Tumor necrosis factor receptor-associated factor 5 protects against intimal hyperplasia by regulation of macrophage polarization via directly targeting PPARγ.

OBJECTIVES: Intimal hyperplasia is a serious clinical problem associated with the failure of therapeutic methods in multiple atherosclerosis-related coronary heart diseases, which are initiated and aggravated by the polarization of infiltrating macrophages. The present study aimed to determine the effect and underlying mechanism by which tumor necrosis factor receptor-associated factor 5 (TRAF5) regulates macrophage polarization during intimal hyperplasia. METHODS: TRAF5 expression was detected in mouse carotid arteries subjected to wire injury. Bone marrow-derived macrophages, mouse peritoneal macrophages and human myeloid leukemia mononuclear cells were also used to test the expression of TRAF5 in vitro. Bone marrow-derived macrophages upon to LPS or IL-4 stimulation were performed to examine the effect of TRAF5 on macrophage polarization. TRAF5-knockout mice were used to evaluate the effect of TRAF5 on intimal hyperplasia. RESULTS: TRAF5 expression gradually decreased during neointima formation in carotid arteries in a time-dependent manner. In addition, the results showed that TRAF5 expression was reduced in classically polarized macrophages (M1) subjected to LPS stimulation but was increased in alternatively polarized macrophages (M2) in response to IL-4 administration, and these changes were demonstrated in three different types of macrophages. An in vitro loss-of-function study with TRAF5 knockdown plasmids or TRAF5-knockout mice revealed high expression of markers associated with M1 macrophages and reduced expression of genes related to M2 macrophages. Subsequently, we incubated vascular smooth muscle cells with conditioned medium of polarized macrophages in which TRAF5 expression had been downregulated or ablated, which promoted the proliferation, migration and dedifferentiation of VSMCs. Mechanistically, TRAF5 knockdown inhibited the activation of anti-inflammatory M2 macrophages by directly inhibiting PPARγ expression. More importantly, TRAF5-deficient mice showed significantly aggressive intimal hyperplasia. CONCLUSIONS: Collectively, this evidence reveals an important role of TRAF5 in the development of intimal hyperplasia through the regulation of macrophage polarization, which provides a promising target for arterial restenosis-related disease management.

The comprehensive incidence and risk factors of fracture in kidney transplant recipients: A meta-analysis.

AIM: Kidney transplant recipients are at high risk of fracture due to many factors such as nutritional status, hyperparathyroidism, acidosis and steroid administration. The current meta-analysis aimed to comprehensively analyse the incidence and risk factors of fracture in kidney transplant recipients. METHODS: A systematic search on Embase, Web of Science, PubMed and Cochrane Library until November 2023 was performed. RStudio software was used to analyse data. RESULTS: Twenty-eight eligible studies containing 310 530 kidney transplant recipients were included in the analysis. The pooled incidence of fracture was 10% (95% confidence interval [CI]: 7%-13%) generally. When divided by regions, it was further observed that the pooled incidence of fracture was 13% (95% CI: 9%-17%) in Europe, 11% (95% CI: 6%-16%) in North America, 7% (95% CI: 3%-11%) in Asia. Regarding the risk factors, pooled analysis revealed that age of recipient (hazard ratio [HR] = 1.50, 95% CI: 1.17-1.91), female sex (HR = 1.45, 95% CI: 1.36-1.53), pretransplantation diabetes (HR = 1.76, 95% CI: 1.58-1.97), pretransplantation fracture history (HR = 2.28, 95% CI: 1.86-2.78), dialysis duration (HR = 1.09, 95% CI: 1.01-1.17) and deceased donor (HR = 1.21, 95% CI: 1.05-1.39) related to higher risk of fracture. The general quality of included studies was acceptable, and no publication bias existed except for the analysis between age of recipient and fracture incidence; further trim and fill method indicated age of recipient showed a correlation trend with the fracture incidence without the statistical significance. CONCLUSION: The pooled incidence of fracture reaches 10% in kidney transplant recipients, which relates to age of recipient, female sex, pretransplantation diabetes or fracture history, dialysis duration and decease donor.

An ensemble model for predicting dispositions of emergency department patients.

