Hierarchical functional differences between gyri and sulci at different scales.

Gyri and sulci are 2 fundamental cortical folding patterns of the human brain. Recent studies have suggested that gyri and sulci may play different functional roles given their structural and functional heterogeneity. However, our understanding of the functional differences between gyri and sulci remains limited due to several factors. Firstly, previous studies have typically focused on either the spatial or temporal domain, neglecting the inherently spatiotemporal nature of brain functions. Secondly, analyses have often been restricted to either local or global scales, leaving the question of hierarchical functional differences unresolved. Lastly, there has been a lack of appropriate analytical tools for interpreting the hierarchical spatiotemporal features that could provide insights into these differences. To overcome these limitations, in this paper, we proposed a novel hierarchical interpretable autoencoder (HIAE) to explore the hierarchical functional difference between gyri and sulci. Central to our approach is its capability to extract hierarchical features via a deep convolutional autoencoder and then to map these features into an embedding vector using a carefully designed feature interpreter. This process transforms the features into interpretable spatiotemporal patterns, which are pivotal in investigating the functional disparities between gyri and sulci. We evaluate the proposed framework on Human Connectome Project task functional magnetic resonance imaging dataset. The experiments demonstrate that the HIAE model can effectively extract and interpret hierarchical spatiotemporal features that are neuroscientifically meaningful. The analyses based on the interpreted features suggest that gyri are more globally activated, whereas sulci are more locally activated, demonstrating a distinct transition in activation patterns as the scale shifts from local to global. Overall, our study provides novel insights into the brain's anatomy-function relationship.

Dual Heterojunctions and Nanobowl Morphology Engineered BiVO4 Photoanodes for Enhanced Solar Water Splitting.

Photoelectrochemical (PEC) water splitting represents an attractive strategy to realize the conversion from solar energy to hydrogen energy, but severe charge recombination in photoanodes significantly limits the conversion efficiency. Herein, a unique BiVO4 (BVO) nanobowl (NB) heterojunction photoanode, which consists of [001]-oriented BiOCl underlayer and BVO nanobowls containing embedded BiOCl nanocrystals, is fabricated by nanosphere lithography followed by in situ transformation. Experimental characterizations and theoretical simulation prove that nanobowl morphology can effectively enhance light absorption while reducing carrier diffusion path. Density functional theory (DFT) calculations show the tendency of electron transfer from BVO to BiOCl. The [001]-oriented BiOCl underlayer forms a compact type II heterojunction with the BVO, favoring electron transfer from BVO through BiOCl to the substrate. Furthermore, the embedded BiOCl nanoparticles form a bulk heterojunction to facilitate bulk electron transfer. Consequently, the dual heterojunctions engineered BVO/BiOCl NB photoanode exhibits attractive PEC performance toward water oxidation with an excellent bulk charge separation efficiency of 95.5%, and a remarkable photocurrent density of 3.38 mA cm-2 at 1.23 V versus reversible hydrogen electrode, a fourfold enhancement compared to the flat BVO counterpart. This work highlights the great potential of integrating dual heterojunctions engineering and morphology engineering in fabricating high-performance photoelectrodes toward efficient solar conversion.

Cortex2vector: anatomical embedding of cortical folding patterns.

Current brain mapping methods highly depend on the regularity, or commonality, of anatomical structure, by forcing the same atlas to be matched to different brains. As a result, individualized structural information can be overlooked. Recently, we conceptualized a new type of cortical folding pattern called the 3-hinge gyrus (3HG), which is defined as the conjunction of gyri coming from three directions. Many studies have confirmed that 3HGs are not only widely existing on different brains, but also possess both common and individual patterns. In this work, we put further effort, based on the identified 3HGs, to establish the correspondences of individual 3HGs. We developed a learning-based embedding framework to encode individual cortical folding patterns into a group of anatomically meaningful embedding vectors (cortex2vector). Each 3HG can be represented as a combination of these embedding vectors via a set of individual specific combining coefficients. In this way, the regularity of folding pattern is encoded into the embedding vectors, while the individual variations are preserved by the multi-hop combination coefficients. Results show that the learned embeddings can simultaneously encode the commonality and individuality of cortical folding patterns, as well as robustly infer the complicated many-to-many anatomical correspondences among different brains.

