Amplified Fluorescence by Hollow-Porous Plasmonic Assembly: A New Observation and Its Application in Multiwavelength Simultaneous Detection.

Surface plasmon coupled emission (SPCE) is a new analytical technique that provides increased and directional radiation based on the near-field interaction between fluorophores and surface plasmons but suffers from the limitation of insufficient sensitivity. The assembly of hollow-porous plasmonic nanoparticles could be the qualified candidate. After the introduction of gold nanocages (AuNCs), fluorescence signal enhancement was realized by factors over 150 and 600 compared with the normal SPCE and free space emission, respectively, with a fluorophore layer thickness of approximately 10 nm; hence, the unique enhancement of SPCE by the AuNCs effectively overcomes the signal quenching induced by resonance energy transfer (in normal SPCE). This enhancement was proven to be triggered by the superior wavelength match, the enhanced electromagnetic field, and new radiation channel and process induced by the AuNC assembly, which provides an opportunity to increase the detection sensitivity and establish an optimal plasmonic enhancement system. The amplified SPCE system was employed for multiwavelength simultaneous enhancement detection through the assembly of mixed hollow nanoparticles (AuNCs and gold nanoshells), which could broaden the application of SPCE in simultaneous sensing and imaging for multianalytes.

[Physiochemical property variation in traditional Chinese medicine decoction before or after precipitation in alcohol and its relationship with wall stickiness in spray drying].

To explore the relationship between the variations of the physiochemical properties of traditional Chinese medicine(TCM) decoction before or after precipitation in alcohol and the wall stickiness in spray drying. In this study, widely used TCMs in clinic were selected to determine the physiochemical properties of TCM decoction before or after precipitation in alcohol separately.Afterwards, the principle component analysis(PCA),Hierarchical cluster analysis(HCA),and orthogonal partial least squares-discriminate analysis(OPLS-DA) were used to evaluate the relationship between the variations of those liquid before or after precipitation in alcohol and hot-melt stickiness in spray drying.Three types of statistical analysis methods all indicated that ethanol precipitation affected physiochemical properties of TCM decoction, and the variations of physical properties showed significant association with hot-melt stickiness in spray drying.The results of PCA-X and HCA suggested that the dynamic surface tension(DST) was impacted most by the alcohol deposition treatment,at the same time,the other 5 physiochemical properties were also affected.OPLS-DA verified that PCA-X and HCA results, and revealed that DST,equilibrium surface tension(EST) and pH were significantly affected by alcohol deposition treatment,and the order of the affecting factors from high to low was DST,EST and pH.Therefore,the downward trend of DST and pH were the important factors that directly affected the hot-melt stickiness of TCM after precipitation in alcohol,which would be probably caused by losing macromolecules alcoholic insoluble components and increasing relative proportions of organic acid and small molecule sugar.

[A new device for determination of adhesive force and its application in predicting hot-melt sticking in spray drying of traditional Chinese medicine].

A new device was designed to measure adhesive force and predict whether traditional Chinese medicine extracts would appear hot-melt sticking in spray drying process．Based on the physical property tester as fundamental test platform, the device was fixed with a camera, a temperature and humidity sensor probe and a set of equipment for hot air. This device could simulate the dry environment of spray dryer and analyze the variables of testing solutions' adhesiveness against drying time. To establish and validate a model of predicting hot-melt sticking in spray drying, data was collected by using data mining. The results of this study proved that the device could be used to predict the hot-melt sticking in spray drying based on the adhesive force of materials (testing solutions). In addition, the study also found that the adhesiveness of the hot-melt sticking materials gradually increased with the evaporation of water, while that of non-sticking materials first increased and then rapidly decreased.

[Correlation between chemical compositions of traditional Chinese medicine extracts and phenomenon of wall stickiness in spray drying].

To explore the correlation between chemical compositions (organic acids, small molecule sugars, protein and others) of traditional Chinese medicine extracts and the wall stickiness in spray drying. In this study, 55 types of most common used Chinese herbs were selected to determine the content of 7 chemical components such as citric acid and fructose from plant extraction. The status of wall stickiness was observed during the drying process. The principle component analysis (PCA-X), hierarchical clustering analysis(HCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were then used to evaluate the correlation between each chemical compositions and wall stickiness, so as to look for the essential chemical compositions associated with the wall stickiness. All of the above 3 statistical analysis methods showed significant results in distinguishing the two groups (sticky or non-sticky). PCA-X score chart and HCA clustering scatter plot suggested that the small molecular substance was the main factor causing wall stickiness, which was then proved by the reality where some of the traditional herb extracts were in non-sticky state after drying but in sticky state after alcohol precipitation. OPLS-DA results revealed that L-malic acid, citric acid, fructose and glucose were the difference factors for the wall stickiness of the extracts. Under small molecular components, L-malic acid, citric acid, fructose and glucose were the crucial factors that directly led to the hot melt sticky wall of the herbal extracts, and macromolecular substances might ameliorate the function of wall stickiness.

