Birth Weight and Risk of Cerebral Aneurysm: A Multivariable Mendelian Randomization Study.

BACKGROUND: Birth weight has been linked with various health outcomes. The association between birth weight and cerebral aneurysm remains unknown. METHODS: The two-sample Mendelian randomization (MR) approach was used to evaluate the causal effect of birth weight on cerebral aneurysm based on genome-wide association studies (GWAS), comprising 261,932 UKB participants for birth weight and 204,060 FinnGen participants for cerebral aneurysm. The inverse variance weighted (IVW) method was used as the primary method. Alternative methods were used for comparison. Sensitivity analysis was conducted to evaluate the robustness of the results. Multivariable MR (MVMR) was further conducted to evaluate the direct effect of the birth weight on cerebral aneurysm. RESULTS: The IVW detected a causal association between higher birth weight and increased risk of cerebral aneurysm (OR = 0.521, 95% CI = 0.356 ∼ 0.763, P = 7.88 × 10-4), which was supported by alternative MR models. Sensitivity analysis did not find any evidence of heterogeneity or pleiotropy. MVMR further identified a direct effect of birth weight on cerebral aneurysm, independent of obesity-related traits or smoking. CONCLUSION: This MR study found evidence of the association between birth weight and cerebral aneurysm, providing novel insight into the etiology of cerebral aneurysm, indicating the promising role of birth weight as a marker for screening populations at higher risk of cerebral aneurysm.

Closed Bipolar Nanoelectrode Array for Ultra-Sensitive Detection of Alkaline Phosphatase and Two-Dimensional Imaging of Epidermal Growth Factor Receptors.

The combination of closed bipolar electrodes (cBPE) with electrochemiluminescence (ECL) imaging has demonstrated remarkable capabilities in the field of bioanalysis. Here, we established a cBPE-ECL platform for ultrasensitive detection of alkaline phosphatase (ALP) and two-dimensional imaging of epidermal growth factor receptor (EGFR). This cBPE-ECL system consists of a high-density gold nanowire array in anodic aluminum oxide (AAO) membrane as the cBPE coupled with ECL of highly luminescent cadmium selenide quantum dots (CdSe QDs) luminophores to achieve cathodic electro-optical conversion. When an enzyme-catalyzed amplification effect of ALP with 4-aminophenyl phosphate monosodium salt hydrate (p-APP) as the substrate and 4-aminophenol (p-AP) as the electroactive probe is introduced, a significant improvement of sensing sensitivity with a detection limit as low as 0.5 fM for ALP on the cBPE-ECL platform can be obtained. In addition, the cBPE-ECL sensing system can also be used to detect cancer cells with an impressive detection limit of 50 cells/mL by labeling ALP onto the EGFR protein on A431 human epidermal cancer cell membranes. Thus, two-dimensional (2D) imaging of the EGFR proteins on the cell surface can be achieved, demonstrating that the established cBPE-ECL sensing system is of high resolution for spatiotemporal cell imaging.

Efficacy of ketamine versus esketamine in the treatment of perioperative depression: A review.

Depression is a significant factor contributing to postoperative occurrences, and patients diagnosed with depression have a higher risk for postoperative complications. Studies on cardiovascular surgery extensively addresses this concern. Several studies report that people who undergo coronary artery bypass graft surgery have a 20% chance of developing postoperative depression. A retrospective analysis of medical records spanning 21 years, involving 817 patients, revealed that approximately 40% of individuals undergoing coronary artery bypass grafting (CABG) were at risk of perioperative depression. Patients endure prolonged suffering from illness because each attempt with standard antidepressants requires several weeks to be effective. In addition, multi-drug combination adjuvants or combination medication therapy may alleviate symptoms for some individuals, but they also increase the risk of side effects. Conventional antidepressants primarily modulate the monoamine system, whereas different therapies target the serotonin, norepinephrine, and dopamine systems. Esketamine is a fast-acting antidepressant with high efficacy. Esketamine is the S-enantiomer of ketamine, a derivative of phencyclidine developed in 1956. Esketamine exerts its effect by targeting the glutaminergic system the glutaminergic system. In this paper, we discuss the current depression treatment strategies with a focus on the pharmacology and mechanism of action of esketamine. In addition, studies reporting use of esketamine to treat perioperative depressive symptoms are reviwed, and the potential future applications of the drug are presented.

