Identification of a dual JAK3/TEC family kinase inhibitor for atopic dermatitis therapy.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by recurrent eczematous lesions and severe itching, for which clinical treatments are limited. Selectively inhibiting Janus Kinase 3 (JAK3) and tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinases is proposed as a promising strategy to treat AD with possible reduced side effects and enhanced efficacy. In this study, we developed a dual JAK3/TEC family kinase inhibitor ZZB, which demonstrated potent inhibitory activity with IC values of 0.

Mrgprb2-mediated mast cell activation exacerbates Modic changes by regulating immune niches.

Modic changes are radiographic features associated with microfracture, low-virulence organism infection and chronic inflammation with inflammatory cell infiltration in the vertebral endplate region. Mast cells, as innate immune cells similar to macrophages, are present in painful degenerated intervertebral discs. However, the involvement and mechanisms of mast cells in the development of Modic changes remain unclear.

Mitigating air pollution benefits multiple sustainable development goals in China.

Achieving the United nations 2030 Sustainable Development Goals (SDGs) remains a significant challenge, necessitating urgent and prioritized strategies. Among the various challenges, air pollution continues to pose one of the most substantial threats to the SDGs due to its widespread adverse effects on human health and ecosystems. However, the connections between air pollution and the SDGs have often been overlooked.

FATP2 regulates osteoclastogenesis by increasing lipid metabolism and ROS production.

Lipid metabolism plays a crucial role in maintaining bone homeostasis, particularly in osteoclasts (OCs) formation. Here, we found that the expression level of FATP2, a transporter for long-chain and very-long-chain fatty acids, was significantly upregulated during OC differentiation and in the bone marrow of mice fed a high-fat diet (HFD). Notably, the use of FATP2 siRNA or a specific inhibitor (Lipofermata) resulted in significant inhibition of OC differentiation, while only slightly affecting osteoblasts.

Induction of cervical disc degeneration and discogenic pain by low concentration Propionibacterium acnes infection: an in vivo animal study.

Background: Although cervical intervertebral disc (IVD) degeneration is closely associated with neck pain, its cause remains unclear. In this study, an animal model of cervical disc degeneration and discogenic neck pain induced by a low concentration of Propionibacterium acnes (P. acnes-L) is investigated to explore the possible mechanisms of cervical discogenic pain.

The role of prevertebral soft tissue swelling in dysphagia after anterior cervical corpectomy fusion: change trends and risk factors.

Objectives: This study aimed to analyze the change trends of prevertebral soft tissue swelling (PSTS) for anterior cervical corpectomy fusion(ACCF) and to evaluate the risk factors of PSTS for postoperative dysphagia.

Methods: There were 309 patients with degenerative cervical diseases who were treated with ACCF from November 2015 and September 2019 in our hospital. According to the symptom of swallowing function after ACCF, those were divided into the dysphagia group and the normal-swallowing function group.

Disc degeneration is easily occurred at the same and adjacent cephalad level in cervical spine when Modic changes are present.

Objective: This research aimed to evaluate the influence of Modic changes (MCs) on disc degeneration at the same and adjacent cephalad levels in the cervical spine.

Methods: This research retrospectively reviewed 1036 patients with neck pain, upper limb pain, or numbness who were treated at our out-patient clinic and underwent cervical MRI and cervical anteroposterior/lateral radiography from Jan, 2016 to Jan, 2021. MCs and disc degeneration parameters at same and nearby cephalad levels of MCs were evaluated.

Mechanism of antibiotic resistance development in an activated sludge system under tetracycline pressure.

The mechanism of antibiotic resistance (AR) development in an activated sludge system under tetracycline (TC) pressure was discussed and analyzed. According to the variation of macro-factors, including TC, COD, TN, TP, NH-N, pH, heavy metals, and reactor settings, the tet genes respond accordingly. Consequently, the enrichment sites of tet genes form an invisible AR selection zone, where AR microorganisms thrive, gather, reproduce, and spread.

A Dual-Targeted Metal-Organic Framework Based Nanoplatform for the Treatment of Rheumatoid Arthritis by Restoring the Macrophage Niche.