Role of CD44 in Chemotherapy Treatment Outcome: A Scoping Review of Clinical Studies.

Cluster of differentiation 44 (CD44), a cell surface adhesion molecule overexpressed in cancer stem cells, has been implicated in chemoresistance. This scoping review, following PRISMA-ScR guidelines, systematically identified and evaluated clinical studies on the impact of CD44 expression on chemotherapy treatment outcomes across various cancer types. The search encompassed PubMed (1985-2023) and SCOPUS (1936-2023) databases, yielding a total of 12,659 articles, of which 40 met the inclusion criteria and were included in the qualitative synthesis using a predefined data extraction table. Data collected included the cancer type, sample size, interventions, control, treatment outcome, study type, expression of CD44 variants and isoforms, and effect of CD44 on chemotherapy outcome. Most of the studies demonstrated an association between increased CD44 expression and negative chemotherapeutic outcomes such as shorter overall survival, increased tumor recurrence, and resistance to chemotherapy, indicating a potential role of CD44 upregulation in chemoresistance in cancer patients. However, a subset of studies also reported non-significant relationships or conflicting results. In summary, this scoping review highlighted the breadth of the available literature investigating the clinical association between CD44 and chemotherapeutic outcomes. Further research is required to elucidate this relationship to aid clinicians in managing CD44-positive cancer patients.

Two-Dimensional Ultrathin Graphic Carbon Nitrides with Extended π-Conjugation as Extraordinary Efficient Hydrogen Evolution Photocatalyst.

Construction of 2D graphic carbon nitrides (g-CNx ) with wide visible light adsorption range and high charge separation efficiency concurrently is of great urgent demand and still very challenging for developing highly efficient photocatalysts for hydrogen evolution. To achieve this goal, a two-step pyrolytic strategy has been applied here to create ultrathin 2D g-CNx with extended the π-conjugation. It is experimentally proven that the extension of π-conjugation in g-CNx is not only beneficial to narrowing the bandgap, but also improving the charge separation efficiency of the g-CNx . As an integral result, extraordinary apparent quantum efficiencies (AQEs) of 57.3% and 7.0% at short (380 nm) and long (520 nm) wavelength, respectively, are achieved. The formation process of the extended π-conjugated structures in the ultrathin 2D g-CNx has been investigated using XRD, FT-IR, Raman, XPS, and EPR. Additionally, it has been illustrated that the two-step pyrolytic strategy is critical for creating ultrathin g-CNx nanosheets with extended π-conjugation by control experiments. This work shows a feasible and effective strategy to simultaneously expand the light adsorption range, enhance charge carrier mobility and depress electron-hole recombination of g-CNx for high-efficient photocatalytic hydrogen evolution.

Microwell Confined Electro-Coalescence for Rapid Formation of High-Throughput Droplet Array.

Droplet array is widely applied in single cell analysis, drug screening, protein crystallization, etc. This work proposes and validates a method for rapid formation of uniform droplet array based on microwell confined droplets electro-coalescence of screen-printed emulsion droplets, namely electro-coalescence droplet array (ECDA). The electro-coalescence of droplets is according to the polarization induced electrostatic and dielectrophoretic forces, and the dielectrowetting effect. The photolithographically fabricated microwells are highly regular and reproducible, ensuring identical volume and physical confinement to achieve uniform droplet array, and meanwhile the microwell isolation protects the paired water droplets from further fusion and broadens its feasibility to different fluidic systems. Under optimized conditions, a droplet array with an average diameter of 85 µm and a throughput of 106 in a 10 cm × 10 cm chip can be achieved within 5 s at 120 Vpp and 50 kHz. This ECDA chip is validated for various microwell geometries and functional materials. The optimized ECDA are successfully applied for digital viable bacteria counting, showing comparable results to the plate culture counting. Such an ECDA chip, as a digitizable and high-throughput platform, presents excellent potential for high-throughput screening, analysis, absolute quantification, etc.

UV/Chlorine Process: An Efficient Advanced Oxidation Process with Multiple Radicals and Functions in Water Treatment.

