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The influence of withdrawal rate (3, 4.5,6,9 and 12 mm/ min) on microstructure and high temperature rupture properties of A3 alloy was investigated by testing the microstructure and properties of the third generation nickel-based single crystal superalloy. The results show that with the increase of withdrawal rate, the dendrite spacing decreased exponentially, the segregation degree of main elements and the content of (γ + γ) eutectic structure decreased, and the size of γ phase decreased. After heat treatment, the eutectic structure was dissolved basically, and the segregation of the forming elements of γ phase is eliminated at different withdrawal rates. The size of γ phase in dendrite is smallest of 372.3μm at 4.5 mm/ min, the pore content is significantly larger than that of as-cast alloy, and decreased firstly and then increased with the increasing of withdrawal rate, which is 0.112% at 4.5 mm/ min and 0.182% at 3 mm/ min. The rupture life of the alloy at 1100 °C/140MPa is the longest at 4.5 mm/ min, which is mainly determined by the precipitation of TCP phase, pore content and γ size.

Abstract: Flavonoids, a series of compounds with C6-C3-C6 structure, mostly originate from plant metabolism. Flavonoids have shown beneficial effects on many aspects of human physiology and health. Recently, many flavonoids with various activities have been discovered, which has led to more and more studies focusing on their physiological and pharmacodynamic activities. The anti-cancer and anti-viral activities especially have attracted the attention of many researchers. Therefore, the discovery and development of flavonoids as anti-disease drugs has great potential and may make significant contribution to fighting diseases. This review focus on the discovery and development of flavonoids in medicinal chemistry in recent years.

Single crystal Ni-based superalloys are the typical structural materials for high-pressure turbine blades, and their microstructure is critical in determining their mechanical properties. The withdrawal rate is a key parameter affecting the microstructure during the single crystal growth process. In the present work the effect of the withdrawal rate on the microstructure of a third-generation single crystal superalloy containing 6.8 ​wt% Re has been investigated, and the creep resistance of the alloy determined. The results showed that increased withdrawal rate refined the dendritic structure, reduced dendritic arm spacing, promoted the growth of secondary tertiary dendrites and decreased solidification segregation with a reduced size of γ′ phase. The porosity density of the as-cast alloy first decreased and then increased with the withdrawal rate, while the minimum porosity densityoccurred when the alloy was under the solidification condition of withdrawal rate of 4.5 ​mm/min. The maximum creep rupture life of 326.4 ​h of the heat-treated alloys under the test condition of 1100 ​°C/140 ​MPa also appeared at the alloys under the withdrawal rates of 4.5 ​mm/min. It is believed that the minimum porosity density and reduced size of the γ′ phase may be the main reasons for the enhanced creep rupture life of the alloys with withdrawal rates of 4.5 ​mm/min. This investigation provides theoretical support and a practical basis for the development of third-generation single crystal superalloys.

Mechanical degrees of freedom, which have often been overlooked in various quantum systems, have been studied for applications ranging from quantum information processing to sensing. Here, we develop a hybrid platform consisting of a magnomechanical cavity and an optomechanical cavity, which are coherently coupled by the straightway physical contact. The phonons in the system can be manipulated either with the magnetostrictive interaction or optically through the radiation pressure. Together with mechanical state preparation and sensitive readout, we demonstrate the microwave-to-optical conversion with an ultrawide tuning range up to 3 GHz. In addition, we observe a mechanical motion interference effect, in which the optically driven mechanical motion is canceled by the microwave-driven coherent motion. Manipulating mechanical oscillators with equal facility through both magnonic and photonic channels enables new architectures for signal transduction between the optical, microwave, mechanical, and magnetic fields.

A method based on mRNA-templated ligation of splice-junction anchored DNA probes followed by PCR amplification of the ligated product has been developed for multiplexed detection of mRNA splice variants with high sensitivity and specificity. The proposed assay can detect as low as 10 aM mRNA splicing variants and has been successfully applied to detect real samples.

The health risks of Decabromodiphenyl ethane (DBDPE) with its cardiovascular toxicity, liver toxicity and cytotoxicity had been generally acknowledged. However, the influence on gut microbiome and short-chain fatty acids (SCFAs) metabolism caused by DBDPE exposure remained unknown. In this study, three exposure groups (5, 50, 500 mg/L) and control group were used to investigate the effect of DBDPE by using simulator of the human intestinal microbial ecosystem (SHIME). 16S rRNA gene high-throughput sequencing illustrated that high dose DBDPE exposure increased the α-diversity of gut microbiota, while reduced the abundance of Firmicutes and Proteobacteria. In addition, the low dose (5 mg/L) DBDPE inhibited the increasing of SCFAs, but the medium and high dose (50 and 500 mg/L) DBDPE promoted the advancement, especially in ascending colon. Notably, DBDPE exposure lead a similar changing of acetic acid and butyric acid contents in different sections of the colon. This study confirmed the alternation of composition and metabolic function in gut microbial community due to DBDPE exposure, indicating an intestinal damage and appealing for more attention concentrated on the health effects of DBDPE exposure.

