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Androgen deprivation therapy (ADT) includes bilateral orchiectomy or long-acting gonadotropin-releasing hormone (GnRH) agonists/antagonists. It remains controversial with respect to ADT associated cardiovascular outcomes. Hereby, we compared the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with prostate cancer receiving either surgical castration or GnRH therapies.Using the Taiwan Cancer Registry and Taiwan's National Health Insurance Research Database, we identified 8,413 patients receiving GnRH therapies compared with 694 receiving surgical castration from 2008 to 2017. The median followup duration was 3 years.The crude incidences of 3-year mortality and MACCEs were 19.90% vs 26.51% and 8.23% vs 8.65% in patients receiving GnRH therapies or surgical castration, respectively. After adjusting for age, cancer stage and comorbidities, despite no significant differences in MACCEs between groups there was a slight increase in the incidence of acute myocardial infarction (AMI) in patients receiving surgical castration compared with those receiving GnRH therapies. The mortality adjusted hazard ratios of MACCEs and AMI among patients receiving surgical castration were 1.11- and 1.8-fold higher than those receiving GnRH therapies. Notably, in subgroup analysis regarding cancer stage, patients with cancer stage IV showed the most significantly increasing risk of AMI in those receiving surgical castration compared with GnRH therapies.Collectively, we indicated an increased risk of AMI in patients with prostate cancer, especially in patients receiving surgical castration rather than those receiving GnRH therapies. Our findings highlight concerns regarding the cardiac safety of surgical castration compared with GnRH therapies.

Zn-5Al eutectic alloy is a promising Pb-free solder suitable for high-temperature electronics packaging. However, the soldering with Zn-5Al alloy is undermined by its poor oxidation resistance and wettability in ambient atmosphere, which also demands significant time to complete if transient liquid phase soldering (TLPS) is required. In this work, the TLPS assisted by ultrasonic vibration (USV) under ambient condition without flux has been performed to enhance and accelerate interfacial reactions between Zn-5Al and Cu or Ni substrate. It has been found that the resultant full intermetallic compounds (IMCs) joints with uniform microstructure can be formed within 1 min and 3 min on Cu and Ni substrate, respectively, without flux or protective inert gases. The IMCs resulted from the interfacial reactions have been identified after the completion of TLPS process. For the ultrasonic-assisted TLPS (U-TLPS) of Zn-5Al onto Cu substrate, the joints consist of three IMC layers, CuZn, Cu5Zn8, and CuZn with the residual oxide fragments remained at the central line inside of IMC Cu5Zn8, where Al is rich likely due to the segregation of element Al during the TLPS process. For the U-TLPS of Zn-5Al onto Ni substrate, three IMC layers, Ni5Zn21, NiAl and Ni5Zn21 IMC were also observed, with the porous Ni5Zn21 IMC layers present in adjacent to the Ni substrate. Both residual oxide fragments in the Zn-5Al/Cu joints and porous Ni5Zn21 IMC in the Zn-5Al/Ni joints could potentially deteriorate mechanical integrity of the joints, which is yet to be understood.

A three-dimensional model has been developed to capture burning properties of ammonium perchlorate(AP)/hydroxyl–terminated polybutadiene(HTPB) composite propellant. Interfacial coupling between condensed domain and gas phase was conducted to obtain the surface temperature and burning rate. The condensed phase was governed by heat transfer equation, and reacting Navier-Stokes equations with pressure dependent 3-step and 12-species global kinetics were adopted. The current model was verified and validated by comparing with analytical and experimental results. Thereafter, the influences of ellipsoidal AP's orientation and aspect ratio on the burning rate were investigated. The flame structure of a typical propellant with ellipsoidal AP particle was examined, and the characteristic heights of multiple flames were determined. Besides, the flame properties of a typical propellant with spherical/ellipsoidal AP particle and different AP topologies were analyzed. Furthermore, the temperature sensitivity coefficients were calculated for composite propellant with different AP contents and sizes, matching reasonably with the experimental results.

BACKGROUND: Long-term survivals of patients with HBV-related hepatocellular carcinoma are limited by the high incidence of tumor recurrence after radiofrequency ablation (RFA), identification of the risk factors and understanding the patterns of recurrence can help to improve the comprehensive management of patients after RFA. Therefore, the purpose of the study is to explore the prognostic value of the age-male-albumin-bilirubin-platelets (aMAP) score in patients with early-stage HBV-related hepatocellular carcinoma (HCC) receiving RFA; investigate the risk factors and patterns of late recurrence (LR); and develop a nomogram to predict recurrence-free survival (RFS). METHODS: A retrospective review of HBV-related HCC patients who underwent primary RFA from March 2012 to December 2020 was conducted. The prognostic value of the aMAP score was evaluated in a primary cohort (n=302) and then further validated in an independent validation cohort (n=143). The optimal threshold of aMAP scores was calculated by X-tile 3.6.1 software. A prognostic nomogram was constructed from multivariate analysis and validated in an external validation cohort. RESULTS: Patients with aMAP scores ≤63.8, 63.8–67.8, and >67.8 were classified into low-, medium-, and high-recurrence risk groups, respectively. The C-index to predict LR was 0.76 (95% CI: 0.700–0.810). The high-risk group was associated with the worst RFS (HR: 5.298; 95% CI, 2.697–10.408; P

BACKGROUND Severe acute pancreatitis (SAP) is a deadly inflammatory disease with complex pathogenesis and lack of effective therapeutic options. N6-methyladenosine (m6A) modification of circRNAs plays important roles in physiological and pathological processes. However, the roles of m6A circRNA in the pathological process of SAP remains unknown. AIM To identify transcriptome-wide map of m6A circRNAs and to determine their biological significance and potential mechanisms in SAP. METHODS The SAP in C57BL/6 mice was induced using 4% sodium taurocholate salt. The transcriptome-wide map of m6A circRNAs was identified by m6A-modified RNA immunoprecipitation sequencing. The biological significance of circRNAs with differentially expressed m6A peaks was evaluated through gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The underlying mechanism of m6A circRNAs in SAP was analyzed by constructing of m6A circRNA-microRNA networks. The expression of demethylases was determined by quantitative polymerase chain reaction and western blot to deduce the possible mechanism of reversible m6A process in SAP. RESULTS Fifty-seven circRNAs with differentially expressed m6A peaks were identified by m6A-modified RNA immunoprecipitation sequencing, of which 32 were upregulated and 25 downregulated. Functional analysis of these m6A circRNAs in SAP found some important pathways involved in the pathogenesis of SAP, such as regulation of autophagy and protein digestion. In m6A circRNA–miRNA networks, several important miRNAs participated in the occurrence and progression of SAP were found to bind to these m6A circRNAs, such as miR-24-3p, miR-26a, miR-92b, miR-216b, miR-324-5p and miR-762. Notably, the total m6A level of circRNAs was reduced, while the demethylase alkylation repair homolog 5 was upregulated in SAP. CONCLUSION m6A modification of circRNAs may be involved in the pathogenesis of SAP. Our findings may provide novel insights to explore the possible pathogenetic mechanism of SAP and seek new potential therapeutic targets for SAP.

