Exploring the causal role of immune cells in vascular dementia: A bidirectional mendelian randomization study.

BACKGROUND: The aim of this study was to explore the causal association between immune cells and VaD based on a two-sample bidirectional Mendelian randomization study. METHODS: Bidirectional two-sample MR analyses based on pooled datasets from publicly available genome-wide association studies were performed using inverse variance weighted (IVW), weighted median (WE), and MR-Egger regressions to evaluate the causal relationships between immune cells and vascular dementia. Heterogeneity was assessed using Cochran's Q statistic. The reliability of the MR analysis results was verified by using the MR-PRESSO method for outlier detection, the MR-Egger method for horizontal multivariate analysis, and the leave-one-out method for sensitivity analysis. RESULTS: Specifically, 27 immunophenotypes were associated with VaD pathogenesis, including Sw mem %lymphocyte (P = 0.043), CD38 on CD20- (P = 0.039), CD11c+ monocyte AC (P = 0.024), DC AC (P = 0.002), CCR2 on CD62L+ myeloid DC (P = 0.039), Resting Treg %CD4 (P = 0.042), Activated & resting Treg %CD4+ (P = 0.038), CD28+ CD45RA- CD8br %CD8br (P = 0.047), NK %CD3- lymphocyte (P = 0.042), CD45 on B cell (P = 0.029), FSC-A on NKT (P = 0.033), CD45 on CD33br HLA DR+ CD14- (P = 0.039) were significantly correlated with increased VaD risk. Additionally, four immune phenotypes, namely, CD19 on CD20-, Resting Treg %CD4, Activated & resting Treg %CD4+, and CD11c+ monocyte AC, showed bidirectional effects on VaD. CONCLUSIONS: MR analysis revealed potential causal relationships between certain immune cells and VaD. Our preliminary exploration through immune cell infiltration analysis highlights the significant value of immune cells in VaD. Therefore, this study may provide a new perspective for the prevention and treatment of VaD.

A hot-emitter transistor based on stimulated emission of heated carriers.

Hot-carrier transistors are a class of devices that leverage the excess kinetic energy of carriers. Unlike regular transistors, which rely on steady-state carrier transport, hot-carrier transistors modulate carriers to high-energy states, resulting in enhanced device speed and functionality. These characteristics are essential for applications that demand rapid switching and high-frequency operations, such as advanced telecommunications and cutting-edge computing technologies1-5. However, the traditional mechanisms of hot-carrier generation are either carrier injection6-11 or acceleration12,13, which limit device performance in terms of power consumption and negative differential resistance14-17. Mixed-dimensional devices, which combine bulk and low-dimensional materials, can offer different mechanisms for hot-carrier generation by leveraging the diverse potential barriers formed by energy-band combinations18-21. Here we report a hot-emitter transistor based on double mixed-dimensional graphene/germanium Schottky junctions that uses stimulated emission of heated carriers to achieve a subthreshold swing lower than 1 millivolt per decade beyond the Boltzmann limit and a negative differential resistance with a peak-to-valley current ratio greater than 100 at room temperature. Multi-valued logic with a high inverter gain and reconfigurable logic states are further demonstrated. This work reports a multifunctional hot-emitter transistor with significant potential for low-power and negative-differential-resistance applications, marking a promising advancement for the post-Moore era.

IL-13Rα2/TGF-ß bispecific CAR-T cells counter TGF-ß-mediated immune suppression and potentiate anti-tumor responses in glioblastoma.

