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Fluorescence imaging is a noninvasive and dynamic real-time imaging technique; however, it exhibits poor spatial resolution in centimeter-deep tissues because biological tissues are highly scattering media for optical radiation. The recently developed ultrasound-controlled fluorescence (UCF) imaging is a novel imaging technique that can overcome this bottleneck. Previous studies suggested that the effective contrast agent and sensitive imaging system are the two pivotal factors for generating high-resolution UCF images ex vivo and/or in vivo. Here, this review highlights the recent advances (2015–2020) in the design and synthesis of contrast agents and the improvement of imaging systems to realize high-resolution UCF imaging of deep tissues. The imaging performances of various UCF systems, including the signal-to-noise ratio, imaging resolution, and imaging depth, are specifically discussed. In addition, the challenges and prospects are highlighted. With continuously increasing research interest in this field and emerging multidisciplinary applications, UCF imaging with higher spatial resolution and larger imaging depth may be developed shortly, which is expected to have a far-reaching impact on disease surveillance and/or therapy.

The synthesis of two-dimensional molybdenum disulfide (MoS2) has invoked much research interest in recent years. In this work, chemical vapor deposition (CVD) was employed to grow a novel molybdenum disulfide. The synthesis reaction was operated in an inert gas environment, with the sulfur precursor placed in the upstream zone of a double zone tube furnace, and the molybdenum trioxide (MoO3) precursor placed in a small tube in the downstream zone. A piece of glass was used as the substrate, which was placed beside the small tube. We intentionally built a high concentration of molybdenum precursor above the substrate. The specific morphology hinged highly on the concentration of molybdenum. Abundant molybdenum atoms adsorbed on the edges of the bottom MoS2 and formed defects, which promoted the nucleation of the top layer MoS2 and preferentially grew from the edges. This result provides an innovative method to controllably synthesize novel bilayer molybdenum disulfide by a one-step method of chemical vapor deposition.

The practical uses of lithium-sulfur batteries are greatly restricted by the sluggish reaction kinetics of lithium polysulfides (LiPSs), leading to low sulfur utilization and poor cyclic stability. Using the heterostructure catalysts is an effective way to solve the above problems, but how to further enhance the conversion efficiency and avoid the surface passivation by the insulative Li2S has not been well investigated. Herein, a heterostructure catalyst with rich heterointerfaces was prepared by modifying Mo2N microbelt with SnO2 nanodots. The formed rich interfaces with high accessibility act as the profitable nucleation sites guiding the Li2S 3D growth, which avoids the catalyst surface passivation and facilitates the LiPS conversion. The introduction of SnO2 nanodots also enhances the LiPS adsorption. Thus, the assembled battery with the above catalyst as the cathode additive shows a high capacity of 738.3 mAh g-1 after 550 cycles at 0.5 C with an ultralow capacity decay of 0.025% per cycle. Even with high sulfur loading of 9.0 mg cm-2, good cyclic stability is also achieved at 0.5 C with a low E/S ratio of 5 μL mgs-1. This work shows an effective way to enhance the LiPS conversion kinetics and guide Li2S deposition in Li-S batteries.

Protein α-N-methylation is an evolutionarily conserved type of post-translational modification; however, little is known about the regulatory mechanisms for this modification. Methylation at the N6 position of adenosine in mRNAs is dynamic and modulates their stability, splicing, and translational efficiency. Here, we found that the expression of N-terminal methyltransferase 1 (NTMT1) protein is altered by depletion of those genes encoding the reader/writer/eraser proteins of N6-methyladenosine (m6A). We also observed that MRG15 is N-terminally methylated by NTMT1, and this methylation could also be modulated by reader/writer/eraser proteins of m6A. Together, these results revealed a novel m6A-based epitranscriptomic mechanism in regulating protein N-terminal methylation.

An efficient and convenient synthesis of pyrrole-fused tetracyclic skeletons is presented. In this protocol using CuI as a catalyst, 1,1′-biphenyl substrates with 2-alkynoyl and 2′-iodo groups react with isocyanoacetates to provide 7-membered cyclic ketones fused with pyrrole and biphenyl rings through tandem [3 + 2] cycloaddition and C–C coupling processes.

For the industrial implementation of electrochemical hydrogen production, the large-scale production of low-cost, high-efficiency, and stable electrocatalysts that work well at high current densities is critical under alkaline conditions. Here, we report a large-scale approach for the production of low-cost and highly efficient molybdenum selenide–nitride (MoSe2–Mo2N) Schottky heterojunction catalysts. Density functional theory (DFT) shows that the construction of the Schottky heterojunction can induce self-driven electron transfer that not only optimizes the electronic structure at heterointerfaces but also tunes the hydrogen adsorption and dissociation behavior. The MoSe2–Mo2N/Mo electrode delivers a high current density of 1000 mA cm−2 at an overpotential of 462 mV for hydrogen evolution in alkaline media, which are superior to those of commercial Pt/C electrodes. The mature manufacturing technology is scalable and has been confirmed as a feasible strategy to access the large-scale synthesis of molybdenum dichalcogenide-based Schottky heterojunction catalysts at industrial levels.

