A new method providing complementary explanation of the blood-enriching function and mechanism of unprocessed Angelica sinensis and its four kinds of processed products based on tissue-integrated metabolomics and confirmatory analysis.

Angelica sinensis (AS) is a common Traditional Chinese Medicine used for tonifying blood in China. Unprocessed AS and its four kinds of processed products (ASs) are used to treat blood deficiency syndrome in the country. The different blood-tonifying mechanisms of ASs remain unclear. In this work, a novel method integrating metabolomics and hematological and biochemical parameters was established to provide a complementary explanation of blood supplementation mechanism of ASs. Our results revealed that different ASs exhibited various blood supplementation effect, and that AS parched with alcohol demonstrated the best blood supplementation effect. Eight metabolites from liver tissue and 12 metabolites from spleen tissue were considered to be potential biomarkers. These biomarkers were involved in four metabolic pathways. Correlation analysis results showed that l-aspartic acid and l-alanine (spleen tissue), linoleic acid, and l-cystathionine (liver tissue) exhibited a high positive or negative correlation with the aforesaid biochemical indicators. The blood-supplementation effect mechanism of ASs were related to four metabolic pathways. l-Aspartic acid and l-alanine (spleen tissue), linoleic acid, and l-cystathionine (liver tissue) were the four key metabolites associated with the blood supplementation effect of ASs. This study gives a complementary explanation of the blood supplementation effect and mechanism of action of ASs.

Circ_0002762 Accelerates Glycolysis Metabolism to Promote Cervical Cancer Progression via the miR-526b-5p/HK2 Axis.

OBJECTIVES: The purpose of this study was to investigate the role and mechanism of circ_0002762 in CC. DESIGN: This study was designed for silencing circ_0002762 in CC cells and xenograft tumor models to investigate the role of circ_0002762 in CC in vitro and in vivo. MATERIALS AND METHODS: The relative expression levels of circ_0002762, miR-526b-5p, and hexokinase2 (HK2) in CC tissues and cells were detected by real-time quantitative polymerase chain reaction or Western blot. Glycolysis-related extracellular acidification rate, glucose production, lactic acid consumption, and ATP levels were measured using the appropriate kits. Cell proliferation was assessed by 5-ethynyl-2'-deoxyuridine and colony formation assay. Cell apoptosis was detected by flow cytometry. The binding relationship between miR-526b-5p and circ_0002762 or HK2 was verified by dual-luciferase reporter assay and RNA pull-down assay. Tumor growth in vivo was detected by xenograft tumor model. RESULTS: The expressions of circ_0002762 and HK2 were up-regulated and miR-526b-5p was down-regulated in CC tissues and cells. Circ_0002762 knockdown inhibited glycolysis and proliferation and promoted apoptosis of CC cells. In addition, miR-526b-5p suppression reversed the inhibition of CC development induced by circ_0002762 silencing. HK2 overexpression eliminated the inhibition of miR-526b-5p on CC progression. Moreover, silencing of circ_0002762 inhibited CC tumor growth in vivo. LIMITATIONS: The practical application of circ_0002762 in clinical practice needs further investigation. CONCLUSION: Circ_0002762 knockdown inhibited CC progression by regulating miR-526b-5p/HK2 axis, suggesting that circ_0002762 was a promising therapeutic strategy for CC.

Step-by-Step Assembly of Metal-Organic Frameworks from Trinuclear Cu3 Clusters.

Two novel metal-organic frameworks (MOFs), HBNU-1 and HBNU-2, have been synthesized successfully. We adopt a step-by-step assembly strategy, which first synthesize the Cu3 cluster Cu3(µ3-OH)(pz)3(CH3COO)2(Hpz), and then react it with H2BDC under different conditions to form final frameworks. In both MOF structures, the Cu3 clusters are maintained, although certain differences are observed. Compared with HBNU-1, the Cu3 cluster dimerizes into Cu6 cluster in HBNU-2. With this step-by-step cluster assembly strategy, MOF structure predicting becomes possible and may give some reference for MOF structure designing.

Curcumin increases the sensitivity of Paclitaxel-resistant NSCLC cells to Paclitaxel through microRNA-30c-mediated MTA1 reduction.