BACKGROUND: Chimeric antigen receptor (CAR)-T cell therapies targeting glioblastoma (GBM)-associated antigens such as interleukin-13 receptor subunit alpha-2 (IL-13Rα2) have achieved limited clinical efficacy to date, in part due to an immunosuppressive tumor microenvironment (TME) characterized by inhibitory molecules such as transforming growth factor-beta (TGF-ß). The aim of this study was to engineer more potent GBM-targeting CAR-T cells by countering TGF-ß-mediated immune suppression in the TME. METHODS: We engineered a single-chain, bispecific CAR targeting IL-13Rα2 and TGF-ß, which programs tumor-specific T cells to convert TGF-ß from an immunosuppressant to an immunostimulant. Bispecific IL-13Rα2/TGF-ß CAR-T cells were evaluated for efficacy and safety against both patient-derived GBM xenografts and syngeneic models of murine glioma. RESULTS: Treatment with IL-13Rα2/TGF-ß CAR-T cells leads to greater T-cell infiltration and reduced suppressive myeloid cell presence in the tumor-bearing brain compared to treatment with conventional IL-13Rα2 CAR-T cells, resulting in improved survival in both patient-derived GBM xenografts and syngeneic models of murine glioma. CONCLUSION: Our findings demonstrate that by reprogramming tumor-specific T-cell responses to TGF-ß, bispecific IL-13Rα2/TGF-ß CAR-T cells resist and remodel the immunosuppressive TME to drive potent anti-tumor responses in GBM.

Integration of single-cell sequencing with machine learning and Mendelian randomization analysis identifies the NAP1L1 gene as a predictive biomarker for Alzheimer's disease.

Background: The most effective approach to managing Alzheimer's disease (AD) lies in identifying reliable biomarkers for AD to forecast the disease in advance, followed by timely early intervention for patients. Methods: Transcriptomic data on peripheral blood mononuclear cells (PBMCs) from patients with AD and the control group were collected, and preliminary data processing was completed using standardized analytical methods. PBMCs were initially segmented into distinct subpopulations, and the divisions were progressively refined until the most significantly altered cell populations were identified. A combination of high-dimensional weighted gene co-expression analysis (hdWGCNA), cellular communication, pseudotime analysis, and single-cell regulatory network inference and clustering (SCENIC) analysis was used to conduct single-cell transcriptomics analysis and identify key gene modules from them. Genes were screened using machine learning (ML) in the key gene modules, and internal and external dataset validations were performed using multiple ML methods to test predictive performance. Finally, bidirectional Mendelian randomization (MR) analysis, regional linkage analysis, and the Steiger test were employed to analyze the key gene. Result: A significant decrease in non-classical monocytes was detected in PMBC of AD patients. Subsequent analyses revealed the inherent connection of non-classical monocytes to AD, and the NAP1L1 gene identified within its gene module appeared to exhibit some association with AD as well. Conclusion: The NAP1L1 gene is a potential predictive biomarker for AD.

Observation of Diverse Asymmetric Structures in High-Dimensional Einstein-Podolsky-Rosen Steering.

Einstein-Podolsky-Rosen (EPR) steering, a distinctive quantum correlation, reveals a unique and inherent asymmetry. This research delves into the multifaceted asymmetry of EPR steering within high-dimensional quantum systems, exploring both theoretical frameworks and experimental validations. We introduce the concept of genuine high-dimensional one-way steering, wherein a high Schmidt number of bipartite quantum states is demonstrable in one steering direction but not reciprocally. Additionally, we explore two criteria to certify the lower and upper bounds of the Schmidt number within a one-sided device-independent context. These criteria serve as tools for identifying potential asymmetric dimensionality of EPR steering in both directions. By preparing two-qutrit mixed states with high fidelity, we experimentally observe asymmetric structures of EPR steering in the C^{3}⊗C^{3} Hilbert space. Our Letter offers new perspectives to understand the asymmetric EPR steering beyond qubits and has potential applications in asymmetric high-dimensional quantum information tasks.

Genetic causal relationship between multiple immune cell phenotypes and Parkinson's disease: a two-sample bidirectional Mendelian randomization study.

