Morphology of human sinoatrial node and its surrounding right atrial muscle in the global obesity pandemic-does fat matter?

Introduction: The sinus node (SN) is the main pacemaker site of the heart, located in the upper right atrium at the junction of the superior vena cava and right atrium. The precise morphology of the SN in the human heart remains relatively unclear especially the SN microscopical anatomy in the hearts of aged and obese individuals. In this study, the histology of the SN with surrounding right atrial (RA) muscle was analyzed from young non-obese, aged non-obese, aged obese and young obese individuals. The impacts of aging and obesity on fibrosis, apoptosis and cellular hypertrophy were investigated in the SN and RA. Moreover, the impact of obesity on P wave morphology in ECG was also analyzed to determine the speed and conduction of the impulse generated by the SN. Methods: Human SN/RA specimens were dissected from 23 post-mortem hearts (preserved in 4% formaldehyde solution), under Polish local ethical rules. The SN/RA tissue blocks were embedded in paraffin and histologically stained with Masson's Trichrome. High and low-magnification images were taken, and analysis was done for appropriate statistical tests on Prism (GraphPad, USA). 12-lead ECGs from 14 patients under Polish local ethical rules were obtained. The P wave morphologies from lead II, lead III and lead aVF were analyzed. Results: Compared to the surrounding RA, the SN in all four groups has significantly more connective tissue (P ≤ 0.05) (young non-obese individuals, aged non-obese individuals, aged obese individuals and young obese individuals) and significantly smaller nodal cells (P ≤ 0.05) (young non-obese individuals, aged non-obese individuals, aged obese individuals, young obese individuals). In aging, overall, there was a significant increase in fibrosis, apoptosis, and cellular hypertrophy in the SN (P ≤ 0.05) and RA (P ≤ 0.05). Obesity did not further exacerbate fibrosis but caused a further increase in cellular hypertrophy (SN P ≤ 0.05, RA P ≤ 0.05), especially in young obese individuals. However, there was more infiltrating fat within the SN and RA bundles in obesity. Compared to the young non-obese individuals, the young obese individuals showed decreased P wave amplitude and P wave slope in aVF lead. Discussion: Aging and obesity are two risk factors for extensive fibrosis and cellular hypertrophy in SN and RA. Obesity exacerbates the morphological alterations, especially hypertrophy of nodal and atrial myocytes. These morphological alterations might lead to functional alterations and eventually cause cardiovascular diseases, such as SN dysfunction, atrial fibrillation, bradycardia, and heart failure.

Silver-Assisted Chemical Etching for the Fabrication of Porous Silicon N-Doped Nanohollow Carbon Spheres Composite Anodes to Enhance Electrochemical Performance.

Silicon (Si) shows great potential as an anode material for lithium-ion batteries. However, it experiences significant expansion in volume as it undergoes the charging and discharging cycles, presenting challenges for practical implementation. Nanostructured Si has emerged as a viable solution to address these challenges. However, it requires a complex preparation process and high costs. In order to explore the above problems, this study devised an innovative approach to create Si/C composite anodes: micron-porous silicon (p-Si) was synthesized at low cost at a lower silver ion concentration, and then porous silicon-coated carbon (p-Si@C) composites were prepared by compositing nanohollow carbon spheres with porous silicon, which had good electrochemical properties. The initial coulombic efficiency of the composite was 76.51%. After undergoing 250 cycles at a current density of 0.2 A·g-1, the composites exhibited a capacity of 1008.84 mAh·g-1. Even when subjected to a current density of 1 A·g-1, the composites sustained a discharge capacity of 485.93 mAh·g-1 even after completing 1000 cycles. The employment of micron-structured p-Si improves cycling stability, which is primarily due to the porous space it provides. This porous structure helps alleviate the mechanical stress caused by volume expansion and prevents Si particles from detaching from the electrodes. The increased surface area facilitates a longer pathway for lithium-ion transport, thereby encouraging a more even distribution of lithium ions and mitigating the localized expansion of Si particles during cycling. Additionally, when Si particles expand, the hollow carbon nanospheres are capable of absorbing the resulting stress, thus preventing the electrode from cracking. The as-prepared p-Si utilizing metal-assisted chemical etching holds promising prospects as an anode material for lithium-ion batteries.

The Honey Bee Colony's Criterion for Candidate Selection: "Ongoing" or "One-Shot"?

