Pivotal role of reversible NiO6 geometric conversion in oxygen evolution.

Realizing an efficient electron transfer process in the oxygen evolution reaction by modifying the electronic states around the Fermi level is crucial in developing high-performing and robust electrocatalysts1-3. Typically, electron transfer proceeds solely through either a metal redox chemistry (an adsorbate evolution mechanism (AEM), with metal bands around the Fermi level) or an oxygen redox chemistry (a lattice oxygen oxidation mechanism (LOM), with oxygen bands around the Fermi level), without the concurrent occurrence of both metal and oxygen redox chemistries in the same electron transfer pathway1-15. Here we report an electron transfer mechanism that involves a switchable metal and oxygen redox chemistry in nickel-oxyhydroxide-based materials with light as the trigger. In contrast to the traditional AEM and LOM, the proposed light-triggered coupled oxygen evolution mechanism requires the unit cell to undergo reversible geometric conversion between octahedron (NiO6) and square planar (NiO4) to achieve electronic states (around the Fermi level) with alternative metal and oxygen characters throughout the oxygen evolution process. Utilizing this electron transfer pathway can bypass the potential limiting steps, that is, oxygen-oxygen bonding in AEM and deprotonation in LOM1-5,8. As a result, the electrocatalysts that operate through this route show superior activity compared with previously reported electrocatalysts. Thus, it is expected that the proposed light-triggered coupled oxygen evolution mechanism adds a layer of understanding to the oxygen evolution research scene.

Dielectric Environment Sensitivity of Carbon Centers in Hexagonal Boron Nitride.

A key advantage of utilizing van-der-Waals (vdW) materials as defect-hosting platforms for quantum applications is the controllable proximity of the defect to the surface or the substrate allowing for improved light extraction, enhanced coupling with photonic elements, or more sensitive metrology. However, this aspect results in a significant challenge for defect identification and characterization, as the defect's properties depend on the the atomic environment. This study explores how the environment can influence the properties of carbon impurity centers in hexagonal boron nitride (hBN). It compares the optical and electronic properties of such defects between bulk-like and few-layer films, showing alteration of the zero-phonon line energies and their phonon sidebands, and enhancements of inhomogeneous broadenings. To disentangle the mechanisms responsible for these changes, including the atomic structure, electronic wavefunctions, and dielectric screening, it combines ab initio calculations with a quantum-embedding approach. By studying various carbon-based defects embedded in monolayer and bulk hBN, it demonstrates that the dominant effect of the change in the environment is the screening of density-density Coulomb interactions between the defect orbitals. The comparative analysis of experimental and theoretical findings paves the way for improved identification of defects in low-dimensional materials and the development of atomic scale sensors for dielectric environments.

Performance improvement in monolayered SnS2 double-gate field-effect transistors via point defect engineering.

Owing to the relatively high carrier mobility and on/off current ratio, monolayered SnS2 has the advantage of suppressing drain-to-source tunneling for short channels, rendering it a promising candidate in field-effect transistor (FET) applications. To extend the scaling limit of the channel length, we propose to rationally modulate the electronic properties of monolayered SnS2 through the customized design of point defects and simulate its performance limit in sub-5 nm double-gate FETs (DGFETs), using density functional theory combined with nonequilibrium Green's function formalism. Among all types of point defects, the Se atom as a substitutional dopant (SeS) can nondegenerately inject electrons into each monolayered (ML) SnS2 2 × 4 × 1 supercell, whereas the Sn vacancy (VSn) defect exhibits an opposite doping effect. By adjusting the lateral Schottky barrier height between electrodes and the channel region, the on-state current (Ion), on/off ratio, delay time, and power-delay product in the formed n-type SeS-doped SnS2 and p-type VSn-doped SnS2 DGFETs with a channel length of 4.5 nm have been remarkably improved, fulfilling the requirements of the International Technology Roadmap for Semiconductors (ITRS) for high-performance applications in the 2028 horizon. Our work unveils the great significance of point defect engineering for applications in ultimately scaled electronics.