The exact etiology of Parkinson's disease (PD), a degenerative disease of the central nervous system, is unclear. It is currently believed that its main pathological basis is a decrease in dopamine concentration in the striatum of the brain. Although many researchers have previously focused on the critical role of the immune response in PD, there has been a lack of valid genetic evidence for a causal association between specific immune cell traits and phenotypes and PD. We employed Mendelian randomization (MR) as an analytical method to effectively assess genetic associations between exposure and outcome. Based on the largest Genome-Wide Association Study (GWAS) dataset to date, causal associations between multiple immune cell phenotypes and PD were validly assessed, controlling for confounding factors by using single-nucleotide polymorphisms (SNPs), which are genetic instrumental variables that are randomly assigned and not subject to any causality. By testing 731 immune cell phenotypes and their association with PD, the results of inverse variance weighting (IVW) analysis suggested that after Bonferroni correction multiple immune cell phenotypes had no statistically significant effect on PD. It is worth mentioning that some phenotypes with unadjusted P values (P < 0.05), including 40 immune phenotypes, that were located on the cDC panel, the Treg panel, the Maturation stages of T cell panel, the TBNK panel, the B cell panel, the Myeloid cell panel, and the Monocyte panel were considered to have nominal associations with PD. In addition, PD could have an effect on certain immunophenotypes located on the Myeloid cell panel and the Monocyte panel; the specific immunophenotypic results and statistical analysis values are shown in the text. The results of sensitivity analyses suggested that none of these observed the presence of horizontal pleiotropy. Our study identified a close link between immune cells and PD, and the results of this study provide ideas for the study of the immune mechanism of PD and the exploration of effective therapeutic means.NEW & NOTEWORTHY In this study, based on the GWAS Immunophenotyping Database, a Mendelian randomization approach was used to assess the genetic causal associations between 731 immunophenotypes and traits and Parkinson's disease (PD), which not only provides a reference for the immune response mechanism of PD but also provides ideas for exploring the effective diagnosis and treatment of PD.

Stimulus-Induced Dynamic Behavior Regulation of Flexible Crystals through the Tuning of Module Rigidity.

Introducing dynamic behavior into periodic frameworks has borne fruit in the form of flexible porous crystals. The detailed molecular design of frameworks in order to control their collective dynamics is of particular interest, for example, to achieve stimulus-induced behavior. Herein, by varying the degree of rigidity of ditopic pillar linkers, two isostructural flexible metal-organic frameworks (MOFs) with common rigid supermolecular building bilayers were constructed. The subtle substitution of single (in bibenzyl-4,4'-dicarboxylic acid; H2BBDC) with double (in 4,4'-stilbenedicarboxylic acid; H2SDC) C-C bonds in pillared linkers led to markedly different flexible behavior of these two MOFs. Upon the removal of guest molecules, both frameworks clearly show reversible single-crystal-to-single-crystal transformations involving the cis-trans conformation change and a resulting swing of the corresponding pillar linkers, which gives rise to Flex-Cd-MOF-1a and Flex-Cd-MOF-2a, respectively. Strikingly, a more favorable gas-induced dynamic behavior in Flex-Cd-MOF-2a was verified in detail by stepwise C3H6/C3H8 sorption isotherms and the corresponding in situ powder X-ray diffraction experiments. These insights are strongly supported by molecular modeling studies on the sorption mechanism that explores the sorption landscape. Furthermore, a consistency between the macroscopic elasticity and microscopic flexibility of Flex-Cd-MOF-2 was observed. This work fuels a growing interest in developing MOFs with desired chemomechanical functions and presents detailed insights into the origins of flexible MOFs.

Evidence for genetic causality between iron homeostasis and Parkinson's disease: A two-sample Mendelian randomization study.

