Uprighting horizontally impacted third molars by super-elastic nickel-titanium wire in patients with an extracted first molar.

Protracting lower second molars and uprighting horizontally impacted third molars is a significant orthodontic challenge in patients who require the extraction of severely decayed first molars. Here, we describe the use of biomechanics to upright 90°-tilted lower third molars following second molar protraction. Herein, we introduce a technique for uprighting the lower third molars by (1) the placement of superelastic nickel titanium archwires, (2) bonding, and (3) repositioning of a buccal tube in a tilted position to compensate for the efficiency of Ni-Ti (nickel-titanium) wire. The treatment mechanics used for our two cases showed that even severely impacted third molars can be uprighted by routine continuous straight-wire techniques. This technique proved to be a simple, efficient and reliable treatment option for uprighting horizontally impacted third molars.

Homogenizing Zn Deposition in Hierarchical Nanoporous Cu for a High-Current, High Areal-Capacity Zn Flow Battery.

A Zn anode can offset the low energy density of a flow battery for a balanced approach toward electricity storage. Yet, when targeting inexpensive, long-duration storage, the battery demands a thick Zn deposit in a porous framework, whose heterogeneity triggers frequent dendrite formation and jeopardizes the stability of the battery. Here, Cu foam is transferred into a hierarchical nanoporous electrode to homogenize the deposition. It begins with alloying the foam with Zn to form Cu5 Zn8 , whose depth is controlled to retain the large pores for a hydraulic permeability ≈10-11  m2 . Dealloying follows to create nanoscale pores and abundant fine pits below 10 nm, where Zn can nucleate preferentially due to the Gibbs-Thomson effect, as supported by a density functional theory simulation. Morphological evolution monitored by in situ microscopy confirms uniform Zn deposition. The electrode delivers 200 h of stable cycles in a Zn-I2 flow battery at 60 mAh cm-2 and 60 mA cm-2 , performance that meets practical demands.

MRAs may have lost their cornerstone position for heart failure treatment in the age of SGLT-2 inhibitors: A meta-analysis of randomized controlled trials.

Mineralocorticoid receptor antagonists (MRAs) are a cornerstone drug class for heart failure therapy. Several clinical studies have demonstrated its role in heart failure therapy. However, due to the recommendation of sodium-glucose cotransporter-2 (SGLT-2) inhibitors for the treatment of heart failure, there is a lack of sufficient evidence regarding whether MRAs can continue to play a cornerstone role in heart failure treatment. A meta-analysis was performed on subgroups of the DAPA-HF and EMPEROR-Reduced trials. Using trial-level data, we performed a meta-analysis to assess the effects of SGLT-2 inhibitors and MRAs on various clinical endpoints of heart failure. The incidence of cardiovascular-related death or heart failure hospitalization was the primary outcome. In addition, we assessed cardiovascular death, all-cause death, heart failure hospitalization, renal outcomes, and hyperkalemia. This study has already been registered with PROSPERO, CRD42022385023. Compared with SGLT-2 inhibitor monotherapy, combined treatment did not demonstrate more significant advantages in terms of heart failure or cardiovascular death (RR = 1.00; 95% CI: 0.78-1.28), cardiovascular death (RR = 0.96; 95% CI: 0.61-1.52), heart failure hospitalization (RR = 0.92; 95% CI: 0.79-1.07), all-cause death (RR = 1.00; 95% CI: 0.63-1.59) and composite kidney endpoint (RR = 0.85; 95% CI: 0.49-1.46). Moreover, in comparison to SGLT-2 inhibitors, combined therapy increased the risk of moderate-severe hyperkalemia (blood potassium > 6.0 mmol/l) (RR = 4.13; 95% CI: 2.23-7.65). In patients with HFrEF who have started MRAs treatment, the addition of an SGLT-2 inhibitor provides significant clinical benefit. However, the addition of MRAs to SGLT-2 inhibitors to treat heart failure is not essential.

Hypoxic preconditioned aged BMSCs accelerates MI injury repair by modulating inflammation, oxidative stress and apoptosis.