Inflammatory infiltration and bone destruction are important pathological features of rheumatoid arthritis (RA), which originate from the disturbed niche of macrophages. Here, we identified a niche-disrupting process in RA: due to overactivation of complement, the barrier function of lining macrophages is disrupted and mediates inflammatory infiltration within the joint, thereby activating excessive osteoclastogenesis and bone resorption. However, complement antagonists have poor biological applications due to superphysiologic dose requirements and inadequate effects on bone resorption.

Alteration of the migration trajectory of antibiotic resistance genes by microplastics in a leachate activated sludge system.

The environmental behavior of emerging contaminants of microplastics (MPs), antibiotics and antibiotic resistance genes (ARGs) in the leachate activated sludge system has been monitored and analyzed comprehensively. The results suggested that MPs could effectively alter the migration trajectory of tetracycline resistance genes (tet genes) in the leachate activated sludge system under intermittent and continuous influent conditions. After adding MPs, the total average abundance of tet genes in leachate increased from 0.

Corrigendum: Can oblique lateral interbody fusion (OLIF) create more lumbosacral lordosis in lumbar spine surgery than minimally invasive transforaminal interbody fusion (MIS-TLIF)?

[This corrects the article DOI: 10.3389/fsurg.2022.

The role of esophageal area for dysphagia after anterior cervical corpectomy fusion: Change trends and risk factors.

The objective of this study is to assess the change trends of perioperative esophageal area for anterior cervical corpectomy fusion (ACCF) and to analyze the risk factors of the area for postoperative dysphagia. We retrospectively analyzed 309 patients who underwent ACCF due to degenerative cervical diseases between November 2015 and September 2019 at our hospital. Patients were divided into 2 groups named the dysphagia group and the normal swallowing function group, according to the swallowing function after ACCF.

Driving forces of nitrogen use efficiency in Chinese croplands on county scale.

Nitrogen use efficiency (NUE, defined as the fraction of N input harvested as product) is an important indicator to understand nitrogen use and losses in croplands as an element of determining sustainable food production. China, as the country with the largest amount of nitrogen fertilizer use globally, research into NUE consistently finds it to be much lower than that in developed countries. Understanding the driving forces of the underlying causes of this low NUE is thus crucial to improve nitrogen use and reduce losses in China.

Vertical distribution of antibiotics and antibiotic resistance genes in a representative municipal solid waste landfill, China.

The vertical distribution of sulfonamides (SAs), tetracyclines (TCs), macrolides (MLs), and their related antibiotic resistance genes (ARGs) were comprehensively investigated and characterized in a representative municipal solid waste (MSW) landfill in China. The total concentrations of target antibiotics in the MSW landfill were SAs > TCs > MLs. The abundances of mexF (10.

Anterior cervical transpedicular screw fixation system in subaxial cervical spine: A finite element comparative study.

Multilevel cervical corpectomy has raised the concern among surgeons that reconstruction with the anterior cervical screw plate system (ACSPS) alone may fail eventually. As an alternative, the anterior cervical transpedicular screw (ACTPS) has been adopted in clinical practice. We used the finite element analysis to investigate whether ACTPS is a more reasonable choice, in comparison with ACSPS, after a 2-level corpectomy in the subaxial cervical spine.

promotes osteoblast differentiation and alleviates osteoporosis via the // axis.

This study was designed to elucidate the role of and functions in postmenopausal osteoporosis. Mice were ovariectomized to establish an osteoporosis model and MC3T3-E1-14 osteoblasts were induced to differentiate. Gain- or loss-of-function approaches were used to manipulate the expression of ,  and , followed by an evaluation of their role in postmenopausal osteoporosis both and .

Different responses of cervical intervertebral disc caused by low and high virulence bacterial infection: a comparative study in rats.

The aims of this study were to investigate the outcomes of low- and high-virulence bacterial cervical intervertebral discs (IVDs) infection and its association with cervical IVDs degeneration in rats. A total of 75 clean grade male rats were used to establish the corresponding animal models of low and high virulent bacterial cervical disc infection via an anterior cervical approach, with injection of Propionibacterium acnes (P. acnes) and Staphylococcus epidermidis (S.