Because of the deterioration of global water quality, the occurrence of chemical and microbial contaminants in water raises serious concerns for the health of the population. Identifying and developing effective and environmentally friendly water treatment technologies are critical to obtain clean water. Among the various technologies for the purification of water, ultraviolet photolysis of chlorine (UV/chlorine), an emerging advanced oxidation process (AOP), has multiple functions for the control of contaminants via the production of hydroxyl radicals (HO·) and reactive chlorine species (RCS), such as Cl·, ClO·, and Cl2·-.This Account centers around the radical chemistry of RCS and HO· in different water matrices and their roles and mechanisms in the abatement of contaminants. The concentrations of Cl·, ClO·, and Cl2·- are comparable to or higher than those of HO· (10-14 to 10-13 M). The reactivities of RCS are more selective than HO· with a broader range of second-order rate constants (k). The k values of Cl· toward most aromatics are higher or similar as compared to those of HO·, while those of Cl2·- and ClO· are less reactive but more selective toward aromatics containing electron-donating functional groups. Their major reaction mechanisms with Cl· are electron transfer and addition, while those with ClO· and Cl2·- primarily involve electron transfer. As for aliphatics, their reactivities with both HO· and RCS are much lower than those of aromatics. The reaction mechanisms for most of them with Cl· and Cl2·- are hydrogen abstraction, except for olefins, which are addition. In addition, RCS greatly contribute to the inactivation of microbial contaminants.Toward future application, the UV/chlorine process has both pros and cons. Compared with the traditional HO·-based AOP of UV/H2O2, UV/chlorine is more efficient and energy-saving for oxidation and disinfection, and its efficiency is less affected by water matrix components. However, the formation of toxic byproducts in UV/chlorine limits its application scenarios. In dissolved organic matter (DOM)-rich water, the formation of halogenated byproducts is enhanced in UV/chlorine. In the presence of ammonia, reactive nitrogen species (RNS) (e.g., ·NO and ·NO2) are involved, and highly toxic nitro(so) products such as nitro(so)-phenolics and N-nitrosodimethylamine are generated. For a niche application, the UV/chlorine process is recommended to be utilized in water with low levels of DOM and ammonia.Strategies should be developed to make full use of highly reactive species (RCS and HO·) for the abatement of target contaminants and to reduce the formation of toxic byproducts. For example, the UV/chlorine process can be used in tandem with other treatments to create multiple barriers for the production of safe water. In addition, halogen radicals are very important in ecosystems as well as other areas such as medical therapy and organic synthesis. UV/chlorine is the most efficient homogeneous system to generate halogen radicals, and thus it provides a perfect system to investigate the fates of halogen radicals for interdisciplinary research.

Enhancement effect of carvacrol on yeast inactivation by mild pressure carbon dioxide.

Saccharomyces cerevisiae is one of the common spoilage microorganisms in fruit juices. This paper investigated the influences of carvacrol on S. cerevisiae inactivation by mild pressure carbon dioxide (MPCO2). The results demonstrated that carvacrol synergistically enhanced the antifungal activity against S. cerevisiae of MPCO2. With the increase of carvacrol concentration (20-160 µg/mL), CO2 pressure (1.5-3.5 MPa), process temperature (20-40 °C), and treatment time (15-60 min), the inactivation effect of carvacrol combined with MPCO2 on S. cerevisiae was gradually increased and significantly stronger than either single treatment. In the presence of carvacrol, MPCO2 severely disordered the plasma membrane of S. cerevisiae, including the increase of membrane permeability, and the loss of membrane potential and integrity. MPCO2 and carvacrol in combination also aggravated the mitochondrial depolarization of S. cerevisiae and reduced intracellular ATP and protein content. This study suggests the potential of carvacrol and pressurized CO2 as an alternative technology for food pasteurization.

Crystalline Metallo-Organic Cage by Triphenylene-Cored Hexaterpyridine for Fast Iodine Capture.

