Cloning and expression profiling of voltage-gated sodium channel gene (VGSC) from Spodoptera frugiperda.

Spodoptera frugiperda is a long-distance migratory pest with strong dispersal ability, fast reproduction speed and destructive feeding, so it is difficult to prevent and control. Pyrethroid insecticides are commonly used in pest insects control, And since the voltage-gated sodium channel (VGSC) serves as a major target of pyrethroids, it is important to study this gene for pest control. VGSC is an integral transmembrane protein consisting of approximately 2,000 amino acid residues found in neurons, myocytes, endocrine cells, and ovarian cells and involved in the initiation and propagation of excitable cellular action potentials. In this study, the cDNA sequence of the VGSC was identified from S. frugiperda by rapid amplification of cDNA ends (RACE) which contained an open reading frame of 6,261 bp encoding a protein of 2,086 amino acids. The molecular weight of this protein was predicted to be 236 kDa, and the theoretical isoelectric point was 5.21. A phylogenetic tree constructed based on lepidopteran insects showed that the VGSC of S. frugiperda was most closely relative to that of Spodoptera litura. VGSC is a highly conserved protein with Ion channel conserved structural domains of transmembrane proteins. qPCR showed that the VGSC gene was highly expressed in the epidermis of 2nd instar larvae, and its expression level was low in other tissues, such as the foregut and Malpighian tubules. In addition, VGSC was also detected in the prepupal stage, then gradually increased in abundance after entering the adult stage, peaked at the adult males on the 4th day of pupal stage, and decreased afterwards. The recombinant plasmid of pSumo-mut-VGSC was constructed and induced to express a His tag fused VGSC protein. Polyclonal antibodies were prepared from purified recombinant VGSC protein. The antibody was ELISA-titered, and the western blotting results showed that it specifically recognized VGSC, whether it was recombinant or endogenous protein. These results have laid the foundation for future studies on the physiological function of this gene in the growth and development of S. frugiperda.

Dissemination of pathogenic bacteria is reinforced by a MARTX toxin effector duet.

Multiple bacterial genera take advantage of the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin to invade host cells. Secretion of the MARTX toxin by Vibrio vulnificus, a deadly opportunistic pathogen that causes primary septicemia, the precursor of sepsis, is a major driver of infection; however, the molecular mechanism via which the toxin contributes to septicemia remains unclear. Here, we report the crystal and cryo-electron microscopy (EM) structures of a toxin effector duet comprising the domain of unknown function in the first position (DUF1)/Rho inactivation domain (RID) complexed with human targets. These structures reveal how the duet is used by bacteria as a potent weapon. The data show that DUF1 acts as a RID-dependent transforming NADase domain (RDTND) that disrupts NAD+ homeostasis by hijacking calmodulin. The cryo-EM structure of the RDTND-RID duet complexed with calmodulin and Rac1, together with immunological analyses in vitro and in mice, provide mechanistic insight into how V. vulnificus uses the duet to suppress ROS generation by depleting NAD(P)+ and modifying Rac1 in a mutually-reinforcing manner that ultimately paralyzes first line immune responses, promotes dissemination of invaders, and induces sepsis. These data may allow development of tools or strategies to combat MARTX toxin-related human diseases.

A Retrospective Study of Long-Term Clinical Outcomes in Patients with Chronic Hepatitis C Treated with Interferon and Ribavirin.

