Portable tri-color ratiometric fluorescence paper sensor for intelligent visual detection of dual-antibiotics and aluminium ion.

The toxicological effect between co-existed antibiotics and metal ions was dangerous to the ecological environment and public health. However, the rapid quantification tools with convenience, accuracy and low cost for the detection of multiple targets were still challenging. Herein, a portable tri-color ratiometric fluorescence paper sensor was constructed by coupling of blue carbon dots and fluorescence imprinted polymer for down/up conversion simultaneous detection of tetracycline and sulfamethazine. Interestingly, the cascade detection of aluminum ion was also realized based on the individual detection system of tetracycline without the assistance of complex coupling reagents. The detection limits of smartphone method for the visual detection of tetracycline, sulfamethazine and aluminum ion were calculated as 0.014 µM, 0.004 µM and 0.019 µM, respectively. The portable fluorescence paper sensor was applied for the visual detection of tetracycline, sulfamethazine and aluminum ion in actual samples successfully with satisfactory recoveries. With the advantages of rapidness, low cost, and portability, the developed portable fluorescence paper sensor provided a new strategy for the visual real-time detection of multiple targets.

Heterologous expression of taxane genes confers resistance to fall armyworm in Nicotiana benthamiana.

KEY MESSAGE: Taxadiene synthase, taxadiene-5α-hydroxylase, and taxane 13α-hydroxylase genes were introduced into Nicotiana benthamiana, and the improved resistance to lepidoptera pest fall armyworm was reported. Fall armyworm (FAW) is a serious agricultural pest. Genetic engineering techniques have been used to create pest-resistant plant varieties for reducing pest damage. Paclitaxel is a diterpenoid natural metabolite with antineoplastic effects in medicine. However, the effects of taxanes on the growth and development of lepidoptera pests, such as the FAW, are unknown. Here, selected paclitaxel precursor biosynthesis pathway genes, taxadiene synthase, taxane 5α-hydroxylase, and taxane 13α-hydroxylase, were engineered in the heterologous host Nicotiana benthamiana plants. Bioassay experiments showed that the transgenic N. benthamiana plants displayed improved resistance to FAW infestation, with degeneration of gut tissues and induced expression of apoptosis-related genes. Cytotoxicity experiment showed that the paclitaxel precursor, 10-deacetylbaccatin III, is cytotoxic to Sf9 cells, causing cell cycle arrest at the G2/M phase and disorder of the cytoskeleton. Metabolome analysis showed that heterologous expression of taxane genes in N. benthamiana affected the digestive system, steroid hormone and purine metabolism pathways of FAW larvae. In summary, this study provides a candidate approach for FAW control.

Low levels of sex hormone-binding globulin predict an increased breast cancer risk and its underlying molecular mechanisms.

Sex hormone-binding globulin (SHBG) is a serum glycoprotein exhibiting the unique feature of binding sex steroids with high affinity and specificity. Over the past few decades, there have been significant breakthroughs in our understanding of the function and regulation of SHBG. The biological role of SHBG has expanded from being considered a simple sex hormone transporter to being associated with several complex physiological and pathological changes in a variety of target tissues. Many factors can affect the plasma SHBG levels, with fluctuations in circulating levels affecting the development of various diseases, such as increasing the risk of developing breast cancer. This article reviews the clinical significance of changes in circulating SHBG levels in the development of breast cancer and the possible influence of these levels on endocrine drug resistance in hormone receptor-positive breast cancer. Higher levels of plasma SHBG significantly reduce the risk of estrogen receptor-positive breast cancer, especially in postmenopausal women. Moreover, the molecular mechanisms by which SHBG affects breast cancer risk are also summarized in detail. Finally, transcriptomics and proteomics data revealed that SHBG expression in breast tissue can effectively distinguish breast cancer from normal tissue. Additionally, the association between SHBG expression levels and various classical tumor-related pathways was investigated.