Surface-phonon-polariton-enhanced photoinduced dipole force for nanoscale infrared imaging.

The photoinduced dipole force (PiDF) is an attractive force arising from the Coulombic interaction between the light-induced dipoles on the illuminated tip and the sample. It shows extreme sample-tip distance and refractive index dependence, which is promising for nanoscale infrared (IR) imaging of ultrathin samples. However, the existence of PiDF in the mid-IR region has not been experimentally demonstrated due to the coexistence of photoinduced thermal force (PiTF), typically one to two orders of magnitude higher than PiDF. In this study, we demonstrate that, with the assistance of surface phonon polaritons, the PiDF of c-quartz can be enhanced to surpass its PiTF, enabling a clear observation of PiDF spectra reflecting the properties of the real part of permittivity. Leveraging the detection of the PiDF of phonon polaritonic substrate, we propose a strategy to enhance the sensitivity and contrast of photoinduced force responses in transmission images, facilitating the precise differentiation of the heterogeneous distribution of ultrathin samples.

Mogroside Alleviates Diabetes Mellitus and Modulates Intestinal Microflora in Type 2 Diabetic Mice.

Mogroside, the main component of Siraitia grosvenorii (Swingle) C. Jeffrey (Cucurbitaceae) is a natural product with hypoglycemic and intestinal microbiota regulating properties. However, whether the alteration of intestinal microbiota is associated with the antidiabetic effect of mogroside remains poorly understood. This study investigated the mechanism underlying the hypoglycemic effect of mogroside in regulating intestinal flora and attenuating metabolic endotoxemia. Kunming mice with type 2 diabetes mellitus (T2DM) induced by high-fat diet and intraperitoneal injection of streptozotocin were randomly divided into model, pioglitazone (2.57 mg/kg) and mogroside (200, 100, and 50 mg/kg) groups. After 28 d of administration, molecular changes related to glucose metabolism and metabolic endotoxemia in mice were evaluated. The levels of insulin receptor substrate-1 (IRS-1), cluster of differentiation 14 (CD14) and toll-like receptor 4 (TLR4) mRNAs were measured, and the composition of intestinal microflora was determined by 16s ribosomal DNA (rDNA) sequencing. The results showed that mogroside treatment significantly improved hepatic glucose metabolism in T2DM mice. More importantly, mogroside treatment considerably reduced plasma endotoxin (inhibition rate 65.93%, high-dose group) and inflammatory factor levels, with a concomitant decrease in CD14 and TLR4 mRNA levels. Moreover, mogroside treatment reduced the relative abundance of Firmicutes and Proteobacteria (the inhibition rate of Proteobacteria was 85.17% in the low-dose group) and increased the relative abundance of Bacteroidetes (growth rate up to 40.57%, high-dose group) in the intestines of diabetic mice. This study reveals that mogroside can relieve T2DM, regulating intestinal flora and improving intestinal mucosal barrier, indicating that mogroside can be a potential therapeutic agent or intestinal microbiota regulator in the treatment of T2DM.

Single-Molecule Discrimination of Saccharides Using Carbon Nitride Nanopores.