A bis(pyridyl)amine-bipyridine-iron(II) framework (Fe(BPAbipy)) of complexes 1-3 is reported to shed light on the multistep nature of CO2 reduction. Herein, photocatalytic conversion of CO2 to CO even at low CO2 concentration (1 %), together with detailed mechanistic study and DFT calculations, reveal that 1 first undergoes two sequential one-electron transfer affording an intermediate with electron density on both Fe and ligand for CO2 binding over proton. The following 2 H+ -assisted Fe-CO formation is rate-determining for selective CO2 -to-CO reduction. A pendant, proton-shuttling α-OH group (2) initiates PCET for predominant H2 evolution, while an α-OMe group (3) cancels the selectivity control for either CO or H2 . The near-unity selectivity of 1 and 2 enables self-sorting syngas production at flexible CO/H2 ratios. The unprecedented results from one kind of molecular catalyst skeleton encourage insight into the beauty of advanced multi-electron and multi-proton transfer processes for robust CO2 RR by photocatalysis.

The clinical challenge of high-accuracy blood glucose detection schemes is to overcome the detection error caused by the background interferences in different individuals. H2O2 as the specific product of glucose oxidation can be involved in the Fe2+/Fe3+ conversion and detected by the time-domain nuclear magnetic resonance (TD-NMR) method sensitively. But, in clinical applications, the oxidation of Fe2+ is susceptible to the complex sample substrates. In this work, we sorted out two kinds of possible interference mechanisms of Fe2+ oxidation in the NMR blood glucose detection method and proposed a feasible scheme that uses sorbitol to weaken the adverse effects of interference. We found that sorbitol-mediated Fe2+ can greatly enhance the sensitivity of the T2 value to H2O2. The chain reaction caused by sorbitol can significantly amplify the efficiency of Fe2+ oxidation at the same concentration of H2O2. Thereby, we can achieve the higher dilution multiple of serum samples to reduce the amount of interfering substances involved in the Fe2+/Fe3+ conversion. We justified the accuracy and availability of our method by successfully detecting and confirming the correlation between the T2 decrease and glucose concentration of the serum samples collected from 16 subjects. The sorbitol-Fe2+ glucose detection method with high sensitivity can be further combined with miniature NMR analyzers to satisfy the calibration requirements of glucose monitoring in diabetic patients instead of frequent medical visits.

Periodontitis, one of the most common chronic inflammatory diseases, affects the quality of life. Osteogenesis makes an important role of the disease. There is a connection between hydrogen sulfide (H2S) and periodontitis, but according to the study has been published, the precise role of H2S in inflammation remains in doubt. The main reason of the lack of research is that H2S is an endogenous gasotransmitter, difficult to discern through testing. So, we synthesis a novel fluorescence probe which can detective H2S in vitro. By using the novel H2S fluorescence probe, we found that H2S changes in osteoblasts mainly by cystathionine-γ-lyase, and H2S increases under LPS stimulation. H2S could be a potential marker for diagnosis of inflammatory diseases of bone, and might help deeper studies of the changes of H2S level and promote the progression on the researches about pathogenesis of periodontitis.

Furin is one of the nine-member proprotein convertase family. Furin cleaves proteins with polybasic residues, which includes many viral glycoproteins such as SARS-Cov-2 spike protein. The cleavage is required for the activation of the proteins. Currently, the mechanisms that regulate Furin activity remain largely unknown. Here we demonstrated that Furin is a novel heparin/heparan sulfate binding protein by the use of biochemical and genetic assays. The KD is 9.78 nM based on the biolayer interferometry assay. Moreover, we found that sulfation degree, site-specific sulfation (N-sulfation and 3-O-sulfation), and iduronic acid are the major structural determinants for the binding. Furthermore, we found that heparin inhibits the enzymatic activity of Furin when pre-mixes heparin with either Furin or Furin substrate. We also found that the Furin binds with cells of different origin and the binding with the cells of lung origin is the strongest one. These data could advance our understanding of the working mechanism of Furin and will benefit the Furin based drug discovery such as inhibitors targeting the interaction between heparan sulfate and Furin for inhibition of viral infection. Supplementary information The online version contains supplementary material available at 10.1007/s10719-021-10018-8.

The direct oxidation of methane (CH4) to methanol (CH3OH) has been a focus of global concern and is quite challenging due to the thermodynamically stable CH4 and uncontrolled overoxidation of the products. Here, we provided a new viewpoint on the role of oxygen vacancies that induce a dual-function center in enhancing the adsorption and activation of both CH4 and O2 reactants for the subsequent selective formation of a CH3OH liquid fuel on two-dimensional BiOCl photocatalysts at atmospheric pressure. The key for the favorable activity lies in the simultaneous ability of the electron-trapped Bi atom in activating CH4 and the formation of •O2- radicals due to the activation of O2 at the adjacent oxygen vacancy site, which immediately attack the activated CH4 to directly produce CH3OH, in initiating the oxidation reaction. What is more, the relatively low reaction barriers and the easy desorption of CH3OH concertedly facilitate the highly selective conversion of CH4 up to 85 μmol of CH3OH, with a small amount of CO2 and CO as the byproducts over the BiOCl nanosheets with an oxygen vacancy concentration of 2.4%. This work could broaden the avenue toward the application of oxygen-defective metal oxides in the photocatalytic selective conversion of CH4 to CH3OH and offer a disparate perspective on the role of oxygen vacancy acting as the surface electron transfer channel in enhancing the photocatalytic performance.