BACKGROUND: Parkinson's disease (PD) is a degenerative disease of the central nervous system, and its specific etiology is still unclear. At present, it is believed that the main pathological basis is the reduction of dopamine concentration in the brain striatum. Although many previous studies have believed that iron as an important nutrient element participates in the occurrence and development of PD, whether there is a causal correlation between total iron binding capacity(TIBC), transferring saturation(TSAT), ferritin and serum iron in iron homeostasis indicators and PD, there has been a lack of effective genetic evidence. METHODS: We used Mendelian randomization (MR) as an analytical method to effectively evaluate the genetic association between exposure and outcome, based on the largest genome-wide association study (GWAS) data to date. By using randomly assigned genetic instrumental variables (SNPs, Single Nucleotide Polymorphisms) that are not affected by any causal relationship, we effectively evaluated the causal relationship between iron homeostasis indicators and PD while controlling for confounding factors. RESULTS: By coordinated analysis of 86 SNPs associated with iron homeostasis markers and 12,858,066 SNPs associated with PD, a total of 56 SNPs were finally screened for genome-wide significance of iron homeostasis associated with PD. The results of inverse variance weighting(IVW) analysis suggested that iron（ ß = - 0.524; 95%cl=-0.046 to -0.002; P=0.032) was considered to have a genetic causal relationship with PD. Cochran's Q, Egger intercept and MR-PRESSO global tests did not detect the existence of heterogeneity and pleiotropy (P>0.05). Mr Steiger directionality test further confirmed our estimation of the potential causal direction of iron and PD (P=0.001). In addition, TIBC (ß=-0.142; 95%Cl=-0.197-0.481; P=0.414), TSAT (ß=-0.316; 95%Cl=-0.861-0.229; P=0.255), and ferritin (ß=-0.387; 95%Cl=-1.179-0.405; P=0.338) did not have genetic causal relationships with PD, and the results were not heterogeneous and pleiotropic (P>0.05). In addition, TIBC (ß=-0.142; 95%Cl=-0.197-0.481; P=0.414), TSAT (ß=-0.316; 95%Cl=-0.861-0.229; P=0.255), and ferritin (ß=-0.101; 95%Cl=--0.987 to -0.405; P=0.823) did not have genetic causal relationships with PD, and the results were not heterogeneous and pleiotropic (P>0.05). TIBC (P=0.008), TSAT (P=0.000) and ferritin (P=0.013) were all consistent with the estimation of MR Steiger directivity test. CONCLUSION: Our study found that among the four iron homeostasis markers, there was a genetic causal association between serum iron and PD, and the serum iron level was negatively correlated with the risk of PD. In addition, TIBC, TSAT, ferritin had no genetic causal relationship with PD.

Genetic causal role of body mass index in multiple neurological diseases.

Body mass index (BMI) is a crucial health indicator for obesity. With the progression of socio-economic status and alterations in lifestyle, an increasing number of global populations are at risk of obesity. Given the complexity and severity of neurological diseases, early identification of risk factors is vital for the diagnosis and prognosis of such diseases. In this study, we employed Mendelian randomization (MR) analysis utilizing the most comprehensive genome-wide association study (GWAS) data to date. We selected single nucleotide polymorphisms (SNPs) that are unaffected by confounding factors and reverse causality as instrumental variables. These variables were used to evaluate the genetic and causal relationships between Body Mass Index (BMI) and various neurological diseases, including Parkinson's Disease (PD), Alzheimer's Disease (AD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Ischemic Stroke (IS), and Epilepsy (EP). The Inverse Variance Weighted (IVW) analysis indicated that there was no significant causal relationship between Body Mass Index (BMI) indicators and PD (P-value = 0.511), AD (P-value = 0.076), ALS (P-value = 0.641), EP (P-value = 0.380). However, a causal relationship was found between BMI indicators and MS (P-value = 0.035), and IS (P-value = 0.000), with the BMI index positively correlated with the risk of both diseases. The Cochran's Q test for MR-IVW showed no heterogeneity in the MR analysis results between the BMI index and the neurological diseases (P > 0.05). The Egger intercept test for pleiotropy revealed no horizontal pleiotropy detected in any of the neurological diseases studied (P > 0.05). It was found that there was no causal relationship between BMI and PD, AD, ALS, EP, and a genetic causal association with MS, and IS. Meanwhile, the increase in BMI can lead to a higher risk of MS and IS, which reveals the critical role of obesity as a risk factor for specific neurological diseases in the pathogenesis of the diseases.