BiVO4 (BVO) is a promising photoanode material for photoelectrochemical (PEC) water splitting. However, it is severely restricted by its short charge diffusion length and poor charge transport. Introducing oxygen vacancies into BVO is an effective method to solve these problems because they serve as surface electron capture sites and facilitate charge separation. In this work, a novel gas reaction method using chemical vapor deposition was used to produce abundant oxygen vacancies in single-crystal BVO. Oxygen vacancies in BVO acted as hole donors. This method effectively reduced the surface agglomeration and produced uniform BVO crystals. The optimized BVO photoanode achieved a photocurrent density of 2.44 mA cm-2 (1.23 V vs. RHE) and an incident photon-to-current efficiency of 90% (450 nm). This work provides an effective strategy to prepare high-performance BVO photoanodes by chemical vapor deposition, electrodeposition and thermal evaporation.

Fabricating robust and flat photoactive materials is essential for high-performance PEC water splitting and other photovoltaic systems. Herein, we demonstrate a new method for the fabrication of flat and bulky BiVO4 (BVO) crystallites on an FTO substrate. This highly reproducible method can prepare highly active and bulky crystalline BVO (diameter ≤ 4 μm) with abundant oxygen vacancies for PEC water splitting. Moreover, the crystal size and oxygen vacancies of BVO can be controlled by adjusting the pH value of the electrodeposition electrolyte of the Bi precursor. For PEC performance, the FTO/BVO-3 photoanode shows the highest photocurrent (∼1.25 mA cm−2) among the samples in water splitting and 1.75 mA cm−2 with the aid of the impregnated Fe–Pi co-catalyst at 1.23 V vs. RHE under AM 1.5 G illumination. The new findings provide a simple yet efficient method to fabricate bulky and high-performance semi-transparent BVO photoanodes for BVO-based multi-layered tandem solar cell devices for commercial applications.

A highly efficient intramolecular asymmetric C-arylation of acyclic β-ester amides is demonstrated. A CuI/chiral diamine ligand catalyzed reaction, with t-BuOLi as the necessary base in MeCN, afforded 3,3′-disubstituted chiral oxindoles with quaternary stereogenic carboncenters in high yields and good to excellent enantioselectivities.

A cooperative catalytic strategy is developed for a copper-catalyzed asymmetric intramolecular C-arylation reaction with ureas as the co-catalysts. By forming hydrogen bonds with 1,3-dicarbonyl structures, ureas can activate the substrates, stabilize the carbanion intermediates and the products, and fix the syn-configurations of 1,3-dicarbonyl structures. They help enhance the reactivity, prevent side reactions and improve the enantioselectivities.

Data on average iodine requirements for the Chinese population are limited following implementation of long-term universal salt iodisation. We explored the minimum iodine requirements of young adults in China using a balance experiment and the ‘iodine overflow’ hypothesis proposed by our team. Sixty healthy young adults were enrolled to consume a sequential experimental diet containing low, medium and high levels of iodine (about 20, 40 and 60 μg/d, respectively). Each dose was consumed for 4 d, and daily iodine intake, excretion and retention were assessed. All participants were in negative iodine balance throughout the study. Iodine intake, excretion and retention differed among the three iodine levels (P < 0·01 for all groups). The zero-iodine balance derived from a random effect model indicated a mean iodine intake of 102 μg/d, but poor correlation coefficients between observed and predicted iodine excretion (r 0·538 for μg/d data) and retention (r 0·304 for μg/d data). As iodine intake increased from medium to high, all of the increased iodine was excreted (‘overflow’) through urine and faeces by males, and 89·5 % was excreted by females. Although the high iodine level (63·4 μg/d) might be adequate in males, the corresponding level of 61·6 μg/d in females did not meet optimal requirements. Our findings indicate that a daily iodine intake of approximately half the current recommended nutrient intake (120 μg/d) may satisfy the minimum iodine requirements of young male adults in China, while a similar level is insufficient for females based on the ‘iodine overflow’ hypothesis.

Undifferentiation is a key feature of nasopharyngeal carcinoma (NPC), which presents as a unique opportunity for intervention by differentiation therapy. In this study, we found that SOX1 inhibited proliferation, promoted differentiation, and induced senescence of NPC cells, which depended on its transcriptional function. RNA-Seq-profiling analysis showed that multiple undifferentiated markers of keratin family, including KRT5, KRT13, and KRT19, were reduced in SOX1 overexpressed NPC cells. Interestingly, gene ontology (GO) analysis revealed genes in SOX1 overexpressed cells were enriched in extracellular functions. The data of LC/MS untargeted metabolomics showed that the content of retinoids in SOX1 overexpressed cells and culture medium was both higher than that in the control group. Subsequently, we screened mRNA level of genes in retinoic acid (RA) signaling or metabolic pathway and found that the expression of UDP-glucuronosyltransferases was significantly decreased. Furtherly, UGT2B7 could rescue the differentiation induced by SOX1 overexpression. Inhibition of UGTs by demethylzeylasteral (T-96) could mimic SOX1 to promote the differentiation of NPC cells. Thus, we described a mechanism by which SOX1 regulated the differentiation of NPC cells by activating retinoid metabolic pathway, providing a potential target for differentiation therapy of NPC.

