"Severe blepharoptosis correction with the fixation of levator complex and conjoint fascial sheath: 12 Years of Experience in a Single Center."

BACKGROUND: The correction of severe blepharoptosis is one of the most challenging surgeries in plastic surgery. This study introduces a novel self-reinforced fixation technique combining the levator complex with conjoint fascial sheath for the correction of severe blepharoptosis and reviews the postoperative results over the preceding 12 years. METHODS: This retrospective review included all patients who underwent self-reinforced fixation with or without conjoint fascial sheath at the authors' center between 2010 and 2022. The clinical data of the two groups were collected and evaluated. RESULTS: All patients were followed up for 6 months to 8 years postoperatively. The mean postoperative MRD1 and LF increased significantly in both groups. Sufficient correction of ptosis was achieved in 32 (65.31%) and 84 (81.56%) eyelids in Groups I and II, respectively. The mean eyelid lagophthalmos was 1.27± 0.91 mm and 0.85 ± 0.89 mm in Groups I and II, respectively. The most common complication was undercorrection of ptosis, which was observed in 14 eyelids (28.57%) and 15 eyelids (14.56%) in Groups I and II, respectively. CONCLUSIONS: The self-reinforced fixation technique was effective in correcting severe congenital ptosis in Chinese patients. The clinical effect was consistent in the long-term follow-up cases, and the recurrence rate was low. Thus, this technique can enhance the strength of the levator muscle and maintain appropriate elasticity of eye closure. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Chronic myeloid leukaemia: Biology and therapy.

Chronic myeloid leukaemia (CML) is caused by BCR::ABL1. Tyrosine kinase-inhibitors (TKIs) are the initial therapy. Several organizations have reported milestones to evaluate response to initial TKI-therapy and suggest when a change of TKI should be considered. Achieving treatment-free remission (TFR) is increasingly recognized as the optimal therapy goal. Which TKI is the best initial therapy for which persons and what depth and duration of molecular remission is needed to achieve TFR are controversial. In this review we discuss these issues and suggest future research directions.

SF3A2 promotes progression and cisplatin resistance in triple-negative breast cancer via alternative splicing of MKRN1.

Triple-negative breast cancer (TNBC) is the deadliest subtype of breast cancer owing to the lack of effective therapeutic targets. Splicing factor 3a subunit 2 (SF3A2), a poorly defined splicing factor, was notably elevated in TNBC tissues and promoted TNBC progression, as confirmed by cell proliferation, colony formation, transwell migration, and invasion assays. Mechanistic investigations revealed that E3 ubiquitin-protein ligase UBR5 promoted the ubiquitination-dependent degradation of SF3A2, which in turn regulated UBR5, thus forming a feedback loop to balance these two oncoproteins. Moreover, SF3A2 accelerated TNBC progression by, at least in part, specifically regulating the alternative splicing of makorin ring finger protein 1 (MKRN1) and promoting the expression of the dominant and oncogenic isoform, MKRN1-T1. Furthermore, SF3A2 participated in the regulation of both extrinsic and intrinsic apoptosis, leading to cisplatin resistance in TNBC cells. Collectively, these findings reveal a previously unknown role of SF3A2 in TNBC progression and cisplatin resistance, highlighting SF3A2 as a potential therapeutic target for patients with TNBC.

Enhanced Fenton-like process over Z-scheme MoO3 surface decorated with Fe2O3 under visible light.

