Evolution of household carbon emissions and their drivers from both income and consumption perspectives in China during 2010-2017.

Household inputs and consumption play important roles in driving carbon emissions in China. However, existing studies have mainly studied consumption-based household carbon emissions in specific years to highlight consumption guidance and management, and little attention has been given to income-based accounting and policy-making focused on primary input behaviors and product allocation behaviors. In the quest for more coordinated and efficient mitigation strategies, we applied input-output analysis (IOA) combined with the biproportional scaling method (RAS) to obtain both income- and consumption-based annual accounting of rural and urban household carbon emissions from 2010 to 2017 and then used structural decomposition analysis (SDA) to determine key driving factors and sectors. Our results revealed that the proportions of income-based household emissions in gross emissions were higher than that of consumption-based household emissions. In terms of driving factors, per capita income/consumption contributed the largest increase in household emissions for most of the period, and population changes also showed a weak positive effect. However, intermediate input/output structure and carbon emission intensity were the main offsetting factors for household emissions. Compared with the consumption-based results, the income-based results can identify some new critical sectors that lead to household emission changes. Furthermore, the discrepant results for rural and urban household carbon emissions from both income and consumption perspectives suggest that differentiated measures of rural and urban households in key sectors are necessary. Finally, we propose industrial chain adjustment strategies and household input and consumption behavior recommendations in the context of urbanization.

Synthesis, biological evaluation, and structure-activity relationships of new tubulin polymerization inhibitors based on 5-amino-1,2,4-triazole scaffold.

Based on our previous research, thirty new 5-amino-1H-1,2,4-triazoles possessing 3,4,5-trimethoxyphenyl moiety were synthesized, and evaluated for antiproliferative activities. Among them, compounds IIa, IIIh, and IIIm demonstrated significant antiproliferative activities against a panel of tumor cell lines, and the promising compound IIIm dose-dependently caused G2/M phase arrest in HeLa cells. Furthermore, analogue IIa exhibited the most potent tubulinpolymerization inhibitory activity with an IC50 value of 9.4 µM, and molecular modeling studies revealed that IIa formed stable interactions in the colchicine-binding site of tubulin, suggesting that 5-amino-1H-1,2,4-triazole scaffold has potential for further investigation to develop novel tubulin polymerization inhibitors with anticancer activity.

Stakeholders of the world, unite!: Hospitality in the time of COVID-19.

The COVID-19 pandemic created a global, complex crisis, without a clear end in sight, presenting an existential threat to many hospitality businesses. Drawing on stakeholder theory, we develop a framework for recovery strategy development for COVID-19, which engages salient stakeholders in the process of recognizing challenges, rationalizing changes needed and refashioning ways of working. The framework is used to analyze the process of development of a recovery strategy for a boutique hotel in England, UK, via a case study methodology. The analysis brings to the fore the interdependencies between the hotel owners and its employees, customers, governments, suppliers and communities, at local, national and international levels. Moreover, the analysis shows how collaborating with these stakeholders leads to the identification of revenue streams for the hotel, operational modifications and even the development of new commercial partnerships.

X-box-binding protein 1 is required for pancreatic development in Xenopus laevis.

X-box-binding protein 1 (XBP1) is a protein containing the basic leucine zipper structure. It belongs to the cAMP-response element binding protein (CREB)/activating transcription factor transcription factor family. As the main transcription factor, spliced XBP1 (XBP1s) participates in many physiological and pathological processes and plays an important role in embryonic development. Previous studies showed that XBP1-knockout mice died because of pancreatic exocrine function deficiency, indicating that XBP1 plays an important role in pancreatic development. However, the exact role of XBP1 in pancreatic development remains unclear. This study aimed to investigate the role of XBP1 in the pancreatic development of Xenopus laevis embryos. Whole-mount in situ hybridization and quantitative real-time PCR results revealed that the expression levels of pancreatic progenitor marker genes pdx1, p48, ngn3, and sox9 were downregulated in XBP1s morpholino oligonucleotide (MO)-injected embryos. The expression levels of pancreatic exocrine and endocrine marker genes insulin and amylase were also downregulated. Through the overexpression of XBP1s, the phenotype and gene expressions were opposite to those in XBP1s MO-injected embryos. Luciferase and chromatin immunoprecipitation assays showed that XBP1s could bind to the XBP1-binding site in the foxa2 promoter. These results revealed that XBP1 is required in the pancreatic development of Xenopus laevis and might function by regulating foxa2.

