PPP2R2A inhibition contributes to preeclampsia by regulating the proliferation, apoptosis, and angiogenesis modulation potential of mesenchymal stem cells.

BACKGROUND: The precise mechanisms underlying preeclampsia (PE) pathogenesis remain unclear. Mesenchymal stem cells (MSCs) are involved in the pathology of PE. The aim of our study was to identify the effects of protein phosphatase 2 regulatory subunit B α (PPP2R2A) on MSCs and ascertain its latent role in the progression of PE. METHODS: Reverse-transcription quantitative polymerase chain reaction and western blot analyses were performed to determine the expression of PPP2R2A in decidual tissue and decidual (d)MSCs from healthy pregnant women and patients with PE as well as the expression levels of Bax and Bcl-2 in dMSCs. The levels of p-PI3K, PI3K, p-AKT, and AKT were determined using western blotting. Cell growth, apoptosis, and migration were analyzed using MTT, flow cytometry, and Transwell assays, respectively. Human umbilical vein endothelial cell (HUVEC) tube formation ability was assayed using a HUVEC capillary-like tube formation assay. RESULTS: PPP2R2A was downregulated in decidual tissues and dMSCs of patients with PE when compared with that in healthy pregnant women. Moreover, upregulation of PPP2R2A enhanced cell proliferation, reduced apoptotic dMSC, inhibited Bax expression, and increased Bcl-2 levels. Conditioned medium from PPP2R2A-overexpressing dMSCs promoted HTR-8/SVneo cell migration and angiogenesis of HUVEC. Furthermore, the PPP2R2A plasmid suppressed PI3K/AKT pathway activation in dMSCs. However, these effects were partially reversed by LY2940002 treatment. CONCLUSION: PPP2R2A inhibition contributes to PE by regulating the proliferation, apoptosis, and angiogenesis of MSCs, providing a new therapeutic target for PE diagnosis and treatment.

Clinical characteristics analysis of pediatric spinal cord injury without radiological abnormality in China: a retrospective study.

PURPOSE: This study aims to analyze the clinical characteristics of Chinese children with spinal cord injury (SCI) without radiographic abnormality (SCIWORA) and explore their contributing factors and mechanisms of occurrence. METHODS: A retrospective analysis was conducted on the clinical data of pediatric patients diagnosed with SCIWORA from January 2005 to May 2020. Epidemiological, etiological, mechanistic, therapeutic, and outcome aspects were analyzed. RESULTS: A total of 47 patients with SCIWORA were included in this study, comprising 16 males and 31 females. The age range was 4 to 12 years, with an average age of 7.49 ± 2.04 years, and 70% of the patients were below eight. Sports-related injuries constituted 66%, with 70% attributed to dance backbend practice. Thoracic segment injuries accounted for 77%. In the American Spinal Injury Association (ASIA) classification, the combined proportion of A and B grades accounted for 88%. Conservative treatment was chosen by 98% of the patients, with muscle atrophy, spinal scoliosis, hip joint abnormalities, and urinary system infections being the most common complications. CONCLUSION: SCIWORA in Chinese children is more prevalent in those under eight years old, with a higher incidence in females than males. Thoracic spinal cord injuries are predominant, dance backbend as a primary contributing factor, and the social environment of "neijuan" is a critical potential inducing factor. Furthermore, the initial severity of the injury plays a decisive role in determining the prognosis of SCIWORA.

MicroRNA-223-3p downregulates the inflammatory response in preeclampsia placenta via targeting NLRP3.

OBJECTIVE: To investigate the regulatory role of miR-223-3p in the inflammatory response of PE placenta. METHODS: PE and normal placental tissues were collected to measure the expression of NLRP3 and miR-223-3p. The targeting relationship between NLRP3 and miR-223-3P was verified by bioinformatics analysis and classical double-luciferase reporter gene assay. Lipopolysaccharide (LPS) was used to induce HTR8/SVneo cells as PE placental cell inflammation model. Then we transfected miR-223-3p overexpression/miR-223-3p negative control plasmid into the LPS-induced HTR8/SVneo cells. Next, the expressions of NLRP3, Caspase-1, GSDMD, IL-1ß and IL-18 were evaluated to elucidate the regulatory effect of miR-223-3p on the inflammatory response mediated by NLRP3 in PE placenta. RESULTS: Compared with normal controls, NLRP3 was significantly up-regulated in PE placenta, while miR-223-3p was down-regulated. In addition, NLRP3 was a direct target of miR-223-3p. Further research revealed that the expression of NLRP3, Caspase-1, GSDMD, IL-1ß and IL-18 could be obviously promoted in HTR8/SVneo cells treated with LPS (500 ng/ml) for 24 h, nevertheless it could be significantly suppressesed under the overexpression of miR-223-3p. CONCLUSION: MiR-223-3p suppressed NLRP3 inflamariomes activation, downstream inflammatory factors secretion and pyroptosis in LPS-induced HTR8/SVneo cells indicating that miR-223-3p could serve as an anti-inflammatory factor in preeclampsia.