Photocatalysts consisting of Z-scheme heterojunctions are commonly used in wastewater treatment due to their exceptional reactivity in photocatalysis and highly efficient visible-light utilization. In this work, Fe2O3-decorated MoO3 rods were synthesized through a two-step method and their photodegradation of methylene blue (MB) was evaluated. The Fe2O3/MoO3 rods were characterized by XRD, SEM, micro-Raman, XPS, UV-Vis DRS, and PL to investigate their structural, morphological, and optical properties. The results indicate that the photodegradation efficiency of Fe2O3/MoO3 improved through a reduction in the gap energy and persistence of a 1D hexagonal prism structure. The degradation rate of MB was enhanced from 31.7 to 91.5% after irradiation for 180 min owing to electron-hole separation and Fenton-like process. Formation of the OH radical is a key factor in the photodegradation reaction and with the addition of H2O2 the efficiency can further improve via a Fenton-like mechanism. Furthermore, the Z-scheme mechanism concurrently delineated. The Fe2O3/MoO3 rod composites were also found to retain high photocatalytic efficiency after being reused five times, which may be useful for future applications.

Advanced brain aging in Parkinson's disease with cognitive impairment.

Patients with Parkinson's disease and cognitive impairment (PD-CI) deteriorate faster than those without cognitive impairment (PD-NCI), suggesting an underlying difference in the neurodegeneration process. We aimed to verify brain age differences in PD-CI and PD-NCI and their clinical significance. A total of 94 participants (PD-CI, n = 27; PD-NCI, n = 34; controls, n = 33) were recruited. Predicted age difference (PAD) based on gray matter (GM) and white matter (WM) features were estimated to represent the degree of brain aging. Patients with PD-CI showed greater GM-PAD (7.08 ± 6.64 years) and WM-PAD (8.82 ± 7.69 years) than those with PD-NCI (GM: 1.97 ± 7.13, Padjusted = 0.011; WM: 4.87 ± 7.88, Padjusted = 0.049) and controls (GM: -0.58 ± 7.04, Padjusted = 0.004; WM: 0.88 ± 7.45, Padjusted = 0.002) after adjusting demographic factors. In patients with PD, GM-PAD was negatively correlated with MMSE (Padjusted = 0.011) and MoCA (Padjusted = 0.013) and positively correlated with UPDRS Part II (Padjusted = 0.036). WM-PAD was negatively correlated with logical memory of immediate and delayed recalls (Padjusted = 0.003 and Padjusted < 0.001). Also, altered brain regions in PD-CI were identified and significantly correlated with brain age measures, implicating the neuroanatomical underpinning of neurodegeneration in PD-CI. Moreover, the brain age metrics can improve the classification between PD-CI and PD-NCI. The findings suggest that patients with PD-CI had advanced brain aging that was associated with poor cognitive functions. The identified neuroimaging features and brain age measures can serve as potential biomarkers of PD-CI.

Visual outcome of various dose of glucocorticoids treatment in nonarteritic anterior ischemic optic neuropathy- a retrospective analysis.

BACKGROUND AND PURPOSE: The objective of this investigation was to assess the therapeutic efficacy of distinct glucocorticoid therapy dosages in the management of acute nonarteritic anterior ischemic optic neuropathy (NAION). MATERIALS AND METHODS: This retrospective, unmasked, and non-randomized study included a total of 85 patients. The patients were categorized into four groups: Group 1 (control) consisted of 15 patients who did not receive glucocorticoids, Group 2 included 16 patients administered with oral prednisone at a dosage of 1 mg/kg/d for 14 days, Group 3 comprised 30 patients who received 250 units of methylprednisolone once daily for 3 days, followed by oral prednisone at a dosage of 1 mg/kg/d for 11 days, and Group 4 encompassed 24 patients who received 500 units of methylprednisolone once daily for 3 days, followed by oral prednisone at a dosage of 1 mg/kg/d for 11 days. The best-corrected visual acuity (BCVA) was assessed at baseline and the final follow-up (> 7 days post-treatment). The changes in visual acuity between baseline and the 7-14 day follow-up, as well as between baseline and the concluding appraisal, were employed as metrics for assessing the extent of visual enhancement. RESULTS: No significant differences were noted in the final visual outcomes or in the changes between final visual acuity and baseline across the four groups. In Group 1 (control), the best-corrected visual acuity (BCVA) remained unchanged during final follow-ups compared to baseline. Conversely, the intervention groups exhibited statistically significant enhancements in BCVA during final follow-up (p = 0.012, p = 0.03, and p = 0.009 for Group 2, Group 3, and Group 4, respectively) when compared to baseline. During the 7-14 day follow-up, there was a significant difference in the changes between baseline BCVA and follow-up BCVA across the groups (p = 0.035). Go a step further by Bonferroni correction for multiple comparisons, group 4 showed a greater change in vision compared with group1 (p = 0.045). CONCLUSION: Our study on acute nonarteritic anterior ischemic optic neuropathy (NAION) showed no significant final visual outcome differences. Nevertheless, Groups 2, 3, and 4 demonstrated improved best-corrected visual acuity (BCVA) during the final follow-up. Notably, a 500-unit dose of methylprednisolone resulted in short-term BCVA enhancement. This suggests potential consideration of 500 units of methylprednisolone for short-term NAION vision improvement, despite its limited long-term impact.