Differential cytokine expression detected by protein microarray screening in peripheral blood of patients with refractory Graves' disease.

OBJECTIVE: The prognosis of Graves' disease (GD) varies among patients. However, the immune pathogenesis of refractory GD is still unknown. The aim of this study was to explore the cytokine expression profile associated with refractory GD. METHODS: Preliminary cytokine protein microarray screening was performed to detect differentially expressed cytokines in the plasma of four patients with refractory GD and four patients with stable GD. Some differentially expressed cytokines were then validated in plasma by enzyme-linked immunosorbent assay (ELISA) and in peripheral blood mononuclear cells (PBMCs) by quantitative real-time polymerase chain reaction (qRT-PCR) on another independent set of samples. RESULTS: We found that 21 cytokines were differentially expressed between patients with intractable GD and those in remission, including 18 upregulated and 3 downregulated cytokines with a fold change >1·30 and <0·77, respectively. Intractability-related elevation of three cytokines (IL-4, IL-6 and IL-10) was validated by ELISA in plasma on another GD cohort with 30 patients in recurrence and 14 in remission (t-test, P = 0·035, 0·033 and 0·041, respectively). Furthermore, mRNA expression of IL-4, IL-6 and IL-10 in PBMCs, detected by qRT-PCR, was significantly elevated in patients with refractory GD compared with those in remission (P = 0·039, 0·047 and 0·042, respectively). CONCLUSION: The severity of GD is associated with the aberrant expression and secretion of several cytokines that may serve as potential biomarkers and predictors for disease prognosis. Targeting these cytokines or their receptors may also lead to a novel therapeutic intervention for GD.

Increased IL-21/IL-21R expression and its proinflammatory effects in autoimmune thyroid disease.

To determine the potential role of interleukin-21 (IL-21) / IL-21 receptor (IL-21R) in the pathogenesis of autoimmune thyroid disease (AITD) mainly known as Graves' disease (GD) and Hashimoto's thyroiditis (HT). IL-21 and IL-21R of peripheral blood samples and/or thyroid tissues from AITD patients and healthy controls were analyzed by ELISA, quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry and immunohistochemistry. In vitro, the mRNA and protein of inflammatory cytokines of cultured peripheral blood mononuclear cells (PBMCs) upon recombinant human IL-21 (rhIL-21) stimulation were detected. There was an increased serum concentration of IL-21 in untreated GD and HT patients, and IL-21(+)CD3(+)CD8(-)T cells were significantly increased in PBMCs of HT patients compared with healthy volunteers. The IL-21 mRNA expression in PBMCs increased dramatically in GD and HT patients, and marked augmentations of IL-21 and IL-21R mRNA in thyroid tissues of HT patients were observed. Immunohistochemical staining confirmed the expression of IL-21R protein in HT thyroid cells and lymphocytes. In vitro, PBMCs from GD cultured with rhIL-21 induced increased IL-17A but decreased IL-4 production, while from HT stimulated by rhIL-21 induced augmented production of IFN-γ. In conclusion, the expression of IL-21 and IL-21R were up-regulated in AITD and may be involved in the pathogenesis of the disease through augmenting aberrant immune cascade.

Characteristics and indications of hydrogen and oxygen isotopes distribution in lake ice body.

Stable isotopes have been used to identify the characteristics of precipitation, evaporation, basin hydrology, and residence times. However, lakes in the cold regions are usually covered by ice for 5-6 months. To get a better understanding of stable isotopes characteristics and indications in lake ice bodies, ice and water were sampled during the icebound season in both the ice and water bodies in Dali Lake, and deuterium, oxygen-18 total nitrogen (TN), and the major ions were analyzed. The results showed that deuterium and oxygen-18 compositions (δD-δ¹8O) compositions in the ice body were greater than in the water body beneath, scattered on a straight line, and deviating downward from the global meteoric water line in the top right. The ice profile showed that the δD-δ¹8O compositions increased from the ice surface downward and decreased near to the bottom. In contrast, the TN and the major ions in the ice decreased from the ice surface downward and increased near to the bottom, meaning that the concentrations of δ¹8O had a negative correlation with the concentrations of TN and major ions. These indicated that stable isotopes can be used for tracing the nutriment and ion transport processes in the ice body.

