Continuous Myocardial Perfusion during Distal Anastomosis of Acute Type A Aortic Dissection.

BACKGROUND: The effect of continuous myocardial perfusion (CMP) on the surgical results of acute type A aortic dissection (ATAAD) remains unclear. METHODS: From January 2017 to March 2022, 141 patients who underwent ATAAD (90.8%) or intramural hematoma (9.2%) surgery were reviewed. Fifty-one patients (36.2%) received proximal-first aortic reconstruction and CMP during distal anastomosis. Ninety patients (63.8%) underwent distal-first aortic reconstruction and were placed in traditional cold blood cardioplegic arrest (CA; 4°C, 4:1 blood-to-Plegisol) throughout the procedure. The preoperative presentations and intraoperative details were balanced using inverse probability of treatment weighting (IPTW). Their postoperative morbidity and mortality were analyzed. RESULTS: The median age was 60 years. The incidence of arch reconstruction in the unweighted data was higher in the CMP compared with the CA group (74.5 vs 52.2%, p = 0.017) but was balanced after IPTW (62.4 vs 58.9%, p = 0.932, standardized mean difference = 0.073). The median cardiac ischemic time was lower in the CMP group (60.0 vs 130.9 minutes, p < 0.001), but cerebral perfusion time and cardiopulmonary bypass time were similar. The CMP group did not demonstrate any benefit in the reduction of the postoperative maximum creatine kinase-MB ratio (4.4 vs 5.1% in CA, p = 0.437) or postoperative low cardiac output (36.6 vs 24.8%, p = 0.237). Surgical mortality was comparable between groups (15.5% in CMP vs 7.5% in the CA group, p = 0.265). CONCLUSION: Application of CMP during distal anastomosis in ATAAD surgery, irrespective of the extent of aortic reconstruction, reduced myocardial ischemic time but did not improve cardiac outcome or mortality.

Discovery of a New Compound, Erinacerin W, from the Mycelia of Hericium erinaceus, with Immunomodulatory and Neuroprotective Effects.

One new compound with an isoindolinone skeleton, along with erinacines A, C, and S, was isolated from the mycelia of Hericium erinaceus, an edible fungus with a long history of use in traditional Chinese medicine. Based on analysis of MS and NMR spectral data, the structure of the compound was identified as (2E,6E)-8-(2-(1-carboxy-3-methylbutyl)-4,6-dihydroxy-1-oxoisoindolin-5-yl)-2,6-dimethylocta-2,6-dienoic acid. In light of this discovery, we have given this compound the name erinacerin W. Using a co-culture in vitro LPS-activated BV2 microglia-induced SH-SY5Y neuroinflammation model, the results showed that erinacerin W demonstrated protection against the LPS-activated BV-2 cell-induced overexpression of IL-6, IL-1ß, and TNF-α on SH-SY5Y cells. This finding may provide potential therapeutic approaches for central nervous disorders.

Spontaneous chaos and extreme events in a solid-state laser with the transverse-mode-degenerate cavity configuration.

In this Letter, we theoretically analyze cavity beam propagation in a gain medium and cavity using the rate equation and generalized Huygens integral, respectively. Spontaneous chaos and extreme events (EEs) occurred around the transverse-mode-degenerate cavity configuration because of transverse-mode competition. A closed occurrence region relating to varying pump power and cavity length was observed. The experimental results in a continuous-wave Nd:YVO4 laser agreed with the aforementioned numerical results. Because gain effect is essential to a laser, we assume that EEs can be intrinsic and universal in a well-aligned laser system if it satisfies the specific transverse-mode competition.

Vitamin D and Diabetic Kidney Disease.

Vitamin D is a hormone involved in many physiological processes. Its active form, 1,25(OH)2D3, modulates serum calcium-phosphate homeostasis and skeletal homeostasis. A growing body of evidence has demonstrated the renoprotective effects of vitamin D. Vitamin D modulates endothelial function, is associated with podocyte preservation, regulates the renin-angiotensin-aldosterone system, and has anti-inflammatory effects. Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease worldwide. There are numerous studies supporting vitamin D as a renoprotector, potentially delaying the onset of DKD. This review summarizes the findings of current research on vitamin D and its role in DKD.