Structural complexity brings a huge challenge to the analysis of sugar chains. As a single-molecule sensor, nanopores have the potential to provide fingerprint information on saccharides. Traditionally, direct single-molecule saccharide detection with nanopores is hampered by their small size and weak affinity. Here, a carbon nitride nanopore device is developed to discern two types of trisaccharide molecules (LeApN and SLeCpN) with minor structural differences. The resolution of LeApN and SLeCpN in the mixture reaches 0.98, which has never been achieved in solid-state nanopores so far. Monosaccharide (GlcNAcpN) and disaccharide (LacNAcpN) can also be discriminated using this system, indicating that the versatile carbon nitride nanopores possess a monosaccharide-level resolution. This study demonstrates that the carbon nitride nanopores have the potential for conducting structure analysis on single-molecule saccharides.

Customizable Organic Charge-Transfer Cocrystals for the Dual-Mode Optoelectronics in the NIR (II) Window.

Organic molecules have been regarded as ideal candidates for near-infrared (NIR) optoelectronic active materials due to their customizability and ease of large-scale production. However, constrained by the intricate molecular design and severe energy gap law, the realization of optoelectronic devices in the second near-infrared (NIR (II)) region with required narrow band gaps presents more challenges. Herein, we have originally proposed a cocrystal strategy that utilizes intermolecular charge-transfer interaction to drive the redshift of absorption and emission spectra of a series BFXTQ (X = 0, 1, 2, 4) cocrystals, resulting in the spectra located at NIR (II) window and reducing the optical bandgap to ∼0.98 eV. Significantly, these BFXTQ-based optoelectronic devices can exhibit dual-mode optoelectronic characteristics. An investigation of a series of BFXTQ-based photodetectors exhibits detectivity (D*) surpassing 1013 Jones at 375 to 1064 nm with a maximum of 1.76 × 1014 Jones at 1064 nm. Moreover, the radiative transition of CT excitons within the cocrystals triggers NIR emission over 1000 nm with a photoluminescence quantum yield (PLQY) of ∼4.6% as well as optical waveguide behavior with a low optical-loss coefficient of 0.0097 dB/µm at 950 nm. These results promote the advancement of an emerging cocrystal approach in micro/nanoscale NIR multifunctional optoelectronics.

The inverted U-shaped relationship between epinephrine and pancreatic ductal adenocarcinoma patients' survival with compensation of lymphocyte.

BACKGROUND: The relationship between epinephrine and cancer can be dose-dependent in in vivo study. Whether it is the same in human body still needs verification. METHOD: We used frozen human pancreatic ductal adenocarcinoma (PDAC) tissues to detect epinephrine content and analyzed its relationship with survival using the K-M method and Cox regression. Disturbance of blood cell count and C-reactive protein and identification of related potent intermediary factors were also analyzed. RESULTS: K-M plot and Cox regression all showed the inverted U-shaped relationship between epinephrine and PDAC survival. Lymphocyte adjustment can increase the HRs of epinephrine for PDAC death by >10%. CONCLUSION: Epinephrine played an anti-tumor or pro-tumor effect depending on the specific concentration. Circulating lymphocyte count was elevated and might acted as a compensation pathway to reduce the pro-tumor effect of epinephrine to PDAC.

Panax notoginseng saponins prevent dementia and oxidative stress in brains of SAMP8 mice by enhancing mitophagy.