OBJECTIVE: The healthcare challenge driven by an aging population and rising demand is one of the most pressing issues leading to emergency department (ED) overcrowding. An emerging solution lies in machine learning's potential to predict ED dispositions, thus leading to promising substantial benefits. This study's objective is to create a predictive model for ED patient dispositions by employing ensemble learning. It harnesses diverse data types, including structured and unstructured information gathered during ED visits to address the evolving needs of localized healthcare systems. METHODS: In this cross-sectional study, 80,073 ED patient records were amassed from a major southern Taiwan hospital in 2018-2019. An ensemble model incorporated structured (demographics, vital signs) and pre-processed unstructured data (chief complaints, preliminary diagnoses) using bag-of-words (BOW) and term frequency-inverse document frequency (TF-IDF). Two random forest base-learners for structured and unstructured data were employed and then complemented by a multi-layer perceptron meta-learner. RESULTS: The ensemble model demonstrates strong predictive performance for ED dispositions, achieving an area under the receiver operating characteristic curve of 0.94. The models based on unstructured data encoded with BOW and TF-IDF yield similar performance results. Among the structured features, the top five most crucial factors are age, pulse rate, systolic blood pressure, temperature, and acuity level. In contrast, the top five most important unstructured features are pneumonia, fracture, failure, suspect, and sepsis. CONCLUSIONS: Findings indicate that utilizing ensemble learning with a blend of structured and unstructured data proves to be a predictive method for determining ED dispositions.

Causes of recurrence of paediatric inguinal hernia after single-port laparoscopic closure.

PURPOSE: This paper explores the causes of paediatric inguinal hernia (PIH) recurrence after single-port laparoscopic percutaneous extraperitoneal closure (SPLPEC). METHOD: From January 2015 to December 2020, the clinical data of 3480 children with PIHs who underwent SPLPEC were retrospectively reviewed, including 644 children who underwent SPLPEC with a homemade single-hook hernia needle from January 2015 to December 2016 and 2836 children who underwent the SPLPEC with a double-hook hernia needle and hydrodissection from January 2017 to December 2020. There were 39 recurrences (including communicating hydrocele) during the 2-5 years of follow-up. The findings of redo-laparoscopy were recorded and correlated with the revised video of the first operation to analyse the causes of recurrence. RESULT: Thirty-three males and 6 females experienced recurrence, and 8 patients had a unilateral communicating hydrocele. The median time to recurrence was 7.1 months (0-38). There were 20 cases (3.11%) in the single-hook group and 19 cases (0.67%) in the double-hook group. Based on laparoscopic findings, recurrence most probably resulted from multiple factors, including uneven tension of the ligation (10 cases), missing part of the peritoneum (14 cases), loose ligation (8 cases), broken knot (5 cases), and knot reaction (2 cases). All children who underwent repeat SPLPEC were cured by double ligations or reinforcement with medial umbilical ligament. CONCLUSION: The main cause of recurrence is improper ligation. Tension-free and complete PIH ligation are critical to the success of surgery, which requires avoiding the peritoneum skip area and the subcutaneous and muscular tissues. Redo-laparoscopic surgery was suitable for the treatment of recurrent inguinal hernia (RIH). For giant hernias, direct ligation of the internal ring incorporating the medial umbilical ligament (DIRIM) may be needed.

Left Atrial Expansion Index for Ischemic Stroke Prediction in Patients with Atrial Fibrillation.