[Efficiency Characteristics and Evolution Patterns of Urban Carbon Metabolism of Production-Living-Ecological Space in Beijing-Tianjin-Hebei Region].

This study explored the carbon metabolism efficiency of a production-living-ecological space system, which is of great significance for regional factor integration and spatial optimization. In this study, the material flow analysis method was introduced to establish a framework for evaluating the carbon metabolism efficiency of the production-living-ecological space system, and the super-efficiency DEA model and Malmquist index were used to empirically analyze the spatio-temporal distribution, dynamic change, and evolution patterns of the carbon metabolism efficiency of production-living-ecological space in the Beijing-Tianjin-Hebei Region, China, from 2000 to 2020 on the basis of the urban metabolic perspective. The results showed that:① the carbon metabolism efficiency of the production-living-ecological space showed a fluctuating growth trend, indicating the significant spatial differentiation of carbon metabolism efficiency in each city. There was a low overall carbon metabolism efficiency level, with a distribution pattern of being high in the middle and low in the north and south. ② The Malmquist index showed that the Total Factor Productivity (TFP) of carbon metabolism efficiency was greater than 1, and both the Technical Change (TC) and Pure Efficiency Change (PEC) were less than 1, in which the TFP showed an increasing trend, whereas there was no significant contribution of technological progress or pure technical efficiency to carbon metabolism efficiency. The total factor productivity of more than 50% of the cities showed an improving trend, only 38.46% of which made technological progress in improving carbon metabolism efficiency, and more than half of the urban pure technical efficiency showed a decreasing trend, in which the technical efficiency change and scale efficiency change were greater than 1 in most cities. ③ There were different types of carbon efficiency characteristics in each city, and according to the movement rules of the corresponding points in the quartile map, the evolution patterns of tourism industry efficiency were classified into stable, reciprocating, progressive, and abrupt. Therefore, local governments should adopt differentiated strategies to reasonably allocate spatial resources of production-living-ecological space and improve the technical level and scale efficiency, so as to improve the efficiency of urban carbon metabolism.

Outer membrane vesicles of avian pathogenic Escherichia coli induce necroptosis and NF-κB activation in chicken macrophages via RIPK1 mediation.

