Metabolites, Healthy Lifestyle, and Polygenic Risk Score Associated with Upper Gastrointestinal Cancer: Findings from the UK Biobank Study.

Previous metabolomics studies have highlighted the predictive value of metabolites on upper gastrointestinal (UGI) cancer, while most of them ignored the potential effects of lifestyle and genetic risk on plasma metabolites. This study aimed to evaluate the role of lifestyle and genetic risk in the metabolic mechanism of UGI cancer. Differential metabolites of UGI cancer were identified using partial least-squares discriminant analysis and the Wilcoxon test. Then, we calculated the healthy lifestyle index (HLI) score and polygenic risk score (PRS) and divided them into three groups, respectively. A total of 15 metabolites were identified as UGI-cancer-related differential metabolites. The metabolite model (AUC = 0.699) exhibited superior discrimination ability compared to those of the HLI model (AUC = 0.615) and the PRS model (AUC = 0.593). Moreover, subgroup analysis revealed that the metabolite model showed higher discrimination ability for individuals with unhealthy lifestyles compared to that with healthy individuals (AUC = 0.783 vs 0.684). Furthermore, in the genetic risk subgroup analysis, individuals with a genetic predisposition to UGI cancer exhibited the best discriminative performance in the metabolite model (AUC = 0.770). These findings demonstrated the clinical significance of metabolic biomarkers in UGI cancer discrimination, especially in individuals with unhealthy lifestyles and a high genetic risk.

How does the SARS-CoV-2 reinfection rate change over time? The global evidence from systematic review and meta-analysis.

BACKGROUND: There is a significant increase in the number of SARS-CoV-2 reinfection reports in various countries. However, the trend of reinfection rate over time is not clear. METHODS: We searched PubMed, Web of Science, Medline, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang for cohort studies, case-control studies, and cross-sectional studies up to March 16, 2023, to conduct a meta-analysis of global SARS-CoV-2 reinfection rate. Subgroup analyses were performed for age, country, study type, and study population, and time-varying reinfection rates of SARS-CoV-2 were estimated using meta-regression. The risk of bias was assessed using the Newcastle-Ottawa Scale and the Joanna Briggs Institute critical appraisal tool. RESULT: A total of 55 studies involving 111,846 cases of SARS-CoV-2 reinfection were included. The pooled SARS-CoV-2 reinfection rate was 0.94% (95% CI: 0.65 -1.35%). In the subgroup analyses, there were statistically significant differences in the pooled reinfection rates by reinfection variant, and study type (P < 0.05). Based on meta-regression, the reinfection rate fluctuated with time. CONCLUSION: Meta-regression analysis found that the overall reinfection rate increased and then decreased over time, followed by a period of plateauing and then a trend of increasing and then decreasing, but the peak of the second wave of reinfection rate was lower than the first wave. SARS-CoV-2 is at risk of reinfection and the Omicron variant has a higher reinfection rate than other currently known variants. The results of this study could help guide public health measures and vaccination strategies in response to the Coronavirus Disease 2019 (COVID-19) pandemic.

Association between TB delay and TB treatment outcomes in HIV-TB co-infected patients: a study based on the multilevel propensity score method.

BACKGROUND: HIV-tuberculosis (HIV-TB) co-infection is a significant public health concern worldwide. TB delay, consisting of patient delay, diagnostic delay, treatment delay, increases the risk of adverse anti-TB treatment (ATT) outcomes. Except for individual level variables, differences in regional levels have been shown to impact the ATT outcomes. However, few studies appropriately considered possible individual and regional level confounding variables. In this study, we aimed to assess the association of TB delay on treatment outcomes in HIV-TB co-infected patients in Liangshan Yi Autonomous Prefecture (Liangshan Prefecture) of China, using a causal inference framework while taking into account individual and regional level factors. METHODS: We conducted a study to analyze data from 2068 patients with HIV-TB co-infection in Liangshan Prefecture from 2019 to 2022. To address potential confounding bias, we used a causal directed acyclic graph (DAG) to select appropriate confounding variables. Further, we controlled for these confounders through multilevel propensity score and inverse probability weighting (IPW). RESULTS: The successful rate of ATT for patients with HIV-TB co-infection in Liangshan Prefecture was 91.2%. Total delay (OR = 1.411, 95% CI: 1.015, 1.962), diagnostic delay (OR = 1.778, 95% CI: 1.261, 2.508), treatment delay (OR = 1.749, 95% CI: 1.146, 2.668) and health system delay (OR = 1.480 95% CI: (1.035, 2.118) were identified as risk factors for successful ATT outcome. Sensitivity analysis demonstrated the robustness of these findings. CONCLUSIONS: HIV-TB co-infection prevention and control policy in Liangshan Prefecture should prioritize early treatment for diagnosed HIV-TB co-infected patients. It is urgent to improve the health system in Liangshan Prefecture to reduce delays in diagnosis and treatment.