Non-small-cell lung cancer is one of the most lethal cancers in the worldwide. Although Paclitaxel-based combinational therapies have long been used as a standard treatment in aggressive non-small-cell lung cancers, Paclitaxel resistance emerges as a major clinical problem. It has been demonstrated that Curcumin from Curcuma longa as a traditional Chinese medicine can inhibit cancer cell proliferation. However, the role of Curcumin in Paclitaxel-resistant non-small-cell lung cancer cells is not clear. In this study, we investigated the effect of Curcumin on the Paclitaxel-resistant non-small-cell lung cancer cells and found that Curcumin treatment markedly increased the sensitivity of Paclitaxel-resistant non-small-cell lung cancer cells to Paclitaxel. Mechanically, the study revealed that Curcumin could reduce the expression of metastasis-associated gene 1 (MTA1) gene through upregulation of microRNA-30c in Paclitaxel-resistant non-small-cell lung cancer cells. During the course, MTA1 reduction sensitized Paclitaxel-resistant non-small-cell lung cancer cells and enhanced the effect of Paclitaxel. Taken together, our studies indicate that Curcumin increases the sensitivity of Paclitaxel-resistant non-small-cell lung cancer cells to Paclitaxel through microRNA-30c-mediated MTA1 reduction. Curcumin might be a potential adjuvant for non-small-cell lung cancer patients during Paclitaxel treatment.

Facile synthesis of an ultra-stable metal-organic framework with excellent acid and base resistance.

A novel ultra-stable metal-organic framework, MCIF-1, [Cu2(DCI)2](MeCN), based on dicyanoimidazole and Cu(i), has been synthesized at room temperature successfully. MCIF-1 shows excellent water stability and can retain crystallinity after soaking in water for about one week. In addition, MCIF-1 also shows exceptional resistance under both acidic and basic conditions within a large pH range from 0 to 13.5. What is more, after modifying the synthesis procedure slightly, we can produce this material in a large scale during a very short time. Mild synthesis conditions, excellent stability and ease of large scale production give MCIF-1 great potential for practical use.

An Amino-Coordinated Metal-Organic Framework for Selective Gas Adsorption.

A novel 3D porous metal organic framework, JUC-141, constructed by 5-aminoisophthalic acid and Cu(NO3)2, has been synthesized successfully. The carboxyl groups in the ligand coordinate to Cu2+ to form the classic Cu2(COO)4 paddle wheel SBU, and the assembly of the SBUs with the isophthalic acid moieties leads to a kagome lattice. Interestingly, the amino groups in the ligand also take part in the coordination and link to the dipole of the paddle wheel as pillars, thus forming a 3D porous framework with eea topology. The sizes of the channels are 5.2 Å in the direction of [111] and 10.9 Å in the direction of [001]. Gas sorption tests show that the CO2 adsorption capacities of JUC-141 are 79.94 and 51.39 cm3 g-1 at 273 and 298 K under 1 atm pressure, respectively. However, the N2 adsorption capacities of JUC-141 are 13.90 and 6.76 cm3 g-1 at 273 and 298 K under 1 atm pressure, respectively. IAST calculations indicate that the selectivity values of CO2/N2 are 21.62 at 273 K and 27.60 at 298 K under 101 kPa, respectively. Good selective adsorption of CO2 over N2 makes JUC-141 possible for CO2 storage and separation.

Two Finite Binuclear [M2(µ2-OH)(COO)2] (M = Co, Ni) Based Highly Porous Metal-Organic Frameworks with High Performance for Gas Sorption and Separation.

Two highly porous MOFs, [Co2(µ2-OH)(bpdc)(Htpim)2][SiF6]·3.5DMA·2.5CH3OH (JLU-Liu37, H2bpdc = biphenyl-4,4'-dicarboxylate, Htpim = 2,4,5-tri(4-pyridyl)imidazole) and [Ni2(µ2-OH)(bpdc)(Htpim)2][SiF6]·7.5DMA·6CH3OH (JLU-Liu38), have been solvothermally synthesized by using the mixed ligand strategy. Both of the compounds possess finite binuclear [M2(µ2-OH)(COO)2] (M = Co, Ni) secondary building units (SBUs) which formed with a polar functional group, µ2-OH. JLU-Liu37 and JLU-Liu38 exhibit notable adsorption capacities for CO2 and light hydrocarbons (CH4, C2H6, and C3H8). Moreover, both of the materials exhibit arrestive natural gas selective separation ability, especially for C3H8/CH4 (206 for an equimolar mixture under 1 bar and 298 K, for JLU-Liu37). Both of the MOFs may be effectively applied in the separation of industrial light hydrocarbons.

