Newcastle disease virus activates diverse signaling pathways via Src to facilitate virus entry into host macrophages.

As an intrinsic cellular mechanism responsible for the internalization of extracellular ligands and membrane components, caveolae-mediated endocytosis (CavME) is also exploited by certain pathogens for endocytic entry [e.g., Newcastle disease virus (NDV) of paramyxovirus]. However, the molecular mechanisms of NDV-induced CavME remain poorly understood. Herein, we demonstrate that sialic acid-containing gangliosides, rather than glycoproteins, were utilized by NDV as receptors to initiate the endocytic entry of NDV into HD11 cells. The binding of NDV to gangliosides induced the activation of a non-receptor tyrosine kinase, Src, leading to the phosphorylation of caveolin-1 (Cav1) and dynamin-2 (Dyn2), which contributed to the endocytic entry of NDV. Moreover, an inoculation of cells with NDV-induced actin cytoskeletal rearrangement through Src to facilitate NDV entry via endocytosis and direct fusion with the plasma membrane. Subsequently, unique members of the Rho GTPases family, RhoA and Cdc42, were activated by NDV in a Src-dependent manner. Further analyses revealed that RhoA and Cdc42 regulated the activities of specific effectors, cofilin and myosin regulatory light chain 2, responsible for actin cytoskeleton rearrangement, through diverse intracellular signaling cascades. Taken together, our results suggest that an inoculation of NDV-induced Src-mediated cellular activation by binding to ganglioside receptors. This process orchestrated NDV endocytic entry by modulating the activities of caveolae-associated Cav1 and Dyn2, as well as specific Rho GTPases and downstream effectors. IMPORTANCE: In general, it is known that the paramyxovirus gains access to host cells through direct penetration at the plasma membrane; however, emerging evidence suggests more complex entry mechanisms for paramyxoviruses. The endocytic entry of Newcastle disease virus (NDV), a representative member of the paramyxovirus family, into multiple types of cells has been recently reported. Herein, we demonstrate the binding of NDV to induce ganglioside-activated Src signaling, which is responsible for the endocytic entry of NDV through caveolae-mediated endocytosis. This process involved Src-dependent activation of the caveolae-associated Cav1 and Dyn2, as well as specific Rho GTPase and downstream effectors, thereby orchestrating the endocytic entry process of NDV. Our findings uncover a novel molecular mechanism of endocytic entry of NDV into host cells and provide novel insight into paramyxovirus mechanisms of entry.

Superassembled Mesoporous Carbon-Fe2O3 Heterochannels for Photothermal-Enhanced Hyaluronidase Sensing.

Developing an activity detection platform for hyaluronidase (HAase) is crucial for diagnosing and treating cancer. However, traditional detection of HAase is based on changes in the flow rate caused by viscosity or requires complex modifications and processing, which limits the detection accuracy and sensitivity. Herein, hyaluronic acid (HA)-modified mesoporous-based heterochannels (mesoporous carbon-doped γ-Fe2O3 nanoparticles/anodized aluminum oxide, MC-γ-Fe2O3/AAO) featuring ordered 3D transport frameworks and a photothermal property were developed for high performance HAase detection. The HA molecules on the surface of the mesoporous layer provide abundant active sites for HAase detection. An improved ionic current was realized after enzymatic hydrolysis reactions between HA and HAase due to enhanced surface charges and more hydrophilicity, leading to highly sensitive and accurate HAase detection. Notably, the detection performance can be further upgraded with the assistance of the photothermal property of γ-Fe2O3. An amplified detection current signal was achieved owing to a synergistic effect between ion currents and photoresponsive currents. A wide linear detection range from 1 to 50 U/mL and a low detection limit of 0.348 U/mL were obtained, achieving a 2% improvement under illumination. Importantly, the heterochannels have also been successfully applied for HAase detection in fetal bovine serum samples, manifesting considerable application prospects. This work provides a new strategy in constructing photoresponsive nanochannels with a photothermal property for a highly efficient biosensing platform.

Quantifying carboxymethyl lysine and carboxyethyl lysine in human plasma: clinical insights into aging research using liquid chromatography-tandem mass spectrometry.

