Signatures of a strange metal in a bosonic system.

Fermi liquid theory forms the basis for our understanding of the majority of metals: their resistivity arises from the scattering of well defined quasiparticles at a rate where, in the low-temperature limit, the inverse of the characteristic time scale is proportional to the square of the temperature. However, various quantum materials1-15-notably high-temperature superconductors1-10-exhibit strange-metallic behaviour with a linear scattering rate in temperature, deviating from this central paradigm. Here we show the unexpected signatures of strange metallicity in a bosonic system for which the quasiparticle concept does not apply. Our nanopatterned YBa2Cu3O7-δ (YBCO) film arrays reveal linear-in-temperature and linear-in-magnetic field resistance over extended temperature and magnetic field ranges. Notably, below the onset temperature at which Cooper pairs form, the low-field magnetoresistance oscillates with a period dictated by the superconducting flux quantum, h/2e (e, electron charge; h, Planck's constant). Simultaneously, the Hall coefficient drops and vanishes within the measurement resolution with decreasing temperature, indicating that Cooper pairs instead of single electrons dominate the transport process. Moreover, the characteristic time scale τ in this bosonic system follows a scale-invariant relation without an intrinsic energy scale: h/τ ≈ a(kBT + γµBB), where h is the reduced Planck's constant, a is of order unity7,8,11,12, kB is Boltzmann's constant, T is temperature, µB is the Bohr magneton and γ ≈ 2. By extending the reach of strange-metal phenomenology to a bosonic system, our results suggest that there is a fundamental principle governing their transport that transcends particle statistics.

C-H Functionalization-Enabled 11-Step Semisynthesis of (-)-Veragranine A and Characterization of Synthetic Analogs in Osteoarthritis-related Pain Treatment.

We report an efficient semisynthesis of the cholestane steroidal alkaloid (-)-veragranine A with a 6/6/6/5/6/6 hexacyclic ring system, eight stereocenters, and a unique C12-C23 linkage. Our synthesis features a Schönecker-Baran C-H oxidation at C12, a Suzuki-Miyaura cross-coupling to form the C12-C23 bond, and a hydrogen atom transfer (HAT)-initiated Minisci C-H cyclization to forge the C20-C22 bond with desired stereochemistry at C20. These enabling transformations significantly enhanced the overall synthetic efficiency and delivered (-)-veragranine A in 11 steps and over 200 mg from cheap and readily available dehydroepiandrosterone. In addition, this approach allowed flexible syntheses of novel synthetic analogs for biological evaluations in sensory neurons in vitro and in an in vivo model of arthritic pain, from which two novel lead compounds were identified for further development.

Fe-Based Metal Organic Framework-Derived FeNiP/N-Doped Carbon Heterogeneous Core-Shell Structures for Oxygen Evolution.

It is of great significance to explore high activity, low overpotential, and outstanding durability electrocatalysts without precious metals for oxygen evolution reaction to reduce the energy consumption in the electrolysis of water to product hydrogen. Metal organic frameworks (MOFs) with periodic structure and uniform pore distribution have been widely used as precursors for the synthesis of transition metal electrocatalysts. Herein, we first synthesized nanoscale Fe-soc-MOFs with relatively high specific surface area and in situ converted it into nickel-iron double layer hydroxide/MOF (FeNi LDH/MOF) by Ni2+ etching. Finally, a nickel-iron phosphide/nitrogen-doped carbon cubic nanocage (FeNiP/NC) was obtained by calcination and phosphating. FeNiP/NC with its unique core-shell structure has an overpotential of only 240 mV at a current density of 10 mA/cm2 and can be continuously electrolyzed for 45 h. High catalytic activity of FeNiP/NC is mainly attributed to the action of Fe and Ni bimetals and the synergistic effect between FeNiP and N-doped porous carbon, which was confirmed by the calculation of density functional theory (i.e., Gibbs free energy). After a long period of electrolysis, FeNiP was converted to MOOH (M = Fe and Ni) and became the new active site. This study provides a feasible optimization strategy for the development of high-efficiency three-dimensional electrode materials without precious metals.