Chemically Recyclable Ester-Linked Polypropylene.

Polyolefins represent the largest class of commodity materials due to their excellent material properties; however, they have limited pathways to chemical recycling and are often difficult to mechanically recycle. Here we demonstrate a new catalyst for the isoselective copolymerization of propylene and butadiene capable of favoring 1,4-insertion over 1,2-insertion while maintaining good molecular weights and turnover frequencies. This isotactic propylene copolymer with main-chain unsaturation was depolymerized to a telechelic macromonomer using an olefin metathesis catalyst and 2-hydroxyethyl acrylate. After hydrogenation, the telechelic macromonomer was repolymerized to form an ester-linked polypropylene material. This polymer shows thermal and mechanical properties comparable to linear low-density polyethylene. Finally, the telechelic macromonomer could be regenerated through the depolymerization of the ester-linked polypropylene material, which allows for the chemical recycling to macromonomer. This process provides a route to transform partially unsaturated polyolefins to chemically recyclable materials with similar properties to their parent polymers.

Whole-exome sequencing identified mutational profiles of urothelial carcinoma post kidney transplantation.

Kidney transplantation is a lifesaving option for patients with end-stage kidney disease. In Taiwan, urothelial carcinoma (UC) is the most common de novo cancer after kidney transplantation (KT). UC has a greater degree of molecular heterogeneity than do other solid tumors. Few studies have explored genomic alterations in UC after KT. We performed whole-exome sequencing to compare the genetic alterations in UC developed after kidney transplantation (UCKT) and in UC in patients on hemodialysis (UCHD). After mapping and variant calling, 18,733 and 11,093 variants were identified in patients with UCKT and UCHD, respectively. We excluded known single-nucleotide polymorphisms (SNPs) and retained genes that were annotated in the Catalogue of Somatic Mutations in Cancer (COSMIC), in the Integrative Onco Genomic cancer mutations browser (IntOGen), and in the Cancer Genome Atlas (TCGA) database of genes associated with bladder cancer. A total of 14 UCKT-specific genes with SNPs identified in more than two patients were included in further analyses. The single-base substitution (SBS) profile and signatures showed a relative high T > A pattern compared to COMSIC UC mutations. Ingenuity pathway analysis was used to explore the connections among these genes. GNAQ, IKZF1, and NTRK3 were identified as potentially involved in the signaling network of UCKT. The genetic analysis of posttransplant malignancies may elucidate a fundamental aspect of the molecular pathogenesis of UCKT.

Energy Efficiency of Inference Algorithms for Clinical Laboratory Data Sets: Green Artificial Intelligence Study.

BACKGROUND: The use of artificial intelligence (AI) in the medical domain has attracted considerable research interest. Inference applications in the medical domain require energy-efficient AI models. In contrast to other types of data in visual AI, data from medical laboratories usually comprise features with strong signals. Numerous energy optimization techniques have been developed to relieve the burden on the hardware required to deploy a complex learning model. However, the energy efficiency levels of different AI models used for medical applications have not been studied. OBJECTIVE: The aim of this study was to explore and compare the energy efficiency levels of commonly used machine learning algorithms-logistic regression (LR), k-nearest neighbor, support vector machine, random forest (RF), and extreme gradient boosting (XGB) algorithms, as well as four different variants of neural network (NN) algorithms-when applied to clinical laboratory datasets. METHODS: We applied the aforementioned algorithms to two distinct clinical laboratory data sets: a mass spectrometry data set regarding Staphylococcus aureus for predicting methicillin resistance (3338 cases; 268 features) and a urinalysis data set for predicting Trichomonas vaginalis infection (839,164 cases; 9 features). We compared the performance of the nine inference algorithms in terms of accuracy, area under the receiver operating characteristic curve (AUROC), time consumption, and power consumption. The time and power consumption levels were determined using performance counter data from Intel Power Gadget 3.5. RESULTS: The experimental results indicated that the RF and XGB algorithms achieved the two highest AUROC values for both data sets (84.7% and 83.9%, respectively, for the mass spectrometry data set; 91.1% and 91.4%, respectively, for the urinalysis data set). The XGB and LR algorithms exhibited the shortest inference time for both data sets (0.47 milliseconds for both in the mass spectrometry data set; 0.39 and 0.47 milliseconds, respectively, for the urinalysis data set). Compared with the RF algorithm, the XGB and LR algorithms exhibited a 45% and 53%-60% reduction in inference time for the mass spectrometry and urinalysis data sets, respectively. In terms of energy efficiency, the XGB algorithm exhibited the lowest power consumption for the mass spectrometry data set (9.42 Watts) and the LR algorithm exhibited the lowest power consumption for the urinalysis data set (9.98 Watts). Compared with a five-hidden-layer NN, the XGB and LR algorithms achieved 16%-24% and 9%-13% lower power consumption levels for the mass spectrometry and urinalysis data sets, respectively. In all experiments, the XGB algorithm exhibited the best performance in terms of accuracy, run time, and energy efficiency. CONCLUSIONS: The XGB algorithm achieved balanced performance levels in terms of AUROC, run time, and energy efficiency for the two clinical laboratory data sets. Considering the energy constraints in real-world scenarios, the XGB algorithm is ideal for medical AI applications.

