Printing 3D Metallic Structures in Porous Matrix.

The fabrication of metallic micro/nanostructures has great potential for advancing optoelectronic microdevices. Over the past decade, femtosecond laser direct writing (FsLDW) technology has played a crucial role in driving progress in this field. In this study, silica gel glass is used as a supporting medium, and FsLDW is employed to reduce gold and palladium ions using 7-Diethylamino-3-thenoylcoumarin (DETC) as a two-photon sensitizer, enabling the printing of conductive multilayered and 3D metallic structures. How the pore size of the silica gel glass affects the electrical conductivity of printed metal wires is systematically examined. This 3D printing method is versatile and offers expanded opportunities for applying metallic micro/nanostructures in optoelectronic devices.

Identification of overlay differentially expressed genes in both rats and goats with blast lung injury through comparative transcriptomics.

PURPOSE: To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment. METHODS: This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay. RESULTS: Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation. CONCLUSIONS: Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.

Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer.

BACKGROUND: Injectable luteinizing hormone-releasing hormone agonists (e.g., leuprolide) are the standard agents for achieving androgen deprivation for prostate cancer despite the initial testosterone surge and delay in therapeutic effect. The efficacy and safety of relugolix, an oral gonadotropin-releasing hormone antagonist, as compared with those of leuprolide are not known. METHODS: In this phase 3 trial, we randomly assigned patients with advanced prostate cancer, in a 2:1 ratio, to receive relugolix (120 mg orally once daily) or leuprolide (injections every 3 months) for 48 weeks. The primary end point was sustained testosterone suppression to castrate levels (<50 ng per deciliter) through 48 weeks. Secondary end points included noninferiority with respect to the primary end point, castrate levels of testosterone on day 4, and profound castrate levels (<20 ng per deciliter) on day 15. Testosterone recovery was evaluated in a subgroup of patients. RESULTS: A total of 622 patients received relugolix and 308 received leuprolide. Of men who received relugolix, 96.7% (95% confidence interval [CI], 94.9 to 97.9) maintained castration through 48 weeks, as compared with 88.8% (95% CI, 84.6 to 91.8) of men receiving leuprolide. The difference of 7.9 percentage points (95% CI, 4.1 to 11.8) showed noninferiority and superiority of relugolix (P<0.001 for superiority). All other key secondary end points showed superiority of relugolix over leuprolide (P<0.001). The percentage of patients with castrate levels of testosterone on day 4 was 56.0% with relugolix and 0% with leuprolide. In the subgroup of 184 patients followed for testosterone recovery, the mean testosterone levels 90 days after treatment discontinuation were 288.4 ng per deciliter in the relugolix group and 58.6 ng per deciliter in the leuprolide group. Among all the patients, the incidence of major adverse cardiovascular events was 2.9% in the relugolix group and 6.2% in the leuprolide group (hazard ratio, 0.46; 95% CI, 0.24 to 0.88). CONCLUSIONS: In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events. (Funded by Myovant Sciences; HERO ClinicalTrials.gov number, NCT03085095.).

Potential-Resolved Electrochemiluminescence Multiplex Immunoassay for Florfenicol and Chloramphenicol in a Single Sample.

The simultaneous detection of multiple antibiotic residues in food is of great significance for food safety. In this work, a novel dual-potential electrochemiluminescence (ECL) immunoassay was designed for the simultaneous detection of chloramphenicol and fluorfenicol residues in food. Ru@MOF was used as an anodic probe, and SnS2 QDs-PEI-Au-MoS2 was used as a cathodic probe. Notably, the coreactant for both luminophores was K2S2O8, avoiding interactions caused by different kinds of coreactants. Au nanoparticles functionalized with a nitrogen- and sulfur-doped graphene oxide-modified glassy carbon electrode to improve the electron transfer efficiency and provide a larger surface area for immobilization of antigen. The linear range for the detection of florfenicol was determined to be 0.1-1000 ng mL-1 with a detection limit of 0.03 ng mL-1, and the linear range for the detection of chloramphenicol was 0.01-1000 ng mL-1 with a detection limit of 3.2 pg mL-1 by recording the ECL responses at two different excitation potentials. The proposed immunoassay achieved a more stable recovery in the detection of actual samples and provided a new analytical method for the simultaneous detection of florfenicol and chloramphenicol residues with high sensitivity and specificity.