Large Neutral Amino Acids Moderate the Effects of Metabolic Syndrome on Cognitive Performance in Middle-Aged Adults.

Introduction Two large neutral amino acids (LNAA), tryptophan and tyrosine, are precursors to cerebral neurotransmitters and are involved in cognitive function. Higher levels of LNAA in young adults are associated with improved cognition, although these associations appear to reverse over time. Given that exposure to metabolic syndrome (MetS) may induce premature cognitive aging, the current project aims to fill the gap in the literature by examining the effect of LNAA on cognitive performance in midlife adults with metabolic risks. Methods Eighty-eight adults, ages 40-61 years, participated in this cross-sectional study. LNAA metabolites were quantified, MetS components were measured using high-performance liquid chromatography, and MetS components were assessed in the laboratory. Composite verbal memory and executive functioning scores were computed using principal component analysis. We used linear regression models to test the interaction between LNAA and MetS while covarying for sex, age, and education. Results The kynurenine/tryptophan ratio (KTR) moderated the relation between MetS and verbal memory, even after adjusting for relevant covariates. Tyrosine metabolites were not significant moderators of the association between MetS and executive functioning. Conclusion Our findings suggest that the detected weaker memory performance in adults with a high number of MetS components may be related to relative tryptophan depletion and possible decreases in serotonin production. Further investigation is warranted to examine the potential role of LNAA in associations between cognitive performance and metabolic risks over time.

Copper-Catalyzed Dearomative 1,2-Hydroamination.

Catalytic olefin hydroamination reactions are some of the most atom-economical transformations that bridge readily available starting materials-olefins and high-value-added amines. Despite significant advances in this field over the last two decades, the formal hydroamination of nonactivated aromatic compounds remains an unsolved challenge. Herein, we report the extension of olefin hydroamination to aromatic π-systems by using arenophile-mediated dearomatization and Cu-catalysis to perform 1,2-hydroamination on nonactivated arenes. This strategy was applied to a variety of substituted arenes and heteroarenes to provide general access to structurally complex amines. We conducted DFT calculations to inform mechanistic understanding and rationalize unexpected selectivity trends. Furthermore, we developed a practical, scalable desymmetrization to deliver enantioenriched dearomatized products and enable downstream synthetic applications. We ultimately used this dearomative strategy to efficiently synthesize a collection of densely functionalized small molecules.

Unveiling Low Temperature Assembly of Dense Fe-N4 Active Sites via Hydrogenation in Advanced Oxygen Reduction Catalysts.

The single-atom Fe-N-C is a prominent material with exceptional reactivity in areas of sustainable energy and catalysis research. It is challenging to obtain the dense Fe-N4 site without the Fe nanoparticles (NPs) sintering during the Fe-N-C synthesis via high-temperature pyrolysis. Thus, a novel approach is devised for the Fe-N-C synthesis at low temperatures. Taking FeCl2 as Fe source, a hydrogen environment can facilitate oxygen removal and dichlorination processes in the synthesis, efficiently favouring Fe-N4 site formation without Fe NPs clustering at as low as 360 °C. We shed light on the reaction mechanism about hydrogen promoting Fe-N4 formation in the synthesis. By adjusting the temperature and duration, the Fe-N4 structural evolution and site density can be precisely tuned to directly influence the catalytic behaviour of the Fe-N-C material. The FeNC-H2-360 catalyst demonstrates a remarkable Fe dispersion (8.3 wt %) and superior acid ORR activity with a half-wave potential of 0.85 V and a peak power density of 1.21 W cm-2 in fuel cell. This method also generally facilitates the synthesis of various high-performance M-N-C materials (M=Fe, Co, Mn, Ni, Zn, Ru) with elevated single-atom loadings.

The cardiovascular and renal effects of glucagon-like peptide 1 receptor agonists in patients with advanced diabetic kidney disease.