Safety Time and Optimal Temperature of Unilateral Antegrade Cerebral Perfusion in Acute Type A Aortic Dissection: A Single-Center 15-Year Experience.

Background: The optimal level of hypothermia and safe time of unilateral antegrade cerebral perfusion (uACP) in acute type A aortic dissection (ATAAD) repair remain controversial. Objectives: To analyze the association of uACP time and circulatory arrest temperature with surgical outcomes of ATAAD. Methods: We retrospectively analyzed 263 patients who had undergone ATAAD repair between 2006 and 2020 using uACP. The patients were stratified by three chronologically equivalent periods (period 1, 2006 to 2010; period 2, 2011 to 2015; period 3, 2016 to 2020) to demonstrate the decade-long evolution of surgical strategy and outcomes. Results: The mean age of the patients was 59.4 ± 12.5 years, and 68.8% were male. The hospital mortality rates were 15.1%, 12.9%, and 11.0% from period 1 to 3 (p = 0.740). The median circulatory arrest temperatures were 20, 23, and 25 °C (p < 0.001), respectively, and the median uACP times were 72, 59, and 41 minutes (p < 0.001). The incidence rates of postoperative permanent neurologic deficits were 13.2%, 10.9%, and 18.3% (p = 0.312), and those of transient neurologic deficits were 9.4%, 10.9%, and 11.9% (p = 0.936), respectively. Multivariate logistic regression analysis showed that uACP time ≥ 60 minutes was an independent predictor of hospital mortality rather than postoperative stroke. ROC curve analysis estimated an optimal cutoff value of 52 minutes of uACP time when the circulatory arrest temperature was ≥ 25 °C to predict hospital mortality (area under the curve: 0.72). Conclusions: Unilateral antegrade cerebral perfusion time was associated with hospital mortality after ATAAD surgery. A safe threshold of 50 to 60 minutes of uACP should be considered.

Preclinical Bioavailability, Tissue Distribution, and Protein Binding Studies of Erinacine A, a Bioactive Compound from Hericium erinaceus Mycelia Using Validated LC-MS/MS Method.

Erinacine A, derived from the mycelia of Hericium erinaceus, has attracted much attention due to its neuroprotective properties. However, very few studies have been conducted on the bioavailability, tissue distribution, and protein binding of erinacine A. This study aimed to investigate the bioavailability, tissue distribution, and protein binding of erinacine A in Sprague-Dawley rats. After oral administration (po) and intravenous administration (iv) of 2.381 g/kg BW of the H. erinaceus mycelia extract (equivalent to 50 mg/kg BW of erinacine A) and 5 mg/kg BW of erinacine A, respectively, the absolute bioavailability of erinacine A was estimated as 24.39%. Erinacine A was detected in brain at 1 h after oral dosing and reached the peak at 8 h. Protein binding assay showed unbound erinacine A fractions in brain to blood ratio is close to unity, supporting passive diffusion as the dominating transport. Feces was the major route for the elimination of erinacine A. This study is the first to show that erinacine A can penetrate the blood-brain barrier of rats by the means of passive diffusion and thus support the development of H. erinaceus mycelia for the improvement of neurohealth.

