Retinol dehydrogenase 12 (RDH12) knock out may cause hyperuricemia phenotype in mice.

Hyperuricemia is a chronic metabolic disease caused by purine metabolism disorder. And several gene loci and transporter proteins that associated with uric acid transport functions have been identified. Retinol Dehydrogenase 12 (RDH12), recognized for its role in safeguarding photoreceptors, and our study investigated the potential impact of Rdh12 mutations on other organs and diseases, particularly hyperuricemia. We assessed Rdh12 mRNA expression levels in various tissues and conducted serum biochemical analyses in Rdh12-/- mice. Compared with the wild type, significant alterations in serum uric acid levels and kidney-related biochemical indicators have been revealed. Then further analysis, including quantitative RT-PCR of gene expression in the liver and kidney, highlighted variations in the expression levels of specific genes linked to hyperuricemia. And renal histology assessment exposed mild pathological lesions in the kidneys of Rdh12-/- mice. In summary, our study suggests that Rdh12 mutations impact not only retinal function but also contribute to hyperuricemia and renal disease phenotypes in mice. Our finding implies that individuals with Rdh12 mutations may be prone to hyperuricemia and gout, emphasizing the significance of preventive measures and regular examinations in daily life.

In Silico Design of Heterogeneous Microvascular Trees Using Generative Adversarial Networks and Constrained Constructive Optimization.

OBJECTIVE: Designing physiologically adequate microvascular trees is of crucial relevance for bioengineering functional tissues and organs. Yet, currently available methods are poorly suited to replicate the morphological and topological heterogeneity of real microvascular trees because the parameters used to control tree generation are too simplistic to mimic results of the complex angiogenetic and structural adaptation processes in vivo. METHODS: We propose a method to overcome this limitation by integrating a conditional deep convolutional generative adversarial network (cDCGAN) with a local fractal dimension-oriented constrained constructive optimization (LFDO-CCO) strategy. The cDCGAN learns the patterns of real microvascular bifurcations allowing for their artificial replication. The LFDO-CCO strategy connects the generated bifurcations hierarchically to form microvascular trees with a vessel density corresponding to that observed in healthy tissues. RESULTS: The generated artificial microvascular trees are consistent with real microvascular trees regarding characteristics such as fractal dimension, vascular density, and coefficient of variation of diameter, length, and tortuosity. CONCLUSIONS: These results support the adoption of the proposed strategy for the generation of artificial microvascular trees in tissue engineering as well as for computational modeling and simulations of microcirculatory physiology.

Advances, challenges and opportunities of phylogenetic and social network analysis using COVID-19 data.

Coronavirus disease 2019 (COVID-19) has attracted research interests from all fields. Phylogenetic and social network analyses based on connectivity between either COVID-19 patients or geographic regions and similarity between syndrome coronavirus 2 (SARS-CoV-2) sequences provide unique angles to answer public health and pharmaco-biological questions such as relationships between various SARS-CoV-2 mutants, the transmission pathways in a community and the effectiveness of prevention policies. This paper serves as a systematic review of current phylogenetic and social network analyses with applications in COVID-19 research. Challenges in current phylogenetic network analysis on SARS-CoV-2 such as unreliable inferences, sampling bias and batch effects are discussed as well as potential solutions. Social network analysis combined with epidemiology models helps to identify key transmission characteristics and measure the effectiveness of prevention and control strategies. Finally, future new directions of network analysis motivated by COVID-19 data are summarized.

Mitogen-activated protein kinase 2 specifically regulates photorespiration in rice.

