Inhibition of CCL7 improves endothelial dysfunction and vasculopathy in mouse models of diabetes mellitus.

Diabetic vascular disease is a major complication of diabetes mellitus (DM). Chemokine C-C motif ligand 7 (CCL7) attracts macrophages and monocytes, amplifying inflammatory processes in the vasculature. We hypothesized a causal role for CCL7 in diabetic vasculopathy. CCL7 concentrations were higher in the plasma of patients with type 2 DM, as well as in supernatants from their endothelial progenitor cells (EPCs). High-glucose stimulation increased the secretion of CCL7 from human dermal microvascular endothelial cells (HDMECs) through the c-Fos and c-Jun signaling pathways. CCL7 inhibition using knockdown or neutralization antibody treatment reversed the high glucose-induced impaired tube formation and migration abilities of EPCs, human aortic endothelial cells, human coronary artery endothelial cells, and HDMECs. Administration of recombinant human CCL7 protein impaired tube formation and migration abilities by down-regulating the AKT-endothelial nitric oxide synthase and AKT/nuclear factor erythroid 2-related factor 2/heme oxygenase-1/vascular endothelial growth factor/stromal cell-derived factor-1 pathways and by up-regulating ERK/phosphorylated p65/interleukin-1ß/interleukin-6/tumor necrosis factor-α pathways through CC chemokine receptor 3 in endothelial cells. Ccl7 knockout in streptozotocin-treated mice showed improved neovasculogenesis in ischemic limbs and accelerated wound repair, with increased circulating EPCs and capillary density. CCL7 antibody treatment in db/db mice and high-fat diet-induced hyperglycemia mice showed improved neovasculogenesis in ischemic limbs and wound areas, accompanied by up-regulation of angiogenic proteins and down-regulation of inflammatory proteins. Endothelial cell-specific Ccl7-knockout mice showed ameliorated diabetic vasculopathy in streptozotocin-induced DM. This study highlights the potential of CCL7 as a therapeutic target for diabetic vasculopathy.

Preoperative endoscopic ultrasound-guided biopsy for resectable pancreatic head tumors increases operative time but not complications - a single center cohort study.

BACKGROUND: Endoscopic ultrasound-guided aspiration or biopsy allows preoperative confirmation of malignancy but is not necessary for resectable pancreatic cancer. Preoperative biopsy may induce pancreatitis, making surgery difficult and complex. Therefore, we performed a retrospective study to evaluate the association between preoperative endoscopic ultrasound-guided biopsy and surgical outcomes in patients with resectable pancreatic head tumors. MATERIALS AND METHODS: A prospectively enrolled cohort from a single high-volume pancreatic center was analyzed. Between 2007 and 2019, a total of 518 patients with resectable pancreatic head tumors underwent pancreaticoduodenectomy. This analysis was performed to determine the association of preoperative endoscopic ultrasound-guided biopsy with operating time and major complications. RESULTS: In 518 patients who received pancreaticoduodenectomy, 164 patients (31.6%) underwent preoperative endoscopic ultrasound-guided biopsy. Endoscopic ultrasound-guided biopsy increased surgical time (46.9 min, confidence interval: 25.1-68.8, P-value <0.05) without increasing complications (odds ratio: 0.53, confidence interval: 0.31-1.29, P-value=0.29). CONCLUSION: Preoperative endoscopic ultrasound-guided biopsy for pancreatic head tumors may increase operative time but is not associated with an increased risk of mortality and complications.

The surgical role of C1 nerve root identification for the disconnection of the spinal dural arteriovenous fistula at the craniocervical junction: a single center restrospective experience.