BACKGROUND: The key endpoint for treatment efficacy in chronic hepatitis C (CHC) is the absence of a detectable virus at 24 weeks after treatment. This study aims to determine the long-term clinical outcomes in patients with CHC after interferon and ribavirin treatment and the factors that influence them. METHODS: A retrospective study was conducted on 259 patients with CHC between 2003 and 2021, and the patients were divided into treated (n = 159) and untreated (n = 100) groups. The median observation duration was four years for the treated group (range: 1-15 years) and four years for untreated groups (range: 1-14 years). RESULTS: The mean ages of the treated and untreated groups were 47.38 ± 9.07 and 51.17 ± 8.38 years, respectively. Regardless of whether antiviral therapy had been administered, patients with undetectable hepatitis C virus (HCV) load had a lower risk of developing liver cirrhosis and hepatocellular carcinoma (HCC) than patients with detectable HCV load (p < 0.05). Furthermore, patients with HCV genotype 1b were more likely to develop cirrhosis and HCC than patients with HCV non-genotype 1b (p < 0.05). Based on the results of multivariate analysis, age of 50 years and above (hazard ratio [HR] = 6.74, 95% confidence interval [CI] = 2.79-16.28) and infection with HCV genotype 1b (HR = 2.43, 95% CI = 1.06-5.56) were significant predictors of liver cirrhosis and HCC development, whereas undetectable HCV RNA load (HR = 0.14, 95% CI = 0.43-0.46) was a protective factor. CONCLUSIONS: During the long-term follow-up, no cases of HCC were discovered in patients with undetectable HCV RNA load. Nevertheless, long-term monitoring is still required in patients with liver cirrhosis, since it increases the risk for developing liver cancer.

Secreted Akkermansia muciniphila threonyl-tRNA synthetase functions to monitor and modulate immune homeostasis.

Commensal bacteria are critically involved in the establishment of tolerance against inflammatory challenges, the molecular mechanisms of which are just being uncovered. All kingdoms of life produce aminoacyl-tRNA synthetases (ARSs). Thus far, the non-translational roles of ARSs have largely been reported in eukaryotes. Here, we report that the threonyl-tRNA synthetase (AmTARS) of the gut-associated bacterium Akkermansia muciniphila is secreted and functions to monitor and modulate immune homeostasis. Secreted AmTARS triggers M2 macrophage polarization and orchestrates the production of anti-inflammatory IL-10 via its unique, evolutionary-acquired regions, which mediates specific interactions with TLR2. This interaction activates the MAPK and PI3K/AKT signaling pathways, which converge on CREB, leading to an efficient production of IL-10 and suppression of the central inflammatory mediator NF-κB. AmTARS restores IL-10-positive macrophages, increases IL-10 levels in the serum, and attenuates the pathological effects in colitis mice. Thus, commensal tRNA synthetases can act as intrinsic mediators that maintain homeostasis.

Outcomes and Hemodynamic Performances of Transcatheter Aortic Valve Replacement with Two Generations of Self-Expanding Transcatheter Aortic Valves.

Background: The superiority of the new-generation self-expanding Evolut R compared with the first-generation CoreValve with regards to outcomes after transcatheter aortic valve replacement (TAVR) is unclear. The aim of this study was to investigate the hemodynamic and clinical performance of Evolut R compared with its direct predecessor, CoreValve, in a Taiwanese population. Methods: This study included all consecutive patients who underwent TAVR with either CoreValve or Evolut R between March 2013 and December 2020. Thirty-day Valve Academic Research Consortium-2 (VARC-2)-defined outcomes and hemodynamic performances were investigated. Results: There were no significant differences in baseline demographic characteristics between the patients receiving CoreValve (n = 117) or Evolut R (n = 117). Aortic valve-in-valve procedures for failed surgical bioprosthesis and procedures under conscious sedation were performed significantly more often with Evolut R. Pre-dilatation was performed significantly more often and contrast media volume was significantly higher with CoreValve. Stroke (0% vs. 4.3%, p = 0.024) and the need for emergent conversion to open surgery (0% vs. 5.1%, p = 0.012) were significantly lower in Evolut R than in CoreValve recipients. Evolut R significantly reduced 30-day composite safety endpoint (4.3% vs. 15.4%, p = 0.004). Conclusions: Advancements in transcatheter valve technologies have resulted in improved outcomes for patients undergoing TAVR with self-expanding valves. With the new-generation Evolut R, device success was high and the 30-day composite safety endpoint was significantly reduced after TAVR compared with CoreValve.