Integrating Intelligent Logic Gate Dual-Nanozyme Cascade Fluorescence Capillary Imprinted Sensors for Ultrasensitive Simultaneous Detection of 2,4-Dichlorophenoxyacetic Acid and 2,4-Dichlorophenol.

Herein, a dual-nanozyme cascade catalysis triemission fluorescence capillary imprinted sensor integrated with intelligent logic gates was constructed for simultaneous detection of 2,4-dichlorophenoxyacetic acid (2,4-DA) and 2,4-dichlorophenol (2,4-DCP). The novel nanozyme fluorescence organic framework (Bi, Co-MOF) was grafted on the surface of Fe3O4 modified with histidine to form a nanozyme composite (FBM) with dual-enzyme activity, which was imprinted with 2,4-DA to prepare a fluorescence molecularly imprinted polymer (FBM@MIP). Carbon dots (CDs) coupling with FBM@MIP (FBM@MIP/CDs) was inhaled into a capillary to construct a dual-nanozyme capillary imprinted sensor directly. The FBM@MIP/CDs capillary sensor realized to detect 2,4-DA and 2,4-DCP simultaneously within a linear concentration range of 1.0 × 10-12-1.2 × 10-9 M and 1.0 × 10-12-4.8 × 10-9 M with the detection limit of 0.75 and 0.68 pM, respectively. Interestingly, a smartphone-assisted portable capillary fluorescence intelligent sensing platform was developed that can detect 2,4-DA and 2,4-DCP visually without tedious operations such as soaking and drying. Combined with a smartphone, the linear relationships between RGB ratios and concentrations of 2,4-DA and 2,4-DCP were established with the detection limit of 0.93 and 0.81 pM, respectively. The integrated logic gates provided a promising way for intelligent sensing of multiple targets simultaneously, which provided a new strategy for ultrasensitive simultaneous detection of multiple pollutants with a microvolume (18 µL/time) in complex environments.

Complementary Alu sequences mediate enhancer-promoter selectivity.

Enhancers determine spatiotemporal gene expression programs by engaging with long-range promoters1-4. However, it remains unknown how enhancers find their cognate promoters. We recently developed a RNA in situ conformation sequencing technology to identify enhancer-promoter connectivity using pairwise interacting enhancer RNAs and promoter-derived noncoding RNAs5,6. Here we apply this technology to generate high-confidence enhancer-promoter RNA interaction maps in six additional cell lines. Using these maps, we discover that 37.9% of the enhancer-promoter RNA interaction sites are overlapped with Alu sequences. These pairwise interacting Alu and non-Alu RNA sequences tend to be complementary and potentially form duplexes. Knockout of Alu elements compromises enhancer-promoter looping, whereas Alu insertion or CRISPR-dCasRx-mediated Alu tethering to unregulated promoter RNAs can create new loops to homologous enhancers. Mapping 535,404 noncoding risk variants back to the enhancer-promoter RNA interaction maps enabled us to construct variant-to-function maps for interpreting their molecular functions, including 15,318 deletions or insertions in 11,677 Alu elements that affect 6,497 protein-coding genes. We further demonstrate that polymorphic Alu insertion at the PTK2 enhancer can promote tumorigenesis. Our study uncovers a principle for determining enhancer-promoter pairing specificity and provides a framework to link noncoding risk variants to their molecular functions.

Combined Effect of Dynapenia and Abdominal Obesity on the Prevalence of Peripheral Artery Disease in Older Adults Over 75 Years Old in China.