Photorespiration begins with the oxygenation reaction catalyzed by Rubisco and is the second highest metabolic flux in plants after photosynthesis. Although the core biochemical pathway of photorespiration has been well characterized, little is known about the underlying regulatory mechanisms. Some rate-limiting regulation of photorespiration has been suggested to occur at both the transcriptional and posttranslational levels, but experimental evidence is scarce. Here, we found that mitogen-activated protein kinase 2 (MAPK2) interacts with photorespiratory glycolate oxidase and hydroxypyruvate reductase, and the activities of these photorespiratory enzymes were regulated via phosphorylation modifications in rice (Oryza sativa L.). Gas exchange measurements revealed that the photorespiration rate decreased in rice mapk2 mutants under normal growth conditions, without disturbing photosynthesis. Due to decreased photorespiration, the levels of some key photorespiratory metabolites, such as 2-phosphoglycolate, glycine, and glycerate, significantly decreased in mapk2 mutants, but those of photosynthetic metabolites were not altered. Transcriptome assays also revealed that the expression levels of some flux-controlling genes in photorespiration were significantly downregulated in mapk2 mutants. Our findings provide molecular evidence for the association between MAPK2 and photorespiration and suggest that MAPK2 regulates the key enzymes of photorespiration at both the transcriptional and posttranslational phosphorylation levels in rice.

Weak Bimetal Coupling-Assisted MN4 Catalyst for Enhanced Carbon Dioxide Reduction Reaction.

The design of multimetal catalysts holds immense significance for efficient CO2 capture and its conversion into economically valuable chemicals. Herein, heterobimetallic catalysts (MiMo)L were exploited for the CO2 reduction reactions (CO2RR) using relativistic density functional theory (DFT). The octadentate Pacman-like polypyrrolic ligand (H4L) accommodates two metal ions (Mo, W, Nd, and U) inside (Mi) and outside (Mo) its month, rendering a weak bimetal coupling-assisted MN4 catalytically active site. Adsorption reactions have access to energetically stable coordination modes of -OCO, -OOC, and -(OCO)2, where the donor atom(s) are marked in bold. Among all of the species, (UiMoo)L releases the most energy. Along CO2RR, it favors to produce CO. The high-efficiency CO2 reduction is attributed to the size matching of U with the ligand mouth and the effective manipulation of the electron density of both ligand and bimetals. The mechanism in which heterobimetals synergetically capture and reduce CO2 has been postulated. This establishes a reference in elaborating on the complicated heterogeneous catalysis.

Removal of Horizontally Impacted Mandibular Third Molars Using the Three-Piece or T-Shaped Tooth Sectioning Method.

BACKGROUND: The extraction of horizontally impacted mandibular third molars (HM3) can be a complicated surgery. Appropriate tooth sectioning methods can reduce the operation time and postoperative complications. PURPOSE: The current study compares operative time and postoperative pain between HM3 removed using the three-piece or T-shaped tooth sectioning techniques. STUDY DESIGN, SETTING, SAMPLE: A randomized single-blind prospective clinical trial on HM3 extraction was carried out between June and December 2022 in the Department of Oral and Maxillofacial Surgery, the Affiliated Stomatological Hospital, Southwest Medical University. Patients with local or systemic infection, poor oral hygiene, and systemic disease were excluded. PREDICTOR VARIABLE: The predictor variable was the tooth sectioning method. The subjects were randomized to a three-piece or T-shaped group. MAIN OUTCOME VARIABLE(S): The primary outcome variables were the operative time and postoperative pain measured using a visual analog scale (VAS). The secondary outcome variables were the rates of primary bleeding, mouth opening reduction, swelling, patient satisfaction measured using a VAS, and quality of life measured using a postoperative symptom severity scale. COVARIATES: The covariates included age, sex, side and classification of HM3, and the relationship of HM3 to the inferior alveolar nerve canal. ANALYSES: The data were analyzed using the independent samples t-test, paired t-test, χ2, and rank sum test. A significance level set at P < .05. RESULTS: The sample included 60 patients in the three-piece group and 66 patients in the T-shaped group. The operative time of the three-piece group (14.73 ± 3.21 minutes) was shorter than that of the T-shaped group (19.25 ± 4.29 minutes) (P < .05). On days 3 and 7, VAS of pain were 2.24 ± 1.89 and 0.15 ± 0.40 in the three-piece group and 3.95 ± 2.44 and 0.48 ± 0.68 in the T-shaped group (P < .05). The VAS of patient satisfaction in the three-piece group (6.05 ± 1.29) was better than the T-shaped group (4.90 ± 1.05) on day 7 (P < .05). CONCLUSION AND RELEVANCE: The three-piece tooth sectioning for HM3 removal was associated with shorter duration, slighter postoperative symptoms, and higher patient satisfaction and may be considered as a recommended practice for dentists.

