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Abstract Background Prosthetically guided orthodontics (PGO) can correct the malocclusion for better prosthetic rehabilitation in esthetic rehabilitation. Unlike conventional orthodontic treatment, only minor tooth movement is designed in PGO according to the requirement of subsequent restoration. For better appearance during the treatment, PGO is often performed with clear aligners, which have no metal brackets. It has been proven that the PGO with clear aligners can achieve generally satisfactory outcomes. However, its risk has not been fully known due to the paucity of relevant studies. Case presentation Three patients who needed esthetic rehabilitation with mild malocclusion were included in this study. After evaluation, a prosthetic solution alone was considered insufficient to provide optimal outcomes. Thus, they were treated using PGO with clear aligners (Invisalign Go, Align Technology, Santa Clara, California, USA) and accomplished prosthetic rehabilitation subsequently. Dental history and X-ray examination revealed that endodontically treated teeth (ETT) existed in all the cases. Intraoral photographs were collected to compare the pre-treatment and post-treatment dentition. After PGO, posterior ETT did not maintain their position as scheduled and lost occlusal contacts, while all the anterior teeth, including anterior ETT, were moved to the designed position. Corresponding prosthetic rehabilitation was used to solve it after consulting with the patients. Conclusions Occlusal contact loss of posterior ETT is a potential risk in PGO with clear aligners, affecting the orthodontic result.

Abstract The cementation of desert aeolian sand is a key method to control land desertification and dust storms, so an economical, green and durable process to reach the binding between sand grains needs to be searched. The method based on the microbially induced calcite precipitation (MICP) appeared in recent years as a promising process that proved its efficiency. The feasibility of the MICP technique to treat aeolian sand composed by low clay content, fine particles, low water content and characterized by weak permeability was demonstrated in the present paper. The effects of initial dry density, cementation number and curing time on the permeability and strength of MICP-treated aeolian sand were investigated using permeability tests and unconfined compressive strength (UCS) tests. The microstructure of aeolian sand was observed by scanning electron microscopy (SEM) tests and X-ray diffraction (XRD), aiming to reveal the solidification principle of MICP. The tests result indicated that when the initial dry density and the cementation number rose, the hydraulic conductivity of aeolian sand decreased while the mechanical strength given by UCS values improved. When the initial dry density was 1.65 g/cm3, the curing time was 3 h and the cementation number reached 20, the hydraulic conductivity and UCS reached 0.00151 cm/s and 1050.30 kPa, respectively. With increasing curing time, the hydraulic conductivity first decreased, followed by an increase, while the UCS exhibited an up and then a downtrend. Furthermore, the correlation between UCS values and the CaCO3 content reached a high R 2 value equal to 0.912, which confirmed that the cementation occurred in sandy material and governed the soil strengthening. Indeed, the calcium carbonate crystals observed by SEM and XRD enhanced the friction between particles when they wrapped around the sand grains surface, while carbonates reduced the soil permeability when filling the pores and sticking the sand particles together. Finally, the theoretical and scientific knowledge brought by the present study should help in managing sand in desert areas.

Abstract Background Widespread neuropathic pain usually affects a wide range of body areas and inflicts huge suffering on patients. However, little is known about how it happens and effective therapeutic interventions are lacking. Methods Widespread neuropathic pain was induced by partial infraorbital nerve transection (p-IONX) and evaluated by measuring nociceptive thresholds. In vivo/vitro electrophysiology were used to evaluate neuronal activity. Virus tracing strategies, combined with optogenetics and chemogenetics, were used to clarify the role of remodeling circuit in widespread neuropathic pain. Results We found that in mice receiving p-IONX, along with pain sensitization spreading from the orofacial area to distal body parts, glutamatergic neurons in the ventral posteromedial nucleus of the thalamus (VPMGlu) were hyperactive and more responsive to stimulations applied to the hind paw or tail. Tracing experiments revealed that a remodeling was induced by p-IONX in the afferent circuitry of VPMGlu, notably evidenced by more projections from glutamatergic neurons in the dorsal column nuclei (DCNGlu). Moreover, VPMGlu receiving afferents from the DCN extended projections further to glutamatergic neurons in the posterior insular cortex (pIC). Selective inhibition of the terminals of DCNGlu in the VPM, the soma of VPMGlu or the terminals of VPMGlu in the pIC all alleviated trigeminal and widespread neuropathic pain. Conclusion These results demonstrate that hyperactive VPMGlu recruit new afferents from the DCN and relay the extra-cephalic input to the pIC after p-IONX, thus hold a key position in trigeminal neuropathic pain and its spreading. This study provides novel insights into the circuit mechanism and preclinical evidence for potential therapeutic targets of widespread neuropathic pain.

