Lentinan mitigates pemetrexed chemoresistance by the PI3K/Akt pathway in non-small cell lung cancer.

Pemetrexed is a folate analog metabolic inhibitor that is given for therapy of non-small cell lung cancer (NSCLC). Drug resistance affects the efficacy of pemetrexed in NSCLC. Lentinan is a polysaccharide extracted from Shiitake mushrooms which has antitumor roles in multiple cancers, including lung cancer. However, the effects of lentinan on pemetrexed resistance in NSCLC remain unclear. In present study, The pemetrexed-resistant NSCLC cells were established and exposed to pemetrexed and lentinan. Oxidative stress was investigated via mitochondrial membrane potential (JC-1 staining), levels of MDA and SOD.The phosphorylation and total of PI3K and Akt levels were actuated using specific activator 740Y-P and measured through western blot. We observed that Lentinan decreased IC50 of pemetrexed in resistant NSCLC cells. Lentinan aggravated pemetrexed-induced proliferation inhibition of resistant NSCLC cells via reducing PCNA levels. Lentinan exacerbated pemetrexed-triggered oxidative stress through increasing ROS and MDA levels, and reducing mitochondrial membrane potential and SOD levels. Lentinan inhibited PI3K/Akt signaling activation in pemetrexed-treated cells. Activated PI3K/Akt pathway using activator 740Y-P reversed the effects of lentinan on pemetrexed-mediated proliferation inhibition and oxidative stress. Our findings uncover that Lentinan mitigates pemetrexed resistance in NSCLC through inhibiting cell proliferation and inducing oxidative stress by suppressing PI3K/Akt signaling.

Anti-inflammatory discovery of sesquiterpenoids and a jasmonic acid derivative from Artemisia stolonifera.

Eleven previously undescribed sesquiterpenoids (8-18), one undescribed jasmonic acid derivative (35) and 28 known compounds were isolated from the leaves of Artemisia stolonifera. Undescribed compounds with their absolute configurations were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction and ECD calculation. Compound 8 was identified as a rare sesquiterpenoid featuring a rearranged 5/8 bicyclic ring system, whereas compound 17 was found to be an unprecedented monocyclic sesquiterpenoid with methyl rearrangement. Evaluation of biological activity showed that compounds 1-5 and 7 displayed cytotoxicity against six tumor cells. In the meantime, compounds 11, 12, 18 and 35 exhibited inhibitory effects against LPS-stimulated NO production in RAW 264.7 macrophage cells and reduced the transcription of IL-6 and IL-1ß in a dose-dependent manner at 25, 50 and 100 µM. Moreover, the anti-inflammatory-based network pharmacology and molecular docking analyses revealed potential target proteins of 11, 12, 18 and 35.

Development and validation of a novel nomogram for predicting overall survival patients with neuroblastoma.

PURPOSE: The aim of this study was to develop a nomogram specially for predicting overall survival (OS) for Chinese patients with neuroblastoma (NB). METHODS: Patients with pathologically confirmed NB who were newly diagnosed and received treatments at our hospital from October 2013 to October 2021 were retrospectively reviewed. The nomogram for OS were built based on Cox regression analysis. The validation of the prognostic model was evaluated by concordance index (C-index), calibration curves, and decision curve analyses (DCAs). RESULTS: A total of 254 patients with NB were included in this study. They were randomly divided into a training cohort (n = 178) and a validation cohort (n = 76) at a ratio of 7:3. Multivariate analyses revealed that prognostic variables significantly related to the OS were age at diagnosis, bone metastasis, hepatic metastasis, INSS stage, MYCN status and DNA ploidy. The nomogram was constructed based on above 6 factors. The C-index values of the nomogram for predicting 3-year and 5-year OS were 0.926 and 0.964, respectively. The calibration curves of the nomogram showed good consistency between nomogram prediction and actual survival. The DCAs showed great clinical usefulness of the nomograms. Furthermore, patients with low-risk identified by our nomogram had much higher OS than those with high-risk (p < 0.001). CONCLUSION: The nomogram we constructed exhibited good predictive performance and could be used to assist clinicians in their decision-making process.