BACKGROUND: To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) have cardiovascular and renal protective effects in patients with advanced diabetic kidney disease (DKD) with an estimated glomerular filtration rate (eGFR) < 30 mL/min per 1.73 m2. METHODS: In this cohort study, patients with type 2 diabetes mellitus and eGFR < 30 mL/min per 1.73 m2 with a first prescription for GLP-1RAs or dipeptidyl peptidase 4 inhibitors (DPP-4is) from 2012 to 2021 (n = 125,392) were enrolled. A Cox proportional hazard model was used to assess the cardiorenal protective effects between the GLP-1RA and DDP-4i groups. RESULTS: A total of 8922 participants [mean (SD) age 68.4 (11.5) years; 4516 (50.6%) males; GLP-1RAs, n = 759; DPP-4is, n = 8163] were eligible for this study. During a mean follow-up of 2.1 years, 78 (13%) and 204 (13.8%) patients developed composite cardiovascular events in the GLP-1RA and DPP-4i groups, respectively [hazard ratio (HR) 0.88, 95% confidence interval CI 0.68-1.13]. Composite kidney events were reported in 134 (38.2%) and 393 (44.2%) patients in the GLP-1RA and DPP-4i groups, respectively (subdistribution HR 0.72, 95% CI 0.56-0.93). CONCLUSIONS: GLP-1RAs had a neutral effect on the composite cardiovascular outcomes but reduced composite kidney events in the patients with advanced DKD compared with DPP-4is.

Chiral SPINOL-Based Pt(II) Metallacycles For Immunogenic Cell Death.

The incorporation of chirality endows Pt(II)-based metal-organic complexes (MOCs) with unique potentials in several fields such as nonlinear optics and chiral catalysis. However, the exploration of chiral Pt(II) metallacycles in biological responses remains underdeveloped. Herein, we designed and synthesized two chiral Pt(II) metallacycles 1 and 2 via the coordination-driven self-assembly of chiral 1,1'-spirobiindane-7,7'-diol (SPINOL)-derived ligands and cis-Pt(PEt3)2(OTf)2 (90°Pt). Their structures were well characterized by 1H NMR, 31P{1H} NMR, ESI-TOF-MS, and X-ray crystallography, and their photophysical properties were investigated by UV-vis absorption, fluorescence, and circular dichroism (CD) spectroscopies. Then, the antitumor activity of the two chiral metallacycles in vitro was further tested. Complexes 1 and 2 exhibited strong cytotoxicity, especially toward the A549 cells. The destruction of the mitochondrial function, the inhibition of the glutathione (GSH)/glutathione disulfide (GSSG) level, and the inactivation of superoxide dismutase (SOD) induced by complexes 1 and 2 led to the massive accumulation of reactive oxygen species (ROS). The overloaded ROS then triggered apoptotic cell death, and the release of damage-associated molecular patterns (DAMPs) further induced immunogenic cell death (ICD). To the best of our knowledge, this is the first example of Pt(II)-based metallacycles that can induce immunogenic cell death, providing a new strategy for the future design and construction of immune-modulating platinum agents in cancer therapy.

Selective capacitive removal of Pb2+ ion contaminants from drinking water via nickel foam/Mn2CoO4@tannic acid-Fe3+ electrodes.

The health hazards caused by low concentrations of Pb2+ ions in drinking water systems are of significant concern. In order to remove Pb2+ ions and retain Na+, K+, Ca2+ and Mg2+ as harmless competitive ions without simultaneous removal, nickel foam (NF)/Mn2CoO4@tannic acid (TA)-Fe3+ electrodes were prepared by a hydrothermal method and a coating method and an asymmetric capacitive deionization (CDI) system is established using the prepared electrodes and a graphite paper positive electrode. The designed asymmetric CDI system exhibited a high Pb2+ adsorption capacity of 375 mg g-1 with high removal efficiency and significant regeneration behavior at 1.4 V at neutral pH. When the asymmetric CDI system is used to enrich a hydrous solution of mixed Na+, K+, Ca2+, Mg2+ and Pb2+ ions each with a concentration of 10 ppm and 100 ppm by electrosorption at a 1.4 V operating voltage, the removal rate of Pb2+ is as high as 100% and 70.8% respectively, and the relative selectivity coefficients are 4.51-43.22. According to the different adsorption mechanisms of lead ions and coexisting ions, the separation and recovery of ions can be realized by a two-step desorption process, thereby providing a new method for removing Pb2+ ions from drinking water with excellent application potential.