ObjectiveCirculating tumour DNA (ctDNA) sequencing is increasingly used in the clinical management of patients with colorectal cancer. However, the genomic heterogeneity in ctDNA during treatments and its impact on clinical outcomes remain largely unknown.DesignWe conducted a prospective cohort study (NCT04228614) of 171 patients with unresectable metastatic colorectal cancer (mCRC) who underwent first-line treatment and prospectively collected blood samples with or without tumour samples from patients at baseline and sequentially until disease progression or last follow-up.ResultsThe RAS/BRAF alterations in paired baseline tissue and plasma samples from 63 patients displayed a favourable concordance (81.0%, 51/63). After a period of first-line treatment (median time between baseline and last liquid biopsy, 4.67 months), 42.6% (26/61) of RAS-mutant patients showed RAS clearance and 50.0% (5/10) of BRAF-mutant patients showed BRAF clearance, while 3.6% (3/84) and 0.7% (1/135) of patients showed new RAS or BRAF mutations in ctDNA. Patients with plasma RAS/BRAF clearance showed similar progression-free survival (PFS) and overall survival (OS) with patients who remained RAS/BRAF wild-type, while much better outcomes than those who remained RAS/BRAF mutant. Patients who gained new RAS/BRAF mutations showed similar prognosis as those who maintained RAS/BRAF mutations, and shorter PFS and OS than those who remained RAS/BRAF wild-type.ConclusionThis prospective, serial and large-scale ctDNA profiling study reveals the temporal heterogeneity of mCRC-related somatic variants, which should be given special attention in clinical practice, as evidenced by the finding that the shift in plasma RAS/BRAF mutational status can yield a drastic change in survival outcomes.

Carbon quantum dots (CQDs) with an average diameter of 3 nm, exhibiting blue photoluminescence, have been obtained from commercial conductive carbon black by a cost-effective and straightforward exfoliation method using dry ball milling in the presence of sodium carbonate. As a secondary abrasive medium, sodium carbonate provides effective exfoliation of carbon black with a high degree of CQD graphitization and plays an essential role in the functionalization of CQDs with oxygen groups. Due to the low toxicity of CQDs against HeLa cancer cells (cell viability above 90% at a CQD concentration of 200 μg cm−3) and the ability to penetrate cells and emit blue light, CQDs are possibly suitable for biological imaging of cells.

Terpinen-4-ol, the main component of tea tree oil, markedly increases the disease resistance of postharvest strawberry fruit. To understand the mechanism underlying the enhancement of disease resistance, a high-throughput RNA-seq was used to analyze gene transcription in terpinen-4-ol-treated and untreated fruit. The results show that terpinen-4-ol induces the expression of genes in the jasmonic acid (JA) biosynthesis pathway, secondary metabolic pathways such as phenylpropanoid biosynthesis, and pathways involved in plant-pathogen interactions. Terpinen-4-ol treatment reduced disease incidence and lesion diameter in strawberry fruit inoculated with Botrytis cinerea. Terpinen-4-ol treatment enhanced the expression of genes involved in JA synthesis (FaLOX, FaAOC, and FaOPR3) and signaling (FaCOI1), as well as genes related to disease defense (FaPAL, FaCHI, and FaGLU). In contrast, treatment with the JA biosynthesis inhibitor salicylhydroxamic acid (SHAM) accelerated disease development and inhibited the induction of gene expressions by terpinen-4-ol. We conclude that the JA pathway participates in the induction of disease resistance by terpinen-4-ol in strawberry fruit. More generally, the results illuminate the mechanisms by which disease resistance is enhanced by essential oils.

In this paper, a novel H2Ti2O5@MoS2@SiO2 ternary composite material was prepared by a combination of dual hydrothermal method and controlled hydrolysis method, in which H2Ti2O5 nanotubes are tightly combined with hierarchical molybdenum disulfide, and the unique structure of titanate nano whiskers, including the loosely bound alkali metal ions between the titanate layers with high dielectric constant and the large aspect ratio, which induce active response to the electric field. Flower-like molybdenum disulfide provides electrical conductivity, and silicon dioxide as a insulative coating layer can suppress excessive the electrical conductivity of the two-dimensional material. The morphological evolution was studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results of showed that the sheet-shaped molybdenum disulfide coated with curved H2Ti2O5 nanotubes showed a honeycomb structure with uniform size. Silicon oxide acts as a cladding layer to increase the thickness of the flakes. The existence of H2Ti2O5, molybdenum disulfide and silicon dioxide is confirmed by X-ray powder diffractometer (XRD) and Fourier transform infrared spectroscopy (FT-IR). The prepared product was confirmed by XPS, BET test and electrorheological rheometer. Core/shell nanoparticles not only exert the active response characteristics of titanate nanoparticles and molybdenum disulfide to electric field, but also inherit the excellent characteristics of a core-shell structure produced by the interface polarization and the synergistic effect of the polar groups on the surface of the two-dimensional material further enhance the electrorheological effect.

Postsynthesis of the paramagnetic square-shaped complex {[(Tp*Me)Fe(μ-CN)2(CN)][Co(dmbpy)2]}2(BPh4)2·6MeCN·H2O [1, Tp*Me = tris(3,4,5-trimethylpyrazole)-borate; dmbpy = 4,4′-dimethyl-2,2′-bipyridin...

Gastric cancer (GC) is the third leading cause of cancer-associated mortality globally. Although the diagnosis and therapeutic strategies for GC have improved, the prognosis for advanced gastric cancer (AGC) remains poor. Hence, the present study sought to design a zebrafish model established by microinjecting human MGC-803 GC cell line for studying personalized molecular-targeted cancer therapy. Apatinib, a novel molecular-targeted agent, was evaluated for its in vivo efficacy through a comparison among the control groups (no treatment) and subject groups (treatment). Newly formed vessel length and tumor volume were measured in all of the groups for further study. The length of newly formed vessels was obviously shortened after apatinib treatment in the zebrafish model established in this study. Meanwhile, apatinib exhibited the best antitumor growth effect with dose and time dependence by suppressing AKT/GSK3α/β signaling, which may be the mechanism underlying the profound antitumor clinical effect of apatinib. The data indicated that apatinib therapy exerts an anti-angiogenesis effect and it can be recommended as a proper antitumor growth therapy for GC patients. Additionally, zebrafish models could be designed as a potential practical tool to explore new anti-GC cancer drugs.