Biomimetic Hydrogen-Bonded G ⋠C ⋠G ⋠C Quadruplex within a Tetraphenylethene-Based Octacationic Spirobicycle in Water.

In biological systems, nucleotide quadruplexes (such as G-quadruplexes) in DNA and RNA that are held together by multiple hydrogen bonds play a crucial functional role. The biomimetic formation of these hydrogen-bonded quadruplexes captured by artificial systems in water poses a significant challenge but can offer valuable insights into these complex functional structures. Herein, we report the formation of biomimetic hydrogen-bonded G ⋅ C ⋅ G ⋅ C quadruplex captured by a tetraphenylethene (TPE) based octacationic spirobicycle (1). The spirobicyclic compound possesses a three-dimensional (3D) crossing dual-cavity structure, which enables the encapsulation of four d(GpC) dinucleotide molecules, thereby realizing 1 : 4 host-guest complexation in water. The X-ray structure reveals that four d(GpC) molecules further form a two-layer G ⋅ C ⋅ G ⋅ C quadruplex with Watson-Crick hydrogen bonds, which are stabilized within the dual hydrophobic cavities of 1 through the cooperative non-covalent interactions of hydrogen bonds, CH⋅⋅⋅π interactions, and hydrophobic effect. Due to the dynamically-rotational propeller chirality of TPE units, 1 with adaptive chirality can further serve as a chiroptical sensor to exhibit opposite Cotton effects with mirror-image CD spectra for the pH-dependent hydrogen-bonded assemblies of d(GpC) including the Watson-Crick G ⋅ C ⋅ G ⋅ C (pH 9.22) and Hoogsteen G ⋅ C+ ⋅ G ⋅ C+ (pH 5.74) quartets through the host-guest chirality transfer in water.

Efficacy of Random Forest Models in Predicting Multidrug-Resistant Gram-Negative Bacterial Nosocomial Infections Compared to Traditional Logistic Regression Models.

This study evaluates whether random forest (RF) models are as effective as traditional Logistic Regression (LR) models in predicting multidrug-resistant Gram-negative bacterial nosocomial infections. Data were collected from 541 patients with hospital-acquired Gram-negative bacterial infections at two tertiary-level hospitals in Urumqi, Xinjiang, China, from August 2022 to November 2023. Relevant literature informed the selection of significant predictors based on patients' pre-infection clinical information and medication history. The data were split into a training set of 379 cases and a validation set of 162 cases, adhering to a 7:3 ratio. Both RF and LR models were developed using the training set and subsequently evaluated on the validation set. The LR model achieved an accuracy of 84.57%, sensitivity of 82.89%, specificity of 80.10%, positive predictive value of 84%, negative predictive value of 85.06%, and a Yoden index of 0.69. In contrast, the RF model demonstrated superior performance with an accuracy of 89.51%, sensitivity of 90.79%, specificity of 88.37%, positive predictive value of 87.34%, negative predictive value of 91.57%, and a Yoden index of 0.79. Receiver operating characteristic curve analysis revealed an area under the curve of 0.91 for the LR model and 0.94 for the RF model. These findings indicate that the RF model surpasses the LR model in specificity, sensitivity, and accuracy in predicting hospital-acquired multidrug-resistant Gram-negative infections, showcasing its greater potential for clinical application.

N-Heterocyclic Carbene-Catalyzed Formal Intramolecular [3 + 2] Annulations of Cyclohexadienone-Tethered Ynals.

A formal [3 + 2] annulation of cyclohexadienone-tethered ynals is enabled by an N-heterocyclic carbene (NHC) catalyst, affording a tricyclo[6.2.1.04,11]undecane framework. This study represents the first demonstration of using C═C double bonds as the reaction partner in the NHC-catalyzed annulation of ynals. This strategy is characterized by mild reaction conditions and 100% atom economy as well as high catalytic performance and efficiency.

Identification of benzo[b]thiophene-1,1-dioxide derivatives as novel PHGDH covalent inhibitors.

