Heat shock protein family A member 8 is a prognostic marker for bladder cancer: Evidences based on experiments and machine learning.

Heat shock protein member 8 (HSPA8) is one of the most abundant chaperones in eukaryotic cells, but its biological roles in bladder cancer (BC) are largely unclear. First, we observed that HSPA8 was abundant in both cell lines and tissues of BC, and the HSPA8-high group had poorer T stages and overall survival (OS) than the HSPA8-low group in the TCGA patients. Next, when we knocked down HSPA8 in BC cells, the growth and migration abilities were significantly decreased, the apoptosis rates were significantly increased, and the Ki67 fluorescence intensity was decreased in BC cells. Moreover, caspase 3 was significantly decreased with overexpression of HSPA8 in BC cells. After that, a machine learning prognostic model was created based on the expression of HSPA8 by applying LASSO Cox regression in TCGA and GEO patients. The model indicated that the low-risk (LR) group with BC had better tumour stages, lymphovascular invasion, and OS than the high-risk (HR) group. Additionally, the risk score was demonstrated to be an independent risk factor for the prognosis of BC by univariate and multivariate Cox analyses. Moreover, the HR group showed a greater rate of TP53 mutations and was mostly enriched in the ECM-receptor interaction pathway than the LR group. Importantly, lower CD8+ T-cell and NK cell infiltration, higher immune exclusion scores, higher expression of PD-L1 and CTLA4 and poorer immune checkpoint therapy effects were found in the HR group. These findings demonstrated how crucial HSPA8 plays a role in determining the prognosis of bladder cancer.

Suppression of ferroptosis through the SLC7A11/glutathione/glutathione peroxidase 4 axis contributes to the therapeutic action of the Tangshenning formula on diabetic renal tubular injury.

BACKGROUND: Tangshenning (TSN) is a safe and effective formula to treat diabetic nephropathy (DN), and clinical studies have demonstrated that its therapeutic effects are related to oxidative stress improvements in patients. Herein, this study aims to explore the potential mechanism of how TSN alleviates diabetic renal tubular injury. METHODS: The ultrahigh pressure liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-QTOF/MS) was used to identify the chemical composition and serum components of TSN. KK-Ay mice served to investigate the protective effects and regulatory mechanisms of TSN on tubular damage in DN. Furthermore, inhibitors and inducers of ferroptosis were employed in high glucose-cultured tubular epithelial cells (TECs) to verify the potential mechanisms of TSN. The expressions of proteins related to renal tubular injury, ferroptosis and solute carrier family 7, member 11 (SLC7A11)/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis were analyzed by western blot and immunofluorescence. Mitochondrial ultrastructure was observed in kidney tissues and TECs by a transmission electron microscope. Pathological changes in the renal tissues were observed by HE, PAS, and Prussian blue staining. Ferroptosis-related reactive oxygen species (ROS), malondialdehyde (MDA), ferrous ion, the intake of cystine, GSH, and oxidized glutathione (GSSG) were evaluated and contrasted in vivo or in vitro. RESULTS: 51 compounds of TSN powder and 11 components in TSN-containing serum were identified by UPLC-QTOF/MS method. Administration of TSN ameliorated the elevated levels of proteinuria, serum creatinine, blood urea nitrogen, abnormal expression of renal tubular injury markers, and pathological damage to the renal tubules in DN mice model. Intriguingly, a strong inhibition of ferroptosis after TSN treatment occurred in both DN mice model and high glucose-cultured TECs. Notably, induction of ferroptosis by erastin attenuated the protective effect of TSN in high glucose-cultured TECs, while the ferroptosis inhibition by ferrostatin-1 treatment protected renal tubular, which was similar to TSN, suggesting the contribution of TSN-mediated by the inhibition of ferroptosis in DN progression. Mechanistically, TSN upregulated the SLC7A11/GSH/GPX4 axis to inhibit ferroptosis. CONCLUSION: TSN may delay the DN progression and attenuate the renal tubular injury by inhibiting the ferroptosis regulated by the SLC7A11/GSH/GPX4 axis.

JAM3: A prognostic biomarker for bladder cancer via epithelial-mesenchymal transition regulation.