Nanocomposites with gold nanorod/silica core-shell structure as saturable absorber for femtosecond pulse generation in a fiber laser.

Ultrafast fiber lasers play a significant role in our society with many aspects ranging from fundamental physics to industrial purposes. Searching for high-performance saturable absorbers (SAs) is vital to the developments of ultrafast fiber lasers. Gold nanorods (GNRs) have been discovered to possess saturable absorption effect. However, a major obstacle to make the GNRs as high-performance and practical SA is the low optical damage threshold. To overcome this drawback, herein we proposed the nanocomposites with gold nanorods/silica core-shell structure (GNRs@SiO(2)) as a high-performance SA for ultrashort pulse generation in a fiber laser. The GNRs@SiO(2) SA presents a modulation depth of 4.2% and nonsaturable loss of 45.6%. With the proposed GNRs@SiO(2) SA, 379 fs pulse was directly obtained from the fiber laser. The achieved results demonstrated that the GNR@SiO(2) could be indeed a good candidate of high-performance SA towards practical applications in the field of ultrafast photonics.

Noise-like pulse trapping in a figure-eight fiber laser.

We report on the trapping of noise-like pulse in a figure-eight fiber laser mode locked by nonlinear amplifier loop mirror (NALM). After achievement of noise-like vector pulse, it was found that the wavelength shift of the two resolved polarization components responsible for the pulse trapping was very sensitive to the cavity birefringence. By properly rotating the polarization controllers (PCs), the wavelength shift could be up to 4.8 nm, which is much larger than that of conventional soliton trapping. The observed results would shed some light on the fundamental physics of noise-like pulse as well as its vector features in fiber lasers.

Deprotonation-triggered Stokes shift fluorescence of an unexpected basic-stable metal-organic framework.

A new three-dimensional porous metal-organic framework, JUC-119, constructed by a pyrene-based dendritic organic linker, H8TIAPy (H8TIAPy = 1,3,6,8-tetrakis(3,5-isophthalic acid)pyrene), and Eu(III) has been synthesized successfully. JUC-119 shows unexpected stability under a wide range of basic conditions from 0 to 0.01 M NaOH. Furthermore, with two carboxyl groups uncoordinated in each ligand, the crystals of JUC-119 show deprotonation-triggered Stokes shift fluorescence under basic conditions. As the concentration of base increases from 0 to 0.01 M NaOH, the luminescence emission of JUC-119 becomes gradually red shifted from 455 to 485 nm. In addition, the Stokes shift shows a good linear relationship to -log[OH(-)], which makes JUC-119 promising for base sensing.

Microfiber-based, highly nonlinear graphene saturable absorber for formation of versatile structural soliton molecules in a fiber laser.

We reported on the generation of versatile soliton molecules in a fiber laser mode-locked by a microfiber-based graphene saturable absorber (GSA). By virtue of the highly nonlinear effect of the microfiber-based GSA, the soliton molecules could be easily observed. In addition to regular soliton molecules, it is found that the "soliton atoms" in molecules could exhibit different characteristics and show ultra-narrow pulse separations, which was termed as 'structural soliton molecule'. The pulse profiles of 'structural soliton molecules' were further reconstructed theoretically. The obtained results would give further insight towards understanding the dynamics of soliton molecules in fiber lasers.

Dual-wavelength rectangular pulse Yb-doped fiber laser using a microfiber-based graphene saturable absorber.

We reported on the generation of dual-wavelength rectangular pulses in a Yb-doped fiber laser (YDFL) by using a microfiber-based graphene saturable absorber (GSA). The duration of dual-wavelength rectangular pulse could be varied from 1.41 ns to 4.23 ns with the increasing pump power. With a tunable bandpass filter, it was found that the characteristics of the rectangular pulses centered at 1061.8 nm and 1068.8 nm are similar to each other. Moreover, the dual-wavelength switchable operation was also realized by properly rotating the polarization controllers (PCs). The demonstration of the dual-wavelength rectangular pulses from a YDFL would open some applications for fields such as spectroscopy, biomedicine and sensing research.

Femtosecond pulse generation from a topological insulator mode-locked fiber laser.

