SOX-1 antibodies positive Lambert-Eaton myasthenic syndrome with occult small cell lung cancer: A case report.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare paraneoplastic neurological syndrome of the neuromuscular transmission. The symptoms often progress slowly and can be misdiagnosed in early stage. Seropositive SOX-1 antibodies are support for the diagnosis of LEMS and have high specificity for small cell lung cancer (SCLC). In this paper, we report a case of a 56-year-old man with smoking history who was admitted to hospital with progressive muscle weakness of the proximal legs. LEMS was diagnosed by repetitive nerve stimulation (RNS) testing and seropositive SOX-1 antibodies. Primary screening with chest computed tomography (CT) and integrated PET/CT did not reveal any tumor. After continuous follow-up, SCLC was found by chest CT and confirmed with pathological examination 10 months after the diagnosis of LEMS. Long-term follow-up and screening for occult SCLC in LEMS patients with positive SOX-1 antibodies are very important.

Eriocalyxin B alleviated ischemic cerebral injury by limiting microglia-mediated excessive neuroinflammation in mice.

Excessive neuroinflammation mediated by microglia has a detrimental effect on the progression of ischemic stroke. Eriocalyxin B (EriB) was found with a neuroprotective effect in mice with Parkinson's disease via the suppression of microglial overactivation. This study aimed to investigate the roles of EriB in permanent middle cerebral artery occlusion (pMCAO) mice. The pMCAO was induced in the internal carotid artery of the mice by the intraluminal filament method, and EriB (10 mg/kg) was administered immediately after surgery by intraperitoneal injection. The behavior score, 2,3,5-triphenyltetrazole chloride staining, Nissl staining, TUNEL, immunohistochemistry, immunofluorescence, PCR, ELISA, and immunoblotting revealed that EriB administration reduced brain infarct and neuron death and ameliorated neuroinflammation and microglia overactivation in pMCAO mice, manifested by alterations of TUNEL-positive cell numbers, ionized calcium binding adaptor molecule 1 (Iba-1)-positive cell numbers, and expression of tumor necrosis factor-α, interleukin 6, IL-1ß, inducible nitric oxide synthase, and arginase 1. In addition, EriB suppressed ischemia-induced activation of nuclear factor kappa B (NF-κB) signaling in the brain penumbra, suggesting the involvement of NF-κB in EriB function. In conclusion, EriB exerted anti-inflammatory effects in ischemia stroke by regulating the NF-κB signaling pathway, and this may provide insights into the neuroprotective effect of EriB in the treatment of ischemic stroke.

Surface oxygen concentration on the Qinghai-Tibet Plateau (2017-2022).

For the ecologically vulnerable Qinghai-Tibet Plateau (QTP), hypoxia is increasingly becoming an extremely important environmental risk factor that significantly affects the health of both humans and livestock in the plateau region, as well as hindering high-quality development. To focus on the problem of hypoxia, it is especially urgent to study the surface oxygen concentration (i.e., oxygen concentration). However, the existing research is not sufficient, and there is a lack of oxygen concentration data collected on the QTP. In this study, through the Second Tibetan Plateau Scientific Expedition and Research and field measurements, the oxygen concentration data and corresponding geographic environmental data were collected at 807 measurement points on the QTP from 2017 to 2022, and the spatiotemporal oxygen concentration patterns were estimated. This work filled the gaps in the measurement and research of oxygen concentrations on the QTP while providing data support for analyses of the influencing factors and spatiotemporal characteristics of oxygen concentrations, which is of great significance for promoting the construction of ecological civilization in the QTP region.

Investigation of the regulatory mechanism of lijie capsules on gut microbiota in rheumatoid arthritis.