NAA10 Hypomethylation is associated with particulate matter exposure and worse prognosis for patients with non-small cell lung cancer.

Airborne particulate matter (PM) is a major health hazard worldwide and is a key factor in lung cancer, which remains the most common type of malignancy and the leading cause of cancer-related deaths. DNA methylation is a critical mechanism underlying the detrimental effects of PM, however, the molecular link between PM exposure and lung cancer remains to be elucidated. N-α-acetyltransferase 10 (NAA10) is involved in the cell cycle, migration, apoptosis, differentiation, and proliferation. In order to investigate the role of NAA10 in PM-induced pathogenesis processes leading to lung cancer, we determined the expression and methylation of NAA10 in normal human bronchial epithelial (NHBE) cells treated with PM10, PM10-polycyclic aromatic hydrocarbons (PAH), and PM2.5 and evaluated the prognostic value of the NAA10 methylation status in lung cancer patients. Exposure to all PM types significantly increased the expression of NAA10 mRNA and decreased the methylation of the NAA10 promoter in NHBE cells compared with the mock-treated control. NAA10 hypomethylation was observed in 9.3% (13/140) of lung cancer tissue samples and correlated with NAA10 transcriptional upregulation. Univariate and multivariate analyses revealed that NAA10 hypomethylation was associated with decreased survival of patients with lung cancer. Therefore, these results suggest that PM-induced hypomethylation of the NAA10 may play an important role in the pathogenesis of lung cancer and may be used as a potential prognostic biomarker for lung cancer progression. Further studies with large numbers of patients are warranted to confirm our findings.

Design of a microfluidic lung chip and its application in assessing the toxicity of formaldehyde.

In this work, a microfluidic lung chip with membrane supporting cell growth that can produce multiple concentration gradients of gas and liquid is introduced. The chip is composed of a gas gradient layer in the upper part, a porous membrane supporting cell growth in the middle and a liquid gradient layer in the lower part. The gas-liquid interface environment of the cells on the membrane can expose the cells to the gas in the upper layer and the liquid in the lower layer at the same time. Then, the chip is applied to the toxicity testing of formaldehyde in A549 cells. The results showed that at 6 × 10-5 mol/L formaldehyde, the survival rate of the cells in four channels were 90, 87, 81, and 71%, which shows a dose-response trend under the influence of different concentrations of formaldehyde. ROS staining results also showed that formaldehyde exposure at 6 × 10-5 mol/L lead to the increase of ROS level in the cells. These results suggest that the chip based on cell growth on membrane could be used for toxicological evaluation of environmental polluting gases.

In Silico and In Vivo Pharmacokinetic Evaluation of 84-B10, a Novel Drug Candidate against Acute Kidney Injury and Chronic Kidney Disease.

Acute kidney injury (AKI) and chronic kidney disease (CKD) have become public health problems due to high morbidity and mortality. Currently, drugs recommended for patients with AKI or CKD are extremely limited, and candidates based on a new mechanism need to be explored. 84-B10 is a novel 3-phenylglutaric acid derivative that can activate the mitochondrial protease, Lon protease 1 (LONP1), and may protect against cisplatin-induced AKI and unilateral ureteral obstruction- or 5/6 nephrectomy [5/6Nx]-induced CKD model. Preclinical studies have shown that 84-B10 has a good therapeutic effect, low toxicity, and is a good prospect for further development. In the present study, the UHPLC-MS/MS method was first validated then applied to the pharmacokinetic study and tissue distribution of 84-B10 in rats. Physicochemical properties of 84-B10 were then acquired in silico. Based on these physicochemical and integral physiological parameters, a physiological based pharmacokinetic (PBPK) model was developed using the PK-Sim platform. The fitting accuracy was estimated with the obtained experimental data. Subsequently, the validated model was employed to predict the pharmacokinetic profiles in healthy and chronic kidney injury patients to evaluate potential clinical outcomes. Cmax in CKD patients was about 3250 ng/mL after a single dose of 84-B10 (0.41 mg/kg), and Cmax,ss was 1360 ng/mL after multiple doses. This study may serve in clinical dosage setting in the future.