We reported on the generation of femtosecond pulse in a fiber ring laser by using a polyvinyl alcohol (PVA)-based topological insulator (TI), Bi2Se3 saturable absorber (SA). The PVA-TI composite has a low saturable optical intensity of 12 MW/cm2 and a modulation depth of ~3.9%. By incorporating the fabricated PVA-TISA into a fiber laser, mode-locking operation could be achieved at a low pump threshold of 25 mW. After an optimization of the cavity parameters, optical pulse with ~660 fs centered at 1557.5 nm wavelength had been generated. The experimental results demonstrate that the PVA could be an excellent host material for fabricating high-performance TISA, and also indicate that the filmy PVA-TISA is indeed a good candidate for ultrafast saturable absorption device.

Mechanisms predictive of Tibetan Medicine Sophora moorcroftiana alkaloids for treatment of lung cancer based on the network pharmacology and molecular docking.

BACKGROUND: Leguminous Sophora moorcroftiana (SM) is a genuine medicinal material in Tibet. Many research results have reveal the Sophora moorcroftiana alkaloids (SMA), as the main active substance, have a wide range of effects, such as antibacterial, antitumor and antiparasitic effects. However, there are few reports on the inhibition of lung cancer (LC) and its inhibitory mechanism, and the pharmacological mechanism of SMA is still unclear, Therefore, exploring its mechanism of action is of great significance. METHODS: The SMA active components were obtained from the literature database. Whereas the corresponding targets were screened from the PubChem and PharmMapper database, UniProt database were conducted the correction and transformation of UniProt ID on the obtained targets. The GeneCards and OMIM databases identified targets associated with LC. Venny tools obtained the intersection targets of SMA and LC. R language and Cytoscape software constructed the visual of SMA - intersection targets - LC disease network. The intersection targets protein-protein interaction (PPI) network were built by the STRING database. The functions and pathways of the common targets of SMA and LC were enriched by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking And A549 cells vitro experiment were performed to further validate our finding. RESULTS: We obtained six kinds of alkaloids in SM, 635 potential targets for these compounds, and 1,303 genes related to LC. SMA and LC intersection targets was 33, including ALB, CCND1, ESR1, NOTCH1 and AR. GO enrichment indicated that biological process of SMA was mainly involved in the positive regulation of transcription and nitric oxide biosynthetic process, and DNA-templated, etc. Biological functions were mainly involved in transcription factor binding and enzyme binding, etc. Cell components were mainly involved in protein complexes, extracellular exosome, cytoplasm and nuclear chromatin, etc., Which may be associated with its anti-LC effects. KEGG enrichment analysis showed that main pathways involved in the anti-LC effects of SMA, including pathway in cancer, non small-cell lung cancer, p53, PI3K-Akt and FOXO signaling pathways. Molecular docking analyses revealed that the six active compounds had a good binding activity with the main therapeutic targets 2W96, 2CCH and 1O96. Experiments in vitro proved that SMA inhibited the proliferation of LC A549 cells. CONCLUSIONS: Results of the present study, we have successfully revealed the SMA compounds had a multi-target and multi-channel regulatory mechanism in treatment LC, These findings provided a solid theoretical reference of SMA in the clinical treatment of LC.

Opioid receptors mediate enhancement of ACh-induced aorta relaxation by chronic intermittent hypobaric hypoxia.

The present study was designed to investigate the role of opioid receptors in the vasorelaxation effect of chronic intermittent hypobaric hypoxia (CIHH) in thoracic aorta rings and the underlying mechanism in rats. Adult male Sprague-Dawley (SD) rats were randomly divided into 2 groups: CIHH treatment group and control group. The rats in CIHH group were exposed to hypoxia in a hypobaric chamber (simulated 5 000 m altitude) for 28 days, 6 h per day. The rats in control group were kept in the same environment as CIHH rats except no hypoxia exposure. The relaxation of thoracic aorta rings was recorded by organ bath perfusion technique, and expression of opioid receptors was measured by Western blot. Results are shown as follows. (1) The acetylcholine (ACh)-induced endothelium-dependent relaxation of thoracic aorta in CIHH rats was increased obviously in a concentration-dependent manner compared with that in control rats (P < 0.05). (2) This enhancement of ACh-induced relaxation in CIHH rats was abolished by naloxone, a non-specific opioid receptor blocker (P < 0.05). (3) The expressions of δ, µ and κ opioid receptors in thoracic aorta of CIHH rats were up-regulated compared with those in control rats (P < 0.05). (4) The enhancement of CIHH on relaxation of thoracic aorta was reversed by glibenclamide, an ATP-sensitive potassium channel (KATP) blocker (P < 0.05). The results suggest that opioid receptors are involved in CIHH-enhanced ACh-induced vasorelaxation of thoracic aorta through KATP channel pathways.