BACKGROUND: Mitochondrial dysfunction is one of the distinctive features of neurons in patients with Alzheimer's disease (AD). Intraneuronal autophagosomes selectively phagocytose and degrade the damaged mitochondria, mitigating neuronal damage in AD. Panax notoginseng saponins (PNS) can effectively reduce oxidative stress and mitochondrial damage in the brain of animals with AD, but their exact mechanism of action is unknown. METHODS: Senescence-accelerated mouse prone 8 (SAMP8) mice with age-related AD were treated with PNS for 8 weeks. The effects of PNS on learning and memory abilities, cerebral oxidative stress status, and hippocampus ultrastructure of mice were observed. Moreover, changes of the PTEN-induced putative kinase 1 (PINK1)-Parkin, which regulates ubiquitin-dependent mitophagy, and the recruit of downstream autophagy receptors were investigated. RESULTS: PNS attenuated cognitive dysfunction in SAMP8 mice in the Morris water maze test. PNS also enhanced glutathione peroxidase and superoxide dismutase activities, and increased glutathione levels by 25.92% and 45.55% while inhibiting 8-hydroxydeoxyguanosine by 27.74% and the malondialdehyde production by 34.02% in the brains of SAMP8 mice. Our observation revealed the promotion of mitophagy, which was accompanied by an increase in microtubule-associated protein 1 light chain 3 (LC3) mRNA and 70.00% increase of LC3-II/I protein ratio in the brain tissues of PNS-treated mice. PNS treatment increased Parkin mRNA and protein expression by 62.80% and 43.80%, while increasing the mRNA transcription and protein expression of mitophagic receptors such as optineurin, and nuclear dot protein 52. CONCLUSION: PNS enhanced the PINK1/Parkin pathway and facilitated mitophagy in the hippocampus, thereby preventing cerebral oxidative stress in SAMP8 mice. This may be a mechanism contributing to the cognition-improvement effect of PNS.

Synergistic Al-Al Dual-Atomic Site for Efficient Artificial Nitrogen Fixation.

Synthesis of ammonia by electrochemical nitrogen reduction reaction (NRR) is a promising alternative to the Haber-Bosch process. However, it is commonly obstructed by the high activation energy. Here, we report the design and synthesis of an Al-Al bonded dual atomic catalyst stabilized within an amorphous nitrogen-doped porous carbon matrix (Al2NC) with high NRR performance. The dual atomic Al2-sites act synergistically to catalyze the complex multiple steps of NRR through adsorption and activation, enhancing the proton-coupled electron transfer. This Al2NC catalyst exhibits a high Faradaic efficiency of 16.56±0.3 % with a yield rate of 29.22±1.2 µg h-1 mgcat -1. The dual atomic Al2NC catalyst shows long-term repeatable, and stable NRR performance. This work presents an insight into the identification of synergistic dual atomic catalytic site and mechanistic pathway for the electrochemical conversion of N2 to NH3.

Regulating ion affinity and dehydration of metal-organic framework sub-nanochannels for high-precision ion separation.

Membrane consisting of ordered sub-nanochannels has been pursued in ion separation technology to achieve applications including desalination, environment management, and energy conversion. However, high-precision ion separation has not yet been achieved owing to the lack of deep understanding of ion transport mechanism in confined environments. Biological ion channels can conduct ions with ultrahigh permeability and selectivity, which is inseparable from the important role of channel size and "ion-channel" interaction. Here, inspired by the biological systems, we report the high-precision separation of monovalent and divalent cations in functionalized metal-organic framework (MOF) membranes (UiO-66-(X)2, X = NH2, SH, OH and OCH3). We find that the functional group (X) and size of the MOF sub-nanochannel synergistically regulate the ion binding affinity and dehydration process, which is the key in enlarging the transport activation energy difference between target and interference ions to improve the separation performance. The K+/Mg2+ selectivity of the UiO-66-(OCH3)2 membrane reaches as high as 1567.8. This work provides a gateway to the understanding of ion transport mechanism and development of high-precision ion separation membranes.

Molecular architectures of iron complexes for oxygen reduction catalysis-Activity enhancement by hydroxide ions coupling.

Developing cost-effective and high-performance electrocatalysts for oxygen reduction reaction (ORR) is critical for clean energy generation. Here, we propose an approach to the synthesis of iron phthalocyanine nanotubes (FePc NTs) as a highly active and selective electrocatalyst for ORR. The performance is significantly superior to FePc in randomly aggregated and molecularly dispersed states, as well as the commercial Pt/C catalyst. When FePc NTs are anchored on graphene, the resulting architecture shifts the ORR potentials above the redox potentials of Fe2+/3+ sites. This does not obey the redox-mediated mechanism operative on conventional FePc with a Fe2+-N moiety serving as the active sites. Pourbaix analysis shows that the redox of Fe2+/3+ sites couples with HO- ions transfer, forming a HO-Fe3+-N moiety serving as the ORR active sites under the turnover condition. The chemisorption of ORR intermediates is appropriately weakened on the HO-Fe3+-N moiety compared to the Fe2+-N state and thus is intrinsically more ORR active.