A linker selective retention strategy to construct hierarchical porous metal-organic frameworks with high catalytic activity for oxidative desulfurization.

In order to improve the oxidative desulfurization (ODS) performance of MOF materials, an effective way is to convert a microporous MOF into a hierarchical porous MOF (HP-MOF) by utilizing the linker selective retention strategy. Herein, UiO-66 with the introduction of an unstable linker ligand (dihydro-1,2,4,5-tetrazine-3,6-dicarboxylate, dhtz) can selectively remove dhtz ligands to form HP-MOF (HP-UiO-66-dhtz) through heat treatment at high temperature. While maintaining the original structure of UiO-66, HP-UiO-66-dhtz features mesopores and abundant Lewis acid sites, showing excellent ODS performance for diphenylthiophene (DBT).

Ferulic Acid Activates SIRT1-Mediated Ferroptosis Signaling Pathway to Improve Cognition Dysfunction in Wilson's Disease.

Background: Wilson's disease (WD), an autosomal recessive genetic disease, is characterized by copper metabolism disorder. WD patients may have a series of cognitive deficits in terms of neurological symptoms. Ferroptosis (FPT), a type of programmed cell death, is involved in the pathological progression of various cognitive disorders, and silent information regulator 1 (SIRT1) is considered to be a key factor in FPT. Ferulic acid (FA) is a traditional Chinese medicine monomer, with a remarkable effect in the clinical treatment of cognitive impairment-related disease. However, its intrinsic effect on FPT is still unclear. This study aims to investigate the protective effect of FA on cognitive impairment in animal and cell models of WD, and whether the pharmacological mechanism is related to the SIRT1-mediated FPT signaling pathway. Methods: Copper-loaded WD rats and PC12 cells WD were used as models of cognitive dysfunction in vivo and in vitro, respectively. Morris Water Maze (MWM) was used to evaluate the spatial exploration and memory abilities of rats. HE staining was used to observe neuronal damage in the CA1 region of the rat hippocampus. Immunofluorescence (IF) was used to detect the expression of GPX4 protein. Transmission electron microscopy (TEM) was used to observe the ultrastructure of neurons. The levels of Fe2+, MDA, SOD, GSH, 4HNE, and ROS were detected. Western blot and qRT-PCR were used to detect the protein and mRNA levels of SIRT1, Nrf2, SCL7A11, and GPX4. Results: In the WD copper-loaded model rats, MWM, TEM, and IF results showed that FA could promote the repair of learning and memory function, improve the morphological damage to hippocampal neurons, and maintain mitochondria integrity. In the PC12 cell experiment, the MTT method showed that FA increased the viability of copper-overloaded cell models. Western blot and qRT-PCR results confirmed that FA significantly increased the expression of proteins and mRNA in SIRT1, Nrf2, SCL7A11, and GPX4. In addition, FA reversed the expression of oxidative stress-related indicators, including MDA, SOD, GSH, 4HNE, and ROS. Conclusion: FA alleviates hippocampal neuronal injury by activating SIRT1-mediated FPT, providing a valuable candidate for traditional Chinese medicine monomer for the clinical therapeutics of WD cognitive impairment.

Fabrication of N-doped carbon-coated MnO/ZnMn2O4 cathode materials for high-capacity aqueous zinc-ion batteries.