Patient-Derived Tumor Chemosensitization of GKB202, an Antrodia Cinnamomea Mycelium-Derived Bioactive Compound.

Oral cancers, hepatocellular carcinoma, and colorectal cancers are the three most common cancers, leading to 18,000 cases of cancer-related mortality in Taiwan per year. To bridge the gap towards clinical translation, we developed a circulating tumor cell (CTC) organoid culture workflow that efficiently expands CTC from patients to test Antrodia Cinnamomea mycelium-derived bioactive compounds. Three ACM-derived bioactive compounds were evaluated for tumor chemosensitization characteristics. Significant and consistent cytotoxic/5-FU sensitizing effects of GKB202 were found on 8 different patient-derived tumors. Acute toxicity profile and hepatic metabolism of GKB202 in rats suggest GKB202 is rapidly cleared by liver and is well tolerated up to the dose of 20 mg/kg. This comprehensive study provides new evidence that liquid fermentation of Antrodia cinnamomea mycelium (ACM) contains bioactive compounds that lead to effective control of CTC, especially when combined with 5-FU. Together, these data suggest ACM-derived GKB202 may be considered for further clinical investigation in the context of 5-FU-based combination therapy.

Rosuvastatin Failed to Improve Arteriovenous Fistula Patency for Hemodialysis in Diabetic Patients - A Randomized Clinical Trial.

BACKGROUND: Very limited therapeutic strategies exist to prevent the primary failure of arteriovenous (AV) fistulas in patients with diabetes. OBJECTIVES: To investigate whether rosuvastatin could improve the primary patency of AV fistulas in diabetic patients with stage 5 chronic kidney disease (CKD). METHODS: This was a double-blind randomized clinical trial. From July 2012 to September 2018, patients aged between 18 and 65 years with type 2 diabetes and stage 5 CKD were randomized to receive placebo or rosuvastatin (5 mg/day) for 7 days prior to the creation of an AV fistula on the forearm until the 21st day after surgery. Patients were followed up for 180 days after the operation. The primary composite endpoint was the development of fistula immaturity or stenosis. The secondary endpoints were changes in inflammatory markers, oxidative stress, and occurrence of postoperative complications. RESULTS: A total of 60 patients were enrolled in the study. Rosuvastatin resulted in a 20% reduction in total cholesterol from postoperative day 0 to 28 (p = .0006). The overall rate of AV fistula failure (immaturity or stenosis) was 30%, with no significant difference between patients receiving rosuvastatin and those receiving the placebo (33.3% vs. 26.7%, p = .5731). Although not statistically significant, the administration of rosuvastatin might have increased the incidence of postoperative complications (2.99 vs. 2.39 event rate per 1000 patient-days; odds ratio, 1.33; p = .5986). CONCLUSIONS: Rosuvastatin showed no significant beneficial effects on the primary patency of AV fistulas in diabetic patients with stage 5 CKD, but might have been associated with the risk of drug-related complications.

Post-Coronary Artery Bypass Medications in Dialysis Patients: Do We Need to Change Strategies?

BACKGROUND: Coronary artery bypass grafting (CABG) is frequently performed in patients with end-stage renal disease (ESRD) together with severe coronary artery disease, after which, patients with ESRD have higher surgical risk and poorer long-term outcomes. We report our experience in patients with ESRD who survived in CABG and identify predictors of long-term outcomes. METHODS: We retrospectively investigated 93 consecutive patients with ESRD who survived to discharge after isolated CABG between January 2005 and December 2016 at our institution. Long-term outcomes, including all-cause mortality after discharge, readmission due to major adverse cardiac events, and reintervention, were evaluated. Predictors affecting long-term outcomes were also analyzed. RESULTS: The rates of freedom from all-cause mortality after discharge in 1, 3, 5, and 10 years were 92.1, 81.3, 71.9, and 34.9%, respectively. The rates of freedom from readmission due to major adverse cardiac events in 1, 3, 5, and 10 years were 90.7, 79.1, 69.9, and 55.6%, respectively. The rates of freedom from reintervention in 1, 3, 5, and 10 years were 95.3, 86.5, 79.0, and 66.6%, respectively. Postoperative ß-blocker and statin use significantly improved overall long-term survival (ß-blocker, p = 0.013; statin, p = 0.009). After case-control matching, patients who received statins showed better long-term survival than those without statins. The comparison of long-term survival between patients with and without ß-blockers showed no significant difference after matching. CONCLUSIONS: After CABG, dialysis patients who survived to discharge had acceptable long-term overall survival. Post-CABG statin use in dialysis patients is a predictor of better long-term survival.