Understanding the intricate relationship between prognosis, immune function, and molecular markers in bladder cancer (BC) demands sophisticated analytical methods. To identify novel biomarkers for predicting prognosis and immune function in BC patients, we combined weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression analysis. This was conducted using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Ultimately, we screened the junctional adhesion molecule 3 (JAM3) as an independent risk factor in BC. High levels of JAM3 were linked to adverse clinical parameters, such as higher T and N stages. Additionally, a JAM3-based nomogram model accurately predicted 1-, 3- and 5-year survival rates of BC patients, indicating potential clinical utility. Functional enrichment analysis revealed that high JAM3 expression activated the calcium signaling pathway, the extracellular matrix (ECM)-receptor interaction, and the PI3K-Akt signaling pathway, and was positively correlated with genes associated with epithelial-mesenchymal transition (EMT). Subsequently, we found that overexpression of JAM3 promoted the migration and invasion abilities in BC cells, regulating the expression levels of N-cadherin, matrix metallopeptidase 2 (MMP2), and Claudin-1 thereby promoting EMT levels. Additionally, we showed that JAM3 was negatively correlated with anti-tumor immune cells such as CD8+ T cells, while positively correlated with pro-tumor immune cells such as M2 macrophages, suggesting its involvement in immune cell infiltration. The immune checkpoint CD200 also showed a positive correlation with JAM3. Our findings revealed that elevated JAM3 levels are predictive of poor prognosis and immune cell infiltration in BC patients by regulating the EMT process.

Comprehensive analysis of integrin αvß3/α6ß1 in prognosis and immune escape of prostate cancer.

Integrin αvß3/α6ß1 are crucial in the transduction of intercellular cancer information, while their roles in prostate cancer (PCa) remain poorly understood. Here, we systematically analyzed the transcriptome, single nucleotide polymorphisms (SNPs) and clinical data of 495 PCa patients from the TCGA database and verified them in 220 GEO patients, and qPCR was used to validate the expression of the model genes in our patients. First, we found that integrin αvß3/α6ß1 was negatively correlated with most immune cell infiltration and immune functions and closely associated with poor survival in TCGA patients. Then, we divided these patients into two groups according to the expression level of αvß3/α6ß1, intersected differentially expressed genes of the two groups with the GEO dataset and identified eight biochemical recurrence-related genes (BRGs), and these genes were verified by qPCR in our patients. Next, these BRGs were used to construct a prognostic risk model by applying LASSO Cox regression. We found that the high-risk (HR) group showed poorer OS, PFS, biochemical recurrence and clinical characteristics than the low-risk (LR) group. In addition, the HR group was mainly enriched in the cell cycle pathway and had a higher TP53 mutation rate than the LR group. More importantly, lower immune cell infiltration and immune function, higher expression of PD-L1, PD-1, and CTLA4, and higher immune exclusion scores were identified in the HR group, suggesting a higher possibility of immune escape. These findings suggested the key role of integrin αvß3/α6ß1 in predicting prognosis, TP53 mutation and immune escape in PCa.

A new immune-related gene signature predicts the prognosis and immune escape of bladder cancer.

BACKGROUND: The biological roles of immune-related genes (IRGs) in bladder cancer (BC) need to be further elucidated. OBJECTIVE: To elucidate the predictive value of IRGs for prognosis and immune escape in BC. METHODS: We comprehensively analyzed the transcriptomic and clinical information of 430 cases, including 19 normal and 411 BC patients from the TCGA database, and verified 165 BC cases in the GSE13507 dataset. The risk model was constructed based on IRGs by applying LASSO Cox regression and exploring the relationship between the risk score and prognosis, gene mutations, and immune escape in BC patients. RESULTS: We identified 4 survival-related genes (PSMC1, RAC3, ROBO2 and ITGB3) among 6,196 IRGs in both the TCGA and GES13507 datasets,, which were used to establish a gene risk model by applying LASSO Cox regression. The results showed that the high-risk (HR) group was closely associated with poor survival or advanced pathological stage of BC. Furthermore, the risk score was found to be an independent risk factor for prognosis of BC patients. In addition, high-risk individuals showed a greater prevalence of TP53 mutations lower CD8+ T-cell and NK cell infiltration, higher Treg cell infiltration, higher expression of PD-L1, and higher immune exclusion scores than those in the low-risk (LR) group. Finally, the experimental verification shows that the model construction gene, especially PMSC1, plays an important role in the growth and metastasis of bladder cancer. CONCLUSIONS: These evidences revealed the vital role of IRGs in predicting prognosis, TP53 mutation and immune escape in BC patients.

Metabolic profiling integrated with pharmacokinetics to reveal the material basis of Xiaokeyinshui extract combination in the treatment of type 2 diabetes in rats.

