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BACKGROUND: 1.8 million Veterans are estimated to need legal services, such as for housing eviction prevention, discharge upgrades, and state and federal Veterans benefits. While having ones legal needs met is known to improve ones health and its social determinants, many Veterans legal needs remain unmet. Public Law 116-315 enacted in 2021 authorizes VA to fund legal services for Veterans (LSV) by awarding grants to legal service providers including nonprofit organizations and law schools legal assistance programs. This congressionally mandated LSV initiative will award grants to about 75 competitively selected entities providing legal services. This paper describes the protocol for evaluating the initiative. The evaluation will fulfill congressional reporting requirements, and inform continued implementation and sustainment of LSV over time. METHODS: Our protocol calls for a prospective, mixed-methods observational study with a repeated measures design, aligning to the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) and Integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) frameworks. In 2023, competitively selected legal services-providing organizations will be awarded grants to implement LSV. The primary outcome will be the number of Veterans served by LSV in the 12 months after the awarding of the grant. The evaluation has three Aims. Aim 1 will focus on measuring primary and secondary LSV implementation outcomes aligned to RE-AIM. Aim 2 will apply the mixed quantitative-qualitative Matrixed Multiple Case Study method to identify patterns in implementation barriers, enablers, and other i-PARIHS-aligned factors that relate to observed outcomes. Aim 3 involves a mixed-methods economic evaluation to understand the costs and benefits of LSV implementation. DISCUSSION: The LSV initiative is a new program that VA is implementing to help Veterans who need legal assistance. To optimize ongoing and future implementation of this program, it is important to rigorously evaluate LSVs outcomes, barriers and enablers, and costs and benefits. We have outlined the protocol for such an evaluation, which will lead to recommending strategies and resource allocation for VAs LSV implementation.

Hepcidin reduces iron absorption by binding to the intestinal iron transporter ferroportin, thereby causing its degradation. Although short-term administration of testosterone or growth hormone (GH) has been reported to decrease circulating hepcidin levels, little is known about how hepcidin is influenced in human endocrine conditions associated with anemia.We used a sensitive and specific dual-monoclonal antibody sandwich immunoassay to measure hepcidin-25 in patients (a) during initiation of in vitro fertilization when endogenous estrogens were elevated vs. suppressed, (b) with GH deficiency before and after 12 months substitution treatment, (c) with hyperthyroidism before and after normalization, and (d) with hyperprolactinemia before and after six months of treatment with a dopamine agonist.In response to a marked stimulation of endogenous estrogen production, median hepcidin levels decreased from 4.85 to 1.43 ng/mL (p < 0.01). Hyperthyroidism, hyperprolactinemia, or GH substitution to GH-deficient patients did not influence serum hepcidin-25 levels.In humans, gonadotropin-stimulated endogenous estrogen markedly decreases circulating hepcidin-25 levels. No clear and stable correlation between iron biomarkers and hepcidin-25 was seen before or after treatment of hyperthyroidism, hyperprolactinemia or growth hormone deficiency.

To characterize treatment-seeking young adults (16-25 years) with severe obesity, particularly mental health problems.Cross-sectional study of 165 participants (132 women, 33 men) with BMI ≥35 kg/m2 or ≥30 kg/m2 with comorbidities, enrolling in a multidisciplinary obesity treatment program.Data collection at admission of present and life-time health issues including symptomatology of anxiety, depression (Hospital Anxiety and Depression Scale) and attention-deficit/hyperactivity disorder (Adult ADHD Self-Report scale); self-esteem (Rosenberg Self-Esteem Scale), suicide attempts, health-related quality of life (Short Form-36 Health Survey), psychosocial functioning related to obesity (Obesity-related Problems Scale), cardiorespiratory fitness (Astrand's bicycle ergometer test), somatic and psychiatric co-morbidities, cardiometabolic risk factors, and micronutritional status. We used multiple regression analysis to identify variables independently associated with present anxiety and depressive symptomatology.Mean body mass index was 39.2 kg/m2 (SD = 5.2). We found evidence of poor mental health, including present psychiatric diagnoses (29%), symptomatology of anxiety (47%), depression (27%) and attention-deficit/hyperactivity disorder (37%); low self-esteem (42%), attempted suicide (12%), and low quality of life (physical component score = 46, SD = 11.2; mental component score = 36, SD = 13.9, P

Interruption of the enterohepatic circulation of bile acids increases cholesterol catabolism, thereby stimulating hepatic cholesterol synthesis from acetate. We hypothesized that such treatment should lower the hepatic acetate pool which may alter triglyceride and glucose metabolism. We explored this using mice deficient of the ileal sodium-dependent BA transporter (Slc10a2) and ob/ob mice treated with a specific inhibitor of Slc10a2. Plasma TG levels were reduced in Slc10a2-deficient mice, and when challenged with a sucrose-rich diet, they displayed a reduced response in hepatic TG production as observed from the mRNA levels of several key enzymes in fatty acid synthesis. This effect was paralleled by a diminished induction of mature sterol regulatory element-binding protein 1c (Srebp1c). Unexpectedly, the SR-diet induced intestinal fibroblast growth factor (FGF) 15 mRNA and normalized bile acid synthesis in Slc10a2-/- mice. Pharmacologic inhibition of Slc10a2 in diabetic ob/ob mice reduced serum glucose, insulin and TGs, as well as hepatic mRNA levels of Srebp1c and its target genes. These responses are contrary to those reported following treatment of mice with a bile acid binding resin. Moreover, when key metabolic signal transduction pathways in the liver were investigated, those of Mek1/2-Erk1/2 and Akt were blunted after treatment of ob/ob mice with the Slc10a2 inhibitor. It is concluded that abrogation of Slc10a2 reduces hepatic Srebp1c activity and serum TGs, and in the diabetic ob/ob model it also reduces glucose and insulin levels. Hence, targeting of Slc10a2 may be a promising strategy to treat hypertriglyceridemia and diabetes.