Lijie Capsules (LJJN) are a classical Chinese herbal formula adopted to treat rheumatoid arthritis (RA) clinically, yet the regulatory mechanism underlying the protection of LJJN against RA has not been fully elucidated. Here, the animal model of RA was established by complete Freund's adjuvant administration in mice. About 60 mg/ml of LJJN was used for treatment. The histological change of ankle joint was measured by hematoxylin and eosin staining. The inflammatory cytokines were detected using ELISA kits. The protein associated with inflammation and GLUD2 was detected using Western blot. The mice feces were analyzed by 16S rRNA sequencing. The levels of glutamate (Glu) and α-ketoglutarate (α-KG) were detected using their detection kits. In addition, fibroblast-like synoviocytes (FLSs) were stimulated by Glu to induce an injured synoviocytes model in vitro, with or without LJJN treatment for 48 h. It was demonstrated that LJJN alleviated ankle joint swelling and synovial injury in RA mice. Meanwhile, LJJN inactivated nuclear factor kappa B signaling and suppressed inflammation of RA mice. The disordered gut microbiota composition in RA mice was partly restored by LJJN. Bacteroides-mediated Glu metabolism was impacted in RA mice, and LJJN contributed to the conversion of Glu to α-KG in RA mice. In addition, the in vitro results revealed that LJJN could block Glu-induced inflammation in FLSs but had no direct influence on α-KG and GLUD2 levels. In summary, LJJN exerted a protective role against ankle joint injury and inflammation in RA, which might be partly associated with gut microbiota-mediated Glu metabolism.

Electrochemical synthesis of Co/Ni bimetal-organic frameworks: A high-performance SERS platform for detection of tetracycline.

Surface-enhanced Raman scattering (SERS) enables food contaminants monitoring become facile and efficient. Herein, a facile strategy of integrating three-dimensional Ni form with Co/Ni bimetal-organic frameworks combining Ag nanoparticles via electrochemical synthesis method was proposed to develop a high-performance SERS substrate (CoNi-ZIFs@Ag@NF) for efficient detection of tetracycline. The flexible Ni foam (NF) acted as scaffold which can contribute to dramatically enhancing intrinsic electrical conductivity and endowing prepared substrate with high stability and uniform distribution of Ag nanoparticles. Furthermore, the pre-concentration effect of CoNi-ZIFs@Ag@NF for target molecules enhanced SERS performance dramatically. Besides, tetracycline was sensitively detected using CoNi-ZIFs@Ag@NF with low limit of detection (1.0 × 10-11 M) and wide linear detection range (10-10 - 10-5 M) in aqueous solution. Also, the satisfactory recovery (94.45 - 114.25 %) was realized with less than 6.78 % of RSD in real samples. This method would provide a potential and high-performance substrate for SERS monitoring of tetracycline in food and environment.

The Identified Hub Gene GlcN in Osteoarthritis Progression and Treatment.

BACKGROUND: As a chronic disease, osteoarthritis has caused great trouble to the health of middle-aged and elderly people. Studies have shown that glucosamine (GlcN) can be used to abate the progression and improve this disease. Based on this point of view, we try to verify the connection between GlcN and osteoarthritis and find more effective biomarkers. METHODS: We downloaded the GSE72575 data set from the GEO database, and used the R language to perform DEG analysis on the gene expression profile of the samples. Next, the GO function and the KEGG signaling pathways were analyzed through the DAVID database, and then, the KEGG pathways enriched in the gene set were analyzed based on GSEA. Then, the PPI network of DEGs was constructed based on the STRING online database, and finally, the hub genes were selected by Cytoscape. RESULTS: Three GlcN-treated MH7A cell treatment groups and 3 control groups in the GSE72575 data set were studied. Through analysis, there were 52 DEGs in these samples. Then, through GO, KEGG, and GSEA, regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway, FoxO signaling pathway, JAK-STAT signaling pathway, PI3K-Akt signaling pathway, TGF-beta signaling pathway, and ECM receptor interaction were involved in the regulatory mechanisms of the osteoarthritis pathogenesis. After that, the hub genes IL6 and DDIT3 were identified through PPI network construction and analysis. And it was found that IL6 was lowly expressed in the group with GlcN-treated MH7A cells, while DDIT3 was highly expressed. CONCLUSION: The above results provide a basis for GlcN to participate in the treatment of osteoarthritis and a possibility for finding effective therapeutic targets.