In the honey bee, the queen's death severely threatens the survival of the colony. In an emergency, new queens are reared from young worker larvae, where nepotism is thought to influence the choice of queen candidates by the workers. This article simulates the emergency queen-rearing process in a colony under natural conditions and records the results of colony selection (without nepotism). In queenless colonies, worker larvae aged three days or younger were preferred for queen rearing, and 1-day-old larvae were the first to be selected for the queen-cell cups. In the capping stage, the number of capped queen cells selected from the 1-day-old larvae was much higher than the 3-day-old larvae. On the first day, the number of emerging queens reared from 1-day-old larvae was significantly higher than the queens reared from 2-day-old and 3-day-old larvae. However, there was no significant difference in the birth weights of queens reared from 1-day-old, 2-day-old, or 3-day-old larvae. When the newly emerged queens were introduced into the original queenless colony, 1-day-old larval queens triggered more worker followers than 2-day-old larval queens. The expression of ovarian development-related genes (vg, hex110, and Jh) was higher in queens reared from 1-day-old larvae than those reared from 2-day-old and 3-day-old larvae, indicating that the quality of the queens reared from 1-day-old larvae is superior. This study shows that in the absence of nepotism, the colony selection of queen candidates at the larval stage, capping stage, and emerging stage is not final, but is gradually optimized to maximize colony development through a "quality control" process.

Sphingosine d18:1 promotes nonalcoholic steatohepatitis by inhibiting macrophage HIF-2α.

Non-alcoholic steatohepatitis (NASH) is a severe type of the non-alcoholic fatty liver disease (NAFLD). NASH is a growing global health concern due to its increasing morbidity, lack of well-defined biomarkers and lack of clinically effective treatments. Using metabolomic analysis, the most significantly changed active lipid sphingosine d18:1 [So(d18:1)] is selected from NASH patients. So(d18:1) inhibits macrophage HIF-2α as a direct inhibitor and promotes the inflammatory factors secretion. Male macrophage-specific HIF-2α knockout and overexpression mice verified the protective effect of HIF-2α on NASH progression. Importantly, the HIF-2α stabilizer FG-4592 alleviates liver inflammation and fibrosis in NASH, which indicated that macrophage HIF-2α is a potential drug target for NASH treatment. Overall, this study confirms that So(d18:1) promotes NASH and clarifies that So(d18:1) inhibits the transcriptional activity of HIF-2α in liver macrophages by suppressing the interaction of HIF-2α with ARNT, suggesting that macrophage HIF-2α may be a potential target for the treatment of NASH.

Interlukin-22 improves ovarian function in polycystic ovary syndrome independent of metabolic regulation: a mouse-based experimental study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder with multiple metabolic abnormalities. Most PCOS patients have concomitant metabolic syndromes such as insulin resistance and obesity, which often lead to the development of type II diabetes and cardiovascular disease with serious consequences. Current treatment of PCOS with symptomatic treatments such as hormone replacement, which has many side effects. Research on its origin and pathogenesis is urgently needed. Although improving the metabolic status of the body can alleviate reproductive function in some patients, there is still a subset of patients with metabolically normal PCOS that lacks therapeutic tools to address ovarian etiology. METHODS: The effect of IL-22 on PCOS ovarian function was verified in a non-metabolic PCOS mouse model induced by dehydroepiandrosterone (DHEA) and rosiglitazone, as well as granulosa cell -specific STAT3 knockout (Fshrcre+Stat3f/f) mice (10 groups totally and n = 5 per group). Mice were maintained under controlled temperature and lighting conditions with free access to food and water in a specific pathogen-free (SPF) facility. Secondary follicles separated from Fshrcre+Stat3f/f mice were cultured in vitro with DHEA to mimic the hyperandrogenic environment in PCOS ovaries (4 groups and n = 7 per group) and then were treated with IL-22 to investigate the specific role of IL-22 on ovarian function. RESULTS: We developed a non-metabolic mice model with rosiglitazone superimposed on DHEA. This model has normal metabolic function as evidenced by normal glucose tolerance without insulin resistance and PCOS-like ovarian function as evidenced by irregular estrous cycle, polycystic ovarian morphology (PCOM), abnormalities in sex hormone level. Supplementation with IL-22 improved these ovarian functions in non-metabolic PCOS mice. Application of DHEA in an in vitro follicular culture system to simulate PCOS follicular developmental block and ovulation impairment. Follicles from Fshrcre+Stat3f/f did not show improvement in POCS follicle development with the addition of IL-22. In DHEA-induced PCOS mice, selective ablation of STAT3 in granulosa cells significantly reversed the ameliorative effect of IL-22 on ovarian function. CONCLUSION: IL-22 can improve non-metabolic PCOS mice ovarian function. Granulosa cells deficient in STAT3 reverses the role of IL-22 in alleviating ovary dysfunction in non-metabolic PCOS mice.