Improvement of UCVA, BCVA, and Intraocular Pressure after Phakic Posterior Chamber Intraocular Lens Implantation for Myopia.

Objective: The purpose of this study is to explore the artificial lens planting of the back room shape of the crystal eye eyes and The clinical effect of ICL in patients with myopia. Methods: A Retrospective Study Spanning from 2021 to 2023 within Huai'an First People's Hospital. This study involves the comparative analysis of 100 eyes subjected to 'Crystalline Lens Extraction + IOL' and 100 eyes undergoing 'ICL' treatment. We evaluate various postoperative parameters, including near and distant visual acuity, Visual Acuity (CVA), Best-Corrected Visual Acuity (BCVA), refractive outcomes, endothelial cell count, glare sensitivity, and the incidence of macular edema. The control group underwent Crystalline Lens Extraction + IOL, and the observation group underwent 'ICL' treatment. Visual acuity recovery, intraocular pressure, endothelial cell count, adverse reactions, and therapeutic effect were compared between the two groups. Results: The CVA before treatment and the IOP and endothelial cell count before and after treatment in the observation group were similar to those in the control group, and the differences were not statistically significant (P > .05). The CVA, BCVA, and refraction after treatment in the observation group were all higher than those in the control group, and the differences were statistically significant (P < .05). The number of people with significant and effective treatment effects in the observation group (total effective rate 98.00%) was higher than that in the control group (82.00%), and the difference was statistically significant (P < .05). Conclusions: The implantation of 'ICL' treatment in cases of myopia demonstrates favorable surgical outcomes in clinical practice. It effectively enhances postoperative visual function recovery while minimizing the risk of adverse reactions. The ICL implantation procedure is irreplaceable in the treatment of myopia.

Mediation of metabolic syndrome in the association between long-term exposure to particulate matter and incident cardiovascular disease: Evidence from a population-based cohort in Chengdu.

BACKGROUND: Particulate matter (PM) exposure has been linked with cardiovascular disease (CVD) and metabolic syndrome (MetS), the latter characterized by concurrent multiple metabolic disorders. As a result, the mechanisms assumption from PM to CVD through MetS have emerged, thus requiring further epidemiological evidence. This cohort study aimed to assess whether MetS mediates the associations of PM with CVD risk. METHODS: This study included 14,195 participants from the Chengdu cohort of the China Multi-Ethnic Cohort (CMEC) study in 2018. The primary outcome of incident CVD diagnoses was identified using matched hospital records from the Health Information Center of Sichuan Province. Residence-specific levels of PM with aerodynamic diameters of ≤ 1 µm (PM1), ≤ 2.5 µm (PM2.5), and ≤ 10 µm (PM10) were estimated by spatiotemporal models. Causal mediation analyses were applied to evaluate the indirect effect of MetS. RESULTS: Increased exposure levels to PM were significantly associated with MetS and CVD. Mediation analyses indicated that the associations between PM exposure and CVD were mediated by MetS, with the proportion of multiple mediations being 19.3%, 12.1%, and 13.5% for PM1, PM2.5, and PM10, respectively. Further moderated mediation analyses suggested that male, overweight individuals, alcohol drinkers, and those suffering from indoor air pollution may experience more significant adverse effects from PM exposure on CVD via MetS than others. CONCLUSIONS: Our findings suggest that MetS partially mediates the association between long-term exposure to PM and CVD. These mediation effects appear to be amplified by demographic characteristics and unhealthy lifestyles.

Protein-sparing effects of lipids in the diet of golden pompano (Trachinotus ovatus): evaluation of growth, feed utilization, and lipid metabolism.

