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Excessive greenhouse gas emissions might be the major culprit for environmental degradation, which have direct and indirect adverse impacts in various ways. As the largest emitter of carbon emissions, China suffered great harm from climate change during the past 40 years. Therefore, it becomes necessary to study the impact of carbon emissions on health issues and their potential mechanism. Using the panel data from 30 provinces in China between 2002 and 2017, this study employes and extends the Stochastic Impacts by Regression on Population, Affluence, and Technology (STIRPAT) model and mediating effect model to analyze the direct and indirect effects of carbon emissions. The main results are as follows: (1) Carbon emissions has a certain negative impact on public health, which would increase with the rise of temperature. (2) The increase in carbon emissions has a more significant negative effect on health with the average temperature exceeding 17.75 °C, indicating that the temperature has a threshold effect. (3) The potential health risks become higher with the development of urbanization, but there is no obvious spillover effect in the health consequences. The results remain robust after controlling other factors. This study supplements the literature of climate governance and human health, potentially contributing to the next stage of high-quality and sustainable development.

COVID-19 pandemic and its recovery bring opportunities and threats for global climate governance and further challenge climate related assets. In this study, we analyze the efficiency of government response policies and fiscal policies on green recovery by observing the variation characteristics of carbon allowance prices in the EU emission trading system (EU ETS). Using the OLS and threshold methods in the original time scales, we find that: (1) The EUA prices had an inverted U-shaped relationship with the number of new confirmed cases and deaths. (2) Government response policies had a better effect than fiscal policies when mitigating the negative impact of the pandemic. After decomposing and reconstructing the time series, the multiscale analysis indicates that: (3) The carbon price fluctuated in the short term with the increasing number of newly confirmed cases (or deaths) but gradually recovered due to the recovery policies. (4) Government response policies had a “stop-loss” effect in the short term, and then working alongside fiscal policies, sustained and promoted the development of the EU ETS and green recovery. In the post-COVID-19 era, we suggest the combination of various policies to convert the current health crisis into opportunities for climate change mitigation.

Under the pressure of economic uncertainty and environmental protection in the post-COVID-19 era, achieving a new round of employment dividends has become one practical choice. Using the panel data of 30 Chinese provinces from 2007 to 2019, this study estimates the employment outcomes of carbon ETS pilots based on the difference-in-differences model. The findings of this study indicate the following: (1) Carbon ETS pilots can positively increase employment scales with an average effect of 7.12%. (2) This promoting effect will become more significant in provinces with high education levels, provinces with high average wages, and eastern region provinces. But there is no obvious difference between gender. (3) This positive effect can be transferred and enhanced by market competition and energy consumption. At the crossroads of green economic recovery, it will be greatly beneficial to formulate the national carbon market development roadmap under the carbon neutrality strategy.

This paper aims to contribute to the theorisation of the expectations for the future life (EFL) of floating people whose household registration books (hukou) are not registered locally in China’s mega-cities. Although the EFL of many rural-urban migrants is explicit, the EFL type of other floating cohorts such as educated migrants and the formation mechanism of EFL of floating people are much less well understood. We argue that EFL is a person’s pre-judgment or estimation of living conditions in the future based on his/her perception of current human well-being or utility of life and its main concern is whether he/she expects to live in the mega-city in the future. Based on the social production functions (SPF) theory, three types of EFL for floating population are identified by using data collected from in-depth interviews with 30 Beijing’s migrants. This paper reveals that the EFL of floating population is formed by comparing their current actual utility of life with the “normative utility” in the specific life course stage, which is the life utility that people should have in their specific life course stage expected by the society. Finally, these findings are checked out that the theoretical saturation has been reached by applying another 9 copies of transcripts of interviewees.

Carbon regulation might threaten corporate competitiveness and thus guide their production and investment behaviours. Using the difference-in-differences (DID) model, we analyze the impact of China's carbon emission trading (CET) pilots on the fixed asset and its investment. The main findings are as follows: (1) CET reduces the fixed assets value and investment of regulated companies. (2) The decline in the fixed asset and its investment represents more significantly in the economically developed areas, pilots with grandfathering allocation, energy and manufacturing industries, and state-owned enterprises. (3) Potential influence channel estimation indicates that the fixed-asset investment decreases through investment diversion, rather than operation transfer. (4) CET reduces the over-investment in the fixed assets of regulated companies and improves their fixed-asset investment efficiency. This study supplements the literature on carbon regulation and corporate behaviours, potentially contributing to the next stage of climate governance and global decarbonization.

