Does green credit really increase green technology innovation?

Considering China's green credit policy (GCP) as a quasi-natural experiment, this study discusses the effect of GCP on enterprise green innovation (GI) using a difference-in-difference method based on data from Chinese listed companies from 2009 to 2020. The results indicate that green credit enhances the strategic GI of heavy polluters while significantly inhibiting essential GI, thus suggesting the nonexistence of the Porter effect. In addition, the inhibition effect is attributed to an increase in financing constraints and a reduction in government subsidies, firm research and development investment, and employment scale. This disincentive effect is particularly pronounced in privately owned firms, small cities, and capital-intensive low-profitability firms. Resource misallocation caused by the GCP fails to stimulate the green transformation of heavily polluting industries through the Porter effect. Hence, governments should establish a diversified green financial system, integrate green venture capital and GI elements, and guide the flow of social capital toward green industries.

Qualitative and quantitative recognition of chiral drugs based on terahertz spectroscopy.

Chiral drugs are drugs with chiral or asymmetric centres in their molecular structure. Different enantiomers of the same chiral drug have noticeably different pharmacological activities and pharmacokinetic properties. However, its distinction has been perplexing scholars for many years in the qualitative and quantitative detection of antagonistic drugs. Conventional detection methods, such as polarimetry, circular dichroism, and high-performance liquid chromatography, are time consuming, cause sample loss and have cumbersome operations, and they can be applied only to the sampling method. In this paper, we propose a fast, accurate, qualitative and quantitative method for the study of chiral drugs based on linearly polarized terahertz (THz) spectroscopy and imaging technology. Taking ibuprofen as an example, based on the THz absorption spectra of the enantiomers RS-ibuprofen, (R)-(-)-ibuprofen, and (S)-(+)-ibuprofen, their characteristic peak frequencies, peak amplitude differences and peak area differences were extracted to qualitatively and quantitatively distinguish and identify the three substances. THz spectral imaging provides more intuitive results than those obtained from previous methods. In quantitative identification, the stability and detection accuracy of THz spectroscopy are much greater than those of Raman spectroscopy (88.8-99.8% vs. 21.42-94.62%, respectively). The qualitative recognition accuracy was 100%, and the quantitative recognition standard deviation was less than 0.01, and it is also a non-destructive testing method. Furthermore, the above method combined with principal component analysis (PCA) and the support vector machine (SVM) neural network classification algorithm was applied to the analysis of other chiral drugs. These results are significant for the rapid, accurate and non-destructive identification of chiral drugs.

Characterizing disease progression of nonalcoholic steatohepatitis in Leptin-deficient rats by integrated transcriptome analysis.

Nonalcoholic steatohepatitis (NASH) is an aggressive liver disease threatening human health, yet no medicine is developed to treat this disease. In this study, we first discovered that Leptin mutant rats (LepΔI14/ΔI14) exhibit characteristic NASH phenotypes including steatosis, lymphocyte infiltration, and ballooning after postnatal week 16. We then examined NASH progression by performing an integrated analysis of hepatic transcriptome in Leptin-deficient rats from postnatal 4 to 48 weeks. Initially, simple steatosis in LepΔI14/ΔI14 rats were observed with increased expression of the genes encoding for rate-limiting enzymes in lipid metabolism such as acetyl-CoA carboxylase and fatty acid synthase. When NASH phenotypes became well developed at postnatal week 16, we found gene expression changes in insulin resistance, inflammation, reactive oxygen species and endoplasmic reticulum stress. As NASH phenotypes further progressed with age, we observed elevated expression of cytokines and chemokines including C-C motif chemokine ligand 2, tumor necrosis factor ɑ, interleukin-6, and interleukin-1ß together with activation of the c-Jun N-terminal kinase and nuclear factor-κB pathways. Histologically, livers in LepΔI14/ΔI14 rats exhibited increased cell infiltration of MPO+ neutrophils, CD8+ T cells, CD68+ hepatic macrophages, and CCR2+ inflammatory monocyte-derived macrophages associated with macrophage polarization from M2 to M1. Subsequent cross-species comparison of transcriptomes in human, rat, and mouse NASH models indicated that Leptin-deficient rats bear more similarities to human NASH patients than previously established mouse NASH models. Taken together, our study suggests that LepΔI14/ΔI14 rats are a valuable pre-clinical rodent model to evaluate NASH drug safety and efficacy.

Quantitative analysis of homocysteine in liquid by terahertz spectroscopy.

