Porous framework materials for energy&environment relevant applications:A systematic review

Carbon peaking and carbon neutralization trigger a technical revolution in energy&environment related fields.Development of new technologies for green energy production and storage,industrial energy saving and efficiency reinforcement,carbon capture,and pollutant gas treatment is in highly imperious demand.The emerging porous framework materials such as metal–organic frameworks(MOFs),covalent organic frameworks(COFs)and hydrogen-bonded organic frameworks(HOFs),owing to the permanent porosity,tremendous specific surface area,designable structure and customizable functionality,have shown great potential in major energy-consuming industrial processes,including sustainable energy gas catalytic conversion,energy-efficient industrial gas separation and storage.Herein,this manuscript presents a systematic review of porous framework materials for global and comprehensive energy&environment related applications,from a macroscopic and application perspective.

First-line pemetrexed-platinum doublet chemotherapy with or without bevacizumab in non-squamous non-small cell lung cancer: A real-world propensity score-matched study in China

Objective: To evaluate the efficacy and safety profile of first-line bevacizumab(Bev)-containing pemetrexedplatinum chemotherapy in a real-world Chinese cohort with advanced non-squamous non-small cell lung cancer(NS-NSCLC).Methods: A total of 415 eligible patients with NS-NSCLC who received first-line pemetrexed-platinum chemotherapy at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between February 2010 and September 2017 were reviewed retrospectively: 309 Bev(-) and 106 Bev(+) cases. Bev was administered at 7.5 mg/kg every 3 weeks in the Bev(+) group. To reduce the risk of a selection bias, a propensity score-matching(PSM) was conducted and 105 pairs of Bev(-) and Bev(+) cases were identified.Results: The median duration of follow-up was 15.8 months. The median progression-free survival(PFS) was prolonged significantly in the Bev(+) group than in the Bev(-) group in overall(9.8 vs. 7.8 months, P=0.006) and PSM pairs(9.8 vs. 6.6 months, P<0.001). Moreover, patients receiving maintenance therapy with pemetrexed plus Bev had longer PFS than those interrupted after induction chemotherapy, or those receiving mono-maintenance with pemetrexed(12.3 vs. 4.8 vs. 8.6 months;P<0.001). Multivariate analyses revealed Bev to be one of the favorable prognostic factors for PFS, along with the predictor of maintenance therapy.Conclusions: First-line induction and maintenance therapy with Bev(7.5 mg/kg every 3 weeks) combined with pemetrexed-platinum chemotherapy was efficacious and superior to non-Bev chemotherapy in Chinese patients with advanced NS-NSCLC.

Is there an optimal time to initiate adjuvant chemotherapy to predict benefit of survival in non-small cell lung cancer?

Objective: Adjuvant chemotherapy (AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer (NSCLC); however, few studies have reported the correlation between the time to initiation of AC (TTAC) and survival in NSCLC patients. Methods: The clinical data of 925 NSCLC patients who received curative resection and post-operative AC at the Cancer Hospital of Chinese Academy of Medical Sciences between 2003 and 2013 were retrospectively analyzed. TTAC was measured from the date of surgery to the initiation of AC. Disease-free survival (DFS) was defined as the duration from surgery to the time of tumor recurrence or last follow-up evaluation. The optimal cut-off value of TTAC was determined by maximally selected log-rank statistics. The DFS curve was estimated using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to identify risk factors independently associated with DFS. Propensity score matching (PSM) was performed for survival analysis using the match data. Results: The optimal discriminating cut-off value of TTAC was set at d 35 after curative resection based on which the patients were assigned into two groups: group A (<= 35 d) and group B (> 35 d). There was no significant difference in the DFS between the two groups (P=0.246), indicating that the TTAC is not an independent prognostic factor for DFS. A further comparison continued to show no significant difference in the DFS among 258 PSM pairs (P=0.283). Conclusions: There was no significant correlation between the TTAC and DFS in NSCLC patients. Studies with larger samples are needed to further verify this conclusion.