The use of high-sensitivity cardiac troponin T and creatinine kinase-MB as a prognostic markers in patients with acute myocardial infarction and chronic kidney disease.

Background: High-sensitivity cardiac troponin T (hs-cTnT) and creatine kinase (CK)-MB are the most commonly used biomarkers for the diagnosis and prognosis of acute myocardial infarction (AMI). Chronic kidney disease (CKD) often leads to elevated hs-cTnT levels in non-AMI patients. However, studies comparing the prognostic value of both hs-cTnT and CK-MB in patients with AMI and CKD are lacking.Methods: We conducted a retrospective study on AMI patients diagnosed between January 2015 and October 2020. Patients were categorized based on renal function as normal or CKD. Peak hs-cTnT and CK-MB levels during hospitalization were collected, and their diagnostic value was evaluated using receiver operating characteristic (ROC) curves. The impact on in-hospital mortality was analyzed using multivariate logistic regression. The relationship between the hs-cTnT/CK-MB ratio and in-hospital death was examined using a restricted cubic spline (RCS) curve.Results: The study included 5022 AMI patients, of whom 797 (15.9%) had CKD. The AUCs of Hs-cTnT and CK-MB were higher in the CKD group [0.842 (95% CI: 0.789-0.894) and 0.821 (95% CI: 0.760-0.882)] than in the normal renal function group [0.695 (95% CI: 0.604-0.790) and 0.708 (95% CI: 0.624-0.793)]. After full adjustment for all risk factors, hs-cTnT (OR, 2.82; 95% CI, 1.03-9.86; p = 0.038) and CK-MB (OR, 4.91; 95% CI, 1.54-14.68; p = 0.007) above the cutoff values were independent predictors of in-hospital mortality in patients with CKD. However, in patients with normal renal function, only CK-MB above the cutoff (OR, 2.45; 95% CI, 1.02-8.24; p = 0.046) was a predictor of in-hospital mortality, whereas hs-cTnT was not. There was an inverted V-shaped relationship between the hs-cTnT/CK-MB ratio and in-hospital mortality, with an inflection point of 19.61. The ratio within the second quartile (9.63-19.6) was an independent predictor of in-hospital mortality in patients with CKD (OR 5.3, 95% CI 1.66-16.86, p = 0.005).Conclusions: Hs-cTnT independently predicted in-hospital mortality in AMI patients with CKD, whereas its predictive value was not observed in patients with normal renal function. CK-MB was an independent predictor of in-hospital mortality regardless of renal function. Moreover, the hs-cTnT/CK-MB ratio may aid in risk stratification of AMI patients with CKD.

Analysis of Medication Rules of Traditional Chinese Medicine for Malaria Treatment Based on Data Mining.

Objective To analyze the medication rules of traditional Chinese medicine (TCM) for malaria treatment.Methods Statistical analysis was conducted on the basic attributes of TCM drugs with regard to property, therapeutic methods, flavor, and meridian tropism. A complex network of TCM drug associations was constructed. Cluster analysis was applied to obtain the core drugs for malaria treatment. The Apriori algorithm was applied to analyze the association rules of these core drugs.Results A total of 357 herbs were used 3,194 times in 461 prescriptions for malaria treatment. Radix Glycyrrhizae (), Rhizoma Pinelliae (), Radix Bupleuri (), and Radix Dichroae () were the frequently used herbs through supplementing, exterior-releasing, heat-clearing, qi-rectifying, and damp-resolving therapeutic methods. Such herbs had warm, natural, and cold herbal properties; pungent, bitter, and sweet flavors; and spleen, lung, and stomach meridian tropisms. Cluster analysis showed 61 core drugs, including Radix Glycyrrhizae, Rhizoma Pinelliae, Radix Bupleuri, and Radix Scutellariae (). Apriori association rule analysis yielded 12 binomial rules (herb pairs) and 6 trinomial rules (herb combinations). Radix Bupleuri plus Radix Scutellariae was the core herbal pair for treating malaria. This pair could be combined with Rhizoma Atractylodis Macrocephalae () for treating warm or cold malaria, combined with Pericarpium Citri Reticulatae () or Radix Dichroae () for treating miasmic malaria, or combined with turtle shells () for treating malaria with splenomegaly.Conclusions TCM can be used to classify and treat malaria in accordance with the different stages of development. As the core herbal pair, Radix Bupleuri and Radix Scutellariae can be combined with other drugs to treat malaria with different syndrome types.

