Anesthesia/surgery activate MMP9 leading to blood-brain barrier disruption, triggering neuroinflammation and POD-like behavior in aged mice.

Anesthesia and surgery activate matrix metalloproteinase 9 (MMP9), leading to blood-brain barrier (BBB) disruption and postoperative delirium (POD)-like behavior, especially in the elderly. Aged mice received intraperitoneal injections of either the MMP9 inhibitor SB-3CT, melatonin, or solvent, and underwent laparotomy under 3 % sevoflurane anesthesia(anesthesia/surgery). Behavioral tests were performed 24 h pre- and post-operatively. Serum and cortical tissue levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were measured using ELISA. Levels of PDGFRß, MMP9, tight junction, Mfsd2a, caveolin-1, synaptophysin, and postsynaptic densin (PSD)-95 proteins in the prefrontal cortex were assayed using Western blotting. BBB permeability was assessed by detecting IgG in the prefrontal cortex and serum S100ß levels. Anesthesia/surgery-induced peripheral inflammation activated MMP9, which in turn injured pericytes and tight junctions and increased transcytosis, thereby disrupting the BBB. Impaired BBB allowed the migration of peripheral inflammation into the central nervous system (CNS), thereby inducing neuroinflammation, synaptic dysfunction, and POD-like behaviors. However, MMP9 inhibition reduced pericyte and tight junction injury and transcytosis, thereby preserving BBB function and preventing the migration of peripheral inflammation into the CNS, thus attenuating synaptic dysfunction and POD-like behavior. In addition, to further validate the above findings, we showed that melatonin exerted similar effects through inhibition of MMP9. The present study shows that after anesthesia/surgery, inflammatory cytokines upregulation is involved in regulating BBB permeability in aged mice through activation of MMP9, suggesting that MMP9 may be a potential target for the prevention of POD.

Exploring non-coding RNA mechanisms in hepatocellular carcinoma: implications for therapy and prognosis.

Hepatocellular carcinoma (HCC) is a significant contributor to cancer-related deaths in the world. The development and progression of HCC are closely correlated with the abnormal regulation of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Important biological pathways in cancer biology, such as cell proliferation, death, and metastasis, are impacted by these ncRNAs, which modulate gene expression. The abnormal expression of non-coding RNAs in HCC raises the possibility that they could be applied as new biomarkers for diagnosis, prognosis, and treatment targets. Furthermore, by controlling the expression of cancer-related genes, miRNAs can function as either tumor suppressors or oncogenes. On the other hand, lncRNAs play a role in the advancement of cancer by interacting with other molecules within the cell, which, in turn, affects processes such as chromatin remodeling, transcription, and post-transcriptional processes. The importance of ncRNA-driven regulatory systems in HCC is being highlighted by current research, which sheds light on tumor behavior and therapy response. This research highlights the great potential of ncRNAs to improve patient outcomes in this difficult disease landscape by augmenting the present methods of HCC care through the use of precision medicine approaches.

Mouse auditory cortex sub-fields receive neuronal projections from MGB subdivisions independently.

Mouse auditory cortex is composed of six sub-fields: primary auditory field (AI), secondary auditory field (AII), anterior auditory field (AAF), insular auditory field (IAF), ultrasonic field (UF) and dorsoposterior field (DP). Previous studies have examined thalamo-cortical connections in the mice auditory system and learned that AI, AAF, and IAF receive inputs from the ventral division of the medial geniculate body (MGB). However, the functional and thalamo-cortical connections between nonprimary auditory cortex (AII, UF, and DP) is unclear. In this study, we examined the locations of neurons projecting to these three cortical sub-fields in the MGB, and addressed the question whether these cortical sub-fields receive inputs from different subsets of MGB neurons or common. To examine the distributions of projecting neurons in the MGB, retrograde tracers were injected into the AII, UF, DP, after identifying these areas by the method of Optical Imaging. Our results indicated that neuron cells which in ventral part of dorsal MGB (MGd) and that of ventral MGB (MGv) projecting to UF and AII with less overlap. And DP only received neuron projecting from MGd. Interestingly, these three cortical areas received input from distinct part of MGd and MGv in an independent manner. Based on our foundings these three auditory cortical sub-fields in mice may independently process auditory information.