Background: The efficacy of the left atrial (LA) expansion index (LAEI) to predict cerebral ischemic events in patients with atrial fibrillation (AF) is unknown. Methods: We enrolled 177 patients with AF (88 with paroxysmal AF and 89 with persistent AF) and a baseline CHA2DS2-VASc score (at enrollment) of 3.6 ± 2.3. Comprehensive echocardiography was performed at enrollment. The LAEI was calculated as (Volmax - Volmin) × 100%/Volmin, where Volmax and Volmin denoted maximal and minimal LA volumes, respectively. The study endpoint was ischemic stroke. Stroke subtypes were classified into cardioembolic stroke (CE), non-CE with determined mechanism (NCE), embolic stroke of undetermined source (ESUS), or transient ischemic attack (TIA). Results: Over a mean 9.9-year follow-up period, 44 (24.9%) of the patients reached the endpoint (24 with CE, 4 with NCE, 6 with ESUS, and 10 with TIA). The LAEI was lower in the stroke group than in the non-stroke group. Stroke incidence in the lowest LAEI quartile was much higher than that in the other LAEI quartiles; the 10-year cumulative stroke risk was 15.9% (14/88) and 33.7% (30/89) in the patients with paroxysmal and persistent AF, respectively. An LAEI of < 35% predicted the presence of stroke with 77% sensitivity and 78% specificity. In multivariable analysis, the LAEI was independently associated with ischemic stroke (hazard ratio 0.952 per 1% increase, 95% confidence interval 0.932-0.971, p < 0.0001). Conclusions: The LAEI is a useful predictor of ischemic stroke in patients with AF.

Early predicting improvement of severe systolic heart failure by left atrial volume.

Left atrium (LA) modulates left ventricle (LV) filling and cardiac performance. We aimed to assess the effect of heart failure (HF) therapy on LA and LV function, and the relationship between LA/LV improvement and clinical outcome in acute HF with reduced LV ejection fraction (LVEF). Totally, 224 hospitalized patients with acute HF and LVEF < 35% were enrolled and underwent echocardiography. They all received maximal tolerable doses of evidence-based medications. Patients received echocardiographic measurements at each visit including stroke volume, LVEF, LA minimal/maximal volume (LAVmin/LAVmax), LA expansion index, and tissue Doppler parameters. The threshold of LV functional improvement was LVEF > 45% ever occurred before study end. During the mean follow-up of 6.3 years, 62 cases improved well, mean LVEF 49 ± 5% at study end. The reduction of LV filling pressure occurring as early as 2 weeks later, LV systolic function improvement took longer (> 1 month). The reductions in LAVmin and LAVmax between initial stabilization and 2 weeks after HF treatment (Initial-2 W) and the increase of LA expansion index (Initial-2 W) were associated independently with LVEF improvement (p 0.002, 0.006, and 0.007, respectively). The best predictor of LVEF improvement was LAVmin reduction (Initial-2 W) > 5 ml with 77% sensitivity, 76% specificity. Cox proportional hazard regression analyses for cardiovascular events revealed LVEF improvement reduced 74% of events (hazard ratio 0.264, 95% CI 0.192-0.607, p < 0.0001); and LA expansion index (per 1% increase) reduced 14% of events (hazard ratio 0.862, 95% CI 0.771-0.959, p < 0.0001). The early reduction of LAV (Initial-2 W), especially LAVmin, is a powerful early predictor of LVEF improvement. Its occurrence reduces cardiovascular events significantly. ClinicalTrials.gov number: NCT01307722.

The accuracy of artificial intelligence used for non-melanoma skin cancer diagnoses: a meta-analysis.

BACKGROUND: With rising incidence of skin cancer and relatively increased mortality rates, an improved diagnosis of such a potentially fatal disease is of vital importance. Although frequently curable, it nevertheless places a considerable burden upon healthcare systems. Among the various types of skin cancers, non-melanoma skin cancer is most prevalent. Despite such prevalence and its associated cost, scant proof concerning the diagnostic accuracy via Artificial Intelligence (AI) for non-melanoma skin cancer exists. This study meta-analyzes the diagnostic test accuracy of AI used to diagnose non-melanoma forms of skin cancer, and it identifies potential covariates that account for heterogeneity between extant studies. METHODS: Various electronic databases (Scopus, PubMed, ScienceDirect, SpringerLink, and Dimensions) were examined to discern eligible studies beginning from March 2022. Those AI studies predictive of non-melanoma skin cancer were included. Summary estimates of sensitivity, specificity, and area under receiver operating characteristic curves were used to evaluate diagnostic accuracy. The revised Quality Assessment of Diagnostic Studies served to assess any risk of bias. RESULTS: A literature search produced 39 eligible articles for meta-analysis. The summary sensitivity, specificity, and area under receiver operating characteristic curve of AI for diagnosing non-melanoma skin cancer was 0.78, 0.98, & 0.97, respectively. Skin cancer typology, data sources, cross validation, ensemble models, types of techniques, pre-trained models, and image augmentation became significant covariates accounting for heterogeneity in terms of both sensitivity and/or specificity. CONCLUSIONS: Meta-analysis results revealed that AI is predictive of non-melanoma with an acceptable performance, but sensitivity may become improved. Further, ensemble models and pre-trained models are employable to improve true positive rating.