Study of genetic variants of 8q21 and 8q24 associated with prostate cancer in Jing-Jin residents in northern China.

BACKGROUND: To identify the genetic risk of six genetic variants at 8q21 and 8q24 (including rs1512268, A; rs12543663, C; rs10086908, C; rs1016343, T; rs13252298, A, and rs6983561, C) associated with prostate cancer in Beijing and Tianjin (Jing-jin) area residents in northern China. METHODS: 574 subjects were enrolled. Blood samples and clinical information were collected from histologically confirmed prostate cancer cases (n = 286) and clinically evaluated matched normal controls (n = 288) from Chinese men in northern China. Six SNPs at 8q21 and 8q24 were genotyped by high-resolution melt and sequencing in subjects. We compared statistical differences between the prevalence of risk genotypes with prostate cancer in cases and controls and analyzed the association between clinical covariates and risk loci in case groups to infer their relationship with aggressive prostate cancer. RESULTS: Three genotypes of rs10086908, CC (OR = 2.48; 95% CI = 1.02 - 5.98, p = 0.037) rs1016343, TT (OR = 1.64, 95% CI = 1.07 - 2.53, p = 0.023); and rs6983561, CC (OR = 1.91; 95% CI = 1.09 - 3.63, p = 0.044) at 8q24 were identified to be associated with prostate cancer risk in Jing-jin Chinese. The D' values of both two-locus haplotypes (T-A: rs1016343 vs. rs13252298; T-C: rs1016343 vs. rs6983561) were 0.907 and 0.859, respectively, the three-locus haplotype, only TAC constituted by the loci (rs1016343, T; rs13252298, A; rs6983561, C) was also associated with prostate cancer (p = 0.033), revealing rs1016343 vs. rs6983561 with significant differences between cases and controls. According to clinical covariates and odds ratios of risk genotypes relative to non-risk genotypes, rs6983561, CC was associated with age (OR = 2.5; 95% CI = 1.02 - 6.13, p = 0.039), and tumor aggressiveness (OR = 1.15; 95% Cl = 1.06 - 1.23, p = 0.013). CONCLUSIONS: The loci including rs10086908, rs1016343, and rs6983561 at 8q24 could be associated with prostate cancer in Jing-jin residents in northern China. Our results suggest that these loci could influence susceptibility to prostate cancer in the northern Chinese population.

[Correlation of androgen receptor CAG repeats with the risks of benign prostatic hyperplasia and prostate cancer: a meta-analysis].

OBJECTIVE: To explore the association of the androgenic receptor (AR) CAG repeats with the risks of benign prostatic hyperplasia (BPH) and prostate cancer (PCa). METHODS: We searched the major databases at home and abroad for the literature addressing the correlation of the AR gene CAG repeats with BPH and PCa. Based on the results of heterogeneity tests, we used the M-H fixed effect model and random effect model to pool the odds ratio (OR) effect size. We evaluated publication bias by Begg and Egger bias analysis, investigated the association of CAG repeats with the risks of BPH and PCa by systematic review, and stratified their relationship according to the races of the patients. RESULTS: Based on the selection criteria, 4 of the 29 identified studies were included, with 485 cases of BPH, 767 cases of PCa, and 709 controls. There was no heterogeneity between the BPH and control groups, and no correlation between short CAG repeats and BPH after pooling the odds ratio (OR) effect size. Heterogeneity was found among the BPH, PCa and control groups. Random effects model suggested an association of short CAG repeats with the risk of PCa (OR(PCa/control) = 1.45, OR(PCa/BPH) = 1.86, OR(PCa/(BPH + control)) = 1.66), while subgroup analysis with racial stratification indicated inter-ethnic differences between the two. Begg and Egger bias analysis showed no significant publication bias. CONCLUSION: Shorter CAG repeats are positively correlated with the risk of PCa but not with that of BPH.

[Greenhouse Gas Emissions Characteristics and Driving Factors Analysis in the Eutrophic Saline Lake Daihai Lake].