Xiaokeyinshui extract combination (XEC), originating from a traditional Chinese formula Xiaokeyinshui (XKYS) recorded in ancient Bencao, has been reported to exert significant hypoglycemic effects. However, the chemical profiles, metabolic transformation and pharmacokinetic behavior of XEC in vivo were unclear. The research was to investigate the chemical constituents, metabolic profiles and pharmacokinetic behavior of XEC. A UPLC-QE-Orbitrap-HRMS qualification method was developed to identify the chemical constituents in XEC and xenobiotics of XEC in plasma, urine, feces and bile of rats after oral administration. A LC-MS quantification method was established and applied for the pharmacokinetic studies of major active compounds of XEC in normal and T2DM rats and Coptidis Rhizoma extracts (CRE) in T2DM rats. Fifty eight compounds in XEC and a total of 152 xenobiotics were identified in T2DM rats, including 28 prototypes and 124 metabolites. The metabolic pathways were demethylation, demethyleneization, reduction, hydroxylation, hydrolysis and subsequent binding reactions, including glucuronidation, sulfation and methylation. According to the results of chemical constituents and metabolites, 7 ingredients, including berberine, palmatine, coptisine, epiberberine, berberrubine, magnoflorine and aurantio-obtusin were suggested for markers to comparative pharmacokinetics study in normal rats and T2DM rats. Compared with normal rats, the Tmax of berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine was significantly longer. The value of Cmax for palmatine, coptisine, epiberberine and berberrubine was significantly decreased in XEC T2DM group. The value of AUC for alkaloids was higher in diabetic rats. After oral CRE, alkaloids including berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine could be detected in vivo. Compared with T2DM rats after oral administration of CRE, the value of Tmax and Cmax for berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine exhibited significant differences in XEC T2DM group. This research provided an overview of the chemical profiles and metabolic profiling of XEC and elucidated the effect of diabetic state and compatibility on pharmacokinetic behaviors of active components in XEC. This research also can provide the material basis of XEC for subsequent quality control research.

LmTraceMap: A Listeria monocytogenes fast-tracing platform for global surveillance.

Listeria monocytogenes can cause listeriosis, and people with hypoimmunity such as pregnant women, infants and fetuses are at high risk of invasive infection. Although the incidence of listeriosis is low, the fatality rate is high. Therefore, continual surveillance and rapid epidemiological investigation are crucial for addressing L. monocytogenes. Because of the popularity of next-generation sequencing, obtaining the whole-genome sequence of a bacterium is easy. Several genome-based typing methods are available, and core-genome multilocus sequence typing (cgMLST) is the most recognized methods. Using cgMLST typing to compare L. monocytogenes whole-genome sequences (WGS) with those obtained across distinct regions is beneficial. However, the concern is how to incorporate the powerful cgMLST method into investigations, such as by using source tracing. Herein, we present an easy-to-use web service called-LmTraceMap (http://lmtracemap.cgu.edu.tw/hua_map/test/upload.php; http://120.126.17.192/hua_map/test/upload.php) that can help public-health professionals rapidly trace closely related isolates worldwide and visually inspect them in search results on a world map with labeled epidemiological data. We expect the proposed service to improve the convenience of public health investigations.

A highly water-stable dual-emission fluorescent probe based on Eu3+-loaded MOF for the simultaneous detection and quantification of Fe3+ and Al3+ in swine wastewater.

A novel dual-emissive Eu3+-loaded metal-organic framework (MOF) is designed and successfully fabricated by introducing 2-hydroxyterephthalic acid (H2BDC-OH) and Eu3+ ions into an UiO-66-type MOF material. The obtained MOF, here referred to as EuUCH, exhibits dual emission at 450 and 614 nm, and both emissions are quite stable in aqueous media in the pH range of 4-11. EuUCH is characterized by a high selectivity and sensitivity toward Fe3+ and Al3+, which yield different responsive modes. The two emissions of EuUCH are quenched by Fe3+; by contrast, only the emission at 450 nm is quenched by Al3+ showing a ratiometric fluorescence signal. More importantly, as there is no clear interference between the signals of Fe3+ and Al3+, EuUCH is successfully utilized for the simultaneous detection of Fe3+ and Al3+ in their mixtures. In addition, the simultaneous quantification of Fe3+ and Al3+ is achieved in more complicated swine wastewater with good recoveries. This work provides a water-stable dual-emissive probe and the possibility to achieve the simultaneous quantification of Fe3+ and Al3+ in complicated environment wastewater.