Genetic Basis Identification of a NLR Gene, TaRGA5-like, That Confers Partial Powdery Mildew Resistance in Wheat SJ106.

Wheat powdery mildew is an important fungal disease that seriously jeopardizes wheat production, which poses a serious threat to food safety. SJ106 is a high-quality, disease-resistant spring wheat variety; this disease resistance is derived from Wheat-wheatgrass 33. In this study, the powdery mildew resistance genes in SJ106 were located at the end of chromosome 6DS, a new disease resistance locus tentatively named PmSJ106 locus. This interval was composed of a nucleotide-binding leucine-rich repeat (NLR) gene cluster containing 19 NLR genes. Five NLRs were tandem duplicated genes, and one of them (a coiled coil domain-nucleotide binding site-leucine-rich repeat (CC-NBS-LRR; CNL) type gene, TaRGA5-like) expressed 69-836-fold in SJ106 compared with the susceptible control. The genome DNA and cDNA sequences of TaRGA5-like were amplified from SJ106, which contain several nucleotide polymorphisms in LRR regions compared with susceptible individuals and Chinese Spring. Overexpression of TaRGA5-like significantly increased resistance to powdery mildew in susceptible receptor wheat Jinqiang5. However, Virus induced gene silence (VIGS) of TaRGA5-like resulted in only a small decrease of SJ106 in disease resistance, presumably compensated by other NLR duplicated genes. The results suggested that TaRGA5-like confers partial powdery mildew resistance in SJ106. As a member of the PmSJ106 locus, TaRGA5-like functioned together with other NLR duplicated genes to improve wheat resistance to powdery mildew. Wheat variety SJ106 would become a novel and potentially valuable germplasm for powdery mildew resistance.

[Xixin Decoction regulates Th17/Treg balance and transcription factor expression in senescence-accelerated mouse-prone].

This study aims to investigate the effect of Xixin Decoction on the T helper 17 cell(Th17)/regulatory T cell(Treg) ba-lance of intestinal mucosa and the expression of related transcription factors in the senescence-accelerated mouse-prone 8(SAMP8) model. Fifty 14-week male mice of SAMP8 were randomized by the random number table method into model group, probiotics group, and high-, medium-, and low-dose Xixin Decoction groups, with 10 mice in each group. Ten 14-week male mice of senescence-acce-lerated mouse-resistant 1(SAMR1) served as control group. After 10 weeks of feeding, the mice were administrated with correspon-ding drugs for 10 weeks. Morris water maze test was carried out to examine the learning and memory abilities of mice. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the content of secretory immunoglobulin A(SIgA) in the intestinal mucosa, and flow cytometry to detect the percentage content of Th17 and Treg in the intestinal mucosa. Western blot was performed to determine the protein levels of retinoid-related orphan receptor gamma t(RORγt) and forkhead box p3(Foxp3) in the mouse colon tissue. Compared with control group, the escape latency of mice in model group was significantly prolonged(P<0.01), and the number of times of crossing the platform and the residence time in the target quadrant were significantly reduced within 60 s(P<0.01), intestinal mucosal SIgA content was significantly decreased(P<0.01), Th17 content was increased(P<0.05), Treg content was decreased(P<0.01), the expression of RORγt protein was increased and Foxp3 protein was decreased in colon(P<0.01). Compared with the model group, high-dose Xixin Decoction group improved the learning and memory ability(P<0.05 or P<0.01). Probiotics group and high-and medium-dose Xixin Decoction group increased the content of SIgA in intestinal mucosa(P<0.05 or P<0.01), decreased percentage content of Th17 and increased the percentage content of Treg in intestinal mucosa(P<0.05 or P<0.01). Furthermore, they down-regulated the protein level of RORγt and up-regulated the protein level of Foxp3 in the intestinal mucosa(P<0.01). In conclusion, Xixin Decoction may act on intestinal mucosal immune barrier, affect gut-brain information exchange, and improve the learning and memory ability of SAMP8 by promoting SIgA secretion and regulating the Th17/Treg balance and the expression of RORγt and Foxp3.