Rechargeable Li-CO2 batteries as a novel system developed in recent years directly use CO2 as the reactant, which enables deeper penetration of energy storage and CO2 utilization. The Li-CO2 battery system, however, is at an early stage, and many challenges remained to be overcome urgently, especially the problem of high over-potential during the charging process. Here, we report a redox mediator, phenoxathiin, to assist the decomposition of Li2CO3 during the charging process, which effectively reduces the over-potential and improves the cycling performance of the battery. Furthermore, we detect the presence of singlet oxygen during the oxidation of Li2CO3 by phenoxathiin, which reveals more of the underlying science of the reaction mechanism of the Li-CO2 battery.

Carbodicarbene (CDC), unique carbenic entities bearing two lone pairs of electrons are well-known for their strong Lewis basicity. We demonstrate herein, upon introducing a weak Brønsted acid benzyl alcohol (BnOH) as a co-modulator, CDC is remolded into a Frustrated Lewis Pair (FLP)-like reactivity. DFT calculation and experimental evidence show BnOH loosely interacting with the binding pocket of CDC via H-bonding and π-π stacking. Four distinct reactions in nature were deployed to demonstrate the viability of proof-of-concept as synergistic FLP/Modulator (CDC/BnOH), demonstrating enhanced catalytic reactivity in cyclotrimerization of isocyanate, polymerization process for L-lactide (LA), methyl methacrylate (MMA) and dehydrosilylation of alcohols. Importantly, the catalytic reactivity of carbodicarbene is uniquely distinct from conventional NHC which relies on only single chemical feature of nucleophilicity. This finding also provides a new spin in diversifying FLP reactivity with co-modulator or co-catalyst.

Purpose Intrahepatic cholangiocarcinoma is the second most common primary liver cancer, and is associated with a poor prognosis and rising incidence rate. Methods Here, we reported the case of a middle-aged Asian male who presented with a 9.5-cm liver lesion and was diagnosed with intrahepatic cholangiocarcinoma. Results The patient experienced recurrence three times, twice following radical resection and standard adjuvant chemotherapy and once following camrelizumab plus apatinib, after which the tumor progressed with elevated CA 19.9 level. After tissue biopsy for next-generation sequencing, apatinib was replaced by lenvatinib, and the patient achieved disease control again, with a progression-free survival of 10 months. Conclusion Combined immunotherapy and targeted therapy regimens are a promising approach for refractory intrahepatic cholangiocarcinoma. Further well-designed prospective clinical trials are needed to confirm the efficacy and safety. Since intrahepatic cholangiocarcinoma is characterized by high heterogeneity and with complex crosstalk among oncogenic pathways, further exploration is required to more deeply understand the mechanism of action of this treatment approach and guide individualized treatment selection.

Red-light-emitting InP/ZnSexS1-x core/shell quantum dots (QDs) were prepared by one-pot synthesis with optimal hydrogen fluoride (HF) treatment. Most of the surficial oxidative species could be removed, and the dangling bonds would be passivated by Zn ions for the InP cores during HF treatment, which would be beneficial to the subsequent ZnSexS1-x shell coating. Three-dimensional time-resolved photoluminescence spectra of the QD samples were analyzed by singular value decomposition global fitting to determine the radiative and nonradiative lifetimes of charge carriers. A proposed model illustrated that the charge carriers in the InP/ZnSexS1-x QDs with interfacial oxidative layer removal would evidently recombine through radiative pathways, mainly from the conduction band to the valence band (lifetime, 33 ns) and partially from the trap states (lifetime, 150 ns). This work offers the important physical insight into the charge carrier dynamics of low-toxicity QDs which have the desired optical properties for optoelectronic applications.

Photocatalytic materials are proved to effectively eliminate gaseous pollutants and are widely used in the environment. However, as one of the rare experiments focusing on their influence on secondary aerosol formation generated in the gas phase (SAg), our study demonstrated the high-yield SAg formation in the photocatalysis process. In this study, the photodegradation of SO2 by TiO2 under various relative humidity (RH) conditions was deeply explored with multiple methods. Unexpectedly, H2SO4 aerosols (SAg-H2SO4) in yields of 10.10-32.64% were observed under the studied RH conditions for the first time. Gaseous •OH and H2O2 generated from the oxidation of H2O and reduction of O2 by TiO2 were directly detected in the photocatalysis process, and they were identified as the determining factor for SAg-H2SO4 formation. The formation of SAg-H2SO4 was also influenced by RH, the heterogeneous reaction of SO2, and the uptake of H2SO4. The role of the released gaseous •OH and H2O2 on atmospheric chemistry was proved to be unignorable by adopting the obtained parameters into the real environment. These findings provided direct experimental evidence of secondary pollution in the photocatalysis process and are of great significance to the field of atmospheric environment and photocatalytic materials.

Fe/Co metal–organic frameworks (Fe/Co-MOFs) were synthesized by a solvothermal method using terephthalic acid (BDC) and N,N-dimethylformamide (DMF), and the removal of tetracycline (TC) was accomplished with high efficiency. We explored the influence of Co content on the characteristics of the bimetallic MOFs. The structures of the Fe/Co-MOFs were characterized by X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy (FTIR), and nitrogen physisorption analysis. The results showed that Co2+ was well loaded in the Fe-MOFs. Due to the different coordination behaviors of Co2+ and Fe3+ with BDC, the Fe/Co-MOFs formed a new 3D structure with a spike ball-like morphology. The morphology changed dramatically, leading to a large specific surface area, and the activity of the Lewis acid sites was greatly enhanced. Through FTIR and XPS analysis before and after adsorption, the adsorption process was mainly affected by coordination action. The largest TC adsorption capacity was observed when the Fe/Co ratio was equal to 1:3, and the saturated adsorption capacity was 139.8 mg g−1.

Purpose The aim of this study was to evaluate the efficacy of liposome-paclitaxel and carboplatin combination chemoradiotherapy for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Patients and methods Seventy-nine consecutive patients treated with liposome-paclitaxel based concurrent chemoradiotherapy between January 2015 and December 2019 at Cancer hospital of the University of Chinese Academy of Sciences (Zhejiang cancer hospital) were enrolled in this study. The overall response, toxicities, progression-free survival and overall survival were analyzed with SPSS software. Results A total of 302 cycles of weekly chemotherapy were delivered, with a median 4 courses. After concurrent chemoradiotherapy (CCRT), the efficacy was classified as CR in 4 cases (5.1%), PR in 22 cases (28.2%) and SD in 51 cases (65.4%). The median PFS and OS time were 18.2 months and 23.4 months. The 3-year PFS and OS rates were 45.1% and 43.6%, respectively. Conclusions Liposome-paclitaxel and carboplatin concurrent with radiotherapy is a safe and effective modality for locally advanced ESCC. Further clinical investigation are warranted to evaluate the efficacy of this regimen.