Polyketide synthase 13 (Pks13) is an essential enzyme in the synthesis of mycolic acids in Mtb. Therefore, Pks13 is a promising drug target for tuberculosis treatment. We used a structure-guided approach to identify novel chemotype inhibitors of Pks13 and assessed them using a Pks13 enzymatic assay and surface plasmon resonance. The structure–activity relationships (SAR) results demonstrated that the substituents at the 2, 5, and 6 positions of the 4H-chromen-4-one scaffold are critical for maintaining the MIC. Compound 6e with 2-hydroxyphenyl at the 2 position of the 4H-chromen-4-one scaffold, exhibited potent activity against Mtb H37Rv (MIC = 0.45 μg/mL) and displayed good Pks13 affinity and inhibition (IC50 = 14.3 μM). This study described here could provide an avenue to explore a novel inhibitor class for Pks13 and aid the further development of antituberculosis drugs.

The emergence of drug-resistant tuberculosis (TB) constitutes a major challenge to TB control programmes. There is an urgent need to develop effective anti-TB drugs with novel mechanisms of action. Aspartate-semialdehyde dehydrogenase (ASADH) is the second enzyme in the aspartate metabolic pathway. The absence of the pathway in humans and the absolute requirement of aspartate in bacteria make ASADH a highly attractive drug target. In this study, we used ASADH coupled with Escherichia coli type III aspartate kinase (LysC) to establish a high-throughput screening method to find new anti-TB inhibitors. IMB-XMA0038 was identified as an inhibitor of MtASADH with an IC50 value of 0.59 μg/mL through screening. The interaction between IMB-XMA0038 and MtASADH was confirmed by surface plasmon resonance (SPR) assay and molecular docking analysis. Furthermore, IMB-XMA0038 was found to inhibit various drug-resistant MTB strains potently with minimal inhibitory concentrations (MICs) of 0.25–0.5 μg/mL. The conditional mutant strain MTB::asadh cultured with different concentrations of inducer (10−5 or 10−1 μg/mL pristinamycin) resulted in a maximal 16 times difference in MICs. At the same time, IMB-XMA0038 showed low cytotoxicity in vitro and vivo. In mouse model, it encouragingly declined the MTB colony forming units (CFU) in lung by 1.67 log10 dosed at 25 mg/kg for 15 days. In conclusion, our data demonstrate that IMB-XMA0038 is a promising lead compound against drug-resistant tuberculosis.

Industrialization and urbanization have aggravated the contradiction between environmental protection and economic growth, leading to health issues. While there are considerable interests in understanding the health effects of carbon emissions in the context of climate change, little is observed at regional scale and by econometric methods. Applying regression analysis on 2002-2017 Chinese provincial-level panel data, this study explores the intermediary mechanisms and regional differences of carbon emissions on residents' health. The results indicate that: (1) Carbon emissions have a long-term adverse impact on residents' health-a 1% rise in carbon emission adds 0.298% more outpatients and 0.162% more inpatients; (2) The rise in carbon emissions impairs residents' health mainly by raising the temperature; (3) In areas with high levels of industrialization and urbanization, increased carbon emissions bring greater health risks; and (4) In terms of China's unique "leading industrialization and lagging urbanization" situation, only by upgrading industrial structure, improving urbanization quality, and promoting coordinated industrialization and urbanization can the harm of carbon emissions to residents' health be reduced. Therefore, the "one-size-fits-all" policy model is not suitable for China's current situation. To address global "climate change" issues, China must act according to local conditions by applying mitigating (adaptive) measures in economically developed (less developed) regions. Simultaneously, the authorities must focus on the interaction and synergy between industrialization and urbanization.

The emergence of drug-resistant Mycobacterium tuberculosis (Mtb) has hampered treatments for tuberculosis, which consequently now require novel agents to overcome such drug resistance. The genetically stable D-alanine–D-alanine ligase A (DdlA) has been deemed as an excellent therapeutic target for tuberculosis. In the present study, a competitive inhibitor (IMB-0283) of DdlA was obtained via high-throughput screening. The minimum inhibitory concentrations (MIC) of IMB-0283 for the standard and clinical drug-resistant Mtb strains ranged from 0.25 to 4.00 μg/mL, whereas the conventional inhibitor of DdlA, D-cycloserine (DCS), only inhibited the growth of the standard Mtb strain at 16 μg/mL. The lethal effect of IMB-0283 on Mtb was found to act intracellularly in a DdlA-dependent manner. Specifically, IMB-0283 prevented the synthesis of neonatal cell walls but did not damage mature cell walls. Compared with those of DCS, IMB-0283 exhibited lower cytotoxicity and a higher selective index (SI). At the same dosages of treatment, IMB-0283 reduced bacterial load (log CFU/mL) in an acute animal model from 5.58 to 4.40, while DCS did not yield any such treatment efficacy. Taken together, the lower cytotoxicity and more efficacious in vivo activity of IMB-0283 suggest that it is a promising lead compound for antituberculosis drug development.