Control of polymers' amorphous-crystalline transition enables miniaturization and multifunctional integration for hydrogel bioelectronics.

Soft bioelectronic devices exhibit motion-adaptive properties for neural interfaces to investigate complex neural circuits. Here, we develop a fabrication approach through the control of metamorphic polymers' amorphous-crystalline transition to miniaturize and integrate multiple components into hydrogel bioelectronics. We attain an about 80% diameter reduction in chemically cross-linked polyvinyl alcohol hydrogel fibers in a fully hydrated state. This strategy allows regulation of hydrogel properties, including refractive index (1.37-1.40 at 480 nm), light transmission (>96%), stretchability (139-169%), bending stiffness (4.6 ± 1.4 N/m), and elastic modulus (2.8-9.3 MPa). To exploit the applications, we apply step-index hydrogel optical probes in the mouse ventral tegmental area, coupled with fiber photometry recordings and social behavioral assays. Additionally, we fabricate carbon nanotubes-PVA hydrogel microelectrodes by incorporating conductive nanomaterials in hydrogel for spontaneous neural activities recording. We enable simultaneous optogenetic stimulation and electrophysiological recordings of light-triggered neural activities in Channelrhodopsin-2 transgenic mice.

Effects of the ApoE genotype on cognitive function in aging mice fed with a high-fat diet and the protective potential of n-3 polyunsaturated fatty acids.

The ApoE4 allele is the strongest genetic determinant for Alzheimer's disease (AD), while obesity is a strong environmental risk for AD. The modulatory effect of the ApoE genotype on aging-related cognitive function in tandem with a high-fat diet (HFD) remains uncertain. This study aimed to elucidate the effects of ApoE3/ApoE4 genotypes in aged mice exposed to a HFD, and the benefits of n-3 polyunsaturated fatty acids (PUFAs) from fish oil. Remarkably, the HFD led to weight gain and lipid accumulation, more pronounced in ApoE3 mice, while ApoE4 mice experienced exacerbated cerebral insulin resistance, neuroinflammation, and oxidative stress. Critically, n-3 PUFAs modulated the cerebral insulin signaling via the IRS-1/AKT/GLUT4 pathway, mitigated microglial hyperactivity, and reduced IL-6 and MDA levels, thereby counteracting cognitive deficits. These findings highlight the contrasting impacts of ApoE genotypes on aging mice exposed to a HFD, supporting n-3 PUFAs as a strategic nutritional intervention for brain health, especially for ApoE4 carriers.

A synbiotic formulation of Lactobacillus reuteri and inulin alleviates ASD-like behaviors in a mouse model: the mediating role of the gut-brain axis.

Autism Spectrum Disorder (ASD), a complex neurodevelopmental disorder marked by social communication deficits and repetitive behaviors, may see symptom amelioration through gut microbiota modulation. This study investigates the effects of a synbiotic - specifically a probiotic amplified by prebiotic supplementation - on ASD-like mouse model's social deficiencies. This model was established via valproic acid injection into pregnant females. Post-weaning, male progeny received daily synbiotic treatment, a combination of Lactobacillus reuteri (L. reuteri) and inulin, for four weeks. Results indicated that the synbiotic rectified social impairments and attenuated inflammatory cytokine expressions in the brain. Moreover, synbiotic intervention protected gut barrier integrity and altered the gut microbiota composition, enhancing the butyrate-producing Bifidobacterium abundance. The synbiotic elevated metabolites such as butyrate and 3-hydroxybutyric acid (3-HB), alongside upregulated genes associated with 3-HB synthesis in the colon and liver, and brain receptors. Conclusively, the synbiotic combination of L. reuteri and inulin mitigated ASD-related social impairments, partially via their regulatory effect on the gut-brain axis.

Prospective clinical validation of the Empatica EmbracePlus wristband as a reflective pulse oximeter.