Correlation between PTSD and sleep quality in community-dwelling elderly adults in Hunan province of China.

Background: To understand the occurrence of post-traumatic stress disorder (PTSD) and the current status of sleep quality among community-dwelling elderly adults in Hunan Province of China, to explore the correlation between the two, and to analyze the trend of sleep disorders in PTSD elderly adults. Methods: A simple random sample containing 1,173 community-dwelling elderly adults in Hunan Province was established between March and May 2022, and an on-site face-to-face survey was administered using the PTSD Checklist-Civilian Version (PCL-C) with good reliability and validity, the Pittsburgh Sleep Quality Index (PSQI) scale, and a self-designed general condition questionnaire. Results: The incidence of PTSD in the 1,173 participants was 14.3% (168/1,173). The total incidence of sleep disorders was 40.9% (480/1,173); more specifically, the incidence of sleep disorders in participants with no PTSD symptom, in participants with mild-to-moderate PTSD symptoms, and in participants with severe PTSD symptoms was 36.3, 69.8, and 66.7%, respectively. The Spearman's rank correlation analysis showed that the total PTSD score and the scores of each dimension (i.e., re-experiencing symptom cluster, avoidance symptom cluster and hypervigilance symptom cluster) were positively correlated with the total PSQI score and its dimension scores (i.e., sleep quality, time to fall asleep, sleep duration, sleep efficiency, sleep disturbance, hypnotic medication, and daytime function) (P < 0.05). The correlation coefficients ranged from 0.013 to 0.495. For all PSQI dimensions, the differences across participants with different degrees of PTSD were statistically significant (P < 0.05). Conclusions: The overall status of PTSD and sleep quality in community-dwelling elderly adults in Hunan Province was not optimistic. The elderly with PTSD were more prone to sleep disorders, and the more severe the symptoms of PTSD, the poorer the sleep quality was. However, differences were observed in the scores of each dimension of sleep across participants with different degrees of PTSD. Regardless of the degree of PTSD symptoms, the sleep quality of the elderly is severely affected, and the occurrence rate is not unlimited.

Glutamyl-prolyl-tRNA synthetase 1 coordinates early endosomal anti-inflammatory AKT signaling.

The AKT signaling pathway plays critical roles in the resolution of inflammation. However, the underlying mechanisms of anti-inflammatory regulation and signal coordination remain unclear. Here, we report that anti-inflammatory AKT signaling is coordinated by glutamyl-prolyl-tRNA synthetase 1 (EPRS1). Upon inflammatory activation, AKT specifically phosphorylates Ser999 of EPRS1 in the cytoplasmic multi-tRNA synthetase complex, inducing release of EPRS1. EPRS1 compartmentalizes AKT to early endosomes via selective binding to the endosomal membrane lipid phosphatidylinositol 3-phosphate and assembles an AKT signaling complex specific for anti-inflammatory activity. These events promote AKT activation-mediated GSK3ß phosphorylation, which increase anti-inflammatory cytokine production. EPRS1-deficient macrophages do not assemble the early endosomal complex and consequently exacerbate inflammation, decreasing the survival of EPRS1-deficient mice undergoing septic shock and ulcerative colitis. Collectively, our findings show that the housekeeping protein EPRS1 acts as a mediator of inflammatory homeostasis by coordinating compartment-specific AKT signaling.

Impact of preprocedural mesenteric artery stenosis and mesenteric ischemia in patients undergoing transcatheter aortic valve replacement.