To investigate the greenhouse gas emission characteristics and driving factors of eutrophic saline lakes in northern China, considering Daihai Lake in Inner Mongolia as an example, 10 monitoring sites were selected based on hydrological distribution characteristics in April, July, and October 2023. Using headspace gas chromatography and modeling methods, dissolved concentrations and exchange fluxes of carbon dioxide （CO2）, methane （CH4）, and nitrous oxide （N2O） were determined in the nearshore zone, open lake area, and lake center surface water. During the study period, Daihai Lake exhibited significant seasonal variations in greenhouse gas concentration and flux. The average concentrations of CO2, CH4, and N2O in surface water were （26.52 ± 17.58） µmol·L-1, （282.30 ± 172.30） nmol·L-1, and （9.09 ± 1.64） nmol·L-1, respectively. The average fluxes were （5.29 ± 11.98） mmol·ï¼ˆm2·d）-1, （178.24 ± 63.34） µmol·ï¼ˆm2·d）-1, and （-0.74 ± 1.28） µmol·ï¼ˆm2·d）-1, with cumulative emissions of 50 770.77, 543.52, -4.21 kg·km-2 and a global warming potential （expressed in CO2-equivalent） of 50 770.77, 15 218.49, -1 254.48 kg·km-2. Daihai Lake acted as a source of atmospheric CO2 and CH4 but a sink for N2O during the study period. Correlation and stepwise regression analyses revealed that pH and total dissolved solids （TDS） influenced CO2 concentration and flux, while the factors affecting CH4 were water temperature （WT）, water depth （WD）, wind speed （WS）, oxidation-reduction potential （ORP）, and total nitrogen （TN）. For N2O, the influencing factors were WT, WS, and TN. Additionally, Daihai Lake's eutrophication and salinity characteristics influenced the generation and emission of greenhouse gases. This study provides insights into the greenhouse gas dynamics and environmental factors in eutrophic saline lakes like Daihai Lake.

[Whole Process Analysis and Fate Behavior of Microplastics in Urban Wastewater Treatment Plants, Including their Occurrence Forms, Components, and Removal Efficiency].

Microplastics are among the most difficult new pollutants to remove in wastewater treatment plants. In order to explore the occurrence form, size distribution, composition, removal efficiency, migration law, and fate behavior characteristics of microplastic particles in sewage plants, taking a sewage treatment plant in Hohhot as an example, a total of 17 sampling sites were set up. The LAS X software counted the shape, abundance, and size of microplastics and conducted a full-process analysis. The results showed that： fibrous microplastics had the highest abundance and widest distribution and were the main form of existence, accounting for 61.8% of the total abundance； the size of microplastics ranged mainly between 0 and 1.00 mm, and among the four sizes, the abundance of microplastics 0.25 to 0.50 mm in China was the highest, accounting for 32.9%. Among the eight types of plastic components detected, polyester substances （PET, PBT）, cellulose, and polypropylene （PP） were the main components, accounting for 25%, 21%, and 17%, respectively. The influent abundance of the sewage plant was （73 ±5） n·L-1, the effluent abundance was （14 ±2） n·L-1, and the overall removal rate was （80.8 ±12.1）%. Among the three treatment stages of the sewage plant, only the primary treatment played a role in removal, and the abundance of microplastics surged in the secondary treatment. Different structures playing a major role in the removal of microplastics were fine grids （49.2 ±7.4）% and secondary sedimentation tanks （92.4 ±13.9）%. Microplastics mainly existed in the form of fibers, fragments, and films. The proportion of fibers was approximately 70%, and the size of fragments was mainly concentrated between 0.50 and 5.00 mm. Most fragments were in the range of 5.00 mm, accounting for 50%, making them the main form apart from fibrous. The film-like size was mostly concentrated in the range of less than 0.50 mm, accounting for more than 10%. Therefore, improving the removal of small-sized fibrous and film-like microplastics and large-sized fragmented microplastic particles can effectively reduce the pollution risk of microplastics in the environment caused by sewage plant drainage.

[Spatiotemporal Distribution and Source Analysis of Heavy Metals in Surface Sediments in Lake Ulansuhai Based on PCA-APCS-MLR Model].