Introduction: Respiratory diseases such as chronic obstructive pulmonary disease, obstructive sleep apnea syndrome, and COVID-19 may cause a decrease in arterial oxygen saturation (SaO2). The continuous monitoring of oxygen levels may be beneficial for the early detection of hypoxemia and timely intervention. Wearable non-invasive pulse oximetry devices measuring peripheral oxygen saturation (SpO2) have been garnering increasing popularity. However, there is still a strong need for extended and robust clinical validation of such devices, especially to address topical concerns about disparities in performances across racial groups. This prospective clinical validation aimed to assess the accuracy of the reflective pulse oximeter function of the EmbracePlus wristband during a controlled hypoxia study in accordance with the ISO 80601-2-61:2017 standard and the Food & Drug Administration (FDA) guidance. Methods: Healthy adult participants were recruited in a controlled desaturation protocol to reproduce mild, moderate, and severe hypoxic conditions with SaO2 ranging from 100% to 70% (ClinicalTrials.gov registration #NCT04964609). The SpO2 level was estimated with an EmbracePlus device placed on the participant's wrist and the reference SaO2 was obtained from blood samples analyzed with a multiwavelength co-oximeter. Results: The controlled hypoxia study yielded 373 conclusive measurements on 15 subjects, including 30% of participants with dark skin pigmentation (V-VI on the Fitzpatrick scale). The accuracy root mean square (Arms) error was found to be 2.4%, within the 3.5% limit recommended by the FDA. A strong positive correlation between the wristband SpO2 and the reference SaO2 was observed (r = 0.96, P < 0.001), and a good concordance was found with Bland-Altman analysis (bias, 0.05%; standard deviation, 1.66; lower limit, -4.7%; and upper limit, 4.8%). Moreover, acceptable accuracy was observed when stratifying data points by skin pigmentation (Arms 2.2% in Fitzpatrick V-VI, 2.5% in Fitzpatrick I-IV), and sex (Arms 1.9% in females, and 2.9% in males). Discussion: This study demonstrates that the EmbracePlus wristband could be used to assess SpO2 with clinically acceptable accuracy under no-motion and high perfusion conditions for individuals of different ethnicities across the claimed range. This study paves the way for further accuracy evaluations on unhealthy subjects and during prolonged use in ambulatory settings.

Fatigue-resistant hydrogel optical fibers enable peripheral nerve optogenetics during locomotion.

We develop soft and stretchable fatigue-resistant hydrogel optical fibers that enable optogenetic modulation of peripheral nerves in naturally behaving animals during persistent locomotion. The formation of polymeric nanocrystalline domains within the hydrogels yields fibers with low optical losses of 1.07 dB cm-1, Young's modulus of 1.6 MPa, stretchability of 200% and fatigue strength of 1.4 MPa against 30,000 stretch cycles. The hydrogel fibers permitted light delivery to the sciatic nerve, optogenetically activating hindlimb muscles in Thy1::ChR2 mice during 6-week voluntary wheel running assays while experiencing repeated deformation. The fibers additionally enabled optical inhibition of pain hypersensitivity in an inflammatory model in TRPV1::NpHR mice over an 8-week period. Our hydrogel fibers offer a motion-adaptable and robust solution to peripheral nerve optogenetics, facilitating the investigation of somatosensation.

Spatio-temporal evolution and influencing factors of China's ICT service industry.

The ICT service industry has become a burgeoning industry at a high and stable speed. Their equitable distribution can improve national and global positive peace. This paper aimed to verify the characteristics of spatio-temporal evolution and its influencing factors in the ICT service industry. Based on the data from 31 Provinces in China from 2015 to 2019, this paper uses location quotient, spatial autocorrelation methods and spatial econometric analysis to explore the development characteristics, evolution and influencing factors of the ICT service industry, respectively. The main results are shown as follows: (1) China's ICT service industry is mainly concentrated in Beijing, Shanghai, Zhejiang, Tibet, and Guangdong, with a trend of specialisation development. They are not only distributed in cities with relatively superior overall development but also those with superior industrial and development carrier elements. Technological relevance, aggregation, and political difference might have an impact on promoting the emergence and development of these industries. (2) ICT service industry is characterised by stable and highly concentrated development. Numbers between three to five significant provinces and types with high-high (HH) and high-low (HL) clusters of local spatio-temporal association kept stable in the period. The HH was in eastern coastal areas, including Zhejiang, Shanghai, Jiangsu, and Shandong, and the HL was in Guangdong in 2015. There is a definite spatial correlation in spatial distribution with constant strengthening. (3) TUR, NDN, MIAT and the area were shown to have a significant role in promoting the ICT service industry, while NW, GDP and ICT Employment were shown to have a significant negative impact on this industry. Correspondingly, two strategies were put forward here: (1) accelerating the inter-provincial networking development of the ICT service industry, and (2) strengthening government policy guidance for the ICT service industry. These outcomes can not only provide a scientific basis and theoretical support for the distribution of strategies and resources for these industries at the theoretical level but also improve resource integration from the national perspective and the efficiency of resource use at the practical level.