The generation of conditional mutants has been an effective approach to studying bacteria and validating drug targets, and mutants of Mycobacteria are no exception. However unlike other bacteria, there is still a paucity of available tools for Mycobacteria. We constructed a new plasmid containing tetracycline-repressive expression system (TetRr1.7) and Xer Site-Specific recombinase system to generate label-free controllable expression strains. The plasmid was subsequently used to construct a strain of M. tuberculosis expressing the only copy of d-alanine:d-alanine ligase under the control of the tetracycline-repressive promoter. The results showed that the mutant strain lost the ability of colony formation, became more sensitive to d-cycloserine and the cell wall of the mutant strain was disrupted when anhydrotetracycline was added to the medium. Taken together these observations, confirmed that the expression of d-alanine:d-alanine ligase was tightly controlled by the promoter. In conclusion, the new plasmid is a convenient tool for constructing stable conditional mutant strains in Mycobacteria and can be used for future target identification. Electronic supplementary material The online version of this article (10.1186/s13568-018-0537-z) contains supplementary material, which is available to authorized users.

This study provides a comprehensive and accurate measurement of investment facilitation in 66 countries along the Belt and Road from 2007 to 2018. The expanded gravity model analyzes the impact of host country investment facilitation on China's outward foreign direct investment, and the panel threshold model examines the nonlinear relationship between investment facilitation and outward foreign direct investment. The results indicate significant differences in the level of investment facilitation among countries along the Belt and Road. Overall, spatial distribution characteristics are higher in East Asia, Southeast Asia, and Europe compared to other regions. An increase of 1% in the level of investment facilitation provided by the host country can generally promote a 2.173% increase in China's outward foreign direct investment. Market size (GDP) and technological progress rate (Tec) were used as thresholds for dividing countries along the Belt and Road into four economic regions. Countries in the different economic regions have different levels of sensitivity to investment facilitation and first-level indicators. Currently, Chinese outward foreign direct investment is based on market acquisition but will be based on technological upgrading in the future.

Additional file 1. PCR primers used in this study.

One lead 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole was identified as an inhibitor of shikimate dehydrogenase with antitubercular activity. Following up this compound, we optimized the lead through systematic modification of the 3 and 6 positions. The antitubercular activities in vitro, shikimate dehydrogenase inhibitory activities and cytotoxicity of derivatives were determined. We found IMB-SD62 with lower cytotoxicity and better activity. Thus, we studied the in vivo efficacy of IMB-SD62 against Mycobacterium tuberculosis and pharmacokinetics of IMB-SD62. In vivo acute M. tuberculosis H37Rv infection assay, IMB-SD62 showed antitubercular activity with the mean lung CFU counts decreasing 1.7 lg. The plasma pharmacokinetics study in rats showed that the oral bioavailability of IMB-SD62 was 14% and the half time was 1.05 h. The results of tissue distribution indicated that IMB-SD62 was mainly absorbed by liver and lung. In vitro metabolism study suggested that the metabolic ways of IMB-SD62 were dealkylated, oxidized and demethylated. CYP enzyme inhibition of IMB-SD62 in human liver microsomes was also evaluated. IMB-SD62 showed barely inhibition on CYP3A4 and CYP2D6. The excretion study manifested that IMB-SD62 was mainly eliminated by fecal excretion in rats. We concluded that based on these pharmaceutical properties, IMB-SD62 has the potential to be developed into new TB drug.

Two unique cis-fused streptothricins (1 and 2) were isolated from the culture broth of Streptomyces sp. I08A 1776. Their structures were determined by MS, CD, and 1D and 2D NMR spectroscopic data analysis. Compound 2 showed weak antibacterial activities against Bacillus subtilis and Enterococcus faecalis with MIC values of 32 and 64 μg ml(-1), respectively.

Five new streptothricin derivatives with a carbamoyl group substituted at C-12 (1-5) and three known analogues have been isolated from the culture broth of Streptomyces sp. I08A 1776 by ion exchange and hydrophilic interaction chromatographic techniques. Their structures were determined by spectroscopic and chemical methods. Compound 3 was a streptothricin derivative possessing a cis-streptolidine moiety. Its absolute configuration was defined by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. Compound 5 and streptothricin E (6) displayed antibacterial and antifungal activity with MIC values in the range 1-64 μg/mL.

