improved the prognosis of patients with CO poisoning, significantly decreased the value of O2UCc and NSE, and up-regulated BIS. The incidence of DEACMP at 6 months was 27% in the fever group, 23% in the NT group, and 8% in the MH group. The values of Glasgow-Pittsburgh coma scale (G-P score), BIS index and NSE were closely related to the occurrence of DEACMP, the cutoff values were 12.41, 52.17 and 35.20 ng/mL, and the sensitivity and specificity were 79.3%, 77.6%, 79.3% and 67.6%, 89.5%, 88.6% in the receiver operating characteristic curve (ROC), respectively. CONCLUSIONS: Early mild hypothermia treatment could significantly reduce the severity of brain injury after CO poisoning, and might be further popularized in clinic. G-P scores, NSE and BIS index can be regarded as the prediction indicators in the occurrence and development of DEACMP. CLINICAL TRIAL REGISTRATION: The study protocol was granted from Qingdao University Research Ethics Committee (Clinical trial registry and ethical approval number: QD81571283).

Effectiveness of miniscrew-assisted rapid maxillary expansion: a systematic review and meta-analysis.

OBJECTIVES: To compare the effectiveness and side effects of miniscrew-assisted rapid maxillary expansion (MARME) with conventional rapid maxillary expansion (RME) in the treatment of transverse maxillary deficiency. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We searched in the MEDLINE, Embase, and Cochrane Central databases. The quality of included RCTs was evaluated using the Cochrane risk-of-bias tool. The primary outcome was the extent of dentoskeletal expansion achieved. Secondary outcomes were the dental and periodontal side effects. We calculated summary weighted mean differences (MD) with 95% confidence intervals (CI) using random-effects meta-analysis. RESULTS: Six RCTs involving 287 participants met the inclusion criteria. Compared to conventional RME, MARME was associated with a greater palatal suture opening (mm) measured at the anterior nasal spine (MD = 1.21, 95% CI 0.75 to 1.66), first premolars (MD = 1.13, 95% CI 0.72 to 1.55), first molars (MD = 1.18, 95% CI 0.28 to 2.09), and posterior nasal spine (MD = 1.14, 95% CI 0.30 to 1.98), increased palatal width (mm) at the first molars (MD = 0.75, 95% CI 0.30 to 1.20), and reduced buccal inclination (degrees) of the first premolars (MD = - 6.06, 95% CI - 10.36 to - 1.76) and first molars (MD = - 3.17, 95% CI - 5.35 to - 0.99). CONCLUSIONS: MARME is associated with the following advantages over traditional tooth-borne RME: increased palatal suture opening, increased palatal width, and reduced buccal tooth inclination. REGISTRATION: This study is registered with PROSPERO, CRD42021256750. CLINICAL RELEVANCE: MARME may be preferred over conventional RME in cases with fused mid-palatal sutures or where further buccal tooth inclination is undesirable.

Long-term safety and efficacy of angioplasty of femoropopliteal artery disease with drug-coated balloons from the AcoArt I trial.

OBJECTIVE: We evaluated the long-term safety and efficacy of treatment using drug-coated balloons (DCBs) in Chinese patients with severe femoropopliteal artery (FPA) disease (FPAD). METHODS: In this prospective, multicenter, randomized controlled trial, 200 Chinese patients with FPAD were prospectively randomized to undergo percutaneous transluminal angioplasty with a DCB or an uncoated balloon (UCB). The clinical endpoints were all-cause mortality, clinically driven target lesion revascularization, and major amputation of the treated leg within 5 years after treatment. RESULTS: During the 5-year follow-up period, freedom from all-cause mortality was 82.7% in the DCB group compared with 73.2% in the UCB group (log-rank P = .262). Freedom from clinically driven target lesion revascularization was 77.5% in the DCB group vs 59.1% in the UCB group (log-rank P < .001). No device- or procedure-related deaths occurred in either group. Cox regression analysis revealed that coronary heart disease and provisional FPA lesion stenting were associated with an increased mortality risk and the nominal paclitaxel dose was not associated with mortality during the 5-year follow-up period. CONCLUSIONS: We found no significant differences in 5-year mortality between patients with FPAD treated with DCBs vs UCBs. The clinical benefit of DCBs vs UCBs in terms of clinically driven target lesion revascularization persisted for the 5-year period.