Blood coagulation is the process of changing the blood from the flowing state to the gel state. It is an important part of the hemostatic function. Coagulation is a process by which a series of coagulation factors are sequentially activated, and finally thrombin is formed to form fibrin clot. Direct thrombin inhibitors are important anticoagulant drug. These drugs can selectively bind to the active site of thrombin, inhibit thrombin activity, have strong action and high specificity, and have important significance in the clinical treatment of thrombus diseases. Some of them come from natural products of animals or plants, and many of them have been applied in the clinic. The other part is derived from the design, synthesis and activity studies of small molecule inhibitors. This review discusses the progress of direct thrombin inhibitors in recent years.

Immune checkpoint inhibitors are associated with clinical benefit in lung cancer. However, response patterns to immunotherapy, including pseudoprogression and hyperprogression, are difficult to diagnose, and their mechanisms remain unclear. This review aimed to describe two response patterns observed in lung cancer, namely pseudoprogression and hyperprogression, including their epidemiology, diagnostic characteristics, and plausible mechanisms. We performed a comprehensive literature search in the PubMed database, using keywords “pseudoprogression”, “hyperprogression”, and “lung cancer”, among others. The literature was examined for pseudoprogression and hyperprogression characteristics and plausible mechanisms. Pseudoprogression manifests in multiple forms; however, the immune system-related response criteria and biopsy data are helpful to make accurate diagnosis. Serological biomarkers, such as neutrophil-to-lymphocyte ratio (NLR) and circulating tumor DNA (ctDNA), might help distinguish pseudoprogression from true progression. The incidence of hyperprogression ranges within 5–19.2%, depending on definition. The unique response pattern of rapid progression is observed not only with immunotherapy, but also with other treatment regimens. Molecular mutations and amplifications may result in hyperprogression; however, the exact mechanism remains unclear. Atypical response patterns, such as pseudoprogression and hyperprogression, are increasingly common in clinical practice. Immune-related response criteria can help diagnose pseudoprogression. Molecular mechanisms of hyperprogression remain unclear. Biomarkers for pseudoprogression and hyperprogression are required.

The low catalytic efficiency of redox-active cofactor photoregeneration severely limits the performance of photoenzymatic hybrid systems. Herein, we synthesized thiophene-conjugated porous C3N4 nanosheets (CN-ATCN) exhibiting boosted photoregeneration activity of nicotinamide cofactors (NADH and NADPH), which are the most common redox cofactors of oxidoreductases, with regeneration rates of 59.00 μM/min for NADH and 40.99 μM/min for NADPH, ~ 84.3 and 24.7 times higher than those of bulk g-C3N4, respectively. The thin nanosheet structure of CN-ATCN facilitates the exposure of active sites to reactants and favors the diffusion of reactants and products. Upon conjugation of a thiophene moiety into the carbon nitride framework, the optical and photoelectric properties of CN-ATCN were considerably enhanced by an extended π-conjugation system in the frameworks and molecular type II heterojunctions formed between the incorporated and non-incorporated portions of CN-ATCN. Upon coupling NAD(P)H photoregeneration reaction by CN-ATCN with NAD(P)H-dependent enzymatic systems, sustainable synthesis of L-tert-leucine and styrene oxide was achieved with rates of 964 and 14.9 μM/h, respectively.

The Cenozoic in the western Qaidam Basin is rich in oil and gas resources and has good prospects for exploration. The maturity, sedimentary environment, and biological source of the crude oil in the western Qaidam Basin are discussed based on the composition characteristics of biomarkers in crude oil and source rocks. The above is performed to classify the genetic types of crude oil and determine the oil source relationship. It is found that the crude oil shows the characteristics of low mature–mature and is formed in the reducing environment with high salinity. The organic matter is from the mixed source with dominant aquatic plants input. According to the sedimentary environment, parent material types, and maturity characteristics, the crude oil in the western Qaidam Basin can be classified into four types. (1) Type I is from the Shizigou-Yuejin areas, which have a high content of gammacerane, a low value of Pr/Ph, C27 sterane predominance, and “tail-upwarping” phenomenon. (2) Type II is from the Qiekelike-Zhahaquan and Nanyishan-Youquanzi areas, which have C27 sterane predominance and no “tail-upwarping” phenomenon. Its content of gammacerane is lower than type I. (3) Type III is from the Dafengshan and Huangguamao areas, which have C29 sterane predominance and no “tail-upwarping” phenomenon. (4) Type IV is from the Kaitemilike area, which has a C27 sterane predominance, no “tail-upwarping” phenomenon, and lower content of gammacerane than that of others. The result of the oil-source correlation shows that the crude oil is dominantly derived from source rocks of the lower Ganchaigou Formation (E3) and the upper Ganchaigou Formation (N1).