Polymerization-Induced Self-Assembly: An Emerging Tool for Generating Polymer-Based Biohybrid Nanostructures.

The combination of biomolecules and synthetic polymers provides an easy access to utilize advantages from both the synthetic world and nature. This is not only important for the development of novel innovative materials, but also promotes the application of biomolecules in various fields including medicine, catalysis, and water treatment, etc. Due to the rapid progress in synthesis strategies for polymer nanomaterials and deepened understanding of biomolecules' structures and functions, the construction of advanced polymer-based biohybrid nanostructures (PBBNs) becomes prospective and attainable. Polymerization-induced self-assembly (PISA), as an efficient and versatile technique in obtaining polymeric nano-objects at high concentrations, has demonstrated to be an attractive alternative to existing self-assembly procedures. Those advantages induce the focus on the fabrication of PBBNs via the PISA technique. In this review, current preparation strategies are illustrated based on the PISA technique for achieving various PBBNs, including grafting-from and grafting-through methods, as well as encapsulation of biomolecules during and subsequent to the PISA process. Finally, advantages and drawbacks are discussed in the fabrication of PBBNs via the PISA technique and obstacles are identified that need to be overcome to enable commercial application.

Untargeted serum metabolomics reveals potential biomarkers and metabolic pathways associated with the progression of gastroesophageal cancer.

BACKGROUND: Previous metabolic studies in upper digestive cancer have mostly been limited to cross-sectional study designs, which hinders the ability to effectively predict outcomes in the early stage of cancer. This study aims to identify key metabolites and metabolic pathways associated with the multistage progression of epithelial cancer and to explore their predictive value for gastroesophageal cancer (GEC) formation and for the early screening of esophageal squamous cell carcinoma (ESCC). METHODS: A case-cohort study within the 7-year prospective Esophageal Cancer Screening Cohort of Shandong Province included 77 GEC cases and 77 sub-cohort individuals. Untargeted metabolic analysis was performed in serum samples. Metabolites, with FDR q value < 0.05 and variable importance in projection (VIP) > 1, were selected as differential metabolites to predict GEC formation using Random Forest (RF) models. Subsequently, we evaluated the predictive performance of these differential metabolites for the early screening of ESCC. RESULTS: We found a distinct metabolic profile alteration in GEC cases compared to the sub-cohort, and identified eight differential metabolites. Pathway analyses showed dysregulation in D-glutamine and D-glutamate metabolism, nitrogen metabolism, primary bile acid biosynthesis, and steroid hormone biosynthesis in GEC patients. A panel of eight differential metabolites showed good predictive performance for GEC formation, with an area under the receiver operating characteristic curve (AUC) of 0.893 (95% CI = 0.816-0.951). Furthermore, four of the GEC pathological progression-related metabolites were validated in the early screening of ESCC, with an AUC of 0.761 (95% CI = 0.716-0.805). CONCLUSIONS: These findings indicated a panel of metabolites might be an alternative approach to predict GEC formation, and therefore have the potential to mitigate the risk of cancer progression at the early stage of GEC.

Rh-Catalyzed [2,3]-Sigmatropic Rearrangement of Alkynyl Carbenes with Allyl Sulfides to Access Sulfide-Substituted 1,5-Enynes.