Epidemiology of Schmorl's Node in the Thoracic Spine: A Subtype Analysis.

STUDY DESIGN: Retrospective observational study. OBJECTIVE: To describe the epidemiology of Schmorl's nodes (SN) of primarily developmental cause (SNd) and SN of primarily acquired cause (SNa) separately in the thoracic spine in subjects aged 35-90 years old. SUMMARY OF BACKGROUND DATA: The epidemiology of SN and its relationship with age and gender remain controversial. Based on a pathophysiological hypothesis and the different morphological characteristics, two subtypes of SN may exist and should be considered separately. PATIENTS AND METHODS: Chest CT scans of subjects who came to our institution for health check aged 35-90 years old were retrospectively reviewed. Presence or absence of SN was recorded for each thoracic vertebra. The SNs were further classified into SNd and SNa. The prevalence, location and relationship with age, gender and bone mineral density (BMD) were evaluated separately for the two subtypes. RESULTS: Of the 848 subjects (407 female, mean age, 53±12.2 y) included, 15.7% had SNs. Of the 303 SNs, 49.2% were SNd and 48.5% were SNa. Aging increased the prevalence of SNa while it was not related to the prevalence of SNd. Males had significantly more SNd than females (11.3% vs 4.7%, P<0.001), while the prevalence of SNa was not different between the two genders (10.2% vs 9.1%, P=0.666). A similar distribution of SNd and SNa among thoracic vertebral levels was appreciated, with T9 most frequently involved. Subjects with SNa had lower lumbar BMD than controls (P=0.006), while no significant difference in BMD was found between subjects with SNd and controls (P=0.166). CONCLUSIONS: The clinical characteristics of SN differ based on the developmental and acquired subtype, including the relationship with age, gender and BMD. The subtypes may be considered as distinct clinical entities as a result.

Arsenic(III) sorption on organo-ferrihydrite coprecipitates: Insights from maize and rape straw-derived DOM.

The mobility of arsenic (As) specie in agricultural soils is significantly impacted by the interaction between ferrihydrite (Fh) and dissolved organic material (DOM) from returning crop straw. However, additional research is necessary to provide molecular evidence for the interaction of toxic and mobile As (As(III)) specie and crop straw-based organo- Fh coprecipitates (OFCs). This study investigated the As(III) sorption behaviours of OFCs synthesized with maize or rape derived-DOM under various environmental conditions and the primary molecular sorption mechanisms using As K-edge X-ray absorption near edge structure (XANES) spectroscopy. According to our findings, pure Fh adsorbed more As(III) relative to the other two OFCs, and the presence of natural organic matter in the OFCs induced more As(III) adsorption at pH 5.0. Findings from this study indicated a maximum As(III) sorption on Ma (53.71 mg g⁻1) and Ra OFC (52.46 mg g⁻1) at pH 5.0, with a sharp decrease as the pH increased from 5.0 to 8.0. Additionally, As K-edge XANES spectroscopy indicated that ∼30% of adsorbed As(III) on the OFCs undergoes transformation to As(V) at pH 7-8. Functional groups from the DOM, such as O-H, COOH, and CO, contributed to As(III) desorption and its oxidation to As(V), whereas ionic strength analysis revealed inner complexation as the dominant As(III) sorption mechanism on the OFCs. Overall, the results indicate that the interaction of natural organic matter (NOM) with As(III) at higher pH promotes As(III) mobility, which is crucial when evaluating As migration and bioavailability in alkaline agricultural soils.