Preliminary study on a novel biological scaffold loaded with Apelin-13 sustained-release microcapsules for promoting fallopian tube recanalization in rabbits. / è½½Apelin-13ç¼“é‡Šå¾®å›Šçš„æ–°åž‹ç”Ÿç‰©æ”¯æž¶ä¿ƒå ”è¾“åµç®¡å†é€šçš„åˆæ­¥ç ”ç©¶.

OBJECTIVES: Tubal factor infertility severely impairs the natural fertility of women, and there is for genuine tubal recanalization, including restoration of both the anatomy and function of the diseased fallopian tubes. Currently, there is no effective treatment available. This study aims to explore methods for promoting the repair and recanalization of fallopian tubes from these 2 aspects. METHODS: Apelin-13 sustained-release microspheres and poly (lactic-co-glycolic acid) (PLGA) three-dimensional (3D) biodegradable scaffolds were prepared. The basic characteristics and in vivo degradation (mass loss rate) of the biodegradable scaffolds were tested, along with the in vitro drug release (cumulative release rate), the in vivo drug release (Apelin-13 plasma concentration), and in vitro degradation (degradation rate) of the microspheres. The Apelin-13 microspheres (microsphere group)/PLGA 3D scaffolds loaded with Apelin-13 sustained-release microspheres (scaffold-microcapsule group) were injected/placed into the fallopian tubes of New Zealand rabbit of chronic salpingitis models. The patency, microscopic structure, and positive expression of estrogen receptor and progesterone receptor of the fallopian tubes in the control group, the model group, the microcapsule group, and the scaffold-microcapsule group was observed and compared. RESULTS: At the 4th week post-operation, the mass loss rate of the PLGA 3D scaffolds, the degradation rate of the microspheres, and the Apelin-13 sustained-release microspheres-generated cumulative release rate in vitro over 30 days were 98.66%, 70.58%, and 98.68% respectively. The plasma concentration of Apelin-13 reached its peak within 5 days and remained stable for 25 days. Compared with the model and microsphere groups, the scaffold-microsphere group showed a milder inflammatory reaction within the tubal lumen, a higher rate of fallopian tube patency, and higher expression levels of estrogen and progesterone receptors (all P<0.05). The indicators of the scaffold-microsphere group were close to those of the control group. CONCLUSIONS: The PLGA 3D scaffolds loaded with Apelin-13 sustained-release microspheres can comprehensively repair the anatomical structure and physiological function of the fallopian tubes and hold promise for truly effective tubal recanalization.

Discovery of two ent-atisane diterpenoid lactones with AChE inhibitory activity from the roots of Euphorbia fischeriana.

Euphorlactone A (1), a rare rearranged ent-atisane norditerpenoid with an undescribed 3-nor-2,4-olide-ent-atisane scaffold, and euphorlactone B (2), a new ent-atisane diterpenoid with an unprecedented seven-membered lactone ring C, were isolated from the roots of Euphorbia fischeriana. Their planar structures with absolute configurations were extensively elucidated by analysis of 1D and 2D NMR data, electronic circular dichroism (ECD) calculations, Rh2(OCOCF3)4-induced ECD curves, and single-crystal X-ray diffraction. Euphorlactone A (ELA) showed a remarkable AChE (acetylcholinesterase) inhibitory activity (IC50 = 2.13 ± 0.06 µM and Ki = 0.058 µM), which was five times stronger than that of the positive control (rivastigmine, IC50 = 12.46 ± 0.82 µM), and further in vitro enzyme inhibition kinetic analysis and molecular docking studies were performed to investigate the AChE inhibitory mechanism.