Adult localized Langerhans cell histiocytosis: A case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare clonal proliferative disease of Langerhans cells with unknown pathogenesis. An increasing number of clinicians recognize that LCH has a wide clinical spectrum and a highly varied course. Adults rarely develop LCH. Here, we report a case of adult localized LCH. CASE SUMMARY: A 32-year-old woman presented with plaques and ulcers on the vulva and crissum, accompanied by pain that persisted for more than one year. Physical examination revealed a red-infiltrating plaque with ulcerations and exudates in the vulva and crissum. Pathological examination revealed a diffuse infiltration of lymphocytes, eosinophilic granulocytes, and histiocytoid cells in the superficial dermis. Proliferative histiocytoid cells showed mild atypia, partly with kidney-shaped nuclei. Immunohistochemical examination showed that the histiocytoid cells were positive for S100 protein and CD1 and weakly positive for CD68 (20% +), with a Ki-67 index of 30%. Laboratory tests did not reveal any other systemic damage. The patient was diagnosed with adult localized LCH and was prescribed oral prednisone (20 mg) once daily. The skin lesions gradually improved and are still being followed-up. CONCLUSION: Adult localized LCH is rare and must be differentiated from other common conditions.

Palladium-catalyzed stereoselective construction of chiral allenes bearing nonadjacent axial and two central chirality.

It is challenging to enantioselectively construct molecules bearing multiple nonadjacent stereocenters, in contrast to those bearing a single stereocenter or adjacent stereocenters. Herein, we report an enantio- and diastereoselective synthesis of substituted chiral allenes with nonadjacent axial and two central chiral centers through a combination of retro-oxa-Michael addition and palladium-catalyzed asymmetric allenylic alkylation. This methodology exhibits good functional-group compatibility, and the corresponding allenylic alkylated compounds, including flavonoid frameworks, are obtained with good yields and diastereoselectivities and excellent enantioselectivities (all >95% ee). Furthermore, the scalability of the current synthetic protocol was proven by performing a gram-scale reaction.

Enrichment Strategies for Efficient CO2 Electroreduction in Acidic Electrolytes.

Electrochemical CO2 reduction reaction (CO2 RR) has been recognized as an appealing route to remarkably accelerate the carbon-neutral cycle and reduce carbon emissions. Notwithstanding great catalytic activity that has been acquired in neutral and alkaline conditions, the carbonates generated from the inevitable reaction of the input CO2 with the hydroxide severely lower carbon utilization and energy efficiency. By contrast, CO2 RR in an acidic condition can effectively circumvent the carbonate issues; however, the activity and selectivity of CO2 RR in acidic electrolytes will be decreased significantly due to the competing hydrogen evolution reaction (HER). Enriching the CO2 and the key intermediates around the catalyst surface can promote the reaction rate and enhance the product selectivity, providing a promising way to boost the performance of CO2 RR. In this review, the catalytic mechanism and key technique challenges of CO2 RR are first introduced. Then, the critical progress of enrichment strategies for promoting the CO2 RR in the acidic electrolyte is summarized with three aspects: catalyst design, electrolyte regulation, and electrolyzer optimization. Finally, some insights and perspectives for further development of enrichment strategies in acidic CO2 RR are expounded.

Palladium-catalyzed asymmetric allenylic alkylation: construction of multiple chiral thiochromanone derivatives.