OBJECTIVES: We aimed to examine the incidence, etiologies, and consequences of acute mesenteric ischemia as well as the impact of preprocedural subclinical mesenteric artery stenosis in patients undergoing transcatheter aortic valve replacement. METHODS: Among prospective follow-up of 269 consecutive patients undergoing transcatheter aortic valve replacement, diagnosis of acute mesenteric ischemia was confirmed by abdominal computed tomography. Cumulative hazard of 1-year all-cause and cardiovascular mortality according to the absence or presence of mesenteric artery stenosis 70% or greater from preprocedural computed tomography angiography was analyzed. RESULTS: Acute mesenteric ischemia was confirmed in 7 patients (2.6%) during mid-term (median, 33.3 months, interquartile range, 15.0-61.0 months) follow-up. Thrombotic occlusions of previously stenotic mesenteric arteries account for 4 cases (57.1%), and embolic acute mesenteric ischemia constitute the rest (42.9%) of the cases. The mortality rate of acute mesenteric ischemia was 100%. At 30 days, death from acute mesenteric ischemia accounts for 40% of all-cause mortality and 67% of cardiovascular death. By multivariable analysis, higher Society of Thoracic Surgeons score and mesenteric artery stenosis 70% or greater were independently associated with acute mesenteric ischemia. Thirty-two patients (11.9%) with preprocedural mesenteric artery stenosis 70% or greater had an increased risk of all-cause mortality (adjusted hazard ratio, 3.78; 95% confidence interval, 1.74-8.19; P = .001) at 1 year after transcatheter aortic valve replacement. CONCLUSIONS: Acute mesenteric ischemia, an important cause of 30-day mortality, should be considered in patients who become clinically unstable after transcatheter aortic valve replacement, particularly but not exclusively in those with preexisting mesenteric artery stenosis. Mesenteric artery stenosis should be routinely assessed in all patients who are indicated for transcatheter aortic valve replacement considering the dismal prognosis of acute mesenteric ischemia.

Investigation of Tannins Transformation in Sanguisorbae Radix Over Carbonizing by Stir-Frying.

Carbonizing by stir-frying (CSF) is the most common technology in botanical folk medicines to enhance the convergence, hemostasis, and antidiarrheal effects. Sanguisorbae Radix (SR), a well-known herbal medicine in China, has extensive therapeutic functions, while charred SR is known as an additional product obtained from SR after CSF. In this study, mass spectrometry was used to investigate the effect of charring on tannins transformation of SR. The findings showed that the content level of tannins in SR decreased significantly after carbonizing process, while their three categories, gallotannins, ellagitannins, and procyanidins, had downward trends in general. Moreover, CSF also induced the polyphenol in SR to release relevant monomers from its origins. Significant amount of hydrolyzable tannins were detected by mass spectrometry, including gallotannins and ellagitannins, suggesting that hydrolysis during CSF yielded gallic and ellagic acid and their derivatives, in addition to sugar moieties. Subsequently, gallic and ellagic acid can further polymerize to form sanguisorbic acid dilactone. The amount of proanthocyanidins, the oligomers of catechin, including procyanidin, procyanidin C2, procyanidin B3, and 3-O-galloylprocyanidin B3, decreased to form catechin and its derivatives, which may further degrade to protocatechualdehyde. Quantitative analysis illustrated that the amount of gallic, pyrogallic, and ellagic acid and methyl gallate, the essential effectors in SR, significantly increased after CSF, with increased ratios of 1.36, 4.28, 10.33, and 4.79, respectively. In contrast, the contents of cathechin and epigallocatechin dropped remarkably with increased ratios of 0.04 and 0.02. Tannins exhibit moderate absorption, while their relevant monomers have a higher bioavailability. Therefore, CSF is proved here to be an effective technique to the release of active monomers from the original polyphenol precursor. This study explored the mechanism by which tannins are transformed upon CSF of SR.

Pulmonary fibrosis model using micro-CT analyzable human PSC-derived alveolar organoids containing alveolar macrophage-like cells.