The Relationships Among Maternal Meta-emotion Philosophy, Maternal Video-Mediated Cognitions, and Adolescent Behavior Adjustment in Taiwan.

This study examines the relationships among maternal meta-emotion philosophy, maternal video-mediated cognitions, and adolescent behavior adjustment. We adopt video-mediated recall methods to obtain mothers' perceptions of their interaction with their children. In total, 121 pairs of mothers (age, M = 42.55) and their adolescent children (age, M = 12.34) were videotaped for 10 min while discussing daily issues. The mothers reviewed the tape (30 episodes) and rated their own behaviors and the counterparts' behaviors on 8 cognitive or affective dimensions. The mothers also completed a parental meta-emotion philosophy inventory, and the adolescents completed the Youth Self-Report. The results indicate that maternal emotional dysfunction has a positive effect on adolescents' externalizing problem behaviors through mothers' perceptions of conflictual interaction. These findings highlight the importance of considering maternal meta-emotion philosophy in the mother-adolescent interaction process and understanding adolescent problem behaviors.

Intermolecular Non-Bonded Interactions from Machine Learning Datasets.

Accurate determination of intermolecular non-covalent-bonded or non-bonded interactions is the key to potentially useful molecular dynamics simulations of polymer systems. However, it is challenging to balance both the accuracy and computational cost in force field modelling. One of the main difficulties is properly representing the calculated energy data as a continuous force function. In this paper, we employ well-developed machine learning techniques to construct a general purpose intermolecular non-bonded interaction force field for organic polymers. The original ab initio dataset SOFG-31 was calculated by us and has been well documented, and here we use it as our training set. The CLIFF kernel type machine learning scheme is used for predicting the interaction energies of heterodimers selected from the SOFG-31 dataset. Our test results show that the overall errors are well below the chemical accuracy of about 1 kcal/mol, thus demonstrating the promising feasibility of machine learning techniques in force field modelling.

Angiotensin II type-2-receptor stimulation ameliorates focal and segmental glomerulosclerosis in mice.

Podocyte damage and loss are the early event in the development of focal segmental glomerulosclerosis (FSGS). Podocytes express angiotensin II type-2-receptor (AT2R), which may play a key role in maintaining kidney integrity and function. Here, we examined the effects of AT2R deletion and AT2R agonist compound 21 (C21) on the evolution of FSGS. FSGS was induced by adriamycin (ADR) injection in both male wild-type (WT) and AT2R knockout (KO) mice. C21 was administered to WT-FSGS mice either one day before or 7 days after ADR (Pre-C21 or Post-C21), using two doses of C21 at either 0.3 (low dose, LD) or 1.0 (high dose, HD) mg/kg/day. ADR-induced FSGS was more severe in AT2RKO mice compared with WT-FSGS mice, and included profound podocyte loss, glomerular fibrosis, and albuminuria. Glomerular cathepsin L expression increased more in AT2RKO-FSGS than in WT-FSGS mice. C21 treatment ameliorated podocyte injury, most significantly in the Pre C21-HD group, and inhibited glomerular cathepsin L expression. In vitro, Agtr2 knock-down in mouse podocyte cell line given ADR confirmed the in vivo data. Mechanistically, C21 inhibited cathepsin L expression, which protected synaptopodin from destruction and stabilized actin cytoskeleton. C21 also prevented podocyte apoptosis. In conclusion, AT2R activation by C21 ameliorated ADR-induced podocyte injury in mice by the inhibition of glomerular cathepsin L leading to the maintenance of podocyte integrity and prevention of podocyte apoptosis.

Effects of dietary Lactobacillus reuteri and Pediococcus acidilactici on the cultured water qualities, the growth and non-specific immune responses of Penaeus vannamei.