The development of a new strategy for the construction of chiral cyclic sulfide-containing multiple stereogenic centers is highly desirable. Herein, by the combination of base-promoted retro-sulfa-Michael addition and palladium-catalyzed asymmetric allenylic alkylation, the streamlined synthesis of chiral thiochromanones containing two central chiralities (including a quaternary stereogenic center) and an axial chirality (allene unit) was successfully realized with up to 98% yield, 49.0 : 1 dr and >99% ee.

Enriching Reaction Intermediates in Multishell Structured Copper Catalysts for Boosted Propanol Electrosynthesis from Carbon Monoxide.

Fine-tuned catalysts that alter the diffusion kinetics of reaction intermediates is of great importance for achieving high-performance multicarbon (C2+) product generation in carbon monoxide (CO) reduction. Herein, we conduct a structural design based on Cu2O nanoparticles and present an effective strategy for enhancing propanol electrosynthesis from CO. The electrochemical characterization, operando Raman monitoring, and finite-element method simulations reveal that the multishell structured catalyst can realize the enrichment of C1 and C2 intermediates by nanoconfinement space, leading to the possibility of further coupling. Consequently, the multishell copper catalyst realizes a high Faraday efficiency of 22.22 ± 0.38% toward propanol at the current density of 50 mA cm-2.

Brønsted acid-catalyzed C6 functionalization of 2,3-disubstituted indoles for construction of cyano-substituted all-carbon quaternary centers.

We report a Brønsted acid-catalyzed C6 functionalization of 2,3-disubstituted indoles with 2,2-diarylacetonitriles for efficient construction of cyano-substituted all-carbon quaternary centers with excellent yields. The synthetic utility was demonstrated by the conversion of the cyano-group which enables the divergent preparation of aldehydes, primary amines and amides. Control experiments suggested that this process involves C-H oxidation of 2,2-diarylacetonitriles to in situ generate δ,δ-disubstituted p-quinone methide intermediates. This protocol provides an efficient method for C6 functionalization of 2,3-disubstituted indoles to construct all-carbon quaternary centers.

Enriching the Local Concentration of CO Intermediates on Cu Cavities for the Electrocatalytic Reduction of CO2 to C2+ Products.

The electrochemical carbon-dioxide reduction reaction (CO2RR) to high-value multi-carbon (C2+) chemicals provides a hopeful approach to store renewable energy and close the carbon cycle. Although copper-based catalysts with a porous architecture are considered potential electrocatalysts for CO2 reduction to C2+ chemicals, challenges remain in achieving high selectivity and partial current density simultaneously for practical application. Here, the porous Cu catalysts with a cavity structure by in situ electrochemical-reducing Cu2O cavities are developed for high-performance conversion of CO2 to C2+ fuels. The as-described catalysts exhibit a high C2+ Faradaic efficiency and partial current density of 75.6 ± 1.8% and 605 ± 14 mA cm-2, respectively, at a low applied potential (-0.59 V vs RHE) in a microfluidic flow cell. Furthermore, in situ Raman tests and finite element simulation indicated that the cavity structure can enrich the local concentration of CO intermediates, thus promoting the C-C coupling process. More importantly, the C-C coupling should be major through the *CO-*CHO pathway as demonstrated by the electrochemical Raman spectra and density functional theory calculations. This work can provide ideas and insights into designing high-performance electrocatalysts for producing C2+ compounds and highlight the important effect of in situ characterization for uncovering the reaction mechanism.

Palladium-Catalyzed Asymmetric Hydrogenolysis of Aryl Triflates for Construction of Axially Chiral Biaryls.

Here we report the first palladium-catalyzed asymmetric hydrogenolysis of readily available aryl triflates via desymmetrization and kinetic resolution for facile construction of axially chiral biaryl scaffolds with excellent enantioselectivities and s selectivity factors. The axially chiral monophosphine ligands could be prepared from these chiral biaryl compounds and were further applied to palladium-catalyzed asymmetric allylic alkylation with excellent ee values and high branched and linear ratio, which demonstrated the potential utility of this methodology.