Electrochemiluminescence resonance energy transfer immunoassay based on a porphyrin metal-organic framework and AuNPs/NSG for the sensitive detection of zearalenone.

In this study, a novel electrochemiluminescence resonance energy transfer (ECL-RET) immunoassay was developed for the first time for the detection of zearalenone (ZEN). A porphyrin metal-organic framework (PCN-222), an emerging porphyrin-based ECL luminophore, was prepared by a simple hydrothermal method using tetrakis(4-carboxyphenyl) porphyrin, which has excellent ECL emission as well as good ECL efficiency. Because the ECL emission spectrum of PCN-222 is highly matched to the absorption spectrum of gold nanoparticle-modified graphene oxide (AuNPs/NSG) nanocomposites, they were used as donor-acceptor counterparts in this work for the ECL-RET strategy. Under optimal conditions, the ECL immunosensor showed a sensitive response to ZEN in a wide detection range, with a linearity of 0.0005-1000 ng mL-1 and a detection limit of 0.15 pg mL-1. In addition, the sensor showed good potential for application in the detection of wheat and corn samples, providing a new approach for the detection of mycotoxin-like contaminants such as ZEN in food grains.

Reproductive Toxicity and Teratogenicity of Fluorene-9-bisphenol on Chinese Medaka (Oryzias sinensis): A Study from Laboratory to Field.

Fluorene-9-bisphenol (BHPF), a bisphenol A (BPA) substitute, has been increasingly used as a material in syntheses of polymers that are widely used in road markings, artificial tracks, coating floors, building paints, etc., increasing the likelihood of BHPF contamination in the aquatic environment due to its release from the products. However, to date, it is unknown whether it may have actual impacts on fish in real environments. In this study, a 105-day exposure experiment of BHPF at various concentrations (0.01, 0.1, 1, and 10 µg/L) on Chinese medaka (Oryzias sinensis) was performed under laboratory conditions and found decreased fecundity, such as lower egg qualities and quantities, retarded oogenesis, and atretic follicles in the fish and deformed eyes and bodies in its F1 generation. Toxico-transcriptome analyses showed that estrogen-responsive genes were significantly suppressed by BHPF, indicating that antagonist properties of BHPF on estrogen receptors might be causes for the decreased fecundity. Field investigations (Beijing) demonstrated that BHPF was detectable in 60% surface waters, with a mean concentration of 10.49 ± 6.33 ng/L, by gas chromatography-mass spectrometry, and similar effects in wild Chinese medaka were also observed, some of which the parameters were found to be obviously correlated with the BHPF levels in corresponding waters.

I/O Efficient Early Bursting Cohesive Subgraph Discovery in Massive Temporal Networks.

Temporal networks are an effective way to encode temporal information into graph data losslessly. Finding the bursting cohesive subgraph (BCS), which accumulates its cohesiveness at the fastest rate, is an important problem in temporal networks. The BCS has a large number of applications, such as representing emergency events in social media, traffic congestion in road networks and epidemic outbreak in communities. Nevertheless, existing methods demand the BCS lasting for a time interval, which neglects the timeliness of the BCS. In this paper, we design an early bursting cohesive subgraph (EBCS) model based on the k-core to enable identifying the burstiness as soon as possible. To find the EBCS, we first construct a time weight graph (TWG) to measure the bursting level by integrating the topological and temporal information. Then, we propose a global search algorithm, called GS-EBCS, which can find the exact EBCS by iteratively removing nodes from the TWG. Further, we propose a local search algorithm, named LS-EBCS, to find the EBCS by first expanding from a seed node until obtaining a candidate k-core and then refining the k-core to the result subgraph in an optimal time complexity. Subsequently, considering the situation that the massive temporal networks cannot be completely put into the memory, we first design an I/O method to build the TWG and then develop I/O efficient global search and local search algorithms, namely I/O-GS and I/O-LS respectively, to find the EBCS under the semi-external model. Extensive experiments, conducted on four real temporal networks, demonstrate the efficiency and effectiveness of our proposed algorithms. For example, on the DBLP dataset, I/O-LS and LS-EBCS have comparable running time, while the maximum memory usage of I/O-LS is only 6.5 MB, which is much smaller than that of LS-EBCS taking 308.7 MB. Supplementary Information: The online version contains supplementary material available at 10.1007/s11390-022-2367-3.