Outer membrane vesicles (OMVs) are soluble mediators secreted by Gram-negative bacteria that are involved in communication. They can carry a variety of harmful molecules, which induce cytotoxic responses and inflammatory reactions in the absence of direct host cell-bacterium interactions. We previously reported the isolation of OMVs from avian pathogenic Escherichia coli (APEC) culture medium by ultracentrifugation, and characterized them as a substance capable of inducing the production of pro-inflammatory cytokines and causing tissue damage. However, the specific mechanisms by which APEC-secreted OMVs activate host cell death signaling and inflammation are poorly understood. Here, we show that OMVs are involved in the pathogenesis of APEC disease. In an APEC/chicken macrophage (HD11) coculture system, APEC significantly promoted HD11 cell death and inflammatory responses by secreting OMVs. Using western blotting analysis and specific pathway inhibitors, we demonstrated that the induction of HD11 death by APEC OMVs is associated with the activation of receptor interacting serine/threonine kinase 1 (RIPK1)-, receptor interacting serine/threonine kinase 3 (RIPK3)-, and mixed lineage kinase like pseudokinase (MLKL)-induced necroptosis. Notably, necroptosis inhibitor-1 (Nec-1), an RIPK1 inhibitor, reversed these effects. We also showed that APEC OMVs promote the activation of the NF-κB signaling pathway, leading to the phosphorylation of IκB-α and p65, the increased nuclear translocation of p65, and the significant upregulation of interleukin 1ß (IL-1ß) and IL-6 transcription. Importantly, APEC OMVs-induced IL-1ß and IL-6 mRNA expression and the activation of the NF-κB signaling pathway were similarly significantly inhibited by a RIPK1-specific inhibitor. Based on these findings, we have established that RIPK1 plays a dual role in HD11 cells necroptosis and the proinflammatory cytokine (IL-1ß and IL-6) expression induced by APEC OMVs. RIPK1 mediated the induction of necroptosis and the activation of the NF-κB in HD11 cells via APEC OMVs. The results of this study provide a basis for further investigation of the contribution of OMVs to the pathogenesis of APEC.

Metagenome-Based Analysis of the Microbial Community Structure and Drug-Resistance Characteristics of Livestock Feces in Anhui Province, China.

We analyzed metagenome data of feces from sows at different physiological periods reared on large-scale farms in Anhui Province, China, to provide a better understanding of the microbial diversity of the sow intestinal microbiome and the structure of antibiotic-resistance genes (ARGs) and virulence genes it carries. Species annotation of the metagenome showed that in the porcine intestinal microbiome, bacteria were dominant, representing >97% of the microorganisms at each physiological period. Firmicutes and Proteobacteria dominated the bacterial community. In the porcine gut microbiome, the viral component accounted for an average of 0.65%, and the species annotation results indicated that most viruses were phages. In addition, we analyzed the microbiome for ARGs and virulence genes. Multidrug-like, MLS-like, and tetracycline-like ARGs were most abundant in all samples. Evaluation of the resistance mechanisms indicated that antibiotic inactivation was the main mechanism of action in the samples. It is noteworthy that there was a significant positive correlation between ARGs and the total microbiome. Moreover, comparative analysis with the Virulence Factor Database showed that adhesion virulence factors were most abundant.

Avian pathogenic Escherichia coli T6SS effector protein Hcp2a causes mitochondrial dysfunction through interaction with LETM1 protein in DF-1 cells.

The type VI secretion system (T6SS) of avian pathogenic Escherichia coli (APEC) can affect the functions of eukaryotic cells by secreting or injecting effectors. Hemolysin co-regulatory protein (Hcp), one of the markers of the T6SS, is both a structural protein and an effector protein of the T6SS. According to previous studies, mitochondria in eukaryotic cells are targeted by pathogenic bacteria. However, little is known about the regulation of mitochondria in eukaryotic host cells by the T6SS effector protein Hcp of APEC. In our study, DF-1 cells co-incubated with Hcp2a protein for 6 h showed decreased mitochondrial membrane potential, increased Ca2+ concentration, and increased cellular reactive oxygen species (ROS) levels. We therefore conclude that Hcp2a protein causes dysfunction to mitochondria in DF-1 cells. To explain the mechanism that causes mitochondrial dysfunction, we reanalyzed the Hcp2a interaction protein dataset in DF-1 cells, and the Leucine zipper EF-hand-containing transmembrane protein 1 (LETM1), which is associated with mitochondria, was screened. The protein and molecular docking results showed that Hcp2a protein and LETM1 protein have better binding. Finally, subcellular localization results showed that Hcp2a was localized to mitochondria. In summary, Hcp2a effector proteins caused dysfunction to DF-1 cellular mitochondria, and we hypothesize that the interaction of Hcp2a protein with LETM1 protein induces mitochondrial dysfunction and promotes mitochondrial localization of Hcp2a in DF-1 cells.