Novel Toilet Paper-Based Point-Of-Care Test for the Rapid Detection of Fecal Occult Blood: Instrument Validation Study.

BACKGROUND: Colorectal cancer screening by fecal occult blood testing has been an important public health test and shown to reduce colorectal cancer-related mortality. However, the low participation rate in colorectal cancer screening by the general public remains a problematic public health issue. This fact could be attributed to the complex and unpleasant operation of the screening tool. OBJECTIVE: This study aimed to validate a novel toilet paper-based point-of-care test (ie, JustWipe) as a public health instrument to detect fecal occult blood and provide detailed results from the evaluation of the analytic characteristics in the clinical validation. METHODS: The mechanism of fecal specimen collection by the toilet-paper device was verified with repeatability and reproducibility tests. We also evaluated the analytical characteristics of the test reagents. For clinical validation, we conducted comparisons between JustWipe and other fecal occult blood tests. The first comparison was between JustWipe and typical fecal occult blood testing in a central laboratory setting with 70 fecal specimens from the hospital. For the second comparison, a total of 58 volunteers were recruited, and JustWipe was compared with the commercially available Hemoccult SENSA in a point-of-care setting. RESULTS: Adequate amounts of fecal specimens were collected using the toilet-paper device with small day-to-day and person-to-person variations. The limit of detection of the test reagent was evaluated to be 3.75 µg of hemoglobin per milliliter of reagent. Moreover, the test reagent also showed high repeatability (100%) on different days and high reproducibility (>96%) among different users. The overall agreement between JustWipe and a typical fecal occult blood test in a central laboratory setting was 82.9%. In the setting of point-of-care tests, the overall agreement between JustWipe and Hemoccult SENSA was 89.7%. Moreover, the usability questionnaire showed that the novel test tool had high scores in operation friendliness (87.3/100), ease of reading results (97.4/100), and information usefulness (96.1/100). CONCLUSIONS: We developed and validated a toilet paper-based fecal occult blood test for use as a point-of-care test for the rapid (in 60 seconds) and easy testing of fecal occult blood. These favorable characteristics render it a promising tool for colorectal cancer screening as a public health instrument.

Absolute Bioavailability, Tissue Distribution, and Excretion of Erinacine S in Hericium erinaceus Mycelia.

Erinacine S, so far known to have been produced only in Hericium erinaceus mycelia, has just recently been discovered and is able to reduce amyloid plaque growth and improve neurogenesis in aged brain of rats. However, few investigations have been conducted on the absorption, distribution, and excretion study of Erinacine S. This study aimed to investigate the absolute bioavailability, tissue distribution, and excretion of Erinacine S in H. Erinaceus mycelia in eight-week old Sprague-Dawley rats. After oral administration and intravenous administration of 2.395 g/kg body weight of the H. erinaceus mycelia extract (equivalent to 50 mg/kg body weight Erinacine S) and 5 mg/kg of Erinacine S, respectively, the absolute bioavailability was estimated as 15.13%. In addition, Erinacine S was extensively distributed in organs such as brain, heart, lung, liver, kidney, stomach, small intestine, and large intestine. The maximum concentration of Erinacine S was observed in the stomach, 2 h after the oral administration of H. erinaceus mycelia extract, whereas the maximum amount of Erinacine S found in other tissues were seen after 8 h. Total amount of unconverted Erinacine S eliminated in feces and urine in 24 h was 0.1% of the oral dosage administrated. This study is the first to show that Erinacine S can penetrate the blood-brain barrier of rats and thus support the development of H. erinaceus mycelia, for the treatment of neurological diseases.