The predictive value of pyroptosis for the prognosis and immune escape of bladder cancer.

OBJECTIVE: To evaluate the predictive value of pyroptosis-related genes for the prognosis and immune escape of bladder cancer (BC). METHODS: Transcriptomic and single nucleotide polymorphisms (SNPs) data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) portal. Least absolute shrinkage and selection operator (LASSO) analysis was carried out to construct a prognostic risk model for BC patients. RESULTS: Based on the expression of 50 pyroptosis-related genes, BC patients from TCGA database were divided into two clusters, which showed significant differences in overall survival and disease specific survival. Furthermore, we intersected the differentially expressed genes between these two clusters with those identified from the GSE13507 dataset and finally identified eight survival related genes, which was used to construct a prognostic risk model by LASSO Cox regression. According to the model, the high-risk (HR) group was closely associated with poor survival or the advanced pathological stage of BC. In addition, the HR group was mainly enriched in cell cycle and immune-related pathways and had a higher TP53 mutation rate than the low-risk (LR) group. Furthermore, these two risk groups were significantly related to immune cell composition, immune cell infiltration, and immune response. Importantly, a higher expression of PD-1, PD-L1, and CTLA4 as well as higher immune exclusion scores were found in the HR group, suggesting a higher possibility of immune escape. CONCLUSION: Our studies revealed the key role of pyroptosis in predicting the prognosis, TP53 mutation, and immune escape of patients with BC.

A luminescent Eu3+-functionalized MOF for sensitive and rapid detection of tetracycline antibiotics in swine wastewater and pig kidney.

Tetracyclines (TCs), a type of antibiotics, are widely used in human therapy and animal husbandry. Public concerns about tetracyclines residues have been raised due to their negative impact on the environment and food, causing bacterias drug resistance and human health concerns. In this work, a luminescent europium MOF (EuUCBA) is constructed via post-synthetic attachment of Eu3+ into a UiO-66 type MOF. The luminescent of EuUCBA exhibits high stability in aqueous media in the pH range of 4-11. Among 36 common veterinary drugs, the synthesized probe is highly selective and sensitive to six tetracyclines with low detection limits of 0.118 µM, 0.228 µM, 0.102 µM, 0.138 µM, 0.206 µM, and 0.078 µM for oxytetracycline (OTC), chlortetracycline (CTC), methylenetetracycline (MTC), minocycline (MOC), tetracycline (TC), and doxycycline (DOXY), respectively. Furthermore, the probe shows good anti-interference ability and fast response. Finally, EuUCBA was successfully to detect DOXY in swine wastewater and pig kidney with good recoveries. This work provides an excellent fluorescent sensor for highly selective and rapid detection of TCs residues in wastewater and complex biological samples.

Gallium nitride catalyzed the direct hydrogenation of carbon dioxide to dimethyl ether as primary product.

The selective hydrogenation of CO2 to value-added chemicals is attractive but still challenged by the high-performance catalyst. In this work, we report that gallium nitride (GaN) catalyzes the direct hydrogenation of CO2 to dimethyl ether (DME) with a CO-free selectivity of about 80%. The activity of GaN for the hydrogenation of CO2 is much higher than that for the hydrogenation of CO although the product distribution is very similar. The steady-state and transient experimental results, spectroscopic studies, and density functional theory calculations rigorously reveal that DME is produced as the primary product via the methyl and formate intermediates, which are formed over different planes of GaN with similar activation energies. This essentially differs from the traditional DME synthesis via the methanol intermediate over a hybrid catalyst. The present work offers a different catalyst capable of the direct hydrogenation of CO2 to DME and thus enriches the chemistry for CO2 transformations.

Recyclable europium functionalized metal-organic fluorescent probe for detection of tryptophan in biological fluids and food products.

An europium functionalized metal-organic fluorescent probe, Eu3+@UiO-66-FDC was constructed by post-synthetic modification through coordination interactions. Eu3+@UiO-66-FDC displayed high selectivity and sensitivity toward Tryptophan (Trp) among all the 20 natural amino acids and other general compounds in food and biological samples, with a wide linear concentration range (0-1000 µM), low detection limit (0.29 µM), and a rapid response (<1 min). Besides, this probe was utilized to detect Trp in rabbit blood serum and milk samples with good recoveries, which were verified by high-performance liquid chromatography (HPLC). Notably, this fluorescent probe proved to be a recyclable material. Hence, this work provides a reliable and recyclable fluorescent probe applicable toward the detection of Trp in biological fluids and/or food products.