Human lung organoids (hLOs) are useful for disease modelling and drug screening. However, a lack of immune cells in hLOs limits the recapitulation of in vivo cellular physiology. Here, we generated hLOs containing alveolar macrophage (AMφ)-like cells derived from pluripotent stem cells (PSC). To bridge hLOs with advanced human lung high-resolution X-ray computed tomography (CT), we acquired quantitative micro-CT images. Three hLO types were observed during differentiation. Among them, alveolar hLOs highly expressed not only lung epithelial cell markers but also AMφ-specific markers. Furthermore, CD68+ AMφ-like cells were spatially organized on the luminal epithelial surface of alveolar hLOs. Bleomycin-treated alveolar hLOs showed upregulated expression of fibrosis-related markers and extracellular matrix deposits in the alveolar sacs. Alveolar hLOs also showed structural alterations such as excessive tissue fraction under bleomycin treatment. Therefore, we suggest that micro-CT analyzable PSC-derived alveolar hLOs are a promising in vitro model to predict lung toxicity manifestations, including fibrosis.

Technical Characteristics and Feasibility of Coronary Angiography and Percutaneous Coronary Interventions Performed after Transcatheter Aortic Valve Replacement with Self-Expanding Valves.

BACKGROUND: Coronary angiography (CA) or percutaneous coronary intervention (PCI) after transcatheter aortic valve replacement (TAVR) may become technically challenging after implantation of the self-expanding Medtronic CoreValve (MCV) device, which extends above the coronary ostia. The aim of this study was to investigate the incidence and feasibility of CA or PCI and the outcomes of PCI after TAVR with the MCV device. METHODS: From July 2014 to April 2020, among 209 patients treated with TAVR with a MCV device, 14 (7%) underwent CA or PCI after the procedure at a mean duration of 28 ± 15 months at our institution. RESULTS: The mean age of the patients was 83 ± 6 years. Thirteen (93%) patients underwent CA due to angina symptoms with a positive noninvasive test, and 1 underwent CA for acute coronary syndrome. Most of the CA and PCI procedures were performed through a radial approach: 11 patients (79%) via the right radial artery, 1 (7%) the left radial artery, and 2 (14%) through the right femoral artery. CA of the left and right coronary arteries was successfully achieved in 13 patients (93%) with Judkin left (3.5 to 5) diagnostic catheters and in 11 patients (79%) with Judkin right (4) diagnostic catheters. The second-line catheter of choice was the Amplatz left (AL) 1 catheter for the right coronary artery and AL 2 for the left coronary artery. Procedural success was achieved in all 5 patients who underwent post-TAVR PCI without procedural or in-hospital complications. The use of a Guideliner microcatheter facilitated stent delivery in one patient. CONCLUSIONS: Coronary angiography or PCI following TAVR with a MCV device is feasible and safe, but requires understanding of the three-dimensional geometry of the prosthetic valve and its relationship to the coronary ostia.

Membranous septum length predicts conduction disturbances following transcatheter aortic valve replacement.

OBJECTIVES: Insufficient distance between membranous septum (MS) length and implant depth (ID) may aggravate mechanical compression of the conduction tissue by transcatheter aortic valve replacement (TAVR) prosthesis. We investigated the implication of MS length measured in the coronal view (coronal MS length) compared with infra-annular MS length from stretched vessel image to predict conduction disturbances following TAVR with CoreValve/Evolut R valves (Medtronic, Minneapolis, Minn). METHODS: Among 195 consecutive patients undergoing TAVR with CoreValve/Evolut R valves, we evaluated coronal, infra-annular MS lengths and ID, as well as MS length minus ID (ΔMSID) using pre-TAVR computed tomography and postprocedural angiography. RESULTS: Within 30 days, 6 (3.1%) required permanent pacemaker implantation and 31 (16.4%) developed left bundle branch block. When taking into account pre- and postprocedural parameters, multivariable logistic regression analysis revealed either coronal ΔMSID (odds ratio, 0.80; 95% confidence interval, 0.72-0.89; P < .001; cutoff point, 3.2 mm) or infra-annular ΔMSID (odds ratio, 0.84; 95% confidence interval, 0.76-0.92; P < .001; cutoff point, -0.2 mm) emerged as the only modifiable predictor of conduction disturbances. The area under the curve of coronal ΔMSID and infra-annular ΔMSID for predicting the occurrence of conduction disturbances were comparable (0.717 in coronal ΔMSID vs 0.708 in infra-annular ΔMSID; P = .761), but more patients could be guided by coronal MS length than infra-annular MS length (95.9% vs 87.2%; P = .002). CONCLUSIONS: Preprocedural assessment of MS length should be routinely adopted to determine the optimal ID to mitigate individual patient susceptibility to conduction disturbances after TAVR with self-expanding valves.

