A Case Report of Infection After Lumbar Spinal Fixation and Fusion.

(MC) is an aerobic Gram-negative cocci known to cause respiratory tract infections in humans as an opportunistic pathogen, with infections in other body parts being rare. This case involves an elderly female patient with a medical history of hypertension, type 2 diabetes, coronary heart disease, and osteoporosis. Following coronary angiography and lumbar spine surgery prompted by lower back and left lower limb pain, the patient developed persistent pus discharge from the lumbar spine wound post-surgery, which did not respond to conventional anti-infection therapy, leading to her transfer to our hospital.

RBPWorld for exploring functions and disease associations of RNA-binding proteins across species.

RNA-binding proteins (RBPs) play key roles in a wide range of physiological and pathological processes. To facilitate the investigation of RBP functions and disease associations, we updated the EuRBPDB and renamed it as RBPWorld (http://research.gzsys.

Discovery of novel 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives as potent carbonic anhydrase IX inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer.

A novel series of 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives were designed and synthesized as carbonic anhydrase IX (CA IX) inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer (TNBC). The representative compound 9o exhibited more potent inhibitory activity and selective against CA IX over off-target CA II, compared with positive control SLC-0111. Molecular docking study was also performed to gain insights into the binding interactions of 9o in the binding pocket of CAIX.

Climate and soil stressed elevation patterns of plant species to determine the aboveground biomass distributions in a valley-type Savanna.

Introduction: Extreme environments such as prolonged high temperatures and droughts can cause vulnerability of vegetation ecosystems. The dry-hot valleys of Southwestern China, known for their extremely high annual temperature, lack of water, and unique non-zonal "hot island" habitat in the global temperate zone, provide exceptional sites for studying how plant adapts to the prolonged dry and hot environment. However, the specific local biotic-environment relationships in these regions remain incompletely elucidated.

Synthesis and Biological Evaluation of Novel 2-Amino-1,4-Naphthoquinone Amide-Oxime Derivatives as Potent IDO1/STAT3 Dual Inhibitors with Prospective Antitumor Effects.

Indoleamine-2,3-dioxygenase 1 (IDO1) and signal transducer and activator of transcription 3 (STAT3) have emerged as significant targets in the tumor microenvironment for cancer therapy. In this study, we synthesized three novel 2-amino-1,4-naphthoquinone amide-oxime derivatives and identified them as dual inhibitors of IDO1 and STAT3. The representative compound demonstrated effective binding to IDO1 and exhibited good inhibitory activity (hIDO1 IC = 0.

Discovery of novel sulfonamide chromone-oxime derivatives as potent indoleamine 2,3-dioxygenase 1 inhibitors.

A series of chromone-oxime derivatives containing piperazine sulfonamide moieties were designed, synthesized and evaluated for their inhibitory activities against IDO1. These compounds displayed moderate to good inhibitory activity against IDO1 with IC values in low micromolar range. Among them, compound 10m bound effectively to IDO1 with good inhibitory activities (hIDO1 IC = 0.

Rapid Screening of Proanthocyanidins from the Roots of Stapf and its Preventative Effects on Dextran-Sulfate-Sodium-Induced Ulcerative Colitis.

Proanthocyanidins (PACs) have been proven to exert antioxidant and anti-inflammatory effects. In this study, ultra-performance liquid chromatography (UPLC) coupled with linear ion trap-Orbitrap (LTQ-Orbitrap) high-resolution mass spectrometry was first employed to systematically screen PACs from the roots of Stapf, and its ethyl acetate extract (ERE) was found to contain PAC monomers and A-type dimeric proanthocyanidins, which were tentatively identified through characteristic fragmentation patterns. In vitro, the antioxidant activity of ERE was tested through 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays.

UPLC-LTQ-Orbitrap-Based Cell Metabolomics and Network Pharmacology Analysis to Reveal the Potential Antiarthritic Effects of Pristimerin: In Vitro, In Silico and In Vivo Study.

Rheumatoid arthritis (RA) is characterized by systemic inflammation and synovial hyperplasia. Pristimerin, a natural triterpenoid isolated from plants belonging to the Celastraceae and Hippocrateaceae families, has been reported to exhibit anti-inflammation and anti-proliferation activities. Our study aims to reveal the antiarthritic effects of pristimerin and explore its potential mechanism using in vitro, in silico, and in vivo methods.

Metabolomics and molecular docking-directed antiarthritic study of the ethyl acetate extract from Celastrus orbiculatus Thunb.

Ethnopharmacological Relevance: Celastrus orbiculatus Thunb., an important folk medicine, has long been used for the treatment of rheumatoid arthritis and its ethyl acetate extract (COE) has been reported to possess anticancer, antiinflammation and antiarthritic effects. However, the therapeutic effect and mechanism of COE treatment in rheumatoid arthritis has been rarely studied especially from the perspective of metabolomics.

StrandAdvantage test for early-line and advanced-stage treatment decisions in solid tumors.

Comprehensive genetic profiling of tumors using next-generation sequencing (NGS) is gaining acceptance for guiding treatment decisions in cancer care. We designed a cancer profiling test combining both deep sequencing and immunohistochemistry (IHC) of relevant cancer targets to aid therapy choices in both standard-of-care (SOC) and advanced-stage treatments for solid tumors. The SOC report is provided in a short turnaround time for four tumors, namely lung, breast, colon, and melanoma, followed by an investigational report.

Nuclear translocation of MEK1 triggers a complex T cell response through the corepressor silencing mediator of retinoid and thyroid hormone receptor.

MEK1 phosphorylates ERK1/2 and regulates T cell generation, differentiation, and function. MEK1 has recently been shown to translocate to the nucleus. Its nuclear function is largely unknown.