Factors contributing to spatial-temporal variations of observed oxygen concentration over the Qinghai-Tibetan Plateau.

Oxygen (O2) is the most abundant molecule in the atmosphere after nitrogen. Previous studies have documented that oxygen concentration remains nearly constant (20.946%) at all altitudes. Here we show for the first time that oxygen concentration varies significantly from earlier consensus and shows strong spatial and seasonal differences. Field observations on the Qinghai-Tibetan Plateau (QTP) indicate oxygen concentration of 19.94-20.66% (2018, n = 80), 19.98-20.78% (2019, n = 166) and 19.97-20.73% (2020, n = 176), all statistically different from earlier reports (p < 0.001) and are lower than the nearly constant. The mean oxygen concentration in summer (20.47%) is 0.31% higher than that of winter (20.16%) (n = 53) at identical locations in 2019, sampled in the Qilian Mountains, northwest QTP. We used LMG (The Lindeman, Merenda and Gold) method to estimate the relative contributions of altitude, air temperature and vegetation index (Fractional Vegetation Cover, FVC and Leaf Area Index, LAI) to oxygen concentration, which are 47%, 32% and 3% (FVC, R2 = 82%); 45%, 30% and 7% (LAI, R2 = 82%), respectively. These findings provide a new perspective for in-depth understanding on population risk in high altitude regions in the context of global climate change, to ensure the health and safety of residents and tourists in high altitude regions and promoting the stability, prosperity and sustainable development of high-altitude regions worldwide.

Synthesis of substituted 2H-chromenes catalyzed by lipase immobilized on magnetic multiwalled carbon nanotubes.

Porcine pancreas lipase (PPL) was immobilized on magnetic multiwalled carbon nanotubes successfully for the synthesis of substituted 2H-chromenes. The catalytic activity of immobilized PPL was much higher than that of free PPL. Effects of reaction medium, temperature, and enzyme dosage were also investigated. Under optimum reaction conditions (acetylacetone (1 mmol), salicylaldehyde (1 equivalent), methanol (10 equivalent), and immobilized PPL (protein content: 30 mg; 65 °C; DMF 5 mL; 5 H), the immobilized PPL showed an excellent catalytic performance on the synthesis of substituted 2H-chromenes. Moreover, the immobilized PPL exhibited satisfactory thermostability, operational simplicity, and reusability in this reaction.

HOXA5 overexpression promotes osteosarcoma cell apoptosis through the p53 and p38α MAPK pathway.

Osteosarcoma is the most common malignant bone tumor in children and adolescents. Aberrant expression of HOXA5 results in various diseases, including cancers. However, the specific function and molecular mechanism of HOXA5 in osteosarcoma is not fully understood. In the present study, we focused on HOXA5 in U2OS and MG63 cells in vitro. We observed lower expression of HOXA5 in U2OS, MG63, and SaOS2 human osteosarcoma cells, compared with hFOB1.19 human osteoblastic cells. HOXA5 overexpression in U2OS and MG63 cells markedly reduced cell survival and proliferation and elevated cell apoptosis and caspase-3 activity. HOXA5 also activated the p38α MAPK pathway by increasing p53. Treating U2OS and MG63 cells with the p53 inhibitor α-pifithrin or the p38α MAPK inhibitor SB203580 led to higher cell survival and proliferation and lower cell apoptosis, compared with the pcDNA3.1-HOXA5 group. In conclusion, our study showed that the p53 and p38α MAPK signal axis facilitated HOXA5's role in inhibiting growth and stimulating apoptosis of osteosarcoma cells.

IL-6 is involved in malignancy and doxorubicin sensitivity of renal carcinoma cells.