Oxidative damage in the brain may lead to cognitive impairments. There was considerable debate regarding the beneficial effects of physical exercise on cognitive functions because exercise protocols have varied widely across studies. We investigated whether different exercise intensities alter performance on cognitive tasks. The experiment was performed on spontaneously hypertensive rats (6 months at the established phase of hypertension) distributed into 3 groups: sedentary, low‐intensity exercise and high‐intensity exercise. Systolic blood pressure measurements confirmed hypertension in spontaneously hypertensive rats. In comparison to normotensive Wistar‐Kyoto rats, sedentary spontaneously hypertensive rats had similar escape latencies and a similar preference for the correct quadrant in the probe trial. Compared to the sedentary group, the low‐intensity exercise group had significantly better improvements in spatial memory assessed by Morris water maze. Low‐intensity exercise was associated with attenuated reactive oxygen species, as measured by dihydroethidine fluorescence and nitrotyrosine staining in the dentate gyrus of the hippocampus. This was coupled with increased numbers of neurons and dendritic spines as well as a significant upregulation of synaptic density. In contrast, the beneficial effects of low‐intensity exercise are abolished in high‐intensity exercise as shown by increased free radical levels and an impairment in spatial memory. We concluded that exercise is an effective strategy to improve spatial memory in spontaneously hypertensive rats even at an established phase of hypertension. Low‐intensity exercise exhibited better improvement on cognitive deficits than high‐intensity exercise by attenuating free radical levels and improving downstream synaptic plasticity.

A series of 1,4-disubstituted digold–alkynyl complexes, [(PPh3)Au]2(μ-C≡C–Ar–CH≡C)], in which the 1,4-diethenylbenzene bridge contains two alkyl or oligo(ethylene glycol)methylether side chains at different positions (2,5- and 2,3-positions), have been synthesized and structurally characterized by spectroscopic techniques. The structure of [(AuPPh3)2{µ-C≡C–C6H2(OC6H13)2-2,5-C≡C}] (2c) has been established by X-ray crystallography. Their antitumor activities in vitro were investigated by MTT assay against four tumor cell lines. Compared to alkyl-functionalized complexes, the oligo(ethylene glycol)methylether-functionalized complexes showed significant antitumor activity, which may be attributed to the improvement of the hydrophilicity of the complex to achieve the appropriate lipophilicity. In particular, complex [(AuPPh3)2{µ-C≡C–C6H2(OCH2CH2OCH2CH2OCH3)2-2,3-C≡C}] (2j) displayed high activity against the A549 cell line and low cytotoxicity toward normal cell lines. Notably, further investigations are required if complex 2j is to undergo trials as a new potential antitumor agent.

A dilactosyl-dicyanovinyl-functionalized tetraphenylethene (TPELC) was designed, synthesized and used for ratiometric sensing of cyanide. TPELC was comprised of three moieties (tetraphenylethylene, dicyanovinyl group and lactose unit) in one molecule, making TPELC water-soluble and aggregation-induced emission (AIE)-active and selectively reactive to cyanide. Compared with other reported fluorescent probes containing dicyanovinyl group, TPELC is the first AIE luminogen to be assembled as fluorescent organic nanoparticles (FONs) for sensing of cyanide in water without the use of surfactant or the help of organic solvents based on the nucleophilic addition reaction. The detection mechanism was verified by liquid chromatograph mass spectrometry experiments and by protonation of cyanide to reduce the nucleophilicity of cyanide. In addition, TPELC was used for detection of the cyanide content of food samples and test strips were developed to simplify the detection procedure.

Cardiovascular disease (CVD) results in more than half of the mortality and the majority of morbidity in patients with type 2 diabetes. We aim to evaluate the associations of urinary concentrations of phthalate metabolites with CVD in diabetic patients and explore whether CVD risk factors mediate or interact with these associations. A total of 675 type 2 diabetic participants were enrolled from Shanghai, China, in 2018. CVD was defined as a self-reported diagnosis by a physician including coronary heart disease, myocardial infarction, or stroke; it was further reconfirmed in the records from the registration platform. Ten phthalate metabolites were measured in urine. We found positive associations were found among the level of monoethyl phthalate and monoisobutyl phthalate and CVD (OR 1.138, 95% CI 1.032, 1.254; OR 1.369, 95% CI 1.049, 1.786, respectively). Monoisobutyl phthalate and monobenzyl phthalate were marginally and positively associated with carotid intima-media thickness and common carotid artery diameter, respectively. None of the CVD risk factors, including HOMA-IR, body mass index, lipid profile, or blood pressure, significantly mediated the association between the metabolites and CVD. The conditional indirect effect on CVD was significantly stronger for current smoking and dyslipidemia for monoethyl phthalate and for no statin usage and men for monoisobutyl phthalate. In conclusion, phthalate exposure was positively associated with CVD in Chinese with type 2 diabetes. Type 2 diabetic men who are currently smoking, have an uncontrolled lipid profile, and are not using statins might be more susceptible to CVD when exposed to phthalates.

A simple and efficient method for liquid-phase catalytic nitration of 1-nitronaphthalene with NO2 to 1,5-dinitronaphthalene under mild conditions has been developed. The results indicated that the sulfated zirconia (SO42−/ZrO2) as solid superacid catalyst exhibits superior catalytic performance with dioxygen and acetic anhydride. 93.8% conversion of 1-nitronaphthalene and 52.8% 1,5-dinitronaphthalene selectivity were achieved. Furthermore, the physicochemical properties of SO42−/ZrO2 were determined by XRD, Py-FT-IR, BET, FT-IR, Raman spectroscopy and ICP-OES technologies. The possible nitration reaction mechanism over SO42−/ZrO2 catalyst was proposed. The present work provides an easy-to-implement, mild and eco-friendly approach for the efficient preparation of valuable 1,5-dinitronaphthalene, which has extensive industrial application prospects.