ObjectiveIn this experiment, we screened key miRNAs involved in the dexamethasone-induced decrease in osteogenic capacity of mouse precursor osteoblasts MC3T3-E1 over and investigated their specific regulatory mechanisms.MethodsIn this experiment, cell counting kit assay was utilized to act on MC3T3-E1 cells at 0, 5μM, 10μM, 15μM concentrations of dexamethasone for 24h, 48h and 72h to observe the changes in cell viability in order to select the appropriate dexamethasone concentration. Apoptosis and reactive oxygen species were detected by flow cytometry. The transcription of osteogenesis-related genes (Runx2, ALP, OCN, OPN, OPG, COL1A1) and protein expression levels (Runx2, ALP, OCN, OPN) were detected by Western Blot and qRT-PCR to validate the changes in cellular osteogenesis. The differentially expressed miRNAs related to MC3T3-E1 osteogenic differentiation after dexamethasone action were screened out. The expression levels of selected target miRNAs were verified in the experimental group and the control group by qRT-PCR. The miRNA inhibitor was transfected to knock down miRNA in dexamethasone-induced MC3T3-E1 injury. Alkaline phosphatase staining and flow cytometry were performed to detect apoptosis and reactive oxygen species changes. transcript and protein expression levels of osteogenesis-related genes in mouse MC3T3-E1 were detected by qRT-PCR and Western blot experiments. By miRNA target gene prediction, luciferase reporter gene experiments, qRT-PCR and Western blot experiments were used to verify whether the selected target miRNAs targeted the target gene.ResultsFirst, it was determined that 10μM dexamethasone solution was effective in inducing a decrease in osteogenic function in mouse MC3T3-E1 by CCK8 experiments, which showed a significant decrease in alkaline phosphatase activity, a decrease in calcium nodules as shown by alizarin red staining, an increase in apoptosis and reactive oxygen species as detected by flow cytometry, as well as a decrease in the expression of osteogenesis-related genes and proteins. Five target miRNAs were identified: miR-706, miR-296-3p, miR-7011-5p, miR-145a-3p, and miR-149-3p. miR-145a-3p, which had the most pronounced and stable expression trend and was the most highly expressed miRNA, was chosen as the target of this experiment by qRT-PCR analysis. -145a-3p, as the subject of this experiment. Knockdown of miR-145a-3p in MC3T3-E1 cells after dexamethasone action significantly improved the expression of their impaired osteogenic indicators. It was shown that after knocking down the target miRNA, alkaline phosphatase staining was significantly increased compared with the dexamethasone-stimulated group and approached the level of the blank control group. Meanwhile, the expression of osteogenic function-related proteins and genes also increased in the dexamethasone-stimulated group after knocking down miR-145a-3p, and approached the level of the blank control group. A direct targeting relationship between miR-145a-3p and Runx2 was indeed confirmed by luciferase reporter gene assays, qRT-PCR and Western blot experiments.ConclusionsThe results indicated that dexamethasone impaired the osteogenic differentiation ability of MC3T3-E1 cells by inducing the up-regulation of miR-145a-3p expression. MiR-145a-3p inhibited the osteogenic differentiation ability of MC3T3-E1 cells by targeting and suppressing the expression level of Runx2 protein. Inhibition of miR-145a-3p levels significantly improved the osteogenic differentiation ability of MC3T3-E1 cells.

ObjectivesWe set out to evaluate the effect of postnatal exposure to tenofovir-containing antiretroviral therapy on bone mineral density among breastfeeding women living with HIV.DesignIMPAACT P1084s is a sub-study of the PROMISE randomized trial conducted in four African countries (ClinicalTrials.gov number NCT01066858).MethodsIMPAACT P1084s enrolled eligible mother-infant pairs previously randomised in the PROMISE trial at one week after delivery to receive either maternal antiretroviral therapy (Tenofovir disoproxil fumarate / Emtricitabine + Lopinavir/ritonavir-maternal TDF-ART) or administer infant nevirapine, with no maternal antiretroviral therapy, to prevent breastmilk HIV transmission. Maternal lumbar spine and hip bone mineral density were measured using dual-energy x-ray absorptiometry (DXA) at postpartum weeks 1 and 74. We studied the effect of the postpartum randomization on percent change in maternal bone mineral density in an intention-to-treat analysis with a t-test; mean and 95% confidence interval (95%CI) are presented.ResultsAmong 398/400 women included in this analysis, baseline age, body-mass index, CD4 count, mean bone mineral density and alcohol use were comparable between study arms. On average, maternal lumbar spine bone mineral density declined significantly through week 74 in the maternal TDF-ART compared to the infant nevirapine arm; mean difference (95%CI) -2.86 (-4.03, -1.70) percentage points (p-value

Understanding the coagulation process is critical to developing treatments for trauma and coagulopathies. Clinical studies on tranexamic acid (TXA) have resulted in mixed reports on its efficacy in improving outcomes in trauma patients. The largest study, CRASH-2, reported that TXA improved outcomes in patients who received treatment prior to 3 hours after the injury, but worsened outcomes in patients who received treatment after 3 hours. No consensus has been reached about the mechanism behind the duality of these results. In this paper we use a computational model for coagulation and fibrinolysis to propose that deficiencies or depletions of key anti-fibrinolytic proteins, specifically antiplasmin, a1-antitrypsin and a2-macroglobulin, can lead to worsened outcomes through urokinase-mediated hyperfibrinolysis.

[This corrects the article DOI: 10.1371/journal.pone.0074968.].

Due to low labeling efficiency and structural heterogeneity in fluorescence-based single-molecule localization microscopy (SMLM), image alignment and quantitative analysis is often required to make accurate conclusions on the spatial relationships between proteins. Cryo-electron microscopy (EM) image alignment procedures have been applied to average structures taken with super-resolution microscopy. However, unlike cryo-EM, the much larger cellular structures analyzed by super-resolution microscopy are often heterogeneous, resulting in misalignment. And the light-microscopy image library is much smaller, which makes classification challenging. To overcome these two challenges, we developed a method to deform semi-flexible ring-shaped structures and then align the 3D structures without classification. These algorithms can register semi-flexible structures with an accuracy of several nanometers in short computation time and with greatly reduced memory requirements. We demonstrated our methods by aligning experimental Stochastic Optical Reconstruction Microscopy (STORM) images of ciliary distal appendages and simulated structures. Symmetries, dimensions, and locations of protein complexes in 3D are revealed by the alignment and averaging for heterogeneous, tilted, and under-labeled structures.

Objective: In this experiment, we screened key miRNAs involved in the dexamethasone-induced decrease in osteogenic capacity of mouse precursor osteoblasts MC3T3-E1 over and investigated their specific regulatory mechanisms. Methods: In this experiment, cell counting kit assay was utilized to act on MC3T3-E1 cells at 0, 5μM, 10μM, 15μM concentrations of dexamethasone for 24h, 48h and 72h to observe the changes in cell viability in order to select the appropriate dexamethasone concentration. Apoptosis and reactive oxygen species were detected by flow cytometry. The transcription of osteogenesis-related genes (Runx2, ALP, OCN, OPN, OPG, COL1A1) and protein expression levels (Runx2, ALP, OCN, OPN) were detected by Western Blot and qRT-PCR to validate the changes in cellular osteogenesis. The differentially expressed miRNAs related to MC3T3-E1 osteogenic differentiation after dexamethasone action were screened out. The expression levels of selected target miRNAs were verified in the experimental group and the control group by qRT-PCR. The miRNA inhibitor was transfected to knock down miRNA in dexamethasone-induced MC3T3-E1 injury. Alkaline phosphatase staining and flow cytometry were performed to detect apoptosis and reactive oxygen species changes. transcript and protein expression levels of osteogenesis-related genes in mouse MC3T3-E1 were detected by qRT-PCR and Western blot experiments. By miRNA target gene prediction, luciferase reporter gene experiments, qRT-PCR and Western blot experiments were used to verify whether the selected target miRNAs targeted the target gene. Results: First, it was determined that 10μM dexamethasone solution was effective in inducing a decrease in osteogenic function in mouse MC3T3-E1 by CCK8 experiments, which showed a significant decrease in alkaline phosphatase activity, a decrease in calcium nodules as shown by alizarin red staining, an increase in apoptosis and reactive oxygen species as detected by flow cytometry, as well as a decrease in the expression of osteogenesis-related genes and proteins. Five target miRNAs were identified: miR-706, miR-296-3p, miR-7011-5p, miR-145a-3p, and miR-149-3p. miR-145a-3p, which had the most pronounced and stable expression trend and was the most highly expressed miRNA, was chosen as the target of this experiment by qRT-PCR analysis. -145a-3p, as the subject of this experiment. Knockdown of miR-145a-3p in MC3T3-E1 cells after dexamethasone action significantly improved the expression of their impaired osteogenic indicators. It was shown that after knocking down the target miRNA, alkaline phosphatase staining was significantly increased compared with the dexamethasone-stimulated group and approached the level of the blank control group. Meanwhile, the expression of osteogenic function-related proteins and genes also increased in the dexamethasone-stimulated group after knocking down miR-145a-3p, and approached the level of the blank control group. A direct targeting relationship between miR-145a-3p and Runx2 was indeed confirmed by luciferase reporter gene assays, qRT-PCR and Western blot experiments. Conclusions: The results indicated that dexamethasone impaired the osteogenic differentiation ability of MC3T3-E1 cells by inducing the up-regulation of miR-145a-3p expression. MiR-145a-3p inhibited the osteogenic differentiation ability of MC3T3-E1 cells by targeting and suppressing the expression level of Runx2 protein. Inhibition of miR-145a-3p levels significantly improved the osteogenic differentiation ability of MC3T3-E1 cells. [ABSTRACT FROM AUTHOR]