Association Study Between Promoter Polymorphisms of ADAM17 and Progression of Sepsis.

BACKGROUND: A disintegrin and metalloproteinase 17 (ADAM17) has been confirmed to play a significant role in the pathogenesis of sepsis. However, little is known about the clinical relevance of ADAM17 polymorphisms to sepsis onset and development. METHODS: This study analyzed the associations of five ADAM17 promoter polymorphisms (rs55790676, rs12692386, rs11684747, rs1524668 and rs11689958) with sepsis (370 sepsis cases and 400 controls). Genotyping was performed using pyrosequencing and polymerase chain reaction-length polymorphism method. The ADAM17 expression was measured using the real-time PCR method and the concentrations of related cytokines were detected using enzyme-linked immunosorbent assay. RESULTS: No associations were observed between these polymorphisms and sepsis susceptibility, while the rs12692386GA/GG genotypes were overrepresented among the patients with severe sepsis (P=0.002) or septic shock (P=0.0147) compared to those with sepsis subtype, suggesting a susceptible role of rs12692386A>G in the progression of sepsis. Moreover, ADAM17 expression was increased in the sepsis patients with the rs12692386GA/GG genotypes, accompanied by up-regulation of expression of the ADAM17 substrates (TNF-α, IL-6R and CX3CL1) and pro-inflammatory cytokines (IL-1ß and IL-6). CONCLUSION: The present study has provided potentially valuable clinical evidence that the ADAM17 rs12692386 polymorphism is a functional variant that might be used as a relevant risk estimate for the progression of sepsis.

Molecular dynamics investigation on synthesis of a pH- and temperature-sensitive carbon nanotube loaded with doxorubicin.

The many exotic properties of carbon nanotubes (CNTs) make them a powerful attraction in the field of drug delivery systems (DDS). In this work, based on quantum chemical calculation and molecular simulation techniques, polyacrylic acid (PAA) and N-isopropyl acrylamide (NIP) are selected and acted simultaneously on the CNT to form a stable system (FCNT). As a potential DDS, FCNT captures the dispersed doxorubicin (DOX) molecules around it and maintains a stable configuration. In these processes, electrostatic and van der Waals forces act synergistically, with van der Waals forces dominating. Compared to NIP, PAA molecules exhibit stronger adhesion and encapsulation efficiency to CNT and stronger adsorption capacity to DOX. This study reveals the mechanism of action among PAA, NIP, CNT, and DOX, providing feasibility verification and prospective guidance for the experimental synthesis of PAA-NIP-CNT-type multifunctional DDS, and also broadening the idea for exploring more efficient DDS suitable for DOX.

Beyond Conventional Charge Density Wave for Strongly Enhanced 2D Superconductivity in 1H-TaS2 Superlattices.

Noncentrosymmetric transition metal dichalcogenide (TMD) monolayers offer a fertile platform for exploring unconventional Ising superconductivity (SC) and charge density waves (CDWs). However, the vulnerability of isolated monolayers to structural disorder and environmental oxidation often degrade their electronic coherence. Herein, an alternative approach is reported for fabricating stable and intrinsic monolayers of 1H-TaS2 sandwiched between SnS blocks in a (SnS)1.15TaS2 van der Waals (vdW) superlattice. The SnS block layers not only decouple individual 1H-TaS2 sublayers to endow them with monolayer-like electronic characteristics, but also protect the 1H-TaS2 layers from electronic degradation. The results reveal the characteristic 3 × 3 CDW order in 1H-TaS2 sublayers associated with electronic rearrangement in the low-lying sulfur p band, which uncovers a previously undiscovered CDW mechanism rather than the conventional Fermi surface-related framework. Additionally, the (SnS)1.15TaS2 superlattice exhibits a strongly enhanced Ising-like SC with a layer-independent Tc of ≈3.0 K, comparable to that of the isolated monolayer 1H-TaS2 sample, presumably attributed to their monolayer-like characteristics and retained Fermi states. These results provide new insights into the long-debated CDW order and enhanced SC of monolayer 1H-TaS2, establishing bulk vdW superlattices as promising platforms for investigating exotic collective quantum phases in the 2D limit.