Rechargeable aqueous zinc-ion batteries (ZIBs) are highly promising energy storage devices due to their advantages of high energy density, low cost, environmental friendliness, and excellent safety. Investigation of advanced cathode materials featuring high capacity is desired for their applications in high-capacity ZIBs. In this study, a porous N-doped carbon-coated manganese oxide/zinc manganate (MZM@N-C) composite was successfully prepared as an advanced cathode material for aqueous ZIBs. The MZM@N-C cathode demonstrated a superior specific capacity of 772.8 mA h g-1 at 50 mA g-1 and maintained a high specific capacity of 205 mA h g-1 after 300 cycles at a high current density of 500 mA g-1. As compared to the unmodified MnOx cathode, MZM@N-C has a higher reversible capacity and cycling stability which could be assigned to the robust one-dimensional (1D) structure and the synergistic effect of MZM@N-C, providing instructive insight into the design of high-capacity manganese-based cathodes for rechargeable aqueous ZIBs. Furthermore, a soft-pack battery was assembled using the MZM@N-C cathode, demonstrating its potential applications in various devices.

Facile Tuned TSCT-TADF in Donor-Acceptor MOF for Highly Adjustable Photonic Modules based on Heterostructures Crystals.

Highly adjustable photonic modules were constructed based on the heterostructures crystals of a new series of donor-acceptor metal-organic framework (D-A MOF) featuring highly tunable thermally activated delayed fluorescence (TADF). By introducing N-phenylcarbazole and derivatives as donor guests into the acceptor host NKU-111, highly tunable through-space charge transfer based TADF could be achieved through the engineering of heavy atom effect, which result in modulatable emission wavelength (540 to 600 nm) and enhanced quantum yield (up to 30.86 %). Furthermore, by rationally integrating the D-A MOFs with distinctive emissions, rod-like heterostructures crystals featuring excitation position dependent tip emissions in wide wavelength range (495 to 598 nm) could be fabricated, which could serve as highly potential photonic modules for photonic circuit applications.

Highly Tunable MOF Luminophores Featuring Anthracene Directed Assembly and Fluorescence Regulation.

Metal-organic frameworks (MOFs) have been recognized as a potential platform for the development of tunable luminophores owing to their highly modulable structures and components. Herein, two MOF luminophores based on Cd(II) ions, 1,3,5-tri(4-pyridinyl)benzene (TPB), and 1,4-dicarboxybenzene (H2BDC) were constructed. The directed assembly of the metal ions and organic linkers results in [Cd2(BDC)2(TPB)(H2O)]·x(solvent) (MOF-1) featuring TPB-based blue fluorescence centered at 425 nm. By introducing anthracene as the structure directing agent (SDA) for assembly regulation, [Cd2(BDC)(TPB)2(NO3)2]·x(solvent) (MOF-2) was obtained, which reveals anthracene feeding-dependent high tunable emission in the 517-650 nm range. Detailed components, photophysical properties, and structural characteristics investigations of MOF-2 indicate the TPB and NO3- interactions as the origin of its redshifted emission compared with that of MOF-1. Furthermore, the fluorescence of MOF-2 was found to be regulatable by the anthracene feeding based on the SDA-determined crystallinity of the crystalline sample. All these results provided a unique example of the structural and fluorescence regulation of MOF luminophores.

Tuning the Trade-Off between Ethane/Ethylene Selectivity and Adsorption Capacity within Isoreticular Microporous Metal-Organic Frameworks by Linker Fine-Fluorination.

The pore dimension and surface property directly dictate the transport of guests, endowing diverse gas selective adsorptions to porous materials. It is highly relevant to construct metal-organic frameworks (MOFs) with designable functional groups that can achieve feasible pore regulation to improve their separation performances. However, the role of functionalization in different positions or degrees within framework on the separation of light hydrocarbon has rarely been emphasized. In this context, four isoreticular MOFs (TKL-104-107) bearing dissimilar fluorination are rationally screened out and afforded intriguing differences in the adsorption behavior of C2 H6 and C2 H4 . Ortho-fluoridation of carboxyl allows TKL-105-107 to exhibit enhanced structural stabilities, impressive C2 H6 adsorption capacities (>125 cm3 g-1 ) and desirable inverse selectivities (C2 H6 over C2 H4 ). The more modified ortho-fluorine group and meta-fluorine group of carboxyl have improved the C2 H6 /C2 H4 selectivity and adsorption capacity, respectively, and the C2 H6 /C2 H4 separation potential can be well optimized via linker fine-fluorination. Meanwhile, dynamic breakthrough experiments proved that TKL-105-107 can be used as highly efficient C2 H6 -selective adsorbents for C2 H4 purification. This work highlights that the purposeful functionalization of pore surfaces facilitates the assembly of highly efficient MOF adsorbents for specific gas separation.