Background: Intractable xerostomia is defined as the subjective perception of dry mouth and persistent salivary gland hypofunction. Pilocarpine is an approved salivary sialagogue that is frequently prescribed for the treatment of intractable xerostomia; however, it often exhibits more side effects at high-doses and limited effectiveness at low-doses. Baekhogainsam-Tang (BIT) is a common herbal formula used by patients complaining of sore throats and thirst. It seems that BIT can compensate for the insufficient effect of low-dose pilocarpine. However, no clinical trials have studied the efficacy of combined administration of BIT and low-dose pilocarpine for intractable xerostomia. We aim to assess the non-inferior efficacy and fewer side effects of combined administration of BIT and low-dose pilocarpine compared with the administration of high-dose pilocarpine. Methods: A randomized, open-label, parallel-group, multi-center trial will be conducted. A total of 120 patients with Sjogren's syndrome having an unstimulated salivary flow rate (SFR) ≤0.1 mL/min or who have undergone radiotherapy to the head and neck with an unstimulated SFR ≤0.25 mL/min will be recruited competitively. They will be randomly allocated to either the experimental or control groups. The experimental group will receive BIT herbal granules three times and pilocarpine (2.5-mg) four times daily; meanwhile, the control group will receive only 5-mg pilocarpine four times daily for 12 weeks. The primary outcome is unstimulated SFR after 12 weeks of treatment. Secondary outcomes are stimulated SFR after 12 weeks of medication, as well as differences and mean percentage changes in unstimulated and stimulated SFR, visual analog scale, salivary scintigraphy, and questionnaires for both oral symptoms and quality of life during the clinical trial. An independent T test or Mann-Whitney U test will be performed to compare values between the two groups. The Paired T test or Wilcoxon signed-rank test will be performed to compare intragroup continuous values. Conclusion: This trial will be significant evidence on the efficacy and safety of combined use of BIT and low-dose pilocarpine to treat intractable xerostomia. Clinical trial registration: The Clinical Research Information Service of the Republic of Korea (ISRCTN, KCT0005982). Registered on 10 February 2021. [ABSTRACT FROM AUTHOR]

Coix lacryma-jobi L. belongs to family Poaceae, is widely cultivated in tropical Asian countries for its nutritional and medicinal values. Coix is often threatened by lepidopteran such as Mythimna separata during its life cycle, resulting in severe yield reduction. Insect feeding can trigger defense signaling and increased defense responses in many other crops, yet little is known about whether simulated armyworm feeding on Coix leaves could induce anti-herbivory responses and whether armyworm feeding could activate priming in systemic leaves. In this study, Mythimna separata simulated herbivory elicited increased jasmonic acid (JA) level, JA-Ile (JA-isoleucine conjugate) and altered transcriptome in the Coix leaves. Meanwhile, M. separata simulated herbivory in local leaves primed the systemic leaves for increased accumulation of jasmonic acid and enhanced resistance to M. separata. Consistently, transcriptome analysis showed the systemic leaves were primed, which were up- or down-regulated comparing with the non-primed systemic leaves. In this study, we first reported Mythimna separata simulated herbivory induced increased defense response in leaves of Coix, also Mythimna separata herbivory primed Coix resistance in systemic leaves. This study provides new insight into the regulation of defense responses of Coix against M. separata and the ecological function of priming in Coix. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) and urinary incontinence (UI) are two prevalent health conditions with significant impacts on individuals' quality of life. Although they appear distinct in nature, a growing body of evidence suggests a potential interrelationship between these conditions. Our objective was to explore the association between the risk of OSA and the occurrence of UI within a nationally representative sample of U.S. adults. Utilizing cross-sectional data from the National Health and Nutrition Examination Survey spanning the years 2015 to 2020, we conducted an analysis on a sample comprising 8,647 adults who provided comprehensive self-reported information on both UI and sleep apnea symptoms. The included cohorts were analyzed based on their sex. We employed the Multivariate Apnea Prediction (MAP) index to evaluate the risk of OSA. Subgroup analyses were conducted, categorizing them according to different types of UI. The association between OSA risk and UI was estimated through multivariable binary logistic regression models. After adjusting for relevant confounders, our results revealed a positive correlation between OSA risk and UI in both males (OR = 5.68, 95% CI = 1.74–18.47) and females (OR = 5.99, 95% CI = 2.68–13.41). The subgroup analysis illustrates that an elevated risk of OSA heightens the likelihood of experiencing stress urinary incontinence (SUI), urge urinary incontinence (UUI), and mixed urinary incontinence (MUI) in both male and female populations. Our study findings imply that an elevated risk of OSA exacerbates the likelihood of UI, SUI, UUI and MUI. [ABSTRACT FROM AUTHOR]

Purpose: This study compared field-of-view (FOV) optimized and constrained undistorted single-shot diffusion-weighted imaging (FOCUS DWI) with deep-learning-based reconstruction (DLR) to conventional DWI for breast imaging. Methods: This study prospectively enrolled 49 female patients suspected of breast cancer from July to December 2023. The patients underwent conventional and FOCUS breast DWI and data were reconstructed with and without DLR. Two radiologists independently evaluated three images per patient using a 5-point Likert scale. Objective evaluations, including signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC), were conducted using manual region of interest-based analysis. The subjective and objective evaluations were compared using the Friedman test. Results: The scores for the overall image quality, anatomical details, lesion conspicuity, artifacts, and distortion in FOCUS-DLR DWI were higher than in conventional DWI (all P < 0.001). The SNR of FOCUS-DLR DWI was higher than that of conventional and FOCUS DWI (both P < 0.001), while FOCUS and conventional DWI were similar (P = 0.096). Conventional, FOCUS, and FOCUS-DLR DWI had similar CNR and ADC values. Conclusion: Our findings indicate that images produced by FOCUS-DLR DWI were superior to conventional DWI, supporting the applicability of this technique in clinical practice. DLR provides a new approach to optimize breast DWI. [ABSTRACT FROM AUTHOR]