Unveiling the destabilization of sp3 and sp2 bonds in transition metal-modified borohydrides to improve reversible dehydrogenation and rehydrogenation.

Borohydrides offer promise as potential carriers for hydrogen storage due to their high hydrogen concentration. However, the strong chemical bonding within borohydrides poses challenges for efficient hydrogen release during usage and restricts the re-hydrogenation process when attempting to regenerate the material. These high thermodynamic and kinetic barriers present obstacles in achieving reversible de-hydrogenation and re-hydrogenation of borohydrides, impeding their practical application in hydrogen storage systems. Employing density functional theory calculations, we conduct a comprehensive investigation into the influence of transition metals on both the BH4 cluster, a fundamental building block of borohydrides, and pure boron, which is formed as the end product following hydrogen release. Our research reveals correlations among the d-band center, work function, and surface energy of 3d and 4d transition metals. These correlations are directly linked to the weakening of bonding within the BH4 cluster when adsorbed on catalyst surfaces. On the other hand, we also explore how various intrinsic properties of transition metals influence the formation of boron vacancies and the hydrogen bonding process. By establishing a comprehensive correlation between the weakening of sp3 hybridization in the BH4 cluster and the sp2 hybridization in boron, we facilitate the identification and screening of optimal candidates capable of achieving reversible de-hydrogenation and re-hydrogenation in borohydrides.

Study on crystal growth of Ge/Si quantum dots at different Ge deposition by using magnetron sputtering technique.

We investigated the growth and evolution of Si-based Ge quantum dots (Ge/Si QDs) under low Ge deposition (1.2-4.4 nm thick) using magnetron sputtering. The morphology and structure of QDs were analyzed with the help of an atomic force microscope (AFM), scanning electron microscope, transmission electron microscope, Raman, surface energy theory and dynamics theory, the photoelectric properties of QDs were characterized by photoluminescence (PL) spectra. The results showed that the growth mechanism of QDs conformed to Stranski-Krastanow mode, but the typical thickness of the wetting layer was nearly three times higher than those derived from conventional technologies such as molecular beam epitaxy, chemical vapor deposition, solid phase epitaxy and so on. Meanwhile, the shape evolution of QDs was very different from existing reports. The specific internal causes of these novel phenomena were analyzed and confirmed and reported in this paper. In addition, the AFM, Raman, and PL tests all indicated that the QDs grown when 3.4 nm Ge was deposited have the most excellent morphology, structure, and optoelectronic performance. Our work lays a foundation for further exploration of the controllable growth of QDs at high deposition rates, which is a new way to realize the industrialization of QDs used for future devices.

N-Octadecane Encapsulated by Assembled BN/GO Aerogels for Highly Improved Thermal Conductivity and Energy Storage Capacity.

The rapid development of industry has emphasized the importance of phase change materials (PCMs) with a high latent-heat storage capacity and good thermal stability in promoting sustainable energy solutions. However, the inherent low thermal conductivity and poor thermal-cycling stability of PCMs limit their application. In this study, we constructed three-dimensional (3D) hybrid graphene aerogels (GBA) based on synergistic assembly and cross-linking between GO and modified hexagonal boron nitride (h-BN). Highly thermally conductive GBA was utilized as the supporting optimal matrix for encapsulating OD, and further implied that composite matrix n-octadecane (OD)/GBA composite PCMs were further prepared by encapsulating OD within the GBA structure. Due to the highly thermally conductive network of GBA, the latent heat of the composite PCMs improved to 208.3 J/g, with negligible changes after 100 thermal cycles. In addition, the thermal conductivity of the composite PCMs was significantly enhanced to 1.444 W/(m·k), increasing by 738% compared to OD. These results sufficiently confirmed that the novel GBA with a well-defined porous structure served as PCMs with excellent comprehensive performance offer great potential for thermal energy storage applications.