Synthesis of Purine Analogues: Photocatalyst-Free Visible-Light-Enhanced Annulation Approach to Pyrazolo[1,5-a][1,3,5]triazine-2,4-diamines.

A new photocatalyst-free visible-light-enhanced strategy for the synthesis of pyrazolo[1,5-a][1,3,5]triazine-2,4-diamines via the formation of electron donor-acceptor (EDA) complexes is reported. The in situ generated pyrazolthiourea intermediates from 1H-pyrazol-3-amines and isothiocyanates undergo formal [4 + 2] annulation with 1,1,3,3-tetramethylguanidines (TMG) to deliver the corresponding products involved in three C-N bond formations in a one-pot protocol. The formation of EDA complex from pyrazolthiourea and TMG is confirmed by UV-vis spectroscopy and 1H NMR experiments. Moreover, this mild reaction proceeds in the absence of any external transition metals, oxidants, bases, and ligands. This efficient methodology for the synthesis of purine analogues pyrazolo[1,5-a][1,3,5]triazine-2,4-diamines provides potential synthetic applications in the field of drug research and development.

Metal- and Oxidant-Free Green Three-Component Desulfurization and Deamination Condensation Approach to Fully Substituted 1H-1,2,4-Triazol-3-amines and Their Photophysical Properties.

A metal- and oxidant-free three-component desulfurization and deamination condensation of amidines, isothiocyanates, and hydrazines for the synthesis of structurally diverse fully substituted 1H-1,2,4-triazol-3-amines is described. The reaction proceeds without the requirement of any external catalysts, metals, ligands, or oxidants. This [2 + 1 + 2] cyclization strategy involves C-N and C-S bond cleavage and the formation of new C-N bonds in one pot. This transformation provides a series of full substituted 1H-1,2,4-triazol-3-amines with advantages of a broad substrates scope, mild reaction conditions, environmental friendliness, and easy gram-scale applications. The fluorescence and aggregation-induced emission (AIE) properties of selected products were further tested. These synthesized 1H-1,2,4-triazol-3-amines may be worth investigating for further applications in the fields of organic chemistry, medicinal chemistry, and optical materials.

Cytotoxicity and inflammatory effects in human bronchial epithelial cells induced by polycyclic aromatic hydrocarbons mixture.

Polycyclic aromatic hydrocarbons (PAHs) are the most common contaminants in the air pollutants. Inhalation exposure to PAHs could increase the risk of respiratory disease, cardiovascular disease and even cancer. However, the biotoxicity of multi-component PAHs from atmospheric pollutants has been poorly studies. The main topic of this study was to investigate the PAHs mixture, which derived from atmospheric pollutants, induced toxic effects and inflammatory effects on human bronchial epithelial cells in vitro. The results showed that PAHs mixture could decrease the cell viability, increase the apoptosis rate, and induce cell cycle arrest at S-phase. Furthermore, the expression of inflammatory factors IL-1ß and IL-6 were increased and NF-κB signaling pathway was activated in PAHs mixture-treated cells. The findings of this study indicate that PAHs mixture-induced cytotoxicity and inflammation may be related to intracellular ROS generation and to the activated NF-κB signaling pathway.

NF-κB and FosB mediate inflammation and oxidative stress in the blast lung injury of rats exposed to shock waves.

Blast lung injury (BLI) is the major cause of death in explosion-derived shock waves; however, the mechanisms of BLI are not well understood. To identify the time-dependent manner of BLI, a model of lung injury of rats induced by shock waves was established by a fuel air explosive. The model was evaluated by hematoxylin and eosin staining and pathological score. The inflammation and oxidative stress of lung injury were also investigated. The pathological scores of rats' lung injury at 2 h, 24 h, 3 days, and 7 days post-blast were 9.75±2.96, 13.00±1.85, 8.50±1.51, and 4.00±1.41, respectively, which were significantly increased compared with those in the control group (1.13±0.64; P<0.05). The respiratory frequency and pause were increased significantly, while minute expiratory volume, inspiratory time, and inspiratory peak flow rate were decreased in a time-dependent manner at 2 and 24 h post-blast compared with those in the control group. In addition, the expressions of inflammatory factors such as interleukin (IL)-6, IL-8, FosB, and NF-κB were increased significantly at 2 h and peaked at 24 h, which gradually decreased after 3 days and returned to normal in 2 weeks. The levels of total antioxidant capacity, total superoxide dismutase, and glutathione peroxidase were significantly decreased 24 h after the shock wave blast. Conversely, the malondialdehyde level reached the peak at 24 h. These results indicated that inflammatory and oxidative stress induced by shock waves changed significantly in a time-dependent manner, which may be the important factors and novel therapeutic targets for the treatment of BLI.