Abstract Lipid nanoparticle-assisted mRNA inhalation therapy necessitates addressing challenges such as resistance to shear force damage, mucus penetration, cellular internalization, rapid lysosomal escape, and target protein expression. Here, we introduce the innovative “LOOP” platform with a four-step workflow to develop inhaled lipid nanoparticles specifically for pulmonary mRNA delivery. iLNP-HP08LOOP featuring a high helper lipid ratio, acidic dialysis buffer, and excipient-assisted nebulization buffer, demonstrates exceptional stability and enhanced mRNA expression in the lungs. By incorporating mRNA encoding IL-11 single chain fragment variable (scFv), scFv@iLNP-HP08LOOP effectively delivers and secretes IL-11 scFv to the lungs of male mice, significantly inhibiting fibrosis. This formulation surpasses both inhaled and intravenously injected IL-11 scFv in inhibiting fibroblast activation and extracellular matrix deposition. The HP08LOOP system is also compatible with commercially available ALC0315 LNPs. Thus, the “LOOP” method presents a powerful platform for developing inhaled mRNA nanotherapeutics with potential for treating various respiratory diseases, including idiopathic pulmonary fibrosis.

Abstract Background Nematodes are the most abundant and diverse metazoans on Earth, and are known to significantly affect ecosystem functioning. A better understanding of their biology and ecology, including potential adaptations to diverse habitats and lifestyles, is key to understanding their response to global change scenarios. Mitochondrial genomes offer high species level characterization, low cost of sequencing, and an ease of data handling that can provide insights into nematode evolutionary pressures. Results Generally, nematode mitochondrial genomes exhibited similar structural characteristics (e.g., gene size and GC content), but displayed remarkable variability around these general patterns. Compositional strand biases showed strong codon position specific G skews and relationships with nematode life traits (especially parasitic feeding habits) equal to or greater than with predicted phylogeny. On average, nematode mitochondrial genomes showed low non-synonymous substitution rates, but also high clade specific deviations from these means. Despite the presence of significant mutational saturation, non-synonymous (dN) and synonymous (dS) substitution rates could still be significantly explained by feeding habit and/or habitat. Low ratios of dN:dS rates, particularly associated with the parasitic lifestyles, suggested the presence of strong purifying selection. Conclusions Nematode mitochondrial genomes demonstrated a capacity to accumulate diversity in composition, structure, and content while still maintaining functional genes. Moreover, they demonstrated a capacity for rapid evolutionary change pointing to a potential interaction between multi-level selection pressures and rapid evolution. In conclusion, this study helps establish a background for our understanding of the potential evolutionary pressures shaping nematode mitochondrial genomes, while outlining likely routes of future inquiry.

ObjectivePhysical activity (PA) plays an important role in human health. However, the relationship between the PA and dysthyreosis was not clear. This study aimed to explore this question.MethodsWe performed a population-based study on the basis of the participant’s information that was collected from the National Health and Nutrition Examination Survey (NHANES) database. The association of the thyroid hormone and total PA metabolic equivalent task (MET) were assessed via linear regression analysis with adjusting for different covariates. Moreover, we also used path analysis to explore the causality between PA, thyroid hormone index, and dysthyreosis. The restricted cubic spline analysis was used to explore the non-linear relationship between the thyroid hormone index and the PA total MET.ResultsA total of 2118 participants aged≥20, including 969 females and 1149 males, were collected from NHANES. The linear regression with multivariate adjustment suggested a linear relationship between the PA total MET and Thyroid-Stimulating Hormone Index (TSHI), and Thyroid Feedback Quantile-Based Index (TFQI), respectively. And TFQI and dysthyresis occurrence were significantly correlated (P