OBJECTIVE: The objective of this study was to establish a methodology for determining carboxymethyl lysine (CML) and carboxyethyl lysine (CEL) concentrations in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The test results were also used for clinical aging research. METHODS: Human plasma samples were incubated with aqueous perfluorovaleric acid (NFPA), succeeded by precipitation utilizing trichloroacetic acid, hydrolysis facilitated by hydrochloric acid, nitrogen drying, and ultimate re-dissolution utilizing NFPA, followed by filtration. Cotinine-D3 was added as an internal standard. The separation was performed on an Agela Venusil ASB C18 column (50 mm × 4.6 mm, 5 µm) with a 5 mmol/L NFPA and acetonitrile/water of 60:40 (v/v) containing 0.15% formic acid. The multiple reaction monitoring mode was used for detecting CML, CEL, and cotinine-D3, with ion pairs m/z 205.2 > 84.1 (for quantitative) and m/z 205.2 > m/z 130.0 for CML, m/z 219.1 > 84.1 (for quantitative) and m/z 219.1 > m/z 130.1 for CEL, and m/z 180.1 > 80.1 for cotinine-D3, respectively. RESULTS: The separation of CML and CEL was accomplished within a total analysis time of 6 minutes. The retention times of CML, CEL, and cotinine-D3 were 3.43 minutes, 3.46 minutes, and 4.50 minutes, respectively. The assay exhibited linearity in the concentration range of 0.025-1.500 µmol/L, with a lower limit of quantification of 0.025 µmol/L for both compounds. The relative standard deviations of intra-day and inter-day were both below 9%, and the relative errors were both within the range of ±4%. The average recoveries were 94.24% for CML and 97.89% for CEL. CONCLUSION: The results indicate that the developed methodology is fast, highly sensitive, highly specific, reproducible, and suitable for the rapid detection of CML and CEL in clinical human plasma samples. The outcomes of the clinical research project on aging underscored the important indicative significance of these two indicators for research on human aging.

The Facial Artery Perforator Flap for Reconstruction of Facial Defects: Surgical Pearls and Clinical Series.

BACKGROUND: Based on the knowledge of facial vascularity, facial artery perforator flaps could be used as potent tools for facial defect reconstruction. However, lack of experience and misconception of this technique limits the broad application in the clinical background. Here, we discussed surgical techniques based on our previous experience with facial artery perforator (FAP)-based facial defect reconstruction. METHODS: A retrospective review of 12 patients undergoing facial defect reconstruction using an FAP flap was performed, including 8 defects in the mid-facial part and 4 defects in the nasal area generally resulted from basal cell carcinoma (8 patients), squamous cell carcinoma (3 patients), and actinic keratosis (one patient). RESULTS: All patients received one-stage FAP flap reconstruction. The overall follow-up period was 6 to 12 months. All reconstructions were successful with satisfactory patient-reported outcome and no local recurrence. No significant complications were observed in most cases, except for one instance of partial flap loss. CONCLUSIONS: Overall, taking advantage of FAP flaps will contribute to a good functional and esthetic outcome of facial defect reconstructions.

Selecting Flap Transfer Methods to Repair Helix Soft Tissue Defect Based on the Direction of Long Axis.

BACKGROUND: The posterior auricular flap has long been favored for repairing skin defects on the ear's surface. However, achieving optimal esthetic outcomes in ear reconstruction requires a flexible approach to flap transfer methods. While bipedicle advancement flaps are commonly used for body wound coverage, they are rarely used in auricular defect repair. OBJECTIVE: To propose a modified flap transfer approach based on the orientation of the auricular defect's long axis and assess the postoperative esthetic outcomes. METHODS: The authors reported 12 patients treated using 2 distinct flap transfer techniques. Mild to moderate helix soft tissue defects remained after excision of the masses. A direct island flap was created for patients with longitudinal defects to cover the defect. For patients with transverse defects, a combination of bipedicle and island flaps was used for repair. Scar quality and esthetic outcomes were assessed at least 6 months postsurgery using the Scar Cosmesis Assessment and Rating scale. RESULTS: All patients experienced no serious complications and achieved excellent cosmetic results. Patients undergoing combined flap transfer exhibited relatively more favorable esthetic outcomes. CONCLUSION: The authors propose a novel concept for repairing helix soft tissue defects by designing local flaps based on the direction of the defect's long axis. For repairing helix soft tissue defects with a long axis parallel to the auricular edge, the combined utilization of bipedicle advancement flap and island rotation flap transfer should be consideration more.