Confinement effect of network-structured carbon dots/cellulose nanofiber/magnesium hydroxide for enhanced heavy metal ions capture and immobilization.

To solve pollution problem of heavy metal ions (HMIs) and recover them for sustainable development, a high-efficient-sewage treatment agent, carbon dots/cellulose nanofiber/Mg(OH)2 (CCMg), has been fabricated via a simple hydrothermal method. A variety of characterizations show that cellulose nanofiber (CNF) formed a layered-net structure. Hexagonal Mg(OH)2 flakes of about 100 nm has been attached on CNF. Carbon dots (CDs) around 10-20 nm in size were produced from CNF and distributed along CNF. The extraordinary structural feature endows CCMg with high removal performance towards HMIs. The up-taken capacities reach 992.8 and 667.3 mg g-1 for Cd2+ and Cu2+, respectively. The composite bears excellent durability in treating wastewater. Notably, the qualification of the drinking water can be satisfied while applying CCMg to handle Cu2+ wastewater. The mechanism of removal process has been proposed. Practically, Cd2+/Cu2+ ions were immobilized by CNF due to the space confinement effect. It achieves the facile separation and recovery of HMIs from the sewage, and more importantly, eliminates the risk of secondary contamination.

Enhanced Charge Balance for Efficient Electroluminescence from Cesium Copper Halides.

Cesium copper halides have the advantages of high photoluminescence quantum efficiency and good stability, making them attractive for replacing toxic lead halides in the field of perovskite light-emitting diodes (LEDs). However, due to their shallow conduction band and the lack of electron transport layers compatible with it, it remains a great challenge to achieve charge balance in LED devices. This drawback manifests as the accumulation of holes at the interface between the emitting layer and electron transport layer, resulting in nonradiative recombination. Here, we demonstrate an effective approach to address this issue by suppressing hole injection, which is realized through modification of the poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) layer with polyethylenimine. This leads to cesium-copper-halide LEDs with a high external quantum efficiency of 5.6%, representing an advance in device architecture for efficient electroluminescence from cesium copper halides.

Safety and immunogenicity of a mosaic vaccine booster against Omicron and other SARS-CoV-2 variants: a randomized phase 2 trial.

An ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate, named NVSI-06-09, as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. Between May 25 and 30, 2022, 516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group. Interim results showed a similar safety profile between two booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 post-booster, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV. Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants, including Omicron and its sub-lineages.

Prolyl hydroxylase domain protein 2 regulates the intracellular cyclic AMP level in cardiomyocytes through its interaction with phosphodiesterase 4D.

Cyclic adenosine 3',5'-monophosphate (cAMP), which is synthesized by adenylyl cyclase (AC) and degraded by phosphodiesterase (PDE), plays crucial roles in the regulation of multiple cellular functions and physiological processes. Prolyl hydroxylase domain (PHD) proteins, which belong to a family of dioxygenases that function as oxygen sensors through their hydroxylation activity, have been implicated in multiple signaling pathways. Here, we aimed to determine whether PHD played a role in regulating intracellular cAMP level in cardiomyocytes. Through the overexpression/knockdown of the PHD gene and the measurement of the cAMP content, we found that PHD2, but not PHD1 or PHD3, acts as a regulator of intracellular cAMP. In neonatal rat cardiomyocytes and H9c2 cells, the overexpression of PHD2 increased the intracellular cAMP level, whereas the PHD2 knockdown reduced it. There was no alteration in the AC expression or activity in cells that overexpressed or downregulated PHD2. The overexpression of PHD2 decreased both the protein expression and the activity of phosphodiesterase 4D (PDE4D), whereas the PHD2 knockdown increased the PDE4D expression and activity. Co-immunoprecipitation experiments revealed a direct binding between PHD2 and PDE4D and liquid chromatography-tandem mass spectrometry analyses identified the specific hydroxylation sites on PDE4D. In conclusion, PHD2 may directly interact with PDE4D to function as a novel regulator of the intracellular cAMP levels in cardiomyocytes.