Various survival factors such as the pleiotropic cytokine interleukin-6 (IL-6), a major mediator of inflammation and activator of signal transducer and activator of transcription 3 (STAT3), serve to block apoptosis in cancer cells. Our present study revealed that the expression of IL-6, while not other IL-2, IL-4, IL-8, or IL-10, was significantly elevated in resistance of renal carcinoma cells (RCC) when compared with human renal proximal tubule epithelial cell line HK-2. The inhibition of IL-6 by siRNA can suppress the proliferation, migration and invasion of RCC cells and increase the doxorubicin (Dox) sensitivity. While recombination IL-6 can attenuate the inhibition effects of Dox on proliferation of RCC cells. Further studies indicated that inhibition of IL-6 by siRNA can decrease the phosphorylation of STAT3 in RCC cells. Over expression of STAT3 increased the proliferation, migration and invasion of RCC cells and reversed si-IL-6 induced increase of Dox sensitivity of ACHN and A498 cells. In addition, IL-6 treatment can activate ERK1/2 via increasing its phosphorylation. PD98059, the ERK1/2 inhibitor, attenuated IL-6 induced proliferation and synergistically increased the Dox sensitivity of si-IL-6 transfected ACHN cells. Collectively, our data suggested that IL-6 plays an important role in malignancy and Dox sensitivity of RCC. The targeted inhibition of IL-6 signals might be a promising therapeutic strategy for the treatment of renal cancer.

Cardioprotective effect of berberine against myocardial ischemia/reperfusion injury via attenuating mitochondrial dysfunction and apoptosis.

Berberine, an isoquinoline alkaloid originally isolated from the Chinese herb Coptischinensis, has been shown to display a wide range of pharmacological effects. The present study aims to investigate the effect of berberine on myocardial ischemia/reperfusion. Sixty male Sprague-Dawley rats were randomized equally into three groups: sham group, IR group, IR + berberine group. Rats were treated with berberine for 4 weeks and then I/R was performed. Myocardial infarction area was measured. Serum levels of creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin I (cTnI) were assayed. Myocardial apoptosis was detected by terminal dexynucleotidyltransferase (TdT)-mediated dUTP nick end labeling (TUNEL). Mitochondrial function, including MMP and complex I activity, was assayed. Besides, the expression of Bcl-2, Bax and cytochrome c were detected by Western blot. Our results suggested that berberine decreased myocardial infarction area, and decreased serum levels of CK-MB, LDH and cTnI. Berberine attenuates myocardial apoptosis and improved mitochondrial dysfunction. Berberine up-regulates the expression of Bcl-2 and mitochondrial cytochrome c and down-regulates the expression of Bax and cytosolic cytochrome c. In conclusion, berberine protects the heart from ischemia/reperfusion injury via attenuating mitochondrial dysfunction and myocardial apoptosis.

[Separation of 3-substituted-(R,S)-beta-alanine derivatives by high performance liquid chromatography].

3-Substituted-(R,S)-beta-alanines derivatized by 1-fluoro-2,4-dinitro-5-L-valinamide (Marfey's reagent) were successfully separated by reversed-phase high performance liquid chromatography. The separations were performed with gradient elution. The mobile phase A was acetonitrile containing 0.1% (v/v) trifluoroacetic acid and the mobile phase B was 0.1% (v/v) trifluoroacetic acid aqueous solution. Thirty-two pairs of 3-substituted-(R,S)-beta-alanine derivatives, phenyl, substituted phenyl, naphthyl, substituted pyridyl and thienyl, were separated. The mobile phase A content was changed from 35% to 75% in 20 min. All (R-L)-diastereomers were eluted prior to the (S-L) ones. Substituents with larger hydrophobic parameters (pi) gave longer retention times (tR) for their derivatives than those with smaller ones except for 3-hydroxyphenyl and 4-hydroxyphenyl substituents. The positioning of the substituents on benzene ring of beta-alanines (beta-Ala) also influenced tR and separation. 4-Subsituted-phenyl-(R,S)-beta-Ala derivatives gave longer tR and better separation than 2-substituted isomers. The enantiomer excess values of R- and S-beta-Ala were also determined.