Empirical and simulated investigation of the solid waste reverse supply chain: A complex adaptive system perspective.

Solid waste is increasing rapidly worldwide. In this study, the solid waste (household waste, construction and demolition waste and industrial waste) management systems are treated as reverse supply chain to analyze the critical operational issues based on complex adaptive system theory. At the single-layer, the complexity of the various nodes at a layer arises from rational decision-making and behavioral heterogeneity. The solid waste generation layer is employed as an example to investigate the complexity of node behavioral decisions. Regression analysis results reveal that both endogenous (Attitude, Subjective norm, and Perceived behavioral control) and exogenous factors (Economic incentive, Government supervision, Technical support) positively influence sorting behavior. The effect of Economic incentive (ß=0.327P<0.001) and Attitude (ß=0.249P<0.001) on sorting behavior are the largest. In the multi-layer system, different layers communicate with each other through the material and financial flows and have cross-layer impacts. An agent-based model is developed to investigate the multi-layer feedforward influence mechanism of changes in key layers (e.g., sorting rate, disposal rate) and the material and financial flows adaptive adjustment direction of the solid waste reverse supply chain. High rate of participation and accuracy of source sorting can shorten material flow paths and reduce storage and transportation costs. The increase in disposal rate encourages the transition of solid waste from backfill to resource utilization. This study provides a practice reference for solid waste reverse supply chain and related enterprises managers.

Artificial Layer Construction via Cosolvent Enables Stable Ni-Rich Cathodes for Enhanced Lithium Storage.

Ni-rich cathodes have recently gained significant attention as next-generation cathodes for lithium-ion batteries. However, their relatively high oxidative surface should be reduced to control the high surface reactivity because the capacity retention decreases rapidly in the batteries. Herein, a simple and effective method to pretreat LiNi0.8Mn0.1Co0.1O2 (NMC811) particles using a cosolvent for improving the battery performance is reported. Imitating the interfacial reaction in practical cells, an artificial layer is created via a spontaneous redox reaction between the cathode and the organic solvent. The artificial layer comprises metal-organic compounds with reduced transition-metal cations. Benefiting from the artificial layer, the cells deliver high capacity retention at a high current density and better rate capability, which might result from the low and stable interfacial resistance of the modified NMC811 cathode. Our approach can effectively reduce the high oxidative surface of most oxide cathode materials and induce a long cyclic lifespan and high capacity retention in most battery systems.

Sample-to-answer salivary miRNA testing: New frontiers in point-of-care diagnostic technologies.

MicroRNA (miRNA), crucial non-coding RNAs, have emerged as key biomarkers in molecular diagnostics, prognosis, and personalized medicine due to their significant role in gene expression regulation. Salivary miRNA, in particular, stands out for its non-invasive collection method and ease of accessibility, offering promising avenues for the development of point-of-care diagnostics for a spectrum of diseases, including cancer, neurodegenerative disorders, and infectious diseases. Such development promises rapid and precise diagnosis, enabling timely treatment. Despite significant advancements in salivary miRNA-based testing, challenges persist in the quantification, multiplexing, sensitivity, and specificity, particularly for miRNA at low concentrations in complex biological mixtures. This work delves into these challenges, focusing on the development and application of salivary miRNA tests for point-of-care use. We explore the biogenesis of salivary miRNA and analyze their quantitative expression and their disease relevance in cancer, infection, and neurodegenerative disorders. We also examined recent progress in miRNA extraction, amplification, and multiplexed detection methods. This study offers a comprehensive view of the development of salivary miRNA-based point-of-care testing (POCT). Its successful advancement could revolutionize the early detection, monitoring, and management of various conditions, enhancing healthcare outcomes. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices.

Adaptive Regularized Tri-Factor Non-Negative Matrix Factorization for Cell Type Deconvolution.