This study aims to discuss the identification of the C1 nerve root as an effective surgical approach to successfully locate the shunting point of craniocervical junction spinal dural arteriovenous fistula (CCJ-SDAVF) intraoperatively. This study included all patients with CCJ-SDAVF who underwent surgical treatment using the far-lateral transcondylar approach at a single institution from January 2017 to June 2023. Data on patient demographics, clinical and angiographic characteristics of CCJ-SDAVF, surgical details, and treatment outcomes were collected. Follow-up assessments were conducted for all patients until December 31, 2023. The study included a total of 7 patients, comprising 5 men(71.4%) and 2 women (28.6%), with an average age of 57.6 years. Among them, 4 patients (57.1%) developed diffuse subarachnoid hemorrhage(SAH), while 2 patients (28.6%) experienced progressive cervical myelopathy. The shunting points of all CCJ-SDAVFs, which exhibited engorged veins, were identified next to the C1 root. Complete obliteration of CCJ-SDAVFs was successfully achieved in all patients, as confirmed by postoperative angiography one month later. No recurrent CCJ-SDAVFs were observed two years after the operation. Among the patients, 5 (71.4%) experienced good functional recovery, as indicated by an mRS score ranging from 0 to 1, while the remaining 2 patients (28.6%) showed incomplete functional recovery. The surgical interruption of CCJ-SDAVFs is the preferred treatment option, given its high obliteration rate and favorable functional recovery outcomes. We advocate the identification of C1 spinal nerve root as a crucial surgical step to identify the shunting points of CCJ- SDAVFs.

Clinical outcomes among patients with concurrent blunt cerebrovascular injury and traumatic intracranial hemorrhage.

BACKGROUND: Blunt cerebrovascular injury (BCVI) accounts for 1-3 % of patients with blunt trauma, which should be promptly diagnosed and managed due to risk of cerebral infarction and death. Antithrombotic therapy had been proven to reduce risk of stroke and mortality. However, due to concern of hematoma progression, treatment suggestion is still inconclusive for patients with concurrent traumatic intracranial hemorrhage. MATERIALS AND METHODS: We performed a retrospective, observational study from 2002 to 2020 at a Level I trauma center, all patients with BCVI and concurrent traumatic intracranial hemorrhage were recruited. Patients' demographics, initial CT findings, severity of BCVI, treatment and outcomes were documented and analyzed to define possible risk factors of death and stroke. RESULTS: Among all 57 patients, 49 (86.0 %) patients had injury at ICA, 6 (10.5 %) had VA injury, and 2 (3.5 %) suffered from both. Targeted treatments for BCVI were provided to 33 (57.9 %) patient, mostly endovascular intervention (78.8 %), antithrombotic treatment was given to 11 (19.3 %) patients. At 3-month follow-up, 17 (29.8 %) patients expired, and 18 (31.6 %) patients had cerebral infarction due to BCVI. We identified more severe initial CT findings (p = 0.016), higher head Abbreviated Injury Scale (p = 0.049) and initial life-threatening events (p = 0.047) as risk factors of death, and traumatic basal cistern subarachnoid hemorrhage(SAH) (p = 0.040) as single risk factor of cerebral infarction. CONCLUSIONS: Around one-thirds of patients with concurrent BCVI and traumatic intracranial hemorrhage were death or suffered from cerebral infarction within 3 months, with severity of initial head injury and SAH at basal cistern as risk factors, respectively.

Impact of shared decision-making in Taiwanese patients with atrial fibrillation eligible for novel oral anticoagulant therapy.

BACKGROUND/PURPOSE: Shared decision-making (SDM) promotes patient awareness about medical conditions and treatments, facilitating patient involvement in care decisions. This two-stage multicenter study evaluated impacts of SDM in Taiwanese adults with atrial fibrillation (AF) eligible for novel oral anticoagulant (NOAC) therapy. METHODS: Participants were NOAC-naïve (part I) or dabigatran-experienced (part II). During Stage I, part I participants (n = 124) completed a semi-structured survey (understanding evaluation sections only) before and after viewing SDM materials on stroke prevention for AF. Surveys collected data on anxiety about AF, confidence in healthcare professionals, usefulness of the SDM materials, and perception of different NOACs. During Stage II, part I participants after being prescribed NOACs, and part II participants completed another survey to compare impacts of SDM. RESULTS: During Stage I, dabigatran was the preferred NOAC after viewing the SDM materials among 90% of part I participants. During Stage II, both part I (n = 87) and part II participants (n = 104) completed another survey. Fewer part I participants were anxious about AF (p < 0.01), and more had confidence in healthcare professionals (p < 0.01) after viewing SDM materials than before. Most part I participants (≥90%) rated the SDM materials as "very helpful". In Stage II, participants viewing SDM before initiating dabigatran had lower anxiety (part I, 43%; part II, 53%; p < 0.01) and a higher trust (part I, 92%; part II, 84%; p < 0.01). CONCLUSION: In conclusion, SDM reduced anxiety and improved trust in healthcare professionals among NOAC-naïve participants with AF.