The increased de novo serine biosynthesis confers many advantages for tumorigenesis and metastasis. Phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in serine biogenesis, exhibits hyperactivity across multiple tumors and emerges as a promising target for cancer treatment. Through screening our in-house compound library, we identified compound Stattic as a potent PHGDH inhibitor (IC50 = 1.98 ± 0.66 µM). Subsequent exploration in structural activity relationships led to the discovery of compound B12 that demonstrated the increased enzymatic inhibitory activity (IC50 = 0.29 ± 0.02 µM). Furthermore, B12 exhibited robust inhibitory effects on the proliferation of MDA-MB-468, NCI-H1975, HT1080 and PC9 cells that overexpress PHGDH. Additionally, using a [U-13C6]-glucose tracing assay, B12 was found to reduce the production of glucose-derived serine in MDA-MB-468 cells. Finally, mass spectrometry-based peptide profiling, mutagenesis experiment and molecular docking study collectively suggested that B12 formed a covalent bond with Cys421 of PHGDH.

Evaluation of pharmacist-led medication reconciliation at county hospitals in China: A multicentre, open-label, assessor-blinded, nonrandomised controlled study.

Background: Due to a lack of related research, we aimed to determine the effectiveness of a pharmacist-led medication reconciliation intervention in China. Methods: We conducted a multicentre, prospective, open-label, assessor-blinded, cluster, nonrandomised controlled study at six county-level hospitals, with hospital wards serving as the clusters. We included patients discharged from the sampled hospitals who were aged ≥60 years; had ≥1 studied diagnoses; and were prescribed with ≥3 medications at discharge. Patients in the intervention group received a pharmacist-led medication reconciliation intervention and those in the control group received standard care. We assessed the incidence of medication discrepancies at discharge, patients' medication adherence, and health care utilisation within 30 days after discharge. Results: There were 429 patients in the intervention group (mean age = 72.5 years, standard deviation (SD) = 7.0) and 526 patients in the control group (mean age = 73.6 years, SD = 7.1). Of the 1632 medication discrepancies identified at discharge, fewer occurred in the intervention group (1.9 per patient on average) than the control group (2.6 per patient on average).The intervention significantly reduced the incidence of medication discrepancy by 9.6% (95% confidence interval (CI) = -15.6, -3.6, P = 0.002) and improved patients' medication adherence, with an absolute decrease in the mean adherence score of 2.5 (95% CI = -2.8, -2.2, P < 0.001). There was no significant difference in readmission rates between the intervention and control groups. Conclusions: Pharmacist-led medication reconciliation at discharge from Chinese county-level hospitals reduced medication discrepancies and improved patients' adherence among patients aged 60 years or above, though no impact on readmission after discharge was observed. Registration: ChiCTR2100045668.

Urea reduces the sustainability of soil Cd immobilization by upregulating the expression of AmSTOP1 and AmMATE genes in edible amaranth roots.

After cadmium (Cd) immobilization remediation in contaminated farmland soil, which forms of nitrogen fertilizer should be implemented to keep its sustainability? Urea and nitrate were used to compare for their effects on the remobilization of stabilized Cd in the rhizosphere soil of edible amaranth at nitrogen concentrations of 60, 95, and 130 mg kg-1. The results showed that compared to nitrate nitrogen, the Cd content in shoots increased by 76.2%, 65.6%, and 148% after applying three different concentrations of urea, and the total remobilization amount of Cd also increased by 16.0%, 24.9%, and 14.0% respectively. Urea application promotes root secretion of citric acid, malic acid, pyruvate, and γ-aminobutyric acid, crucial in remobilizing stable Cd. The application of urea promoted the expression of genes involved in sucrose transport, glycolysis, the TCA cycle, amino acid secretion, citric acid efflux, and proton efflux. Arabidopsis heterologous expression and yeast one-hybrid assays identify critical roles of AmMATE42 and AmMATE43 in citric acid and fumaric acid efflux, with AmSTOP1 activating their transcription. Inhibition of SIZ1 expression in urea treatment reduce AmSTOP1 SUMOylation, leading to increased expression of AmMATE42 and AmMATE43 and enhanced organic acids efflux. Using edible amaranth as a model vegetable, we discovered that urea is not beneficial to preserving the sustainability of stabilized Cd during the reuse of remediated farmlands contaminated with Cd.