In recent years, radioactive iodine capture has played an important role in nuclear waste treatment. However, most of the adsorbents possess low economic efficiency and undesirable reutilization in practical application. In this work, a terpyridine-based porous metallo-organic cage was assembled for iodine adsorption. Through synchrotron X-ray analysis, the metallo-cage was found to have a porous hierarchical packing mode with inherent cavity and packing channel. By taking advantage of polycyclic aromatic units and charged ⟨tpy-Zn2+-tpy⟩ (tpy = terpyridine) coordination sites in the structure, this nanocage exhibits an excellent ability to capture iodine in both the gas phase and aqueous medium, and the crystal state of the nanocage shows an ultrafast kinetic process of capturing I2 in aqueous solution within 5 min. The calculated maximum sorption capacities for I2 based on the Langmuir isotherm models are 1731 and 1487 mg g-1 for amorphous and crystalline nanocages, which is noticeably higher than most of the reported iodine sorbent materials in the aqueous phase. This work not only provides a rare example of iodine adsorption by a terpyridyl-based porous cage but also expands the applications of terpyridine coordination systems into iodine capture.

Heteroleptic/Heterometallic Sierpinski Triangle with Room Temperature Fluorescence Emission and Photocatalytic Amine Oxidation Activity.

As a result of their optical and redox properties, bipyridyl (bpy) and terpyridyl (tpy) ruthenium complexes play vital roles in numerous domains. Herein, the design and synthesis of two bipyridyl and terpyridyl ruthenium(II) building units L1 and L2 are explained. A [Ru(bpy)3]2+ functionalized triangle S1 and a Sierpinski triangle S2 were synthesized in almost quantitative yields by the self-assembly of L1 with Zn2+ ions and by the heteroleptic self-assembly of L1 and L2 with Zn2+ ions, respectively. The Sierpinski triangle S2 contains the coordination metals [Ru(bpy)3]2+, [Ru(tpy)2]2+, and [Zn(tpy)2]2+. According to research on the catalytic activity of amine oxidation on supramolecules S1 and S2, the benzylamine substrates were nearly entirely transformed to N-benzylidenebenzylamine derivatives after 1 h under a Xe lamp. Furthermore, the observed ruthenium-containing terpyridyl supramolecule S2 maintains high luminous performance at ambient temperature. This discovery opens up new possibilities for the rational molecular design of terpyridyl ruthenium fluorescent materials and catalytic functional materials.

In situanchoring of Fe3O4/CNTs hybrids on basalt fiber for efficient electromagnetic wave absorption.

The development of practical and efficient electromagnetic wave (EMW) absorbing materials is a challenging research problem. A mussel-inspired molecular structure regulation strategy using polydopamine to increase the roughness and functional groups of basalt fiber (BF) surface, which can improve the fiber interfacial adhesion. Herein, a novel BF-Fe3O4/CNTs heterostructure is synthesized through a dip-coating adsorption process. The three-dimensional network structure of Fe3O4/CNTs hybridin situanchored on the surface of BF, which endows the composite to have good intrinsic magnetic and dielectric properties. Modulation of EMW absorption performance by controlling the addition of CNTs, the minimum RL of BF-Fe3O4/7C reaches to -40.57 dB at a thickness of 1.5 mm with CNTs addition of 7%. The enhanced EMW absorption performance of BF-Fe3O4/7C heterostructure may be attributed to the synergistic effects of interfacial polarization between the hollow magnetic Fe3O4spheres and CNTs, conduction loss, magnetic resonance loss and multiple reflection/scattering inside the BF. This work provides a simple pathway to design EMW absorbing materials with good environmental stability.

The Marriage of Sierpinski Triangles and Platonic Polyhedra.

Fractal structures with self-similarity are of fundamental importance in the fields of aesthetic, chemistry and mathematics. Here, by taking advantage of constructs the rational geometry-directed precursor design, we report the construction of two fascinating Platonic solids, the Sierpinski tetrahedron ST-T and the Sierpinski octahedron ST-O, in which each possesses a fractal Sierpinski triangle on their independent faces. These two discrete complexes are formed in near-quantitative yield from the multi-component self-assembly of truncated Sierpinski triangular kernel L1 with tribenzotriquinacene-based hexatopic and anthracene-based tetratopic terpyridine ligands (L3 and L4 ) in the presence of metal ions, respectively. The enhanced stabilities of the 3D discrete structures were investigated by gradient tandem mass spectrometry (gMS2 ). This work provides new constructs for the imitation of complex virus assemblies and for the molecular encapsulation of giant guest molecules.