The benefits of autologous cell therapy for cardiac repair are diminished in aged individuals due to the limited quality and poor tolerance of aged stem cells in the ischemic micro-environment. The safe and efficient methods to improve the therapeutic effect of aged stem cells are needed to treat the increasing number of aged patients with cardiac diseases. In the present study, we aimed to determine whether hypoxic preconditioning can improve the therapeutic effect of aged stem cells even if the responsiveness of aged MSCs is poor, and to seek the underlying mechanism. Using a murine model of MI, our results showed that hypoxic preconditioning promoted the therapeutic effect of aged BMSCs, which was expressed in improved cardiac function, decreased scar size and alleviated cardiac remodeling in vivo. This in vivo effect of hypoxic preconditioned aged BMSCs was associated with alleviated inflammation, oxidative stress and apoptosis in infarcted heart. In vitro studies confirmed that hypoxic preconditioned aged BMSCs exert cytoprotective impacts on H9C2 cells against lethal hypoxia injury via attenuating oxidative stress and apoptosis. Our data support the promise of hypoxic preconditioning as a potential strategy to improve autologous stem cell therapy for ischemic heart injury in aged individuals.

Proteasome activation by insulin-like growth factor-1/nuclear factor erythroid 2-related factor 2 signaling promotes exercise-induced neurogenesis.

Physical exercise-induced enhancement of learning and memory and alleviation of age-related cognitive decline in humans have been widely acknowledged. However, the mechanistic relationship between exercise and cognitive improvement remains largely unknown. In this study, we found that exercise-elicited cognitive benefits were accompanied by adaptive hippocampal proteasome activation. Voluntary wheel running increased hippocampal proteasome activity in adult and middle-aged mice, contributing to an acceleration of neurogenesis that could be reversed by intrahippocampal injection of the proteasome inhibitor MG132. We further found that increased levels of insulin-like growth factor-1 (IGF-1) in both serum and hippocampus may be essential for exercise-induced proteasome activation. Our in vitro study demonstrated that IGF-1 stimulated proteasome activity in cultured adult neural progenitor cells (NPCs) by promoting nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), followed by elevated expressions of proteasome subunits such as PSMB5. In contrast, pretreating adult mice with the selective IGF-1R inhibitor picropodophyllin diminished exercise-induced neurogenesis, concurrent with reduced Nrf2 nuclear translocation and proteasome activity. Likewise, lowering Nrf2 expression by RNA interference with bilateral intrahippocampal injections of recombinant adeno-associated viral particles significantly suppressed exercise-induced proteasome activation and attenuated cognitive function. Collectively, our work demonstrates that proteasome activation in hippocampus through IGF-1/Nrf2 signaling is a key adaptive mechanism underlying exercise-related neurogenesis, which may serve as a potential targetable pathway in neurodegeneration.

NCOA4-mediated ferritinophagy promoted inflammatory responses in periodontitis.

BACKGROUND/OBJECTIVES: Iron homeostasis plays a crucial role in the combat against pathogen invasion. Ferrous iron can trigger generous production of reactive oxygen species (ROS) by Fenton reaction. Nuclear receptor coactivator 4 (NCOA4), a selective cargo receptor to deliver ferritin to lysosome, may trigger release of ferritin-bound iron into the cytosol. The aim of the present study was to explore whether NCOA4-mediated ferritinophagy participated in the pathogenesis of periodontitis, and its role in promoting the periodontal inflammation. METHODS: Inflamed and healthy periodontal tissues were harvested for immunobiological staining of ferritinophagy-related genes in the periodontal tissues, while real-time quantitative PCR (qPCR) was utilized to detect mRNA transcription. Periodontal ligament fibroblasts (PDLFs) were isolated and infected with Porphyromonas gingivalis. The mRNA transcription and protein expression of genes involved in the iron metabolism, including NCOA4, transferrin receptor 1 (TFR1), and ferroportin (SLC40A1) were detected by qPCR and western blot. Levels of labile iron pool and ROS production were detected by flow cytometry and confocal endoscopy. Small interference RNA was utilized to knock down NCOA4. RESULTS: Elevated expression of NCOA4, ferritin heavy chain, and light chain were observed in the diseased periodontal tissues. P. gingivalis infection promoted expression of TFR1, NCOA4, and microtubule-associated protein 1-light chain 3 B (LC3B), enhanced levels of intracellular labile iron pool and ROS production. NCOA4 knockdown reduced ROS generation in PDLFs in response to P. gingivalis and mitigated production of pro-inflammatory monocyte chemoattractant protein-1 and interleukin 6. P. gingivalis triggered activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase signaling pathway. In addition, inhibitors of JNK, SP600125, and inhibitors of p38, SB203580 blocked NCOA4 transcription. CONCLUSION: NCOA4-ferritinophagy participated in the progress of periodontitis progression. P. gingvalis-triggered ferritinophagy aggravated production of ROS and inflammatory responses in PDLFS. These findings suggest iron homeostasis plays an important role in the pathogenesis of periodontitis.