Protein-rich foods, sea foods, and gut microbiota amplify immune responses in chronic diseases and cancers - Targeting PERK as a novel therapeutic strategy for chronic inflammatory diseases, neurodegenerative disorders, and cancer.

The endoplasmic reticulum (ER) is a cellular organelle that is physiologically responsible for protein folding, calcium homeostasis, and lipid biosynthesis. Pathological stimuli such as oxidative stress, ischemia, disruptions in calcium homeostasis, and increased production of normal and/or folding-defective proteins all contribute to the accumulation of misfolded proteins in the ER, causing ER stress. The adaptive response to ER stress is the activation of unfolded protein response (UPR), which affect a wide variety of cellular functions to maintain ER homeostasis or lead to apoptosis. Three different ER transmembrane sensors, including PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme-1 (IRE1), are responsible for initiating UPR. The UPR involves a variety of signal transduction pathways that reduce unfolded protein accumulation by boosting ER-resident chaperones, limiting protein translation, and accelerating unfolded protein degradation. ER is now acknowledged as a critical organelle in sensing dangers and determining cell life and death. On the other hand, UPR plays a critical role in the development and progression of several diseases such as cardiovascular diseases (CVD), metabolic disorders, chronic kidney diseases, neurological disorders, and cancer. Here, we critically analyze the most current knowledge of the master regulatory roles of ER stress particularly the PERK pathway as a conditional danger receptor, an organelle crosstalk regulator, and a regulator of protein translation. We highlighted that PERK is not only ER stress regulator by sensing UPR and ER stress but also a frontier sensor and direct senses for gut microbiota-generated metabolites. Our work also further highlighted the function of PERK as a central hub that leads to metabolic reprogramming and epigenetic modification which further enhanced inflammatory response and promoted trained immunity. Moreover, we highlighted the contribution of ER stress and PERK in the pathogenesis of several diseases such as cancer, CVD, kidney diseases, and neurodegenerative disorders. Finally, we discuss the therapeutic target of ER stress and PERK for cancer treatment and the potential novel therapeutic targets for CVD, metabolic disorders, and neurodegenerative disorders. Inhibition of ER stress, by the development of small molecules that target the PERK and UPR, represents a promising therapeutic strategy.

Rapid Initiation of Antiretroviral Therapy with Coformulated Bictegravir, Emtricitabine, Tenofovir Alafenamide Versus Efavirenz, Lamivudine and Tenofovir Disoproxil Fumarate in HIV-positive Men Who Have Sex with Men in China: Week 48 Results of the Multicenter, Randomized Clinical Trial.

BACKGROUND: Most international treatment guidelines recommend rapid initiation of antiretroviral therapy (ART) for people newly diagnosed with HIV-1 infection, but experiences with rapid ART initiation remain limited in China. We aimed to evaluate the efficacy and safety of efavirenz (400-mg) plus lamivudine and tenofovir disoproxil fumarate (EFV + 3TC + TDF) versus coformulated bictegravir, emtricitabine, tenofovir alafenamide (BIC/FTC/TAF) in rapid ART initiation among HIV-positive men who have sex with men (MSM). METHODS: This multicenter, open-label, randomized clinical trial enrolled MSM aged ≥18 years to start ART within 14 days of confirmed HIV diagnosis. The participants were randomly assigned in a 1:1 ratio to receive EFV(400-mg) + 3TC + TDF or BIC/FTC/TAF. The primary end point was viral suppression (<50 copies/ml) at 48 weeks per FDA Snapshot analysis. RESULTS: Between March 2021 and July 2022, 300 participants were enrolled; 154 were assigned to receive EFV + 3TC + TDF (EFV group) and 146 BIC/FTC/TAF (BIC group). At week 48, 118 (79.2%) and 140 (95.9%) participants in the EFV and BIC group, respectively, were retained in care with viral suppression; and 24 (16.1%) and 1 (0.7%) participant in the EFV and BIC group (p < 0.001), respectively, discontinued treatment due to adverse effects, death, or loss to follow-up. The median increase of CD4 count was 181 and 223 cells/µL (p = 0.020), respectively, for the EFV and BIC group, at week 48. The overall incidence of adverse effects was significantly higher for the EFV group (65.8% vs 37.7%, P < 0.001). CONCLUSION: BIC/FTC/TAF was more efficacious and safer than EFV(400-mg) + 3TC + TDF for rapid ART initiation among HIV-positive MSM in China.