Who is a good neighbor? Analysis of frontrunner cities with comparative advantages in low-carbon development.

A well-developed economy and low-carbon emission intensity are important characteristics of low-carbon cities; they also represent important tasks for achieving global climate change mitigation goals. It is seldom discussed, however, how we should identify frontrunner cities from which low-carbon development experiences can be gleaned and then implemented in neighboring cities. This study, therefore, proposed a simple indicator-the "good neighbor index"-to identify frontrunner cities in low-carbon transformation based on economic and emission performance. Based on this indicator, we identified "good neighbors" in static and dynamic views for China. The results showed that the static good neighbors in 2015 were mostly large cities with higher incomes and better industrial structures whereas the dynamic neighbors achieved better economic growth and emission reductions from 2005 to 2015, though their economic and emissions statuses were generally worse. The good neighbor list is not consistent with the list of national low-carbon pilot cities, which has largely overlooked the experiences of some fast-growing cities. These results have policy implications for the Chinese government in terms of promoting the low-carbon transformation of cities. The study can also provide a reference for other countries in addressing climate change at the city level.

Windmill Flap Nipple Reduction: A New Method of Nipple Plasty.

BACKGROUND: Nipple hypertrophy is a common aesthetic issue for Asian women. Thus, methods to correct this problem are needed. Several nipple reduction procedures have been reported, but all have shortcomings. In this article, we propose a new method to reduce both the height and diameter of the nipple without affecting its function. METHODS: Sixteen female patients, between the ages of 24-41 years, underwent a new nipple reduction method in our department between May 17, 2010, and May 5, 2014. Three crescent-shaped lines were drawn from the top of the side wall of the nipple, extending to the areola. This design reduces both the diameter and height of the nipple with minimal tissue manipulation. RESULTS: Before surgery, the mean diameter and height of the nipple were 15.9 ± 2.7 and 18.3 ± 3.1 mm, respectively, with the patient in the supine position. Immediately after surgery, the mean diameter and height of the nipple were 9.1 ± 1.7 and 7.9 ± 2.1 mm, respectively. No major complications, such as nipple necrosis, infection, delayed wound healing, or loss of sensation, were noted. CONCLUSIONS: This new surgical technique allows the creation of a new nipple of the desired height and diameter with excellent aesthetic results and without significant complications. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Systematic Engineering of Escherichia coli for Efficient Production of Cytidine 5'-Monophosphate.

Cytidine 5'-monophosphate (CMP) was widely applied in the food and pharmaceutical industries. Currently, CMP is mainly produced by enzyme catalysis. However, the starting materials for enzyme catalysis were relatively expensive. Therefore, seeking a low-cost production process for CMP was attractive. In this study, Escherichia coli (E. coli) was systematically modified to produce CMP. First, a the cytidine-producing strain was constructed by deleting cdd, rihA, rihB, and rihC. Second, the genes involved in the pyrimidine precursor competing pathway and negative regulation were deleted to increase cyti dine biosynthesis. Third, the deletion of the genes that caused the loss of CMP phosphatase activity led to the accumulation of CMP, and the overexpression of the rate-limiting step genes and feedback inhibition resistance genes greatly increased the yield of CMP. The yield of CMP was further increased to 1013.6 mg/L by blocking CMP phosphorylation. Ultimately, the yield of CMP reached 15.3 g/L in a 50 L bioreactor. Overall, the engineered E. coli with a high yield of CMP was successfully constructed and showed the potential for industrial production.