The TS-1 particles grown on carbon nanotubes decorated nickel foam (denoted as MTS-1S) are successfully synthesized by a steam-assisted crystallization method that does not waste the gels and is mo...

Molybdenum carbide (Mo2C), a member of transition metal carbides (TMCs), has shown promise in water splitting. Although excellent hydrogen evolution reaction (HER) performance of Mo2C has been achieved both in acid and basic media, the intrinsic hydrogen evolution ability of two-dimensional (2D) Mo2C is still not clear due to the difficulty of calculating the actual active surface area involved in the HER. In this work, the HER activity of Mo2C nanosheets is measured on single 2D Mo2C, which is synthesized through low-temperature carbonization of 2D molybdenum dioxide (MoO2) nanosheets on a SiO2/Si substrate. The edge sites of Mo2C exhibit high catalytic activity with a small Tafel slope of 40.2 mV dec−1 and an overpotential of 152 mV for 10 mA cm−2 in alkaline media. Theoretical analyses reveal that the energy barriers for cleaving the OH–H bond in H2O on the edge of Mo2C are much smaller than those on the basal plane of Mo2C and the Mo site of the edge of Mo2C displays the optimal ΔGH for the H absorption.

Organic–inorganic hybrid perovskite nanowires with well-defined structures have attracted considerable attention for optoelectronic applications. Perovskite nanowires integrated into practical optoelectronic devices are often hindered by the poor crystalline quality. Herein, a ligand-assisted reprecipitation (LARP) strategy is employed to prepare ultralong and freestanding CH3NH3PbI3 nanowires on a large-scale. Oleylamine is adopted as an inhibitor, which can create a passivation layer on the surface of CH3NH3PbI3, to slow down the crystallization rate of CH3NH3PbI3 nanowires. With the low crystallization rate, several millimeters long and high-quality CH3NH3PbI3 nanowires with smooth surfaces can be synthesized on a large scale. Photodetectors fabricated on oleylamine assisted synthesized CH3NH3PbI3 nanowires exhibit high detectivity, which is five times higher than that of non-oleylamine assisted synthesized CH3NH3PbI3 nanowire photoanodes.

Hawthorn including many plants from the genus Crataegus (C.) is used for traditional medicines, herbal drugs, and dietary supplements all over the world. In China, C. pinnatifida Bge. var. major N, E. Br, and C. pinnatifida Bge. are two major species that are used as hawthorn. The purpose of this study is to assay the myocardial protection of hawthorn fruit processed with honey (MSZ) and screen the chemical basis of MSZ on this effect. Firstly, ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UPLC/Q-TOF-MS) was used to analyze the chemical constituents of the sliced dry fruit of hawthorn (SZ) and MSZ. Principal component analysis (PCA) was used to differentiate them. Orthogonal partial least squares-discriminate analysis (OPLS-DA) was applied to screen different compounds between SZ and MSZ, and 32 different compounds were selected. Then a pharmacodynamic test to investigate their protective effect against myocardial ischaemia was carried out. The results demonstrated that the protective effect of MSZ was better than that of SZ on the same dose. Finally, the chemical basis for the protective effect provided by MSZ against myocardial ischaemia was speculated based on correlation analysis. Taken together, all these results suggest that phenylpropanoids, organic acids, tannins, and flavonoids might be the chemical basis of MSZ protecting against myocardial ischaemia.

Transition metal dichalcogenides (TMDs), such as molybdenum diselenide (MoSe2), have poor alkaline hydrogen evolution activities due to their unfavorable hydrogen adsorption and dissociation properties. In this work, we report a Mo2C/MoSe2 hybrid catalyst seamlessly grown on Mo foil. The Mo2C/MoSe2/Mo electrode exhibits outstanding activity for the hydrogen evolution reaction (HER) with a low overpotential of 51 mV at 10 mA cm−2 in 1 M KOH, significantly outperforming the performances of its MoSe2 and Mo2C counterparts and most reported TMD electrocatalysts in alkaline solution. Moreover, the Mo2C/MoSe2/Mo electrode also possesses good catalytic HER performance in acid. Density functional theory (DFT) calculations reveal that metal-induced gap states formed in the interface region of Mo2C and MoSe2 can make the interfacial semiconducting MoSe2 transform into metallic MoSe2. The transformation is beneficial to speeding up charge transfer between the interfaces, promoting H atom adsorption and desorption kinetics, and therefore enhancing the catalytic performance.