Evaluation of chicken chorioallantoic membrane model for tumor imaging and drug development: Promising findings.

BACKGROUND: The chicken chorioallantoic membrane (CAM) model is a potential alternative to the mouse model based on the 3R principles. However, its value for determination of the in vivo behaviors of radiolabeled peptides through positron emission tomography (PET) imaging needed investigation. Herein, the chicken CAM tumor models were established, and their feasibility was evaluated for evaluating the imaging properties of radiolabeled peptides using a 68 Ga-labeled HER2 affibody. METHODS: Two human breast cancer cell lines were inoculated into chicken CAM and mice, respectively. The tumor-targeting potential and pharmacokinetic profile of a 68 Ga-labeled affibody, 68 Ga-MZHER, in both tumor models were also determined. RESULTS: The tumor-formation time in chicken CAM model was shorter than that of mouse model. The uptake values of human epithelial growth factor receptor-2 (HER2)-positive Bcap37 tumors in chicken CAM and mouse models were 5.36 ± 0.26% ID/g and 5.26 ± 0.43% ID/g at 30 min postinjection of 68 Ga-MZHER, respectively. At the same time points, the uptake values of HER2-negative MDA-MB-231 tumors in the chicken CAM models and mouse models were 1.57 ± 0.15% ID/g and 1.67 ± 0.25% ID/g, respectively. Ex vivo biodistribution confirmed that more radioactivity accumulated in Bcap37 tumors than in MDA-MD-231 tumors in both CAM and mouse models. CONCLUSION: In this study, the CAM tumor model was successfully prepared. The chicken CAM model is a novel tool for quickly determining the in vivo properties of radiolabeled peptides targeting biomarkers. It may be beneficial for early monitoring of the therapeutic effect of a new drug through PET imaging with specific peptides.

Machine learning-based prediction model for myocardial ischemia under high altitude exposure: a cohort study.

High altitude exposure increases the risk of myocardial ischemia (MI) and subsequent cardiovascular death. Machine learning techniques have been used to develop cardiovascular disease prediction models, but no reports exist for high altitude induced myocardial ischemia. Our objective was to establish a machine learning-based MI prediction model and identify key risk factors. Using a prospective cohort study, a predictive model was developed and validated for high-altitude MI. We consolidated the health examination and self-reported electronic questionnaire data (collected between January and June 2022 in 920th Joint Logistic Support Force Hospital of china) of soldiers undergoing high-altitude training, along with the health examination and second self-reported electronic questionnaire data (collected between December 2022 and January 2023) subsequent to their completion on the plateau, into a unified dataset. Participants were subsequently allocated to either the training or test dataset in a 3:1 ratio using random assignment. A predictive model based on clinical features, physical examination, and laboratory results was designed using the training dataset, and the model's performance was evaluated using the area under the receiver operating characteristic curve score (AUC) in the test dataset. Using the training dataset (n = 2141), we developed a myocardial ischemia prediction model with high accuracy (AUC = 0.86) when validated on the test dataset (n = 714). The model was based on five laboratory results: Eosinophils percentage (Eos.Per), Globulin (G), Ca, Glucose (GLU), and Aspartate aminotransferase (AST). Our concise and accurate high-altitude myocardial ischemia incidence prediction model, based on five laboratory results, may be used to identify risks in advance and help individuals and groups prepare before entering high-altitude areas. Further external validation, including female and different age groups, is necessary.