Accurate deconvolution of cell types from bulk gene expression is crucial for understanding cellular compositions and uncovering cell-type specific differential expression and physiological states of diseased tissues. Existing deconvolution methods have limitations, such as requiring complete cellular gene expression signatures or neglecting partial biological information. Moreover, these methods often overlook varying cell-type mRNA amounts, leading to biased proportion estimates. Additionally, they do not effectively utilize valuable reference information from external studies, such as means and ranges of population cell-type proportions. To address these challenges, we introduce an Adaptive Regularized Tri-factor non-negative matrix factorization approach for deconvolution (ARTdeConv). We rigorously establish the numerical convergence of our algorithm. Through benchmark simulations, we demonstrate the superior performance of ARTdeConv compared to state-of-the-art semi-reference-based and reference-free methods. In a real-world application, our method accurately estimates cell proportions, as evidenced by the nearly perfect Pearson's correlation between ARTdeConv estimates and flow cytometry measurements in a dataset from a trivalent influenza vaccine study. Moreover, our analysis of ARTdeConv estimates in COVID-19 patients reveals patterns consistent with important immunological phenomena observed in other studies. The proposed method, ARTdeConv, is implemented as an R package and can be accessed on GitHub for researchers and practitioners.

Adipose-derived stem cells enriched with therapeutic mRNA TGF-ß3 and IL-10 synergistically promote scar-less wound healing in preclinical models.

Skin wound healing often leads to scar formation, presenting physical and psychological challenges for patients. Advancements in messenger RNA (mRNA) modifications offer a potential solution for pulsatile cytokine delivery to create a favorable wound-healing microenvironment, thereby preventing cutaneous fibrosis. This study aimed to investigate the effectiveness of human adipose-derived stem cells (hADSCs) enriched with N 1-methylpseudouridine (m1ψ) modified transforming growth factor-ß3 (TGF-ß3) and interleukin-10 (IL-10) mRNA in promoting scar-free healing in preclinical models. The results demonstrated that the modified mRNA (modRNA)-loaded hADSCs efficiently and temporarily secreted TGF-ß3 and IL-10 proteins. In a dorsal injury model, hADSCs loaded with modRNA TGF-ß3 and IL-10 exhibited multidimensional therapeutic effects, including improved collagen deposition, extracellular matrix organization, and neovascularization. In vitro experiments confirmed the ability of these cells to markedly inhibit the proliferation and migration of keloid fibroblasts, and reverse the myofibroblast phenotype. Finally, collagen degradation mediated by matrix metalloproteinase upregulation was observed in an ex vivo keloid explant culture model. In conclusion, the synergistic effects of the modRNA TGF-ß3, IL-10, and hADSCs hold promise for establishing a scar-free wound-healing microenvironment, representing a robust foundation for the management of wounds in populations susceptible to scar formation.

LRP1 facilitates hepatic glycogenesis by improving the insulin signaling pathway in HFD-fed mice.

BACKGROUND: LDL receptor-related protein-1 (LRP1) is a cell-surface receptor that functions in diverse physiological pathways. We previously demonstrated that hepatocyte-specific LRP1 deficiency (hLRP1KO) promotes diet-induced insulin resistance and increases hepatic gluconeogenesis in mice. However, it remains unclear whether LRP1 regulates hepatic glycogenesis. METHODS: Insulin signaling, glycogenic gene expression, and glycogen content were assessed in mice and HepG2 cells. The pcDNA 3.1 plasmid and adeno-associated virus serotype 8 vector (AAV8) were used to overexpress the truncated ß-chain (ß∆) of LRP1 both in vitro and in vivo. RESULTS: On a normal chow diet, hLRP1KO mice exhibited impaired insulin signaling and decreased glycogen content. Moreover, LRP1 expression in HepG2 cells was significantly repressed by palmitate in a dose- and time-dependent manner. Both LRP1 knockdown and palmitate treatment led to reduced phosphorylation of Akt and GSK3ß, increased levels of phosphorylated glycogen synthase (GYS), and diminished glycogen synthesis in insulin-stimulated HepG2 cells, which was restored by exogenous expression of the ß∆-chain. By contrast, AAV8-mediated hepatic ß∆-chain overexpression significantly improved the insulin signaling pathway, thus activating glycogenesis and enhancing glycogen storage in the livers of high-fat diet (HFD)-fed mice. CONCLUSION: Our data revealed that LRP1, especially its ß-chain, facilitates hepatic glycogenesis by improving the insulin signaling pathway, suggesting a new therapeutic strategy for hepatic insulin resistance-related diseases.

[Facial nerve protection in surgery for rare tumors of the internal auditory canal].