Development of Novel N-Acylhydrazone Derivatives with High Anti-obesity Activity and Improved Safety by Exploring the Pharmaceutical Properties of Aldehyde Group.

The discovery of effective and safe antiobesity agents remains a challenging yet promising field. Our previous studies identified Bouchardatine derivatives as potential antiobesity agents. However, the 8a-aldehyde moiety rendered them unsuitable for drug development. In this study, we designed two series of novel derivatives to modify this structural feature. Through a structure-activity relationship study, we elucidated the role of the 8a-aldehyde group in toxicity induction. We identified compound 14d, featuring an 8a-N-acylhydrazone moiety, which exhibited significant lipid-lowering activity and reduced toxicity. Compound 14d shares a similar lipid-lowering mechanism with our lead compound 3, but demonstrates improved pharmacokinetic properties and safety profile. Both oral and injectable administration of 14d significantly reduced body weight gain and ameliorated metabolic syndrome in diet-induced obese mice. Our findings identify 14d as a promising antiobesity agent and highlight the potential of substituting the aldehyde group with an N-acylhydrazone to enhance drug-like properties.

Metabolic Engineering of Escherichia coli for Efficient Production of Pseudouridine.

Pseudouridine-incorporated mRNA vaccines can enhance protein expression and reduce immunogenicity, leading to a high demand for pseudouridine to be used in mRNA drug production. To achieve the low-cost production of pseudouridine, Escherichia coli was systematically modified to utilize inexpensive raw materials to efficiently produce pseudouridine. First, in the pyrimidine biosynthesis pathway, genes related to the precursor competing pathway and the negative regulator were deleted, which increased pseudouridine production. Second, two critical genes, pseudouridine-5'-phosphate glycosidase (psuG) and phosphatase genes from different bacteria, were screened and employed in various genetic constructs, and the pseudouridine yield of the optical strain increased to 599 mg/L. The accumulation of pseudouridine was further increased by the deletion of pseudouridine catabolism-related genes. Ultimately, the pseudouridine titer in a 5 L bioreactor reached 7.9 g/L, and the yield of pseudouridine on glucose was 0.15 g/g. Overall, a cell factory producing pseudouridine was successfully constructed and showed potential for industrial production.

Construction and validation of a prognostic model for tongue cancer based on three genes signature.

Tongue squamous cell carcinoma (TSCC) has a poor prognosis and destructive characteristics. Reliable biomarkers are urgently required to predict disease outcomes and to guide TSCC treatment. This study aimed to develop a multigene signature and prognostic nomogram that can accurately predict the prognosis of patients with TSCC. We screened differentially expressed genes associated with TSCC using The Cancer Genome Atlas dataset. Based on this, we developed a new multi-mRNA gene signature using univariate Cox regression, Least Absolute Shrinkage and Selection Operator regression, and multivariate Cox regression. We used the concordance index to evaluate the accuracy of this new multigene model. Moreover, we performed receiver operating characteristic and Kaplan-Meier survival analyses to assess the predictive ability of the new multigene model. In addition, we created a prognostic nomogram incorporating clinical and pathological characteristics, with the aim of enhancing the adaptability of this model in practical clinical settings. We successfully developed a new prognostic model based on the expression levels of these 3 mRNAs that can be used to predict the prognosis of patients with TSCC. This prediction model includes 3 genes: KRT33B, CDKN2A, and CA9. In the validation set, the concordance index of this model was 0.851, and the area under the curve was 0.778 and 0.821 in the training and validation sets, respectively. Kaplan-Meier survival analysis showed that regardless of whether it was in the training or validation set, the prognosis of high-risk patients was significantly worse than that of low-risk patients (P < .001). Multivariate Cox regression analysis revealed that this model was an independent prognostic factor for patients with TSCC (P < .001). Our study suggests that this 3-gene signature model has a high level of accuracy and predictive ability, is closely related to the overall survival rate of patients with TSCC, and can independently predict the prognosis of TSCC patients with high accuracy and predictive ability.