Older adults with perivascular spaces exhibit cerebrovascular reactivity deficits.

BACKGROUND: Perivascular spaces on brain magnetic resonance imaging (MRI) may indicate poor fluid drainage in the brain and have been associated with numerous neurological conditions. Cerebrovascular reactivity (CVR) is a marker of cerebrovascular function and represents the ability of cerebral blood vessels to regulate cerebral blood flow in response to vasodilatory or vasoconstrictive stimuli. We aimed to examine whether pathological widening of the perivascular space in older adults may be associated with deficits in CVR. METHODS: Independently living older adults free of dementia or clinical stroke were recruited from the community and underwent brain MRI. Pseudo-continuous arterial spin labeling MRI quantified whole brain cerebral perfusion at rest and during CVR to hypercapnia and hypocapnia induced by visually guided breathing exercises. Perivascular spaces were visually scored using existing scales. RESULTS: Thirty-seven independently living older adults (mean age = 66.3 years; SD = 6.8; age range 55-84 years; 29.7% male) were included in the current analysis. Multiple linear regression analysis revealed a significant negative association between burden of perivascular spaces and global CVR to hypercapnia (B = -2.0, 95% CI (-3.6, -0.4), p = .015), adjusting for age and sex. Perivascular spaces were not related to CVR to hypocapnia. DISCUSSION: Perivascular spaces are associated with deficits in cerebrovascular vasodilatory response, but not vasoconstrictive response. Enlargement of perivascular spaces could contribute to, or be influenced by, deficits in CVR. Additional longitudinal studies are warranted to improve our understanding of the relationship between cerebrovascular function and perivascular space enlargement.

Hypobaric hypoxia triggers pyroptosis in the retina via NLRP3 inflammasome activation.

Hypobaric hypoxia initiates multiple impairment to the retina and is the major cause contributing to retinal function deficits such as high altitude retinopathy. However, the underlying molecular mechanism has not been clearly defined so far and remains to be clarified. In the present study, we have undertaken an approach to mimic 5000 m altitude with a low-pressure oxygen cabin and evaluated if pyroptosis is involved in the mechanisms by which hypobaric hypoxia triggers retinal impairment. We also used Radix Astragali seu Hedysari Compound (RAHC) to determine whether RAHC is capable of exerting protective effects on the hypobaric hypoxia-induced retinal dysfunction. We found that hypobaric hypoxia stress activated inflammasome complex through increasing NOD-like receptor family pyrin domain-containing 3 (NLRP3), caspase-1, and apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) protein levels. The protein expression of gasdermin-D, a master executor of pyroptosis, and NADPH oxidase 4, which is regarded as a main generator of reactive oxygen species (ROS), also elevated upon hypobaric hypoxia exposure. In addition, hypobaric hypoxia induced a significant increase in pro-inflammatory cytokines expression including interleukin-1ß and interleukin-18 in the rat retina. Our results indicate that hypobaric hypoxia initiates pyroptosis in the rat retina. RAHC attenuates hypobaric hypoxia-triggered retinal pyroptosis via inhibiting NLRP3 inflammasome activation and release of pro-inflammatory cytokines. The involvement of pyroptosis pathway in the retina in response to hypobaric hypoxia supports a novel insight to clarify the pathogenesis of hypobaric hypoxia-induced retinal impairment and provides a feasibility of inflammasome modulation for preserving retinal function.