SP3-induced Timeless transcription contributes to cell growth of lung adenocarcinoma cells.

BACKGROUND: Timeless is well-known for its key role in replication checkpoints. Recent studies reveal the involvement of Timeless and specificity protein (SP) 1 in human malignancies. However, no evidence proved the interaction between SP3 and Timeless in lung adenocarcinoma (LUAD). METHODS: The expression and clinical significance of Timeless were analyzed using the LUAD dataset downloaded from the Cancer Genome Atlas (TCGA). Lentivirus-mediated Timeless knockdown in A549 cells was used to examine the role of Timeless in cell proliferation and pemetrexed (PEM) resistance. Transcription factors (TFs) bound to the Timeless promoter were identified by DNA pull-down technology with HPLC-MS/MS analysis and analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Dual-luciferase reporter assay was used to determine the activity of SP3 in Timeless transcription. RESULTS: Timeless was overexpressed in LUAD samples, and it could serve as a potential diagnostic or prognostic biomarker for LUAD patients. shTimeless-mediated knockdown of Timeless reduced cell viability and proliferation and sensitized PEM-resistant A549 cells to PEM. Four fragments (F1: 1-373 bp), (F2: 374-962 bp), (F4: 1274-1645 bp), and (F5: 1646-2000bp) were confirmed as the TF binding profiles of the Timeless promoter. KEGG analysis showed that the TFs bound to the Timeless promoter had relevance to spliceosome, RNA transport, and mRNA surveillance pathways. SP3 promoted the transcription of Timeless via the F2 fragment (374-962 bp) binding motif. CONCLUSION: Upregulation of Timeless mediated by SP3 promotes LUAD cell proliferation, providing evidence to support that targeting the SP3/Timeless axis may be a potential therapeutic strategy against LUAD.

Discovery of natural catechol derivatives as covalent SARS-CoV-2 3CLpro inhibitors.

The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a threat to public health, and extensive research by scientists worldwide has also prompted the development of antiviral therapies. The 3C-like protease (3CLpro) is critical for SARS-CoV-2 replication and acts as an effective target for drug development. To date, numerous of natural products have been reported to exhibit inhibitory effects on 3CLpro, which encourages us to identify other novel inhibitors and elucidate their mechanism of action. In this study, we first screened an in-house compound library of 101 natural products using FRET assay, and found that oleuropein showed good inhibitory activity against SARS CoV-2 3CLpro with an IC50 value of 4.18 µM. Further studies revealed that the catechol core is essential for activity and can covalently bind to SARS-CoV-2 3CLpro. Among other 45 catechol derivatives, wedelolactone, capsazepine and brazilin showed better SARS-CoV-2 3CLpro inhibitory activities with IC50 values of 1.35 µM, 1.95 µM and 1.18 µM, respectively. These catechol derivatives were verified to be irreversible covalent inhibitors by time-dependent experiments, enzymatic kinetic studies, dilution and dialysis assays. It also exhibited good selectivity towards different cysteine proteases (SARS-CoV-2 PLpro, cathepsin B and cathepsin L). Subsequently, the binding affinity between brazilin and SARS-CoV-2 3CLpro was determined by SPR assay with KD value of 0.80 µM. Molecular dynamic (MD) simulations study showed the binding mode of brazilin in the target protein. In particular, brazilin displayed good anti-SARS-CoV-2 activity in A549-hACE2-TMPRSS2 cells with EC50 values of 7.85 ± 0.20 µM and 5.24 ± 0.21 µM for full time and post-infection treatments, respectively. This study provides a promising lead compound for the development of novel anti-SARS-CoV-2 drugs.

Long non-coding RNA Linc00657 up-regulates Skp2 to promote the progression of cervical cancer through lipid reprogramming and regulation of immune microenvironment.