Desmoplasia is a hallmark of intrahepatic cholangiocarcinoma (ICC), which constitutes a barrier to infiltration of lymphocyte, but not myeloid cells. Given that dense desmoplastic stroma has been reported to be a barrier to infiltration of lymphocyte, but not myeloid cells. We here investigated whether fibroblastic FAP influenced ICC progression via non-T cell-related immune mechanisms. We demonstrated fibroblastic FAP expression was critical for STAT3 activation and CCL2 production, and ICC-CAFs were the primary source of CCL2 in human ICC microenvironment by using ICC-Fbs from six ICC patients. Fibroblastic knockdown of FAP significantly impaired the ability of ICC-CAFs to promote ICC growth, MDSCs infiltration and angiogenesis, which was restored by adding exogenous CCL2. Furthermore, interestingly, the tumor-promoting effect of fibroblastic FAP is dependent on MDSCs via secretion of CCL2, as depletion of Gr-1+ cells reversed the restoring effects of exogenous CCL2 on tumor growth and angiogenesis. In vitro migration assay confirmed that exogenous CCL2 could rescue the impaired ability of ICC-Fbs to attract Gr-1+ cells caused by fibroblastic FAP knockdown. In contrast, fibroblastic FAP knockdown had no effect on ICC cell proliferation and apoptotic resistance. Depletion MDSCs by anti-Gr-1 monoclonal antibody in subcutaneous transplanted tumor model abrogated tumor promotion by ICC-CAFs suggested that the pro-tumor function of Fibroblastic FAP relied on MDSCs. Mechanical, flow cytometry and chamber migration assay were conducted to find Fibroblastic FAP was required by the ability of ICC-CAFs to promote MDSC migration directly. Moreover, fibroblastic FAP knockdown had no effect on cell proliferation and apoptotic resistance. Here, we revealed the T-cell independent mechanisms underlying the ICC-promoting effect of fibroblastic FAP by attracting MDSCs via CCL2, which was mainly attributed to the ability of FAP to attract MDSCs and suggests that specific targeting fibroblastic FAP may represent a promising therapeutic strategy against ICC.

Herein, we report a facile solid-state synthesis strategy for the synthesis of a three-dimensional (3D) macroporous framework molybdenum disulfide-carbide (MoS2-Mo2C) heterojunction. The MoS2-Mo2C/Mo electrode exhibits excellent HER activity with low overpotentials of 56 and 446 mV at current densities of 10 and 1000 mA cm-2, respectively, in alkaline electrolytes.

Background and aims We previously demonstrated that cancer-associated fibroblasts (CAFs) promote tumor growth via recruiting of myeloid-derived suppressor cells (MDSCs). 5-lipoxygenase (5-LO) is highly expressed in myeloid cells and critical for synthesizing leukotriene B4 (LTB4), which is involved in tumor progression via acting its receptor Leukotriene B4 receptor type 2 (BLT2). In this study, we investigated whether and how CAFs regulate MDSC function to enhance cancer stemness, the driving force of the cancer aggressiveness and chemotherapy refractoriness, in highly desmoplastic intrahepatic cholangiocarcinoma (ICC). Approach and results RNA-sequencing analysis revealed enriched metabolic pathways but decreased inflammatory pathways in cancer MDSCs compared with blood MDSCs from ICC patients. Co-injection of ICC patient-derived CAFs promoted cancer stemness in an orthotopic ICC model, which was blunted by MDSC depletion. Conditioned media (CM) from CAF-educated MDSCs drastically promoted tumorsphere formation efficiency and stemness marker gene expression in ICC cells. CAF-CM stimulation increased expression and activity of 5-LO in MDSCs while 5-LO inhibitor impaired the stemness-enhancing capacity of MDSCs in vitro and in vivo. Furthermore, IL-6 and IL-33 mainly expressed by CAFs mediated hyperactivated 5-LO metabolism in MDSCs. We identify the LTB4-BLT2 axis as the critical downstream metabolite signaling of 5-LO in promoting cancer stemness, as treatment with LTB4 that were elevated in CAF-educated MDSCs or blockade of BLT2 that was preferentially expressed in stem-like ICC cells significantly reduced stemness-enhancing effects of CAF-educated MDSCs. Finally, BLT2 blockade augmented chemotherapeutic efficacy in ICC patient derived-xenograft (PDX) models. Conclusions Our study reveals a previously unrecognized role for CAFs in orchestrating the optimal cancer stemness-enhancing microenvironment by educating MDSCs and suggests 5-LO/LTB4-BLT2 axis as promising therapeutic targets for ICC chemoresistance by targeting cancer stemness.

Tumor complexity makes the development of highly sensitive tumor imaging probes an arduous task. Here, we construct a peptide-based near-infrared probe that is responsive to fibroblast activation protein-α (FAP-α), and specifically forms nanofibers on the surface of cancer-associated fibroblasts (CAFs) in situ. The assembly/aggregation-induced retention (AIR) effect results in enhanced accumulation and retention of the probe around the tumor, resulting in a 5.5-fold signal enhancement in the tumor 48 h after administration compared to that of a control molecule that does not aggregate. The probe provides a prolonged detectable window of 48 h for tumor diagnosis. The selective assembly of the probe results in a signal intensity over four- and fivefold higher in tumor than in the liver and kidney, respectively. With enhanced tumor imaging capability, this probe can visualize small tumors around 2 mm in diameter.

The morphology and crystallographic surface can influence the catalytic HER activity of electrocatalyst. With sufficient active sites and surface area, nanoporous materials with three-dimensional interconnected porous networks have shown the promising application in electrocatalyst. In this work, we report a simple method that can synthesize the self-supported nanoporous cobalt phosphosulfate (CoP|S) electrocatalyst. Theoretical calculation shows that the phosphorus substitution by sulfur can control the electronic structures of the active sites and accelerate charge transfer of CoP, therefore improving HER activity. The experimental study shows that nanoporous CoP|S electrodes present the improved HER performance compared with CoP in alkaline media and acidic media, respectively.