Homocysteine (C4H9NO2S) is a variant of the amino acid cysteine, a harmful substance to the human body, which is closely related to cardiovascular disease, senile dementia, fractures, et al. At present, conventional methods for detecting homocysteine in biological samples include high performance liquid chromatography (HPLC), fluorescence polarization immunoassay (FPIA), and enzymatic cycling methods. These methods have the disadvantages of being time-consuming, sample-losing, chemical reagent-using and operation-cumbersome. Here, we present a method for the quantitative detection of homocysteine in liquid based on terahertz spectroscopy. Considering the strong absorption of water for terahertz beam, we also put forward a pretreatment method for drying samples at low temperature. These methods make the detection limit for homocysteine reach 10 µmol/L (human normal concentration). Based on the linear relationship between the homocysteine concentration and the THz spectral intensity, we can successfully achieve quantitative, accurate and real-time detection of homocysteine. As compared to Raman spectroscopy, the correlation coefficient of THz spectrum ( R 16.24 THz 2 = 0.99809) is much larger than that of the Raman spectrum ( R 2558.26 c m - 1 2 = 0.80022, R 2937.32 c m - 1 2 = 0.8028). These results are greatly useful for the accurate evaluation of pathological stage.

Quantitative analysis of direct oral anticoagulant rivaroxaban by terahertz spectroscopy.

Rivaroxaban, as a direct oral anticoagulant, has been widely used in the treatment and prevention of thrombosis disease (TD). However, even if the same dose of rivaroxaban is taken, different pathophysiological characteristics of TD patients determine the differences in plasma concentrations between individuals, leading to the difficulties of dosage selection and plasma concentration control. Conventional rivaroxaban detection methods, including prothrombin time method, anti-Xa assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS), are not widely used in clinical practice due to the limitations of accuracy, speed and cost. Here, we present a simple quantitative detection method for rivaroxaban by terahertz (THz) spectroscopy. Combining density functional theory (DFT) method and THz spectroscopy, the THz absorption peaks of rivaroxaban and the corresponding low-frequency vibrational modes are studied theoretically and experimentally. We find linear relationships between the amplitudes of these characteristic peaks and the concentrations of rivaroxaban. Based on these linear functions, we can analyse the rivaroxaban concentration with a detection time of 1 minute per test and the lowest detection limit of 2 µmol mL-1. As compared to Raman spectroscopy method (its detection limit is about 80 µmol mL-1), our method has more potential and is practical for the clinical quantitative detection of rivaroxaban as well as other direct oral anticoagulants.

Carbon nanotubes-CuO/SnO2 based gas sensor for detecting H2S in low concentration.

Porous CuO/SnO2 nanofibers were prepared by co-dissolution and electrospinning, followed by annealing, and compounded with different amounts of carbon nanotubes (CNTs, 0-5 wt%). The performance of the composite based sensor was tested in different concentrations of H2S range from 0.1 to 0.5 ppm. The results showed that the gas sensor based CuO/SnO2 doped by CNTs (CNTs-CuO/SnO2) has a low optimum operating temperature, 40 °C, good behavior in detecting low concentration H2S, short response and recovery time (8.3 and 11.5 s, respectively). And at the same time, compared with other gases, 3 wt% CNTs-CuO/SnO2 composite nanomaterial had excellent selectivity to H2S at low concentrations. The prepared gas sensor had great advantages in detecting low concentration H2S.

A novel immunodeficient rat model supports human lung cancer xenografts.

Patient-derived xenograft (PDX) animal models allow the exogenous growth of human tumors, offering an irreplaceable preclinical tool for oncology research. Mice are the most commonly used host for human PDX models, however their small body size limits the xenograft growth, sample collection, and drug evaluation. Therefore, we sought to develop a novel rat model that could overcome many of these limitations. We knocked out Rag1, Rag2, and Il2rg in Sprague Dawley (SD) rats by clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 technology. The development of lymphoid organs is significantly impaired in Rag1-/-Rag2-/-Il2rg-/Y (designated as SD-RG) rats. Consequently, SD-RG rats are severely immunodeficient with an absence of mature T, B, and NK cells in the immune system. After subcutaneous injection of tumor cell lines of different origin, such as NCI-H460, U-87MG, and MDA-MB-231, the tumors grow significantly faster and larger in SD-RG rats than in nonobese diabetic- Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice. Most important of all, we successfully established a PDX model of lung squamous cell carcinoma in which the grafts recapitulate the histopathologic features of the primary tumor for several passages. In conclusion, the severely immunodeficient SD-RG rats support fast growth of PDX compared with mice, thus holding great potential to serve as a new model for oncology research.-He, D., Zhang, J., Wu, W., Yi, N., He, W., Lu, P., Li, B., Yang, N., Wang, D., Xue, Z., Zhang, P., Fan, G., Zhu, X. A novel immunodeficient rat model supports human lung cancer xenografts.