More and more evidence shows that long non-coding RNA (lncRNA) plays an important role in the biological behavior of many kinds of malignant tumors, but the specific function of lncRNA Linc00657 in cervical cancer is still unknown. The purpose of this study is to explore the effect of Linc00657 on the malignant progression of cervical cancer and its potential mechanism. In two kinds of cervical cancer cell lines and normal cervical epithelial cells, qRT-PCR showed increased expression of Linc00657 in cervical cancer cells. Through MTT, clone formation test, flow cytometry, wound healing test and Transwell test, it has been found that overexpression of Linc00657 could promote the proliferation,migration and invasion of cervical cancer cells，and inhibit apoptosis. Through the StarBase database, it was found that there may be a mutual regulatory relationship between Linc00657 and Skp2, and Skp2 may be the downstream target of Linc00657. QRT-PCR detection confirmed that the expression of Skp2 was increased in cervical cancer cells with overexpression of Linc00657. TIMER2 database found that Skp2 was associated with lipid metabolic enzymes and immune cell infiltration. It was found that Linc00657 knockdown inhibited tumor growth and metastasis and inhibited the expression of Skp2 in vivo. In short, our research shows that Linc00657 has carcinogenic properties in cervical cancer, and LINC00657 promotes the occurrence of cervical cancer by up-regulating the expression of Skp2. We predict that Linc00657/mir30s/Skp2 axis plays a role in the malignant progression of cervical cancer. In addition, Skp2 may participate in cancer immune response and promote lymph node metastasis of cervical cancer through lipid reprogramming. These findings also provide promising targets for the diagnosis and treatment of cervical cancer.

LINC00460 knockdown sensitizes cervical cancer to cisplatin by downregulating TGFBI.

The acquired resistance of cancer to cisplatin (DDP) limits the efficacy of chemotherapy. The prognostic value of long noncoding RNA (lncRNA) LINC00460 has been reported in cervical cancer. However, its effect on DDP sensitivity in cervical cancer remains poorly understood. In present study, LINC00460 was screened out through bioinformatics analysis. The expression levels of mRNAs and proteins were measured by reverse transcription-quantitative PCR (RT-qPCR) or western blot analysis. The sensitivity to DDP was investigated using an CCK8 assay. Cell apoptosis was determined by flow cytometry. The differentially expressed genes that were associated with the poor prognosis of cervical cancer were screened, and their correlations with LINC00460 expression were explored using Pearson's correlation analysis. Tumor xenograft model was used to assess the effect of LINC00460 knockdown on DDP sensitivity in vivo. The interaction between miR-338-3p and LINC00460 or transforming growth factor ß-induced protein (TGFBI) was confirmed by RNA immunoprecipitation (RIP) and luciferase reporter assays. LINC00460 expression was increased in cervical cancer tissues and cells. High expression of LINC00460 was associated with dismal prognosis in cervical cancer patients. Silencing of LINC00460 increased drug sensitivity and induced apoptosis in DDP-resistant-cervical cancer cells. LINC00460 knockdown enhanced DDP sensitivity in cervical cancer cells largely by downregulating TGFBI expression. LINC00460 knockdown enhanced the sensitivity of cervical cancer to DDP in vivo, and this effect was partly mediated by the downregulation of TGFBI. LINC00460 positively regulated TGFBI expression, possibly by acting as a sponge of miR-338-3p. LINC00460 knockdown contributed to DDP sensitivity of cervical cancer by downregulating TGFBI, providing a novel mechanism underlying the acquisition of DDP sensitivity.

Short-term exposure to gaseous pollutants is neglected factors for knee osteoarthritis: evidence from a humid subtropical region of China.