China has attached increasing importance to the overseas dissemination of traditional culture as it continues to strengthen its comprehensive national strength and develop globalization initiatives. The electronic game, as the 'ninth art', with its booming development and inherent cross-cultural communication platform attributes, has taken on the important task of taking culture abroad. This study selects 'Genshin Impact', a game highly praised and well-received globally, which contains an abundance of Chinese cultural elements and cultural elements from various regions of the world, to study cultural interaction in cross-cultural communication of electronic games. This study conducts text sentiment analysis and semantic network analysis on the comments of 'Genshin Impact' videos on the overseas video platform YouTube and studies the cultural interaction in the cross-cultural communication of the 'ninth art', telling the cultural stories of China and the world from a multicultural perspective. The study found that games and derivative videos triggered positive emotional responses from audiences both at home and abroad. While experiencing pleasure and surprise, audiences also arouse deeper emotions such as admiration, identification, and expectation. Meanwhile, in the complex art form of the 'ninth art', audiences can absorb the cultural elements of different cultures, resonate with the elements of their cultural circle, and even trigger further profound thinking. Finally, this study provides constructive suggestions on using the 'ninth art' to better 'tell China's stories and disseminate China's voice'. [ABSTRACT FROM AUTHOR]

In order to improve the accuracy of the transformer fault identification using nature-inspired algorithms, an identification method based on the GWO (Grey Wolf Optimizer)-optimized Dual-channel MLP (Multilayer Perceptron)-Attention is proposed. First, a Dual-channel model is constructed by combining the AM (Attention Mechanism) and MLP. Subsequently, the GWO algorithm is used to optimize the number and the nodes of the hidden layer in the Dual-channel MLP-Attention model. Typical transformer faults are simulated using DDRTS (Digital Dynamic Real-Time Simulator) system. Experiments showed that the GWO- optimized method has an accuracy rate of 95.3%-96.7% in identifying the transformer faults. Compared with BP, SVM, MLP, and single-channel M-A models, the proposed method improved the accuracy by14.1%, 9.6%, 9.3%, and 3.3% respectively. This result indicates the rationality and effectiveness of the proposed method in transformer fault identification. [ABSTRACT FROM AUTHOR]

Background: It remains unclear whether chronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer after excluding confounding factors such as smoking, age, sex, body mass index (BMI), comorbidities, etc. Methods: Data from 11,440 participants (≥ 40 years old) in the National Health and Nutrition Examination Survey (NHANES) 2013–2018 were analyzed. Weighted multivariable logistic regression models were used to assess the association between COPD and lung cancer risk. Subgroup analyses were based on age, sex, BMI, and smoking. Results: This study included 660 patients with COPD and 10,780 participants without COPD. The prevalence of lung cancer was significantly higher in patients with COPD compared to participants without COPD (3.39% vs 0.14%). After adjusting for confounding factors, COPD was associated with a significantly increased risk of lung cancer (OR, 12.24, 95% CI, 4.99–30.06, p < 0.001). This association remained significant in all subgroups, particularly in individuals aged > 65 years (OR, 20.05, 95% CI, 6.85–58.72, p < 0.001), smokers (OR, 19.38, 95% CI, 2.02–185.66, p = 0.010), males (OR, 17.39, 95% CI, 5.28–57.31, p < 0.001), individuals who quit smoking within 10 years (OR, 12.86, 95% CI, 2.59, 63.99, p = 0.002), and individuals with a BMI > 25 kg/m2 (OR, 14.56, 95% CI, 3.88–54.69, p < 0.001). Conclusions: COPD is an independent risk factor for lung cancer, especially in certain subgroups. The combination of COPD and smoking greatly amplifies the lung cancer risk. These findings highlight the importance of early lung cancer screening in patients with COPD. [ABSTRACT FROM AUTHOR]

This study retrospectively reviewed the microbiological and clinical characteristics of patients diagnosed with bacteremia. Results from the first positive blood cultures were consecutively collected from July 2022 to June 2023 at a public secondary hospital, a university-affiliated tertiary hospital, and a university-affiliated secondary hospital in the Seoul metropolitan area. Antibiotic spectrum coverage (ASC) scores were calculated on the day the blood culture was performed (B0) and on two days after the blood culture results were reported (R+2). A total of 3,397 isolates were collected from 3,094 patients. Among these, 949 isolates obtained from 893 patients were classified as multidrug-resistant organisms (MDRO), including 170 imipenem-resistant gram-negative bacteria, 714 methicillin-resistant staphylococci, and 65 vancomycin-resistant enterococci. Interestingly, 13 and 42 gram-positive isolates were resistant to linezolid and quinupristin/dalfopristin, respectively. Moreover, 44 and 181 gram-negative isolates were resistant to amikacin and tigecycline, respectively. The proportion of ASC scores corresponding to broad or extremely broad-spectrum coverage was not significantly different between MDRO and non-MDRO groups at B0 (p = 0.0925). However, it increased in the MDRO group at R+2 (p <0.001). This study found that resistance to last-resort antimicrobials is emerging. Therefore, developing and incorporating molecular diagnostics using a wide range of resistance targets may facilitate rapid, tailored antimicrobial treatments. [ABSTRACT FROM AUTHOR]

Background and aims: Newborn screening (NBS) for glucose-6-phosphate dehydrogenase (G6PD) deficiency by biochemical tests is being used worldwide, however, the outcomes arising from combined genetic and biochemical tests have not been evaluated. This research aimed to evaluate the outcomes of application of combined genetic and biochemical NBS for G6PD deficiency and to investigate the molecular epidemiological characteristics, variant spectrum, and genotype-phenotype correlation of G6PD deficiency in China. Methods: A population-based cohort of 29,601 newborns were prospectively recruited from eight NBS centers in China between February 21 and December 30, 2021. Biochemical and genetic NBS was conducted simultaneously. Results: The overall prevalence of G6PD deficiency was 1.12% (1.86% for male, and 0.33% for female; 1.94% for South China and 0.08% for North China). Genetic NBS identified 10 male patients undetected by biochemical NBS. The overall positive predictive values (PPVs) of biochemical and genetic NBS were 79.95% and 47.57%, respectively. A total of 15 variants were identified, with the six most common variants being c.1388G > A, c.1376G > T, c.95A > G, c.871G > A, c.1024C > T and c.392G > T (94.2%). The activity of G6PD was correlated with the type and WHO classification of variants. Conclusion: This study highlighted that combined screening could enhance the efficiency of current NBS for diagnosing G6PD deficiency. The prevalence, variant spectrum and allele frequency of G6PD deficiency vary across different regions. Our data provide valuable references for clinical practice and optimization of future screening strategies for G6PD deficiency. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of visual rigid laryngoscopy and video laryngoscopy and to provide clinical information for developing a more suitable intubation tool for elderly patients. Methods: In 75 consecutive elderly patients undergoing elective surgery in a single institution, tracheal intubation was randomly performed by 2 experienced anaesthesiologists using visual rigid laryngoscopy (Group I, n = 38) or video laryngoscopy (Group II, n = 37). The primary outcome was intubation time. Secondary outcomes were the first-attempt success rate of tracheal intubation, haemodynamic responses at 1, 3, and 5 min after intubation and the incidence of postoperative airway complications, including immediate complications and postoperative complaints. Results: The intubation times were 35.0 (30.0–41.5) s and 42.5 (38.0–51.3) s in Groups I and II, respectively (P < 0.001). The difference in direct complications between the two groups was statistically significant (P < 0.05). In contrast, there was no significant difference between the two groups regarding the follow-up of the main complaint 30 min and 24 h after tracheal extubation (P > 0.05). There was no difference in the intubation success rate between the 2 groups (P > 0.05). The haemodynamic responses at 1, 3, and 5 min after intubation were not significantly different (P > 0.05). Conclusion: Compared with that of video laryngoscopy, the intubation time of visual rigid laryngoscopy in elderly patients was shorter. At the same time, visual rigid laryngoscopy reduced the incidence of immediate complications. However, during endotracheal intubation, there was no significant difference in haemodynamics between the two groups. Clinical trial registration number: ChiCTR2100054174. [ABSTRACT FROM AUTHOR]