This study tested the hypothesis that therapy with double overexpression of miR‐19a‐3p and miR‐20a‐5p (miRDOE) to human inducible pluripotent stem cell–derived mesenchymal stem cells (iPS‐MSCs) was superior to iPS‐MSCs alone for preserving renal function in rat with pre‐existing chronic kidney disease (CKD), followed by ischaemia‐reperfusion (IR) injury. In vitro study demonstrated that the protein expressions of oxidative stress (NOX‐1/NOX‐2/NOX4/oxidized protein/p22phox), inflammatory downstream signalling (TLR2&4/MyD88/TRAF6/IKK‐ß/p‐NFκB/IL‐1ß/IL‐6/MMP‐9) and cell apoptosis/death signalling (cleaved caspase‐3/mitochondrial Bax/p‐ERKs/p‐JNK/p‐p38) at time‐points of 24‐hour/48‐hour cell cultures were significantly increased in p‐Cresol‐treated NRK‐52E cells than in the control that was significantly reversed by miR‐19a‐3p‐transfected iPS‐MSC (all P

Point defects in hexagonal boron nitride (hBN) have attracted growing attention as bright single-photon emitters. However, understanding of their atomic structure and radiative properties remains incomplete. Here we study the excited states and radiative lifetimes of over 20 native defects and carbon or oxygen impurities in hBN using ab initio density functional theory and GW plus Bethe-Salpeter equation calculations, generating a large data set of their emission energy, polarization and lifetime. We find a wide variability across quantum emitters, with exciton energies ranging from 0.3 to 4 eV and radiative lifetimes from ns to ms for different defect structures. Through a Bayesian statistical analysis, we identify various high-likelihood charge-neutral defect emitters, among which the native VNNB defect is predicted to possess emission energy and radiative lifetime in agreement with experiments. Our work advances the microscopic understanding of hBN single-photon emitters and introduces a computational framework to characterize and identify quantum emitters in 2D materials.

The skin barrier of melasma is involved in the pathogenesis of melasma. Previous studies have shown that there are differences in the expression of epidermal lipid genes in melasma, but little is known about the epidermis lipid composition of melasma. Compared with the non-lesional skin, the content of total lipids, phosphatidic acid, phosphatidylserine, and ceramide (Cer) increased significantly in the lesional skin. Multivariate data analysis indicated that 40 individual Cer lipid species were responsible for the discrimination. In terms of acyl chain length in Cer, the expressions of very long chain (VLC) (C20-C26) and ultra-long chain (ULC) (>C26) increased significantly in the lesional skin. However, Cer[AH] had negative correlations with the activation of melanocytes in the lesional skin. Some lipid species had lower expression in lesional skin with high activation of melanocytes, as well as the high darkness. The epidermal thickness of lesional skin was higher compared with the non-lesional skin. These results suggest that Cer increased significantly in the lesional skin of melasma, possibly as a compensatory mechanism to maintain skin barrier function. Between different groups of darkness and activation of melanocytes, the change of ceramides might have correlation with the pigmentation progress of melasma.

This work highlights improved photosensing performance in ITO/ ( Bi 0.93 Sm 0.07 ) FeO 3 /Au heterostructure through a prior electric field poling. Maximal responsivity (R) of 2.0 × 10 − 2 A / W and specific detectivity (D*) of 2.2 × 10 11 Jones were obtained under 405-nm irradiation. The mechanism behind the observed photosensing performance is linked to the combined effects of the polarization-induced electric field and built-in electric fields at the interfaces (i.e., p–n junction and Schottky barrier). The net internal electric field established in the device serves as the driving force for the separation and transport of the photo-generated electron–hole pairs. The reduced direct optical bandgap (Eg) of 2.13 eV, the well-defined ferroelectric polarization hysteresis loops, and the conduction pathways formed by the electric field-stimulated interconnection of domain walls and grain boundaries play significant roles in the remarkable photosensitivity of ( Bi 0.93 Sm 0.07 ) FeO 3 ceramics, thus providing insight into optimizing BiFeO3-based materials for near-UV photodetector.

Background Integrase inhibitors (INIs)-based antiretroviral therapies (ART) are more recommended than efavirenz (EFV)-based ART for people living with HIV/AIDS (PLWHA). Yet, the advantage of integrase inhibitors in treating TB/HIV coinfection is uncertain. Therefore, the objective of this systematic review is to evaluate the effects and safety of INIs- versus EFV-based ART in TB/HIV coinfection, and demonstrate the feasibility of the regimens. Methods Four electronic databases were systematically searched through September 2020. Fixed-effects models were used to calculate pooled effect size for all outcomes. The primary outcomes were virologic suppression and bacteriology suppression for INIs- versus EFV-based ART. Secondary outcomes included CD4+ cell counts change from baseline, adherence and safety. Results Three trials (including 672 TB/HIV patients) were eligible. ART combining INIs and EFV had similar effects for all outcomes, with none of the point estimates argued against the INIs-based ART on TB/HIV patients. Compared to EFV-based ART as the reference group, the RR was 0.94 (95% CI 0.85 to 1.05) for virologic suppression, 1.00 (95% CI 0.95 to 1.05) for bacteriology suppression, 0.98 (95% CI 0.95 to 1.01) for adherence. The mean difference in CD4+ cell counts increase between the two groups was 14.23 cells/μl (95% CI 0− 6.40 to 34.86). With regard to safety (adverse events, drug-related adverse events, discontinuation for drugs, grade 3–4 adverse events, IRIS (grade 3–4), and death), INIs-based regimen was broadly similar to EFV-based regimens. The analytical results in all sub-analyses of raltegravir- (RAL) and dolutegravir (DTG) -based ART were valid. Conclusion This meta-analysis demonstrates similar efficacy and safety of INIs-based ART compared with EFV-based ART. This finding supports INIs-based ART as a first-line treatment in TB/HIV patients. The conclusions presented here still await further validation owing to insufficient data.