Long-term effects of PM2.5 constituents on metabolic syndrome and mediation effects of serum uric acid.

Exposure to particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5) was associated with the risk for metabolic syndrome (MetS) in the general population, but the contributions of individual PM2.5 constituents to this association and the potential pathway between PM2.5 constituents and MetS risk are not well elaborated. This study aimed to investigate associations between PM2.5 constituents and MetS in general populations, relative importance of PM2.5 constituents to and mediation effects of serum uric acid (SUA) on those associations. The 48,148 participants from a provincially representative cohort established in southwest China were included. The 3-year average concentrations of PM2.5 and its constituents (nitrate [NO3-], sulfate [SO42-], ammonium [NH4+], organic matter [OM], and black carbon [BC]) were estimated using a series of machine-learning models. Multivariate logistic regression and weighted quantile sum regression were used to estimate effects of independent PM2.5 constituents on MetS and their contributions to the joint effect. Mediation analysis examined the potential mediation effects of SUA on the associations between PM2.5 constituents and MetS. Each interquartile range (IQR) increase in the concentration of PM2.5 constituents was all positively associated with the increased MetS odds, including SO42- (OR = 1.15 [1.11, 1.19]]), NO3- (OR = 1.12 [1.08, 1.16]), NH4+ (OR = 1.13 [1.09, 1.17]), OM (OR = 1.09 [1.06, 1.13]), and BC (OR = 1.09 [1.06, 1.13]). Their joint associations on MetS were mainly attributed to SO42- (weight=46.1%) and NH4+ (44.0%). The associations of PM2.5 constituents with abnormal MetS components were mainly attributed to NH4+ for elevated BP (51.6%) and reduced HDL-C (97.0%), SO42- for elevated FG (68.9%), NO3- for elevated TG (51.0%), and OM for elevated WC (63.0%). Percentages mediated by SUA for the associations of PM2.5, SO42-, NO3-, and BC with MetS were 13.6%, 13.1%, 10.6%, and 11.1%, respectively. Long-term exposure to PM2.5 constituents, mainly NH4+ and SO42-, was positively associated with MetS odds, partially mediated by SUA.

LAMP assay coupled with a CRISPR/Cas12a system for the rapid and ultrasensitive detection of porcine circovirus-like virus in the field.

A recent outbreak of porcine circovirus-like virus (PCLV), a virus that may be associated with porcine diarrhea, has been reported in swine herds in China. The virus is spreading rapidly, causing huge economic losses to the swine farming industry. To achieve the rapid, inexpensive, and sensitive detection of PCLV, we combined loop-mediated isothermal amplification (LAMP) and the CRISPR/Cas12a system, whose fluorescence intensity readout can detect PCLV ORF4 gene levels as low as 10 copies. To overcome the need for sophisticated equipment, lateral flow strip reading technology was introduced for the first time in a LAMP-Cas12a-based system to detect PCLV. The lateral flow strip (LFS) results were readout by the naked eye, and the method was highly sensitive with a detection limit of 10 copies, with a detection time of about 60 min. In addition, the method is highly specific and has no cross-reactivity with other related viruses. In conclusion, LAMP-CRISPR/Cas12a-based assays have the advantages of rapidity, accuracy, portability, low cost, and visualization of the results. They therefore have great potential, especially for areas where specialized equipment is lacking, and can expect to be an ideal method for early diagnosis and on-site detection of PCLV.

Effect of Tissue Pedicle Position on Postoperative Recovery From Severe Auricular Laceration.