Background: Currently, there is an irrational use of drugs in the treatment of hypoproteinemia. This study evaluates the value of 12 injections to provide a basis for drug selection for the treatment of hypoproteinemia. Methods: The content of the first restrictive amino acid, the comprehensive quality of the total essential amino acid, and the closeness to the whole egg protein or FAO/WHO model were evaluated to compare their value in the amino acid synthesis of human serum albumin. A comparison was made between the matching degree of HA and therapeutic amino acids with the human plasma amino acid profile. Furthermore, the value and safety of synthetic human serum albumin were compared. Results: The lowest synthetic value of human serum albumin was 18AA-V, and the highest was 18AA-II. The CS values of HA, 18AA-V, 18AA-II, 18AA-Ip, 18AA-IIp, and 19AA-Ip were 0.18, 0.58, 0.78, 0.55, 0.54, and 0.59, respectively. The similarity to egg protein was 0.81, 0.92, 0.94, 1.00, 1.18, and 1.18, respectively. The proximity values to FAO/WHO standards were 0.81, 0.85, 0.90, 1.36, 1.54, and 1.54, respectively. The changes in 3AA and the amino acid profile were matched when liver function was abnormal. When the renal function was abnormal, 9AA was matched. During trauma, 18AA-VII was matched. The amino acid profile of HA did not correspond. Conclusion: Patients with normal liver and kidney function should choose compound balanced amino acid injection, while patients with abnormalities should choose 3AA. Patients with renal dysfunction should choose 9AA. Trauma patients should choose 18AA-VII. [ABSTRACT FROM AUTHOR]

Purpose: Stereopsis, the ability of humans to perceive depth through distinct visual stimuli in each eye, is foundational to autostereoscopic technology in computing. However, ensuring stable head position during assessments has been challenging. This study evaluated the utility of artificial intelligence (AI)-enhanced face tracking technology in overcoming this challenge by ensuring that each eye consistently receives its intended image. Methods: The Lume Pad 2, an autostereoscopic tablet with AI-enhanced face tracking, was utilized to simulate quantitative parts of the Stereo Fly test and TNO Stereotests for contour and random dot stereopsis. The study recruited 30 children (14 males and 16 females, mean age of 9.2 ± 0.3 years, age range of 6–12 years) and 30 adults (10 males and 20 females, mean age of 29.4 ± 1.0 years, age range of 21–42 years) to assess the tablet's inter-session reliability. Agreement between conventional and the autostereoscopic tablet-simulated stereotests was tested in a larger group of 181 children (91 males and 90 females, mean age of 9.1 ± 0.4 years, age range of 6–12 years) and 160 adults (69 males and 91 females, mean age of 38.6 ± 2.1 years, age range of 21–65 years). Inter-session reliability and agreement were analyzed using weighted Kappa coefficient and non-parametric Bland-Altman analysis. Results: The autostereoscopic tablet demonstrated high inter-session reliability (κ all > 0.80), except for the simulated TNO Stereotest in adults, which demonstrated moderate inter-session reliability (κ = 0.571). Non-parametric Bland-Altman analysis revealed zero median differences, confirming consistent inter-session reliability. Similar patterns were observed in comparing AI-based and conventional methods, with both the weighted Kappa coefficient (κ all > 0.80) and non-parametric Bland-Altman analysis indicating significant agreement. The agreement between methodologies was confirmed by permissible differences, which were smaller than the minimum step range. Conclusion: The integration of AI-based autostereoscopic technology with sub-pixel precision demonstrates significant potential for clinical stereopsis measurements. [ABSTRACT FROM AUTHOR]

This study delved into the interplay between CD244 and Src Homology 2 Domain Containing Phosphatase-2 (SHP2) in chronic obstructive pulmonary disease (COPD) pathogenesis, focusing on apoptosis and inflammation in cigarette smoke extract (CSE)-treated human bronchial epithelial (HBE) cells. Analysis of the GSE100153 dataset identified 290 up-regulated and 344 down-regulated differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) highlighted the turquoise module had the highest correlation with COPD samples. Functional enrichment analysis linked these DEGs to critical COPD processes and pathways like neutrophil degranulation, protein kinase B activity, and diabetic cardiomyopathy. Observations on CD244 expression revealed its upregulation with increasing CSE concentrations, suggesting a dose-dependent relationship with inflammatory cytokines (IL-6, IL-8, TNF-α). CD244 knockdown mitigated CSE-induced apoptosis and inflammation, while overexpression exacerbated these responses. Co-immunoprecipitation (Co-IP) confirmed the physical interaction between CD244 and SHP2, emphasizing their regulatory connection. Analysis of Concurrently, the Nuclear Factor-kappa B (NF-κB) and Mitogen-activated protein kinase (MAPK) signaling pathways showed that modulating CD244 expression impacted key pathway components (p-JNK, p-IKKβ, p-ERK, p-P38, p-lkBα, p-P65), an effect reversed upon SHP2 knockdown. These findings underscore the pivotal role of the CD244/SHP2 axis in regulating inflammatory and apoptotic responses in CSE-exposed HBE cells, suggesting its potential as a therapeutic target in COPD treatment strategies. [ABSTRACT FROM AUTHOR]

By utilizing China's 2016 Implementation Plan for the Specific Rectification of Internet Financial Risks as an exogenous shock, we employ a difference-in-differences identification strategy to investigate the impact of FinTech regulation on banks' risk-taking. Our findings indicate that FinTech regulation strengthens banks' deposit franchises and funding liquidity. As reliable and interest-rate-insensitive funding sources, higher deposit franchises weaken banks' incentives for risk-taking. Further analysis, conducted to control for the potential interference of other policies, confirms the stable incremental effect of FinTech regulation. Moreover, we find that FinTech regulation tends to benefit banks with higher capital buffers and smaller sizes from a triple difference (difference-in-difference-in-difference) analysis. By focusing on the external effects of FinTech regulation, we aim to shed light on how regulatory gaps impact the formal financial system and highlight the importance of effectively regulating emerging financial entities. [ABSTRACT FROM AUTHOR]