Blending Donors with Different Molecular Weights: An Efficient Strategy to Resolve the Conflict between Coherence Length and Intermixed Phase in Polymer/Nonfullerene Solar Cells.

Long coherence lengths (CLs) of crystals and proper intermixed phase amount guarantee charge transport and exciton dissociate efficiently, which is crucial for organic solar cells (OSCs) to achieve high device performance. However, extending CLs usually reduces the intermixed phase, leading to an insufficient interface for exciton dissociation. Herein, a strategy using a binary polymer with different molecular weights as donor is employed, that is, poly(3-hexylthiophene-2,5-diyl) (P3HT) with high (P3HT-H) and low (P3HT-L) molecular weight are blended as donor, and (5Z,5'Z)-5,5'-(((4,4,9,9-tetraoctyl-4,9-dihydro-s-indaceno[1,2-b:5,6-b']dithiophene-2,7-diyl)bis(benzo[c][1,2,5]thiadiazole-7,4-diyl))bis(methanylylidene))bis(3-ethyl-2-thioxothiazolidin-4-one) (O-IDTBR) is used as acceptor. In kinetics, the entanglements of P3HT-H are relieved due to the higher molecular diffusivity of P3HT-L. In thermodynamics, the miscibility of P3HT-L/O-IDTBR, P3HT-H/O-IDTBR, and P3HT-L/P3HT-H blends increases in turn. Hence, P3HT forms a more ordered structure with longer CLs after adding P3HT-L, which also drives O-IDTBR dispersed in P3HT crystalline regions diffuse to the O-IDTBR crystalline regions to further self-organize. Consequently, the CLs of both P3HT and O-IDTBR are extended, while keeping the intermixed phase amount proper. The optimized microstructure boosts device performance from 7.03% to 7.80%, which is one of the highest values reported for P3HT/O-IDTBR blends. This is a novel way to solve the conflict mentioned above, which may provide guidance to finely regulating the morphology of the active layer.

Natural alleles of a uridine 5'-diphospho-glucosyltransferase gene responsible for differential endosperm development between upland rice and paddy rice.

Traditional upland rice generally exhibits insufficient grains resulting from abnormal endosperm development compared to paddy rice. However, the underlying molecular mechanism of this trait is poorly understood. Here, we cloned the uridine 5'-diphospho (UDP)-glucosyltransferase gene EDR1 (Endosperm Development in Rice) responsible for differential endosperm development between upland rice and paddy rice by performing quantitative trait loci analysis and map-based cloning. EDR1 was highly expressed in developing seeds during grain filling. Natural variations in EDR1 significantly reduced the UDP-glucosyltransferase activity of EDR1YZN compared to EDR1YD1 , resulting in abnormal endosperm development in the near-isogenic line, accompanied by insufficient grains and changes in grain quality. By analyzing the distribution of the two alleles EDR1YD1 and EDR1YZN among diverse paddy rice and upland rice varieties, we discovered that EDR1 was conserved in upland rice, but segregated in paddy rice. Further analyses of grain chalkiness in the alleles of EDR1YD1 and EDR1YZN varieties indicated that rice varieties harboring EDR1YZN and EDR1YD1 preferentially showed high chalkiness, and low chalkiness, respectively. Taken together, these results suggest that the UDP-glucosyltransferase gene EDR1 is an important determinant controlling differential endosperm development between upland rice and paddy rice.

Survey on natural language processing in medical image analysis. / 自然语言处理在医学影像分析中的应用.

Recent advancement in natural language processing (NLP) and medical imaging empowers the wide applicability of deep learning models. These developments have increased not only data understanding, but also knowledge of state-of-the-art architectures and their real-world potentials. Medical imaging researchers have recognized the limitations of only targeting images, as well as the importance of integrating multimodal inputs into medical image analysis. The lack of comprehensive surveys of the current literature, however, impedes the progress of this domain. Existing research perspectives, as well as the architectures, tasks, datasets, and performance measures examined in the present literature, are reviewed in this work, and we also provide a brief description of possible future directions in the field, aiming to provide researchers and healthcare professionals with a detailed summary of existing academic research and to provide rational insights to facilitate future research.