Wuzi Yanzong pill attenuates MPTP-induced Parkinson's Disease via PI3K/Akt signaling pathway.

Wuzi Yanzong Pill (WYP) was found to play a protective role on nerve cells and neurological diseases, however the molecular mechanism is unclear. To understand the molecular mechanisms that underly the neuroprotective effect of WYP on dopaminergic neurons in Parkinson's disease (PD). PD mouse model was induced by the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Gait and hanging tests were used to assess motor behavioral function. Immunofluorescence assay was used to determine TH-positive neurons in substantia nigra (SN). Apoptosis, dopamine and neurotrophic factors as well as expression of PI3K/Akt pathway were detected by TUNEL staining, ELISA and western blotting, respectively. First, it was observed that WYP intervention improved abnormal motor function in MPTP-induced PD model, alleviated the loss of TH+ neurons in SN, and increased dopamine content in brain, revealing a potential protective effect. Second, network pharmacology was used to analyze the possible targets and pathways of WYP action in the treatment of PD. A total of 126 active components related to PD were screened in WYP, and the related core targets included ALB, GAPDH, Akt1, TP53, IL6 and TNF. Particularly, the effect of WYP on PD may be medicate through PI3K/Akt signaling pathway and apoptotic regulation. The WYP treated PD mice had higher expression of p-PI3K, p-Akt and Bcl-2 but lower expression of Bax and cleaved caspase-3 than the non-WYP treated PD mice. Secretion of brain-derived neurotrophic factor (BDNF) and cerebral dopamine neurotrophic factor (CDNF) were also increased in the treated mice. WYP may inhibit apoptosis and increase the secretion of neurotrophic factor via activating PI3K/ Akt signaling pathway, thus protecting the loss of dopamine neurons in MPTP-induced PD mice.

High-Purity Fucoxanthin Can Be Efficiently Prepared from Isochrysis zhangjiangensis by Ethanol-Based Green Method Coupled with Octadecylsilyl (ODS) Column Chromatography.

The exploitation of new economically valuable microalgae as a sustainable source of minor high-value products can effectively promote the full utilization of microalgae. The efficient preparation of minor products from microalgae remains the challenge, owing to the coexistence of various components with a similar polarity in the microalgae biomass. In this study, a novel approach based on the sustainable-oriented strategy for fucoxanthin (FX) production was proposed, which consisted of four steps, including the culture of microalga, ethanol extraction, ODS column chromatography, and ethanol precipitation. The high-purity FX (around 95%) was efficiently obtained in a total recovery efficiency of 84.28 ± 2.56%. This study reveals that I. zhangjiangensis is a potentially promising feedstock for FX production and firstly provides a potentially eco-friendly method for the scale-up preparation of FX from the microalga I. zhangjiangensis.

High-throughput LC-MS method for the rapid characterisation and comparative analysis of multiple ingredients of four hawthorn leaf extracts.

INTRODUCTION: The comprehensive component characterisation of Chinese herbal medicine is the premise of effectively driving the discovery of pharmacodynamic substances or new drugs in recent years. OBJECTIVE: To use the high-throughput liquid chromatography-mass spectrometry (LC-MS) approach to systematically characterise phytochemical compounds from four hawthorn leaf extracts, along with evaluating their classification. METHODS: In the present study, the compounds from 50% ethanol extract, macro porous resin extract, ethyl acetate extract and standard decoction of hawthorn leaves were completely analysed by ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS). RESULTS: Eight-nine compounds were putatively identified by comparison with secondary MS data and available references. Of these compounds identified, 56 compounds were found for the first time in hawthorn leaves, which was somewhat inconsistent with the findings of other studies. It could be inferred that falconoid, organic acids and nitrogenous compounds were the most abundant in 50% ethanol extract and standard decoction extract, which were considered as better choices for extracting hawthorn leaves. CONCLUSIONS: This work developed a simple, accurate and rapid method for the compound identification of hawthorn leaves, which laid the basis for further discovering pharmacodynamic material basis or new drugs from hawthorn leaves.