To explore the spatial and temporal distribution characteristics of heavy metals in the surface sediments of lakes in cold regions during ice-sealing and non-ice-sealing periods, we analyzed the potential ecological risk degree and the pollution sources. A total of 20 sampling sites in Lake Ulansuhai in cold regions were collected from 2020 to 2021, and 120 surface sediment samples were collected during different periods. The contents of As, Cd, Cr, Cu, Ni, Pb, Zn, and Hg were determined. Correlation analysis, principal component analysis, and the absolute factor score-multiple linear regression (APCS-MLR) receptor model were used to trace the source of heavy metal pollution. The results showed that:① the distribution of heavy metals in lake surface sediments was different between the ice-sealing period and the non-ice-sealing period. The distribution of heavy metals during the ice-sealing period was higher in the north and lower in the south. Cd and Hg were mainly distributed in the central and southern lakes during the non-glacial period. ② Hg, Cd, and As were moderately polluted, and Ni was mildly polluted in the surface sediments of the lake. The overall performance was at a high risk level, and the pollution level during the non-ice-sealing period was higher than that during the ice-sealing period. The main environmental risk factors were Hg and Cd, which showed high risk and moderate risk, respectively. ③ The sources of heavy metals in lake surface sediments were mainly industrial sources from mining and transportation, agricultural sources, and natural sources. As, Ni, Pb, and Hg were mainly affected by industrial sources, with contribution rates of 62.67%, 75.31%, 77.47%, and 80.11%, respectively. The main sources of Cu and Zn were natural sources, and Cd was greatly affected by agricultural sources. The contribution rate was 81.57%. The source of Cr was mainly affected by natural factors, and the influence of human activities and unknown sources require further attention.

Association of single-nucleotide polymorphisms in the STAT3 gene with autoimmune thyroid disease in Chinese individuals.

The aim of this study was to investigate the association between signal transducer and activator of transcription 3 (STAT3) polymorphisms and autoimmune thyroid diseases and clinical features. We genotyped six single-nucleotide polymorphisms (SNPs) rs1053005, rs2293152, rs744166, rs17593222, rs2291281, and rs2291282 of STAT3 gene in 667 patients with autoimmune thyroid disease (417 Graves' disease (GD) and 250 Hashimoto's thyroiditis (HT)) and 301 healthy controls. The allele A from rs1053005 was significantly less frequent in both GD and HT patients (P = 0.0024, OR = 0.6958, 95%CI = 0.5508-0.8788; P = 0.0091, OR = 0.7013, 95%CI = 0.5397-0.9112, respectively). The AA genotype of rs1053005 was less in GD and HT patients too (P = 0.0025,OR = 0.6278, 95%CI = 0.466-0.847) and (P = 0.0036,OR = 0.601, 95%CI = 0.428-0.843). The allele G from rs17593222 increased the susceptibility to the ophthalmopathy development both in autoimmune thyroid disease (AITD) and GD patients (P = 0.0007, OR = 3.980, 95%CI = 1.871-8.464; P = 0.0081, OR = 3.378, 95%CI = 1.441-7.919, respectively). The allele A and AA genotype of SNP rs1053005 may protect individuals from the susceptibility to AITD and their frequency decreased in AITD patients. In addition, the allele G of rs17593222 may increase the ophthalmopathy risk in AITD patients. Our findings suggest the existence of association between STAT3 gene and AITD, thus adding STAT3 gene to the list of the predisposing genes to AITD.

Polymorphisms of interleukin-21 and interleukin-21-receptor genes confer risk for autoimmune thyroid diseases.

BACKGROUND: The abnormality of interleukin-21 (IL-21)-IL-21-receptor (IL-21R) system has been found in many autoimmune diseases including autoimmune thyroid diseases (AITDs). In this study, we investigated whether polymorphisms of the IL-21 and IL-21R are associated with Graves' disease (GD) and Hashimoto's thyroiditis (HT), two major forms of AITDs, among a Chinese population. METHODS: Rs907715, rs4833837, rs2221903 and rs2055979 of the IL-21 gene and rs3093301 and rs2285452 of the IL-21R gene were explored in a case-control study including 405 GD, 228 HT patients and 242 controls. These genes were genotyped by the PCR and restriction fragment length polymorphism (RFLP) analysis and the MASS spectrometry method. RESULTS: For IL-21 gene, we identified and confirmed a higher prevalence of A alleles of rs2221903 (P = 0.018, OR = 1.50 95% CI = 1.07-2.09) in GD patients. We also found a significant association between rs2221903 and HT (allele: P = 0.009, OR = 1.69 95% CI = 1.13-2.51; genotype: recessive P = 0.021, OR = 11.72 95% CI = 1.46-94.13). For the IL-21R gene, compared with controls, the genotype frequencies of rs3093301 and rs2285452 were significantly different in HT patients using dominant genetic model (P = 0.023, OR = 1.61 95% CI = 1.07-2.42; P = 0.031, OR = 1.71 95% CI = 1.05-2.80, respectively). Furthermore, the haplotype AA containing the major alleles of rs4833837 and rs2221903 was associated with increased susceptibility to GD with an OR of 1.50(95% CI =1.08-2.09, P = 0.016), and to HT with an OR of 1.69(95% CI =1.14-2.52, P = 0.009). CONCLUSION: Our results indicated that the SNPs of the IL-21 gene is associated with the development of GD. In addition, we found that individuals with the SNPs of the common IL-21 and IL-21R may have higher risk of HT.