Involvement of KLRK1 in immune infiltration of head and neck squamous cell carcinoma correlates with favorable prognosis.

Head and neck squamous cell carcinoma (HNSCC) is a malignancy commonly found in the head and neck region, with a low 5-year survival rate. Although immunotherapy has made significant progress, its efficacy in HNSCC treatment remains unsatisfactory. Killer cell lectin-like receptor K1 (KLRK1), a marker highly expressed in immune cells, can bind to its ligands expressed by cancer cells to exert its antitumor effect. However, the role of KLRK1 in HNSCC has yet to be studied extensively. This study aimed to explore the involvement of KLRK1 in immune infiltration of HNSCC and its correlation with prognosis. We analyzed KLRK1 expression data from the Cancer Genome Atlas database. The relationship between KLRK1 and immune cell infiltration has also been investigated. Finally, we analyzed the association between the expression of KLRK1 and its ligands and the prognosis of patients with HNSCC. We found that KLRK1 was highly expressed in HNSCC and correlated with better prognosis. KLRK1 expression was correlated with age, histological grade, HPV infection, pT, pN, pTNM stage, primary site, and survival status. High expression levels of KLRK1 have been linked to high levels of immune cell infiltration, particularly CD4/8 (+) T lymphocytes. Among the ligands of KLRK1, UL16 binding protein (ULBP) 1-3 showed high expression, which was associated with an increased risk of death. Notably, the expression of KLRK1 was negatively correlated with ULBP1-3. Patients with high levels of ULBP2/3 expression in tonsil carcinoma had poorer prognosis than those with low levels (P < .01), whereas ULBP1 expression levels had no significant effect on tonsil carcinoma prognosis (P = .770). The expression levels of ULBP1/3 were correlated with worse prognosis in patients with laryngeal cancer (P < .05), whereas there was no significant correlation between ULBP2 expression levels and overall survival (P = .269). Our study revealed that KLRK1 is highly expressed in HNSCC and is associated with a better prognosis and immune infiltration. Patients with high expression of KLRK1 ligands exhibited worse prognoses, possibly because of the expression of more soluble ligands.

Design, synthesis and evaluation of 2-pyrimidinylindole derivatives as anti-obesity agents by regulating lipid metabolism.

Obesity, a global pandemic posing a growing threat to human health, necessitates the development of effective and safe anti-obesity agents. Our previous studies highlighted the lipid-lowering effects of indolylquinazoline Bouchardatine and its derivatives. In this study, we employed scaffold hopping and simplification strategies to design and synthesize two new series derivatives by modifying the D ring. Extensive discussions have been conducted regarding the structure-activity relationship between lipid-lowering activity and the new compounds. These discussions have resulted in the discovery of 2-pyrimidinylindole derivatives as a promising scaffold for anti-obesity treatment. The new 2-pyrimidinylindole derivatives exhibited comparable lipid-lowering activity to the previously reported indolylquinazoline derivatives, including SYSU-3d and R17, with reduced toxicity. The most potent compound, 5a, demonstrated a larger therapeutic index, improved aqueous solubility and oral bioavailability compared to the previous lead compounds. In vivo evaluation indicated that 5a effectively reduced lipid accumulation in adipose tissue, improved glucose tolerance, and mitigated insulin resistance and liver function damage caused by a high-fat and high-cholesterol diet. Mechanism studies indicated that 5a may regulate lipid metabolism through the modulation of the PPARγ signaling pathway. Overall, our study has identified a highly active compound 5a, and provided the basis for further development of 2-pyrimidinylindole as a promising scaffold for obesity treatment.