Highly sensitive and rapid detection of thiabendazole residues in oranges based on a luminescent Tb3+-functionalized MOF.

Thiabendazole (TBZ), has been extensively employed as a pesticide and/or a fungicide in agriculture, while its residues would threaten to public health and safety. Simple, rapid and sensitive probes for detection of TBZ in real food samples is significantly desirable. In present work, a highly selective and sensitive luminescent sensor for monitoring TBZ in oranges has been constructed based on a Tb3+-functionalized Zr-MOF (Tb3+@1). Tb3+@1 exhibited many attractive sensing properties toward TBZ, including broad linear range (0-80 µM), high selectivity, low LOD (0.271 µM) and rapid response time (less than1 min). Moreover, the probe was employed to determine TBZ in real orange samples, in which good recoveries from 98.41 to 104.48% were obtained. It only takes 35 min for the whole process of detection TBZ in real orange samples combined with QuEChERS method. Therefore, this work provided a reliable and rapid method for monitoring the TBZ in real orange samples.

Highly selective detection of Cu2+ in aqueous media based on Tb3+-functionalized metal-organic framework.

In this work, a metal-organic framework UiO-66-(COOH)2 has been synthesized and is further functionalized with Tb3+ through coordination interactions. The functionalized MOF, denoted as Tb3+@UiO-66-(COOH)2, is fully characterized and further developed as an excellent fluorescent probe to monitor Cu2+ ions in aqueous media by fluorescence quenching effect. Tb3+@UiO-66-(COOH)2 exhibits high selectivity and sensitivity, broad linear concentration range (0-200 µM), low detection limits (0.23 µM), fast response speed (within 1 min), as well as in situ naked eye observation under UV light for sensing Cu2+ ion. Furthermore, this probe was successfully employed to detect Cu2+ ion in real water with good recovery. Hence, this work developed a very excellent fluorescent sensor with high potential practical applications for detection of Cu2+ ion in environmental water samples.

[Study on the epidemiology and etiologic agent of Dengue fever outbreaks in Fuzhou in 2004].

OBJECTIVE: To study the epidemiology and etiologic characteristics of a Dengue fever outbreak in Fuzhou from the beginning of September to the end of October in 2004 in order to understand the source of infection. METHODS: Data on descriptive epidemiology was collected to study the characteristics and related factors to the epidemic. Dengue virus was isolated through the use of C6/36 cell line while viral serotypes were identified by indirect immunofluorecent assay with type-specific monoclonal antibody. The sources of infection were traced by nucleotide sequencing. RESULTS: During the epidemic, 93 cases occured consistently with the region entomoplily growth and decay. The viruses of 6 strains isolated from 10 patients' blood specimens were identified as dengue virus type 1. Phylogenetic evidence suggested that the viral isolate had high genetic relation with the isolates from Kampuchea (DENV-1/KHM/2001; GenBank Accession No. L0904278). CONCLUSION: The epidemic was caused by introduction of patients migrating into Fuzhou.

[Phylogenetic analysis of enterovirus 71 isolated from patients with hand, foot and mouth disease in Guangdong and Fujian provinces, 2000-2001].

OBJECTIVE: To identify enterovirus 71 (EV71) strains isolated from patients with hand, foot and mouth disease (HFMD) in Guangdong and Fujian provinces from 2000 to 2001 by using phylogenetic analysis. METHODS: All 25 samples were first tested for enteric viruses by RT-PCR using enterovirus specific primers EV-1 and EV-2, and then were identified for EV71 by RT-PCR using EV71 specific primers 159S and 162A. The amplicons of 485bp segment (part of the VP1 gene) were cloned into pGEM-T and sequenced. A phylogenetic tree was constructed by comparison of the sequences with other 12 EV71 strains isolated from China, Japan, Hungary, and the United States including the prototype BrCr. RESULTS: The positive rate of EV71 was about 20%. The sequence analysis showed that the new isolate (GZH2000) shared 94%-96% nucleotide identity with three strains isolated in 1998 and 2000, and 91% with a strain isolated in 1987 from Chinese mainland, but shared only 82%-84% homology with EV71 isolates studied abroad. CONCLUSIONS: EV71 is one of the important pathogens of HFMD in south China. The strains isolated from mainland were closely related with most isolates from Taiwan, but different from most EV71 strains reported abroad. The symptoms of EV71 infection in mainland were not as intensive as those described in Taiwan's outbreak.