Abstract In this study, the mass balance, pharmacokinetics (PK) and metabolism of atuliflapon, a novel 5‐lipoxygenase‐activating protein inhibitor, were investigated in healthy male subjects. A single oral dose of 200 mg [14C]atuliflapon suspension was administered to six healthy male subjects. Mass balance, PK and metabolite profiles of atuliflapon were analyzed using radioactivity monitoring and liquid chromatography with mass spectrometry analysis. The safety of atuliflapon was assessed during the study. Atuliflapon was rapidly absorbed with a median tmax of 1.5 h, followed by a biphasic decline in plasma exposure rendering a terminal half‐life of ~20 h. Unchanged atuliflapon was the predominant radioactive component in plasma, accounting for 40.1% of the total drug‐related exposure (DRE), while a direct N‐glucuronide was the only metabolite exceeding 10% of DRE, accounting for 20.9%. Renal excretion of intact atuliflapon accounted for

Electrocatalytic carbon dioxide reduction reaction (CO2RR) holds the promise of both overcoming the greenhouse effect and synthesizing a wealth of chemicals. Electrocatalytic CO2 reduction toward carbon-containing products, including C1 products (carbon monoxide, formic acid, etc), C2 products (ethylene, ethanol, etc.) and multi-carbon products (e.g., n-propanol), provides beneficial fuel and chemicals for industrial production. The complexity of the multi-proton transfer processes and difficulties of C-C coupling in electrochemical CO2 reduction toward multi-carbon(C2+) products have attracted increasing concerns on the design of catalysts in comparison with those of C1 products. In this paper, we review the main advances in the syntheses of multi-carbon products through electrocatalytic carbon dioxide reduction in recent years, introduce the basic principles of electrocatalytic CO2RR, and detailly elucidate two widely accepted mechanisms of C-C coupling reactions. Among abundant nanomaterials, copper-based catalysts are outstanding catalysts for the preparation of multi-carbon chemicals in electrochemical CO2RR attributing to effective C-C coupling reactions. Regarding the different selectivity of multi-carbon chemicals but extensively applied copper-based catalysts, we classify and summarize various Cu-based catalysts through separating diverse multi-carbon products, where the modification of spatial and electronic structures is beneficial to increase the coverage of CO or lower the activation energy barrier for forming C-C bond to form the key intermediates and increase the production of multi-carbon products. Challenges and prospects involving the fundamental and development of copper-based catalysts in electrochemical CO2 reduction reaction are also proposed.

The interactions between plants and herbivorous insects are complex and involve multiple factors, driving species formation and leading to the beginning of co-evolution and diversification of plant and insect molecules. Various molecular processes regulate the interactions between plants and herbivorous insects. Here, we discuss the molecular patterns of plant perception of herbivorous insect feeding through activation of early signaling components, crosstalk of plant defense network composed of multiple plant hormones, and various adaptive changes in insect responses to plant defenses. Both plant defenses and insect counter-defenses are molecular adaptation processes to each other. Molecular models of plant-herbivorous insect interactions can more intuitively help us to understand the co-evolutionary arms race between plants and herbivorous insects. These results will provide detailed evidence to elucidate and enrich the interaction network of plant-herbivorous insects.

Objectives Hemodialysis patients with end-stage renal disease (ESRD) are susceptible to infections and dysbiosis. Catheter-related infections are typically caused by opportunistic skin pathogens. This study aims to compare the skin microbiota changes around the exit site of tunneled cuffed catheters (peri-catheter group) and the contralateral site (control group).Methods ESRD patients on hemodialysis were recruited. The skin microbiota were collected with moist skin swabs and analyzed using high-throughput sequencing of the 16S rDNA V3–V4 region. After denoising, de-replication, and removal of chimeras, the reads were assigned to zero-radius operational taxonomic units (ZOTU).Results We found significantly reduced alpha diversity in the peri-catheter group compared to the control group, as indicated by the Shannon, Jost, and equitability indexes, but not by the Chao1 or richness indexes. Beta diversity analysis revealed significant deviation of the peri-catheter microbiota from its corresponding control group. There was an overrepresentation of Firmicutes and an underrepresentation of Actinobacteria, Proteobacteria, and Acidobacteria at the phylum level in the peri-catheter group. The most abundant ZOTU (Staphylococcus spp.) drastically increased, while Cutibacterium, a commensal bacterium, decreased in the peri-catheter group. Network analysis revealed that the skin microbiota demonstrated covariance with both local and biochemical factors.Conclusions In conclusion, there was significant skin microbiota dysbiosis at the exit sites compared to the control sites in ESRD dialysis patients. Managing skin dysbiosis represents a promising target in the prevention of catheter-related bacterial infections.