To investigate the influences of dietary protein and lipid levels on the growth, feed utilization, morphometric parameters, body composition, serum biochemical parameters, and lipid metabolism of golden pompano (Trachinotus ovatus), nine test diets containing three protein levels (35%, 40%, and 45%) and three lipid levels (8%, 13%, and 18%) were designed in the present study. Each diet (named D1-D9) was randomly assigned to feed triplicate groups of golden pompano juvenile (initial weight ~ 70 g) for 50 days. The results showed that the dietary lipid levels positively correlated with weight gain, specific growth rate, and protein efficiency ratio (PER), suggesting that the high lipid diets (18%) can be efficiently utilized in this fish species. The dietary protein levels have no significant influences on the growth and feed utilization except for the PER. Increasing dietary protein levels resulted in a decrease in hepatosomatic index (HSI), viscerosomatic index (VSI), and intestinal somatic index (ISI), while the dietary lipid level did not have a significant impact on morphological indices except for ISI. The dietary protein and lipid levels had no significant influences on the contents of crude lipid, crude ash, and moisture of whole body, while the crude protein contents was significantly affected by the dietary protein levels. Serum biochemical indexes, including cholesterol (CHO), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL), as well as HDL/LDL ratio were significantly affected by the dietary lipid levels, but not by the dietary protein levels. The expression levels of genes and their associated proteins involved in hepatic lipogenesis (Srebp-1c and Fas) and fatty acids ß-oxidation (Pparα and Cpt-1) were up-regulated with increasing dietary lipid levels, while the former was up-regulated, and the latter was down-regulated with increasing dietary protein levels. Considering the present results in terms of growth performance, feed utilization, morphometric parameters, and lipid metabolism, the recommended dietary protein and lipid levels for golden pompano are 40% and 18%, respectively. The findings suggested that this species exhibits a significant protein-sparing effect on lipid utilization.

Dynamic and fluctuating generation of hydrogen peroxide via photorespiratory metabolic channeling in plants.

The homeostasis of hydrogen peroxide (H2 O2 ), a key regulator of basic biological processes, is a result of the cooperation between its generation and scavenging. However, the mechanistic basis of this balance is not fully understood. We previously proposed that the interaction between glycolate oxidase (GLO) and catalase (CAT) may serve as a molecular switch that modulates H2 O2 levels in plants. In this study, we demonstrate that the GLO-CAT complex in plants exists in different states, which are dynamically interchangeable in response to various stimuli, typically salicylic acid (SA), at the whole-plant level. More crucially, changes in the state of the complex were found to be closely linked to peroxisomal H2 O2 fluctuations, which were independent of the membrane-associated NADPH oxidase. Furthermore, evidence suggested that H2 O2 channeling occurred even in vitro when GLO and CAT worked cooperatively. These results demonstrate that dynamic changes in H2 O2 levels are physically created via photorespiratory metabolic channeling in plants, and that such H2 O2 fluctuations may serve as signals that are mechanistically involved in the known functions of photorespiratory H2 O2 . In addition, our study also revealed a new way for SA to communicate with H2 O2 in plants.

Identification of Chicken CD44 as a Novel B Lymphocyte Receptor for Infectious Bursal Disease Virus.

Infectious bursal disease virus (IBDV), which targets bursa B lymphocytes, causes severe immunosuppressive disease in chickens, inducing huge economic losses for the poultry industry. To date, the functional receptor for IBDV binding and entry into host cells remains unclear. This study used mass spectrometry to screen host proteins of chicken bursal lymphocytes interacting with VP2. The chicken transmembrane protein cluster of differentiation 44 (chCD44) was identified and evaluated for its interaction with IBDV VP2, the major capsid protein. Overexpression and knockdown experiments showed that chCD44 promotes replication of IBDV. Furthermore, soluble chCD44 and the anti-chCD44 antibody blocked virus binding. The results of receptor reconstitution indicated that chCD44 overexpression conferred viral binding capability in nonpermissive cells. More important, although we found that IBDV could not replicate in the chCD44-overexpressed nonpermissive cells, the virus could enter nonpermissive cells using chCD44. Our finding reveals that chCD44 is a cellular receptor for IBDV, facilitating virus binding and entry in target cells by interacting with the IBDV VP2 protein. IMPORTANCE Infectious bursal disease virus (IBDV) causes severe immunosuppressive disease in chickens, inducing huge economic losses for the poultry industry. However, the specific mechanism of IBDV invading host cells of IBDV was not very clear. This study shed light on which cellular protein component IBDV is used to bind and/or enter B lymphocytes. The results of our study revealed that chCD44 could promote both the binding and entry ability of IBDV in B lymphocytes, acting as a cellular receptor for IBDV. Besides, this is the first report about chicken CD44 function in viral replication. Our study impacts the understanding of the IBDV binding and entry process and sets the stage for further elucidation of the infection mechanism of IBDV.