This study describes the development of Rh-catalyzed [2,3]-sigmatropic rearrangement of alkynyl carbenes with allyl sulfides. The protocol exhibits equitable functional group tolerance and allows the formation of a variety of synthetically valuable sulfide-substituted 1,5-enyne products. To the best of our knowledge, this is the first example of [2,3]-sigmatropic rearrangement of alkynyl carbenes. DFT analysis supports the involvement of rhodium carbene generation, sulfonium ylides formation, and [2,3]-sigmatropic rearrangement pathway.

[Xixin Decoction improves learning and memory ability of SAMP8 by enhancing neuroprotective effect and inhibiting neuroinflammation].

This study aimed to explore the possible effect of Xixin Decoction(XXD) on the learning and memory ability of Alzheimer's disease(AD) model senescence-accelerated mouse-prone 8(SAMP8) and the related mechanism in enhancing neuroprotective effect and reducing neuroinflammation. Forty SAMP8 were randomly divided into a model group(10 mL·kg~(-1)·d~(-1)), a probiotics group(0.39 g·kg~(-1)·d~(-1)), a high-dose group of XXD granules(H-XXD, 5.07 g·kg~(-1)·d~(-1)), a medium-dose group of XXD granules(M-XXD, 2.535 g·kg~(-1)·d~(-1)), and a low-dose group of XXD granules(L-XXD, 1.267 5 g·kg~(-1)·d~(-1)). Eight senescence-accelerated mouse-resistant 1(SAMR1) of the same age and strain were assigned to the control group(10 mL·kg~(-1)·d~(-1)). After ten weeks of intragastric administration, the Morris water maze was used to test the changes in spatial learning and memory ability of mice after treatment. Meanwhile, immunofluorescence staining was used to detect the positive expression of receptor for advanced glycation end products(AGER), Toll-like receptor 1(TLR1), and Toll-like receptor 2(TLR2) in the hippocampal CA1 region of mice. Western blot was employed to test the protein expression levels of silencing information regulator 2 related enzyme 1(SIRT1), AGER, TLR1, and TLR2 in the hippocampus of mice. Enzyme linked immunosorbent assay(ELISA) was applied to assess the levels of Aß_(1-42) in the hippocampus of mice and the levels of nuclear factor κB p65(NF-κB p65), NOD-like receptor protein 3(NLRP3), tumor necrosis factor-α(TNF-α), and interleukin-1ß(IL-1ß) in the serum and hippocampus of mice. Compared with the model group, XXD significantly improved the spatial learning and memory ability of SAMP8, increased the expression of neuroprotective factors in the hippocampus, decreased the levels of neuroinflammatory factors, and inhibited the expression of Aß_(1-42). In particular, H-XXD significantly increased the expression of SIRT1 in the hippocampus of mice, reduced the expression levels of NF-κB p65, NLRP3, TNF-α, and IL-1ß in the serum and hippocampus of mice, and decreased the expression of AGER, TLR1, and TLR2 in the hippocampus of mice(P<0.05 or P<0.01). XXD may improve the spatial learning and memory ability of AD model SAMP8 by enhancing the neuroprotective effect and inhibiting neuroinflammation.

Direct gem-Difluoroalkenylation of X-H Bonds with Trifluoromethyl Ketone N-Triftosylhydrazones for Synthesis of Tetrasubstituted Heteroatomic gem-Difluoroalkenes.

The direct gem-difluoroalkenylation of X-H bonds represents the most straightforward approach to access heteroatomic gem-difluoroalkenes that, as the isostere of the carbonyl group, have great potency in drug discovery. However, the construction of tetrasubstituted heteroatomic gem-difluoroalkenes by this strategy is still an unsolved problem. Here, we report the first direct X-H bond gem-difluoroalkenylation of amines and alcohols with trifluoromethyl ketone N-triftosylhydrazones under silver (for (hetero)aryl hydrazones) or rhodium (for alkyl hydrazones), thereby providing a most powerful method for the synthesis of tetrasubstituted heteroatomic gem-difluoroalkenes. This method features a broad substrate scope, high product yield, excellent functional group tolerance, and operational simplicity (open air conditions). Moreover, the site-specific replacement of the carbonyl group with a gem-difluorovinyl ether bioisostere in drug Trimebutine and the post-modification of bioactive molecules demonstrates potential use in medicinal research. Finally, the reaction mechanism was investigated by combining experiments and DFT calculations, and disclosed that the key step of HF elimination occurred via five-membered ring transition state, and the difference in the electrophilicity of Ag- and Rh-carbenes as well as the multiple intermolecular interactions rendered the effectiveness of Rh catalyst selectively for alkyl hydrazones.