The role of low-level lactate production in airway inflammation in asthma.

Warburg and coworkers (Warburg O, Posener K, Negelein E. Z Biochem 152: 319, 1924) first reported that cancerous cells switch glucose metabolism from oxidative phosphorylation to aerobic glycolysis, and that this switch is important for their proliferation. Nothing is known about aerobic glycolysis in T cells from asthma.

[Comparison study of HBV-P mutation detection by MALDI-TOF Ms and direct PCR sequencing].

Objective: To compare the sensitivities of MALDI-TOF MS and direct PCR sequencing on gene mutations detection of hepatitis B virus.

Methods: 100 serum samples from chronic hepatitis B patients were collected, which consisted of 90 serum samples (study group) from 90 chronic hepatitis B patients received nucleoside analogues (NA) therapy for more than 1 year and HBV DNA titer still higher than 500 copies/ml and 10 serum samples (blank group) from 10 chronic hepatitis B patients never treated with antiviral therapy and HBV-DNA titer higher than 1 x 10(5) copies/ml. 9 known mutations associated with HBV P gene in these samples were detected by MALDI-TOF MS and direct PCR sequencing at the same time, TYPE4.

Varicella-zoster virus infection of differentiated human neural stem cells.

Primary varicella-zoster virus (VZV) infection in humans produces varicella (chickenpox), after which the virus becomes latent in ganglionic neurons. Analysis of the physical state of viral nucleic acid and virus gene expression during latency requires postmortem acquisition of fresh human ganglia. To provide an additional way to study the VZV-host relationship in neurons, we developed an in vitro model of infected differentiated human neural stem cells (NSCs).

IL-2 and IL-4 stimulate MEK1 expression and contribute to T cell resistance against suppression by TGF-beta and IL-10 in asthma.

The T cell-driven airway inflammation in chronic asthma is uninhibited and sustained. We examined the resistance of T cells from asthmatic patients against suppression by TGF-β, IL-10 and glucocorticoids and explored its signaling mechanism. CD4(+)CD25(-) T cells from allergic asthmatic subjects demonstrated increased TCR-stimulated proliferation as compared with healthy and chronic obstructive pulmonary disease controls.

Uncoordinated 119 preferentially induces Th2 differentiation and promotes the development of asthma.

The Th2 bias is a hallmark of allergic diseases. In this study, we show that the Th1 versus Th2 balance and the development of allergic asthma are strongly affected by the signaling protein uncoordinated 119 (Unc119). The expression of this adaptor protein is significantly increased in Th2 cells.

Establishment of extracellular signal-regulated kinase 1/2 bistability and sustained activation through Sprouty 2 and its relevance for epithelial function.

Our objective was to establish an experimental model of a self-sustained and bistable extracellular signal-regulated kinase 1/2 (ERK1/2) signaling process. A single stimulation of cells with cytokines causes rapid ERK1/2 activation, which returns to baseline in 4 h. Repeated stimulation leads to sustained activation of ERK1/2 but not Jun N-terminal protein kinase (JNK), p38, or STAT6.

Uncoordinated 119 protein controls trafficking of Lck via the Rab11 endosome and is critical for immunological synapse formation.

The activation of T cells through the TCR is essential for development of the adaptive immune response. TCR does not have any enzymatic activity and relies on the plasma membrane-associated lymphocyte-specific protein tyrosine kinase (Lck) for initiation of signaling. Here we uncover a mechanism that is responsible for plasma membrane targeting of Lck.

Combined sensitization of mice to extracts of dust mite, ragweed, and Aspergillus species breaks through tolerance and establishes chronic features of asthma.

Background: Existing asthma models develop tolerance when chronically exposed to the same allergen.

Objective: We sought to establish a chronic model that sustains features of asthma long after discontinuation of allergen exposure.

Methods: We immunized and exposed mice to a combination of single, double, or triple allergens (dust mite, ragweed, and Aspergillus species) intranasally for 8 weeks.

Cell-specific activation profile of extracellular signal-regulated kinase 1/2, Jun N-terminal kinase, and p38 mitogen-activated protein kinases in asthmatic airways.

Background: Many airway cells manifest signs of chronic activation in asthma. The mechanism of this chronic activation is unknown.

Objectives: We sought to study the activation of the mitogen-activated protein kinase (MAPK) signaling pathway in airway cells.

A phosphosite screen identifies autocrine TGF-beta-driven activation of protein kinase R as a survival-limiting factor for eosinophils.

The differential usage of signaling pathways by chemokines and cytokines in eosinophils is largely unresolved. In this study, we investigate signaling similarities and differences between CCL11 (eotaxin) and IL-5 in a phosphosite screen of human eosinophils. We confirm many previously known pathways of cytokine and chemokine signaling and elucidate novel phosphoregulation in eosinophils.

MK2 controls the level of negative feedback in the NF-kappaB pathway and is essential for vascular permeability and airway inflammation.

We demonstrate that mitogen-activated protein kinase-activated kinase-2 (MK2) is essential for localized Th2-type inflammation and development of experimental asthma. MK2 deficiency does not affect systemic Th2 immunity, but reduces endothelial permeability, as well as adhesion molecule and chemokine expression. NF-kappaB regulates transcription of adhesion molecules and chemokines.

Differential regulation of interleukin 5-stimulated signaling pathways by dynamin.

Through the yeast two-hybrid screen we have identified dynamin-2 as a molecule that interacts with the alpha subunit of the interleukin (IL) 5 receptor. Dynamin-2 is a GTPase that is critical for endocytosis. We have shown that dynamin-2 interacts with the IL-5 receptor-associated tyrosine kinases, Lyn and JAK2, in eosinophils.