Residues L55 and W69 of Tva Mediate Entry of Subgroup A Avian Leukosis Virus.

The receptor of the subgroup A avian leukosis virus (ALV-A) in chicken is Tva, which is the homologous protein of human CD320 (huCD320), contains a low-density lipoprotein (LDL-A) module and is involved in the uptake of transcobalamin bound vitamin B12/cobalamin (Cbl). To map the functional determinants of Tva responsible for ALV-A receptor activity, a series of chimeric receptors were created by swapping the LDL-A module fragments between huCD320 and Tva. These chimeric receptors were then used for virus entry and binding assays to map the minimal ALV-A functional domain of Tva. The results showed that Tva residues 49 to 71 constituted the minimal functional domain that directly interacted with the ALV-A gp85 protein to mediate ALV-A entry. Single-residue substitution analysis revealed that L55 and W69, which were spatially adjacent on the surface of the Tva structure, were key residues that mediate ALV-A entry. Structural alignment results indicated that L55 and W69 substitutions did not affect the Tva protein structure but abolished the interaction force between Tva and gp85. Furthermore, substituting the corresponding residues of huCD320 with L55 and W69 of Tva converted huCD320 into a functional receptor of ALV-A. Importantly, soluble huCD320 harboring Tva L55 and W69 blocked ALV-A entry. Finally, we constructed a Tva gene-edited cell line with L55R and W69L substitutions that could fully resist ALV-A entry, while Cbl uptake was not affected. Collectively, our findings suggested that amino acids L55 and W69 of Tva were key for mediating virus entry. IMPORTANCE Retroviruses bind to cellular receptors through their envelope proteins, which is a crucial step in infection. While most retroviruses require two receptors for entry, ALV-A requires only one. Various Tva alleles conferring resistance to ALV-A, including Tvar1 (C40W substitution), Tvar2 (frame-shifting four-nucleotide insertion), Tvar3, Tvar4, Tvar5, and Tvar6 (deletion in the first intron), are known. However, the detailed entry mechanism of ALV-A in chickens remains to be explored. We demonstrated that Tva residues L55 and W69 were key for ALV-A entry and were important for correct interaction with ALV-A gp85. Soluble Tva and huCD320 harboring the Tva residues L55 and W69 effectively blocked ALV-A infection. Additionally, we constructed gene-edited cell lines targeting these two amino acids, which completely restricted ALV-A entry without affecting Cbl uptake. These findings contribute to a better understanding of the infection mechanism of ALV-A and provided novel insights into the prevention and control of ALV-A.

TRIM25 inhibits infectious bursal disease virus replication by targeting VP3 for ubiquitination and degradation.

Infectious bursal disease virus (IBDV), a double-stranded RNA virus, causes immunosuppression and high mortality in 3-6-week-old chickens. Innate immune defense is a physical barrier to restrict viral replication. After viral infection, the host shows crucial defense responses, such as stimulation of antiviral effectors to restrict viral replication. Here, we conducted RNA-seq in avian cells infected by IBDV and identified TRIM25 as a host restriction factor. Specifically, TRIM25 deficiency dramatically increased viral yields, whereas overexpression of TRIM25 significantly inhibited IBDV replication. Immunoprecipitation assays indicated that TRIM25 only interacted with VP3 among all viral proteins, mediating its K27-linked polyubiquitination and subsequent proteasomal degradation. Moreover, the Lys854 residue of VP3 was identified as the key target site for the ubiquitination catalyzed by TRIM25. The ubiquitination site destroyed enhanced the replication ability of IBDV in vitro and in vivo. These findings demonstrated that TRIM25 inhibited IBDV replication by specifically ubiquitinating and degrading the structural protein VP3.

PEEP application during mechanical ventilation contributes to fibrosis in the diaphragm.

