Novel Tet(L) Efflux Pump Variants Conferring Resistance to Tigecycline and Eravacycline in Staphylococcus Spp.

Tigecycline is regarded as one of the few important last-resort antibiotics to treat complicated skin and intra-abdominal infections. Members of the genus Staphylococcus are zoonotic pathogens and pose a serious threat to public health. Tigecycline resistance in this species appears to be a rare phenomenon, and the mechanisms underlying tigecycline resistance have not been fully elucidated. Here, we report two novel variants of the tet(L) gene in Staphylococcus spp. from swine in China, designed as tet(L)F58L and tet(L)A117V. The tet(L)F58L was located within a 18,720 bp chromosomal multidrug resistance gene cluster flanked by two copies of IS257 in Staphylococcus cohnii 11-B-312, while the tet(L)A117V was located on a 6,292 bp plasmid in S. haemolyticus 11-B-93, which could be transferred to S. aureus by electrotransformation. Cloning of each of the two tet(L) variants into S. aureus RN4220 showed 16- or 8-fold increases in the minimal inhibition concentrations (MICs), which can fully confer the resistance to tigecycline (MICs from 0.125 to 2 mg/liter) and eravacycline (MICs from 0.125 to 1 or 2 mg/liter), but no increase in the MICs of omadacycline, compared with the MICs of the recipient strain S. aureus RN4220. In the in vivo murine sepsis and in the murine pneumonia models, an increase in CFU of S. aureus 29213_pT93 carrying the tet(L)A117V was seen despite tigecycline treatment. This observation suggests that the tet(L)A117V and its associated gene product compromise the efficacy of tigecycline treatment in vivo and may lead to clinical treatment failure. Our finding, that novel Tet(L) efflux pump variants which confer tigecycline and eravacycline resistance have been identified in Staphylococcus spp., requires urgent attention. IMPORTANCE Tigecycline and eravacycline are both important last-resort broad spectrum antimicrobial agents. The presence of novel Tet(L) efflux pump variants conferring the resistance to tigecycline and eravacycline in Staphylococcus spp. and its potential transmission to S. aureus will compromise the efficacy of tigecycline and eravacycline treatment for S. aureus associated infection in vivo and may lead to clinical treatment failure

The OX40/OX40L Axis Regulates T Follicular Helper Cell Differentiation: Implications for Autoimmune Diseases

T Follicular helper (Tfh) cells, a unique subset of CD4+ T cells, play an essential role in B cell development and the formation of germinal centers (GCs). Tfh differentiation depends on various factors including cytokines, transcription factors and multiple costimulatory molecules. Given that OX40 signaling is critical for costimulating T cell activation and function, its roles in regulating Tfh cells have attracted widespread attention. Recent data have shown that OX40/OX40L signaling can not only promote Tfh cell differentiation and maintain cell survival, but also enhance the helper function of Tfh for B cells. Moreover, upregulated OX40 signaling is related to abnormal Tfh activity that causes autoimmune diseases. This review describes the roles of OX40/OX40L in Tfh biology, including the mechanisms by which OX40 signaling regulates Tfh cell differentiation and functions, and their close relationship with autoimmune diseases

InstructBrush: Learning Attention-based Instruction Optimization for Image Editing

In recent years, instruction-based image editing methods have garnered significant attention in image editing. However, despite encompassing a wide range of editing priors, these methods are helpless when handling editing tasks that are challenging to accurately describe through language. We propose InstructBrush, an inversion method for instruction-based image editing methods to bridge this gap. It extracts editing effects from exemplar image pairs as editing instructions, which are further applied for image editing. Two key techniques are introduced into InstructBrush, Attention-based Instruction Optimization and Transformation-oriented Instruction Initialization, to address the limitations of the previous method in terms of inversion effects and instruction generalization. To explore the ability of instruction inversion methods to guide image editing in open scenarios, we establish a TransformationOriented Paired Benchmark (TOP-Bench), which contains a rich set of scenes and editing types. The creation of this benchmark paves the way for further exploration of instruction inversion. Quantitatively and qualitatively, our approach achieves superior performance in editing and is more semantically consistent with the target editing effects.Comment: Project Page: https://royzhao926.github.io/InstructBrush

Comparison of housing facility management between mainland China and Taiwan region