Comparative Analysis of Botrytis cinerea in Response to the Microbial Secondary Metabolite Benzothiazole Using iTRAQ-Based Quantitative Proteomics.

Benzothiazole is a microbial volatile compound with strong antifungal activity against the phytopathogenic fungus Botrytis cinerea, but its mode of action against fungi remains largely unknown. Understanding the molecular mechanisms underlying its activity could aid the design and synthesis of similar compounds against pathogenic fungi. Based on the results of morphological and antifungal activity assays, B. cinerea was exposed to 2.5 µl/liter of benzothiazole for 12, 24, and 48 h, and an isobaric tags for relative and absolute quantitation-based quantitative proteomic analysis showed that 378 out of 5,110 identified proteins were differentially expressed proteins (DEPs). The majority of these DEPs were associated with carbohydrate metabolism, oxidation reduction processes, and energy production. Further analysis showed that benzothiazole inhibited mitochondrial membrane organization and decreased the mitochondrial membrane potential of B. cinerea. In addition, the key enzymes of the glyoxylate cycle were downregulated after benzothiazole treatment, and a biochemical analysis indicated that inhibition of the glyoxylate cycle by benzothiazole blocked nutrient availability and interfered with adenosine triphosphate generation. This study provides markers for future research of the molecular responses of B. cinerea to benzothiazole stress.

Porphyromonas gingivalis triggers inflammatory responses in periodontal ligament cells by succinate-succinate dehydrogenase-HIF-1α axis.

Metabolic reprogramming from oxidative phosphorylation to glycolysis have been implicated in the pathogenesis of inflammatory diseases, such as pulmonary hypertension, rheumatoid arthritis and sepsis. Whether metabolic reprogramming participates in the progression of bacteriogenic periodontitis has never been reported. In the present study, we explored metabolic changes in periodontal ligament cells (PDLSCs) in response to Porphyromonas gingivalis. (P. gingivalis)-infected PDLSCs showed distinct metabolomics with metabolic reprogramming from oxidative phosphorylation to glycolysis. In addition, bacteria invasion triggered fundamental changes in glycolysis and tricarboxylate acid (TCA) cycle-related genes, such as the hexokinase (HK), isocitrate dehydrogenase (IDH) and succinate dehydrogenase (SDH). Moreover, P. gingivalis-infected PDLSCs showed accumulation of succinate, elevation in succinate dehydrogenase activity, pileup of reactive oxygen species and activation of hypoxia inducible factor-1α (HIF-1α) pathway. HIF-1α and succinate inhibitors, as well as SDH knockdown alleviated proinflammatory cytokine expression in P. gingivalis-infected PDLSCs. Therefore, targeting metabolic reprogramming by regulating the succinate-SDH-HIF-1α axis may facilitate host modulation therapy of chronic periodontitis.

miR-512-3p Overcomes Resistance to Cisplatin in Retinoblastoma by Promoting Apoptosis Induced by Endoplasmic Reticulum Stress.