This study discussed the effects of two types of lactic acid bacteria, Lactobacillus reuteri (L. reuteri) and Pediococcus acidilactici (P. acidilactici), on the growth and nonspecific immunity of Penaeus vannamei (P. vannamei) and developed probiotic applications for shrimp cultivation. This study incorporated two types of lactic acid bacteria in shrimp feed through spraying. The shrimps were grouped according to the type and concentration of effective bacteria incorporated into their feed. This research was separated into 3 individual feeding treatment as control, L. reuteri (Lr groups) and P. acidilactici (Pa groups). The shrimp was feeding with 103, 105, and 107 cfu/feed (g) L. reuteri namely as Lr3, Lr5, and Lr7. The shrimp was feeding with 103, 105, and 107 cfu/feed (g) P. acidilactici were named Pa3, Pa5, and Pa7, respectively. Through 8 weeks of feeding, the results revealed that the use of shrimp feed incorporated with lactic acid bacteria did not cause negative effects on water quality. The testing items include ammonia-nitrogen concentration, nitrite-nitrogen concentration, and total vibrio count in the water. In addition, the lactic acid bacteria concentration in the water were in the range of 1.33 ± 0.58 × 101 to 9.77 ± 1.34 × 102 cfu/mL. Observations of the growth performance of the white shrimps after 8 weeks of feeding revealed that both bacteria were beneficial to shrimp growth. In particular, group Lr7 had the highest percentage weight gain (107.99 ± 3.92%), special growth rate (1.93 ± 0.07%), feed conversion ratio (3.34 ± 0.05), and survival rate (97.22 ± 4.81%). Furthermore, observations of the nonspecific immunity reactions of the white shrimps after 4 weeks of feeding indicated that on day 4, the total number of haemocyte in shrimps in groups Lr5, Lr7, Pa3, and Pa5 significantly increased. On days 1 and 4, the phenoloxidase activity and superoxide axion production rates of the Lr group and Ls group increased. This phenomenon was the most significant in group Lr7, and the effect continued until day 28. After day 7, the phagocytic rate of groups Lr5 and Lr7 significantly increased. In addition, Lr and Pa groups exhibited significant increases in the phagocytic index after days 4 and 14, respectively. This phenomenon was also the most significant in group Lr7.

Anisotropic Full-Gap Superconductivity in 2M-WS2 Topological Metal with Intrinsic Proximity Effect.

Layered 2M-WS2 is recently observed to show Majorana bound states in vortices, but its superconducting pairing mechanism remains unknown, hindering the understanding of its topological superconducting nature. Using the ab initio Migdal-Eliashberg theory and electron-phonon Wannier interpolation, we demonstrate that both bulk and bilayer 2M-WS2 have a single anisotropic full-gap superconducting order of s-wave symmetry. We successfully reproduce the experimental superconducting critical temperature for the bulk and predict the bilayer 2M-WS2, a two-dimensional (2D) Z2 topological metal with nontrivial edge states right at the Fermi energy, to superconduct at 7 K, much higher than that in most 2D transition metal dichalcogenides (TMDs). A distinct proximity-enhanced surface superconductivity is further revealed by simulating quasiparticle density of states. This work unveils a universal electron-phonon full-gap pairing in 2M group VI TMDs and suggests a strong intrinsic surface-bulk proximity effect for 2M-WS2, paving the way to engineering topological superconductivity in TMD-based nanoscale devices.

Deletion of heterogeneous nuclear ribonucleoprotein F in renal tubules downregulates SGLT2 expression and attenuates hyperfiltration and kidney injury in a mouse model of diabetes.