Objective:To explore strategies for preserving facial nerve function during surgeries for rare tumors of the internal auditory canal. Methods:A total of 235 cases of internal auditory canal tumors treated between 2010 and 2023 were included, encompassing vestibular schwannomas, cavernous hemangiomas, meningiomas, and other rare tumors. Various data, including clinical presentations, imaging classifications, and treatment processes, were meticulously analyzed to delineate the characteristics of rare tumors and assess pre-and postoperative facial nerve function. Results:Among all internal auditory canal tumors, vestibular schwannomas accounted for 91.9%. In rare tumors, facial nerve schwannomas constituted 5.3%, cavernous hemangiomas 26.3%, meningiomas 15.8%, and arterial aneurysms 10.5%. Significantly, patients with cavernous hemangiomas displayed pronounced invasion of the facial nerve by the tumor, in contrast to other tumor types where clear boundaries with the facial nerve were maintained. During surgery, individualized approaches and strategies for facial nerve protection were implemented for different tumor types, involving intraoperative dissection, tumor excision, and facial nerve reconstruction. Conclusion:Preservation of the facial nerve is crucial in the surgical management of rare tumors of the internal auditory canal. Accurate preoperative diagnosis, appropriate timing of surgery, selective surgical approaches, and meticulous intraoperative techniques can maximize the protection of facial nerve function. Personalized treatment plans and strategies for facial nerve functional reconstruction are anticipated to enhance surgical success rates, reduce the risk of postoperative facial nerve dysfunction, and ultimately improve the quality of life for patients.

Novel compound heterozygous mutations of the FBP1 gene in a patient with hypoglycemia and lactic acidosis: A case report.

BACKGROUND: Fructose-1,6-bisphosphatase (FBPase) deficiency, caused by an FBP1 mutation, is an autosomal recessively inherited metabolic disorder characterized by impaired gluconeogenesis. Due to the rarity of FBPase deficiency, the mechanism by which the mutations cause enzyme activity loss still remains unclear. METHODS: We report a pediatric patient with typical FBPase deficiency who presented with hypoglycemia, hyperlactatemia, metabolic acidosis, and hyperuricemia. Whole-exome sequencing was used to search for pathogenic genes, Sanger sequencing was used for verification, and molecular dynamic simulation was used to evaluate how the novel mutation affects FBPase activity and structural stability. RESULTS: Direct and allele-specific sequence analysis of the FBP1 gene (NM_000507) revealed that the proband had a compound heterozygote for the c. 490 (exon 4) G>A (p. G164S) and c. 861 (exon 7) C>A (p. Y287X, 52), which he inherited from his carrier parents. His father and mother had heterozygous G164S and Y287X mutations, respectively, without any symptoms of hypoglycemia. CONCLUSION: Our results broaden the known mutational spectrum and possible clinical phenotype of FBP1.

Genome-wide identification and characterization of the AP2/ERF gene family in loblolly pine (Pinus taeda L.).

The loblolly pine (Pinus taeda L.) is one of the most profitable forest species worldwide owing to its quick growth, high wood yields, and strong adaptability. The AP2/ERF gene family plays a widespread role in the physiological processes of plant defense responses and the biosynthesis of metabolites. Nevertheless, there are no reports on this gene family in loblolly pine (P. taeda). In this study, a total of 303 members of the AP2/ERF gene family were identified. Through multiple sequence alignment and phylogenetic analysis, they were classified into four subfamilies, including AP2 (34), RAV (17), ERF (251), and Soloist (1). An analysis of the conservation domains, conserved motifs, and gene structure revealed that every PtAP2/ERF transcription factor (TF) had at least one AP2 domain. While evolutionary conservation was displayed within the same subfamilies, the distribution of conserved domains, conserved motifs, and gene architectures varied between subfamilies. Cis-element analysis revealed abundant light-responsive elements, phytohormone-responsive elements, and stress-responsive elements in the promoter of the PtAP2/ERF genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of potential target genes showed that the AP2/ERF gene family might play a critical role in plant growth and development, the response to environmental stresses, and metabolite biosynthesis. Utilizing quantitative real-time PCR (qRT-PCR), we examined the expression patterns of 10 randomly selected genes from Group IX after 6 h of treatments with mechanical injury, ethephon (Eth), and methyl jasmonate (MeJA). The AP2/ERF gene family in the loblolly pine was systematically analyzed for the first time in this study, offering a theoretical basis for exploring the functions and applications of AP2/ERF genes.

Whole-Genome Resequencing Revealed Selective Signatures for Growth Traits in Hu and Gangba Sheep.