The objective is to examine the separate and joint effects of dynapenia and abdominal obesity on the prevalence of peripheral artery disease (PAD) in older adults of different ages (60-74 and over 75 years old). This study comprised 1293 community-dwelling Chinese participants recruited from Shanghai, China, who were aged at least 60 years (753 women; mean age: 72.0 ± 5.9 years). Dynapenia was defined as low-grip strength (<28.0 kg for males and <18.0 kg for females) but normal skeletal muscle index (≥7.0 kg/m2 for males and ≥5.7 kg/m2 for females). Abdominal obesity was determined according to waist circumference (≥90 cm for males and ≥85 cm for females), and PAD was diagnosed by an ankle-brachial index ≤ 0.9. Binary logistic regression models were performed to determine associations between dynapenia, abdominal obesity, and the combination of dynapenia and abdominal obesity and PAD. According to dynapenia and abdominal obesity status stratified by age (60-74 or over 75), the patients were divided into 4 groups: normal, dynapenia alone, abdominal obesity alone, and co-occurring groups. A logistic regression showed that the co-occurring groups (odds ratio = 4.63, 95% confidence interval = 1.41-15.21) had a higher prevalence of PAD than the normal group after adjusting for the covariates in older adults over 75 years of age. The combination of dynapenia and abdominal obesity increase the prevalence of PAD in older adults over 75 years. The present findings have important implications for the early identification of older adults with PAD and appropriate interventions should be implemented.

Characteristics and sources of PM2.5-bound elements in Shanghai during autumn and winter of 2019: Insight into the development of pollution episodes.

Elemental composition of PM2.5 dispersed in the atmosphere has received increasing attention due to its health effect and catalytic activities. In this study, the characteristics and source apportionment of PM2.5-bound elements were investigated using hourly measurements. K is the most abundant metal element, followed by Fe > Ca > Zn > Mn > Ba > Pb > Cu > Cd. With an average of 8.8 ± 4.1 ng m-3, Cd was the only element whose pollution level exceeded the limits of Chinese standards and WHO guidelines. The concentrations of As, Se, and Pb doubled in December compared to November, indicating a large increase in coal consumption in winter. The enrichment factors of As, Se, Hg, Zn, Cu, Cd, and Ag were larger than 100, indicating that anthropogenic activities greatly affected them. Ship emissions, coal combustion, soil dust, vehicle emissions, and industrial emissions were identified as major sources of trace elements. In November, the pollution from coal burning and industrial activities was significantly reduced, demonstrating the remarkable achievement of coordinated control measures. For the first time, hourly measurements of PM2.5-bound elements and secondary sulfate and nitrate were used to investigate the development of dust and PM2.5 events. During a dust storm event, secondary inorganic salts, potentially toxic elements, and crustal elements sequentially reached peak concentrations, indicating different source origins and formation mechanisms. During the winter PM2.5 event, the sustained increase of trace elements was attributed to the accumulation of local emissions, while regional transport was responsible for the explosive growth before the end of the event. This study highlights the important role of hourly measurement data in distinguishing local accumulation from regional and long-range transport.

Oxygen-independent alkyl radical nanogenerator enhances breast cancer therapy.

The hypoxic microenvironment of breast cancer substantially reduces oxygen-dependent free radical generation. Overexpression of glutathione (GSH) in tumor cells mitigates the impact of free radical generation. In this study, we designed and developed an oxygen-independent alkyl radical nanogenerator (copper monosulfide/2,2'-azabis(2-imidazoline) dihydrochloride@bovine serum albumin; CuS/AIPH@BSA) with spatiotemporally controlled properties and GSH consumption to enhance breast cancer therapy. We encapsulated the alkyl radical initiator, AIPH, in hollow mesoporous CuS nanoparticles with photothermal conversion effect and enveloped them in BSA. AIPH was released and decomposed to generate alkyl radicals in hypoxic breast cancer with the photothermal conversion effect of CuS under near-infrared laser irradiation. CuS consumed high GSH levels in tumor cells because it could form complex with GSH and thereby enhanced free radical treatment. In vivo and in vitro assays demonstrated the anti-tumor efficacy of the rationally designed free-radical nanogenerator in hypoxic microenvironment of breast cancer without showing systemic toxicity.

Cellular retinol-binding protein 1: a therapeutic and diagnostic tumor marker.