BACKGROUND: Positive end-expiratory airway pressure (PEEP) is a potent component of management for patients receiving mechanical ventilation (MV). However, PEEP may cause the development of diaphragm remodeling, making it difficult for patients to be weaned from MV. The current study aimed to explore the role of PEEP in VIDD. METHODS: Eighteen adult male New Zealand rabbits were divided into three groups at random: nonventilated animals (the CON group), animals with volume-assist/control mode without/ with PEEP 8 cmH2O (the MV group/ the MV + PEEP group) for 48 h with mechanical ventilation. Ventilator parameters and diaphragm were collected during the experiment for further analysis. RESULTS: There was no difference among the three groups in arterial blood gas and the diaphragmatic excursion during the experiment. The tidal volume, respiratory rate and minute ventilation were similar in MV + PEEP group and MV group. Airway peak pressure in MV + PEEP group was significantly higher than that in MV group (p < 0.001), and mechanical power was significantly higher (p < 0.001). RNA-seq showed that genes associated with fibrosis were enriched in the MV + PEEP group. This results were further confirmed on mRNA expression. As shown by Masson's trichrome staining, there was more collagen fiber in the MV + PEEP group than that in the MV group (p = 0.001). Sirius red staining showed more positive staining of total collagen fibers and type I/III fibers in the MV + PEEP group (p = 0.001; p = 0.001). The western blot results also showed upregulation of collagen types 1A1, III, 6A1 and 6A2 in the MV + PEEP group compared to the MV group (p < 0.001, all). Moreover, the positive immunofluorescence of COL III in the MV + PEEP group was more intense (p = 0.003). Furthermore, the expression of TGF-ß1, one of the most potent fibrogenic factors, was upregulated at both the mRNA and protein levels in the MV + PEEP group (mRNA: p = 0.03; protein: p = 0.04). CONCLUSIONS: We demonstrated that PEEP application for 48 h in mechanically ventilated rabbits will cause collagen deposition and fibrosis in the diaphragm. Moreover, activation of the TGF-ß1 signaling pathway and myofibroblast differentiation may be the potential mechanism of this diaphragmatic fibrosis. These findings might provide novel therapeutic targets for PEEP application-induced diaphragm dysfunction.

Tuning the Alkyl Chain of Nitrilotriacetamide for Selectively Extracting Trivalent Am over Eu Ions.

The successful management and safe disposal of high-level nuclear waste necessitate the efficient separation of actinides (An) from lanthanides (Ln), which has emerged as a crucial prerequisite. Mixed donor ligands incorporating both soft and hard donor atoms have garnered interest in the field of An/Ln separation and purification. One such example is nitrilotriacetamide (NTAamide) derivatives, which have demonstrated selectivity in extracting minor actinide Am(III) ions over Eu(III) ions. Nevertheless, the Am/Eu complexation behavior and selectivity remain underexplored. In the work, a comprehensive and systematic investigation has been conducted for [M(RL)(NO3)3] complexes (M = Am and Eu) utilizing relativistic density functional theory. The NTAamide ligand (RL) is substituted with various alkyl groups, namely, methyl, ethyl, propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, and n-octyl. Thermodynamic calculations show that the alkyl chain length in NTAamide is capable of tuning the separation selectivity of Am and Eu. Moreover, the differences in calculated free energies between Am and Eu complexes are more negative for R = Bu-Oct than Me-Pr. This indicates that elongation of the alkyl chain can increase the efficiency of selective separation of Am(III) from Eu(III). Based on the quantum theory of atoms in molecules and charge decomposition analyses, it has been observed that the strength of Am-RL bonds is higher than that of Eu-RL bonds. This disparity is attributed to a greater degree of covalency in Am-RL bonds and a higher level of charge transfer from ligands to Am within complexes containing these bonds. Energies of occupied orbitals with the central N character are recognized overall lower for [Am(OctL)(NO3)3] than for [Eu(OctL)(NO3)3], indicative of stronger complexation stability of the former. These results offer valuable insights into the separation mechanism of NTAamide ligands, which can help guide the development of more powerful agents for An/Ln separation in future applications.

Cellular senescence contributes to mechanical ventilation-induced diaphragm dysfunction by upregulating p53 signalling pathways.