During in vitro maturation, excess levels of reactive oxygen species (ROS) are a major cause of developmental defects in embryos. Betulinic acid (BA) is a naturally produced antioxidant in white birch bark. Recent studies have shown that BA exhibits antioxidant properties in various cells through the activation of antioxidant genes. Therefore, we investigated the effect of BA treatment on porcine oocytes and its underlying mechanism during oocyte maturation. Treatment with 0.1 μM BA significantly increased the proportion of MII oocytes compared with controls, and BA-treated oocytes had significantly higher development rates, trophectoderm cell numbers, and cell survival rates than controls. These results demonstrate that BA treatment improved the developmental competence of oocytes. Following BA treatment, oocytes exhibited reduced ROS levels and elevated glutathione (GSH) levels, accompanied by the enhanced expression of antioxidant genes, compared with control oocytes. To evaluate the antioxidant effects of BA, oocytes were exposed to H2O2, a potent ROS activator. Impaired nuclear maturation, ROS levels, and GSH levels induced in oocytes by H2O2 exposure was restored by BA treatment. As these antioxidant genes are regulated by the Nrf2/Keap1 signaling pathway, which is involved in antioxidant responses, we applied the Nrf2 inhibitor brusatol to investigate the effects of BA on this pathway. The negative effects of brusatol on meiotic maturation and oocyte quality, including levels of ROS, GSH, and antioxidant-related gene expression, were mitigated by BA treatment. Our results suggested that BA plays an effective role as an antioxidant in porcine oocyte maturation through adjusting the Nrf2/Keap1 signaling pathway. This finding provides valuable insights into the mechanisms governing oocyte maturation and embryonic development. [ABSTRACT FROM AUTHOR]

Background: The relationship between dysregulation of the immune system and reproductive health, particularly in the context of abortion, is an area of critical research. Identifying the immunological factors that contribute to abortion could provide valuable insights into its prevention and management. Methods: This study used bidirectional two-sample Mendelian Randomization (MR) approach to evaluate the causal link between 731 immune cell features and the risk of abortion. The study analyzed GWAS data from 257,561 Europeans, including 7,069 cases and 250,492 controls, by utilizing genetic variation as instrumental variables. The immune phenotypes included several cell types, including B cells, T cells, TBNK cells, Treg cells, and monocytes. These were analyzed using the 'TwoSampleMR' package in R software. Results: The study identified 34 immune phenotypes that have a significant causal relationship with abortion risk. Notably, Results from the B cell group showed a positive correlation between abortion and certain phenotypes, including Unsw mem %B cell, PB/PC %B cell, IgD+ CD24+ %B cell and Naive-mature B cell %lymphocyte. In the T cell group, certain maturation stages such as Naive CD8br %T cell and CD4 on CD45RA+ CD4+ exhibited negative causal links, whereas CCR7 on naive CD8br showed a positive association. The group of Treg cells showed both positive and negative causal relationships with abortion, highlighting the complexity of immune regulation in reproductive health. Conclusions: This study reflects the causal relationship between different subtypes of different immune cells and abortion. The results underscore the importance of the immune system in reproductive health and suggest potential therapeutic interventions targeting these immunological pathways. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease (CD) is a chronic inflammatory condition primarily affecting the digestive system. When dealing with complex cases like intestinal blockages or perforations, surgery becomes the primary treatment option. However, surgery doesn't offer a complete cure, and the possibility of recurrence remains. To manage CD recurrence after surgery, various treatment choices are available, including steroids, monoclonal antibodies, immunomodulators, and further surgery. Regrettably, the current body of evidence doesn't definitively establish which of these treatments is the most effective and safe. Thus, our research aims to provide insights into the Validity and security of different treatment approaches for managing CD recurrence after surgery. Methods: Search of EMBASE, PubMed, Web of Science Core Collection and the Cochrane Central Register of Controlled Trials will be conducted to include researches that examine the validity of treatments for recurrent CD after surgery. Our analysis will distinguish between two types of studies: randomized controlled trials (RCTs) and non-randomized studies with at least two different treatments, each evaluated separately. We will employ Bayesian network meta-analyses to systematically compare the effectiveness and safety of these treatments. Additionally, subgroup analyses will be performed according to recurrence status and postoperative prophylactic medication. To clarify the variation of studies, sensitivity analyses will be performed. And we may use meta-regression as an additional approach if relevant data are available. We will also rigorously access the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Discussion: This analysis will provide a comprehensive assessment of the latest evidence on available treatments for patients with postoperative recurrence of CD, which will provide recommendations for clinical practice. Trial registration: Systematic review registration INPLASY2023110021. (DOI: 10.37766/inplasy2023.11.0021). [ABSTRACT FROM AUTHOR]

The short-distance continuous diversion area plays a crucial role within mountainous urban expressway systems, significantly enhancing the efficiency of specialized road sections through capacity analysis. This study develops a capacity calculation model tailored to the diversion area's unique characteristics and principal capacity-influencing factors. Initially, the research focuses on a specific short-distance continuous diversion area of a mountainous urban expressway, employing video trajectory tracking technology to gather trajectory data. This data serves as the basis for analyzing road and traffic characteristics. Subsequently, the model computes the capacity influenced by eight variables, including diversion point spacing and deceleration lane length, using VISSIM simulation experiments. A gray correlation analysis identifies key factors, which guide the establishment of the model's fundamental structure through two-factor surface fitting results. Mathematical statistical methods are then applied to resolve the model's parameters, culminating in a robust capacity calculation model. The findings reveal that diversion point spacing, along with primary and secondary diversion ratios, significantly influence capacity. Notably, the capacity exhibits a marked quadratic polynomial relationship with the primary diversion ratio and diversion point spacing, and a linear relationship with the secondary diversion ratio. The model's validity is confirmed through a case study at the diversion area north of Huacun Interchange in Chongqing Municipality, where the discrepancy between calculated and actual capacities is under 5%, underscoring the model's high accuracy. These results offer valuable theoretical and methodological support for the planning, design, and traffic management of diversion areas. [ABSTRACT FROM AUTHOR]

Depression is accompanied by dyslipidemia, which may increase the risk of stroke and coronary heart disease. This study sought to quantitatively summarize the clinical data comparing peripheral blood triglyceride (TG) concentrations between patients with major depressive disorder (MDD) and healthy controls (HCs). Studies were searched in PubMed, EMBASE, PsycINFO, and Cochrane Databases up to March 2023. We also reviewed the reference lists of obtained articles. Mean (±SD) for TG concentrations were extracted, combined quantitatively using random-effects meta-analysis, and summarized as a standardized mean difference (SMD). Subgroup analysis and meta-regression was performed to explore the resource of heterogeneity. Thirty-eight studies measuring the concentrations of peripheral blood TG in 2604 patients with MDD and 3272 HCs were included. Meta-analysis results indicated that TG levels were significant higher in patients with MDD than in HCs (SMD = 0.31, 95% confidence interval [CI]: 0.16 to 0.46, Z46 = 4.05, p < 0.01). Heterogeneity was detected (χ2 = 269.97, p < 0.01, I2 = 85%). Subgroup analysis demonstrated significant differences in TG levels between patients with MDD and HCs depended on age, body mass index and drug use (p < 0.05), but no differences between groups. Meta-regression also found no significant variables. TG level was significantly elevated in depression, which may explain the increased risk of cardiovascular and cerebrovascular events in depression. [ABSTRACT FROM AUTHOR]