Recently, mainland China has experienced the fastest urbanization in the world; however, the development of structural regulations regarding facility management (FM) services for housing is relatively recessive. As a result, disputes and conflicts in facility management of the private housing sector have become a serious problem in urban communities, affecting social sustainable development of the building industry. Comparatively, the private housing FM system in the urban areas in the Taiwan region was developed much earlier; thus, it is more advanced and mature than that in mainland China. This paper intends to compare the FM sectors between the two regions to provide suggestions for improving the service quality of the FM system in mainland China.Natural Science Foundation of Shandong (Grant No. ZR2013GQ014) and Independent Innovation Foundation of Shandong University (Grant No. IFW12108; IFW12065).http://ascelibrary.org/journal/jpcfevhb2016Graduate School of Technology Management (GSTM

Macro-meso mechanical properties of gas hydrate bearing coal under triaxial compression with flexible boundary condition

To explore the influence of confining pressure on the macro-meso mechanical characteristics of gas hydrate bearing coal (GHBC) under different boundary conditions, the biaxial discrete element tests were carried out subjected to the confining pressures of 12，16 and 20 MPa for GHBC with saturation of 80%. Firstly, the biaxial numerical models of GHBC were established for flexible and rigid boundaries, using the linear model of the rolling resistance and the parallel bonding model. These numerical models incorporated the influences of particle shape effect, the hydrate cementation and the heat-shrinkable pipe. Then, the reliability of the numerical model was verified, by comparing with the indoor test results (stress-strain curves, bulk strain curves, internal friction angle cohesion and specimen failure modes). It is found that the flexible boundary can better reflect the deviatoric, stress-axial strain, the shear expansion and the strength characteristics of the sample. Based on the established numerical model, the roles of the confining pressure and the boundary condition on the macro-meso mechanical properties of GHBC were clarified from the perspectives of the internal displacement field, the mean mechanical coordination number, the mean porosity, the contact force chain and the hydrate bond failure. The results show that: ① with the increase of confining pressure, the numerical sample with the rigid boundary mostly exhibits the single inclined plane shear failure, while that with the flexible boundary varies from the single fork shear failure to the single inclined plane shear failure. ② With the increase of confining pressure, for the two boundaries, the mean mechanical coordination numbers increase and the mean porosity decrease, leading to a denser and higher strength of the sample. ③ With the increase of confining pressure, the normal contact force between particles continues to increase, and the sample strength increases. The normal contact force distributed near the axial direction increases, while that near the horizontal direction varies weakly. The higher the confining pressure is, the more difference between the vertical and the horizontal normal contact forces have, the more prominent the anisotropy is. The normal contact force increases by 54.50%, at the flexible boundary, and increases by 45.70%, at the peak strength point, with the confining pressure increasing from 12 MPa to 20 MPa. ④ Under different confining pressures and boundary conditions, the samples fail with two different failure modes, tensile and shear. The samples mainly crack from the shear between the hydrate and coal. The research results reveal the mechanism of the influence of confining pressure on the strength deformation and failure of GHBC on the mesoscale

Recent Progress in Graphene-Based Electrocatalysts for Hydrogen Evolution Reaction

Hydrogen is regarded as a key renewable energy source to meet future energy demands. Moreover, graphene and its derivatives have many advantages, including high electronic conductivity, controllable morphology, and eco-friendliness, etc., which show great promise for electrocatalytic splitting of water to produce hydrogen. This review article highlights recent advances in the synthesis and the applications of graphene-based supported electrocatalysts in hydrogen evolution reaction (HER). Herein, powder-based and self-supporting three-dimensional (3D) electrocatalysts with doped or undoped heteroatom graphene are highlighted. Quantum dot catalysts such as carbon quantum dots, graphene quantum dots, and fullerenes are also included. Different strategies to tune and improve the structural properties and performance of HER electrocatalysts by defect engineering through synthetic approaches are discussed. The relationship between each graphene-based HER electrocatalyst is highlighted. Apart from HER electrocatalysis, the latest advances in water electrolysis by bifunctional oxygen evolution reaction (OER) and HER performed by multi-doped graphene-based electrocatalysts are also considered. This comprehensive review identifies rational strategies to direct the design and synthesis of high-performance graphene-based electrocatalysts for green and sustainable applications

The Role of Type 2 Innate Lymphoid Cells in Allergic Diseases

Allergic diseases are significant diseases that affect many patients worldwide. In the past few decades, the incidence of allergic diseases has increased significantly due to environmental changes and social development, which has posed a substantial public health burden and even led to premature death. The understanding of the mechanism underlying allergic diseases has been substantially advanced, and the occurrence of allergic diseases and changes in the immune system state are known to be correlated. With the identification and in-depth understanding of innate lymphoid cells, researchers have gradually revealed that type 2 innate lymphoid cells (ILC2s) play important roles in many allergic diseases. However, our current studies of ILC2s are limited, and their status in allergic diseases remains unclear. This article provides an overview of the common phenotypes and activation pathways of ILC2s in different allergic diseases as well as potential research directions to improve the understanding of their roles in different allergic diseases and ultimately find new treatments for these diseases