AIMS/HYPOTHESIS: We previously reported that renal tubule-specific deletion of heterogeneous nuclear ribonucleoprotein F (Hnrnpf) results in upregulation of renal angiotensinogen (Agt) and downregulation of sodium-glucose co-transporter 2 (Sglt2) in HnrnpfRT knockout (KO) mice. Non-diabetic HnrnpfRT KO mice develop hypertension, renal interstitial fibrosis and glycosuria with no renoprotective effect from downregulated Sglt2 expression. Here, we investigated the effect of renal tubular Hnrnpf deletion on hyperfiltration and kidney injury in Akita mice, a model of type 1 diabetes. METHODS: Akita HnrnpfRT KO mice were generated through crossbreeding tubule-specific (Pax8)-Cre mice with Akita floxed-Hnrnpf mice on a C57BL/6 background. Male non-diabetic control (Ctrl), Akita, and Akita HnrnpfRT KO mice were studied up to the age of 24 weeks (n = 8/group). RESULTS: Akita mice exhibited elevated systolic blood pressure as compared with Ctrl mice, which was significantly higher in Akita HnrnpfRT KO mice than Akita mice. Compared with Akita mice, Akita HnrnpfRT KO mice had lower blood glucose levels with increased urinary glucose excretion. Akita mice developed kidney hypertrophy, glomerular hyperfiltration (increased glomerular filtration rate), glomerulomegaly, mesangial expansion, podocyte foot process effacement, thickened glomerular basement membranes, renal interstitial fibrosis and increased albuminuria. These abnormalities were attenuated in Akita HnrnpfRT KO mice. Treatment of Akita HnrnpfRT KO mice with a selective A1 adenosine receptor inhibitor resulted in an increase in glomerular filtration rate. Renal Agt expression was elevated in Akita mice and further increased in Akita HnrnpfRT KO mice. In contrast, Sglt2 expression was increased in Akita and decreased in Akita HnrnpfRT KO mice. CONCLUSIONS/INTERPRETATION: The renoprotective effect of Sglt2 downregulation overcomes the renal injurious effect of Agt when these opposing factors coexist under diabetic conditions, at least partly via the activation of tubuloglomerular feedback.

Fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism.

BACKGROUND: Patients with salt-sensitive hypertension are often accompanied with severe renal damage and accelerate to end-stage renal disease, which currently lacks effective treatment. Fibroblast growth factor 21 (FGF21) has been shown to suppress nephropathy in both type 1 and type 2 diabetes mice. Here, we aimed to investigate the therapeutic effect of FGF21 in salt-sensitive hypertension-induced nephropathy. METHODS: Changes of FGF21 expression in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice were detected. The influence of FGF21 knockout in mice on DOCA-salt-induced nephropathy were determined. Recombinant human FGF21 (rhFGF21) was intraperitoneally injected into DOCA-salt-induced nephropathy mice, and then the inflammatory factors, oxidative stress levels and kidney injury-related indicators were observed. In vitro, human renal tubular epithelial cells (HK-2) were challenged by palmitate acid (PA) with or without FGF21, and then changes in inflammation and oxidative stress indicators were tested. RESULTS: We observed significant elevation in circulating levels and renal expression of FGF21 in DOCA-salt-induced hypertensive mice. We found that deletion of FGF21 in mice aggravated DOCA-salt-induced nephropathy. Supplementation with rhFGF21 reversed DOCA-salt-induced kidney injury. Mechanically, rhFGF21 induced AMPK activation in DOCA-salt-treated mice and PA-stimulated HK-2 cells, which inhibited NF-κB-regulated inflammation and Nrf2-mediated oxidative stress and thus, is important for rhFGF21 protection against DOCA-salt-induced nephropathy. CONCLUSION: These findings indicated that rhFGF21 could be a promising pharmacological strategy for the treatment of salt-sensitive hypertension-induced nephropathy.

Angiotensin II up-regulates sodium-glucose co-transporter 2 expression and SGLT2 inhibitor attenuates Ang II-induced hypertensive renal injury in mice.

Clinical trials indicate that sodium/glucose co-transporter 2 (SGLT2) inhibitors (SGLT2i) improve kidney function, yet, the molecular regulation of SGLT2 expression is incompletely understood. Here, we investigated the role of the intrarenal renin-angiotensin system (RAS) on SGLT2 expression. In adult non-diabetic participants in the Nephrotic Syndrome Study Network (NEPTUNE, n=163), multivariable linear regression analysis showed SGLT2 mRNA was significantly associated with angiotensinogen (AGT), renin, and angiotensin-converting enzyme (ACE) mRNA levels (P<0.001). In vitro, angiotensin II (Ang II) dose-dependently stimulated SGLT2 expression in HK-2, human immortalized renal proximal tubular cells (RPTCs); losartan and antioxidants inhibited it. Sglt2 expression was increased in transgenic (Tg) mice specifically overexpressing Agt in their RPTCs, as well as in WT mice with a single subcutaneous injection of Ang II (1.44 mg/kg). Moreover, Ang II (1000 ng/kg/min) infusion via osmotic mini-pump in WT mice for 4 weeks increased systolic blood pressure (SBP), glomerulosclerosis, tubulointerstitial fibrosis, and albuminuria; canaglifozin (Cana, 15 mg/kg/day) reversed these changes, with the exception of SBP. Fractional glucose excretion (FeGlu) was higher in Ang II+Cana than WT+Cana, whereas Sglt2 expression was similar. Our data demonstrate a link between intrarenal RAS and SGLT2 expression and that SGLT2i ameliorates Ang II-induced renal injury independent of SBP.