Impact of Prosthesis-Patient Mismatch After Transcatheter Aortic Valve Replacement in Asian Patients.

BACKGROUND: Little is known about the incidence of prosthesis-patient mismatch (PPM) and its impact after transcatheter aortic valve replacement with self-expanding valves in an Asian population. We aimed to assess postprocedural effective orifice area with standardized methods and the impact of PPM on midterm outcomes after CoreValve or Evolut R (Medtronic) implantation in an Asian population. METHODS: Among 201 consecutive patients undergoing CoreValve or Evolut R implantation, PPM was assessed at 30 days and defined based on core laboratory measured indexed effective orifice area as severe (less than 0.65 cm2/m2) or moderate (0.65 to 0.85 cm2/m2). Multivariable regression models were utilized to examine predictors of PPM as well as mortality and rehospitalization for heart failure at midterm follow-up. RESULTS: Moderate and severe PPM were observed after self-expanding valves in 37 patients (18.4%) and 3 patients (1.5%), respectively. These 40 patients were included in the PPM group. Predictors of PPM included female sex, larger body surface area, and lower left ventricular ejection fraction. At midterm (median 30.4 months; interquartile range, 17 to 57.8) follow-up, patients with PPM had an increased risk of all-cause death (adjusted hazard ratio 1.95; 95% confidence interval, 1.08 to 3.53; P = .027), cardiovascular mortality (adjusted hazard ratio 3.38; 95% confidence interval, 1.04 to 10.99; P = .043), and rehospitalization for heart failure (adjusted hazard ratio 2.40; 95% confidence interval, 1.11 to 5.17; P = .025). CONCLUSIONS: Patient-prosthesis mismatch was associated with higher midterm mortality and rehospitalization for heart failure in an Asian population. The expected postprocedural effective orifice area for any given valve size may be helpful in preprocedural decision making to avoid PPM.

The IT2 Survey: contextual knowledge (XK) influences on teacher candidates' intention to integrate technology.

Prior to this study, a testable model for the influence of contextual knowledge (XK) on teacher candidates' intention to integrate technology into classroom instruction had not been established. We applied the Decomposed Theory of Planned Behavior (DTPB) to aid us in this effort. Our work (a) provided a theoretical conceptualization for factors of XK through application of the DTPB, (b) represented the synergistic effects among these factors, and (c) allowed us to explore their influences on teacher candidates' intentions to teach with technology. To assess our model, which includes factors such as teacher candidates' beliefs, attitudes, and efficacy, we developed an instrument, the Intention to Teach with Technology (IT2) Survey. Results from the structural equation model of the survey data indicated our model fit the data very well and readily accounted for various XK factors, the relations among these factors, and their influence on teacher candidates' intentions to integrate technology into teaching. Given the complexity of the context in any teaching situation, its relation to and influence on technology integration, and the previously limited examination of context in research and teacher development, the results indicate the proposed model is quite plausible, accounting for 75% of the variation in intention. The study demonstrates the IT2 Survey is an effective instrument to examine factors associated with XK and their influences on technology integration. Our work extends theory about technology integration by including XK and has implications for researchers as well as practitioners who seek to advance technology integration in preparation programs.