Inorganic photocatalyst-enzyme systems are a prominent platform for the photoreduction of CO2 to value-added chemicals and fuels. However, poor electron transfer kinetics and enzyme deactivation by reactive oxygen species in the photoexcitation process severely limit catalytic efficiency. In chloroplast, enzymatic CO2 reduction and photoexcitation are compartmentalized by the thylakoid membrane, which protects enzymes from photodamage, while the tightly integrated photosystem facilitates electron transfer, promoting photocatalysis. By mimicking this strategy, we constructed a novel functionally compartmental inorganic photocatalyst-enzyme system for CO2 reduction to formate. To accomplish efficient electron transfer, we first synthesized an integrated artificial photosystem by conjugation of the cocatalyst (a Rh complex) onto thiophene-modified C3N4 (TPE-C3N4), demonstrating an NADH regeneration rate of 9.33 μM·min-1, 2.33 times higher than that of a homogeneous counterpart. The enhanced NADH regeneration activity was caused by the tightly conjugated structure of the artificial photosystem, enabling rapid electron transfer from TPE-C3N4 to the Rh complex. To protect formate dehydrogenase (FDH) from photoinduced deactivation, FDH was encapsulated into MAF-7, a metal-organic framework (MOF) material, to compartmentalize FDH from the toxic photoexcitation process, similar to the function of the thylakoid membrane. Moreover, the triazole linkers of MAF-7 possess both hydrophilicity and pH-buffering capacity providing a stable microenvironment for FDH, which could enhance enzyme stability in photosynthesis. The synergy between the enhanced electron transfer of TPE-C3N4 for NADH cofactor regeneration and MOF-protection of the redox enzyme enables the construction of a functionally compartmental inorganic photocatalyst-enzyme association system, promoting CO2 photoconversion to formic acid with a yield of 16.75 mM after 9 h of illumination, 3.24 times greater than that of the homogeneous reaction counterpart.

Abiotic–biological hybrid systems that combine the advantages of abiotic catalysis and biotransformation for the conversion of carbon dioxide (CO2) to value-added chemicals and fuels have emerged as an appealing way to address the global energy and environmental crisis caused by increased CO2 emission. We illustrate the recent progress in this field. Here, we first review the natural CO2 fixation pathways for an in-depth understanding of the biological CO2 transformation strategy and why a sustainable feed of reducing power is important. Second, we review the recent progress in the construction of abiotic–biological hybrid systems for CO2 transformation from two aspects: (i) microbial electrosynthesis systems that utilize electricity to support whole-cell biological CO2 conversion to products of interest and (ii) photosynthetic semiconductor biohybrid systems that integrate semiconductor nanomaterials with CO2-fixing microorganisms to harness solar energy for biological CO2 transformation. Lastly, we discuss potential approaches for further improvement of abiotic–biological hybrid systems.

The effect of trace B on the microstructure and creep properties under 1100 °C/130 MPa in three single crystal superalloys with various levels of B (0, 0.01 and 0.02 wt %) additions was investigated. Compared with the boron-free alloy, the creep rupture life decreased slightly for the alloy with 0.01 wt % B, but dropped obviously for the 0.02 wt% B contained alloy. The low B addition had a slight effect on the main element compositions of γ/γ′ by the high precision atom probe tomography (APT) analysis and no significant change of γ/γ′ misfit was observed. However, the contents of Re, Mo, Cr in γ phase were decreased with the high B addition, resulting in the decrease of γ/γ′ misfit and increase of the spacing of γ/γ′ interfacial dislocation networks. Meanwhile, the residual (γ+γ′) eutectics and borides with a large volume fraction obviously decreased the creep rupture properties in the high B addition alloy. This study is helpful for understanding the boron's role of strengthening mechanism in high temperature creep of Ni-base single crystal superalloys.