Manipulating spatial alignment of donor and acceptor in host-guest MOF for TADF.

Thermally activated delayed fluorescence (TADF) was achieved when electron-rich triphenylene (Tpl) donors were confined to a cage-based porous metal-organic framework (MOF) host (NKU-111) composed of electron-deficient 2,4,6-tri(pyridin-4-yl)-1,3,5-triazine (Tpt) acceptor as the ligand. The spatially separated donor and acceptor molecules in a face-to-face stacking pattern generated strong through-space charge transfer (CT) interactions with a small energy splitting between the singlet and triplet excited states (∼0.1 eV), which enabled TADF. The resulting Tpl@NKU-111 exhibited an uncommon enhanced emission intensity as the temperature increased. Extensive steady-state and time-resolved spectroscopic measurements and first-principles simulations revealed the chemical and electronic structure of this compound in both the ground and low-lying excited states. A double-channel (T1, T2) intersystem crossing mechanism with S1 was found and explained as single-directional CT from the degenerate HOMO-1/HOMO of the guest donor to the LUMO+1 of one of the nearest acceptors. The rigid skeleton of the compound and effective through-space CT enhanced the photoluminescence quantum yield (PLQY). A maximum PLQY of 57.36% was achieved by optimizing the Tpl loading ratio in the host framework. These results indicate the potential of the MOFs for the targeted construction and optimization of TADF materials.

Construction of CeRNA regulatory network based on WGCNA reveals diagnosis biomarkers for colorectal cancer.

BACKGROUND: Colorectal cancer is the third most common cause of death among cancers in the world. Although improvements in various treatments have greatly improved the survival time of colorectal cancer patients, since colorectal cancer is often at an advanced stage when diagnosed, the prognosis of patients is still very poor. Since the ceRNA regulatory network was proposed in 2011, it has greatly promoted the study of the molecular mechanism of colorectal cancer occurrence and development. OBJECTIVE: Exploring the new molecular mechanism of colorectal cancer occurrence and development and providing new targets for the diagnosis and treatment of colorectal cancer. METHOD: We analyzed the RNA-seq data of CRC from TCGA, such as differential expression analysis, weighted gene co-expression network analysis (WGCNA) and construction of ceRNA regulatory network. RESULTS: We constructed a ceRNA network using RNA-seq data of CRC from TCGA. In the ceRNA regulatory network, 19 hub molecules with significant prognostic effects were ultimately identified, including 8 lncRNAs, 2 mRNAs and 9 miRNAs. These hub molecules constitute the lncRNA-miRNA, miRNA-mRNA or lncRNA-miRNA-mRNA axis. CONCLUSION: In this article, some new ceRNA regulatory axes have been discovered, which may potentially disclose new molecular mechanisms for the occurrence and development of colorectal cancer, thereby providing an important blueprint for the treatment and prognosis assessment of CRC patients.

Uncovering the Mechanism of the Xingnaojing Injection against Ischemic Stroke Using a Combined Network Pharmacology Approach and Gut Microbiota Analysis.