Endometrial thickness is an independent risk factor of hypertensive disorders of pregnancy: a retrospective study of 13,458 patients in frozen-thawed embryo transfers.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are an important cause of maternal and fetal mortality, and its potential risk factors are still being explored. Endometrial thickness (EMT), as one of the important monitoring indicators of endometrial receptivity, has been confirmed to be related to the incidence of HDP in fresh embryo transfer. Our study was designed to investigate whether endometrial thickness is associated with the risk of hypertensive disorders of pregnancy in frozen-thawed embryo transfer (FET). METHODS: This respective cohort study enrolled 13,458 women who received vitrified embryo transfer and had a singleton delivery in the Reproductive Hospital affiliated to Shandong University from January 2015 to December 2019. We set strict screening criteria and obtained the information from the hospital electronic medical system. Statistical methods including logistic regression analysis, receiver operating characteristic curve and restricted cubic spline were used to evaluate the relationship between endometrial thickness and the incidence of pregnancy-induced hypertension. RESULTS: The incidences of HDP in a thin endometrial thickness group (< 0.8 cm) and a thick endometrial thickness group (> 1.2 cm) were significantly greater than in a reference group (0.8 cm-1.2 cm) (7.98 and 5.24% vs 4.59%, P <  0.001). A nonlinear relationship between endometrial thickness and risk of hypertensive disorders of pregnancy was examined by restricted cubic spline (P <  0.001). The thin endometrial thickness and thick endometrial thickness groups were significantly associated with the risk of HDP after adjusting for confounding variables by stepwise logistic regression analysis. Subsequently, subgroup logistic regression analysis based on endometrial preparation regimens showed that thin endometria were still significantly associated with a higher morbidity rate in the artificial cycle group, while in the natural cycle group, thick endometria were closely associated with increased morbidity. CONCLUSION: Our study manifested that both the thin and thick endometria were associated with an increased risk of hypertensive disorders of pregnancy in frozen embryo transfer cycles. Reproductive clinicians should focus on adjusting endometrial thickness in different preparation regimens; and obstetricians should be mindful of the risk of hypertension during pregnancy, when women with thin (< 0.8 cm) or excessively thicker (> 1.2 cm) endometrial thickness achieve pregnancy through frozen-thawed embryo transfer.

The inhibition of bone morphogenetic protein 1 attenuates endometriosis lesions in vivo and in vitro.

PURPOSE: To investigate the potential role of Bone morphogenetic protein 1 (BMP1) in endometriosis lesions. METHODS: Endometriosis model in mice was established. The expression of BMP1-3 expression in mice of endometriosis lesions was evaluated. The effect of the treatment with anti-BMP1 antibodies on the expression of MMP2, MMP9, TGF-ß, IL-17, IL-1ß, Col1a1 and Col1a2 levels in mice was evaluated. In endometriosis cell model, the expression of IL-17, IL-1ß, MMP2 and MMP9 levels and MIF, YWHAZ, ß-catenin and CAP39 mRNA levels was also detected. RESULTS: The expression of BMP1-3 expression was upregulated in mice of endometriosis lesions (p < 0.01). Treatment with anti-BMP1 antibodies dose-dependently reduced MMP2, MMP9, TGF-ß, IL-17, IL-1ß, Col1a1 and Col1a2 levels in mice (p < 0.01). Treatment with anti-BMP1 antibodies suppressed TGF-ß/PI3K/Akt signaling pathway. In vitro cell, si-BMP1 suppressed TGF-ß/PI3K/Akt signaling pathway. CONCLUSION: The data support the hypothesis that the inhibition of BMP1 is involved in the pathogenesis of endometriosis lesions.

The Marriage of Protein and Lanthanide: Unveiling a Time-Resolved Fluorescence Sensor Array Regulated by pH toward High-Throughput Assay of Metal Ions in Biofluids.