BACKGROUND: Mechanical ventilation can cause acute atrophy and injury in the diaphragm, which are related to adverse clinical results. However, the underlying mechanisms of ventilation-induced diaphragm dysfunction (VIDD) have not been well elucidated. The current study aimed to explore the role of cellular senescence in VIDD. METHODS: A total of twelve New Zealand rabbits were randomly divided into 2 groups: (1) spontaneously breathing anaesthetized animals (the CON group) and (2) mechanically ventilated animals (for 48 h) in V-ACV mode (the MV group). Respiratory parameters were collected during ventilation. Diaphragm were collected for further analyses. RESULTS: Compared to those in the CON group, the percentage and density of sarcomere disruption in the MV group were much higher (p < 0.001, both). The mRNA expression of MAFbx and MuRF1 was upregulated in the MV group (p = 0.003 and p = 0.006, respectively). Compared to that in the CON group, the expression of MAFbx and MuRF1 detected by western blotting was also upregulated (p = 0.02 and p = 0.03, respectively). Moreover, RNA-seq showed that genes associated with senescence were remarkably enriched in the MV group. The mRNA expression of related genes was further verified by q-PCR (Pai1: p = 0.009; MMP9: p = 0.008). Transverse cross-sections of diaphragm myofibrils in the MV group showed more intensive positive staining of SA-ßGal than those in the CON group. p53-p21 axis signalling was elevated in the MV group. The mRNA expression of p53 and p21 was significantly upregulated (p = 0.02 and p = 0.05, respectively). The western blot results also showed upregulation of p53 and p21 protein expression (p = 0.03 and p = 0.05, respectively). Moreover, the p21-positive staining in immunofluorescence and immunohistochemistry in the MV group was much more intense than that in the CON group (p < 0.001, both). CONCLUSIONS: In a rabbit model, we demonstrated that mechanical ventilation in A/C mode for 48 h can still significantly induce ultrastructural damage and atrophy of the diaphragm. Moreover, p53-dependent senescence might play a role in mechanical ventilation-induced dysfunction. These findings might provide novel therapeutic targets for VIDD.

Analysis of the Macular Region Following Panretinal Photocoagulation for the Treatment of Diabetic Retinopathy Using Optical Coherence Tomography.

Background: Diabetic retinopathy (DR) is the most prevalent microvascular complication of diabetes. Panretinal photocoagulation (PRP) is the established treatment for mitigating severe visual impairment resulting from proliferative DR. Objective: This study aims to investigate the impact of PRP on the macular region in patients with DR, utilizing optical coherence tomography (OCT) for assessment. Design: An experimental study was meticulously designed, implementing PRP as the primary intervention. Setting: The investigation was conducted within the Department of Ophthalmology at the Affiliated Huaian No.1 People's Hospital, Huai'an, Jiangsu, China. Participants: A total of 120 participants diagnosed with DR and undergoing treatment at our hospital were enrolled in the study. Interventions: The participants were randomly assigned to either the control group (CG, n = 60) or the study group (SG, n = 60). The CG received conventional drug treatment involving oral iodized lecithin, while the SG received PRP. OCT was employed to monitor changes in macular fovea volume and macular retinal thickness. Primary Outcome Measures: Evaluation criteria encompassed clinical efficacy, macular fovea volume, macular retinal thickness, IL-6 and VEGF levels, incidence of adverse reactions, and quality of life in both groups. Results: The study resulted in a higher total effective rate in the SG (96.67%) compared to the CG (80.00%) (χ2 = 8.09, P < .05). Post-treatment, reductions were observed in macular fovea volume and macular retinal thickness, with significantly lower SG values than CG values (P < .05). Both serum IL-6 and VEGF levels exhibited reductions in both groups after treatment, with the SG displaying a more significant decrease compared to the CG (P < .05). The occurrence of adverse reactions significantly decreased in the SG relative to the CG (P < .05). Quality of life scores for the SG was notably elevated compared to the CG (P < .05). Conclusions: PRP emerges as a highly valuable approach in the management of DR. It contributes to retinal thickness improvement within the macular region and inflammation reduction, and also enhances therapeutic outcomes, minimizes adverse reactions, and optimizes patients' quality of life. These findings warrant further clinical adoption and widespread promotion.