Cellular Retinol Binding Protein 1 (CRBP1) gene is a protein coding gene located on human chromosome 3q21, which codifies a protein named CRBP1. CRBP1 is widely expressed in many tissues as a chaperone protein to regulate the uptake, subsequent esterification and bioavailability of retinol. CRBP1 combines retinol and retinaldehyde with high affinity to protect retinoids from non-specific oxidation, and transports retinoids to specific enzymes to promote the biosynthesis of retinoic acid. The vital role of CRBP1 in retinoids metabolism has been gradually discovered, which has been implicated in tumorigenesis. However, the precise functions of CRBP1 in different diseases are still poorly understood. The purpose of this review is to provide an overview of the role of CRBP1 in various diseases, especially in both the promotion and inhibition of cancers, which may also offer a novel biomarker and potential therapeutic target for human diseases.

Characteristics of aerosol chemistry and acidity in Shanghai after PM2.5 satisfied national guideline: Insight into future emission control.

With continuous endeavors to control air pollutant emissions, the average concentration of PM2.5 in Shanghai in 2019-2020 satisfied the national secondary standard (35 µg m-3) for the first time. In this study, the two-year dataset of hourly resolution PM2.5 compositions observed in downtown Shanghai was used to investigate the relative contribution of sulfate and nitrate as well as particulate acidity. The average concentration of SO2 was reduced to 7.7 µg m-3, while the concentration of NOx remained above 40 µg m-3, indicating that the control of SO2 was more effective than that of NOx during the 13th Five-Year Plan period. Thus, the sulfate pollution was significantly reduced whereas the nitrate loading remained almost constant. The monthly N/S ratio varied from below 0.6 to above 2.0, indicating that the contribution of automobile exhaust to PM2.5 is seasonally dependent. Contrary to sulfate, the nitrate fraction increased rapidly with the increase of PM2.5 mass, suggesting that the explosive growth of nitrate has become a major driver of haze formation. ISORROPIA simulations show that PM2.5 was moderately acidic with pH values following the trend of winter > spring > autumn > summer. The diurnal variation of nitrate was related to the changes in aerosol water content, indicating the effect of heterogeneous aqueous reactions on secondary aerosol formation. The effectiveness of emission control for reducing inorganic PM2.5 varied with different gas precursors and seasons. The abatement of NH3 emissions will increase particle acidity and acid rain pollution, although it is more effective than that of NOx when the emission reduction is larger than 60%. This study suggests that the control of vehicle exhaust should be given priority in the Yangtze River Delta for coordinately mitigating PM2.5 and acid rain pollution.

Automated fast computational adaptive optics for optical coherence tomography based on a stochastic parallel gradient descent algorithm.

The transverse resolution of optical coherence tomography is decreased by aberrations introduced from optical components and the tested samples. In this paper, an automated fast computational aberration correction method based on a stochastic parallel gradient descent (SPGD) algorithm is proposed for aberration-corrected imaging without adopting extra adaptive optics hardware components. A virtual phase filter constructed through combination of Zernike polynomials is adopted to eliminate the wavefront aberration, and their coefficients are stochastically estimated in parallel through the optimization of the image metrics. The feasibility of the proposed method is validated by a simulated resolution target image, in which the introduced aberration wavefront is estimated accurately and with fast convergence. The computation time for the aberration correction of a 512 × 512 pixel image from 7 terms to 12 terms requires little change, from 2.13 s to 2.35 s. The proposed method is then applied for samples with different scattering properties including a particle-based phantom, ex-vivo rabbit adipose tissue, and in-vivo human retina photoreceptors, respectively. Results indicate that diffraction-limited optical performance is recovered, and the maximum intensity increased nearly 3-fold for out-of-focus plane in particle-based tissue phantom. The SPGD algorithm shows great potential for aberration correction and improved run-time performance compared to our previous Resilient backpropagation (Rprop) algorithm when correcting for complex wavefront distortions. The fast computational aberration correction suggests that after further optimization our method can be integrated for future applications in real-time clinical imaging.

Nonnull interferometric testing of spherical gratings under Littrow conditions with opposite diffraction orders.