Molluscicides against the snail-intermediate host of Schistosoma: a review.

Schistosomiasis, a neglected tropical disease (NTD), is one of the most prevalent parasitoses in the World. Certain freshwater snail species are the intermediate host in the life cycle of schistosome species. Controlling snails employing molluscicides is an effective, quick, and convenient intervention strategy to prevent the spread of Schistosoma species in endemic regions. Advances have been made in developing both synthetic molluscicides and molluscicides derived from plants. However, at present, the development of molluscicides is not adapted to the actual demand for snails and schistosoma controlling. We undertake a systematic review of exploitation and application of synthetic molluscicides and molluscicides derived from plants to combat intermediate host snails. The detailed molluscicidal activity, structure-activity relationship, structural feature, and possible mechanism of some molluscicides are also highlighted, which may afford an important reference for the design of new, more effective molluscicides with low environmental impact and realize the aim of controlling schistosome at transmission stages.

A near-infrared phosphorescent iridium(iii) complex for fast and time-resolved detection of cysteine and homocysteine.

Thiol-containing amino acids, cysteine (Cys) and homocysteine (Hcy), play crucial roles in the biosystem; their abnormal contents in the cells are linked to many diseases. Herein, we designed and synthesized a novel near-infrared (NIR) phosphorescent iridium(iii) complex-based probe (FNO1) that can detect Cys and Hcy in real-time in the biosystem. Due to the advantages of the iridium complex, the FNO1 probe had excellent chemical stability and photostability, high luminescence efficiency, and long luminescence lifetime. In addition, the probe showed a fast response, high sensitivity, and low cytotoxicity. As verified by high resolution mass spectra (HR-MS) and density functional theory (DFT) calculations, the detection was achieved through the addition of the α,ß-unsaturated ketone group in FNO1 by the nucleophilic thiol group in Cys and Hcy. Through time-resolved emission spectroscopy (TRES) and in the presence of a strongly fluorescent dye rhodamine B, the FNO1 probe could detect Cys and Hcy due to its long luminescence lifetime (260/197 ns). Finally, owing to its NIR-emitting properties, the FNO1 probe was successfully applied in the imaging of Cys and Hcy in living cells, zebrafish, and mice.

Global gene expression profiling of blast lung injury of goats exposed to shock wave.

PURPOSE: Blast lung injury (BLI) is the most common damage resulted from explosion-derived shock wave in military, terrorism and industrial accidents. However, the molecular mechanisms underlying BLI induced by shock wave are still unclear. METHODS: In this study, a goat BLI model was established by a fuel air explosive power. The key genes involved in were identified. The goats of the experimental group were fixed on the edge of the explosion cloud, while the goats of the control group were 3 km far away from the explosive environment. After successful modeling for 24 h, all the goats were sacrificed and the lung tissue was harvested for histopathological observation and RNA sequencing. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis were performed to identify the main enriched biological functions of differentially expressed genes (DEGs). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the consistency of gene expression. RESULTS: Of the sampled goat lungs, 895 genes were identified to be significantly differentially expressed, and they were involved in 52 significantly enriched GO categories. KEGG analysis revealed that DEGs were highly enriched in 26 pathways, such as cytokine-cytokine receptor interaction, antifolate resistance, arachidonic acid metabolism, amoebiasis and bile secretion, JAK-STAT, and IL-17 signaling pathway. Furthermore, 15 key DEGs involved in the biological processes of BLI were confirmed by qRT-PCR, and the results were consistent with RNA sequencing. CONCLUSION: Gene expression profiling provide a better understanding of the molecular mechanisms of BLI, which will help to set strategy for treating lung injury and preventing secondary lung injury induced by shock wave.

Visible-Light-Promoted Three-Component Coupling Annulation: Synthesis of 2-Iminothiazolidin-4-ones via in Situ Formed Electron Donor-Acceptor Complexes.