Therapeutic glycan-specific antibody binding mediates protection during primary amoebic meningoencephalitis.

Naegleria fowleri (N. fowleri) infection via the upper respiratory tract causes a fatal CNS disease known as primary amoebic meningoencephalitis (PAM). The robust in vivo immune response to N. fowleri infection underlies the immunopathology that characterizes the disease. However, little is known about why this pathogen evades immune control. Infections occur in seemingly healthy individuals and effective clinical options are lacking, thus a nearly 98% fatality rate. It is unclear how or if host factors may contribute to susceptibility or disease exacerbation, yet mechanistic studies of the in vivo immune response and disease progression are hampered by a lack of tools. In this study, we have generated monoclonal antibodies to N. fowleri surface antigens and shown them to be excellent tools for studying the in vivo immune response. We also identified one monoclonal, 2B6, with potent inherent anti-amoebastatic activity in vitro. This antibody is also able to therapeutically prolong host survival in vivo and furthermore, recombinant antibodies with an isotype more capable of directing immune effector activity further improved survival when given therapeutically. Thus, we report the generation of a novel monoclonal antibody to N. fowleri that can enhance beneficial immune functions, even when given therapeutically during disease. We believe this provides evidence for the potential of therapeutic antibody treatments in PAM.IMPORTANCENaegleria fowleri (N. fowleri) is a free-living amoeba that is found ubiquitously in warm freshwater. While human exposure is common, it rarely results in pathogenesis. However, when N. fowleri gains access to the upper airway, specifically the olfactory mucosa, infection leads to a lethal disease known as primary amoebic meningoencephalitis (PAM). As a free-living amoeba, N. fowleri does not need a mammalian host; indeed, it can be accurately described as an accidental opportunistic pathogen. While most opportunistic infections occur in humans who are immunocompromised, there are no reported immune dysfunctions associated with N. fowleri infection. Therefore, the basis for N. fowleri opportunism is not known, and the reasons why some humans develop PAM while others do not are simply not well understood. It is reasonable to speculate that local or acute immune failures, potentially even a lack of prior adaptive immunity, are related to disease susceptibility. Careful immune profiling and characterization of the in vivo immune response to N. fowleri in a mammalian host are desperately needed to understand which host factors are critical to defense, and how these responses might be compromised in a way that results in lethal infection. To identify genes and pathways that provide resistance against in vivo N. fowleri infection, we generated surface reactive monoclonal antibodies (Abs) that provide rapid amoeba detection and quantification in vivo. Interestingly, N. fowleri binding Abs have been readily detected in the serum and saliva of humans and animals suggesting that non-lethal exposure drives a humoral immune response against the amoeba. Yet, how Abs might interact with Naegleria in vivo or contribute to preventing lethal infection is not well understood. In this study, we have generated and characterized a monoclonal antibody (Ab), Clone 2B6, that recognizes a glycosylated surface antigen present in cultured in vitro N. fowleri as well as mouse passaged N. fowleri. When clone 2B6 binds to N. fowleri, it inhibits amoeba motility and feeding behavior, leading to strong growth inhibition. Mice treated systemically and intracerebrally with Ab displayed a delayed disease onset and prolonged survival. In addition, we found that enhancing immune-directed effector activity via antibody isotype could further enhance survival without obvious immunopathogenic side effects. These findings show the potential for antibody treatment as an additional therapeutic to those used currently in PAM.

Urine Phthalate Metabolites are Elevated in Patients with Esophageal Squamous Cell Carcinoma and Associated with Advanced Cancer Stage and Poor Survival.