Diffracted wavefront measurements are qualitative and comprehensive verifications for the spherical grating that was manufactured to specifications. Direct interferometric testing of the diffracted wavefront is convenient and implemented by tilting the spherical grating at a Littrow angle to obtain autoreflection and then results in a nonnull interferometric testing configuration. The diffracted wavefront of the spherical grating contains not only wavefront errors induced by the manufacturing imperfections but also inherent wavefront contributions from the autoreflection testing setup. The magnitudes of the latter are affected by both the spherical substrate and the groove pattern. Through the analysis of geometric aberrations of spherical gratings, the groove pattern contributions are demonstrated to be contrary for the opposite diffraction orders. A nonnull interferometric testing of spherical gratings is proposed without foreknowledge of the groove pattern, in which the wavefront errors contributed only by the manufacturing imperfections are derived from dual measurements under Littrow conditions with opposite diffraction orders. Simulations are implemented for varied line spacing (VLS) spherical gratings with an F-number slower than 1.5 and groove density varying from 150 to 300 lp/mm, and the residual error less than 0.004λ RMS is obtained. The residual misalignment error after conventionally removing defocus and tilt is further analyzed and discussed. A VLS grating in which the NA is 0.13 and groove density is 200 lp/mm is chosen as an experimental sample, and the diffracted wavefront error with 0.018λ RMS is obtained.

Subaperture stitching interferometry based on the combination of the phase correlation and iterative gradient methods.

Subaperture stitching interferometry (SAS) is an important method for map testing of large aperture optical components, in which a mechanical structure is often employed for the testing of each subaperture. By eliminating the phase deviation of the corresponding points in the overlapping regions of every adjacent subaperture, the whole aperture map can be obtained. Accurate subaperture positioning is an important guarantee for precise stitching. In this paper, a hybrid optimization algorithm is proposed to realize subpixel-level positioning accuracy in SAS based on the combination of the phase correlation and iterative gradient methods. The phase correlation method is adopted to calculate the pixel-level positioning deviation first, and the subpixel deviation is derived and then corrected by iterative optimization through the gradient method. The subpixel-level positioning accuracy of the proposed optimization algorithm is verified by simulations and a 76.2 mm off-axis parabolic mirror is chosen as an experimental testing sample. The surface map obtained from the proposed hybrid optimization method is consistent with the full aperture testing result, which also verifies that the proposed optimization algorithm is a powerful tool with subpixel-level positioning accuracy in SAS testing.

[Investigation of the content of multiple elements in the fruit planted in Shaoxing].

OBJECTIVE: To investigate the contents of forty-four elements in the common fruits grown in Shaoxing. METHODS: The determination of 44 elements in 216 samples of ten kinds of fruits from Shaoxing was performed by national standard for food safety GB 5009. 94-2012 and GB 5009. 268-2016. Macroelements(K, Ca, Na, Mg), microelements(Li, B, Al, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Sr, Mo, Ag, Cd, Sn, Sb, Ba, Hg, Tl, Pb) and rare earth elements(Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) were analyzed and discussed. RESULTS: The fruits were rich in K, Mg and Ca with the median value of 1673. 28, 93. 76 and 56. 80 mg/kg, respectively, and the contents of K, Mg and Ca in Actinidia were the highest among all kinds of fruits, with the median value of 2932. 87、193. 91 and 253. 77 mg/kg, respectively. The contents of microelements(Fe, B and Mn) in fruit were relatively high, the detection rate was 100. 0%, and the median value was 2. 31, 2. 27 and 1. 41 mg/kg, respectively. The contents of Sb, Li, As, Hg, V, Se and Ag were very low with the detection rates below 20. 0%. The contents of 16 kinds of rare earth elements in all kinds of fruits were low with the detection rates below 50. 0% except Ce. CONCLUSION: The fruits planted in Shaoxing are rich in macroelements(K, Ca and Mg) and microelements(Fe, B and Mn), the pollution of toxic elements(Pb, Cd, Hg and As) are not serious, cadmium(Cd) in 13. 8% of strawberry is excess compared with the maximum levels of contaminants in foods(GB 2762-2017) and the contents of the 16 rare earth elements are very low.