BACKGROUND Retinoblastoma (RB) seriously endangers the vision and even the life of patients. This study aimed to explore the endoplasmic reticulum stress (ERS) and drug resistance of RB and verify the effect of miR-512-3p as a regulator of XBP-1 shearing mechanism on ERS, proliferation, apoptosis, and autophagy levels of RB cells. MATERIAL AND METHODS Y79, weri-RB1, and HXO-RB44 cells were treated with cisplatin (DDP) gradient concentration to construct DDP-resistant cells. The drug inhibition rate and cell proliferation were assessed by CCK-8 assay. The cell transfection and cell apoptosis were detected by RT-qPCR analysis and TUNEL assay, respectively. The protein expression was detected by Western blot analysis. Dual-luciferase reporter assay confirmed the combination of miR-512-30p and XBP-1 transcript 1/2. RESULTS DDP inhibition rates for DDP-resistant RB cells were lower than that for RB cells. The XBP-1 expression was increased in DDP-resistant RB cells, and Y79 cells were chosen for the subsequent experiments. After transfection, miR-512-3p overexpression obviously inhibited the proliferation of DDP-resistant Y79 cells (Y79/DDP cells). miR-512-3p overexpression increased the DDP inhibition rate for Y79/DDP cells and apoptosis of Y79/DDP cells. miR-512-3p overexpression downregulated the expression of LC3 II/I in Y79/DDP cells. The effect of miR-512-3p inhibition on Y79/DDP cells was not as obvious as the effect of miR-512-3p overexpression on Y79/DDP cells. Furthermore, miR-512-3p was confirmed to be combined with XBP-1 transcript variant 1. CONCLUSIONS miR-512-3p improved the DDP resistance of RB cells by promoting ERS-induced apoptosis and inhibiting the proliferation and autophagy of RB cells.

High-order mode conversion in a few-mode fiber via laser-inscribed long-period gratings at 1.55 µm and 2 µm wavebands.

We demonstrate high-order mode conversion in a few-mode fiber (FMF) via CO2 laser inscribed long-period fiber gratings (LPFGs) at both the 1.55 µm and 2 µm wavebands. At the 1.55 µm waveband, five high-order core modes (the LP11, LP21, LP02, LP31, and LP12 modes) can be coupled from the LP01 mode with high efficiency by the FMF-LPFGs. The orbital angular momentum beams with different topological charges (±1,±2,±3) are experimentally generated by adjusting the polarization controllers. At the 2 µm waveband, three high-order modes (the LP11, LP21, and LP02 mode) can be coupled by the FMF-LPFGs with different grating periods. The proposed LPFG-based mode converters could have a potential prospects in mode-division multiplexing and multiwindow broadband optical communication applications.

Torque expression by active and passive self-ligating brackets in patients with four premolar extractions: A retrospective study.

OBJECTIVE: Appropriate torque expression contributes to ideal treatment outcomes both clinically and aesthetically. Whether active and passive self-ligating brackets (SLBs) have different torque-control capability in vivo has never been reported. The purpose of present study was to explore whether there was difference in torque expression in active and passive SLBs. SETTING AND SAMPLE POPULATION: In this retrospective study, 225 patients with four first premolar extractions were enrolled. For each patient, the digital lateral cephalometric radiographs were taken before and after treatment. MATERIALS AND METHODS: The study consisted of 2 groups: 111 subjects were treated with passive SLBs (Damon Q, Ormco) and 114 subjects with active SLBs (Empower 2, American Orthodontics). Measurements to determine skeletal changes and incisor inclination were obtained from cephalometric tracings using Dolphin software (version 11.8, USA). Comparisons in both groups and intergroups were compared using t tests and chi-square test. RESULTS: Significant differences in the variation of U1-SN(°), U1-NA(°), L1-NB(°) and L1-FH(°) were found between two groups. More labially inclined maxillary incisors were found in active SLB group, while more labially inclined mandibular incisors were observed in passive SLB group. CONCLUSIONS: With the present prescription set in the two brackets, active SLBs achieved more proclined maxillary incisors and retroclined mandibular incisors. Clinicians should take torque expression of brackets into consideration during orthodontic treatment.

Erbin plays a critical role in human umbilical vein endothelial cell migration and tubular structure formation via the Smad1/5 pathway.