Few studies were performed on the impact of exposure to gaseous pollutants on the risk of knee osteoarthritis (KOA). We conducted this study to analyze the association between short-term exposure to gaseous pollutants and the risk of hospitalizations for KOA. A total of 2952 KOA hospitalizations derived from two hospitals in Hefei, and the relationship between gaseous pollutants and KOA hospitalizations was analyzed by a distributed lag non-linear model combined with a generalized linear model. We found that the decreased risk of hospitalizations for KOA were both related to exposure to NO2 (RR = 0.993, lag19 day) and O3 (RR = 0.984, lag0 day), while exposure to CO could increase the risk of hospitalizations for KOA (RR = 1.076, lag2 day). Stratified analyses suggested that the KOA patients < 65 years were more susceptible to O3 exposure, and the female, male, patients ≥ 65 years, and patients < 65 years were both more sensitive to CO exposure. Our findings demonstrated that exposure to NO2, O3 resulted in a decreased risk for KOA hospitalizations, and CO exposure might increase the risk of KOA hospitalizations.

Silicon nutrition improves the quality and yield of rice under dry cultivation.

BACKGROUND: Dry cultivation of rice is a water-saving, emission reduction and labor-saving rice farming method. However, the development of rice under dry cultivation is hampered by the limitations of dry cultivation on rice yield and rice quality. We hypothesized that additional silicon (Si) would be a measure to address these limitations or challenges. RESULTS: In the present study, we set up field trials with three treatments: flooded cultivation (W), dry cultivation (D) and dry cultivation plus Si. Yield and quality were reduced under D treatment compared to W treatment. The addition of Si promoted root development, increased plant height and leaf area, increased photosynthetic enzyme activity, net photosynthetic rate and SPAD values, and increased biomass under dry crop conditions. Under the drought conditions, silica up-regulated the expression of AGPSI, SBEI, SBEIIb, SSI and SSII-1 genes and the activities of ADP-glucose pyrophosphorylase (AGPase), soluble starch synthetase (SSS) and starch branching enzyme (SBE) enzymes, which reduced protein, amylose, chalkiness percentage and chalkiness degree, increased brown rice rate, milled rice rate and head milled rice rate, and also improved rice quality. In addition, the increase of AGPase, SSS and SBE enzyme activities promoted the filling rate and the number of spikes was guaranteed, whereas the yield was improved by promoting the seed setting rate and 1000-grain weight. CONCLUSION: The results of the present study indicate that adding appropriate amounts of Si fertilizer can improve the yield and quality of rice under dry cultivation by regulating source supply capacity and grain starch synthesis. © 2023 Society of Chemical Industry.

Association of lncRNA THRIL, HOTAIR genes variations and expression levels with pulmonary tuberculosis.

BACKGROUND: Long non-coding RNA (lncRNA) has been implicated in the pathogenesis of pulmonary tuberculosis (PTB). This study aims to investigate the involvement of lncRNA THRIL and HOTAIR gene single nucleotide polymorphisms (SNPs) and their expression levels in PTB susceptibility. METHODS: A total of 456 PTB patients and 464 healthy controls participated in our study. we genotyped six SNPs of THRIL and HOTAIR genes using an improved multiple ligase detection reaction (iMLDR). Additionally, real-time reverse-transcriptase polymerase chain reaction was employed to detect the expression levels of THRIL and HOTAIR in peripheral blood mononuclear cells (PBMC) from 78 PTB patients and 84 healthy controls. RESULTS: No significant differences in allele and genotype frequencies were observed for THRIL rs1055472, rs11058000, and HOTAIR rs12427129, rs1899663, rs4759314, and rs7958904 polymorphisms between PTB patients and healthy controls (all P > 0.05). Moreover, genotype frequencies of all SNPs did not show any association with PTB susceptibility in the dominant-recessive model. However, the frequencies of rs7958904 CC genotype and C allele in the HOTAIR gene were significantly correlated with leukopenia in PTB patients. Furthermore, the expression levels of the HOTAIR gene were significantly elevated in PTB patients compared to controls. CONCLUSIONS: Our study indicates that THRIL and HOTAIR gene SNPs might not contribute to PTB susceptibility, while the level of HOTAIR was increased in PTB patients.

The Methylation in B7-H4 and BTLA Genes are Associated with the Risk of Pulmonary Tuberculosis.