Evolution of defects and deformation mechanisms in different tensile directions of solidified lamellar Ti-Al alloy

Two-phaseγ-TiAl/α_(2)-Ti_(3)Al lamellar intermetallics have attracted considerable attention because of their excellent strength and plasticity.However,the exact deformation mechanisms remain to be investigated.In this paper,a solidified lamellar Ti-Al alloy with lamellar orientation at 0°,17°,and 73°with respect to the loading direction was stretched by utilizing molecular dynamics(MD)simulations.The results show that the mechanical properties of the sample are considerably influenced by solidified defects and tensile directions.The structure deformation and fracture were primarily attributed to an intrinsic stacking fault(ISF)accompanied by the nucleated Shockley dislocation,and the adjacent extrinsic stacking fault(ESF)and ISF formed by solidification tend to form large HCP structures during the tensile process loading at 73°.Moreover,cleavage cracking easily occurs on theγ/α_(2)interface under tensile deformation.The fracture loading mechanism at 17°is grain boundary slide whereas,at 73°and 0°,the dislocation piles up to form a dislocation junction.

Improved methods for cloning and detection in the yeast two hybrid assay

The yeast two-hybrid (Y2H) mating assay is a powerful method for detecting protein-protein interactions. Firstly, the gene of interest is cloned into specific Y2H vectors. Although multiple innovations in cloning methods were made in the past two decades, the conventional cloning method of restriction-enzyme (RE) digestion followed by ligation is still widely used. Unfortunately, many researchers, especially new-comers, often encounter difficulties in cloning a gene into a desired vector. Secondly, interaction between two proteins is commonly detected by growth of the diploids in specific media. This step takes about two weeks. Here, we describe improved cloning and detection procedures for the Y2H assay that accelerate the research progress. The changes in procedures involve running an agarose gel after the doubly digested vector and insert are ligated in the cloning step to determine the efficiency of RE digestion and ligation, and performing an additional replica-plating on plates for earlier assessment of interaction in the detection step. We show an example of Y2H interaction between Trs23 and Trs120 (respective subunits of TRAPP I and TRAPP II), as a proof of concept. By following the improved methods described here, the chances of successful cloning increased and the time for the whole Y2H experimental process is significantly shorter.

Methyl functionalization of trimesic acid in copper-based metal-organic framework for ammonia colorimetric sensing at high relative humidity

Exhaled ammonia(NH_(3))can be used as a crucial biomarker of kidney and liver diseases.However,the high humidity in the detection conditions remains a challenge for accurate detection by gas sensors.Herein,a copper-based metal-organic framework(CH_(3)-Cu-BTC)with methyl(CH_(3)^(-))functionalization of trimesic acid was synthesized for NH_(3) colorimetric sensing.The CH_(3)-Cu-BTC exhibited a strong response for 5 ppm NH_(3) with high selectivity under high relative humidity(75%RH).Density functional theory(DFT)simulations indicated that the NH_(3) molecules interacted more strongly with CH_(3)-Cu-BTC than H_(2)O molecules did,and the corresponding color switching was attributed to the lone-pair electron in NH_(3) changing the coordination environment of Cu^(2+)ions,leading to an obviously visible color switching response from ruby green to blue.Based on the tailor-made pore chemistry,the precise detection of trace amounts of NH_(3) in exhaled air was realized through functionalized MOF materials.The strategy used in this study not only offers a new pathway for the rapid detection of low concentration NH_(3) under humid conditions,but also shows a method for early respiration diagnosis of kidney and liver diseases.

Erratum to:Potential unreliability of ALK variant allele frequency in the efficacy prediction of targeted therapy in NSCLC

The original version of this article unfortunately contained a mistake.In original Fig.1A(Page 495),the frequency of ALK fusions detected by FISH was erroneously stated as“326/4670”,and the correct value should be“359/4670”.The other elements of the figure remain the same,and the interpretation of the results remains unchanged.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.

Potential unreliability of ALK variant allele frequency in the efficacy prediction of targeted therapy in NSCLC

Anaplastic lymphoma kinase(ALK)is the most common fusion gene involved in non-small cell lung cancer(NSCLC),and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors(ALK-TKIs).However,the clinical efficacy is highly variable.Pre-existing intratumoral heterogeneity(ITH)has been proven to contribute to the poor treatment response and the resistance to targeted therapies.In this work,we investigated whether the variant allele frequencies(VAFs)of ALK fusions can help assess ITH and predict targeted therapy efficacy.Through the application of next-generation sequencing(NGS),7.2%(326/4548)of patients were detected to be ALK positive.On the basis of the adjusted VAF(adjVAF,VAF normalization for tumor purity)of four different threshold values(adjVAF<50%,40%,30%,or 20%),the association of ALK subclonality with crizotinib efficacy was assessed.Nonetheless,no statistical association was observed between median progression-free survival(PFS)and ALK subclonality assessed by adjVAF,and a poor correlation of adjVAF with PFS was found among the 85 patients who received first-line crizotinib.Results suggest that the ALK VAF determined by hybrid capture-based NGS is probably unreliable for ITH assessment and targeted therapy efficacy prediction in NSCLC.

Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation:A multicenter,case-series study in China

Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explore the factors influencing the efficacy and safety.Methods:A longitudinal,consecutive case-series,multicenter study with mixed prospective and retrospective data was conducted.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included duration of treatment(DOT),overall survival(OS),objective response rate(ORR),disease control rate(DCR)and safety.Results:A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included.The median follow-up time for these patients was 20.4 months.Among 134 patients with evaluable lesions,the ORR was 70.9%and the DCR was 96.3%.The median PFS was 16.3[95%confidence interval(95%CI),13.7−18.9]months.Multivariate Cox regression analysis suggested that the baseline brain metastasis(BM)status[with vs.without BM:hazard ratio(HR),1.331;95%CI,0.720−2.458;P=0.361]and initial doses(45 mg vs.30 mg:HR,0.837;95%CI,0.427−1.641;P=0.604)did not significantly affect the median PFS.The median DOT was 21.0(95%CI,17.5−24.6)months and the median OS was not reached.Genetic tests were performed in 64 patients after progression,among whom 29(45.3%)patients developed the EGFR 20T790M mutation.In addition,among the 46 patients who discontinued dacomitinib treatment after progression,31(67.4%)patients received subsequent third-generation EGFR-tyrosine kinase inhibitors.The most common grade 3−4 adverse events were rash(10.4%),diarrhea(9.1%),stomatitis(7.1%)and paronychia(4.5%).The incidence of grade 3−4 rash was significantly higher in the 45 mg group than that in the 30 mg group(21.9%vs.7.5%,P=0.042).Conclusions:First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.

Risk factors for ventilator-associated pneumonia among patients undergoing major oncological surgery for head and neck cancer

Patients undergoing major oncological surgery for head and neck cancer （SHNC） have a particularly high risk of nosocomial infections. We aimed to identify risk factors for ventilator-associated pneumonia （VAP） in patients undergoing SHNC. The study included 465 patients who underwent SHNC between June 2011 and June 2014. The rate of VAP, risk factors for VAP, and biological aspects of VAP were retrospectively evaluated. The incidence of VAP was 19.6~0 （n = 95） in patients who required more than 48 h of mechanical ventilation. Staphylococcus （37.7%）, Enterobacteriaceae （32.1%）, Pseudomonas （20.8%）, and Haemophilus （16.9~） were the major bacterial species that caused VAP. The independent risk factors for VAP were advanced age, current smoking status, chronic obstructive pulmonary disease, and a higher simplified acute physiology score system II upon admission. Tracheostomy was an independent protective factor for VAP. The median length of stay in the ICU for patients who did or did not develop VAP was 8.0 and 6.5 days, respectively （P = 0.006）. Mortality among patients who did or did not develop VAP was 16.8% and 8.4%, respectively （P 〈 0.001）. The potential economic impact of VAP was high because of the significantly extended duration of ventilation. A predictive regression model was developed with a sensitivity of 95.3% and a specificity of 69.4%. VAP is common in patients who are undergoing SHNC and who require more than 48 h of mechanical ventilation. Therefore, innovative preventive measures should be developed and applied in this high-risk population.

Semiparametric quantile-difference estimation for length-biased and right-censored data

Prevalent cohort studies frequently involve length-biased and right-censored data, a fact that has drawn considerable attention in survival analysis. In this article, we consider survival data arising from lengthbiased sampling, and propose a new semiparametric-model-based approach to estimate quantile differences of failure time. We establish the asymptotic properties of our new estimators theoretically under mild technical conditions, and propose a resampling method for estimating their asymptotic variance. We then conduct simulations to evaluate the empirical performance and efficiency of the proposed estimators, and demonstrate their application by a real data analysis.