One-step thermal polymerization synthesis of nitrogen-rich g-C3N4 nanosheets enhances photocatalytic redox activity.

Graphitic carbon nitride (g-C3N4) has attracted enormous attention as a visible-light-responsive carbon-based semiconductor photocatalyst. However, fast charge recombination seriously limits its application. Therefore, it is urgent to modify the electronic structure of g-C3N4 to obtain excellent photocatalytic activity. Herein, we reported a one-step thermal polymerization synthesis of nitrogen-rich g-C3N4 nanosheets. Benefiting from the N self-doping and the ultrathin structure, the optimal CN-70 exhibits its excellent performance. A 6.7 times increased degradation rate of rhodamine B (K = 0.06274 min-1), furthermore, the hydrogen evolution efficiency also reached 2326.24 µmol h-1 g-1 (λ > 420 nm). Based on a series of characterizations and DFT calculations, we demonstrated that the N self-doping g-C3N4 can significantly introduce midgap states between the valence band and conduction band, which is more conducive to the efficient separation of photogenerated carriers. Our work provides a facile and efficient method for self-atom doping into g-C3N4, providing a new pathway for efficient photocatalysts.

Cadmium Sulfide-Reinforced Double-Shell Microencapsulated Phase Change Materials for Advanced Thermal Energy Storage.

Phase change materials (PCMs) are widely used to improve energy utilization efficiency due to their high energy storage capacity. In this study, double-shell microencapsulated PCMs were constructed to resolve the liquid leakage issue and low thermal conductivity of organic PCMs, which also possess high thermal stability and multifunctionality. We used assembly to construct an inorganic-organic double shell for microencapsulate PCMs, which possessed the unprecedented synergetic properties of a cadmium sulfide (CdS) shell and melamine-formaldehyde polymeric shell. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images confirmed the well-designed double-shell structure of the microcapsules, and the CdS was successfully assembled as the second shell on the surface of the polymer shell. The differential scanning calorimeter (DSC) showed that the double-shell microcapsules had a high enthalpy of 114.58 J/g, which indicated almost no changes after experiencing 100 thermal cycles, indicating good thermal reliability. The microcapsules also showed good shape stability and antileakage performance, which displayed no shape change and leakage after heating at 60 °C for 30 min. In addition, the photothermal conversion efficiency of the double-shell microcapsules reached 91.3%. Thus, this study may promote the development of microencapsulated PCMs with multifunctionality, offering considerable application prospects in intelligent temperature management for smart textiles and wearable electronic devices in combination with their solar thermal energy conversion and storage performance.

Catalytic Hydrogen Evolution of NaBH4 Hydrolysis by Cobalt Nanoparticles Supported on Bagasse-Derived Porous Carbon.

As a promising hydrogen storage material, sodium borohydride (NaBH4) exhibits superior stability in alkaline solutions and delivers 10.8 wt.% theoretical hydrogen storage capacity. Nevertheless, its hydrolysis reaction at room temperature must be activated and accelerated by adding an effective catalyst. In this study, we synthesize Co nanoparticles supported on bagasse-derived porous carbon (Co@xPC) for catalytic hydrolytic dehydrogenation of NaBH4. According to the experimental results, Co nanoparticles with uniform particle size and high dispersion are successfully supported on porous carbon to achieve a Co@150PC catalyst. It exhibits particularly high activity of hydrogen generation with the optimal hydrogen production rate of 11086.4 mLH2∙min-1∙gCo-1 and low activation energy (Ea) of 31.25 kJ mol-1. The calculation results based on density functional theory (DFT) indicate that the Co@xPC structure is conducive to the dissociation of [BH4]-, which effectively enhances the hydrolysis efficiency of NaBH4. Moreover, Co@150PC presents an excellent durability, retaining 72.0% of the initial catalyst activity after 15 cycling tests. Moreover, we also explored the degradation mechanism of catalyst performance.