Role of BMI and age in predicting pathologic vertebral fractures in newly diagnosed multiple myeloma patients: A retrospective cohort study.

Vertebral fractures affect approximately 30% of myeloma patients and lead to a poor impact on survival and life quality. In general, age and body mass index (BMI) are reported to have an important role in vertebral fractures. However, the triangle relationship among age, BMI, and vertebral fractures is still unclear in newly diagnosed multiple myeloma (NDMM) patients. This study recruited consecutive 394 patients with NDMM at Taipei Veterans General Hospital between January 1, 2005 and December 31, 2015. Risk factors for vertebral fractures in NDMM patients were collected and analyzed. The survival curves were demonstrated using Kaplan-Meier estimate. In total, 301 (76.4%) NDMM patients were enrolled in the cohort. In the median follow-up period of 18.0 months, the median survival duration in those with vertebral fractures ≥ 2 was shorter than those with vertebral fracture < 2 (59.3 vs 28.6 months; P = 0.017). In multivariate Poisson regression, BMI < 18.5 kg/m2 declared increased vertebral fractures compared with BMI ≥ 24.0 kg/m2 (adjusted RR, 2.79; 95% CI, 1.44-5.43). In multivariable logistic regression, BMI < 18.5 kg/m2 was an independent risk factor for vertebral fractures ≥ 2 compared with BMI ≥ 24.0 kg/m2 (adjusted OR, 6.05; 95% CI, 2.43-15.08). Among age stratifications, patients with both old age and low BMI were at a greater risk suffering from increased vertebral fractures, especially in patients > 75 years and BMI < 18.5 kg/m2 (adjusted RR, 12.22; 95% CI, 3.02-49.40). This is the first study that demonstrated that age had a significant impact on vertebral fractures in NDMM patients with low BMI. Elder patients with low BMI should consider to routinely receive spinal radiographic examinations and regular follow-up.

Gamma-Secretase Inhibitors Attenuate Neurotrauma and Neurogenic Acute Lung Injury in Rats by Rescuing the Accumulation of Hypertrophic Microglia.

BACKGROUND/AIMS: In response to traumatic brain injury (TBI), activated microglia exhibit changes in their morphology from the resting ramified phenotype toward the activated hypertrophic or amoeboid phenotype. Here, we provide the first description of the mechanism underlying the neuroprotective effects of γ-secretase inhibitors on TBI outcomes in rats. METHODS: The neuroprotective effects of γ-secretase inhibitors such as LY411575 or CHF5074 on TBI-induced neurotoxicity were analysed using a neurological motor function evaluation, cerebral contusion assay, immunohistochemical staining for microglia phenotypes, lung injury score and Evans Blue dye extravasation assay of brain and lung oedema. RESULTS: Hypertrophic or amoeboid microglia accumulated in the injured cortex, the blood-brain-barrier was disrupted and neurological deficits and acute lung injury were observed 4 days after TBI in adult rats. However, a subcutaneous injection of LY411575 (5 mg/kg) or CHF5074 (30 mg/kg) immediately after TBI and once daily for 3 consecutive days post-TBI significantly attenutaed the accumulation of hypertrophic microglia in the injured brain, neurological injury, and neurogenic acute lung injury. CONCLUSION: Gamma-secretase inhibitors attenuated neurotrauma and neurogenic acute lung injury in rats by reducing the accumulation of hypertrophic microglia in the vicinity of the lesion.

Risk of stroke in patients with newly diagnosed multiple myeloma: a retrospective cohort study.