TREM2 promotes natural killer cell development in CD3-CD122+NK1.1+ pNK cells.

BACKGROUND: Triggering receptor expressed on myeloid cells 2 (TREM2) signaling is considered to regulate anti-inflammatory responses in macrophages, dendritic cell maturation, osteoclast development, induction of obesity, and Alzheimer's disease pathogenesis. However, little is known regarding the effect of TREM2 on natural killer (NK) cells. RESULTS: Here, we demonstrated for the first time that CD3-CD122+NK1.1+ precursor NK (pNK) cells expressed TREM2 and their population increased in TREM2-overexpressing transgenic (TREM2-TG) mice compared with that in female C57BL/6 J wild type (WT) mice. Both NK cell-activating receptors and NK cell-associated genes were expressed at higher levels in various tissues of TREM2-TG mice than in WT mice. In addition, bone marrow-derived hematopoietic stem cells (HSCs) of TREM2-TG mice (TG-HSCs) successfully differentiated into NK cells in vitro, with a higher yield from TG-HSCs than from WT-HSCs. In contrast, TREM2 signaling inhibition by TREM2-Ig or a phosphatidylinositol 3-kinase (PI3K) inhibitor affected the expression of the NK cell receptor repertoire and decreased the expression levels of NK cell-associated genes, resulting in significant impairment of NK cell differentiation. Moreover, in melanoma-bearing WT mice, injection of bone marrow cells from TREM2-TG mice exerted greater antitumor effects than that with cells from WT control mice. CONCLUSIONS: Collectively, our data clearly showed that TREM2 promoted NK cell development and tumor regression, suggesting TREM2 as a new candidate for cancer immunotherapy.

Four-wave mixing-based photonic crystal fiber microfluid sensor with embedded U-shape microslits.

In this paper, we propose a four-wave mixing-based photonic crystal fiber (PCF) microfluid sensor, and two U-shape microslits fabricated by a femtosecond laser are embedded into the sensor for real-time microfluid measurement. Theoretical and experimental results prove that the signal wavelength is sensitive to both the refractive index (RI) and the material dispersion property of the liquid sample filled into the air channels. For different aqueous target samples at low concentrations, the responses of signal wavelength are consistent with each other. The obtained RI sensitivity is approximately 881.36 nm/RIU, and the sensing resolution is around 1.6 × 10-4 RIU. The proposed sensor also shows a better figure of merit (FOM) as high as 313.65 RIU-1 when compared with the fiber SPR sensors. Besides, the signal wavelengths present different responses with the increasing aqueous concentration due to the separated dispersion characteristics of the filled liquid samples, which can be potentially applied for the discrimination of liquid samples with a well-designed wavelength-coded sensor array in the future.

Cyclophilin A is an endogenous ligand for the triggering receptor expressed on myeloid cells-2 (TREM2).

Triggering receptor expressed on myeloid cells 2 (TREM2) is a cell surface receptor expressed on macrophages, microglial cells, and pre-osteoclasts, and that participates in diverse cellular function, including inflammation, bone homeostasis, neurological development, and coagulation. In spite of the indispensable role of the TREM2 protein in the maintenance of immune homeostasis and osteoclast differentiation, the exact ligand for TREM2 has not yet been identified. Here, we report a putative TREM2 ligand which is secreted from MC38 cells and identified as a cyclophilin A (CypA). A specific interaction between CypA and TREM2 was shown at both protein and cellular levels. Exogenous CypA specifically interacted and co-localized with TREM2 in RAW264.7 cells, and the physical interactions were shown to regulate TREM2 signaling transduction. The Pro144 residue in the extracellular domain of TREM2 was found to be the specific binding site of CypA. When considered together, this provides evidence that CypA interacts specifically with TREM2 as a potent ligand.