Maize is one of the main food crops in the world, and cultivating high-yield and high-quality maize varieties is of great significance in addressing food security issues. Leaves are crucial photosynthetic organs in maize, and leaf senescence can result in the degradation of chlorophyll. This, in turn, impacts photosynthetic activity and the accumulation of photosynthetic products. Delaying leaf senescence and increasing carbon assimilation can enhance grain yield and biomass production. The stay green of maize is an important trait closely related to yield, feed quality and resistance. Therefore, this study employed multi-generation joint analysis of major genes and a polygene model to investigate the genetic inheritance of stay green-related traits. Four populations (P1, P2, F1 and F2) were obtained by crossing T01 (stay green) × Xin3 (non-stay green) and T01 (stay green) × Mo17 (non-stay green) under two environments. Six stay green-related traits, including visual stay green (VSG), number of green leaves (GLNM), SPAD value of ear leaf at anthesis (SPADS), SPAD value of ear leaf at maturity (SPADM), absolute green leaf area (GLAD), grain yield per plant (GYP), displayed continuous variations with kurtosis and skewness values of absolute value less than 1 and distribution close to normal. They were characterized by typical inheritance of quantitative traits, with these traits demonstrating the transgressive segregation. The correlation analysis among the traits revealed that five stay green traits have a positive impact on yield. VSG, GLNM and SPADM in the two populations were regulated by the two major genes of additive effects plus additive-dominance polygene model with a major gene heritability varying from 89.03 to 95.95% in the F2 generation. GLAD in TMF2 was controlled by two major genes of equal-additive dominance effects with high heritability (93.47%). However, in TXF2, GLAD was regulated by two major genes of additive-dominance interaction effects plus additive-dominance polygene model. These results provide important genetic information for breeding, which could guide the improvement of stay green-related traits. They also lay a foundation for quantitative trait loci mapping of the stay stay-green traits in maize. [ABSTRACT FROM AUTHOR]

Background: The lipid accumulation product (LAP) and the visceral adiposity index (VAI) are suggested as dependable measures for assessing visceral fat levels. Prediabetes is recognized as a condition that precedes the potential onset of diabetes. The objective of this research is to investigate how VAI and LAP are related to prediabetes among the adult population in the United States. Methods: Information from the 2007–2020 National Health and Nutrition Examination Survey (NHANES) was scrutinized in a cross-sectional study. To evaluate the connection between VAI or LAP and the presence of prediabetes, both univariate analysis and multivariate logistic regression were utilized. Threshold effect analysis and fitted smoothing curves were used to delve into the non-linear association between VAI or LAP and prediabetes. Additional analyses were performed on specific subgroups, along with tests to explore potential interactions. Results: In general, 12,564 American adults were included. After full adjustment, prediabetes with VAI (OR: 1.128, 95% CI: 1.073–1.185) or LAP (OR: 1.006, 95% CI: 1.004–1.008) showed a positive correlation. Individuals in the 4th VAI quartile group faced a significant 61.9% elevated risk for prediabetes (OR: 1.619, 95% CI: 1.354–1.937) when contrasted to those in the 1st VAI quartile. Participants in the 4th LAP quartile group had a significant 116.4% elevated risk for prediabetes (OR: 2.164, 95% CI: 1.747–2.681) when contrasted to individuals of the 1st LAP quartile. Smooth curve fitting analysis revealed a nonlinear correlation of VAI or LAP and prediabetes, and threshold effect analysis was used to determine an inflection point of 4.090 for VAI and 68.168 for LAP. Conclusions: The values of VAI and LAP are positively associated with the prevalence of prediabetes. The VAI and LAP indices may be used as predictors of prediabetes. [ABSTRACT FROM AUTHOR]

This study examines the impact of status inconsistency on status-threatening activities within NCAA Division I men's basketball teams. Specifically, we focus on a nested form of status that includes both individual and group-level elements. We argue that organizations dealing with status inconsistency stemming from such nested form face challenges in reducing status inconsistency. To maintain their deserved status, these status-inconsistent organizations tend to avoid activities that could further threaten their status, despite potential economic gains. An analysis of NCAA Division I men's basketball scheduling data from 2000 to 2019 provides robust support to our theoretical arguments. Our findings suggest that the status inconsistency between a team's status and its conference status diminished the likelihood of scheduling games with non-Division I teams, a behavior considered counter-normative in this context. This effect is most prominent among teams in "Mid Major" conferences, while teams with recent participation in the NCAA Tournament show a mitigated effect. [ABSTRACT FROM AUTHOR]

On the basis of predecessors' coordination optimization of active and reactive power in distribution network, For the necessity of the optimal operation in the distribution network, part of power generated from photovoltaic (PV) cannot be sold to users, and cannot enjoy subsidies. Similarly, the network loss in the power transmission will also bring a certain economic loss. This paper comprehensively considers the economic loss caused by the network loss and PV abandon of the distribution system, and establishes a model to minimize the economic loss. To solve this problem efficiently, the method of DistFlow equation and mixed integer second order cone programming (MISOCP) is used to solve the problem, in this method, the original mixed integer nonlinear programming non-convex problem is transformed into a convex problem, which makes the optimization problem easy to solve. The modified IEEE 33 and IEEE 69 distribution networks are tested by the above method. The optimized results are able to meet the target and have very small relaxation gaps, and the voltage level is also optimized. This coordinated optimization approach helps to optimize the economic operation for active distribution networks with PVs. [ABSTRACT FROM AUTHOR]

In this study, we investigated the neuroprotective effect of a water extract of ginseng (WEG) obtained via low–temperature extraction of the brain of mice with Parkinson's disease (PD) and the ameliorative effect on the damaged intestinal system for the treatment of dyskinesia in PD mice. MPTP (1–methyl–4–phenyl–1,2,3,6–tetrahydropyridine) was injected intraperitoneally into male C57BL/6 mice to establish a PD model, and WEG was given via oral gavage. The results indicated that WEG could protect the damaged neuronal cells of the mice brain, inhibit the aggregation of α-synuclein (α–Syn) in the brain, and increase the positive expression rate of tyrosine hydroxylase (TH). WEG significantly improved intestinal damage and regulated intestinal disorders (P<0.05). WEG intervention increased the levels of beneficial bacteria, such as Lactobacillus, and normalized the abundance and diversity of colonies in the intestine of mice. Our results suggested that WEG protected neurons in the brain of PD mice via inhibiting the aggregation of α–Syn in the brain and increasing the positive expression level of TH in the brain. WEG regulated the gut microbiota of mice, improved the behavioral disorders of PD mice, and offered some therapeutic effects on PD mice. [ABSTRACT FROM AUTHOR]

Tunnel widening is a frequent problem following arthroscopic ligament reconstruction surgery that may primarily arise from a graft-tunnel mismatch caused by errors in surgical instruments and methods. The present study aimed to observe the influence of current surgical instruments and methods on graft-tunnel matching. We established an in vitro model using porcine Achilles tendons and tibias, and compared traditional surgical instruments (control group) with custom instruments (experimental group). Graft measurements, bone-tunnel creation, and measurements of the maximum pullout force of the graft from the bone tunnel were performed. Results indicated that the measuring gauge developed by our research group (capable of accurate measurement of graft diameters) may mitigate errors arising from graft-diameter measurement using traditional measuring cylinders. Therefore, errors caused by current surgical instruments and surgical methods led to an increase in graft-tunnel mismatches. The degree of mismatch was greater at the tibial end than at the femoral end. [ABSTRACT FROM AUTHOR]