Cerebrovascular events are a common complication among patients with cancer, increasing morbidity and mortality. However, the association between multiple myeloma and cerebrovascular events remains unclear. We therefore investigated multiple myeloma patients' risk factors for stroke to devise a better stroke-prevention strategy. This study includes consecutive patients 20 years and older who were newly diagnosed with symptomatic multiple myeloma at Taipei Veterans General Hospital, a tertiary medical center, between January 1, 2002 and December 31, 2014. The primary outcome was stroke development. Patients with head injuries, brain tumors, brain parenchymal invasions, or antecedent malignancies were excluded. Hazard ratios (HRs) of stroke risk factors for multiple myeloma patients were estimated by Cox proportional regression analysis. Overall, 395 patients with a median age of 70 years were investigated. In the median follow-up period of 18 months, cerebrovascular events occurred in 16 patients, including 10 ischemic strokes and 6 hemorrhagic strokes. The 5-year estimated cumulative incidence rate was 7.45%. In the multivariate analysis, the κ light chain isotype (adjusted HR, 8.37; 95% confidence interval [CI], 1.91-39.8), previous cerebrovascular accidents (adjusted HR, 5.16; 95% CI, 1.48-17.9), and serum creatinine > 2 mg/dL (adjusted HR, 4.21; 95% CI, 1.10-16.0) were identified as independent risk factors for stroke. Subgroup analysis showed that atrial fibrillation (adjusted HR, 8.07) and previous cerebrovascular accident (adjusted HR, 4.89) are significant risk factors for ischemic stroke. Serum creatinine > 2 mg/dL (adjusted HR, 30.6) and previous cerebrovascular accident (adjusted HR, 13.9) are significant for hemorrhagic stroke. Moreover, therapeutic strategies for multiple myeloma were not associated with stroke in our study. This study demonstrates that risk of stroke increases in myeloma patients with a κ light chain isotype, previous cerebrovascular events, and renal impairment. Further prospective clinical studies to clarify the relationship between multiple myeloma and stroke are warranted.

A photo-cleavable biotin affinity tag for the facile release of a photo-crosslinked carbohydrate-binding protein.

The use of photo-crosslinking glycoprobes represents a powerful strategy for the covalent capture of labile protein complexes and allows detailed characterization of carbohydrate-mediated interactions. The selective release of target proteins from solid support is a key step in functional proteomics. We envisaged that light activation can be exploited for releasing labeled protein in a dual photo-affinity probe-based strategy. To investigate this possibility, we designed a trifunctional, galactose-based, multivalent glycoprobe for affinity labeling of carbohydrate-binding proteins. The resulting covalent protein-probe adduct is attached to a photo-cleavable biotin affinity tag; the biotin moiety enables specific presentation of the conjugate on streptavidin-coated beads, and the photolabile linker allows the release of the labeled proteins. This dual probe promotes both the labeling and the facile cleavage of the target protein complexes from the solid surfaces and the remainder of the cell lysate in a completely unaltered form, thus eliminating many of the common pitfalls associated with traditional affinity-based purification methods.

N(6)-(2-Hydroxyethyl)adenosine in the Medicinal Mushroom Cordyceps cicadae Attenuates Lipopolysaccharide-Stimulated Pro-inflammatory Responses by Suppressing TLR4-Mediated NF-κB Signaling Pathways.

Natural products play an important role in promoting health with relation to the prevention of chronic inflammation. N(6)-(2-Hydroxyethyl)adenosine (HEA), a physiologically active compound in the medicinal mushroom Cordyceps cicadae, has been identified as a Ca(2+) antagonist and shown to control circulation and possess sedative activity in pharmacological tests. The fruiting body of C. cicadae has been widely applied in Chinese medicine. However, neither the anti-inflammatory activities of HEA nor the fruiting bodies of C. cicadae have been carefully examined. In this study, we first cultured the fruiting bodies of C. cicadae and then investigated the anti-inflammatory activities of water and methanol extracts of wild and artificially cultured C. cicadae fruiting bodies. Next, we determined the amount of three bioactive compounds, adenosine, cordycepin, and HEA, in the extracts and evaluated their synergistic anti-inflammatory effects. Moreover, the possible mechanism involved in anti-inflammatory action of HEA isolated from C. cicadae was investigated. The results indicate that cordycepin is more potent than adenosine and HEA in suppressing the lipopolysaccharide (LPS)-stimulated release of pro-inflammatory cytokines by RAW 264.7 macrophages; however, no synergistic effect was observed with these three compounds. HEA attenuated the LPS-induced pro-inflammatory responses by suppressing the toll-like receptor (TLR)4-mediated nuclear factor-κB (NF-κB) signaling pathway. This result will support the use of HEA as an anti-inflammatory agent and C. cicadae fruiting bodies as an anti-inflammatory mushroom.