Background: The aim of this study was to investigate the role of phthalate in patients with esophageal squamous cell carcinoma (ESCC). Methods: A total of 116 ESCC patients and 58 controls without any known histories of malignancies were enrolled. All eight urine phthalate metabolites were measured to assess phthalate levels. Clinical and urine phthalate metabolite profiles were compared between subgroups to identify differences, and the effects of phthalates on clinical ESCC outcomes were also examined. Results: The concentrations of some urine phthalate metabolites were higher in the ESCC group than in the control group, including mono-(3-carboxypropyl) phthalate (MCPP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MnBP). Higher concentrations of urine phthalate metabolites were associated with clinical T3-T4 status. Patients with higher concentration of mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-2-ethylhexyl phthalate (MEHP), and MEOHP had lower 1-year and 2-year overall survival (OS) rates than those with lower concentrations of these metabolites in our univariate analysis. Multivariate analysis showed that urinary MEHP of ≥3 µg/L and clinical stage IVB were independent prognostic factors for worse OS. Conclusion: The results of our study showed that urine phthalate metabolites are elevated in ESCC patients and associated with advanced tumor stage, and that a high urinary concentration of MEHP is an independent prognostic factor of worse OS.

Grouting technique-combining transvenous Onyx and coils for the embolization of complex non-cavernous intracranial dural arteriovenous fistulas.

Objective: Incomplete occlusion of cerebral dural arteriovenous fistula (DAVF) may lead to fistula recurrence and rebleeding, which may necessitate several embolizations and lead to worse clinical outcomes. Herein, we describe a grouting technique for endovascular embolization and its outcomes in a series of patients with complex intracranial DAVF. Methods: A total of 20 patients with aggressive type or symptomatic intracranial non-cavernous DAVF underwent endovascular transvenous embolization combining detachable coils and Onyx. Two microcatheters were positioned either in the distal segment of the involved sinus or near the draining veins. To achieve tight occlusion of the involved sinus, coils were carefully delivered through the first microcatheter, starting from the distal segment and then to the proximal segment. Next, Onyx was injected through the second microcatheter to reinforce and fill (grout) the interspace of coil mass and gradually refluxed to the mural channels and para-sinus cortical veins until the fistula was completely occluded. Results: Successful embolization was achieved in all 20 patients. The initial angiographic results revealed the achievement of complete occlusion in 19 patients (95%). At the postembolization follow-up, complete obliteration of the fistula was achieved in all patients (100%). No symptom or angiographic recurrence was observed at the 2- to 5-year follow-ups. No patient required additional embolization or stereotactic radiosurgery. Conclusion: The proposed grouting technique combining detachable coils and Onyx appears to be promising for the elimination of complex intracranial non-cavernous DAVFs.

Clinical Predictors of Nontuberculous Mycobacteria Lung Disease and Coisolates of Potential Pathogenic Microorganisms in Noncystic Fibrosis Bronchiectasis.

Background: In bronchiectasis, nontuberculous mycobacteria (NTM) lung disease (NTM-LD) is a well-known coexisting infection. However, microorganism coisolates and clinical NTM-LD predictors are poorly studied. Methods: Patients with bronchiectasis diagnosed by means of computed tomography between January 2017 and June 2020 were screened, using the date of computed tomography as the index date. Those with a major bronchiectasis diagnosis in ≥2 follow-up visits after the index date were enrolled in the study, and NTM-LD occurrence and its association with pneumonia and hospitalization within 1 year were analyzed. Results: Of the 2717 participants, 79 (2.9%) had NTM-LD diagnosed. The factors associated with NTM-LD included hemoptysis, postinfectious bronchiectasis, a tree-in-bud score ≥2, a modified Reiff score ≥4, and chronic obstructive pulmonary disease (adjusted odds ratios, 1.80, 2.36, 1.78, 2.95, and 0.51, respectively). Compared with patients in the non-NTM group, those with NTM-LD had higher rates of hospitalization (15.9% vs 32.9%; P < .001) and pneumonia (9.8% vs 20.3%; P = .003). Pseudomonas aeruginosa was the most common microorganism in those with NTM-LD and those in the non-NTM group (10.1% vs 7.8%; P = .40). However, compared with those in the non-NTM group, Acinetobacter baumannii and Escherichia coli were more prevalent in patients with NTM-LD (0.7% vs 3.8% [P = .03%] and 1.0% vs 3.8% [P = .05], respectively). Conclusions: Postinfectious bronchiectasis with hemoptysis, higher radiological involvement, and a tree-in-bud pattern were associated with NTM-LD risk. The rate of A baumannii and E coli coisolation was higher in bronchiectasis populations with NTM-LD.