Greigite (Fe3S4) nanoparticles (NPs) were fabricated by the thermal decomposition method using two different surfactants: oleylamine (OLA) and 1-hexadecylamine (HDA). In both cases, the synthesized NPs were characterized as the Fe3S4 nanocrystals with minor inclusions of Fe9S11 phase. FT-IR spectroscopy and thermo-gravimetric analysis allow concluding about OLA or HDA shells covering magnetic core of NPs. Mossbauer spectra has revealed deviations of iron ions distribution among crystal positions from that presented in literature for pure greigite. In accordance with these deviations, the pronounce changes are observed in the magnetic circular dichroism (MCD) spectra which manifest themselves as the spectrum shift to higher energies of electromagnetic waves and redistribution of the MCD maximum intensities. These effects are associated with a change in the density of electronic states in the samples due to the redistribution of iron ions between octahedral and tetrahedral positions in nanocrystals under the influence of surfactants.

In this study, CuO–ZnO and Fe2O3–Cr2O3 were prepared by coprecipitation and their catalytic activity in supercritical water gasification (SCWG) was evaluated at 500 and 600 °C. Both catalysts impro...

This study is aimed at exploring the release of bound polyphenols (BP) from insoluble dietary fiber (IDF) and its mechanism by solid-state fermentation (SSF) via Trichoderma viride. The results indicated that BP released by SSF (5.55 mg GAE/g DW) was significantly higher than by alkaline hydrolysis. In addition, 39 polyphenols and catabolites were detected, and the related biotransformation pathways were speculated. Quantitative analysis showed that SSF released more ferulic acid, p-coumaric acid, and organic acids, which led to advances in antioxidant, α-amylase, and α-glucosidase inhibitory activities. Furthermore, structural characteristics (scanning electron microscopy, X-ray diffraction, thermos gravimetric analysis, and Fourier transform infrared spectroscopy) and dynamic changes of carbohydrate-hydrolyzing enzymes indicated that the destruction of hemicellulose and the secretion of xylanase were vital for releasing BP. Overall, this study demonstrated that SSF was beneficial to release BP from IDF, which could provide insight into utilizing agricultural byproducts in a more natural and economical way.

4-Aminobiphenyl (4-ABP) may cause DNA damage in human liver cells (HepG2 and L-02). Propolis exhibits antioxidant properties through reactive oxygen species (ROS) scavenging. We determined the effects of propolis in alleviating 4-ABP -induced DNA damage using the comet assay. Results revealed that propolis could significantly alleviated oxidative damaged DNA by 4-ABP. Furthermore, we proved that inhibition of cytochrome P450 2E1 (CYP2E1) expression by propolis could contribute to the decreased oxidative DNA damage in the treated cells, as the conversion of 4-ABP into its metabolite, N-hydroxy-ABP (HOABP), was blocked; after all, HOABP showed more genotoxic than its parent chemical, 4-ABP. With the homologous recombination assay, propolis failed to induce DNA repair enzymes. Furthermore, the expression of RAD51, Ku70/Ku80, and OGG1 in treated cells were determined with the western blot, revealing that the expression of these protein were unchanged in comparison with those in nontreated cells. However, propolis could protect the treated cells from DNA damage. In conclusion, propolis could antagonize 4-ABP-induced oxidative DNA damage though the removal of ROS and inhibition of CYP2E1 expression in the treated cells.

Background Circ_ATRNL1 is significantly high-expressed in cartilage tissues of patients with osteoarthritis. This study explored the role and mechanism of circ_ATRNL1 in cartilage differentiation of human adipose-derived mesenchymal stem cells (hAMSCs). Methods hAMSCs were isolated and identified by flow cytometry. The degree of chondrocyte and adipogenic differentiation was assessed using Alcian blue staining and Oil Red O staining, respectively. The expressions of cartilage- and adipogenic-related genes, circ_ATRNL1 and SOX9 were detected by reverse transcription quantitative-PCR. The correlation between SOX9 and circ_ATRNL1 was analyzed using Pearson test. Bioinformatics and luciferase analysis were used to detect the overlapped target miRNAs of circ_ATRNL1 and SOX9. The role of circ_ATRNL1/miRNA/SOX9 was examined using functional rescue assays. Results HAMSCs were identified as CD90-, CD105- and CD44-positive. The degree of cartilage differentiation of hAMSCs was significantly enhanced after two weeks. Cartilage-related genes circ_ATRNL1 and SOX9 were significantly up-regulated, and positively correlated with each other. Circ_ATRNL1 overexpression enhanced hAMSC proliferation and differentiation into chondrogenesis, and promoted the expressions of COL2, Aggrecan and SOX9. Overexpression of circ_ATRNL1 inhibited the adipogenic differentiation of hAMSCs and the expressions of adipogenic-related genes. miR-145-5p was a target miRNA for circ_ATRNL1 and SOX9. miR-145-5p mimic inhibited hAMSC differentiation towards cartilage, and inhibited the expression of cartilage-related factors. miR-145-5p mimic effectively reversed the regulating effect of circ_ATRNL1 on hAMSCs. Conclusion Circ_ATRNL1 regulates the inhibition of SOX9 expression to promote chondrogenic differentiation of hAMSCs mediated by miR-145-5p. This article is protected by copyright. All rights reserved.

Mesoporous zeolite and hybrid zeolite are indispensable materials for the chemical industry; however, their fabrication always involved high production cost, long times, and adverse environmental i...

A novel quality evaluation method of Corydalis yanhusuo was established by researching the high-performance liquid chromatography behavior of alkaloids under different buffer solutions and exploring the correlation between alkaloids in C. yanhusuo. The retention times of tetrahydropalmatine and corydaline were significantly influenced by pH, while the peak shape was affected by buffer types and ionic strength. The resolution of compounds in fingerprint was satisfactory under acetonitrile-0.2% phosphoric acid buffer (adjusted pH to 5.0 with triethylamine). Twelve common peaks were found by comparing 20 batches of C. yanhusuo fingerprints, and three tertiary alkaloids and four quaternary alkaloids were identified. The fingerprints were analyzed by similarity analysis, hierarchical cluster analysis, principal component analysis, and partial least squares discriminant analysis. All samples were divided into three groups, and the contents of dehydrocorydaline and coptisine from Zhejiang province were relatively higher than other origins. There were six components performing more contributions to the quality of C. yanhusuo. The correlations between alkaloids were conducted by Pearson correlation analysis and mathematical model analysis. The content correlation between palmatine and berberine was y = 0.28x2 + 0.03x + 0.03, and the dehydrocorydaline and coptisine was y = -7.54/(1 + (x/0.14)0.5 ) + 2.61. The established mathematical model of alkaloids provided a guiding significance for the quality control of C. yanhusuo.