Multielement Synergetic Effect of Boron Nitride and Multiwalled Carbon Nanotubes for the Fabrication of Novel Shape-Stabilized Phase-Change Composites with Enhanced Thermal Conductivity.

Shape-stabilized phase-change composites (SSPCCs) have been widely applied for thermal energy storage and thermal management because of their excellent properties. To further improve their thermal conductivity and thermal cycling stability, we successfully designed and synthesized a series of SSPCCs with three-dimensional (3D) thermally conductive networks by exploiting the synergistic effect between one-dimensional (1D) carbon nanotubes (CNTs) and two-dimensional (2D) hexagonal boron nitride (h-BN). The interconnected thermally conductive network composed of h-BN and multiwalled carbon nanotubes (MWCNTs) enhanced the SSPCC performance. The micromorphologies of the prepared SSPCCs revealed that well-dispersed MWCNTs, hydroxylated h-BN, and polyethylene glycol (PEG) molecular chains effectively bonded into a 3D cross-linking structure of the SSPCCs. Moreover, the chemical and crystalline structural and thermal properties and thermal cycling stability of the novel SSPCCs were systematically investigated by various characterization techniques. The presence of a 3D thermally conductive network in the as-synthesized SSPCCs evidently improved the shape stability, phase-change behavior, and thermal stability. Benefiting from the 3D nanostructural uniqueness of SSPCCs, the thermal conductivity of SSPCC-2 was up to 1.15 W m-1 K-1, which represented a significant enhancement of 239.7% compared with that of pure PEG. Meanwhile, the efficient synergistic effect of h-BN and MWCNTs remarkably enhanced the heat-transfer rate of the SSPCCs. These results demonstrate that the prepared SSPCCs have potential for applications in thermal energy storage and thermal management systems. This study opens a new avenue toward the development of SSPCCs with good comprehensive properties.

Hydrolytic dehydrogenation of NH3BH3 catalyzed by ruthenium nanoparticles supported on magnesium-aluminum layered double-hydroxides.

Ammonia borane (AB, NH3BH3) with extremely high hydrogen content (19.6 wt%) is considered to be one of the most promising chemical hydrides for storing hydrogen. According to the starting materials of AB and H2O, a hydrogen capacity of 7.8 wt% is achieved for the AB hydrolytic dehydrogenation system with the presence of a highly efficient catalyst. In this work, ruthenium nanoparticles supported on magnesium-aluminum layered double hydroxides (Ru/MgAl-LDHs) were successfully synthesized via a simple method, i.e., chemical reduction. The effect of Mg/Al molar ratios in MgAl-LDHs on the catalytic performance for AB hydrolytic dehydrogenation was systematically investigated. Catalyzed by the as-synthesized Ru/Mg1Al1-LDHs catalyst, it took about 130 s at room temperature to complete the hydrolysis reaction of AB, which achieved a rate of hydrogen production of about 740 ml s-1 g-1. Furthermore, a relatively high activity (TOF = 137.1 molH2 molRu -1 min-1), low activation energy (E a = 30.8 kJ mol-1) and fairly good recyclability of the Ru/Mg1Al1-LDHs catalyst in ten cycles were achieved toward AB hydrolysis for hydrogen generation. More importantly, the mechanism of AB hydrolysis catalyzed by Ru/MgAl-LDHs was simulated via density functional theory. The facile preparation and high catalytic performance of Ru/MgAl-LDHs make it an efficient catalyst for hydrolytic dehydrogenation of AB.

Materializing efficient methanol oxidation via electron delocalization in nickel hydroxide nanoribbon.