Dynamically imaging collision electrochemistry of single electrochemiluminescence nano-emitters.

The quest for new techniques to measure single nanomaterials is a great impetus to research efforts to understand individual behaviours. Here, we develop an electrochemiluminescence (ECL) microscopy for visualization of stochastic collision electrochemistry of single nano-emitters without the interference of current and optical background. This design uses a water-immersion objective to capture the ECL emission of nanoparticles near the specular electrode surface for enhancing light collection efficiency. The approach enables us to trace the collision trajectory of multiple nanoparticles and spatially distinguish simultaneous collisions. Results reveal that collision types, frequencies and ECL intensities significantly depend on surface natures, particle concentrations, and diffusion fluxes. By recording successive collisions, we develop a "relay probe" sensing platform for long-term research. This imaging technique displays great potential for applications in single-particle electrochemical and analytical research.

Generation and characterization of a hypothyroidism rat model with truncated thyroid stimulating hormone receptor.

Thyroid stimulating hormone receptor (TSHR), a G-protein-coupled receptor, is important for thyroid development and growth. In several cases, frameshift and/or nonsense mutations in TSHR were found in the patients with congenital hypothyroidism (CH), however they have not been functionally studied in an animal model. In the present work, we generated a unique Tshr Df/Df rat model that recapitulates the phenotypes in TSHR Y444X patient by CRISPR/Cas genome editing technology. In this rat model, TSHR is truncated at the second transmembrane domain, leading to CH phenotypes as what was observed in the patients, including dwarf, thyroid aplasia, infertility, TSH resistant as well as low serum thyroid hormone levels. The phenotypes can be reversed, at least partially, by levothyroxine (L-T4) treatment after weaning. The thyroid development is severely impaired in the Tshr Df/Df rats due to the suppression of the thyroid specific genes, i.e., thyroperoxidase (Tpo), thyroglobulin (Tg) and sodium iodide symporter (Nis), at both mRNA and protein levels. In conclusion, the Tshr Df/Df rat serves as a brand new genetic model to study CH in human, and will greatly help to shed light into the development of terminal organs that are sensitive to thyroid hormones.

Host-associated selection of a P3 mutant of zucchini yellow mosaic virus affects viral infectivity in watermelon.

In this study, we found that the infectivity of zucchini yellow mosaic virus (ZYMV) in watermelon lines H1 and K6 changed from partial to complete after propagation in the susceptible watermelon line ZXG637. When using cucumber infected with strain ZYMV-CH87 as an inoculum (named ZYMV-CH87C), the mean incidences of infection in lines H1 and K6 were 6% and 11%, respectively. However, when these lines were inoculated with ZXG637 infected with ZYMV-CH87C (named ZYMV-637), 100% of the plants became infected. Sequencing of ZYMV from these different inoculums revealed two nucleotide changes in the P3 cistron in ZYMV-637, which resulted in changes in the amino acids at positions 768 and 857 of the P3 protein, compared with the original strain ZYMV-CH87. We named this variant the M768I857-variant. The M768I857-variant was detected at low levels (3.9%) in ZYMV-CH87C. When ZYMV-CH87C was passaged with ZXG637, the M768I857-variant was selected by the host, and the original sequence was replaced entirely after two passages. These results may be explained by host-associated selection due to an unknown host-encoded factor. Using the M768I857-variant as an inoculum, 100% of the H1 and K6 plants showed systemic symptoms. These results suggest that (1) changing the individual amino acids at the end of the P3 N-terminus induces resistance-breaking, and (2) the P3 N-terminus may be involved in host recognition.

A Spectral Shift-Based Electrochemiluminescence Sensor for Hydrogen Sulfide.

Classic electrochemiluminescence (ECL) assays relying on the change in luminescence intensity face a challenge in the quantitative analysis of complex samples. Here, we report the design and implementation of a new sensing strategy, using the maximum luminescence wavelength (λmax) shift as the readout to achieve quantitative detection. This approach includes an ECL luminophore (RuSiO2@GO) and a H2S-sensitive inner filter absorber (CouMC). The absorbance of CouMC illustrates a dependence on the H2S concentration, which induces a change in the maximum luminescence wavelength (Δλmax) of the ECL luminophore. Both experimental and simulated results suggest that the spectral shift of ECL effectively avoids the interference of the total luminescence intensity fluctuations, enabling a highly reliable quantitative analysis. This spectral shift-based ECL assay strategy offers a wide application potential by extending types of ECL luminophores and absorptive chemodosimeters, based on an inner filter effect.