Angiogenesis is an important process in atherosclerosis. ErbB2 was proved to have an important role in vascular development, but it is still unclear whether Erbin expresses in vessels as well as its location and function in the vessels. In the current study, we investigated the location and function of Erbin in human umbilical veins. The human umbilical veins were prepared, and immunofluorescent analysis was performed to determine the expression of Erbin. Human umbilical vein endothelial cells (HUVECs) were cultured and the lentivirus (LV) containing Erbin RNAi was also prepared. After transfection with the lentivirus, CCK-8 assay and Annexin V-PI assay were used for cell proliferation and apoptosis, respectively. Cell migration was studied using the scratch wound healing assay and the transwell assay. The capillary-like tube formation assay was performed to illustrate the effect of Erbin on HUVEC tube formation. Expression of signaling pathway molecules was assessed with Western blot. The immunofluorescent analysis suggested that Erbin expressed in human umbilical veins and the majority of the Erbin is strongly colocalized in endothelial cells. Although knockdown of Erbin did not affect HUVEC proliferation and apoptosis, it significantly suppressed HUVEC migration and tubular structure formation. Erbin knockdown showed no effect on the ERK1/2 and Smad2/3 signaling pathways but significantly promoted Smad1/5 phosphorylation and nuclear translocation. Ablation of the Smad1/5 pathway decreased the effects of Erbin on endothelial cells. Erbin is mainly localized in endothelial cells in human umbilical veins and plays a critical role in endothelial cell migration and tubular formation via the Smad1/5 pathway.

Ultra-broadband fiber mode converter based on apodized phase-shifted long-period gratings.

We have demonstrated an ultra-broadband fiber mode converter based on CO2-laser inscribed length apodized phase-shifted long-period gratings (LPGs) with a three-section linear length apodization profile, where a π-phase shift was introduced between two adjacent grating sections. The grating parameters were optimized theoretically to achieve the broadband mode conversion between the LP01 mode and LP11 mode. The demonstrated device provides mode conversion efficiency higher than 90% over an ultra- broad bandwidth of ∼182nm. The insertion loss of the LPGs is negligible. Orbital angular momentum modes with left- and right-handed circular polarization can be generated from the demonstrated ultra-broadband mode converter successfully.

Broadband and low-loss mode scramblers using CO2-laser inscribed long-period gratings.

We demonstrate broadband and low-loss three-mode and six-mode scramblers employing CO2-laser inscribed long-period gratings (LPGs) for space-division multiplexing. Step-index (SI) few-mode fibers are used to avoid mode coupling to the cladding modes. We characterize the mode scramblers using a swept-wavelength interferometer. Mode-dependent loss (MDL) and modal transfer matrices over the C+L band are presented. Demonstrated LPGs with negligible MDL and low insertion loss contributed to high-performance CO2-laser inscription. The total MDLs induced by the SI fiber with LPGs in three-mode and six-mode scramblers are measured to be 2 and 4 dB, respectively.

Simultaneous directional curvature and temperature sensor based on a tilted few-mode fiber Bragg grating.

We demonstrate a directional curvature sensor based on tilted few-mode fiber Bragg gratings (FM-FBGs) inscribed by a UV laser. The eigenmodes of LP01 and LP11 mode groups are simulated along with the fiber bending. The directional curvature sensor is based on the LP11 mode resonance in the tilted FM-FBG. For curvature from 4.883 to 7.625 m-1, the curvature sensitivities at direction of 0° and 90° are measured to be -2.67 and 0.128 dB/m-1, respectively. The temperature variation barely affects the resonance depth of LP11 mode. The proposed curvature sensor clearly demonstrates the potential to simultaneous directional curvature and temperature measurement with the resolutions of 9.15×10-4 m-1 and 0.952°C, respectively.

Evaluation of bioactivity and control efficacy of tetramycin against Corynespora cassiicola.

Tetramycin is a novel polyene antibiotic that has exhibited excellent inhibitory activity against many plant pathogens. In this study, the sensitivity of Corynespora cassiicola to tetramycin was assessed in vitro using a series of 91 isolates, and its effects on hyphae and conidia were evaluated. Preventive and curative efficacies of tetramycin against Corynespora leaf spot were evaluated using detached cucumber leaves and potted cucumber plants. The control efficacy of tetramycin against the pathogen was also determined under field conditions. Measurement of baseline sensitivity suggested that the frequency distribution of tetramycin fits a unimodal curve. Among several life stages, spore germination was most severely inhibited by tetramycin, whereas mycelial growth was found to be the least sensitive. Microscopy observation revealed that tetramycin treatment leads to abnormal morphological development of C. cassiicola. Overall, tetramycin exhibited excellent curative and preventive activities against C. cassiicola on both cucumber leaves and potted cucumber plants. Furthermore, tetramycin significantly reduced the disease severity of Corynespora leaf spot in the field. The results from this study showed that tetramycin may play an important role in Corynespora leaf spot disease management and promote its introduction into fungicide-application programs.