Integrated strategy of RNA-sequencing and network pharmacology for exploring the protective mechanism of Shen-Shi-Jiang-Zhuo formula in rat with non-alcoholic fatty liver disease.

CONTEXT: Shen-Shi-Jiang-Zhuo formula (SSJZF) exhibits a definite curative effect in the clinical treatment of non-alcoholic fatty liver disease (NAFLD). OBJECTIVE: To explore the therapeutic effect and mechanism of SSJZF on NAFLD. MATERIALS AND METHODS: Sprague Dawley rats were randomly divided into control, NAFLD, positive drug (12 mg/kg/day), SSJZF high-dose (200 mg/kg/day), SSJZF middle-dose (100 mg/kg/day), and SSJZF low-dose (50 mg/kg/day) groups. After daily intragastric administration of NAFLD rats for 8 weeks, lipid metabolism and hepatic fibrosis were evaluated by biochemical indices and histopathology. Then we uncovered the main active compounds and mechanism of SSJZF against NAFLD by integrating RNA-sequencing and network pharmacology, and PI3K/AKT pathway activity was verified by western blot. RESULTS: High dose SSJZF had the best inhibitory effect on hepatic lipid accumulation and fibrosis in rats with NAFLD, which significantly down-regulated total triglycerides (58%), cholesterol (62%), aspartate aminotransferase (57%), alanine aminotransferase (41%) andγ-glutamyl transpeptidase (36%), as well as the expression of ACC (5.3-fold), FAS (12.1-fold), SREBP1C (2.3-fold), and CD36 (4.4-fold), and significantly reduced collagen deposition (67%). Then we identified 23 compounds of SSJZF that acted on 25 key therapeutic targets of NAFLD by integrating RNA-sequencing and network pharmacology. Finally, we also confirmed that high dose SSJZF increased p-PI3K/PI3K (1.6-fold) and p-AKT/AKT (1.6-fold) in NAFLD rats. DISCUSSION AND CONCLUSION: We found for first time that SSJZF improved NAFLD in rats by activating the PI3K/Akt pathway. These findings provide scientific support for SSJZF in the clinical treatment of NAFLD and contribute to the development of new NAFLD drugs.

Anthracene-Triphenylamine-Based Platinum(II) Metallacages as Synthetic Light-Harvesting Assembly.

Two trigonal prismatic metallacages 1 and 2 bearing triphenylamine and anthracene moieties are designed and synthesized to fabricate artificial light-harvesting systems (LHSs). These two cages are prepared via the coordination-driven self-assembly of two anthracene-triphenylamine-based tripyridyl ligand 3, three dicarboxylates, and six 90° Pt(II) acceptors. The design of the anthracene-triphenylamine chromophore makes possible the tunable excited-state property (like the emissive transition energy and lifetime) as a function of the solvent polarity, temperature, and concentration. The synergistic photophysical footprint of these metallacages, defined by their high absorptivity and emission quantum yield (QY) relative to the free ligand 3, signifies them as a superior light sensitizer component in an LHS. In the presence of the fluorescent dye Nile Red (NR) as an energy acceptor, the metallacages display efficient (>93%) excited energy transfer to NR through an apparent static quenching mechanism in viscous dimethyl sulfoxide solvent.

Telmisartan use and risk of dementia in type 2 diabetes patients with hypertension: A population-based cohort study.