A novel colchicine-myricetin heterozygous molecule: design, synthesis, and effective evaluations on the pathological models of acute lung injury in vitro and in vivo.

Acute lung injury (ALI) is an inflammatory condition and there are no effective treatments. A novel new compound----colchicine-myricetin hybrid (CMyrH) was herein designed and synthesized. To evaluate the activity of CMyrH in ALI, we used a bleomycin (BLM) induced BEAS-2B injury model in vitro and established a well-recognized rat model of BLM-induced lung injury in vivo. The results demonstrated that colchicine-myricetin hybrid protected BEAS-2B cells against BLM-induced cell injury in an increased dose manner, and reduced wet/dry weight ratio, histological scoring, and inflammation cytokines IL-1ß, IL-6, IL-18, and TNF-α levels of lung tissue of the rats. Furthermore, we found colchicine-myricetin hybrid inhibited caspase-1, ASC, GSDMD, and NLRP-3 expression in vivo. Meanwhile, we used molecular docking to analyze the binding mode of colchicine-myricetin hybrid and human neutrophil elastase (HNE), it revealed that colchicine-myricetin hybrid showed strong binding affinity toward human neutrophil elastase when compared to its parent molecules. In conclusion, It is suggested that colchicine-myricetin hybrid antagonized acute lung injury by focusing on multi-targets via multi-mechanisms, and might be served as a potential therapeutic agent for acute lung injury.

[Efficacy of Tyrosine Kinase Inhibitor Combined with Decitabine, Homoharringtonine, Interferon in the Maintenance Therapy of Blast Phase Chronic Myeloid Leukemia].

OBJECTIVE: To explore the efficacy of tyrosine kinase inhibitor (TKI) combined with decitabine, homoharringtonine, and interferon regimen as maintenance therapy for blast phase chronic myeloid leukemia (CML-BP). METHODS: The clinical data of CML-BP patients who received the first major hematological response after induction therapy at The Affiliated Cancer Hospital of Zhengzhou University from June 2015 to December 2021 were analyzed retrospectively. The event-free survival, duration of remission, and overall survival of patients in TKI combined with decitabine, homoharringtonine, interferon group(n=18) and TKI combined with conventional chemotherapy group(n=10) were compared by log-rank test. RESULTS: A total of 28 patients were included, with a median age of 46 (24-58) years old. Kaplan-Meier survival analysis showed that patients in TKI combined with decitabine, homoharringtonine, interferon group had longer event-free survival (7.4 vs 4.3 months, P=0.043, HR＝0.44, 95% CI: 0.17-1.14), duration of overall remission (16.1 vs 6.6 months, P=0.005, HR＝0.32, 95% CI: 0.11-0.89), overall survival (34.3 vs 13.5 months, P=0.006, HR＝0.29, 95% CI: 0.10-0.82) compared with patients in TKI combined with conventional chemotherapy group. CONCLUSION: The TKI combined with decitabine, homoharringtonine and interferon regimen can significantly prolong the survival of CML-BP patients who obtained the major hematological response compared with TKI combined with conventional chemotherapy regimen.

Chaihu Shugan San ameliorated cognitive deficits through regulating gut microbiota in senescence-accelerated mouse prone 8.

Background: Traditional Chinese medicines exhibit promising preventive effects on Alzheimer's disease. Chaihu Shugan San (CSS) is a well-known traditional herbal formula whose several kinds of ingredients have the potential of ameliorating Alzheimer's disease. The present study aimed to evaluate the effects of CSS on the microbiota-gut-brain axis and cognitive deficits of senescence-accelerated mouse prone 8 (SAMP8) mice as well as investigate the underlying mechanisms. Methods: Thirty 5-month-old SAMP8 mice were randomly divided into the model group (SAMP8), CSS low-dose treatment group (CSSL), and CSS high-dose treatment group (CSSH). Ten SAMR1 mice were used as the normal control, and ten SAMP8 mice treated with donepezil were used as the positive control of cognitive function. CSS was orally administrated to SAMP8 mice for 8 weeks. The Morris water maze test was used to evaluate cognitive function. Histological staining was used to observe neuronal injury and Aß deposition. Transmission electron microscopy was used to observe the synaptic ultrastructure. 16S rRNA gene analysis was performed to measure the changes in intestinal microbiota. Results: The results showed that CSS significantly improved the learning function and memory deficits of aged SAMP8 mice in the Morris water maze examination. CSS ameliorated neuronal injury, synaptic injuries, and Aß deposition in the brain of SAMP8 mice. In addition, CSS also significantly improved microbiota composition in terms of elevating Lactobacillus reuteri and decreasing Staphylococcus xylosus in the feces of aged SAMP8 mice. Conclusion: These findings suggested that CSS might have a preventive potential for cognitive deficits in aging through regulating gut microbiota, which paved the way for the application of CSS for prevention and therapeutic purposes for mild cognitive impairment as well as Alzheimer's disease.