Sublethal effects of chlorfenapyr on the life table parameters, nutritional physiology and enzymatic properties of Bradysia odoriphaga (Diptera: Sciaridae).

Bradysia odoriphaga (Diptera: Sciaridae) is the major pest affecting Chinese chive production. Chlorfenapyr is a halogenated pyrrole-based pro-insecticide that is currently used to control insects and mites on a variety of crops. In the present study, fourth-instar larvae of B. odoriphaga were exposed to chlorfenapyr at LC1, LC20 and LC50 concentrations. The developmental duration of the treated larvae was not significantly different, but fecundity was significantly increased in the LC1 and LC20 treatment groups compared with the control group. The population parameters of the LC1 treatment group were increased significantly, whereas those of the LC50 treatment group were reduced significantly compared with the control. The food consumption by larvae and pupal weight were significantly increased under the LC1 treatment and decreased under the LC50 treatment compared with the control. Moreover, chlorfenapyr decreased the lipid, carbohydrate and trehalose contents significantly, whereas the total protein content was increased compared with the control. Additionally, the activities of protease, lipase and trehalase were significantly decreased. Chlorfenapyr treatment for 24 h also induced the activities of glutathione S-transferase (GST), carboxylesterase (CarE) and O-demethylation. The results of this study suggest that low lethal concentrations of chlorfenapyr can affect oviposition, population development, the activities of digestion and detoxification enzymes, and nutrient accumulation in B. odoriphaga. This study provides valuable information for the assessment and rational application of chlorfenapyr for effective control of this pest.

Temperature-calibrated high-precision refractometer using a tilted fiber Bragg grating.

We present a refractometer with main- and vernier-scale to measure the refractive index (RI) of liquids with high precision by using the fine spectrum structure of a tilted fiber Bragg grating (TFBG). The absolute RI values are determined by the accurate wavelength of cut-off mode resonances. The main- and vernier-scale are calibrated by measuring large groups of fine spectra at different cut-off mode resonances in a small RI range, and the use of vernier-scale certainly reduces the RI measurement uncertainty resulted from the discrete cladding mode resonances. The performance of the TFBG-based vernier refractometer is experimentally verified by exploring the temperature dependence of RI of anhydrous ethanol in a near infrared region, showing an enhanced accuracy to the order of 10-4, high repeatability and temperature self-calibration capability.

Multi-channel mode converter based on a modal interferometer in a two-mode fiber.

In this Letter, we propose a multi-channel mode converter with the concept of a modal interferometer in a two-mode fiber (TMF). Two lateral stress points in a TMF function as in-line fiber mode couplers to construct the modal interferometer, and both transmission spectra and near-field patterns confirm that the LP01 mode is successfully converted into an LP11 mode at the multiple channels. The measured mode conversion efficiency almost completely follows the theoretical tendency. Finally, the mode conversion is realized at 20 channels in the C+L wavelength band with conversion efficiency up to 99.5% and insertion loss as low as 0.6 dB. Furthermore, the channel spacing can be freely tailored by adjusting the distance between two stress points.

All-fiber mode converter based on long-period fiber gratings written in few-mode fiber.

We investigated an all-fiber mode converter based on long-period fiber gratings (LPFGs) written in the few-mode fiber. Mode conversion between the fundamental core mode and different higher-order core modes (LP11, LP21, and LP02 modes) can be realized via a single LPFG with an efficiency of 99% at the resonance wavelength. Moreover, optimized mode conversion between the LP01 and LP21 modes can be realized by cascading two LPFGs with different grating pitches. The maximum conversion efficiency is estimated to be ∼99.5% at 1553 nm. The orbital angular momentum states with different topological charges (±1,±2) are demonstrated experimentally. The all-fiber LPFG mode converters could have promising applications in the mode-division multiplexing optical communications.