Achieving a functional and durable non-platinum group metal-based methanol oxidation catalyst is critical for a cost-effective direct methanol fuel cell. While Ni(OH)2 has been widely studied as methanol oxidation catalyst, the initial process of oxidizing Ni(OH)2 to NiOOH requires a high potential of 1.35 V vs. RHE. Such potential would be impractical since the theoretical potential of the cathodic oxygen reduction reaction is at 1.23 V. Here we show that a four-coordinated nickel atom is able to form charge-transfer orbitals through delocalization of electrons near the Fermi energy level. As such, our previously reported periodically arranged four-six-coordinated nickel hydroxide nanoribbon structure (NR-Ni(OH)2) is able to show remarkable methanol oxidation activity with an onset potential of 0.55 V vs. RHE and suggests the operability in direct methanol fuel cell configuration. Thus, this strategy offers a gateway towards the development of high performance and durable non-platinum direct methanol fuel cell.

A modified 'skeleton/skin' strategy for designing CoNiP nanosheets arrayed on graphene foam for on/off switching of NaBH4 hydrolysis.

CoNiP nanosheet array catalysts were successfully prepared on three-dimensional (3D) graphene foam using hydrothermal synthesis. These catalysts were prepared using 3D Ni-graphene foam (Ni/GF), comprising nickel foam as the 'skeleton' and reduced graphene oxide as the 'skin'. This unique continuous modified 'skeleton/skin' structure ensure that the catalysts had a large surface area, excellent conductivity, and sufficient surface functional groups, which promoted in situ CoNiP growth, while also optimizing the hydrolysis of sodium borohydride. The nanosheet arrays were fully characterized and showed excellent catalytic performance, as supported by density functional theory calculations. The hydrogen generation rate and activation energy are 6681.34 mL min-1 g-1 and 31.2 kJ mol-1, respectively, outperforming most reported cobalt-based catalysts and other precious metal catalysts. Furthermore, the stability of mockstrawberry-like CoNiP catalyst was investigated, with 74.9% of the initial hydrogen generation rate remaining after 15 cycles. The catalytic properties, durability, and stability of the catalyst were better than those of other catalysts reported previously.

Roles of NUCKS1 in Diseases: Susceptibility, Potential Biomarker, and Regulatory Mechanisms.

Nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) is a 27 kD chromosomal, highly conserved, and vertebrate-specific protein. NUCKS1 gene encodes a nuclear protein and the conserved regions of NUCKS1 contain several consensus phosphorylation sites for casein kinase II (CK2) and cyclin-dependent kinases (Cdk) and a basic DNA-binding domain. NUCKS1 is similar to the high mobility group (HMG) family which dominates chromatin remodeling and regulates gene transcription. Meanwhile, NUCKS1 is a RAD51 associated protein 1 (RAD51AP1) paralog that is significant for homologous recombination (HR) and genome stability and also a transcriptional regulator of the insulin signaling components. NUCKS1 plays an important role in DNA damage response and metabolism, participates in inflammatory immune response, and correlates with microRNA. Although there is still not enough functional information on NUCKS1, evidences suggest that NUCKS1 can be used as the biomarker of several cancers. This review summarizes the latest research on NUCKS1 about its susceptibility in diseases, expression levels, and regulatory mechanisms as well as the possible functions in reference to diseases.

The Gut Microbiota and Alzheimer's Disease.