Background: Diabetic skin wound is a complex problem due to the disruption of normal repairing program and lack of effective remedy. Lucilia sericata larvae (maggot) is a folk method to treat chronic skin wound, while its therapeutic effects on that caused by diabetic remains unknown. Objective: This study aims to investigate the therapeutic effects of maggot extract (M.E.) on diabetic skin wound and its molecular mechanism by establishing the skin wound model of diabetic Sprague Dawley (SD) rats. Methods: Diabetic model was established by injecting intraperitoneally streptozotocin in SD rats under specific pathogen-free (SPF) conditions. The rat fasting blood glucose values were ≧16.7 mmol/L 72 hours after intraperitoneal streptozotocin (60mg/kg body weight) injection. The rats were divided into five groups (n = 10/group): normal group: normal SD rats without any treatment, diabetic blank group: the diabetic rats without any treatment, Vaseline group: the diabetic rats dressed with Vaseline, recombinant human epidermal-growth-factor (rhEGF) group: the diabetic rats dressed with a mixture of Vaseline and 200 μg/g rhEGF, M.E. group: the diabetic rats dressed with a mixture of Vaseline and 150 μg/ml maggot extract. The round open wounds (1.0 cm in diameter) down to the muscle fascia were made on both sides of rat dorsa by removing the skin layer (epidermis and dermis) and were daily photographed for calculating their healing rates. Hematoxylin-eosin (HE) and Masson's trichrome staining were performed on skin wound sections to analyze re-epithelialization and granulation tissue formation. Immunohistochemical (IHC), immunofluorescent (IF) stainings and Western blotting were conducted to analyze the statuses of STAT3 signaling. Results: The average wound healing rates on the 14th day were 91.7% in the normal, 79.6% in M.E., 71% in rhEGF, 55.1% in vaseline and 43.3% in the diabetes blank group. Morphological staining showed more active granulation tissue formation, re-epithelialization and neovascularization in M.E.-group than those in the blank and the vaseline-treated groups. Decreased p-STAT3 nuclear tranlocation and down-regulated Bcl-2, CyclinD1 and vascular endothelial growth factor (VEGF) expression were evidenced in the diabetic rats, which could be improved by rhEGF and especially M.E. Conclusion: Maggot extract would be an alternative and/or adjuvant candidate for the better management of diabetic skin wounds because of its activity in enhancing STAT3 activation. [ABSTRACT FROM AUTHOR]

Obesity and accompanying metabolic disease is negatively correlated with lung health yet the exact mechanisms by which obesity affects the lung are not well characterized. Since obesity is associated with lung diseases as chronic bronchitis and asthma, we designed a series of experiments to measure changes in lung metabolism in mice fed obesogenic diets. Mice were fed either control or high fat/sugar diet (45%kcal fat/17%kcal sucrose), or very high fat diet (60%kcal fat/7% sucrose) for 150 days. We performed untargeted metabolomics by GC-TOFMS and HILIC-QTOFMS and lipidomics by RPLC-QTOFMS to reveal global changes in lung metabolism resulting from obesity and diet composition. From a total of 447 detected metabolites, we found 91 metabolite and lipid species significantly altered in mouse lung tissues upon dietary treatments. Significantly altered metabolites included complex lipids, free fatty acids, energy metabolites, amino acids and adenosine and NAD pathway members. While some metabolites were altered in both obese groups compared to control, others were different between obesogenic diet groups. Furthermore, a comparison of changes between lung, kidney and liver tissues indicated few metabolic changes were shared across organs, suggesting the lung is an independent metabolic organ. These results indicate obesity and diet composition have direct mechanistic effects on composition of the lung metabolome, which may contribute to disease progression by lung-specific pathways.

The centrosome serves as the main microtubule-organizing center in metazoan cells, yet despite its functional importance, little is known mechanistically about the structure and organizational principles that dictate protein organization in the centrosome. In particular, the protein-protein interactions that allow for the massive structural transition between the tightly organized interphase centrosome and the highly expanded matrix-like arrangement of the mitotic centrosome have been largely uncharacterized. Among the proteins that undergo a major transition is the Drosophila melanogaster protein centrosomin that contains a conserved carboxyl terminus motif, CM2. Recent crystal structures have shown this motif to be dimeric and capable of forming an intramolecular interaction with a central region of centrosomin. Here we use a combination of in-cell microscopy and in vitro oligomer assessment to show that dimerization is not necessary for CM2 recruitment to the centrosome and that CM2 alone undergoes significant cell cycle dependent rearrangement. We use NMR binding assays to confirm this intramolecular interaction and show that residues involved in solution are consistent with the published crystal structure and identify L1137 as critical for binding. Additionally, we show for the first time an in vitro interaction of CM2 with the Drosophila pericentrin-like-protein that exploits the same set of residues as the intramolecular interaction. Furthermore, NMR experiments reveal a calcium sensitive interaction between CM2 and calmodulin. Although unexpected because of sequence divergence, this suggests that centrosomin-mediated assemblies, like the mammalian pericentrin, may be calcium regulated. From these results, we suggest an expanded model where during interphase CM2 interacts with pericentrin-like-protein to form a layer of centrosomin around the centriole wall and that at the onset of mitosis this population acts as a nucleation site of intramolecular centrosomin interactions that support the expansion into the metaphase matrix.

BackgroundIntrauterine growth restriction (IUGR) results from a lack of nutrients transferred to the developing fetus, particularly oxygen and glucose. Increased expression of the cytoprotective mitochondrial peptide, humanin (HN), and the glucose transporter 8, GLUT8, has been reported under conditions of hypoxic stress. However, the presence and cellular localization of HN and GLUT8 in IUGR-related placental pathology remain unexplored. Thus, we undertook this study to investigate placental expression of HN and GLUT8 in IUGR-affected versus normal pregnancies.ResultsWe found 1) increased HN expression in human IUGR-affected pregnancies on the maternal aspect of the placenta (extravillous trophoblastic (EVT) cytoplasm) compared to control (i.e. appropriate for gestational age) pregnancies, and a concomitant increase in GLUT8 expression in the same compartment, 2) HN and GLUT8 showed a protein-protein interaction by co-immunoprecipitation, 3) elevated HN and GLUT8 levels in vitro under simulated hypoxia in human EVT cells, HTR8/SVneo, and 4) increased HN expression but attenuated GLUT8 expression in vitro under serum deprivation in HTR8/SVneo cells.ConclusionsThere was elevated HN expression with cytoplasmic localization to EVTs on the maternal aspect of the human placenta affected by IUGR, also associated with increased GLUT8 expression. We found that while hypoxia increased both HN and GLUT8, serum deprivation increased HN expression alone. Also, a protein-protein interaction between HN and GLUT8 suggests that their interaction may fulfill a biologic role that requires interdependency. Future investigations delineating molecular interactions between these proteins are required to fully uncover their role in IUGR-affected pregnancies.