Concise Enantioselective Total Synthesis of Isopavine Alkaloids.

Herein, we report a concise asymmetric total synthesis of isopavine alkaloids, which feature a special azabicyclo[3.2.2]nonane tetracyclic skeleton. The key steps include iridium-catalyzed asymmetric hydrogenation of unsaturated carboxylic acids, Curtius rearrangement, and Eschweiler-Clarke methylation, which enable an enantioselective approach to isopavine alkaloids in 6-7 linear steps. Furthermore, for the first time, isopavine alkaloids, especially (-)-reframidine (3), are found to display effective antiproliferative effects on various cancer cell lines.

Fabrication of sodium alginate-melamine@ZIF-67 composite hydrogel and its adsorption application for Pb(II) in wastewater.

A low-cost and environmental-friendly sodium alginate-melamine@zeolitic imidazolate framework-67 (SA-ME@ZIF-67) adsorbent was fabricated by chemical grafting and in situ growth for the removal of lead ions in wastewater. Firstly, melamine (ME) was grafted onto sodium alginate (SA) by amide reaction, and then SA-ME was dropped into a solution of calcium chloride to form hydrogel bead, and ZIF-67 was grown on the SA-ME hydrogel bead by the in situ growth method. The SA-ME@ZIF-67 adsorbent was characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, and X-ray diffraction. The SA-ME@ZIF-67 adsorbent was used to effectively adsorb Pb(II) from aqueous solutions. The initial concentrations of lead ions, adsorbent dose, initial pH of lead ion solution, temperature, and adsorption time for the material were optimized. The adsorption isotherms and kinetics fitted to Langmuir isotherm model (R2 = 0.9281, 0.9420, and 0.9623 at the temperatures of 288.15 K, 298.15 K, and 308.15 K, respectively) and pseudo-second-order kinetic model (R2 = 0.9901) respectively. According to the Langmuir model at 308.15 K, the maximum adsorption capacity of the adsorbent for Pb(II) was 634.99 mg/g. The recycling application of the adsorbent was possible as it was easily collected and reused after five adsorption-regeneration cycles. In addition, the Pb(II) in real wastewater samples has been efficiently removed using the fabricated hydrogel. The results showed that the SA-ME@ZIF-67 adsorbent had high adsorption capacity, removal efficiency, and easy recyclability for Pb(II).

Apelin/APJ system: an emerging therapeutic target for neurological diseases.

Apelin, an endogenous ligand for the G protein-coupled receptor APJ, is extensively expressed in various systems, especially the nervous system. This article reviews the role of apelin/APJ system in neurological diseases. In detail, apelin/APJ system can relieve acute brain injury including subarachnoid hemorrhage, traumatic brain injury, and ischemic stroke. Also, apelin/APJ system has therapeutic effects on chronic neurodegenerative disease models, involving the regulation of neurotrophic factors, neuroendocrine, oxidative stress, neuroinflammation, neuronal apoptosis, and autophagy. In addition, through different routes of administration, apelin/APJ system has a biphasic effect on depression, epilepsy, and pain. However, apelin/APJ system exacerbates the proliferation and invasion of glioblastoma. Thus, apelin/APJ system is expected to be a therapeutic target for the treatment of nervous system diseases.

IL1RAP Knockdown in LPS-Stimulated Normal Human Astrocytes Suppresses LPS-Induced Reactive Astrogliosis and Promotes Neuronal Cell Proliferation.