BACKGROUND: Angiotensin receptor blockers (ARBs) may have protective effects against dementia occurrence in patients with hypertension (HTN). However, whether telmisartan, an ARB with peroxisome proliferator-activated receptor γ (PPAR-γ)-modulating effects, has additional benefits compared to other ARBs remains unclear. METHODS AND FINDINGS: Between 1997 and 2013, 2,166,944 type 2 diabetes mellitus (T2DM) patients were identified from the National Health Insurance Research Database of Taiwan. Patients with HTN using ARBs were included in the study. Patients with a history of stroke, traumatic brain injury, or dementia were excluded. Finally, 65,511 eligible patients were divided into 2 groups: the telmisartan group and the non-telmisartan ARB group. Propensity score matching (1:4) was used to balance the distribution of baseline characteristics and medications. The primary outcome was the diagnosis of dementia. The secondary outcomes included the diagnosis of Alzheimer disease and occurrence of symptomatic ischemic stroke (IS), any IS, and all-cause mortality. The risks between groups were compared using a Cox proportional hazard model. Statistical significance was set at p < 0.05. There were 2,280 and 9,120 patients in the telmisartan and non-telmisartan ARB groups, respectively. Patients in the telmisartan group had a lower risk of dementia diagnosis (telmisartan versus non-telmisartan ARBs: 2.19% versus 3.20%; HR, 0.72; 95% CI, 0.53 to 0.97; p = 0.030). They also had lower risk of dementia diagnosis with IS as a competing risk (subdistribution HR, 0.70; 95% CI, 0.51 to 0.95; p = 0.022) and with all-cause mortality as a competing risk (subdistribution HR, 0.71; 95% CI, 0.53 to 0.97; p = 0.029). In addition, the telmisartan users had a lower risk of any IS (6.84% versus 8.57%; HR, 0.79; 95% CI, 0.67 to 0.94; p = 0.008) during long-term follow-up. Study limitations included potential residual confounding by indication, interpretation of causal effects in an observational study, and bias caused by using diagnostic and medication codes to represent real clinical data. CONCLUSIONS: The current study suggests that telmisartan use in hypertensive T2DM patients may be associated with a lower risk of dementia and any IS events in an East-Asian population.

Localization of nerve entry points and the center of intramuscular nerve-dense regions in the adult pectoralis major and pectoralis minor and its significance in blocking muscle spasticity.

The aims of this study were to localize the body surface position and depth of nerve entry points, and the center of the intramuscular nerve-dense regions of the pectoralis major and pectoralis minor in order to provide guidance for blocking muscle spasticity. Formalin-fixed adult cadavers (66.3 ± 5.2 years) were used. The curved line on the skin from the acromion to the most inferior point of the jugular notch was defined as the horizontal reference line (H). The line from the most inferior point of the jugular notch to the xiphisternal joint was defined as the longitudinal reference line (L). The nerve entry points was anatomically exposed. Sihler's staining, barium sulfate labeling, and computed tomography were employed to determine the projection points (P) on the body surface. The intersection of the longitudinal line through the P point and the H line and the horizontal line through the P point and the L line were recorded as PH and PL , respectively. The projection of the nerve entry points or the center of the intramuscular nerve-dense regions were in the opposite direction across the transverse plane and were recorded as P'. The percentage positions of PH and PL on the H and L lines, as well as the nerve entry points and the center of the intramuscular nerve-dense regions depths, were determined using the Syngo system. The pectoralis major had two nerve entry points, while the pectoralis minor had only one. In addition, two intramuscular nerve-dense regions were found in the pectoralis major, while only one region was found in the pectoralis minor. The PH of the nerve entry points were located at 47.83%, 32.31%, and 34.31%, while the PH of the center of the intramuscular nerve-dense regions were at 41.95%, 55.88%, and 32.58% of line H, respectively. The PL of the nerve entry points were at -9.84%, 36.16%, and 2.44%, while the PL for each of three center of the intramuscular nerve-dense regions was at -3.87%, 25.29%, and -7.13% of line L, respectively. The depth for each of the nerve entry points was at 17.76%, 17.53%, and 25.51% of line P-P'', respectively, and the depth of the center of the intramuscular nerve-dense regions was at 5.23%, 6.75%, and 13.73% of line P-P', respectively. These percentage values are all means. The definition of the surface position and depth of these nerve entry points and center of the intramuscular nerve-dense regions can improve the localization efficiency and efficacy of target blocking for pectoralis major and minor spasticity.