A protein/lanthanide complex (BSA/Tb3+)-based sensor array in two different pH buffers has been designed for high-throughput recognition and time-resolved fluorescence (TRF) detection of metal ions in biofluids. BSA, which acted as an antenna ligand, can sensitize the fluorescence of Tb3+ (i.e., antenna effect), while the presence of metal ions would lead to the corresponding conformational change of BSA for altering the antenna effect accompanied by a substantial TRF performance of Tb3+. This principle has also been fully proved by both experimental characterizations and coarse-grained molecular dynamics (CG-MD) studies. By using Tris-HCl buffer with different pHs (at 7.4 and 8.5), 17 metal ions have been well-distinguished by using our proposed BSA/Tb3+ sensor array. Moreover, the sensor array has the potential to discriminate different concentrations of the same metal ions and a mixture of metal ions. Remarkably, the detection of metal ions in biofluids can be realized by utilizing the presented sensor array, verifying its practical applications. The platform avoids the synthesis of multiplex sensing receptors, providing a new method for the construction of convenient and feasible lanthanide complex-based TRF sensing arrays.

Facile reflux synthesis of polyethyleneimine-capped fluorescent carbon dots for sequential bioassays toward Cu2+ /H2 S and its application for a logic system.

In this work, we present a novel facile strategy for green synthesis of polyethyleneimine (PEI)-capped carbon dots (PEI-CDs), in which citric acid and PEI were chosen as reactants and highly fluorescent PEI-CDs could be readily obtained via a simple one-pot refluxing under 120 °C within 2 H. Fluorescence studies indicate that the as-prepared PEI-CDs exhibit strong fluorescence emission at 446 nm with excitation at 365 nm. Upon the sequential addition of Cu2+ and H2 S, PEI-CDs result in an interesting "ON-OFF-ON" three-state emission responses, promising a bifunctional sensory platform. Moreover, the Cu2+ /H2 S-facilated reversible fluorescence changes of PEI-CDs have demonstrated the design of an INHIBIT logic system based on Boolean logic.

Manganese(II)-doped zinc/germanium oxide nanoparticles as a viable fluorescent probe for visual and time-resolved fluorometric determination of ascorbic acid and its oxidase.

A method is described for the determination of ascorbic acid (AA) in complex biological fluids. It based on maganese(II)-doped zinc/germanium oxide nanoparticles (Mn@ZnGe NPs) with appealing time-resolved phosphorescence (TRP). TRP can provide a background-free reporter signal in analytical methods. The absorption of AA overlaps the excitation band of Mn@ZnGe NPs at 254 nm. This reduces the intensity of fluorescence via an inner filter effect (IFE) with increasing concentration of AA. Typical experimental conditions include an emission peak at 536 nm, a delay time of 50 µs and a counting time of 2 ms. This method can detect AA in a range of 5-500 µM with a 0.13 µM limit of detection. If AA is oxidized by the enzyme AA oxidase (AAOx), dehydroascorbic acid will be formed which doesn't absorb at 254 nm. Hence, the IFE cannot occur and fluorescence is not reduced. The strategy can be used to quantify AAOx in the activity range of 1-4 U·mL-1. By using a handheld UV lamp and a smart phone with a color-scanning feature, the feasibility for visual detection and real-time/onsite quantitative scanometric monitoring of AA and AAOx is demonstrated. Graphical abstract Schematic presentation of a fluorometric method for determination of ascorbic acid (AA) and ascorbic oxidase and a scanometric visual assay. It based on the use of maganese(II)-doped zinc/germanium oxide nanoparticles (Mn@ZnGe NPs) with appealing time-resolved phosphorescence (TRP) and the inner-filter effect (IFE) between AA and Mn@ZnGe NPs.

DNA Encountering Terbium(III): A Smart "Chemical Nose/Tongue" for Large-Scale Time-Gated Luminescent and Lifetime-Based Sensing.