To investigate the effects of lncRNA GAS5 on the proliferation, migration, invasion and apoptosis of brain glioma cells. The expression levels of lncRNA GAS5 and GSTM3 in normal glial cells (HEB) and glioma cells (U251 and U87) were detected by RT-qPCR and western blot, respectively. Glioma cells were transfected with ctrl vector, pcDNA-GAS5, siRNA ctrl (siNC) or GSTM3 siRNA and the effects of lncRNA GAS5 and GSTM3 on the proliferation, migration, invasion and apoptosis of glioma cells were detected by CCK-8 assay, transwell assay and Caspase 3/7 activity assay, respectively. The expression of lncRNA GAS5 was significantly decreased in glioma cell lines U251 and U87 compared with normal glial cells HEB (p

In this work, we report a simple bottom-up approach to synthesize seamless tungsten disulfide (WS2)-tungsten (W) heterojunction electrode for efficient hydrogen evolution reaction (HER). Through one step sulfidation of WO3/W, ultra-thin vertically-arranged WS2 flakes with high surface areas and stepped-structure as well as abundant defects can grow on the W substrate. The synthesized WS2/W electrode exhibits outstanding HER activity with an onset overpotential of as small as approximately 30 mV, and an operating potential of only 108 mV for 10 mA/cm2, which is close to the state-of-the-art transition metal dichalcogenides (TMDs) HER electrocatalyst reported in the literature so far. The abundant exposed edges and defects of WS2 along with excellent electrical contact between WS2 and W substrate contribute to the high HER activity of WS2/W electrode reported in this work.

BACKGROUND This study assessed the effects and underlying molecular mechanisms of ß-asarone on ischemic stroke model rats. MATERIAL AND METHODS Ischemic stroke was induced by middle cerebral artery occlusion (MCAO) in rats. Before and after modeling, cognitive function was evaluated via fear conditioning test and neurological deficit was determined via Longa and Bederson scores. Following treatment with ß-asarone or nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor for 20 consecutive days, the cerebral infarction was detected via TTC staining and Cresyl Violet staining in brain tissues. TUNEL staining and western blot analysis for apoptosis-related proteins were performed to assess the apoptosis of neurons. Nrf2-antioxidant response elements (ARE) pathway-related proteins were examined by RT-qPCR or western blot. RESULTS The cognitive and neurological function was defective in MCAO rats. The infarction volumes and the apoptosis of cortical neurons were significantly increased in brain tissues of model rats, which were ameliorated after treatment with ß-asarone. Meanwhile, the increase in pro-apoptotic proteins and decrease in anti-apoptotic proteins were found in brain tissues of model rats, which were markedly ameliorated by ß-asarone treatment. However, Nrf2 inhibitor worsened the cerebral infarction and the apoptosis of neurons. Western blot results showed that ß-asarone treatment activated the Nrf2-ARE pathway-related proteins in model rats, which was inhibited by Nrf2 inhibitor. CONCLUSIONS Our findings suggest that ß-asarone treatment ameliorated the cerebral infarction in MCAO rats, which could be related to activation of the Nrf2-ARE pathway.

Purpose: The aim of this study was to assess the effect of phillygenin (PHI) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and understand its underlying mechanisms. Methods: Mice were separated into four different groups at random, including LPS, LPS+ PHI (5 mg/kg), LPS + PHI (50 mg/kg) and control group. The two LPS + PHI groups were intraperitoneally administered with PHI after LPS intratracheal administered for 1 h. Subsequently, the lung tissues of different groups were collected and evaluated by H&E staining and W/D (W/D) ratio. The inflammatory cytokines in BALF or lung tissue were also assessed. Western blot assay was applied to examine the expressions of TLR4, MyD88, and NF-κB. Results: The ameliorated pathological changes and lung W/D ratio demonstrated that PHI dramatically suppressed the lung injury levels. PHI strikingly reduced the number of inflammatory cell counts and total protein concentration in BALF. In addition, PHI attenuated expression of IL-1β and TNF-α in BALF and lung tissue. Furthermore, it was confirmed that PHI alleviated LPS-induced ALI via TLR4/MyD88/NF-κB pathway. Conclusions: Together the above results show that PHI attenuates LPS-induced ALI via inactivation of TLR4/MyD88/NF-κB pathway in newborn mice.

Background Interleukin-6 (IL-6) was proposed to be associated with the severity of coronavirus disease 2019 (COVID-19). The present study aimed to explore the kinetics of IL-6 levels, validate this association in COVID-19 patients, and report preliminary data on the efficacy of IL-6 receptor blockade. Methods We conducted a retrospective single-institutional study of 901 consecutive confirmed cases. Serum IL-6 concentrations were tested on admission and/or during hospital stay. Tocilizumab was given to 16 patients with elevated IL-6 concentration. Results 366 patients were defined as common cases, 411 patients as severe, and 124 patients as critical according to the Chinese guideline on diagnosis and treatment of COVID-19. The median concentration of IL-6 was P P P = 0.12). Conclusion Serum IL-6 should be included in diagnostic work-up to stratify disease severity, but the benefit of tocilizumab needs further confirmation. Trial registration retrospectively registered.