The reactivation of astrocytes plays a critical role in spinal cord injury (SCI) repairment. In this study, IL1RAP expression has been found to be upregulated in SCI mice spinal cord, SCI astrocytes, and LPS-stimulated NHAs. Genes correlated with IL1RAP were significantly enriched in cell proliferation relative pathways. In LPS-stimulated NHAs, IL1RAP overexpression promoted NHA cell proliferation, decreased PTEN protein levels, and increased the phosphorylation of Akt and mTOR. IL1RAP overexpression promoted LPS-induced NHA activation and NF-κB signaling activation. Conditioned medium from IL1RAP-overexpressing NHAs inhibited SH-SY5Y cells viability but promoted cell apoptosis. Conclusively, IL1RAP knockdown in LPS-stimulated NHAs could partially suppress LPS-induced reactive astrogliosis, therefore promoting neuronal cell proliferation.

Perturbations in gastrointestinal tract microbiota composition and function in individuals with yellow-greasy tongue coating / 数字中医药（英文）

@#【Objective】  To study the composition and function of tongue coating (TC) and gastrointestinal tract (GIT) microbiota in participants with yellow-greasy tongue coating (YGTC), and to explore the representative metabolite markers and pathways in this group. 【Methods】  Subjects with YGTC or thin-white tongue coating (TWTC) were recruited from December 1, 2021 to October 30, 2022, and the TC and fecal samples were collected. Samples were subjected to both whole-genome shotgun (WGS), and 16S rRNA gene sequencing. The α-diversity analysis, principal component analysis (PCA), and Spearman correlation analysis were performed for two groups. Ultra-performance liquid chromatography combined with tandem mass spectrometry (UPLC–MS/MS) analysis was used to analyze metabolomics and enrichment of metabolic pathways. 【Results】  The results revealed 20 YGTC participates and 19 TWTC participates. At the genus level, the dominant bacterial species of TC flora and intestinal flora in the two groups were roughly the same, but the relative kurtosis difference was marked, and the abundance of potentially pathogenic bacteria in TC and fecal samples of YGTC subjects was higher. There were 9 down-regulated microorganisms in the TC samples, 26 down-regulated microorganisms, and 6 up-regulated microorganisms in YGTC subjects. The α-diversity analysis indicated that the Chao and abundance-based coverage estimator (ACE) indices of TC bacteria in the YGTC subjects showed a decreasing trend, but the difference was not statistically significant (P > 0.05). The α-diversity of fecal samples and the Chao and ACE indices decreased significantly (P < 0.05). PCA showed that the microflora structure of TC and fecal samples were significantly different between the two groups. Spearman correlation analysis showed that there was no correlation between TC and fecal microorganisms at phyla and genus levels in the same subjects (P > 0.05). The metabolomics results demonstrated that fumarate reductase, V/A ATPase, and phosphatidylethanolamine were increased, and glycerate-3p, UDP-glucose, and quinone oxidoreductase metabolites were decreased in YGTC TC samples. Inosine monophosphate (IMP), uridine monophosphate (UMP), and gamma-aminobutyric acid(GABA) were increased in YGTC fecal samples, while the contents of ribo-5P, histidine, biotin,and cobalamin were decreased. Metabolic pathway analysis indicated that the abundance of the TC and fecal samples of the YGTC subjects was relatively low in various metabolic pathways, including amino acid metabolism, carbohydrate metabolism, nitrogen metabolism, and energy metabolism. 【Conclusion】  Structural and functional changes in TC and GIT microbiota or metabolite markers could be potential biological bases of YGTC formation.

Design, synthesis and biological evaluation of a novel colchicine-magnolol hybrid for inhibiting the growth of Lewis lung carcinoma in Vitro and in Vivo.

Colchicine is a bioactive alkaloid originally from Colchicum autumnale and possesses excellent antiproliferative activity. However, colchicine-associated severe toxicity, gastrointestinal side effects in particular, limits its further therapeutic use. In the current study, we thus designed and synthesized a novel hybrid (CMH) by splicing colchicine and magnolol, a multifunctional polyphenol showing favorable gastrointestinal protection. The antitumor activity of CMH in Lewis lung carcinoma (LLC) was then evaluated in vitro and in vivo. Biologically, CMH inhibited the growth of LLC cells with an IC50 of 0.26 µM, 100 times more potently than cisplatin (26.05 µM) did. Meanwhile, the cytotoxicity of CMH was 10-fold lower than that of colchicine in normal human lung cells (BEAS-2B). In C57BL/6 mice xenograft model, CMH (0.5 mg/kg) worked as efficacious as colchicine (0.5 mg/kg) to inhibit tumor growth and 2 times more potently than cisplatin (1 mg/kg). In terms of mortality, 7 out of 10 mice died in colchicine group (0.75 mg/kg), while no death was observed in groups receiving CMH or cisplatin at 0.75 mg/kg. Mechanistic studies using Western blot revealed that CMH dose-dependently suppressed the protein expression of phosphorylated ERK. Molecular docking analysis further indicated that CMH was well fitted in the colchicine binding site of tubulin and formed several hydrogen bonds with tubulin protein. These results enable our novel hybrid CMH as a potential antineoplastic agent with lower toxicity, and provide perquisites for further investigation to confirm the therapeutic potentiality of this novel hybrid.