Recent years have witnessed the rapid development of pattern-based sensors due to their potential to detect and differentiate a wealth of analytes with only few probes. However, no one has found or used the combination of DNA and terbium(III) (Tb) as a pattern recognition system for large-scale mix-and-measure assays. Here we report for the first time that DNA-sensitized Tb (DNA/Tb), as a label-free and versatile "chemical nose/tongue", can be employed for wide-scale time-gated luminescent (TGL) monitoring of metal ions covering nearly the entire periodic table in a cost-effective fashion. A series of guanine/thymine (G/T)-rich DNA ligands was screened to sensitize the luminescence of Tb (referring to the antenna effect) as smart pattern responders to metal ions in solution, and metal ion-DNA interactions can differentially alter the antenna effect of DNA toward Tb as pattern signals. Our results show that as few as 3 DNA/Tb label-free sensors could successfully discriminate 49 analytes, including alkali-metal ions, alkaline-earth-metal ions, transition/post-transition metal ions, and lanthanide ions. A blind test with 49 metals further confirmed the discriminating power of DNA/Tb sensors. Moreover, the lifetime-based pattern recognition application using DNA/Tb sensors was also demonstrated. This DNA/Tb pattern recognition strategy could be extended to construct a series of "chemical noses/tongues" for monitoring various biochemical species by using different responsive DNA ligands, thus promising a versatile and powerful tool for a sensing application and investigation of DNA-involving molecular interactions.

The Chemistry of Europium(III) Encountering DNA: Sprouting Unique Sequence-Dependent Performances for Multifunctional Time-Resolved Luminescent Assays.

Screening functional DNA that can fruitfully interact with metal ions is a long-standing hot topic in the fields of biotechnology, medicine, and DNA-based sensors. In this paper, we focus on the chemistry of europium(III) (Eu) coupled with single-stranded DNA (ssDNA), and we innovatively unveil that cytosine- and thymine-rich ssDNA oligomers (e.g., C16 and T16) can be effective antenna ligands to sensitize the luminescence of Eu. Luminescence lifetime spectroscopy, circular dichroic (CD) spectroscopy, and isothermal titration calorimetry (ITC) have been used to systematically characterize the interaction involved between Eu and ssDNA. In light of the resultant sequence-dependent performances, the long luminescence lifetime Eu/ssDNA-based label-free and versatile probes are further devised as a pattern distinction system for time-resolved luminescent (TRL) sensing applications. The interactions of metal ions and ssDNA can distinctively shift the antenna effect of ssDNA toward Eu as accessible pattern signals. As a result, as few as two Eu/ssDNA label-free TRL probes can discriminate 17 metal ions via principal component analysis (PCA). In addition, thiols can readily capture metal ions to switch the luminescence of Eu/ssDNA probes initially altered by metal ions. Hence, four Eu/ssDNA-metal ion ensembles are demonstrated to be a powerful label-free TRL sensor array for pattern differentiation of eight thiols and even chiral recognition of cysteine enantiomers with different concentrations. Moreover, the sensitive TRL detection of thiols in biofluids can be successfully realized by using our method, promising its potential practical usage. This is the first report of a ssDNA-sensitized Eu-based TRL platform for label-free yet multifunctional background-free sensing and would open a door for sprouting of more novel lanthanide ion/DNA-relevant strategies toward widespread applications.

Bioinspired Copolymers Based Nose/Tongue-Mimic Chemosensor for Label-Free Fluorescent Pattern Discrimination of Metal Ions in Biofluids.

There is a close correlation between body health and the level of biofluid-derived metal ions, which makes it an attractive model analyte for noninvasive health monitoring. The present work has developed a novel nose/tongue-mimic chemosensor array based on bioinspired polydopamine/polyethylenimine copolymers (PDA/PEI n) for label-free fluorescent determination of metal ions in biofluids. Three types of PDA/PEI n (PDA/PEI6, PDA/PEI18, and PDA/PEI48) were prepared by using different concentrations of PEI to construct the proposed sensor array, which would lead to unique fluorescence response patterns upon challenged with metal ions for their pattern discrimination. The results show that as few as 3 PDA/PEI n sensors can successfully realize the largescale sensitive detection of metal ions in biofluids. Moreover, we have demonstrated that PDA/PEI n sensors are qualified for lifetime-based pattern discrimination application. Furthermore, the sensors can distinguish between different concentrations of metal ions, as well as a mixture of different metal ions in biofluids, even the mixtures with different valence states. The method promises the simple, rapid, sensitive, and powerful discrimination of metal ions in accessible biofluids, showing the potential applications in the diagnosis of metal ion-involved diseases.

pH-Regulated Optical Performances in Organic/Inorganic Hybrid: A Dual-Mode Sensor Array for Pattern-Recognition-Based Biosensing.