BACKGROUND: Postoperative recovery from severe auricular lacerations varies significantly. However, few studies have sought to clarify the risk factors associated with the prognosis of severe auricular lacerations, and little attention has been paid to the intraoperative management of severe auricular lacerations and early postoperative intervention. The purpose of this study was to analyze the risk factors that may affect the prognosis of severe auricular lacerations. METHODS: Case data and imaging data of patients with severe auricular lacerations treated in our department between January 2018 and September 2022 were collected. A total of 90 patients (90 severe auricular lacerations) were included in the analysis and were divided into good group (68 cases) and poor group (22 cases) according to postoperative recovery, which was defined as poor postoperative recovery when postoperative auricular blood supply disorders required interventional treatment or second stage plastic surgery. RESULTS: The percentage of ventral tissue pedicles in the poor recovery group was 77.3% ( P <0.001). The proportion of ventral tissue pedicle was significantly higher in the poor postoperative group than in the good postoperative group, and ventral tissue pedicle [odds ratio (OR)=12.22, P =0.002] was an independent risk factor for poor postoperative recovery from severe auricular laceration. CONCLUSIONS: The prognosis of patients with severe auricular lacerations differs between the different tissue pedicle locations, and prophylactic treatment of patients with ventral tissue pedicles is beneficial. In addition, patients with ventral tissue pedicles should be informed in advance of their increased risk of surgical failure.

Gene expression analysis to identify mechanisms underlying improvement of myocardial fibrosis by finerenone in SHR.

Both spironolactone and finerenone treatments significantly reduced SBP and there was no statistical difference in their antihypertensive effects. The differences in body weight (at the end of 1/2/3/4 week) to pre-dose body weight ratio and heart rate (at the end of 1/2/3/4 week) to pre-dose heart rate ratio were not statistically significant in the vehicle, spironolactone, finerenone, and control groups.There was no statistically significant difference in mortality among the vehicle, spironolactone, and finerenone groups. The relative heart mass, ANP, BNP, CVF, Col I, TGF-ß, and Casp-3 were gradually decreased in vehicle group, spironolactone group, and finerenone group. Among them, BNP, CVF, TGF-ß, and Casp-3 were significantly decreased in the finerenone group compared with the vehicle group. HE and Masson staining showed that the cardiomyocytes of rats in the vehicle group and spironolactone group were disorganized, with cell hypertrophy, significantly enlarged cell gaps and a large amount of collagen deposition, whereas the cardiomyocytes of rats in the finerenone group and the control group were more neatly arranged, with smaller cell gaps and a small amount of collagen tissue deposition. RNA sequencing (RNA-seq) showed that there was a total of 119 differentially expressed genes (DEGs) between finerenone treatment and vehicle treatment. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that the signaling pathways involved were mainly in drug metabolism-cytochrome P450, chemical carcinogenesis, IL-17 signaling pathway, axon guidance, and hematopoietic cell lineage. Protein-protein interaction (PPI) analysis showed that the core genes were Oaslf, Nos2, LOC687780, Rhobtb1, Ephb3, and Rps27a.

Avian pathogenic Escherichia coli infection causes infiltration of heterophilic granulocytes of chick tracheal by the complement and coagulation cascades pathway.

BACKGROUND: Avian pathogenic Escherichia coli (APEC) causes tracheal damage and heterophilic granulocytic infiltration and inflammation in infected chicks. In this study, we infected chick tracheal tissue with strain AE17 and produced pathological sections with proteomic sequencing. We compared the results of pathological sections from the APEC-infected group with those from the PBS control group; the pathological sections from the experimental group showed hemorrhage, fibrinization, and infiltration of heterophilic granulocytes in the tracheal tissue. In order to explore the effect on proteomics on inflammation and to further search for the caus. RESULTS: The tandem mass tag-based (TMT) sequencing analysis showed 224 upregulated and 140 downregulated proteins after infection with the AE17 strain. Based on the results of KEGG in Complement and coagulation cascades, differential protein expression in the Protein export pathway was upregulated. CONCLUSIONS: With these results, we found that chemokines produced by the Complement and coagulation cascades pathway may cause infiltration of heterophilic granulocytes involved in inflammation, as well as antimicrobial factors produced by the complement system to fight the infection together.These results suggest that APEC causes the infiltration of heterophilic granulocytes through the involvement of the complement system with serine protease inhibitors.