Current Status of Translational Science in Nursing Across Four Countries.

The raison d'être of nursing is caring for human beings. Mainly due to its close link to the nursing discipline's raison d'être, "caring," translational science is recently getting more attention from nursing scientists across the globe. This paper is to discuss the current status of translational science in nursing across four countries (the USA, Taiwan, South Korea, and Japan). The data used in this discussion paper included: (a) written notes on issues related translational research/science in individual countries; (b) written memos on exemplars/cases from their own experiences; and (c) summaries of literature reviews. The data analysis was conducted using a simple content analysis. Four themes reflecting the current status of translational science across the countries were identified: (a) "contextualized in unique culture and history of nursing"; (b) "connecting basic science to clinical practice"; (c) "an extension of evidence-based practice"; and (d) "highly promoted, but still minimal translation of nursing knowledge."

The Future of Kawasaki Disease Diagnosis: Liquid Biopsy May Hold the Key.

Kawasaki disease (KD) is a febrile illness characterised by systemic inflammation of small- and medium-sized blood vessels, which commonly occurs in young children. Although self-limiting, there is a risk of developing coronary artery lesions as the disease progresses, with delay in diagnosis and treatment. Unfortunately, the diagnosis of KD continues to remain a clinical dilemma. Thus, this article not only summarises the key research gaps associated with KD, but also evaluates the possibility of using circulating endothelial injury biomarkers, such as circulating endothelial cells, endothelial microparticles and vascular endothelial cell-free DNA, as diagnostic and prognostic tools for KD: a "liquid biopsy" approach. The challenges of translating liquid biopsies to use in KD and the opportunities for improvement in its diagnosis and management that such translation may provide are discussed. The use of endothelial damage markers, which are easily obtained via blood collection, as diagnostic tools is promising, and we hope this will be translated to clinical applications in the near future.

Circulating corin concentration is associated with risk of mortality and acute kidney injury in critically ill patients.

Elevated serum corin concentrations in patients with cardiac diseases have been associated with adverse cardiovascular events and progressive renal dysfunction. This study aimed to determine the role of serum corin levels in predicting the incidence of acute kidney injury (AKI) and mortality in critically ill patients admitted to intensive care units (ICUs). We screened 323 patients admitted to the ICU in our institution from May 2018 through December 2019. After excluding patients receiving renal replacement therapy, 288 subjects were enrolled. Cases were divided equally into high (n = 144) and low (n = 144) corin groups according to median serum corin levels, using 910 pg/mL as the cut-off point. Patient characteristics and comorbidities were collected from medical records. The primary outcome was AKI within 48 h after ICU admission, while the secondary outcome was all-cause of mortality within 1 year. Compared with the low corin group, patients in the high corin group had higher prevalence rates of diabetes, cirrhosis, and nephrotoxic agent exposure; higher Sequential Organ Failure Assessment scores, white blood cell counts, proteinuria, and serum N-terminal pro-brain natriuretic peptide levels; but had lower initial estimated glomerular filtration rates. Furthermore, elevated serum corin was associated with higher risks of AKI within 48h of ICU admission (43.1% vs. 18.1%, p < 0.001) and all-cause mortality within one year (63.9% vs. 50.0%, p = 0.024). High corin level showed strongly positive results as an independent predictor of AKI (OR 2.15, 95% CI 1.11-4.19, p = 0.024) but not for the all-cause mortality after adjusting for confounding factors in multivariate analyses. Elevated circulating corin predicted AKI in critically ill patients, but did not predict all-cause mortality within 1 year. As a key enzyme in renin-angiotensin-aldosterone system, corin expression may be regulated through a feedback loop following natriuretic peptide resistance and desensitization of natriuretic peptide receptors in different critically ill status.