Processing herbal medicine is a classic characters of traditional Chinese medicine (TCM) clinic. Stir-frying with bran is a common method of processing Atractylodis Rhizoma (AR), which is considered to enhance the therapeutic effect in TCM theory. However, the processing mechanism remains unclear. In our previous study, we found that bran-fried AR was better than raw AR in regulating gut flora. To further compare the effect of raw and bran-fried AR on the symbiotic metabolism of gut flora and host, we established a fecal metabonomics method of ARs intervention on spleen-deficiency rats by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. 22 potential biomarkers of spleen-deficiency were identified under the positive and negative ion mode. Through the analysis of metabolic pathway, 6 significant changes of metabolic pathway were found, 5 of which were both improved by raw and bran-fried AR. Especially bran-fried AR was better than raw AR in the improvement of tyrosine metabolism and purine metabolism. Correlation analysis between the metabolic potential biomarkers and the microbiological biomarkers published in our previous study revealed that one of the spleen-strengthening mechanisms of ARs could be associated with the improvement of the symbiotic metabolism of gut flora and host by regulating gut-flora. The results can help us to understand the mechanism of AR intervention on spleen deficiency and the enhanced-efficacy mechanism of bran-fried AR.

Leukotriene B4 (LTB4) is a major type of lipid mediator that is rapidly generated from arachidonic acid through sequential action of 5-lipoxygenase (5-LO), 5-lipoxygenase-activating protein (FLAP) and LTA4 hydrolase (LTA4H) in response to various stimuli. LTB4 is well known to be a chemoattractant for leukocytes, particularly neutrophils, via interaction with its high-affinity receptor BLT1. Extensive attention has been paid to the role of the LTB4-BLT1 axis in acute and chronic inflammatory diseases, such as infectious diseases, allergy, autoimmune diseases, and metabolic disease via mediating recruitment and/or activation of different types of inflammatory cells depending on different stages or the nature of inflammatory response. Recent studies also demonstrated that LTB4 acts on non-immune cells via BLT1 to initiate and/or amplify pathological inflammation in various tissues. In addition, emerging evidence reveals a complex role of the LTB4-BLT1 axis in cancer, either tumor-inhibitory or tumor-promoting, depending on the different target cells. In this review, we summarize both established understanding and the most recent progress in our knowledge about the LTB4-BLT1 axis in host defense, inflammatory diseases and cancer.

Free thiols, or unpaired cysteines, are important product quality attributes in the therapeutic proteins due to their potential impact on the protein structure, bioactivity and stability. While many free thiol quantitation methods were developed for specific therapeutic formats, an unmet need still exists for a multiproduct, high-throughput method for free thiol quantitation. In this study, a workflow was established that combines N-cyclohexylmaleimide (NcHM) derivatization and high-throughput reversed-phase ultra-high performance liquid chromatography (RP-UHPLC) separation with superficially porous particle (SPP) column for quantitating total free thiols in monoclonal antibodies (mAbs), fragment antigen-binding (Fab), and bispecific antibodies (BsAbs). The NcHM derivatization increases the hydrophobicity of the free thiol variants and allows the further separation and quantitation with RP-UHPLC. A thorough evaluation of sample preparation, column selection, chromatographic condition and LC-MS peak identification was performed to optimize and characterize the method outputs. Method optimization resulted in a 42-minute total analysis time. Method qualification demonstrated suitable accuracy, precision, linearity, specificity and robustness. This high-throughput method is not only used for quantitation of total free thiols for both in-process testing and drug substance/drug product batch testing, but also for provide the positional distribution of the free thiols in the protein.

LncRNA (long noncoding RNA) is often dysregulated in tumors especially hepatocellular carcinoma (HCC). However, the dysregulation mechanism of lncRNAs is largely unknown. Here, we showed that lncRNA lncAY expression was stimulated in HCC by either endogenous or exogenous sulfatide. Elevated lncAY promoted HCC cell migration or angiogenesis, whereas lncAY silence suppressed HCC cell migration and proliferation. Interestingly, the activity of lncAY gene promoter was enhanced by sulfatide. Then Myb and MEF2C were identified as the transcription factors responsible for the stimulation of lncAY promoter activity and transcription by sulfatide. Both Myb and MEF2C enrichment on lncAY promoter was further confirmed, and their occupancy on lncAY promoter was strengthened by sulfatide for Myb or MEF2C was acetylated. Mutant Myb-K456A exhibited reduced acetylation and weak stimulation for lncAY transcription. However, Myb mutation K456/503A prevented Myb from acetylation induced by sulfatide. The mutant Myb K456/503A further was unable to occupy lncAY promoter and enhance lncAY transcription. In conclusion, this study demonstrated lncAY transcription was abnormally upregulated by sulfatide in HCC through Myb/MEF2C to promote HCC progression.