Control of Polymers' Amorphous-crystalline Transition for Hydrogel Bioelectronics Miniaturization and Multifunctional Integration.

Bioelectronic devices made of soft elastic materials exhibit motion-adaptive properties suitable for brain-machine interfaces and for investigating complex neural circuits. While two-dimensional microfabrication strategies enable miniaturizing devices to access delicate nerve structures, creating 3D architecture for expansive implementation requires more accessible and scalable manufacturing approaches. Here we present a fabrication strategy through the control of metamorphic polymers' amorphous-crystalline transition (COMPACT), for hydrogel bioelectronics with miniaturized fiber shape and multifunctional interrogation of neural circuits. By introducing multiple cross-linkers, acidification treatment, and oriented polymeric crystalline growth under deformation, we observed about an 80% diameter decrease in chemically cross-linked polyvinyl alcohol (PVA) hydrogel fibers, stably maintained in a fully hydrated state. We revealed that the addition of cross-linkers and acidification facilitated the oriented polymetric crystalline growth under mechanical stretching, which contributed to the desired hydrogel fiber diameter decrease. Our approach enabled the control of hydrogels' properties, including refractive index (RI 1.37-1.40 at 480 nm), light transmission (> 96%), stretchability (95% - 111%), and elastic modulus (10-63 MPa). To exploit these properties, we fabricated step-index hydrogel optical probes with contrasting RIs and applied them in optogenetics and photometric recordings in the mouse brain region of the ventral tegmental area (VTA) with concurrent social behavioral assessment. To extend COMPACT hydrogel multifunctional scaffolds to assimilate conductive nanomaterials and integrate multiple components of optical waveguide and electrodes, we developed carbon nanotubes (CNTs)-PVA hydrogel microelectrodes for hindlimb muscle electromyographic and brain electrophysiological recordings of light-triggered neural activities in transgenic mice expressing Channelrhodopsin-2 (ChR2).

Er: YAG laser assisted photodynamic therapy for the management of severe oral epithelial dysplasia with innate and adaptive immune responses.

Oral epithelial dysplasia (OED) in oral potentially malignant disorders (OPMDs) increases the risk of malignant transformation. However, the management of OED is not well defined. Photodynamic therapy (PDT) is a hypotoxic, highly selective and minimally-invasive operation which reduces morbidity and disfigurement greatly. Additionally, laser ablation guaranteed a better penetration for topical application of 5-aminolaevulinic acid (ALA)-PDT. Herein, we present a case of a large lesion of oral leukoplakia (OLK) in left tongue dorsum and lateral margin, pathologically manifested as severe epithelial dysplasia (SED). We firstly discussed the feasibility of Er: YAG laser assisted PDT for the treatment of SED in OPMDs. The patient achieved complete remission at 1 year follow-up. Downregulated number of p53 and Ki67 positive cells were observed in the tissues after Er: YAG laser assisted PDT. In addition, increased CD8+ positive cells infiltrated around the tissues and increased natural killer (NK) cells level were detected in the peripheral blood. In summary, Erbium:yttrium-aluminum-garnet (Er:YAG) laser assisted PDT is an effective and promising treatment for the management of SED in OPMDs with innate and adaptive immune responses.

Identification and characterization of select oxysterols as ligands for GPR17.