Stereotactic Radiosurgery With Versus Without Neoadjuvant Endovascular Embolization for Brain Arteriovenous Malformations With Associated Intracranial Aneurysms.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) with neoadjuvant embolization is a treatment strategy for brain arteriovenous malformations (AVMs), especially for those with large nidal volume or concomitant aneurysms. The aim of this study was to assess the effects of pre-SRS embolization in AVMs with an associated intracranial aneurysm (IA). METHODS: The International Radiosurgery Research Foundation AVM database from 1987 to 2018 was retrospectively reviewed. SRS-treated AVMs with IAs were included. Patients were categorized into those treated with upfront embolization (E + SRS) vs stand-alone SRS (SRS). Primary end point was a favorable outcome (AVM obliteration + no permanent radiation-induced changes or post-SRS hemorrhage). Secondary outcomes included AVM obliteration, mortality, follow-up modified Rankin Scale, post-SRS hemorrhage, and radiation-induced changes. RESULTS: Forty four AVM patients with associated IAs were included, of which 23 (52.3%) underwent pre-SRS embolization and 21 (47.7%) SRS only. Significant differences between the E + SRS vs SRS groups were found for AVM maximum diameter (1.5 ± 0.5 vs 1.1 ± 0.4 cm3, P = .019) and SRS treatment volume (9.3 ± 8.3 vs 4.3 ± 3.3 cm3, P = .025). A favorable outcome was achieved in 45.4% of patients in the E + SRS group and 38.1% in the SRS group (P = .625). Obliteration rates were comparable (56.5% for E + SRS vs 47.6% for SRS, P = .555), whereas a higher mortality rate was found in the SRS group (19.1% vs 0%, P = .048). After adjusting for AVM maximum diameter, SRS treatment volume, and maximum radiation dose, the likelihood of achieving favorable outcome and AVM obliteration did not differ between groups (P = .475 and P = .820, respectively). CONCLUSION: The likelihood of a favorable outcome and AVM obliteration after SRS with neoadjuvant embolization in AVMs with concomitant IA seems to be comparable with stand-alone SRS, even after adjusting for AVM volume and SRS maximum dose. However, the increased mortality among the stand-alone SRS group and relatively low risk of embolization-related complications suggest that these patients may benefit from a combined treatment approach.

Elevated cerebrospinal fluid galectin-3 and associated cytokines after severe traumatic brain injury in patients.

This study aimed to investigate the galectin-3 and associated cytokines levels in the cerebrospinal fluid (CSF) of severe traumatic brain injury (sTBI) patients. Temporal CSF expression of galectin-3 and associated cytokines levels in sTBI patients within 1-week post-injury were studied using the multiplex bead array. STBI patient group was stratified using the Modified Rankin Score (mRS) into 3 groups: mRS 6 (died), mRS 5 (severely disabled) and mRS 1-4 (mild-to-moderately disabled) group. Analysis for bead array data using Kruskal-Wallis test with post hoc Dunn's multiple comparisons test, and temporal changes and correlation analysis using Spearman's correlation were carried out. At day 1 post-injury, CSF galectin-3 and interleukin-6 (IL-6), interleukin-10 (IL-10), cysteine-cysteine motif chemokine ligand-2 (CCL-2), and cysteine-cysteine motif chemokine ligand-20 (CCL-20), but not interleukin-1ß (IL-1ß) and tumor necrosis factor (TNF-α) levels were significantly elevated in mRS 5 group compared to non-TBI controls. Temporal correlation analysis at 1-7 days showed decreased IL-10 level in the mRS 6 group, decreased IL-10 and CCL-2 levels in mRS 5 group, and decreased IL-6, CCL-2, and CCL-20 levels in the mRS 1-4 group. Receiver operating characteristic curve analyses revealed a significant area under the curve for comparison between mRS 6 and mRS 5 groups for galectin-3 and IL-6. No significant differences in sex, age, Glasgow Coma Scale score, C-reactive protein levels and types of TBI-induced hemorrhages were observed between the groups. CSF galectin-3 and associated cytokines, especially IL-6, CCL-2 and CCL-20 levels were different within sub-groups of sTBI patients, suggesting their potential use in sTBI prognostics.