Polarization Conforms Performance Variability in Amorphous Electrodeposited Iridium Oxide pH Sensors: A Thorough Surface Chemistry Investigation.

Electrodeposited amorphous hydrated iridium oxide (IrOx) is a promising material for pH sensing due to its high sensitivity and the ease of fabrication. However, durability and variability continue to restrict the sensor's effectiveness. Variation in probe films can be seen in both performance and fabrication, but it has been found that performance variation can be controlled with potentiostatic conditioning (PC). To make proper use of this technique, the morphological and chemical changes affecting the conditioning process must be understood. Here, a thorough study of this material, after undergoing PC in a pH-sensing-relevant potential regime, was conducted by voltammetry, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Fitting of XPS data was performed, guided by raw trends in survey scans, core orbitals, and valence spectra, both XPS and UPS. The findings indicate that the PC process can repeatably control and conform performance and surface bonding to desired calibrations and distributions, respectively; PC was able to reduce sensitivity and offset ranges to as low as ±0.7 mV/pH and ±0.008 V, respectively, and repeat bonding distributions over ~2 months of sample preparation. Both Ir/O atomic ratios (shifting from 4:1 to over 4.5:1) and fitted components assigned hydroxide or oxide states based on the literature (low-voltage spectra being almost entirely with suggested hydroxide components, and high-voltage spectra almost entirely with suggested oxide components) trend across the polarization range. Self-consistent valence, core orbital, and survey quantitative trends point to a likely mechanism of ligand conversion from hydroxide to oxide, suggesting that the conditioning process enforces specific state mixtures that include both theoretical Ir(III) and Ir(IV) species, and raising the conditioning potential alters the surface species from an assumed mixture of Ir species to more oxidized Ir species.

Ultrasensitive Plasmon-Enhanced Infrared Spectroelectrochemistry.

IR spectroelectrochemistry (EC-IR) is a cutting-edge operando method for exploring electrochemical reaction mechanisms. However, detection of interfacial molecules is challenged by the limited sensitivity of existing EC-IR platforms due to the lack of high-enhancement substrates. Here, we propose an innovative plasmon-enhanced infrared spectroelectrochemistry (EC-PEIRS) platform to overcome this sensitivity limitation. Plasmonic antennae with ultrahigh IR signal enhancement are electrically connected via monolayer graphene while preserving optical path integrity, serving as both the electrode and IR substrate. The [Fe(CN)6 ]3- /[Fe(CN)6 ]4- redox reaction and electrochemical CO2 reduction reaction (CO2 RR) are investigated on the EC-PEIRS platform with a remarkable signal enhancement. Notably, the enhanced IR signals enable a reconstruction of the electrochemical curve of the redox reactions and unveil the CO2 RR mechanism. This study presents a promising technique for boosting the in-depth understanding of interfacial events across diverse applications.

Lateral epitaxial growth of two-dimensional organic heterostructures.

Two-dimensional organic lateral heterostructures (2D OLHs) are attractive for the fabrication of functional materials. However, it is difficult to control the nucleation, growth and orientation of two distinct components. Here we report the combination of two methods-liquid-phase growth and vapour-phase growth-to synthesize 2D OLHs from perylene and a perylenecarboxaldehyde derivative, with a lateral size of ~20 µm and a tunable thickness ranging from 20 to 400 nm. The screw dislocation growth behaviour of the 2D crystals shows the spiral arrangement of atoms within the crystal lattice, which avoids volume expansion and contraction of OLH, thereby minimizing lateral connection defects. Selective control of the nucleation and sequential growth of 2D crystals leads to structural inversion of the 2D OLHs by the vapour-phase growth method. The resulting OLHs show good light-transport capabilities and tunable spatial exciton conversion, useful for photonic applications. This synthetic strategy can be extended to other families of organic polycyclic aromatic hydrocarbons, as demonstrated with other pyrene and perylene derivatives.