Topologically convergent and divergent morphological gray matter networks in early-stage Parkinson's disease with and without mild cognitive impairment

Patients with Parkinson's disease with mild cognitive impairment (PD‐M) progress to dementia more frequently than those with normal cognition (PD‐N), but the underlying neurobiology remains unclear. This study aimed to define the specific morphological brain network alterations in PD‐M, and explore their potential diagnostic value. Twenty‐four PD‐M patients, 17 PD‐N patients, and 29 healthy controls (HC) underwent a structural MRI scan. Similarity between interregional gray matter volume distributions was used to construct individual morphological brain networks. These were analyzed using graph theory and network‐based statistics (NBS), and their relationship to neuropsychological tests was assessed. Support vector machine (SVM) was used to perform individual classification. Globally, compared with HC, PD‐M showed increased local efficiency (p = .001) in their morphological networks, while PD‐N showed decreased normalized path length (p = .008). Locally, similar nodal deficits were found in the rectus and lingual gyrus, and cerebellum of both PD groups relative to HC; additionally in PD‐M nodal deficits involved several frontal and parietal regions, correlated with cognitive scores. NBS found that similar connections were involved in the default mode and cerebellar networks of both PD groups (to a greater extent in PD‐M), while PD‐M, but not PD‐N, showed altered connections involving the frontoparietal network. Using connections identified by NBS, SVM allowed discrimination with high accuracy between PD‐N and HC (90%), PD‐M and HC (85%), and between the two PD groups (65%). These results suggest that default mode and cerebellar disruption characterizes PD, more so in PD‐M, whereas frontoparietal disruption has diagnostic potential

Refining the relationship between gut microbiota and common hematologic malignancies: insights from a bidirectional Mendelian randomization study

BackgroundThe relationship between gut microbiota and hematologic malignancies has attracted considerable attention. As research progresses, it has become increasingly clear that the composition of gut microbiota may influence the onset and progression of hematologic malignancies. However, our understanding of this association remains limited.MethodsIn our study, we classified gut microbiota into five groups based on information at the phylum, class, order, family, and genus levels. Subsequently, we obtained data related to common hematologic malignancies from the IEU Open GWAS project. We then employed a bidirectional Mendelian Randomization (MR) approach to determine whether there is a causal relationship between gut microbiota and hematologic malignancies. Additionally, we conducted bidirectional MR analyses to ascertain the directionality of this causal relationship.ResultsThrough forward and reverse MR analyses, we found the risk of lymphoid leukemia was significantly associated with the abundance of phylum Cyanobacteria, order Methanobacteriales, class Methanobacteria, family Peptococcaceae, family Methanobacteriaceae, and genera Lachnospiraceae UCG010, Methanobrevibacter, Eubacterium brachy group, and Butyrivibrio. The risk of myeloid leukemia was significantly associated with the abundance of phylum Actinobacteria, phylum Firmicutes, order Bifidobacteriales, order Clostridiales, class Actinobacteria, class Gammaproteobacteria, class Clostridia, family Bifidobacteriaceae, and genera Fusicatenibacter, Eubacterium hallii group, Blautia, Collinsella, Ruminococcus gauvreauii group, and Bifidobacterium. The risk of Hodgkin lymphoma was significantly associated with the abundance of family Clostridiales vadinBB60 group, genus Peptococcus, and genus Ruminococcaceae UCG010. The risk of malignant plasma cell tumor was significantly associated with the abundance of genera Romboutsia and Eubacterium rectale group. The risk of diffuse large B-cell lymphoma was significantly associated with the abundance of genera Erysipelatoclostridium and Eubacterium coprostanoligenes group. The risk of mature T/NK cell lymphomas was significantly associated with the abundance of phylum Verrucomicrobia, genus Ruminococcaceae UCG013, genus Lachnoclostridium, and genus Eubacterium rectale group. Lastly, the risk of myeloproliferative neoplasms was significantly associated with the abundance of genus Coprococcus 3 and Eubacterium hallii group.ConclusionOur study provided new evidence for the causal relationship between gut microbiota and hematologic malignancies, offering novel insights and approaches for the prevention and treatment of these tumors