Correlation between left atrial expansion index and stroke subtype: A 10-Year Follow-Up Study.

PURPOSE: Although left atrial (LA) expansion index predicts cardiovascular events, its efficacy for predicting cerebral events is unknown. METHODS: This study enrolled 2205 patients who had sinus rhythm after echocardiography in their first visit. LA expansion index was calculated as (Volmax -Volmin ) x100%/Volmin , where Volmax was defined as maximal LA volume and Volmin as minimal LA volume. The study endpoint was ischemic stroke. Stroke subtype was classified as cardioembolic stroke (CE), noncardioembolic stroke with determined mechanism (NCE), or embolic stroke of undetermined source (ESUS). RESULTS: Over a 10-year (mean 9.7 years) follow-up period, 128 (5.8%) participants reached endpoint, including 46 with CE, 33 with NCE, and 49 with ESUS. Regardless of stroke subtype, LA expansion index was lower in the event groups compared to the nonevent group. The lowest quartile of LA expansion index was associated with high CHA2 DS2 -VASc score at enrollment and more events, including CE, ESUS, atrial fibrillation (AF), heart failure, and all-cause mortality, relative to other quartiles. The LA expansion index was an independent predictor of CE (HR 0.82; 95% CI 0.723-0.912, per 10% increase in LA expansion index; P < .0001) and ESUS (HR 0.92; 95% CI 0.881-0.976, per 10% increase in LA expansion index; p 0.003). An LA expansion index <68% predicts the presence of AF after ESUS with 84% sensitivity and 70% specificity. CONCLUSION: LA expansion index is useful for predicting CE and ESUS. It is also associated with AF, heart failure hospitalization, and all-cause mortality.

Tumor Suppressor p14ARF Enhances IFN-γ-Activated Immune Response by Inhibiting PIAS1 via SUMOylation.

The ability of cells to induce the appropriate transcriptional response to inflammatory stimuli is crucial for the timely induction of host defense mechanisms. Although a role for tumor suppressor p14ARF (ARF) in the innate immune response was previously demonstrated, the underlying mechanism is still unclear. ARF is a potent upregulator of protein SUMOylation; however, no association of this function with the immune system has been made. In this study, we show the unique role of ARF in IFN-γ-induced immune response using human cell lines. Through a systematic search of proteins SUMOylated by ARF, we identified PIAS1, an inhibitor of IFN-activated transcription factor STAT1, as a novel ARF-binding partner and SUMOylation target. In response to IFN-γ treatment, ARF promoted PIAS1 SUMOylation to inhibit the ability of PIAS1 to attenuate IFN-γ response. Wild-type, but not ARF mutants unable to enhance PIAS1 SUMOylation, prevented the PIAS1-mediated inhibition of IFN-γ response. Conversely, the SUMO-deconjugase SENP1 deSUMOylated PIAS1 to reactivate PIAS1 that was inhibited by ARF. These findings suggest that PIAS1 function is negatively modulated by SUMO modification and that SUMOylation by ARF is required to inhibit PIAS1 activity and restore IFN-γ-induced transcription. In the presence of ARF, in which case PIAS1 is inhibited, depletion of PIAS1 did not have an additive effect on IFN-γ response, suggesting that ARF-mediated enhancement of IFN-γ response is mainly due to PIAS1 inhibition. Our findings reveal a novel function of ARF to inhibit PIAS1 by enhancing SUMOylation to promote the robust induction of IFN-γ response.