BACKGROUND AND PURPOSE: G-protein coupled receptor 17 (GPR17) is an orphan receptor involved in the process of myelination, due to its ability to inhibit the maturation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes. Despite multiple claims that the biological ligand has been identified, it remains an orphan receptor. EXPERIMENTAL APPROACH: Seventy-seven oxysterols were screened in a cell-free [35 S]GTPγS binding assay using membranes from cells expressing GPR17. The positive hits were characterized using adenosine 3',5' cyclic monophosphate (cAMP), inositol monophosphate (IP1) and calcium mobilization assays, with results confirmed in rat primary oligodendrocytes. Rat and pig brain extracts were separated by high-performance liquid chromatography (HPLC) and endogenous activator(s) were identified in receptor activation assays. Gene expression studies of GPR17, and CYP46A1 (cytochrome P450 family 46 subfamily A member 1) enzymes responsible for the conversion of cholesterol into specific oxysterols, were performed using quantitative real-time PCR. KEY RESULTS: Five oxysterols were able to stimulate GPR17 activity, including the brain cholesterol, 24(S)-hydroxycholesterol (24S-HC). A specific brain fraction from rat and pig extracts containing 24S-HC activates GPR17 in vitro. Expression of Gpr17 during mouse brain development correlates with the expression of Cyp46a1 and the levels of 24S-HC itself. Other active oxysterols have low brain concentrations below effective ranges. CONCLUSIONS AND IMPLICATIONS: Oxysterols, including but not limited to 24S-HC, could be physiological activators for GPR17 and thus potentially regulate OPC differentiation and myelination through activation of the receptor.

Identification of a Prognostic Pyroptostic-Related Model for Head and Neck Squamous Cell Carcinoma Based on LASSO-Cox Regression Analysis.

Pyroptosis is associated with the biological behavior of the tumor and with tumor immunity. We investigated the effect of pyroptosis on the tumor microenvironment and tumor immunity in head and neck squamous cell carcinoma (HNSCC). RNA sequencing data and clinical information of HNSCC were downloaded from TCGA. Differentially expressed pyroptosis-related genes in HNSCC were identified between HNSCC and normal tissue. Pyroptosis-related classification of HNSCC was conducted based on consensus clustering analysis. LASSO-Cox regression analysis was used to construct a prognostic risk model-based pyroptosis-related gene. Evaluation of the immune microenvironment was conducted in prognostic risk signature based on pyroptosis-related genes. Total 22 differentially expressed pyroptosis-related genes were identified in HNSCC. Six prognostic-related genes were included to construct a LASSO regression model with a prognostic risk score = (0.133 ∗ GSDME (DFNA5) + 0.084 ∗ NOD1 + 0.039 ∗ IL6 + 0.003 ∗ IL1B + 0.084 ∗ CASP3 + 0.028 ∗ NLRP2). Higher fraction of resting memory CD4+ T cells and macrophages M1 was infiltrated in the high-risk group compared with the low-risk group in HNSCC. Furthermore, the PI3K-Akt signaling pathway and the IL-17 signaling pathways were identified to be involved in the development of high-risk HNSCC. Our study constructed a prognostic risk signature based on pyroptosis-related genes, which emphasizes the critical importance of pyroptosis in HNSCC and provided a novel perspective of HNSCC therapy.

Submetric Spatial Resolution ROTDR Temperature Sensor Assisted by Wiener Deconvolution.

A submetric spatial resolution Raman optical time-domain reflectometry (ROTDR) temperature sensor assisted by the Wiener deconvolution postprocessing algorithm has been proposed and experimentally demonstrated. Without modifying the typical configuration of the ROTDR sensor and the adopted pump pulse width, the Wiener demodulation algorithm is able to recover temperature perturbations of a smaller spatial scale by deconvoluting the acquired Stokes and anti-Stokes signals. Numerical simulations have been conducted to analyze the spatial resolution achieved by the algorithm. Assisted by the algorithm, a typical ROTDR sensor adopting pump pulses of 20 ns width can realize the distributed temperature sensing with a spatial resolution of 0.5 m and temperature accuracy of 1.99 °C over a 2.1-km sensing fiber.

Hexagonal Cages and Lewis Acid-Base Sites in a Metal-Organic Framework for Synergistic CO2 Capture and Conversion under Mild Conditions.

The cycloaddition reaction of carbon dioxide (CO2) is a highly economic solution to becoming carbon-neutral. Herein, we have designed and synthesized a robust zinc(II)-organic framework (Zn-Ade-TCPE) by a function-directed strategy. Zn-Ade-TCPE possesses uncommon hexagonal cages with Lewis acid-base bifunctional sites and displays a high adsorption capacity for CO2. At room temperature and atmospheric pressure, Zn-Ade-TCPE exhibits outstanding activity, selectivity, and recyclability in the cycloaddition reaction of epoxides with CO2 because of the synergistic effect of multiple active sites and confined cavities.