A systematic review and meta-analysis of effects of spironolactone on blood pressure, glucose, lipids, renal function, fibrosis and inflammation in patients with hypertension and diabetes.

PURPOSE: Hypertension commonly co-exists with diabetes mellitus (DM), and both are closely related to adverse health outcomes. The activation of aldosterone and mineralocorticoid receptor (MR) may play important roles in this process. Therefore, we aim to evaluate the efficacy of MR antagonists on cardiovascular risk factors, including blood pressure (BP), glucose, lipids, renal function, fibrosis and inflammatory and its safety in patients with both hypertension and DM. METHODS: We searched PubMed, Embase, Web of Science and Cochrane databases for clinical trials published until December 31, 2019. Studies comparing the effect of spironolactone to placebo in patients with hypertension and DM were included. Mean difference with 95% confidence intervals was used to report outcomes. RESULTS: Eleven randomised placebo-controlled trials with 640 participants were finally included with mean follow-up of 5 months. Compared to placebo, spironolactone significantly reduced office systolic (-6.57, 95%CI: -9.21, -3.93) and diastolic BP (-2.63, 95%CI: -4.25, -1.02) as well as ambulatory BP; increased glycosylated haemoglobin by 0.3 but no clear effect on fasting glucose. Spironolactone induced a significantly reduction of urinary albumin but increased serum creatinine (7.60, 95%CI: 4.94, 10.27) and decreased glomerular filtration rate (-4.28, 95%CI: -6.38, -2.18). Markers of fibrosis and inflammation, including NIIINP, PICP, hs-CRP and TNF-α were also decreased after spironolactone therapy. For lipid metabolism, there was no significant difference between groups. Spironolactone mildly increased serum potassium (0.30, 95%CI: 0.23, 0.37). 2.5% subjects treated with spironolactone experienced mild to moderate hyperkalaemia and received medication or dietary advice and another 1.6% developed severe hyperkalaemia and withdrawn from the studies. CONCLUSION: Spironolactone reduced BP and urinary albumin, improve fibrosis and inflammation, whereas slightly increases the glycosylated haemoglobin and serum creatinine in patients with hypertension and diabetes. Long-term RCTs to assess the effects of spironolactone on cardiovascular events in this population are warranted.

A wideband tonpilz transducer with a transverse through-hole in the radiating head.

We propose a rectangular transverse through-hole wideband tonpilz transducer using multimode coupling. To excite a vibration mode that can be coupled with the longitudinal vibration for broadening the frequency band, a rectangular through-hole is opened at a certain distance from the front head of the conventional longitudinal vibration tonpilz transducer. To achieve the best bandwidth, the finite element method was used to optimize the length and width of the through-hole and the distance between the front end of the hole and the end surface of the front head. In addition, to obtain the best hole position and size, a prototype tonpilz transducer was developed. The test results show that the transducer has three main operating modes within 12-32.5 kHz, and the latter two modes contribute to the widening of operating bandwidth. A longitudinal vibration tonpilz transducer of the same size with no hole has a 3 dB bandwidth of only 3 kHz, whereas the holed transducer has a bandwidth of 10.5 kHz. Effectively expanding the working bandwidth shows that the theoretical calculations and experimental results are in good agreement.

Fostering green development with green finance: An empirical study on the environmental effect of green credit policy in China.