Summary Objective Screen and identify novel inhibitors of isocitrate lyase (ICL) as potent antitubercular agents against Mycobacterium tuberculosis and determine their inhibitory characteristics, antitubercular activities and mechanisms of action. Methods Recombinant ICL of M. tuberculosis was expressed and purified, which was used for high-throughput screening (HTS) and the following experiments. A total of 71,765 compounds were screened to identify ICL inhibitors which were then evaluated for their roles as potent antitubercular agents. To determine the inhibitory characteristics of the agents against latent M. tuberculosis in persistent infections, a macrophage model (mouse J774A.1 cell) infected with Mycobacterium marinum BAA-535 strain was built and assessed. The potent antitubercular agents were identified using the macrophage model. Then, the inhibitory intensity and mode of the agents that exhibit on ICL protein of M. tuberculosis were analyzed, and the interaction mechanisms were preliminarily clarified according to the parameters of enzyme kinetics, circular dichroism experiments, fluorescence quenching assay, and molecular docking. Results The previously established ICL inhibitor screening model was evaluated to be suitable for HTS assay. Of the 71,765 compounds, 13 of them were identified to inhibit ICL effectively and stably. IMBI-3 demonstrated the most significant inhibitory activity with IC 50 of 30.9 μmol/L. Its minimum inhibitory concentration (MIC) for M. tuberculosis , including extensively drug-resistant tuberculosis (XDR-TB) and multidrug-resistant tuberculosis (MDR-TB), were determined in the range of 0.25–1 μg/mL. When IMBI-3 is used in combination with isoniazid, the colony-forming units (CFU) counting of latent M. tuberculosis in J774A.1 macrophage cells decreased significantly as IMBI-3 concentration increased. The inhibition mode of IMBI-3 on ICL was probably competitive inhibition with an inhibition constant ( K i ) of approximate 1.85 μmol/L. The interaction between IMBI-3 and ICL of M. tuberculosis was also confirmed by circular dichroism experiments and fluorescence quenching assay. And seven possible active amino acids of ICL of M. tuberculosis were identified in the active site through molecular docking. Conclusion IMBI-3, a novel potent antitubercular agent targeting ICL of M. tuberculosis , was identified and evaluated. It inhibited both log-phase M. tuberculosis in vitro and dormant M. tuberculosis in macrophages. It was the first representative compound of this family with the ICL enzyme inhibition and antimycobacterial activities.

Tuberculosis is a serious threat to world-wide public health usually caused in humans by Mycobacterium tuberculosis (M. tuberculosis). It exclusively utilizes the methylerythritol phosphate (MEP) pathway for biosynthesis of isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP), the precursors of all isoprenoid compounds. The 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase (IspD; EC 2.7.7.60) is the key enzyme of the MEP pathway. It is also of interest as a new chemotherapeutic target, as the enzyme is absent in mammals and ispD is an essential gene for growth. A high-throughput screening method was therefore developed to identify compounds that inhibit IspD. This process was applied to identify a lead compound, domiphen bromide (DMB), that may effectively inhibit IspD. The inhibitory action of DMB was confirmed by over-expressing or down-regulating IspD in Mycobacterium smegmatis (M. smegmatis), demonstrating that DMB inhibit M. smegmatis growth additionally through an IspD-independent pathway. This also led to higher levels of growth inhibition when combined with IspD knockdown. This novel IspD inhibitor was also reported to exhibit antimycobacterial activity in vitro, an effect that likely occurs as a result of perturbation of cell wall biosynthesis.

Mycobacterium tuberculosis pantothenate synthetase is a potential anti-tuberculosis target, and a high-throughput screening system was previously developed to identify its inhibitors. Using a similar system, we screened a small library of compounds and identified actinomycin D (ActD) as a weak inhibitor of pantothenate synthetase. A new method was established to discover more effective inhibitors by determining the molecular mechanism of ActD inhibition followed by structure-based virtual screening. The molecular interaction of inhibition was determined by circular dichroism and tryptophan fluorescence quenching. The structure-based search and virtual screening were performed using the Molecular Operating Environment (MOE) program and SYBYL 7.5, respectively. Two inhibitors were identified with an IC(50) for pantothenate synthetase that was at least ten times better than that of ActD.

We used the VAR model to construct a new model in order to assess the impact of China’s central bank note issuance and repurchase business on the overall price level of the market. We also used the impulse response function to analyze the impact of the base currency. The central bank invested it or withdrew it from circulation through the central bank note issuance and repurchase business, on prices and the time required producing such impact. We conclude that the impact of central bank bills on prices lasts a relatively long time and is relatively large; while repurchase can work more quickly, and then its impact will decline rapidly. Then, we propose the focus of open market operations in the present context of relatively high inflation.