Synthesis of Tridentate PNO Ligands with Planar Chirality and Application in Iridium-Catalyzed Asymmetric Hydrogenation of Simple Ketones.

A series of [2,2]paracyclophane-based tridentate PNO ligands with planar chirality were designed and synthesized. The easily prepared chiral tridentate PNO ligands were successfully applied to the iridium-catalyzed asymmetric hydrogenation of simple ketones, giving chiral alcohols with high efficiency and excellent enantioselectivities (up to 99% yield and >99% ee). Control experiments revealed the indispensability of both N-H and O-H in the ligands.

A small H2O-soluble ingredient of royal jelly lower cholesterol levels in liver cells by suppressing squalene epoxidase.

Excessive cholesterol in the liver is harmful for our health and may cause many diseases, such as fatty liver disease. Many studies in human and animal models have reported that royal jelly (RJ) can be used to treat atherosclerosis. However, the real mechanisms behind this action is unclear. In this study, we investigated the efficacy of RJ on gene expression of squalene epoxidase (SE) a major enzyme involved in cholesterol biosynthesis in HepG2 cells. We found that the expression of SE was decreased in response to RJ treatment. We also found that the origin of the RJ affected its strength. To find out the active fraction of RJ in cholesterol suppression, we separated RJ into two parts based on the molecular weights using ultrafiltration membrane. We found that the fraction <10kDa from RJ had comparable effect on SE expression, especially its water-soluble part. Taken together, we think RJ suppresses cholesterol by decreasing SE gene expression in liver. The active fraction of RJ in this action is <10kDa in water-soluble form.

Endoscopic submucosal tunnel dissection for early esophageal squamous cell carcinoma in patients with cirrhosis: A propensity score analysis.

BACKGROUND: Although early esophageal squamous cell carcinoma (EESCC) with cirrhosis is a relatively rare clinical phenomenon, the management of EESCC in cirrhotic patients continues to be a challenge. AIM: To evaluate the feasibility, safety, efficacy and long-term survival outcomes of endoscopic submucosal tunnel dissection (ESTD) for treating EESCC in patients with cirrhosis. METHODS: This was a single-center retrospective cohort study. We examined 590 EESCC patients who underwent ESTD between July 14, 2014, and May 26, 2021, from a large-scale tertiary hospital. After excluding 25 patients with unclear lesion areas or pathological results, the remaining 565 patients were matched at a ratio of 1:3 by using propensity score matching. A total of 25 EESCC patients with comorbid liver cirrhosis and 75 matched EESCC patients were ultimately included in the analysis. Parametric and nonparametric statistical methods were used to compare the differences between the two groups. The Kaplan-Meier method was used to create survival curves, and differences in survival curves were compared by the log-rank test. RESULTS: Among 25 patients with liver cirrhosis and 75 matched noncirrhotic patients, there were no significant differences in intraoperative bleeding (P = 0.234), 30-d post-ESTD bleeding (P = 0.099), disease-specific survival (P = 0.075), or recurrence-free survival (P = 0.8196). The mean hospitalization time and costs were significantly longer (P = 0.007) and higher (P = 0.023) in the cirrhosis group than in the noncirrhosis group. The overall survival rate was significantly lower in the cirrhosis group (P = 0.001). CONCLUSION: ESTD is technically feasible, safe, and effective for patients with EESCC and liver cirrhosis. EESCC patients with Child-Pugh A disease seem to be good candidates for ESTD.

Hierarchical S-modified Cu porous nanoflakes for efficient CO2 electroreduction to formate.