A novel and efficient three-component coupling annulation strategy for the synthesis of 2-iminothiazolidin-4-ones from amines, isothiocyanates, and alkyl acetylenedicarboxylates under visible-light irradiation conditions has been demonstrated. In this transformation, the in situ formed photoactive electron donor-acceptor (EDA) complexes facilitate the reaction and smoothly generate the corresponding products with a high adaptability under mild conditions. This protocol provides a cost-efficient and practical route to 2-iminothiazolidin-4-ones and promotes potential applications on the synthetic drugs.

Visible-Light-Catalyzed [3 + 1 + 2] Coupling Annulations for the Synthesis of Unsymmetrical Trisubstituted Amino-1,3,5-triazines.

A visible-light catalyzed [3 + 1 + 2] annulation for the synthesis of unsymmetrical trisubstituted amino-1,3,5-triazines from amidines, isothiocyanates, and 1,1,3,3-tetramethylguanidines has been developed. This method exhibits the advantages of easily available starting materials, insensitive to air and moisture, wide substrate scopes, high step economy, mild, metal- and ligand-free conditions, which has potential applications in the organic, medicinal, and material chemistry.

Photodriven Photocatalyst/Metal-Free Direct C-C/C-N Bond Formation: Synthesis of Indoles via EDA Complexes.

The photodriven direct C-C/C-N bond formation initiated by electron donor-acceptor (EDA) complexes for the synthesis of indoles has been accomplished via [3+2] annulations of secondary arylamines with alkynes using IC4F9 as oxidants in the absence of any photocatalysts and metals. This green transformation exhibits the advantages of operational simplicity, good functional tolerances, and mild reaction conditions. The in situ generated EDA complexes derived from arylamines with alkynes were characterized by UV-vis absorption spectrometry and NMR titration experiments.

G-triplex based molecular beacon with duplex-specific nuclease amplification for the specific detection of microRNA.

High sequence homology among miRNA members challenges miRNA analysis. In this paper, we developed a simple and highly selective method based on a novel G-triplex molecular beacon (MBG3) and duplex-specific nuclease signal amplification (DSNSA) for miRNA detection. Herein, this MBG3 is a label-free molecular beacon with a special G-triplex probe. The excellent controllablity of the G-triplex probe allowed our MBG3 to have a short stem, which protected it from DSN digestion. Therefore, DSN cleavage induced false positive signals in most DSN signal amplification strategies have been minimised efficiently without special modifications. Importantly, the improved recognition ability of MBG3, together with the sensitive substrate selectivity of DSN, makes our novel method suitable for miRNA detection with high selectivity. The signal response of similar miRNA sequences with one-base difference has been reduced from 37% to 8% compared to the traditional linear ssDNA probe-DSN-based method.

Stable and Label-Free Fluorescent Probe Based on G-triplex DNA and Thioflavin T.

G-triplexes have recently been identified as a new kind of DNA structures. They perhaps possess specific biological and chemical functions similar as identified G-quadruplex but can be formed by shorter G-rich sequences with only three G-tracts. However, until now, limited G-triplexes sequences have been reported, which might be due to the fact that their stability is one of the biggest concerns during their functional studies and application research. Herein, we found a G-rich sequence (5'-TGGGTAGGGCGGG-3') which can form a stable G-triplex (Tm ∼ 60 °C) at room temperature. The stable G-triplex can combine with thioflavin T and function as an efficient fluorescence light-up probe. Comparing with the traditional G-quadruplex based probe, this triplex based probe was easy to be controlled and excited. Finally, the probe was successfully applied into constructing a label-free molecular beacon for miRNA detection. Taking advantage of these abilities of the G-triplex based fluorescent probe, the challenges faced during designing G-rich sequences based fluorescent biosensors can be efficiently solved. These findings provide important information for the future application of G-triplex.

Direct Photocatalytic S-H Bond Cyanation with Green "CN" Source.

Herein we report a novel C-S bond cleavage and reconstruction strategy for the synthesis of thiocyanates through direct photocatalytic S-H bond cyanation from thiols and inorganic thiocyanate salts. In our strategy, the unprecedented example of cutting off C-S bond of SCN- to deliver the green "CN" sources is demonstrated. This transformation features nontoxic and inexpensive "CN" sources, available starting materials, metal-/base-/ligand-/peroxide-free, high step economy and mild conditions. It leads to the construction of various thiocyanates and some medicinally and biologically active thiocyanate-containing molecules.