A genomic study was conducted to uncover the selection signatures in sheep that show extremely significant differences in growth traits under the same breed, age in months, nutrition level, and management practices. Hu sheep from Gansu Province and Gangba sheep from the Tibet Autonomous Region in China were selected. We collected whole-genome data from 40 sheep individuals (24 Hu sheep and 16 Gangba sheep), through whole-genome sequencing. Selection signals were analyzed using parameters such as FST, π ratio, and Tajima's D. We have identified several candidate genes that have undergone strong selection, particularly those associated with growth traits. Specifically, five growth-related genes were identified in both the Hu sheep group (HDAC1, MYH7B, LCK, ACVR1, GNAI2) and the Gangba sheep group (RBBP8, ACSL3, FBXW11, PLAT, CRB1). Additionally, in a genomic region strongly selected in both the Hu and Gangba sheep groups (Chr 22: 51,425,001-51,500,000), the growth-associated gene CYP2E1 was identified, further highlighting the genetic factors influencing growth characteristics in these breeds. This study analyzes the genetic basis for significant differences in sheep phenotypes, identifies candidate genes related to sheep growth traits, lays the foundation for molecular genetic breeding in sheep, and accelerates the genetic improvement in livestock.

Identification and validation of ferroptosis-related lncRNA signature in intervertebral disc degeneration.

Low back pain influences people of every age and is one of the major contributors to the global cost of illness. Intervertebral disc degeneration (IVDD) is a major contributor to low back pain, but its pathogenesis is unknown. Recently, ferroptosis has been shown to have a substantial role in modulating IVDD progression. However, the function of ferroptosis-related long non-coding RNAs (lncRNAs) has rarely been reported in IVDD. Consequently, the research was conducted to explore the ferroptosis-related lncRNA signature in the IVDD occurrence and development. We analyzed two datasets (GSE167199 and GSE167931) archived in the NCBI Gene Expression Omnibus (GEO) public database. We screened differentially expressed genes (DEGs) and differentially expressed lncRNAs (DELncs) in these datasets using the limma package. Ferroptosis-related genes (FRGs) were derived from the FerrDb V2 website and the intersection of DEGs and FRGs was considered as differentially expressed ferroptosis-related genes (DFGs). These genes were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Correlations between DFGs and DELncs were shown by Pearson test to determine differential expression of ferroptosis-related lncRNAs. The Pearson test showed that CPEB1-HTR2A-AS1 and ACSL3-DNAJC27-AS1 pairs had correlation coefficients over 0.9. Twenty ferroptosis-related lncRNAs were identified and validated in IVDD. Eight of these lncRNAs were upregulated in IVDD nucleus pulposus cells, including HTR2A-AS1, MIF-AS1, SLC8A1-AS1, LINC00942, DUXAP8, LINC00161, LUCAT1 and LINC01615. Twelve were downregulated in IVDD nucleus pulposus cells, including DNAJC27-AS1, H19, LINC01588, LINC02015, FLNC1, CARMN, PRKG1-AS1, APCDD1L-DT, LINC00839, LINC00536, LINC00710 and LINC01535. Eighteen of the 20 lncRNAs (excluding H19 and LUCAT1) were identified as ferroptosis-related lncRNAs for the first time and verified in IVDD. We have identified a ferroptosis-related lncRNA signature involved in IVDD and revealed a close relationship between CPEB1 and HTR2A-AS1, and between ACSL3 and DNAJC27-AS1. Our findings indicate that ferroptosis-related lncRNAs are a new target set for the early detection and therapy of IVDD.

Batch production prediction for the mechanical cutting industry based on process capability.

In the mechanical cutting industry, trial production is used for predicting and evaluating the quality of product processes before batch production, and it can be expressed through the qualification rate. However, it cannot objectively and comprehensively evaluate the quality of product processes. This study optimizes the analysis of outliers and stability in mathematical statistics to better apply it in the mechanical cutting industry; then, it combines them with process capability analysis. Simultaneously, considering the non-normal distribution of process parameters, a batch production-prediction model is proposed. The reliability of batch production-prediction model is verified by the diameter, roundness and roughness of structural common samples. Meanwhile, for other mechanical parts in the mechanical cutting industry, the model proposed in this paper can be used to quickly and accurately predict and evaluate batch production.

Salvia miltiorrhiza ameliorates endometritis in dairy cows by relieving inflammation, energy deficiency and blood stasis.