A capillary-driven LoC-SERS device integrated with catalytic hairpin assembly amplification technology for NSCLC-related biomarkers detection.

In this study, we apply catalytic hairpin assembly (CHA) as the signal amplification strategy for the quantification of carcinoembryonic antigen (CEA) and cytokeratin fragment antigen 21-1 (CYFRA21-1) with a surface-enhanced Raman scattering (SERS) microfluidic chip (LoC-SERS) as the carrier. Herein, antibody-DNA conjugates are designed to assist the application of CHA amplification in protein detection. In the presence of protein biomarkers, antibody-DNA conjugates can specifically bind to the target proteins, forming the antigen@antibody-DNA conjugates. The terminal free part of the DNA on the conjugates can trigger the CHA events to connect SERS nanotags to capture nanoprobes. Then, micro-magnet can gather the CHA products in a rectangular chamber, resulting in the aggregation of SERS nanotags, which can ultimately generate abundant "hot spots" for SERS signal enhancement. Using this strategy, CEA and CYFRA21-1 can be successfully determined with a limit of detection (LOD) as low as pg mL-1, much lower than recently reported methods. Meanwhile, a non-small cell lung cancer (NSCLC)-xenografted mouse model was established, and SERS was applied to analyze the expression level of CEA and CYFRA21-1 in tumorigenesis and development. The comparison between SERS results and those of the ELISA method demonstrated a high degree of consistency, suggesting that the proposed CHA-assisted LoC-SERS device has satisfying accuracy. Thus, introducing the CHA strategy via the design of antibody-DNA conjugates opens new gates to ultra-sensitive and specific SERS detection of protein biomarkers.

Protection against H2O2-evoked toxicity in HT22 hippocampal neuronal cells by geissoschizine methyl ether via inhibiting ERK pathway.

Oxidative stress is considered as an important mechanism underlying the pathology of neurodegenerative disorders. In this study, we utilized an in vitro model where oxidative stress process was evoked by exogenous hydrogen peroxide (H2O2) in HT22 murine hippocampal neurons and evaluated the neuroprotective effects of geissoschizine methyl ether (GME), a naturally occurring alkaloid from the hooks of Uncaria rhynchophylla (Miq.) Jacks. After a 24 h H2O2 (350 µM) insult, a significant decrease in cell survival and a sharp increase in intracellular reactive oxygen species were observed in HT22 cells. Encouragingly, GME (10-200 µM) effectively reversed these abnormal cellular changes induced by H2O2. Moreover, mechanistic studies using Western blot revealed that GME inhibited the increase of phospho-ERK protein expression, but not phospho-p38, caused by H2O2. Molecular docking simulation further revealed a possible binding mode that GME inhibited ERK protein, showing that GME favorably bound to ERK via multiple hydrophobic and hydrogen bond interactions. These findings indicate that GME provide effective neuroprotection via inhibiting ERK pathway and also encourage further ex vivo and in vivo pharmacological investigations of GME in treating oxidative stress-mediated neurological disorders.

Efficient synthesis of novel colchicine-magnolol hybrids and evaluation of their inhibitory activity on key proteases of 2019-nCoV replication and acute lung injury.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV), is a life-threatening infectious condition. Acute lung injury is a common complication in patients with COVID-19. 3-chymotrypsin-like protease (3CLpro) of 2019-nCoV and neutrophil elastase are critical targets of COVID-19 and acute lung injury, respectively. Colchicine and magnolol are reported to exert inhibitory effects on inflammatory response, the severe comorbidity in both COVID-19 and acute lung injury. We thus designed and synthesized a series of novel colchicine-magnolol hybrids based on a two-step synthetic sequence. It was found that these novel hybrids provided unexpected inhibition on 3CLpro and neutrophil elastase, a bioactivity that colchicine and magnolol did not possess. These findings not only provide perquisites for further in vitro and in vivo investigation to confirm the therapeutic potentiality of novel colchicine-magnolol hybrids, but also suggest that the concurrent inhibition of 3CLpro and neutrophil elastase may enable novel colchicine-magnolol hybrids as effective multi-target drug compounds.