[Association of TET2, LMTK2 and FAM84B gene expression with prostate cancer risk in Chinese patients].

OBJECTIVE: To explore the association between the common variations of TET2 (rs7679673, A), MTK2 (rs6465657, T) and FAM84B (rs12543663, C) genes and prostate cancer (Pca) risk in Chinese population in Beijing, and to understand the relationship between genotypes and phenotypes including clinical characteristics and life style, etc. in patients with prostate cancer. METHODS: Based on a case-control study, 124 patients with prostate cancer and 138 age-matched control subjects were recruited. Information of clinical phenotype and life style, etc. in the prostate cancer patients was collected. We compared the differences of allele and genotype frequencies of TET2 (rs7679673, A), LMTK2 (rs6465657, T) and FAM84B (rs12543663, C) gene expressions between the two groups for the allele and genotype frequencies, and explored the relationship between different genotypes and clinical features such as patient age, BMI, Gleason score, PSA level and tumor stage, by Chi-square test in patients with PCa. Multifactor dimensionality reduction was used to detect the gene-gene interactions. RESULTS: The FAM84B (rs12543663, C) C carriers frequency had significant difference between the case group and the control group (χ(2) = 3.980 P = 0.046; OR = 1.883; 95%CI = 1.006-3.526). The allele and genotype frequencies of TET2 gene (rs7679673, A) and LMTK2 gene (rs6465657, T) were not significantly different between the case group and the control group (P > 0.05). Analysis of the genotypes and clinical phenotypes showed that the genetic type of FAM84B C carriers [CX (CC + CA)] were significantly associated with cancer stage (χ(2) = 9.585; P = 0.002; OR = 3.740; 95%CI = 1.580 - 8.853). Association between three loci and 12 kind of relevant outcomes was found in TET2 A carriers and the smoking and drinking patients (all P < 0.05). Significant correlation was also found between LMTK2 (rs6465657, T) TX carriers and surgery (χ(2) = 8.612; P = 0.003; OR = 0.174; 95%CI 0.049 - 0.620). No significant correlation was seen with other covariates (P > 0.05). Dendrogram analysis among the three loci showed that the best model consisted of the three sites (P = 0.0270), cross validation consistency: 10/10, and testing balanced accuracy: 0.5120. There may be gene-gene interaction among TET2 (rs7679673, A), LMTK2 (rs6465657, T), and FAM84B (rs12543663, C). CONCLUSIONS: There may be obvious association of FAM84B (rs12543663, C) gene with prostate cancer risk and the stages, and the synergistic effects of TET2 (rs7679673, A), LMTK2 (rs6465657, T) and FAM84B (rs12543663, C) genes may have an association with prostate cancer risk in Chinese population.

Circadian Clock REV-ERBs Agonist SR9009 Induces Synergistic Antitumor Activity in Multiple Myeloma by Suppressing Glucose-Regulated Protein 78-Dependent Autophagy and Lipogenesis.