The Peanut Skin Procyanidins Attenuate DSS-Induced Ulcerative Colitis in C57BL/6 Mice.

Polyphenols from peanut skin have been reported to possess many beneficial functions for human health, including anti-oxidative, antibacterial, anticancer, and other activities. To date, however, its anti-inflammatory effect and the underlying mechanism remain unclear. In this study, the anti-inflammatory effect of peanut skin procyanidins extract (PSPE) and peanut skin procyanidins (PSPc) were investigated by a dextran sodium sulfate (DSS)-induced colitis mouse model. The results showed that both PSPE and PSPc supplementation reversed the DSS-induced body weight loss and reduced disease activity index (DAI) values, accompanied by enhanced goblet cell numbers and tight junction protein claudin-1 expression in the colon. PSPE and PSPc treatment also suppressed the inflammatory responses and oxidative stress in the colon by down-regulating IL-1ß, TNF-α, and MDA expressions. Meanwhile, PSPE and PSPc significantly altered the gut microbiota composition by increasing the relative abundance of Clostridium XlVb and Anaerotruncus, and inhibiting the relative abundance of Alistipes at the genus level. PSPE and PSPc also significantly elevated the production of short-chain fatty acids (SCFAs) in mice with colitis. The correlation analysis suggested that the protective effects of PSPE and PSPc on colitis might be related to the alteration of gut microbiota composition and the formation of SCFAs. In conclusion, the current research indicates that supplementation of PSPE and PSPc could be a promising nutritional strategy for colitis prevention and treatment.

Sesamol Attenuates Scopolamine-Induced Cholinergic Disorders, Neuroinflammation, and Cognitive Deficits in Mice.

Alzheimer's disease (AD) is a neurodegenerative disease, characterized by memory loss and cognitive deficits accompanied by neuronal damage and cholinergic disorders. Sesamol, a lignan component in sesame oil, has been proven to have neuroprotective effects. This research aimed to investigate the preventive effects of sesamol on scopolamine (SCOP)-induced cholinergic disorders in C57BL/6 mice. The mice were pretreated with sesamol (100 mg/kg/d, p.o.) for 30 days. Behavioral tests indicated that sesamol supplement prevented SCOP-induced cognitive deficits. Sesamol enhanced the expression of neurotrophic factors and postsynaptic density (PSD) in SCOP-treated mice, reversing neuronal damage and synaptic dysfunction. Importantly, sesamol could balance the cholinergic system by suppressing the AChE activity and increasing the ChAT activity and M1 mAChR expression. Sesamol treatment also inhibited the expression of inflammatory factors and overactivation of microglia in SCOP-treated mice. Meanwhile, sesamol improved the antioxidant enzyme activity and suppressed oxidative stress in SCOP-treated mice and ameliorated the oxidized cellular status and mitochondrial dysfunction in SCOP-treated SH-SY5Y cells. In conclusion, these results indicated that sesamol attenuated SCOP-induced cognitive dysfunction via balancing the cholinergic system and reducing neuroinflammation and oxidative stress.

Mechanism and Regulation of Microglia Polarization in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is the most lethal subtype of stroke, but effective treatments are lacking, and neuroinflammation plays a key role in the pathogenesis. In the innate immune response to cerebral hemorrhage, microglia first appear around the injured tissue and are involved in the inflammatory cascade response. Microglia respond to acute brain injury by being activated and polarized to either a typical M1-like (pro-inflammatory) or an alternative M2-like (anti-inflammatory) phenotype. These two polarization states produce pro-inflammatory or anti-inflammatory. With the discovery of the molecular mechanisms and key signaling molecules related to the polarization of microglia in the brain, some targets that regulate the polarization of microglia to reduce the inflammatory response are considered a treatment for secondary brain tissue after ICH damage effective strategies. Therefore, how to promote the polarization of microglia to the M2 phenotype after ICH has become the focus of attention in recent years. This article reviews the mechanism of action of microglia's M1 and M2 phenotypes in secondary brain injury after ICH. Moreover, it discusses compounds and natural pharmaceutical ingredients that can polarize the M1 to the M2 phenotype.