Effect of oxygen partial pressure on the performance of homojunction amorphous In-Ga-Zn-O thin-film transistors.

In this study, the homojunction thin-film transistors (TFTs) with amorphous indium gallium zinc oxide (a-IGZO) as active channel layers and source/drain electrodes were fabricated by RF magnetron sputtering. The effect of oxygen partial pressure on the phase, microstructure, optical and electrical properties of IGZO thin films was investigated. The results showed that amorphous IGZO thin films always exhibit a high transmittance above 90% and wide band gaps of around 3.9 eV. The resistivity increases as the IGZO thin films are deposited at a higher oxygen partial pressure due to the depletion of oxygen vacancies. In addition, the electrical behaviors in homojunction IGZO TFTs were analyzed. When the active channel layers were deposited with an oxygen partial pressure of 1.96%, the homojunction IGZO TFTs exhibited optimal transfer and output characteristics with a field-effect mobility of 13.68 cm2V-1s-1. Its sub-threshold swing, threshold voltage and on/off ratio are 0.6 V/decade, 0.61 V and 107, respectively.

A microfluidic chip using Au@SiO2 array-based highly SERS-active substrates for ultrasensitive detection of dual cervical cancer-related biomarkers.

In this work, a microfluidic chip using Au@SiO2 array-based highly active SERS substrates was developed for quantitative detection of squamous cell carcinoma antigen (SCCA) and carcinoembryonic antigen (CEA) associated with cervical cancer. The chip consisted of six functional units with pump-free design, enabling parallel detection of multiple samples in an automatic manner without external pumps and improving the portability. Ag nanocubes (AgNCs) were labeled with Raman reporters and coupled with antibodies (labeling) to prepare SERS tags, while the Au nanoparticle-modified SiO2 microsphere (Au@SiO2) array was conjugated with antibodies (coating) to generate the highly SERS-active capturing substrate. In the presence of target biomarkers, they were captured by SERS tags and capturing substrate, resulting in the formation of "sandwich" structures which were trapped in the detection chamber. As the immune reaction proceeded, a large number of "hot spots" were generated by the proximity of the Au@SiO2 array substrate and AgNCs, greatly amplifying SERS signals. With this chip, the limits of detection of the SCCA and CEA levels in human serum were estimated to be as low as 0.45 pg mL-1 and 0.36 pg mL-1, respectively. Furthermore, the good selectivity and reproducibility of this chip were confirmed. Finally, clinical serum samples were analyzed by this chip, and the outcomes were consistent with those of enzyme-linked immunosorbent assay (ELISA). Thus, the proposed microfluidic chip can be potentially applied for the clinical diagnosis of cervical cancer.

Roles of apelin/APJ system in cancer: Biomarker, predictor, and emerging therapeutic target.

Cancer is a disease that seriously endangers human health and is mainly characterized by a high metastasis rate, a high recurrence rate, and a high mortality rate. The treatment of cancer has always been an important research direction of scientific research. A number of studies have shown that the apelin/APJ system is involved in the development and poor prognosis of a variety of cancers, such as lung cancer, liver cancer, cholangiocarcinoma, breast cancer, glioblastoma, prostate cancer, ovarian cancer, and so on. Accumulating evidence has also shown that the apelin/APJ system acts as a biomarker and predictor of postoperative effects in multiple cancers, which can also affect the tumor microenvironment and the efficacy of cancer immunotherapy. Considering that the apelin/APJ system may be a potential target for cancer treatment, it is of great significance for the study of new cancer treatment targets. To better understand the role of the apelin/APJ system on the occurrence and development of cancer, this article reviews the role of the apelin/APJ system in the occurrence and development of various cancers, angiogenesis, tumor stem cells, tumor microenvironment, drug resistance, poor prognosis, and the research progress of related anticancer drugs.