The gut microbiota comprises a complex community of microorganism species that resides in our gastrointestinal ecosystem and whose alterations influence not only various gut disorders but also central nervous system disorders such as Alzheimer's disease (AD). AD, the most common form of dementia, is a neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-ß peptides (Aß). Most notably, the microbiota-gut-brain axis is a bidirectional communication system that is not fully understood, but includes neural, immune, endocrine, and metabolic pathways. Studies in germ-free animals and in animals exposed to pathogenic microbial infections, antibiotics, probiotics, or fecal microbiota transplantation suggest a role for the gut microbiota in host cognition or AD-related pathogenesis. The increased permeability of the gut and blood-brain barrier induced by microbiota dysbiosis may mediate or affect AD pathogenesis and other neurodegenerative disorders, especially those associated with aging. In addition, bacteria populating the gut microbiota can secrete large amounts of amyloids and lipopolysaccharides, which might contribute to the modulation of signaling pathways and the production of proinflammatory cytokines associated with the pathogenesis of AD. Moreover, imbalances in the gut microbiota can induce inflammation that is associated with the pathogenesis of obesity, type 2 diabetes mellitus, and AD. The purpose of this review is to summarize and discuss the current findings that may elucidate the role of the gut microbiota in the development of AD. Understanding the underlying mechanisms may provide new insights into novel therapeutic strategies for AD.

Association study of MCP-1 promoter polymorphisms with the susceptibility and progression of sepsis.

Previous studies have indicated that the monocyte chemo-attractant protein 1 (MCP-1), also referred to as C-C motif chemokine ligand 2 (CCL2), plays a significant role in the pathogenesis of sepsis, and this study investigated the clinical relevance of two MCP-1 gene polymorphisms on sepsis onset and progression. The Multiplex SNaPshot genotyping method was used to detect MCP-1 gene polymorphisms in the Chinese Han population (403 sepsis patients and 400 controls). MCP-1 mRNA expression levels were measured using real-time quantitative PCR, and enzyme-linked immunosorbent assays were used to analyze MCP-1, tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and interleukin-1 beta (IL-1ß) plasma concentrations. The rs1024611 polymorphism analysis showed lower frequencies of minor homozygous genotype (AA) and allele (A) in sepsis patients compared to the healthy controls (19.4% vs. 31.5%, P = 0.0001 and 45.9% vs. 54.8%, P = 0.0004, respectively). And the frequencies of GG genotype and G allele were lower in sepsis patients compared to the controls (19.6% vs. 31.3%, P = 0.0002 and 46.0% vs. 54.5%, P = 0.0007, respectively). The rs1024611 AG/GG and rs2857656 GC/CC genotypes were both overrepresented in patients with severe sepsis (both P = 0.0005) and septic shock (P = 0.010 and P = 0.015, respectively) compared to the patients with mild sepsis. Moreover, among sepsis patients, the rs1024611 AG/GG and rs2857656 GC/CC carriers exhibited significant increases in expression levels of MCP-1 (P = 0.025), TNF-α (P = 0.034) and IL-6 (P = 0.043) compared with the rs1024611 AA or rs2857656 GG carriers. This study provides valuable clinical evidence that the MCP-1/CCL2 polymorphisms rs1024611 and rs2857656 are associated with sepsis susceptibility and development. We conclude that MCP-1/CCL2 plays a significant role in the pathogenesis of sepsis, which has potentially important therapeutic implications.

The influence of two functional genetic variants of GRK5 on tau phosphorylation and their association with Alzheimer's disease risk.

Our work explores the relationship between G protein-coupled receptor kinase-5 (GRK5) single nucleotide polymorphisms and Alzheimer's disease risk. We confirmed that GRK5 translocates from the cellular membrane to the cytosol in the hippocampus of Alzheimer's disease mice and that GRK5 deficiency promotes tau hyperphosphorylation, a hallmark of Alzheimer's disease pathology. Our results indicate that one functional variant, or mutant, of GRK5 (GRK5-Gln41Leu) decreased GRK5 translocation from the membrane to the cytoplasm and reduced tau hyperphosphorylation, whereas, another GRK5 mutant (GRK5-Arg304His) increased GRK5 translocation to the cytoplasm and promoted tau hyperphosphorylation. In addition, case-control studies revealed that GRK5-Gln41Leu is associated with a lower risk of late-onset Alzheimer's disease. Our findings suggest that the GRK5-Gln41Leu mutant may resist tau hyperphosphorylation by promoting GRK5 membrane stability and, in effect, may contribute to lower Alzheimer's disease risk.