Bamboo powder and its dissolution process in ionic liquids were analyzed according to Fourier Transform Infrared Spectroscopy (FT-IR) coupled with two-dimensional correlation spectroscopy and chemometrics. Second derivative spectroscopy was applied to enhance the spectra resolution, obtaining more molecular vibration information. After executing the principal component analysis (PCA) on ATR-FTIR spectra of undissolved bamboo powder residue, we obtained a three-staged dissolution process model. In addition, the conclusion that cellulose/hemicellulose dissolving prior to lignin was summarized through the PCA loading spectrum. Point-line moving window two dimensional correlation spectroscopy (PL-MW2DCOS) furtherly unveiled the dissolution details. This work provided us a clear dissolution process of biomass using a rapid, label-free and easy-operation method.

The ultrathin insulator layer in the silicon metal–insulator–semiconductor (MIS) photoanode plays important roles in determining the performance of water oxidation. We report that an insulator oxid...

An asymmetric oxidative C-N bond-forming reaction is developed using a chiral diiodospirobiindane derivative as the catalyst and mCPBA as a terminal oxidant. The protocol is based on an asymmetric desymmetrization strategy and affords lactams or spirolactams according to the different substituents on the substrates. The products are obtained in good yields and moderate to high enantioselectivities.

Objective: Yiqi Huoxue Decoction (YQHX) has been widely used for clinical treatment of ischemic heart disease. While oxidative stress plays a key role in the pathogenesis of ischemic heart disease, the function and molecular mechanism underlying antioxidative protective effects of YQHX on H9c2 cardiomyocytes against ischemia/hypoxia (I/H) have yet to be well clarified. Methods: H9c2 cells were subjected to 12 h of hypoxia with serum-free conditions and then treated with or without YQHX (100–400 μg/mL). Cell viability was examined using a CCK-8 assay. Maleic dialdehyde (MDA) and superoxide dismutase (SOD) activity were detected using commercial kits. Intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential were measured using fluorescence microscopy and confocal laser-scanning microscopy, respectively. Ultrastructural details of mitochondria in H9c2 cells were observed using transmission electron microscopy. The antioxidative protective pathway was assessed by measuring mRNA and protein expression of Nrf2 and HO-1, as well as AMPK activation. Results: I/H injury gradually induced oxidative stress. Treatment with YQHX significantly increased cell viability and reversed I/H-induced oxidative stress, including reducing the production of oxidative stress products (ROS and MDA), increasing SOD levels, improving mitochondrial morphology, and increasing mitochondrial membrane potential. YQHX was also observed to increase I/H-induced expression of Nrf2 and HO-1, and the activation effects of YQHX were blocked by an AMPK inhibitor. In addition, HPLC analysis showed that YQHX contained two active antioxidative constituents (calycosin and ferulic acid). Conclusion: The results suggest that anti-oxidative effects exerted by YQHX in H9c2 cardiomyocytes may be linked to upregulation of the AMPK-mediated Nrf2/HO-1 pathway. Keywords: Hypoxia, Yiqi Huoxue Decoction, Chinese medicine, Cardiomyocytes, Oxidative stress

Background Several latest guidelines and consensus statements from Europe and the United States specify that there is no need for fasting prior to routine lipid tests. However, the latest Chinese guidelines still recommend fasting tests owing to a lack of local evidence. This study aimed to investigate postprandial lipid concentrations and daytime biological variation of lipids in a healthy Chinese population. Methods Venous blood samples were collected from 41 ostensibly healthy Chinese volunteers at five time points during the day (06:30, 09:00, 12:00, 15:00, and 18:30). The same batch of reagents was used to determine lipid concentrations. A nested ANOVA was performed to calculate within-subject biological variation (CV(I)) and between-subject biological variation (CV(G)). Results Postprandial concentrations of triglyceride were higher than fasting concentrations, with the maximum change occurring at 12:00 (0.5 hours after lunch, 0.21±0.65 mmol/L difference). The daytime biological variation of triglycerides was relatively high (CV(I)=25%, CV(G)=35.9%). The postprandial concentrations of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1, and apolipoprotein B were mostly lower than the fasting concentrations, and their daytime biological variations were relatively low (CV(I)=2.4-4.4%, CV(G)=11.8-18.7%). Conclusions As most daytime lipid concentrations changed only slightly, non-fasting samples could be used for routine lipid tests. However, in cases of abnormal postprandial triglyceride concentrations, dietary factors and fasting time should be considered when interpreting the results.

Ni catalyst is a low-cost catalyst for oxygen evolution reaction (OER) on silicon metal–insulator–semiconductor photoanode. We found that Au nanoparticles incorporated with Ni nanoparticles can enhance the OER activity and stability of Ni nanoparticles due to the local surface plasmon resonance (LSPR) effect of the Au nanoparticles. The efficiency of NiAu/TiO2/n-Si photoanode can be boosted at least three times under the illumination (100 mW/cm2) by LSPR effect of the Au nanoparticles. A small onset potential of 1.03 V versus reversible hydrogen electrode (overpotential, η0 = −0.20 V) and a current density of 18.80 mA/cm2 at 1.23 V versus reversible hydrogen electrode can be obtained. The NiAu/TiO2/n-Si photoanode exhibits a high saturation current density of 35 mA/cm2, which is greater than that of most of the state-of-the-art silicon photoanodes.