Electrochemical reduction of CO2 into liquid fuels is a promising approach to achieving a carbon-neutral energy cycle but remains a great challenge due to the lack of efficient catalysts. Here, the hierarchical architectures assembled by ultrathin and porous S-modified Cu nanoflakes (Cu-S NFs) are designed and constructed as an efficient electrocatalyst for CO2 conversion to formate with high partial current density. Specifically, when integrated into a gas diffusion electrode in a flow cell, Cu-S NFs are capable of delivering the ultrahigh formate current density up to 404.1 mA cm-2 with a selectivity of 89.8%. Electrochemical tests and theoretical calculations indicate that the superior performance of the designed catalysts may be attributed to the unique structure, which can provide abundant active sites, fast charge transfer, and highly active edge sites.

Metal-Based Aerogels Catalysts for Electrocatalytic CO2 Reduction.

General strategies for metal aerogel synthesis, including single-metal, transition-metal doped, multi-metal-doped, and nano-metal-doped carbon aerogel are described. In addition, the latest applications of several of the above-mentioned metal aerogels in electrocatalytic CO2 reduction are discussed. Finally, considering the possibility of future applications of electrocatalytic CO2 reduction technology, a vision for industrialization and directions that can be optimized are proposed.

Asymmetric Transfer Hydrogenation of 2,3-Disubstituted Flavanones through Dynamic Kinetic Resolution Enabled by Retro-Oxa-Michael Addition: Construction of Three Contiguous Stereogenic Centers.

A ruthenium-catalyzed asymmetric transfer hydrogenation of 2,3-disubstituted flavanones was developed for the construction of three contiguous stereocenters under basic conditions through a combination of dynamic kinetic resolution and retro-oxa-Michael addition, giving chiral flavanols with excellent enantioselectivities and diastereoselectivities. The reaction proceeded via a base-catalyzed retro-oxa-Michael addition to racemize two stereogenic centers simultaneously in concert with a highly enantioselective ketone transfer hydrogenation step. The asymmetric transfer hydrogenation could be achieved at gram scale without loss of the activity and enantioselectivity.

In situ formed N-containing copper nanoparticles: a high-performance catalyst toward carbon monoxide electroreduction to multicarbon products with high faradaic efficiency and current density.

Developing efficient catalysts for electrochemical carbon monoxide reduction (ECOR) with high faradaic efficiency (FE) and current density is highly desirable. In this work, we demonstrate that the N-containing Cu nanoparticles formed in situ by the reconstruction of cuprous 7,7,8,8-tetracyanoquinodimethane possess high-performance ECOR ability. Impressively, the N-containing Cu nanoparticle catalyst presented the highest FE of 81.31% towards multicarbon products with a high commercial-grade partial current density of 162.62 mA cm-2, which is among the best of the reported Cu-based ECOR catalysts at -0.69 V versus the reversible hydrogen electrode. The retained ligand on the formed catalyst via the convenient in situ formation is crucial for the selectivity of multicarbon products. This work will arouse enthusiasm for the utilization of reconstruction features for designing ligand-containing catalysts with enhanced artificial carbon fixation ability.

The effects of case management for breast cancer patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Female breast cancer is the most common cancer nowadays, and its treatment has a significant impact on patients both physically and psychologically. Many randomized trials have proved that case management (CM) can effectively care for patients. However, there is a lack of systematic scientific evaluation, so this systematic evaluation aims to explore the impact of CM on breast cancer patients. METHODS: PubMed, Embase, Cochrane Library, Scopus, CINAHL were searched. Chinese repositories included China National Knowledge, Infrastructure Database (CNKI), Wan fang Database, China Biology Medicine Database. We will also search unpublished literature at ClinicalTrials.gov. Randomized controlled trials were collected from them. The literature will be screened according to inclusion and exclusion criteria, and 2 researchers will extract the literature independently. The primary outcome indicator for this study will be patient satisfaction. Statistics were performed using RevMan 5.4 software. The quality of each outcome will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: This study will provide the most recent evidence for evaluating the impact of CM on breast cancer patients. CONCLUSION: To evaluate the impact of CM on patients with breast cancer. REGISTRATION NUMBER: DOI:10.17605/OSF.IO/ZJKHX.