Design and Synthesis of Bouchardatine Derivatives as a Novel AMP-Activated Protein Kinase Activator for the Treatment of Colorectal Cancer.

Metabolic reprogramming is a crucial hallmark of tumorigenesis. Modulating the reprogrammed energy metabolism is an attractive anticancer therapeutic strategy. We previously found a natural product, bouchardatine, modulated aerobic metabolism and inhibited proliferation in the colorectal cancer cell (CRC). Herein, we designed and synthesized a new series of bouchardatine derivatives to discover more potential modulators. We applied the dual-parametric high-content screening (HCS) to evaluate their AMP-activated protein kinase (AMPK) modulation and CRC proliferation inhibition effect simultaneously. And we found their antiproliferation activities were highly correlated to AMPK activation. Among them, 18a was identified with nanomole-level antiproliferation activities against several CRCs. Interestingly, the evaluation found that 18a selectively upregulated oxidative phosphorylation (OXPHOS) and inhibited proliferation by modulating energy metabolism. Additionally, this compound effectively inhibited the RKO xenograft growth along with AMPK activation. In conclusion, our study identified 18a as a promising candidate for CRC treatment and suggested a novel anti-CRC strategy by AMPK activating and OXPHOS upregulating.

[Speciation analysis of Cd in PM10 and PM2.5 during heating period in Urumqi].

PM2.5 and PM10 samples were collected on campus of Xinjiang Agricultural University during Dec. 14-28, 2009, and the speciation of Cd in PM10 and PM2.5 and its health risk index was analyzed. The results showed that the pollution caused by PM10 and PM2.5 was severe here during the heating period; Cd in PM10 and PM2.5 was of concentration 3.642 and 1.964 ng x m(-3) respectively, mainly in the form of residue; however, Cd in PM2.5 had a higher bioavailability than that in PM10. The carcinogenic risk of Cd in PM10 and PM2.5 was 6.56 x 10(-6) and 3.46 x 10(-6) respectively, which were both acceptable.

Global food-miles account for nearly 20% of total food-systems emissions.

Food trade plays a key role in achieving global food security. With a growing consumer demand for diverse food products, transportation has emerged as a key link in food supply chains. We estimate the carbon footprint of food-miles by using a global multi-region accounting framework. We calculate food-miles based on the countries and sectors of origin and the destination countries, and distinguish the relevant international and domestic transport distances and commodity masses. When the entire upstream food supply chain is considered, global food-miles correspond to about 3.0 GtCO2e (3.5-7.5 times higher than previously estimated), indicating that transport accounts for about 19% of total food-system emissions (stemming from transport, production and land-use change). Global freight transport associated with vegetable and fruit consumption contributes 36% of food-miles emissions-almost twice the amount of greenhouse gases released during their production. To mitigate the environmental impact of food, a shift towards plant-based foods must be coupled with more locally produced items, mainly in affluent countries.

Discovery of a Novel G-Quadruplex and Histone Deacetylase (HDAC) Dual-Targeting Agent for the Treatment of Triple-Negative Breast Cancer.

The development of triple-negative breast cancer (TNBC) is highly associated with G-quadruplex (G4); thus, targeting G4 is a potential strategy for TNBC therapy. Because concomitant histone deacetylases (HDAC) inhibition could amplify the impact of G4-targeting compounds, we designed and synthesized two novel series of G4/HDAC dual-targeting compounds by connecting the zinc-binding pharmacophore of HDAC inhibitors to the G4-targeting isaindigotone scaffold (1). Among the new compounds, a6 with the potent HDAC inhibitory and G4 stabilizing activity could induce more DNA G4 formation than SAHA and 1 in TNBC cells. Remarkably, a6 caused more G4-related DNA damage and G4-related differentially expressed genes, consistent with its effect on disrupting the cell cycle, invasion, and glycolysis. Furthermore, a6 significantly suppresses the proliferation of various TNBC cells and the MDA-MB-231 xenograft model without evident toxicity. Our study suggests a novel strategy for TNBC therapeutics through dual-targeting HDAC and G4.