Background: The important roles of B7 homologous body 4 (B7-H4), B and T lymphocyte attenuator (BTLA) in patients with pulmonary tuberculosis (PTB) have been reported. This study aims to evaluate the association among B7-H4 and BTLA genes polymorphism, methylation and PTB susceptibility. Methodology: Here, we assessed the possible relationship of 10 single nucleotide polymorphisms (SNPs) in B7-H4, BTLA genes with PTB susceptibility in a Chinese population (496 PTB patients and 502 controls) by SNPscan technique. Then, the B7-H4, BTLA genes methylation levels among 98 PTB patients and 97 controls were detected using MethylTarget technique. Results: This study found no significant differences in allele and genotype frequencies of B7-H4 gene rs10754339, rs10801935, rs10923223, rs1937956, rs3738414, BTLA gene rs1982809, rs2971205, rs75368388, rs9288953 variants between PTB patients and controls. Haplotype analysis suggested that the lower frequencies of B7-H4 AATTG haplotype, BTLA GATT haplotype and the higher frequency of BTLA AGTC haplotype were found in PTB patients when compared with controls. We also found that the frequency of BTLA gene rs9288953 C allele was significantly increased in PTB patients with drug resistance. Moreover, the methylation levels of B7-H4 and BTLA genes in PTB patients were greater than that in controls, and rs10754339 variant in B7-H4 gene could affect its methylation level in PTB patients. Conclusion: B7-H4, BTLA genes polymorphism might not affect PTB susceptibility, while the abnormal methylation levels of B7-H4, BTLA genes were associated with the genetic background of PTB.

[The Effects of IGHG1 on the Proliferation and Apoptosis of Human Acute Myeloid Leukemia THP-1 Cells].

OBJECTIVE: To investigate the effects of the immunoglobulin G1 heavy chain constant region (IGHG1) on the proliferation and apoptosis of acute myeloid leukemia (AML) THP-1 cells and its possible mechanism of action. METHODS: Human AML THP-1 cells were cultured in vitro and divided into control (normally cultured THP-1 cells), pcDNA3.1 ï¼»THP-1 cells transfected with IGHG1 overexpression (pcDNA3.1-IGHG1) negative control plasmidï¼½, pcDNA3.1-IGHG1 (THP-1 cells transfected with plasmid containing pcDNA3.1-IGHG1), LY364947 ï¼»transforming growth factor-ß (TGF-ß)/signal transduction protein (Smad) inhibitor LY364947 20 µmol/L treated THP-1 cellsï¼½, si-NC ï¼»THP-1 cells transfected with IGHG1-small interfering RNA (siRNA) negative controlï¼½, si-IGHG1 (THP-1 cells transfected with IGHG1-siRNA), and si-IGHG1+LY364947 (IGHG1-siRNA and LY364947 co-treated THP-1 cells) a total of 7 groups. Fluorescence quantitative PCR was used to detect the expression of IGHG1 and immunoglobulin G (IgG) mRNA of THP-1 cells in each group; CCK-8 was used to detect THP-1 cells proliferation activity; flow cytometry was used to detect THP-1 cells apoptosis and cell cycle in each group; Western blot was used to detect the THP-1 cells proliferation, apoptosis and the expression of TGF-ß/Smad signaling pathway related proteins. RESULTS: Compared with the control group, after overexpression of IGHG1, the expression of IGHG1 and IgG mRNA, cell proliferation viability, S phase cell ratio, expressions of Cyclin D1, B cell lymphoma-2 (Bcl-2), IgG, TGF-ß1, phosphorylated Smad3 (p-Smad3)/Smad3 protein in THP-1 cells were significantly increased (P<0.05), the apoptosis rate, G0/G1 phase cell ratio, expression of p21, Bcl-2 related X protein (Bax), Caspase-3 protein were significantly reduced (P<0.05); after inhibiting TGF-ß/Smad signaling pathway or silencing IGHG1, the expression of IGHG1 and IgG mRNA, cell proliferation viability, S phase cell ratio, expression of Cyclin D1, Bcl-2, IgG, TGF-ß1, p-Smad3/Smad3 protein in THP-1 cells were significantly reduced (P<0.05), the apoptosis rate, G0/G1 phase cell ratio, expressions of p21, Bax, and Caspase-3 protein were significantly increased (P<0.05); and compared with silencing IGHG1, after co-treatment of IGHG1 gene silencing and TGF-ß/Smad pathway inhibition, the expression of IGHG1 and IgG mRNA, cell proliferation viability, S phase cell ratio, expressions of Cyclin D1, Bcl-2, IgG, TGF-ß1, p-Smad3/Smad3 protein in THP-1 cells were significantly reduced (P<0.05), the apoptosis rate, G0/G1 phase cell ratio, expression of p21, Bax, and Caspase-3 protein were significantly increased (P<0.05). CONCLUSION: Silencing IGHG1 gene can down-regulate the expression of IgG, inhibit the proliferation of human AML THP-1 cells, block cell cycle progression, and induce cell apoptosis; its mechanism may be related to the inhibition of the TGF-ß/Smad pathway activation.