In this study, we report NiFe/ZrO2/n-Si photoanodes with efficient photoelectrocatalytic activity for ethanol oxidation reaction (EOR) in alkaline medium (1.0 M KOH). NiFe/ZrO2/n-Si electrode exhibits apparently improved EOR activity with the mass-specific activity of 34.4 mA∙cm-2 under visible light illumination, which is approximately 2.53 times higher than that in the dark (13.6 mA∙cm-2). NiFe/ZrO2/n-Si electrode presents obviously enhanced stability under visible light illumination due to the acceleration of the oxidation of intermediate products adsorbed on the surface of the catalyst. Additionally, NiFe/ZrO2/n-Si photoanode displays better EOR activity compared with Pt(Pd)/ZrO2/n-Si photoanodes, which shows the potential to replace the Pt or Pd in EOR using silicon photoanode.

Anemone flaccida Fr. Shmidt (Ranunculaceae), known as 'Di Wu' in China, is a perennial herb which has long been used to treat arthritis. The rhizome of A. flaccida contains pharmacologically active components i.e. oleanane-type triterpenoid saponins. Oleanolic acid is natural triterpenoid in plants with diverse biological activities. The biosynthesis of oleanolic acid involves cyclization of 2,3-oxidosqualene to the oleanane-type triterpenoid skeleton, followed by a series of oxidation reactions catalyzed by cytochrome P450 monooxygenase (CYP450). Previously, we identified four possible cytochrome P450 genes belonging to CYP716A subfamily from the transcriptome of A. flaccida. In this study, we identified one of those genes "CYP716A254" encoding a cytochrome P450 monooxygenase from A. flaccida that catalyzes the conversion of the β-amyrin into oleanolic acid. The heterologous expression of CYP716A254 in yeast resulted in oxidation of β-amyrin at the C-18 position to oleanolic acid production. These results provide an important basis for further studies of oleanane-type triterpenoid saponins synthesis in A. flaccida.

A methylene blue-based near-infrared fluorescent probe was designed for the selective determination of hypochlorite (ClO−), over other reactive oxygen species or interfering agents. Acetylated methylene blue was synthesized by introducing the acetyl group into the methylene blue framework, which can specifically recognize exogenous and endogenous ClO−. The acetylated methylene blue fluorescent probe was characterized by 1H NMR, 13C NMR and HRMS. The response process and possible mechanism were studied using products of the probe. The emission response of the probe to ClO− presented good linear relationship in the 0–60 μM concentration range, with the detection limit of 0.1 μM (measured at 660 nm and 690 nm). The absorption and emission wavelengths of acetylated methylene blue are both in the near-infrared region; in addition, the probe itself and the degradation products were well-dissolved in water and have almost no toxicity. The probe was used for intracellular ClO− imaging and showed a large fluorescence enhancement (about 200-fold increase).

Lithium-sulfur batteries (LSBs) have gained wide attention in the past decades for its high energy density and low cost. However, LSBs practical application is hindered by the severe shuttling of soluble intermediate lithium polysulfides (LiPSs), and the uncontrollable deposition of insulating Li2S, which limits the active species utilization and decelerates the redox kinetics. In this study, MoO2/α-MoC nanocomposite was investigated as a multifunctional electrocatalyst to address above problems. Not only does such electrocatalyst immobilizes LiPSs on its surface but also facilitate the subsequent conversion reaction, further enable the heterogeneous Li2S nucleation and induce three-dimensional precipitation of Li2S. MoO2/α-MoC-containing LSBs exhibit excellent rate performance, promising cycling stability, and a high specific capacity of 1177 mAh g−1 at 0.2 C and 695 mAh g−1 at 3 C with a low-capacity deterioration. Good cyclic stability was achieved at 0.5 C even with a high sulfur loading of 5 mg cm−2 and a low E/S ratio of 6–7 μL mg−1 by employing a MoO2/α-MoC interlayer.

A series of hyperbranched graft copolymers with hyperbranched polyethylenimine (HPEI) as core and hyperbranched polyglycerol (HPG) as shell (HPEI-g-HPG) were used as nanoreactors and stabilizers for the synthesis of CdS quantum dots (QDs). The preparation conditions were optimized to obtain CdS QDs with a stronger fluorescence. Stable CdS QDs could be prepared by using HPEI-g-HPGs or HPEI homopolymer, but not HPG homopolymer. The CdS QDs capped by HPEI-g-HPGs emitted stronger than those capped by HPEI. Moreover, the photoluminescence intensity increased pronouncedly with increasing the HPG shell content of HPEI-g-HPG stabilizer. The measurements of UV–vis spectroscopy, transmission electron microscopy and dynamic light scattering further verified the formation of CdS QDs. Compared with the CdS QDs capped by HPEI, those capped by HPEI-g-HPGs showed a better storing stability in solution at 4 °C. The as-prepared CdS QDs were only stable in the pH range of 7.0–9.0. It was found that increasing the HPG shell content of HPEI-g-HPG stabilizer could effectively raise the selectivity of the as-prepared CdS QDs towards Hg2+. As the ratiometric fluorescence sensors, CdS QDs capped by HPEI-g-HPGs were most sensitive to Hg2+ and the limit of detection was ca. 1.5 × 10−8 M.