A minimum quantum chemistry CCSD(T)/CBS dataset of dimeric interaction energies for small organic functional groups.

We have performed a quantum chemistry study on the bonding patterns and interaction energies for 31 dimers of small organic functional groups (dubbed the SOFG-31 dataset), including the alkane-alkene-alkyne (6 + 4 + 4 = 14, AAA) groups, alcohol-aldehyde-ketone (4 + 4 + 3 = 11, AAK) groups, and carboxylic acid-amide (3 + 3 = 6, CAA) groups. The basis set superposition error corrected super-molecule approach using the second order Møller-Plesset perturbation theory (MP2) with the Dunning's aug-cc-pVXZ (X = D, T, Q) basis sets has been employed in the geometry optimization and energy calculations. To calibrate the MP2 calculated interaction energies for these dimeric complexes, we perform single-point calculations with the coupled cluster with single, double, and perturbative triple excitations method at the complete basis set limit [CCSD(T)/CBS] using the well-tested extrapolation methods. In order to gain more physical insights, we also perform a parallel series of energy decomposition calculations based on the symmetry adapted perturbation theory (SAPT). The collection of these CCSD(T)/CBS interaction energy values can serve as a minimum quantum chemistry dataset for testing or training less accurate but more efficient calculation methods. As an application, we further propose a segmental SAPT model based on chemically recognizable segments in a specific functional group. These model interactions can be used to construct coarse-grained force fields for larger molecular systems.

Design and analysis of refractive index sensors based on slotted photonic crystal nanobeam cavities with sidewall gratings.

We propose and numerically investigate a refractive index sensor based on a one-dimensional slotted photonic crystal nanobeam cavity with sidewall gratings for refractive index sensing in a gaseous environment. By using the three-dimensional finite-difference time-domain method, we demonstrate that our proposed sensor simultaneously possesses a high quality factor of $ 3.71 \times {10^6} $3.71×106 and a high sensitivity of 508 nm/RIU (refractive index unit) at the resonant wavelength near 1583 nm, yielding a detection limit as low as $ 1.97 \times {10^{ - 6}} $1.97×10-6 RIU. Moreover, the mode volume of the cavity's fundamental resonant mode is found to be as small as $ 0.022(\lambda /n)^3 $0.022(λ/n)3, resulting in a very compact effective sensing area. We finally study and assess the effect of fabrication disorder on the performances of our proposed sensor. We believe our proposed sensor will be a promising candidate for applications not only in multiplexed biochemical sensing and multielement mixture detection, but also in optical trapping of single biomolecules or nanoparticles.

Relationship of left atrial expansion index to exercise tolerance, pretest probability of restenosis, and positive predictive value of treadmill test in coronary artery disease.

BACKGROUND: Whether left atrial (LA) expansion index is associated with coronary restenosis, and exercise capacity (EC) reduction in coronary artery disease has not been established. METHODS: This study analyzed 342 consecutive patients who had received a coronary stent implant. A treadmill exercise test (TET) was administered in all participants. The LA expansion indices were measured immediately before and after TET. Maximal EC measured on a breath-by-breath basis by a metabolic cart with gas analyzers and recorded as metabolic equivalent task. All patients with positive TET results received angiography, and those with restenosis received complete revascularization by either percutaneous coronary intervention (PCI) or bypass surgery. The LA expansion index and EC before and 1 month after PCI were then compared. RESULTS: Out of 342 patients, 74 had positive TET results, and 54 had restenosis in angiography. Low LA expansion index was associated with poor EC. In patients with LA expansion index > 200%, only 5% had restenosis with 38.5% positive predictive value (PPV) of TET. In patients with LA expansion index < 100%, however, 64.3% had restenosis with 94.7% PPV of TET. Restenosis induced low pre-TET LA expansion index and further decline during TET. The LA expansion index significantly (P .001) improved from 133 ± 64% before PCI to184 ± 86% after PCI, and the improvement corresponded with EC recovery. A 10% reduction in LA expansion index was associated with a 15% increase in pretest probability of restenosis. CONCLUSION: The LA expansion index is associated with EC, pretest probability of restenosis, and PPV of TET. Revascularization improves both EC and LA expansion index.