Introduction: According to traditional Chinese veterinary medicine, endometritis is caused by a combination of Qi deficiency, blood stasis, and external evil invasion. Salvia miltiorrhiza is a traditional Chinese medicine that counteracts blood stasis and has additional demonstrated effects in boosting energy and restraining inflammation. Salvia miltiorrhiza has been employed in many traditional Chinese prescriptions that have proven effective in healing clinical dairy cow endometritis. Methods: the in vivo effect of Salvia miltiorrhiza in treating endometritis was evaluated in dairy cows. In addition, bovine endometrial epithelium cell inflammation and rat blood stasis models were employed to demonstrate the crosstalk between energy, blood circulation and inflammation. Network analysis, western blotting, qRT-PCR and ELISA were performed to investigate the molecular mechanism of Salvia miltiorrhiza in endometritis treatment. Results: The results demonstrate that treatment with Salvia miltiorrhiza relieves uterine inflammation, increases blood ATP concentrations, and prolongs blood clotting times. Four of the six Salvia miltiorrhiza main components (SMMCs) (tanshinone IIA, cryptotanshinone, salvianolic acid A and salvianolic acid B) were effective in reversing decreased ATP and increased IL-1ß, IL-6, and IL-8 levels in an in vitro endometritis model, indicating their abilities to ameliorate the negative energy balance and external evil invasion effects of endometritis. Furthermore, in a blood stasis rat model, inflammatory responses were induced in the absence of external infection; and all six SMMCs inhibited thrombin-induced platelet aggregation. Network analysis of SMMC targets predicted that Salvia miltiorrhiza may mediate anti-inflammation via the Toll-like receptor signaling pathway; anti-aggregation via the Platelet activation pathway; and energy balance via the Thermogenesis and AMPK signaling pathways. Multiple molecular targets within these pathways were verified to be inhibited by SMMCs, including P38/ERK-AP1, a key molecular signal that may mediate the crosstalk between inflammation, energy deficiency and blood stasis. Conclusion: These results provide mechanistic understanding of the therapeutic effect of Salvia miltiorrhiza for endometritis achieved through Qi deficiency, blood stasis, and external evil invasion.

Interdisciplinary collaborative eye examinations to protect preterm infant neurodevelopment: a quality improvement project.

Introduction: Infants born <31 weeks gestational age with birth weight ≤ 1,500 grams receive routine eye examinations to screen for Retinopathy of Prematurity (ROP) while in the Neonatal Intensive Care Unit (NICU) to help prevent vision threatening complications; however, preterm infants' sensory systems are underdeveloped, and repeated exposure to painful stimuli is associated with worse developmental outcomes. Methods: An interdisciplinary NICU team designed a collaborative eye exam model (CEEM) incorporating best practice recommendations for infant pain control during exams. Pain scores and vital signs were recorded before, during, and after exams. Two sets of mixed-effects regression models with a random intercept on infants were established to investigate relationships between the intervention, birth gestational age (BGA), postmenstrual age (PMA), and outcomes associated with painful stimuli. Survey feedback was elicited from NICU stakeholders about the CEEM. Results: Thirty standard of care (SC) and 35 CEEM exams of 37 infants were included in final analysis. In infants of the same BGA, the number of desaturation events was significantly reduced in the CEEM group (p = 0.003) and became 1.53 times smaller with each additional week of BGA (p = 0.009). Probability of heart rate recovery within 15 min lowered significantly in the CEEM group (p = 0.04). In SC or CEEM or between infants of the same PMA, no differences were observed for bradycardia, heart rate range, chance of heart rate recovery, or pain scores. Increases in tachycardia (p < 0.001) events and desaturations p = 0.006 were discovered in the CEEM group. When considering interaction effects, the CEEM appeared to reduce the number of desaturations to a greater degree for infants at earliest BGAs with attenuation of this effect with greater BGA. Regarding PMA, bradycardia and tachycardia events were reduced for infants across PMAs in the CEEM, but the effect for tachycardia improves with age, while the effect for bradycardia diminishes with age. Stakeholders agreed that the infant's eye exam experience and the staff experience was "very much" improved by the CEEM. Discussion: Despite variable findings in selected outcome measures, the CEEM was positively viewed by staff. Infants may benefit from the CEEM differently based on BGA and PMA.