Aging effects on residential biomass burning emissions under quasi-real atmospheric conditions.

Emissions from biomass burning (BB) vastly contribute to the atmospheric trace gases and particles, which affect air quality and human health. After emission, the chemical evolution changes the mass and composition of organic aerosol (OA) in the diluted and aged plume. In this study, we used a quasi-real atmospheric smog chamber system to conduct aging experiments and investigated the multiphase oxidation of primary organic aerosol (POA) and the formation of secondary organic aerosols (SOA) in residential biomass burning plumes. We found that the emissions in the gas and particle phases were interlinked during the plume evolution. During photochemical aging, more oxidized OA was produced, and SOA formation increased by a factor of 2 due to functionalization reactions of gaseous precursors such as furans, phenols, and carbonyls. On the other hand, dark aging resulted in a lower OA mass enhancement by a factor of 1.2, with weaker oxidation from gaseous reactions. Dark aging experiments resulted in the generation of substantial quantities of nitrogen-containing organic compounds in both gas and particulate phases, while photochemical aging led to a notable increase in the concentration of gaseous carboxylic acids. Our observations show that the properties of SOA are influenced by exposure to sunlight radiation and oxidants such as OH or NO3 radicals. These results reflect the aging process of BB plumes in real-world atmospheric conditions and highlight the importance of considering various aging mechanisms.

Hereditary transthyretin cardiac amyloidosis proven by endomyocardial biopsy: a single-centre retrospective study and literature review.

BACKGROUND: This study aimed to report the genotypes and phenotypes of hereditary transthyretin cardiac amyloidosis (hATTR-CA) in a Western Chinese cohort and review the genetic profiles of this disorder in the Chinese population. METHODS: Transthyretin (TTR) gene sequencing of probands diagnosed with TTR cardiac amyloidosis and their relatives was performed at West China Hospital of Sichuan University from January 2018 to December 2021. All patients underwent endomyocardial biopsy for light and electron microscopy examinations. Clinical and essential examination materials were retrospectively collected and analysed. RESULTS: TTR gene alteration was demonstrated in five probands and their two relatives. Three TTR variants were identified, namely, Ser23Asn, Glu54Leu and Thr60Ala. This study is the first to report Glu54Leu as pathogenic mutations in Chinese hATTR-CA patients. The Ser23Asn mutation was the most common mutation in this cohort. Five probands, including two males and three females, were all ethnic Han-Chinese. The median age at diagnosis and delay in diagnosis (interval from onset to diagnosis) was 56 years (range, 54-69 years) and 8 years (range, from 1 to 30 years), respectively. Three cases showed a defined family history of amyloidosis. Endomyocardial biopsies and TTR immunohistochemistry showed positive results in all patients. Two probands died 17.0 months and 21.0 months after diagnosis. CONCLUSIONS: We identified one novel TTR variants causing hATTR-CA in the West Han Chinese population. To avoid misdiagnosis or delayed diagnosis of hATTR-CA, TTR genotypic screening and endomyocardial biopsy should be performed as soon as possible in cases with heightened clinical suspicion.