Dual-mode optical assays are becoming more popular and attractive because they would provide robust detailed information in biochemical analysis. We herein unveil a novel dual-mode optical (i.e., UV-vis absorption and fluorescence) method for multifunctional sensing of phosphate compounds (PCs) (e.g., nucleotides and pyrophosphate) based on pattern recognition, which innovatively employs only one kind of porphyrin/lanthanide-doped upconversion nanoparticles (Ln-UCNPs) hybrid integrated with a facile pH-regulated strategy as the sensor array. An easy-to-obtain porphyrin hydrate (tetraphenylporphyrin tetrasulfonic acid hydrate, TPPS) can assemble onto the ligand-free Ln-UCNPs to construct the organic/inorganic hybrid (TPPS/Ln-UCNPs), leading to a new absorption band to quench the upconversion fluorescence of Ln-UCNPs due to fluorescence resonance energy transfer (FRET). The dual-mode optical performances of TPPS/Ln-UCNPs are characteristically correlated with the pH in aqueous solution. Thus, as a proof-of-concept design, three types of TPPS/Ln-UCNPs (TPPS/Ln-UCNPs4, TPPS/Ln-UCNPs4.5, and TPPS/Ln-UCNPs5) were prepared by using buffers with different pH (at 4, 4.5, and 5) to form our proposed sensor array, which would result in individual dual-mode optical response patterns upon being challenged with PCs for their pattern recognition through a competitive mechanism between TPPS and PCs. The results show that three TPPS/Ln-UCNPs n sensors can successfully permit the sensitive detection of 14 PCs and differentiate them between different concentrations, as well as a mixture of them. The pH-dependent TPPS/Ln-UCNPs promises the simple, yet powerful discrimination of PCs via pattern recognition, would prospectively stimulate and expand the use of organic/inorganic hybrid toward more biosensing applications.

Kidney Protection Effect of Ginsenoside Re and Its Underlying Mechanisms on Cisplatin-Induced Kidney Injury.

BACKGROUND/AIMS: Cisplatin (CDDP) was the first platinum-containing anti-cancer drug. However, CDDP causes nephrotoxicity as a side effect, which limits its clinic application. The aim of this study was to investigate the renoprotective effect of ginsenoside Re (G-Re) in a murine model of CDDP-induced acute kidney injury. METHODS: Male ICR mice were divided into 4 groups. G-Re was administered to the mice by oral gavage once a day at a dose of 25 mg/kg for 10 days. On the 7th day, a single injection of CDDP (25 mg/kg) was given at 1 h after G-Re treatment. RESULTS: CDDP administration resulted in renal dysfunction, as evidenced by an increase in the serum levels of creatinine and urea nitrogen. Oxidative stress in the CDDP group was reflected by an increase of malondialdehyde and a depletion of reduced glutathione and catalase in renal tissue. These findings were supported by increased 4-hydroxynonenal expression, which was significantly reduced by G-Re. Simultaneously, the overexpression of cytochrome P450 E1 was inhibited. G-Re inhibited the inflammatory response by the reduction of the protein expression of cyclooxygenase-2 and inducible nitric oxide synthase. Furthermore, CDDP increased the expression of Bax and decreased Bcl-2 expression in renal tissue. Hematoxylin and eosin, Hoechst 33258, and TUNEL staining also confirmed the presence of acute tubular necrosis and apoptosis. G-Re significantly decreased the levels of indicators of renal dysfunction, inflammatory cytokines, apoptosis, and malondialdehyde in the kidney and also significantly attenuated the histopathological changes associated with acute renal failure. CONCLUSIONS: Collectively, the results of this study suggest that the nephroprotective potential of G-Re may, in part, be related to its anti-oxidant, anti-inflammatory, and anti-apoptotic effects.