The panorama of antibiotics and the related antibiotic resistance genes (ARGs) in landfill leachate.

Landfill leachate is an important source and sink of antibiotics and antibiotic resistance genes (ARGs), which poses a potential threat to human health and ecological environment. Ten antibiotics and 8 ARGs in leachates collected from Zhejiang Province, China, were systematically investigated. The effects of multiple factors were considered: leachate age, season when the leachate was sampled (dry or rainy), heavy metal concentrations, and leachate quality parameters.

[Establishment of finite element model of anterior cervical transpedicular system for reconstruction of cervical stability after subtotal resection of two segments of lower cervical spine].

Objective: To establish the fixation model of anterior cervical transpedicular system (ACTPS) after subtotal resection of two segments of lower cervical spine(C-C) in order to provide a finite element modeling method for anterior cervical reconstruction.

Methods: The CT data of the cervical segment (C-T) of a 30-year-old adult healthy male volunteer was collected. Used Mimics 10.

The role of serum creatine kinase levels in anterior cervical spinal surgery: Change trends and risk factors.

This study aimed to describe change trends in serum creatine kinase (CK) values for patients undergoing anterior cervical spinal surgery and identify risk factors that affect the CK values perioperatively, intending to decrease the degree of the iatrogenic invasiveness of the procedure.We retrospectively analyzed 122 patients undergoing anterior cervical spinal surgery from January 2019 to May 2020. For all patients, CK level was measured 1 day before the operation.

Discovery of seneciobipyrrolidine derivatives for the amelioration of glucose homeostasis disorders through 4E-BP1/Akt/AMPK signaling activation.

Modulating the glucose transport in skeletal muscle is a promising strategy for ameliorating glucose homeostasis disorders. However, the complicated mechanisms of glucose transport make it difficult to find compounds therapeutically relevant molecular mechanisms of action, while phenotypic screening is thought to be an alternative approach to mimic the cell state of interest. Here, we report (±)-seneciobipyrrolidine (1a) is first found to enhance glucose uptake in L6 myotubes through phenotype-based screening.

Design, synthesis and biological evaluation of quinazoline derivatives as potent and selective FGFR4 inhibitors.

Aberrant activation of the fibroblast growth factor 19-fibroblast growth factor receptor 4 (FGF19-FGFR4) signaling pathway has been proved to promote hepatocellular carcinoma (HCC) proliferation. It is assumed that the first FGFR4 inhibitor BLU9931 did not enter clinical studies, presumably due to its rapid metabolism in liver microsomes. Here, we report the development of series of quinazoline derivatives based on FGFR4 inhibitor BLU9931 through structural modification of its solvent region pocket to minimize its potential metabolic liability.

Discovery of -((3,4)-4-(3,4-Difluorophenyl)piperidin-3-yl)-2-fluoro-4-(1-methyl-1-pyrazol-5-yl)benzamide (Hu7691), a Potent and Selective Akt Inhibitor That Enables Decrease of Cutaneous Toxicity.

Rash is one of the primary dose-limiting toxicities of Akt (protein kinase B) inhibitors in clinical trials. Here, we demonstrate the inhibition of Akt2 isozyme may be a driver for keratinocyte apoptosis, which promotes us to search for new selective Akt inhibitors with an improved cutaneous safety property. According to our previous research, compound is selected for further optimization for overcoming the disadvantages of compound , including high Akt2 inhibition and high toxicity against HaCaT keratinocytes.

[Imaging study of soft tissue swelling after anterior cervical corpectomy].

Objective: To study the changes of anterior soft tissue swelling after anterior cervical subtotal corpectomy, titanium mesh fusion and internal fixation.

Methods: From November 2015 to July 2018, 151 patients with cervical spondylotic myelopathy were treated with anterior single corpectomy, titanium mesh fusion and internal fixation, including 109 males and 42 females, aged 44 to 81 (59.77±8.