Measurement, outcomes and interventions of cognitive function after breast cancer treatment: A narrative review.

Cancer-related cognitive impairment (CRCI) is a common complaint in breast cancer patients, especially related to chemotherapy. It is characterized as cognitive disorders in areas of memory, attention and executive function, which can negatively affect patients' quality of life and their ability to work. While various assessment methods of CRCI cause highly diverse results in CRCI-related studies. Currently, it is not clear how cerebral structure and function change in breast cancer patients and underlying mechanisms of developing CRCI are still undefined. Intervention research is limited. This article reviews the results of CRCI-related studies and research progress and discusses the advantages and limits of various methods. Besides, the mechanisms and intervention strategies are reviewed.

Analysis of driving factors on China's industrial solid waste generation: Insights from critical supply chains.

Industrial solid waste (ISW) poses a huge potential threat to human health and the environment. To prevent pollution at its source, it is necessary to analyze the socioeconomic drivers and identify the key supply chains that cause changes in ISW generation. In this study, based on monetary input-output tables (MIOTs) in China from 2011 to 2015, structural decomposition analysis (SDA) was used to study the influence of socioeconomic drivers on common industrial solid waste (CISW) and hazardous waste (HW) generation. Structural path decomposition (SPD) was used to further trace the effects of drivers at the supply chain level and obtain more meaningful results for policy formulation. Economic expansion was found to play the most crucial role in the increase in total ISW generation while the reduction of generation intensity effectively slowed the growth trend. From the final demand perspective, fixed capital formation contributed the most to ISW generation growth, accounting for 65.05% of the total final demand effect. Construction was the primary trigger. For CISW, the supply chain with the greatest overall influence was "metal ore mining industry → fixed capital formation" (including intermediate consumption of metal smelting, general and special machinery, and construction), reflecting how fixed capital formation indirectly affected the metal ore mining industry. The supply chain with the greatest influence on HW generation was "paper industry → exports." Based on the findings, corresponding policy adjustments are proposed.

Sealing the emotions genie: the effects of physical enclosure on psychological closure.

This research investigated whether the physical act of enclosing an emotionally laden stimulus can help alleviate the associated negative emotions. Four experiments found support for this claim. In Experiments 1a and 1b, emotional negativity was reduced for participants who placed a written recollection of a regretted past decision or unsatisfied strong desire inside an envelope. However, enclosing a stimulus unrelated to the emotional experience did not have the same effect (Experiment 2). In Experiment 3, we showed that the effect was not driven by participants simply doing something extra with the materials, and that the effect of physical enclosure was mediated by the psychological closure that participants felt toward the event.

Forward and backward critical sectors for CO2 emissions in China based on eigenvector approaches.

China had taken measures to reduce the emissions of CO2 these years as a staunch supporter of the Paris Agreement. However, it is not such an easy task for the authority to decide which sectors should take responsibility on the process of CO2 emissions reduction in the context of highly connected supply chains. Based on the sectoral CO2 emissions and input-output table of China, this study provided both forward and backward perspectives based on eigenvector approaches to identify the critical sectors that are critical for the CO2 emissions in value chains, including a backward method called power-of-pull method that identifies the pulling effect of demand side and a forward method called power-of-push method that identifies the pushing power of supply side. The results showed that the electricity and hot water production and supply was the most influential pulling sector in the studying period, followed by the metal mining in the backward direction. In the forward direction, the electricity and hot water production and supply was also the top 1 important sector while coal mining ranked the second. The results suggest that electricity and hot water production and supply played a vital role in the CO2 emission in the system. During the studied period from 2007 to 2015, the power of nonmetal mining to pull CO2 emissions showed a notable increase. Our proposed approach could be helpful for policy-making because of its user-friendliness comparing with other method as well as providing a new perspective.