To direct financial resources to cleaner production enterprises and achieve the goal of environmental governance, the Chinese government has devoted increasing efforts to facilitating green finance. As one of the major policies of green finance, the Green Credit Policy (GCP) was issued in 2012. Evaluating whether the GCP can promote green development has important significance, but few studies have explored its policy effects for the investment and financing behavior of "two high" (high energy consumption and high pollution) enterprises and environmental quality from both micro and macro perspectives. Taking the promulgation of the GCP as a quasi-natural experiment, based on a panel dataset involving 945 A-share listed companies and 30 provinces for the period of 2004-2017, this paper adopts the difference-in-difference model to explore the investment and financing behavior changes of enterprises and environmental impacts of the GCP. The following conclusions are derived. (1) The GCP provides incentives for the short-term financing behavior of "two high" enterprises, but it has a punitive effect in the long term and significantly inhibits the investment behavior of such enterprises. (2) The GCP contributes to the mitigation of sulfur dioxide and wastewater emissions. (3) The GCP has a greater effect on investment and financing behavior among state-owned and large-scale "two high" enterprises than among medium-sized and micro enterprises. (4) There exists regional heterogeneity in the effects of the GCP on the investment and financing of "two high" enterprises and environmental quality. The GCP has positive impacts in the eastern and western regions, and the policy effect is not obvious in the central region.

LMNB2 is a prognostic biomarker and correlated with immune infiltrates in hepatocellular carcinoma.

BACKGROUND: Previous studies have suggested Lamin B2 (LMNB2) as an oncogene in lung cancer. However, the role of LMNB2 in hepatocellular carcinoma (HCC) remains unclear. METHOD: The expression of LMNB2 was compared between HCC samples and non-tumor samples in multiple datasets. In addition, the prognostic value of LMNB2 in HCC was also investigated. Furthermore, the cBioPortal was utilized to analyze the genomic alternation of LMNB2 in HCC. Besides, co-expression genes and functional enrichment analysis were evaluated using LinkedOmics to determine the function of LMNB2. Finally, the correlation between LMNB2 and immune infiltration was assessed using Tumor Immune Estimation Resource (TIMER). RESULTS: Elevated LMNB2 expression level was identified in HCC patients in multiple datasets. Moreover, increased levels of LMNB2 were associated with poor overall survival (OS) and disease-free survival (DFS). The functional enrichment analysis revealed that LMNB2 plays an essential role via the cell cycle pathway, spliceosome, hippo-signaling pathway, and metabolic pathways. Besides, copy number variation (CNV) and methylation were significantly associated with LMNB2 expression. Additionally, increased levels of LMNB2 were significantly associated with B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. CONCLUSION: LMNB2 is a potential HCC prognostic and diagnostic biomarker.

FURIN Inhibition Reduces Vascular Remodeling and Atherosclerotic Lesion Progression in Mice.

Objective- Atherosclerotic coronary artery disease is the leading cause of death worldwide, and current treatment options are insufficient. Using systems-level network cluster analyses on a large coronary artery disease case-control cohort, we previously identified PCSK3 (proprotein convertase subtilisin/kexin family member 3; FURIN) as a member of several coronary artery disease-associated pathways. Thus, our objective is to determine the role of FURIN in atherosclerosis. Approach and Results- In vitro, FURIN inhibitor treatment resulted in reduced monocyte migration and reduced macrophage and vascular endothelial cell inflammatory and cytokine gene expression. In vivo, administration of an irreversible inhibitor of FURIN, α-1-PDX (α1-antitrypsin Portland), to hyperlipidemic Ldlr-/- mice resulted in lower atherosclerotic lesion area and a specific reduction in severe lesions. Significantly lower lesional macrophage and collagen area, as well as systemic inflammatory markers, were observed. MMP2 (matrix metallopeptidase 2), an effector of endothelial function and atherosclerotic lesion progression, and a FURIN substrate was significantly reduced in the aorta of inhibitor-treated mice. To determine FURIN's role in vascular endothelial function, we administered α-1-PDX to Apoe-/- mice harboring a wire injury in the common carotid artery. We observed significantly decreased carotid intimal thickness and lower plaque cellularity, smooth muscle cell, macrophage, and inflammatory marker content, suggesting protection against vascular remodeling. Overexpression of FURIN in this model resulted in a significant 67% increase in intimal plaque thickness, confirming that FURIN levels directly correlate with atherosclerosis. Conclusions- We show that systemic inhibition of FURIN in mice decreases vascular remodeling and atherosclerosis. FURIN-mediated modulation of MMP2 activity may contribute to the atheroprotection observed in these mice.