Surface functionalization of Polymers of Intrinsic Microporosity(PIMs)membrane by polyphenol for efficient CO_(2)separation

Membrane separation technology offers a green,efficient and energy-saving approach for biogas upgrading.Membranes with high selectivity and high permeability are the key to achieve high performance.Polymers of Intrinsic Microporosity(PIMs)materials have shown excellent gas permeability but low selectivity which limits their practical application.Herein,a polyphenol,tannic acid,was coated on the PIM-1 membrane surface by a facile dipping method to fabricate composite membranes.Tannic acid containing a large number of polar oxygencontaining groups(quinone,phenolic hydroxyl)self-polymerized on the membrane surface to form a CO2-philic,defect-free and thin layer.The CO2/CH4 selectivity of the resultant composite membranes was increased after tannic acid coating while the permeability remained comparable to or even higher than pristine PIM-1 membrane,exceeding the reported 2008 upper bound.

Coordination-driven structure reconstruction in polymer of intrinsic microporosity membranes for efficient propylene/propane separation

Polymers of intrinsic microporosity(PIMs),integrating unique microporous structure and solution-processability,are one class of the most promising membrane materials for energy-efficient gas separations.However,the micropores generated from inefficient chain packing often exhibit wide pore size distribution,making it very challenging to achieve efficient olefin/paraffin separations.Here,we propose a coordination-driven reconstruction(CDR)strategy,where metal ions are incorporated into amidoxime-functionalized PIM-1(AO-PIM)to in situ generate coordination crosslinking networks.By varying the type and content of metal ions,the resulting crosslinking structures can be optimized,and the molecular sieving capability of PIM membranes can be dramatically enhanced.Particularly,the introduction of alkali or alkaline earth metals renders more precise micropores contributing to superior C3H6/C3H8 separation performance.K+incorporated AO-PIM membranes exhibit a high ideal C3H6/C3H8 selectivity of 50,surpassing almost all the reported polymer membranes.Moreover,the coordination crosslinking structure significantly improves the membrane stability under higher pressure as well as the plasticization resistant performance.We envision that this straightforward and generic CDR strategy could potentially unlock the potentials of PIMs for olefin/paraffin separations and many other challenging gas separations.

Potential underlying genetic associations between keratoconus and diabetes mellitus

Background:Keratoconus(KC)is the most common ectatic corneal disease,characterized by significantly localized thinning of the corneal stroma.Genetic,environmental,hormonal,and metabolic factors contribute to the pathogenesis of KC.Additionally,multiple comorbidities,such as diabetes mellitus,may affect the risk of KC.Main Text:Patients with diabetes mellitus(DM)have been reported to have lower risk of developing KC by way of increased endogenous collagen crosslinking in response to chronic hyperglycemia.However,this remains a debated topic as other studies have suggested either a positive association or no association between DM and KC.To gain further insight into the underlying genetic components of these two diseases,we reviewed candidate genes associated with KC and central corneal thickness in the literature.We then explored how these genes may be regulated similarly or differentially under hyperglycemic conditions and the role they play in the systemic complications associated with DM.Conclusions:Our comprehensive review of potential genetic factors underlying KC and DM provides a direction for future studies to further determine the genetic etiology of KC and how it is influenced by systemic diseases such as diabetes.

Seed amplification assay of nasal swab extracts for accurate and non-invasive molecular diagnosis of neurodegenerative diseases

Nasal swabs are non-invasive testing methods for detecting diseases by collecting samples from the nasal cavity or nasopharynx.Dysosmia is regarded as an early sign of coronavirus disease 2019(COVID-19),and nasal swabs are the gold standard for the detection.By nasal swabs,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)nucleic acids can be cyclically amplified and detected using real-time reverse transcriptase-polymerase chain reaction after sampling.Similarly,olfactory dysfunction precedes the onset of typical clinical manifestations by several years in prion diseases and other neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,dementia with Lewy bodies,and multiple system atrophy.In neurodegenerative diseases,nasal swab tests are currently being explored using seed amplification assay(SAA)of pathogenic misfolded proteins,such as prion,α-synuclein,and tau.These misfolded proteins can serve as templates for the conformational change of other copies from the native form into the same misfolded form in a prion-like manner.SAA for misfolded prion-like proteins from nasal swab extracts has been developed,conceptually analogous to PCR,showing high sensitivity and specificity for molecular diagnosis of degenerative diseases even in the prodromal stage.Cyclic amplification assay of nasal swab extracts is an attractive and feasible method for accurate and non-invasive detection of trace amount of pathogenic substances for screening and diagnosis of neurodegenerative disease.