Tetradentate Pt(II) complexes based on xylenylamino linked dual pyrazolate chelates for organic light emitting diodes.

In this work, we report the syntheses of three Pt(II) emitters, namely, Pt4N1, Pt4N2, and Pt4N3, to which their tetradentate chelates were assembled by linking two pyrazolate chelates with a single xylenylamino entity. Functionalization of Pt4N1 was achieved upon addition of electronegative CF3 substituent on pyridinyl groups and switching to more electron deficient pyrazinyl groups in giving Pt4N2 and Pt4N3, respectively. The vertical arranged xylenylamino entity has effectively suppressed the inter-molecular π-π stacking and Pt···Pt interaction, as shown by the single crystal X-ray structural analyses. Upon fabrication of OLED devices, Pt4N2 and Pt4N3 based devices delivered efficient cyan and green emission, with an EQEmax of 15.2% and 11.2%, respectively, affirming the successfulness of the tetradentate chelating strategy.

Genetic parameters for pelvic organ prolapse in purebred and crossbred sows.

This study aimed to investigate genetic parameters for sow pelvic organ prolapse in purebred and crossbred herds. Pelvic organ prolapse was recorded as normal or prolapsed on the individual sow level across 32 purebred and 8 crossbred farms. In total, 75,162 purebred Landrace sows from a single maternal line were recorded between 2018 and 2023, while 18,988 commercial two-way crossbred (Landrace x Large White) sows were available between 2020 and 2023. There were 5,122,005 animals included in the pedigree. The prolapse in purebreds and crossbreds was considered two different traits in the model. Pedigrees of the crossbred sows were determined based on genotypes through parentage assignment. The average incidence rates were 1.81% and 3.93% for purebreds and crossbreds, respectively. The bivariate model incorporated fixed effects of parity group and region with random effects of contemporary group (farm and mating year and month at the first parity), additive genetic, and residual. Genetic parameter estimates were obtained using BLUPF90+ with the AIREML option. The estimated additive variance was larger in crossbreds than in purebreds. Estimates of heritability in the observed scale were 0.09 (0.006) for purebreds and 0.11 (0.014) for crossbreds, with a genetic correlation of 0.83 using a linear model. Results suggested that including data from crossbreds with higher incidence rate is beneficial and selection to reduce the prolapse incidence in purebred sow herds would also benefit commercial crossbred sow herds.

Transcriptome analysis of Drosophila suzukii reveals molecular mechanisms conferring pyrethroid and spinosad resistance.

Drosophila suzukii lay eggs in soft-skinned, ripening fruits, making this insect a serious threat to berry production. Since its 2008 introduction into North America, growers have used insecticides, such as pyrethroids and spinosads, as the primary approach for D. suzukii management, resulting in development of insecticide resistance in this pest. This study sought to identify the molecular mechanisms conferring insecticide resistance in these populations. We sequenced the transcriptomes of two pyrethroid- and two spinosad-resistant isofemale lines. In both pyrethroid-resistant lines and one spinosad-resistant line, we identified overexpression of metabolic genes that are implicated in resistance in other insect pests. In the other spinosad-resistant line, we observed an overexpression of cuticular genes that have been linked to resistance. Our findings enabled the development of molecular diagnostics that we used to confirm persistence of insecticide resistance in California, U.S.A. To validate these findings, we leveraged D. melanogaster mutants with reduced expression of metabolic or cuticular genes that were found to be upregulated in resistant D. suzukii to demonstrate that these genes are involved in promoting resistance. This study is the first to characterize the molecular mechanisms of insecticide resistance in D. suzukii and provides insights into how current management practices can be optimized.

Inhibition of MARCKS phosphorylation attenuates of dendritic cell migration in a murine model of acute asthma.