Background: Proteasome inhibitors, such as bortezomib, have demonstrated efficacy in the therapeutic management of multiple myeloma (MM). However, it is important to note that these inhibitors also elicit endoplasmic reticulum stress, which subsequently triggers the unfolded protein response (UPR) and autophagy, which have been shown to facilitate the survival of tumor cells. The disruption of the circadian clock is considered a characteristic feature of cancer. However, how disrupted circadian clock intertwines with tumor metabolism and drug resistance is not clearly clarified. This work explores the antitumor effectiveness of bortezomib and the circadian clock agonist SR9009, elucidating their impact on glucose-regulated protein 78 (GRP78), the autophagy process, and lipogenesis. Methods: The antitumor effects of bortezomib and SR9009 were evaluated using human MM cell lines (RPMI8226 and U266) in vitro and in vivo nonobese diabetic/severe combined immunodeficient (NOD/SCID) murine xenograft MM model. The assessment of cell viability was conducted using the cell counting kit-8 (CCK8) method, whereas the measurement of cell proliferation was performed with the inclusion of EdU (5-ethynyl-2'-deoxyuridine). Apoptosis was assessed by flow cytometry. The cells were transduced using adenovirus-tf-LC3, which was labeled with dual fluorescence. Subsequently, confocal imaging was employed to observe and examine the autophagosomes. REV-ERBα knockdown leads to upregulation of ATG5 and BENC1 at the protein level with immunoblot. Changes in the expression levels of GRP78, LC3, stearoyl-CoA desaturase 1 (SCD1), and fatty acid synthase (FASN) were assessed through the utilization of quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Results: Our results showed that both bortezomib and circadian clock REV-ERBs agonist SR9009 decreased MM viability, proliferation rate and induced an apoptotic response in a dose-dependent manner in vitro. However, the two differ greatly in their mechanisms of action. Bortezomib upregulated GRP78 and autophagy LC3, while circadian clock agonist SR9009 inhibited GRP78 and autophagy LC3. Combined SR9009 with bortezomib induced synergistic cytotoxicity against MM cells. REV-ERBα knockdown lead to upregulation of ATG5, BENC1 and significant upregulation of FASN, and SCD1. Mechanically, SR9009 inhibited the core autophagy gene ATG5 and BECN1, and two essential enzymes for de novo lipogenesis FASN and SCD1. SR9009 had synergistic effect with bortezomib and slowed down murine xenograft models of human MM tumor growth in vivo. Conclusions: Taken together, these results demonstrated that the circadian clock component REV-ERBs agonist SR9009 could inhibit GRP78-induced autophagy and de novo lipogenesis processes and had a synergistic effect with proteasome inhibitors in both in vitro and in vivo models of MM. Our findings shed light on how a disrupted circadian clock interacts with metabolic mechanisms to shape proteasome inhibitor drug resistance and suggest that SR9009 may be able to overcome the inherent drug resistance of proteasome inhibitors.

[The application of a high resolution melting-based genotyping method in studying the association between FTO rs9930506 polymorphism and metabolic syndrome in Beijing population].

OBJECTIVE: To set up a new method, which is sensitive, low cost, rapid and suitable for clinical application for FTO gene rs9930506 variant genotyping basing on high resolution melting (HRM) platform, and to preliminarily put into practice in susceptibility analysis for metabolic syndrome (MS) in Beijing. METHODS: Unlabelled probe with C3-spacer block specific for rs9930506 variant has been designed according to the Refseq from GenBank. With LC-Green plus dye pre-mixed, we scanned the signal for the genotype analysis after PCR amplification and HRM reaction. Restriction fragment length polymorphism (RFLP) and PCR-sequencing methods were designed as 2 control genotyping methods for the evaluation of accuracy and convenience. Afterwards, the HRM-based method was put into practice in metabolic syndrome patients (n = 500) and control groups (n = 500) for rs9930506 genotyping, and primarily study the association between rs9930506 and MS. RESULTS: All the 3 methods could genotype rs9930506 appropriately, although the 2 control methods seemed to be a little time-inefficient. The call rate of HRM-method was 100% and sampling accuracy reached 99.3% according to sequencing results. In the MS group, AA, AG and GG genotypes were found in 290, 185 and 25 cases, respectively. And in the control group, those were found in 344, 138 and 18 cases. No genotype distribution difference was detected between control group and HapMap-CHB data (P = 0.520). The genotype distributions were all in Hardy-Weinberg equilibrium in each group. AA genotype of rs9930506 seemed to reduce the risk for MS (OR = 0.626, 95%CI = 0.483 - 0.812). CONCLUSIONS: The AA genotype of rs9930506 variant in FTO might be a protective factor for MS in Beijing population. The susceptibility related genotyping in clinical samples could be more rapid, precise and inexpensive with the development of HRM in genotyping.

[Association of prostate cancer with PDLIM5, SLC22A3 and NKX3-1 in Chinese men].