Low-cycle fatigue (LCF) behaviors of a second-generation nickel-based single-crystal superalloys with [001] orientation at 760 °C have been investigated. Different strain amplitudes were introduced to investigate the creep-fatigue effects. The LCF life of none tensile holding (NTH) was higher than that of the 60-s tensile hold (TH) at any strain amplitude. As the strain amplitude was 0.7%, the stacking and cross-slip dislocations appeared together at the γ/γ’ coherent microstructure in both TH and NTH specimens. At the strain amplitude of 0.9%, plenty of the cross-slip dislocations appeared in γ channel and other dislocations were stacking at γ/γ’ interfaces. However, the SFs still appeared in γ’ phase with 60-s TH which caused cyclic softening. As the strain amplitude increased up to 1.2%, the dislocations are piling up at the γ/γ’ interfaces and cutting through the γ’ phase in both TH and NTH tests, which caused cyclic hardening. The influences of strain amplitude and holding time were complicated. Different stress response behaviors occurred in different loading conditions. The surface characteristic and fracture mechanism were observed by scanning electron microscopy. This result is helpful for building the relationship of various blade fatigue failure modes, cyclic stress response and microstructure deformation under different strain amplitudes.

A method based on mRNA-templated ligation of splice-junction anchored DNA probes followed by PCR amplification of the ligated product has been developed for multiplexed detection of mRNA splice variants with high sensitivity and specificity. The proposed assay can detect as low as 10 aM mRNA splicing variants and has been successfully applied to detect real samples.

Axl, a Receptor Tyrosine Kinase (RTK) belonging to the TAM (Axl, Mer, Tyro3) family, participates in many signal transduction cascades after mostly being stimulated by Growth arrestspecific 6(Gas6). Axl is widely expressed in many organs, such as macrophages, endothelial cells, heart, liver and skeletal muscle. Over-expression and activation of Axl are associated with promoting chemotherapy resistance, cell proliferation, invasion and metastasis in many human cancers, such as breast, lung, and pancreatic cancers. Therefore, the research and development of Axl inhibitors is of great significance to strengthen the means of cancer treatment, especially to solve the problem of drug resistance. Axl inhibitors have attracted more and more researchers' attention in recent years. This review discusses the research progress of Axl inhibitors in recent years.

Fusion genes, playing a causal role in human tumorigenesis and developments, are deemed as gold standard molecular biomarkers in cancer diagnosis, therapy, and prognosis. A rapid, robust, and sensitive method of detection of fusion genes for point-of-care (POC) diagnosis is urgently needed. Here, taking the advantages of the superior specificity of the ligation reaction and the highly amplified efficiency of isothermal exponential amplification with a pH indicator, we developed a colorimetric method for visual detection of fusion genes with high sensitivity and specificity by the naked eye. More importantly, we first found that fusion genes can be accurately quantified in a wide dynamic range (2 zmol to 2 fmol) by an open-source app with a smartphone-assisted RGB (red, green, and blue value) reading mode. The proposed method for Visual detection of Fusion genes by Ligation-triggered Isothermal Exponential Amplification is termed Vis-Fusion LIEXA. We have demonstrated that the Vis-Fusion LIEXA is a practical and reliable method for accurate quantitative detection of the fusion gene in a complex biological sample at zmol level in 40 min only with a smartphone, thereby providing a user-friendly and point-of-care testing (POCT) tool for molecular diagnostics.

Novel g-C3N4@Bi/BiOBr ternary heterostructured composites were successfully fabricated by a facile solvothermal method, in which ethylene glycol functioned as both a solvent and a reductant. As observed by scanning electron microscopy (SEM), Bi/BiOBr nanoplates were embedded on the surface of layered g-C3N4 to form three-dimensional hierarchical structure. Under visible-light irradiation, the ternary g-C3N4@Bi/BiOBr composites displayed notably boosted photocatalytic performance for photodegrading tetracycline and rhodamine B. As revealed via the UV–visible diffuse reflection spectra (UV–vis DRS) and photocurrent experiments, the three-dimensional hierarchical structure obviously enhanced the visible-light photoresponse and the ternary heterojunction greatly promoted the separation of photo-induced carriers, thus leading to the high photocatalytic performance. Based on the results of trapping radical experiments and the energy band potentials, an indirect Z-scheme system was proposed to illuminate the possible photodegradation mechanism. This work provides a novel strategy to design the multiple heterostructured photocatalysts with high efficiency for environmental purification and energy conversion.