BACKGROUND: MARCKS (myristoylated alanine-rich C kinase substrates) serves as a substrate for protein kinase C, residing in the plasma membrane while acts as an actin filament crosslinking protein. This investigation aims to elucidate phosphorylated MARCKS (p-MARCKS) levels and activity in allergic asthma patients and explore the therapeutic potential of peptide inhibitors targeting p-MARCKS in an acute mouse model of allergic asthma. METHODS: Immunohistochemistry and histology staining were employed on lung tissue slides to evaluate p-MARCKS expression and allergic asthma symptoms. Airway resistance was measured using invasive whole-body plethysmography. Flow cytometry detected lung dendritic cell migration, and migration/maturation assays were conducted on isolated murine bone marrow-derived dendritic cells (BM-DCs). RESULTS: Elevated p-MARCKS expression was observed in both human asthmatic tissues and animal models immunized with ovalbumin or Alternaria alternata. Remarkably, asthmatic individuals showed elevated high p-MARCKS expression in lung tissues. Intraperitoneal injection of the peptide MPS, targeting the MARCKS phosphorylation site domain, before allergen challenged, effectively suppressed MARCKS phosphorylation in murine lung tissues. MPS inhibited both in vivo and in vitro migration and maturation of dendritic cells (BM-DCs) and reduced Th2-related lymphocyte activation in bronchoalveolar lavage fluid (BALF). MPS pretreatment additionally suppressed all symptoms associated with allergic airway asthma, including a reduction in inflammatory cell influx, airway mucous cell metaplasia, and airway hyperreactivity. CONCLUSION: These findings suggest that phosphorylated MARCKS occurs in asthmatic lung tissue, and the inhibition of MARCKS phosphorylation by the MPS peptide reduces dendritic cell migration and Th2-related lymphocytes in the lungs in a murine model of acute asthma.

One-stage burr hole surgery and middle meningeal arterial embolization for treating chronic subdural hematoma in a hybrid operative angiography suite.

BACKGROUND: Chronic subdural hematoma (CSDH) is a prevalent neurosurgical condition that is known to recur and that leads to unfavorable clinical outcomes. Middle meningeal artery embolization (MMAE) has emerged as an alternative treatment to prevent recurrence. This study investigated the efficacy of combined two therapies in a hybrid operative suite for high-risk patients. METHODS: This retrospective review provides evidence for the indications and benefits of one-stage combined therapy in a hybrid neurovascular operative suite. The procedures include burr hole craniostomy, irrigation, and drainage followed by adjuvant MMAE at the lesion site. Subsequently, routine cone beam computed tomography is conducted after the whole process. RESULTS: Five patients with symptomatic CSDH and mass effect were enrolled in this study. Among them, three patients had undergone burr hole surgery previously but experienced hematoma recurrence. Two patients presented with a history of recent cardiac stent placement due to coronary artery disease, precluding the cessation of antiplatelet or anticoagulant therapy. All patients experienced symptom resolution and demonstrated no evidence of CSDH recurrence during the follow-up period. CONCLUSION: In our initial case experiences, one-stage burr hole surgery and adjuvant MMAE for treating chronic subdural hematoma in a hybrid operative angiography suite could be a feasible and effective treatment modality.

Formability Prediction Using Machine Learning Combined with Process Design for High-Drawing-Ratio Aluminum Alloy Cups.

Deep drawing has been practiced in various manufacturing industries for many years. With the aid of stamping equipment, materials are sheared to different shapes and dimensions for users. Meanwhile, through artificial intelligence (AI) training, machines can make decisions or perform various functions. The aim of this study is to discuss the geometric and process parameters for A7075 in deep drawing and derive the formable regions of sound products for different forming parameters. Four parameters-forming temperature, punch speed, blank diameter and thickness-are used to investigate their effects on the forming results. Through finite element simulation, a database is established and used for machine learning (ML) training and validation to derive an AI prediction model. Importing the forming parameters into this prediction model can obtain the forming results rapidly. To validate the formable regions of sound products, several experiments are conducted and the results are compared with the prediction results to verify the feasibility of applying ML to deep drawing processes of aluminum alloy A7075 and the reliability of the AI prediction model.