A Theoretical Study on the Underlying Factors of the Difference in Performance of Organic Solar Cells Based on ITIC and Its Isomers.

Recently, non-fullerene-based organic solar cells (OSCs) have made great breakthroughs, and small structural differences can have dramatic impacts on the power conversion efficiency (PCE). We take ITIC and its isomers as examples to study their effects on the performance of OSCs. ITIC and NFBDT only differed in the side chain position, and they were used as models with the same donor molecule, PBDB-T, to investigate the main reasons for the difference in their performance in terms of theoretical methods. In this work, a detailed comparative analysis of the electronic structure, absorption spectra, open circuit voltage and interfacial parameters of the ITIC and NFBDT systems was performed mainly by combining the density functional theory/time-dependent density functional theory and molecular dynamics simulations. The results showed that the lowest excited state of the ITIC molecule possessed a larger ∆q and more hybrid FE/CT states, and PBDB-T/ITIC had more charge separation paths as well as a larger kCS and smaller kCR. The reason for the performance difference between PBDB-T/ITIC and PBDB-T/NFBDT was elucidated, suggesting that ITIC is a superior acceptor based on a slight modulation of the side chain and providing a guiding direction for the design of superior-performing small molecule acceptor materials.

Thermal Behaviors and Interaction Mechanism of Ammonium Dinitramide with Nitrocellulose.

The initial interaction mechanism is very important for the design and safety of nano-scale composite energetic materials composed of ammonium dinitramide (ADN) and nitrocellulose (NC). The thermal behaviors of ADN, NC and an NC/ADN mixture under different conditions were studied by using differential scanning calorimetry (DSC) with sealed crucibles, an accelerating rate calorimeter (ARC), a self-developed gas pressure measurement instrument and a DSC-thermogravimetry (TG)-quadrupole mass spectroscopy (MS)-Fourier transform infrared spectroscopy (FTIR) combined technique. The results show that the exothermic peak temperature of the NC/ADN mixture shifted forward greatly in both open and closed circumstances compared to those of NC or ADN. After 585.5 min under quasi-adiabatic conditions, the NC/ADN mixture stepped into the self-heating stage at 106.4 °C, which was much less than the initial temperatures of NC or ADN. The significant reduction in net pressure increment of NC, ADN and the NC/ADN mixture under vacuum indicates that ADN initiated the interaction of NC with ADN. Compared to gas products of NC or ADN, two new kinds of oxidative gases O2 and HNO2 appeared for the NC/ADN mixture, while NH3 and aldehyde disappeared. The mixing of NC with ADN did not change the initial decomposition pathway of either, but NC made ADN more inclined to decompose into N2O, which resulted in the formation of oxidative gases O2 and HNO2. The thermal decomposition of ADN dominated the initial thermal decomposition stage of the NC/ADN mixture, followed by the oxidation of NC and the cation of ADN.

Mechanism of symbiotic nodulation between nitrogen and peanut.

Nitrogen is critical for peanut growth and development, and symbiotic nodulation and nitrogen fixation is one of the main ways for peanut to obtain nitrogen. The influence of exogenous nitrogen on nodule nitrogen fixation involves complex regulatory mechanisms, revealing the regulatory mechanisms of nitrogen on nodule nitrogen fixation is of great significance for realizing the potential of biological nitrogen fixation. In this review, we summarize the mechanism of "Crack entry" in the formation of peanut root nodule, the mechanism of symbiotic nodulation and quantitative regulation of peanut, and the regulatory mechanism of nitrogen affecting peanut nodulation. At present, the molecular mechanism by which nitrogen affects the interaction between Bradyrhizobium and peanut, thereby regulating nodulation, is still unclear. Therefore, future research should focus on the signal exchange, nodule number regulation, and nutrient exchange mechanism of nitrogen effects on Bradyrhizobium and peanut, which would provide a theoretical basis for improving nodule nitrogen fixation efficiency and peanut yield, and reduce chemical nitrogen fertilizer application.