Objective: To explore the brain protection mechanism of Xingnaojing injection (XNJ) against ischemic stroke (IS) by the network pharmacology approach and gut microbiota analysis. Methods: We used network pharmacology analysis to identify the active components of XNJ and its potential targets against IS and inflammatory bowel disease (IBD) and carried out network analysis, functional annotation, and pathway enrichment analysis. Then, transient middle cerebral artery occlusion (tMCAO) mice model was used to verify the molecular mechanism of XNJ. Results: 36 active compounds were identified from XNJ, and the effect of XNJ against IS was related to the VEGF signaling pathway, NF-kappa B signaling pathway, and gap junction. The effect of XNJ against IBD was related to the T cell receptor signaling pathway, NF-kappa B signaling pathway, and gap junction. In vitro experiments showed that XNJ significantly improved the neurological function of tMCAO mice, reduced the size of cerebral infarction, decreased the permeability of blood-brain barrier (BBB), downregulated the expressions of TLR4, MyD88, and NF-kappa B in the ischemic site, and upregulated the expressions of occludin and ZO-1 in the colon. High-throughput 16S rDNA gene sequencing showed that XNJ upregulated the levels of Akkermansia and downregulated the levels of Flavobacteriaceae, Deferribacteraceae, and Deferribacteres. XNJ increased the concentrations of the short-chain fatty acids (SCFAs) PA (propionate), VA (valerate), IBA (isobutyrate), and IVA (isovalerate) in the feces of the sham germ-free experiment group (SGFEG) mice. Conclusion: IS causes dysbiosis of some specific bacteria in the gut microbiota. XNJ is an effective treatment for IS, and its mechanism was related to improving intestinal barrier function and regulating intestinal flora and SCFAs. Network pharmacology revealed that XNJ acts through multiple targets and multiple pathways.

How Reproducible are Surface Areas Calculated from the BET Equation?

Porosity and surface area analysis play a prominent role in modern materials science. At the heart of this sits the Brunauer-Emmett-Teller (BET) theory, which has been a remarkably successful contribution to the field of materials science. The BET method was developed in the 1930s for open surfaces but is now the most widely used metric for the estimation of surface areas of micro- and mesoporous materials. Despite its widespread use, the calculation of BET surface areas causes a spread in reported areas, resulting in reproducibility problems in both academia and industry. To prove this, for this analysis, 18 already-measured raw adsorption isotherms were provided to sixty-one labs, who were asked to calculate the corresponding BET areas. This round-robin exercise resulted in a wide range of values. Here, the reproducibility of BET area determination from identical isotherms is demonstrated to be a largely ignored issue, raising critical concerns over the reliability of reported BET areas. To solve this major issue, a new computational approach to accurately and systematically determine the BET area of nanoporous materials is developed. The software, called "BET surface identification" (BETSI), expands on the well-known Rouquerol criteria and makes an unambiguous BET area assignment possible.

Modulation of Hierarchical Pores in Metal-Organic Frameworks for Improved Dye Adsorption and Electrocatalytic Performance.

The hierarchical porous metal-organic framework (HP-MOF) has emerged as a hot topic in porous materials in consideration of their advantages in storage capacity and catalysis performance. Herein, we report the construction and property investigation of a series of HP-MOFs. A series of isoreticular microporous MOFs featuring the pacs topology network based on 2,4,6-tris(4-pyridyl)-1,3,5-triazine and different carboxylic acid ligands are found to be potential precursors to construct HP-MOFs. Through the decarboxylation of carboxylate ligands at high temperatures, a hierarchical porous structure could be obtained with the reservation of a crystalline framework. The formation of hierarchical pores is highly dependent on the structural and component nature (carboxylate ligands and metal centers) of the pristine MOF and the pyrolysis conditions (temperature and treatment time), indicating the highly tunable hierarchical pore characteristic of the HP-MOFs. By taking advantage of the increased pore volume and more exposed activation sites, the HP-MOFs reveal enhanced anionic dye adsorption capacity (800 mg·g-1 for Congo red and 140 mg·g-1 for methyl blue) and catalytic activity toward electrocatalytic oxygen reduction reaction (overpotential of 0.302 V at a current density of 10 mA·cm-2, 51 mV lower than that of the pristine MOF).