Both the fabricating of heterojunction and oxygen vacancy are the effective methods for boosting the performance of semiconductor photocatalyst. However, the fast recombination of charge carriers and limited light absorption in ubiquitous binary heterojunction are still inherent problems that hinder the practical application of photocatalysts. Herein, a ternary heterojunction of Bi2S3@Bi2WO6/WO3 was fabricated by the facile hydrothermal route combining with an in-situ growth method, and was confirmed by employing elemental mapping and high-resolution transmission electron microscopy. The oxygen vacancy was introduced into Bi2S3@Bi2WO6/WO3 ternary heterojunction as demonstrated by X-ray photoelectron spectroscopy. Compared with Bi2S3 and Bi2WO6/WO3 samples, the obtained Bi2S3@Bi2WO6/WO3 composites exhibited higher photocatalytic activity in photodegrading rhodamine B and Tetracycline. The high photocatalytic activity was attributed to the synergistic effect of Z-scheme/traditional heterojunction and oxygen vacancy that extended the visible-light absorption range and promoted the effective separation of photo-generated electron–hole pairs. Based on the trapping experiments and calculated positions of energy band, the photocatalytic mechanisms of the Z-scheme/traditional heterojunction with oxygen vacancy were also proposed.

Human telomerase is a universal cancer biomarker and a promising anticancer therapeutic target. Sensitive and specific detection of telomerase activity is of great significance for cancer diagnosis and treatment. Up to now, many methods have been established to detect the activity of telomerase, but most of these methods require complex probe design and tedious experimental steps generally including telomere extension reaction, amplification of the extended products and signal detection. Herein, we propose a one-pot method to detect the telomerase activity via RNA FRET probes and RNase H-assisted signal cycling amplification, and the proposed assay can integrate the telomere extension reaction, signal amplification and readout in one step without requirement of amplification of the extended products, which greatly simplifies the experimental design and operation steps. Additionally, the proposed one-pot method has high sensitivity and can unequivocally detect the telomerase activity in as few as 5 cancer cells, which holds great potential in telomerase-related fundamental and clinical studies.

Loop-mediated isothermal amplification (LAMP) has been increasingly applied in nucleic acid detection for clinical diagnosis and monitoring pathogenic microorganisms due to its isothermal nature and high sensitivity. However, the false-positive signal resulting from the non-specific amplification and the complexity of primer design are still technically challenging for wide applications. In this paper, we developed the CRISPR/Cas12a-assisted sequence-specific detection of LAMP products to eliminate the effect of non-specific amplification from primer dimers and spurious amplicons. Moreover, by designing a pair of target-specific stem-loop DNA probes, we greatly simplified the primer design for LAMP. The DNA probes could be ligated to form a double-stem-loop DNA template by the detected target, which initiated LAMP reaction and achieved one-nucleotide resolution due to the highly specific ligase reaction. Using microRNAs (miRNAs) as the model targets, the CRISPR/Cas12a-assisted ligation-initiated loop-mediated isothermal amplification (CAL-LAMP) can sensitively detect as low as 0.1 fM miRNAs with high specificity.

Background. Simultaneous multiple primary lung cancer has been detected increasingly nowadays with the development of image technology. However, the clinicopathologic characteristics and outcomes are not clear. Methods. All consecutive patients diagnosed as simultaneous multiple primary lung cancer according to Martini–Melamed and American College of Chest Physicians criteria from June 2010 to June 2019 in our center were enrolled. The clinicopathologic characteristics and outcomes were compared between patients with the same histological type and different histological types. Results. A total of 336 patients were enrolled, consisting of 297 (88.4%) patients with the same histological type and 39 (11.6%) patients with different histological types. Compared to patients with the same histological type, patients with different histological types were more commonly males (87.2% vs. 34.0%; p < 0.001 ) with an older age (65 [62–69] vs. 59 [52–65] yrs; p < 0.001 ) at diagnosis. Also, patients with different histological types showed worse respiratory function and more advanced stage according to TNM staging. The 1-, 2-, and 3-year overall survival of overall patients was 97.7%, 96.1%, and 92.2%, and the 1-, 2-, and 3-year recurrence-free survival of overall patients was 96.8%, 92.9% and 85.7%, respectively. Importantly, patients with different histological types showed worse overall survival ( p < 0.001 ) and recurrence-free survival ( p = 0.002 ) than patients with same histological type. The multivariable Cox proportional hazard model revealed that presence of different histological types was significant predictor for worse overall survival (adjusted hazard ratio: 10.00; 95% confidence interval: 2.92–34.48; p < 0.001 ) and recurrence-free survival (adjusted hazard ratio: 2.59; 95% confidence interval: 1.14–5.88; p = 0.023 ). Conclusions. Although relatively less common in simultaneous multiple primary lung cancer, patients with different histological types showed worse clinical characteristics and outcomes.