OBJECTIVE: To investigate the association of prostate cancer (PCa) with PDLIM5 (rs17021918, T), SLC22A3 (rs9364554, C) and NKX3-1 (rs1512268, A) in Chinese men. METHODS: We included 124 PCa patients and 138 normal controls in this study, compared the alleles and genotypes of PDLIM5 (rs17021918, T) , SLC22A3 (rs9364554, C) and NKX3-1 (rs1512268, A) of the two groups, and explored the association of each of the genes with the age, body mass index (BMI), Gleason score, PSA level and tumor stage of the patients. We analyzed the gene-gene interaction using the multifactor dimensionality reduction method (MDR). RESULTS: There were no statistically significant differences in the frequency distribution of the risk alleles and genotypes of PDLIM5, SLC22A3 and NKX3-1 between the case and control groups (P > 0.05), nor were the three gene loci significantly associated with the age, Gleason score, PSA level and pathological grade of the PCa patients (CP < 0.05). MDR analysis showed no interaction between PDLIM5 and NKX3-1, but tree-diagram analysis revealed a possible synergistic action of the two polymorphism loci. CONCLUSION: PCa might not be associated with PDLIM5 (rs17021918,T), SLC22A3 (rs9364554,C) and NKX3-1 (rs1512268,A) in Chinese men. However, PDLIM5 and NKX3-1 might have a synergistic action on the risk PCa.

Charge Compensation Mechanisms and Oxygen Vacancy Formations in LiNi1/3Co1/3Mn1/3O2: First-Principles Calculations.

Charge compensation mechanisms in the delithiation processes of LiNi1/3Co1/3Mn1/3O2 (NCM111) are compared in detail by the first-principles calculations with GGA and GGA+U methods under different U values reported in the literature. The calculations suggested that different sets of U values lead to different charge compensation mechanisms in the delithiation process. Co3+/Co4+ couples were shown to dominate the redox reaction for 1 ≥ x ≥ 2/3 by using the GGA+U 1 method (U 1 = 6.0 3.4 3.9 for Ni, Co, and Mn, respectively). However, by using the GGA+U 2 (U 2 = 6.0 5.5 4.2) method, the results indicated that the redox reaction of Ni2+/Ni3+ took place in the range of 1 ≥ x ≥ 2/3. Therefore, according to our study, experimental charge compensation processes during delithiation are of great importance to evaluate the theoretical calculations. The results also indicated that all the GGA+U i (i = 1, 2, 3) schemes predicted better voltage platforms than the GGA method. The oxygen anionic redox reactions during delithiation are also compared with GGA+U calculations under different U values. The electronic density of states and magnetic moments of transition metals have been employed to illustrate the redox reactions during the lithium extractions in NCM111. We have also investigated the formation energies of an oxygen vacancy in NCM111 under different values of U, which is important in understanding the possible occurrence of oxygen release. The formation energy of an O vacancy is essentially dependent on the experimental conditions. As expected, the decreased temperature and increased oxygen partial pressure can suppress the formation of the oxygen vacancy. The calculations can help improve the stability of the lattice oxygen.

[Characteristics of Bacterial Community Structure in Wuliangsu Lake During an Irrigation Interval in Hetao Plain].

In order to study the bacterial community composition and corresponding function in Wuliangsu Lake at the end of the Hetao Plain during the irrigation gap period, lake samples were collected in September 2020, and the pH, TN, TP, DIP, DTP, NH4+-N, Chla, EC, SAL, and other indicators were analyzed. The 16S rRNA high-throughput sequencing method was used to explore the attached bacteria and bacterioplankton in 15 samples of the surface water in Wuliangsu Lake. The experimental results showed that:① the alpha diversity Chao and Shannon indices of attached bacteria were greater than that of bacterioplankton, but the median of Shannoneven index was the same. ② In each sampling point, the bacterioplankton of Proteobacteria and Actinobacteria in the top five dominant bacteria phyla were higher than that of attached bacteria, and the abundance of attached bacteria and bacterioplankton of Bacteroidota were staggered. On the contrary, the contents of attached bacteria of Verrucomicrobiota and Cyanobacteria were all higher than that of bacterioplankton. ③ Redundant analysis showed that pH had the most significant effect on dominant attached bacteria, and the effect of conductivity and salinity in dominant bacterioplankton was the most significant. ④ PICRUSt2 function prediction analysis showed that attached bacteria and planktonic bacteria had the strongest metabolic functions, showing abundant metabolic functions. There were 29 nitrogen-related effective KOs and 88 phosphorus-related effective KOs, with the greatest nitrogen-fixing function and strong inorganic phosphorus-dissolving function, and bacterioplankton played a greater role in the two functions.