Background/aims Direct‐acting antivirals (DAAs) are highly effective in treating chronic hepatitis C virus (HCV)‐infected patients. The real‐world treatment outcome in Taiwanese patients on a nationwide basis is elusive. Methods The Taiwan HCV Registry (TACR) programme is a nationwide registry platform including 48 study sites, which is organized and supervised by the Taiwan Association for the Study of the Liver. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA 12 weeks after end‐of‐treatment). Results A total of 13 951 registered patients with SVR12 data available were analysed (mean age, 63.0 years; female, 55.9%; HCV genotype‐1 [GT1], 57.9%; cirrhosis, 38.4%; preexisting hepatocellular carcinoma [HCC], 10.6%; and hepatitis B virus coinfection, 7.7%). The overall SVR12 rate was 98.3%, with 98.7%, 98.0%, 98.4% and 97.4% in treatment‐naïve noncirrhotic, treatment‐naïve cirrhotic, treatment‐experienced noncirrhotic and treatment‐experienced cirrhotic patients, respectively. The SVR12 rate was > 95% across all subgroups except treatment‐experienced cirrhotic patients who received sofosbuvir/ribavirin (88.7%), treatment‐naïve noncirrhotic patients (94.8%) and treatment‐experienced cirrhotic (94.8%) patients who received daclatasvir/asunaprevir. The most important factor associated with treatment failure was DAA adherence

Background: Measuring medicinal compounds to evaluate their quality and efficacy has been recognized as a useful approach in treatment. Rhubarb anthraquinones compounds (mainly including aloe-emodin, rhein, emodin, chrysophanol, and physcion) are the main effective components in purgating drug. In the current Chinese Pharmacopoeia, the total anthraquinones content is designated as its quantitative quality and control index, while the content of each compound has not been specified. Methods: On the basis of forty rhubarb samples, the correlation models between the near infrared spectra and UPLC analysis data were constructed using support vector machine (SVM) and partial least square (PLS) methods, according to the Kennard and Stone algorithm for dividing the calibration/ prediction datasets. Good models mean they have high correlation coefficients (R2) and low root mean squared error of prediction (RMSEP) values. Results: The models constructed by SVM have much better performance than those by PLS methods. The SVM models have high R2 of 0.8951, 0.9738, 0.9849, 0.9779, 0.9411, and 0.9862 that correspond to aloe-emodin, rhein, emodin, chrysophanol, physcion and total anthraquinones contents, respectively. The corresponding RMSEPs are 0.3592, 0.4182, 0.4508, 0.7121, 0.8365, and 1.7910, respectively. 75% of the predicted results have relative differences being lower than 10%. As for rhein and total anthraquinones, all of the predicted results have relative differences being lower than 10%. Conclusion: The non-linear models constructed by SVM showed good performances with predicted values close to the experimental values. This can perform the rapid determination of the main medicinal ingredients in rhubarb medicinal materials.

Achieving a highly crystalized perovskite active layer with a dense, flat surface and a large grain size is very significant for constructing efficient perovskite solar cells (PSCs). Regarding this...

Iron, an essential micronutrient for all kinds of cells, is essential for the balance of body internal environment. Notably, cancer cells exhibit a strong dependence on iron and require a large amount of iron for proliferation. A growing number of studies suggested that iron metabolism imbalance and subsequent excess iron accumulation are closely related to the occurrence and progression of cancer. Precisely, excess iron promotes the development of cancer due to the pro-oxidative nature of iron and its damaging effects on DNA. Simultaneously, tumor cells acquire large amounts of iron to maintain rapid growth and proliferation. Therefore, targeting iron metabolism may provide a new way for the treatment of cancer. Quercetin, a natural flavonoid, has long been regarded as potential drug for cancer treatments owing to its anti-inflammatory, antioxidant and anti-tumor effects. It is proven that quercetin possesses a high iron-chelating capacity, depriving cancer cells of iron or altering iron metabolism. Herein, we conduct a review on the mechanisms of iron imbalance in tumors and the role of quercetin in iron chelation, which will provide insight into the potential for quercetin as an anti-cancer drug.

This paper presents a standardized process for fabricating multifunctional energy storage composites that involves using activated carbon fiber (CF) electrodes and a poly(vinylene fluoride) (PVDF)-...

Investigation of the ethyl acetate-soluble layer from the liquid fermentation of Phialophora lagerbergii, an endophytic fungus isolated from the Taiwanese endemic medicinal plant of Ardisia cornudentata var. cornudentata, led to the isolation of a new sesquiterpenoid, phialolagerol (1). The structure of the isolate was established by spectroscopic methods, including UV, IR, HR-ESI-MS, and extensive 1D and 2D NMR techniques, as well as by comparison with literature reports.

Finding a relationship between kinetics and thermodynamics may be difficult. However, semi-empirical rules exist to compensate for this shortcoming, among which the Bell-Evans-Polanyi (B-E-P) principle is an example for reactions involving bond breakage and reformation. We expand the B-E-P principle to a new territory by probing photoinduced structure planarization (PISP) of a series of dibenz[b,f]azepine derivatives incorporating bent-to-planar and rotation motion. The latter involves twisting of the partial double bond character, thereby inducing a barrier that is substituent dependent at the para N-phenyl position. The transition-state structure and frequency data satisfy and broaden the B-E-P principle to PISP reactions without bond rearrangement. Together with dual emissions during PISP, this makes possible harnessing of the kinetics/thermodynamics relationship and hence ratiometric luminescence properties for excited-state structural transformations.

Formaldehyde scavenger agent can effectively control formaldehyde emissions from wood-based panels, but the existing formaldehyde scavenger agent can only work in the short term. For the purpose of long-term control of formaldehyde emissions from wood-based panels, microencapsulation of formaldehyde scavenger agent was synthesized in this paper. The effect of the emulsifying agent and the core to shell ratio on the microcapsules' morphology and formaldehyde degradation efficiency was investigated. The results showed that microcapsules of optimum morphology with high degradation efficiency can be obtained under the condition of 1% of the sodium dodecyl sulfate emulsifier, 3% of the shell solution, and a core to shell ratio of 1:3 with 1000 r/min stirring speed. The loading ratio and efficiency of the microcapsules achieved 36.25% and 8.05% respectively. Compared with control panels, the formaldehyde released from veneered panels treated with microcapsules was 39.7% and 41.4% lower in short-term and long-term emissions.