[Construction and identification of lentiviral vector containing human ILK-shRNA and mda7 gene].

OBJECTIVE: To construct and identify lentiviral vector containing human ILK-shRNA and mda7 gene. METHODS: Based on the human ILK gene sequences, RNAi target sequences were designed and cloned into the lentiviral vector pSicoR-eGFP by restriction endonuclease HpaI and XhoI double digestion and T4 DNA ligase ligation. Based on the human mda7 gene sequences, PCR primers were designed to clone the full-length mda7, and were cloned into the lentiviral vector pLVX-Puro. After the candidate clones were identified by DNA sequencing, the recombinant plasmid and the three packaging plasmids were co-transfected into the human embryonic kidney 293T cells by lipofectamine 2000 to produce the lentiviral particles. Human prostate cancer PC-3 cells were infected with the constructed lentiviral vector. The ILK and mda7 expression levels in PC-3 cells were quantified by qPCR and Western blot, respectively. The effect of ILK and mda7 on proliferation and migration of PC-3 cells were assessed by MTT method and Transwell assay, respectively. RESULTS: ILK-pSicoR-eGFP and mda7-pLVX-Puro lentiviral vectors were successfully constructed. Strong green fluorescence was observed in the 293T cells under the fluorescent microscope after co-transfection of 293T cells with 4 plasmids of lentiviral vector. The transfection efficiency of the collected virus exceeded 90% in the 293T cells and the PC-3 cells were infected with the lentiviral particles with high efficiency. The A and B lentiviral vector inhibited the expression of ILK at both the mRNA and protein levels in PC-3 cells significantly. The mda7-pLVX-Puro lentiviral vector increased the expression of mda7 in PC-3 cells, and the ability was maintained for one month. Within 96 h, ILK and mad7 significantly inhibited the proliferation and migration of PC-3 cells (Ps<0.05). CONCLUSION: The lentiviral vectors of ILK knockdown and mda7 over-expression have been successfully constructed and identified. The recombinant lentivirus can efficiently infect human prostate cancer PC-3 cells, in which ILK expression is inhibited and mda7 is over-expressed.

Preoperative Cyfra21-1 and SCC-Ag serum titers predict survival in patients with stage II esophageal squamous cell carcinoma.

BACKGROUND: The purpose of this study is to evaluate the predictive significance of preoperative serum level of cytokeratin 19 fragments (Cyfra21-1) and squamous cell carcinoma antigen (SCC-Ag) after complete resection in patients with stage II esophageal squamous cell carcinoma (ESCC). METHODS: Between 1995 and 2006, a total of 379 patients in stage II ESCC who underwent complete resection were consecutively recruited. Statistical analyses were applied to test the associations between preoperative serum titers of Cyfra21-1 and SCC-Ag, clinicopathological factors and prognoses. RESULTS: Preoperative high and normal serum level of Cyfra21-1 and SCC-Ag were found in 47.8%, 52.2% and 72.8%, 27.2%, respectively. The 1-, 3-, 5-year overall survival rate for the entire cohort of patients was 95%, 78%, and 56%, respectively. Median overall survival (OS) was 45.3 months longer in patients with low preoperative serum level of Cyfra21-1 (91.9 months) than those with high preoperative serum level of Cyfra21-1 (46.6 months) (P < 0.001). Median OS among patients with SCC-Ag-low level was also longer than those with SCC-Ag-high level (89.7 vs. 63.7 months, P < 0.001), especially for those with stage IIB (P < 0.001). After multivariate analysis, along with pTNM stage, preoperative serum level of Cyfra21-1 and SCC-Ag were independently and significantly predictive factors (P < 0.001, P < 0.001). Furthermore, the five-year survival rate in double-low subset, either-low subset and double-high subset was 100%, 83% and 27%, respectively (P < 0.001). CONCLUSIONS: The preoperative serum level of Cyfra21-1 and SCC-Ag are independently significant predictors which negatively affected the survivals of patients with stage II ESCC.