Furan Dearomatization: A Route to Diverse Fluoroalkyl/Aryl Triazoles.

The 5-fluoroalkyl-1,2,3-triazoles, serving as a pivotal element in medicinal chemistry, hold substantial research significance. In this work, we developed a furan dearomatization reaction for the synthesis of various 5-fluoroalkyl-1,2,3-triazoles, which contains -CF3, -CF2H, -CF2CF3, -CF2CF2CF3, -CF2CO2Et, and -C6F5. This methodology relies on the intermolecular [3 + 2] cycloaddition/furan ring-opening triggered by α-fluoroalkyl furfuryl cation with azides to stereoselectively synthesize a series of (E)-fluoroalkyl enone triazoles. The reaction proceeds without metal participation, exhibits excellent substrate tolerance, and has excellent synthetic utility.

Phosphorous nitride dots induced efficient advanced oxidation with intrinsic chemiluminescence for organic pollutant degradation.

In this work, we introduced new metal-free catalysts, phosphorus nitride dots (PNDs), into an environmentally friendly H2O2-SO32- system to generate abundant reactive oxygen species (O2˙-, ˙OH and SO4˙-) with strong intrinsic chemiluminescence (CL). The excellent catalytic ability of PNDs not only improved the degradation efficiency of organic pollutants, but also provided a promising prospect for deeply probing the mechanism of advanced oxidation processes (AOPs) by combining with CL.

Intratumoral injection of norcantharidin liposome emulsion hybrid delivery system amplifies the cancer-fighting effects of oral sorafenib against hepatocellular carcinoma.

Interventional therapies are increasingly used in clinical trials for hepatocellular carcinoma (HCC). Sorafenib is the front-line remedy for HCC, however, chemoresistance occurs immutably and affects the effectiveness of treatment. In a previous study, a norcantharidin liposome emulsion hybrid (NLEH) delivery system for HCC was developed. This study aims to examine the therapeutic effects of the combination of intratumoral injection of NLEH and sorafenib in treating HCC. Sorafenib combined with NLEH activated the apoptosis pathway by synergistically upregulating caspase-9, promoting cytotoxicity, apoptosis (64.57%), and G2/M cell cycle arrest (48.96%). Norcantharidin could alleviate sorafenib resistance by counteracting sorafenib-induced phosphorylation of Akt. Additionally, intratumoral injection of NLEH exhibited a sustained accumulation in the tumor within 24 h and didn't distribute to other major organs. Intratumoral injection of NLEH in combination with oral sorafenib displayed the most potent tumor growth inhibitory effect (77.91%) in vivo. H&E staining results and the indicators of the renal and liver function tests demonstrated the safety of this combination therapy. Overall, these results showed that intratumoral injection of NLEH in combination with oral sorafenib treatment represented a rational potential therapeutic option for HCC.

Europium-Functionalized Graphitic Carbon Nitride for Efficient Chemiluminescence Detection of Singlet Oxygen.

Enhancing the sensitivity and selectivity of chemiluminescence (CL) sensors for detecting chemical species in complex samples poses a significant challenge in nanoparticle surface engineering. Graphitic carbon nitride (CN) shows promise but suffers from weak CL intensity and unknown luminescence mechanisms. In this study, we propose a nitrogen defect strategy to enhance the CL efficiency of europium-functionalized graphitic carbon nitride (Eu-CNNPs). By controlling the dosage of the europium modification, we can adjust the nitrogen defect content to reduce the energy gap and improve the CL performance. Remarkably, Eu-CNNPs with rich nitrogen defects exhibit strong chemiluminescence emission specifically for singlet oxygen (1O2) without responding to other reactive oxygen species (ROS). Building upon this finding, we developed a direct, selective, and sensitive CL sensing platform for 1O2 in PM2.5 and monitored 1O2 production in photosensitizers without interference from metal ions. Through extensive experiments, we attribute the 1O2-driven CL response to the presence of abundant nitrogen defects in the CN material, accelerating electron transfer and yielding a high generation of 1O2. Furthermore, chemiluminescence resonance energy transfer (CRET) between (1O2)2* (1O2 dimeric aggregate) and Eu-CNNPs contributes to strong CL emission. This work provides insights into enhancing the CL performance of CN and offers new possibilities for advancing the practical analysis of nanomaterials using the intriguing mechanism of nitrogen defects.

Modulated oxygen vacancies in europia clusters/black phosphorus induced signal amplification for efficient chemiluminescence sensing.

In this work, we proposed an oxygen vacancy engineering strategy to boost the chemiluminescence (CL) efficiency in europia clusters/black phosphorus quantum dots (Eu2O3/BPQDs), which could dramatically amplify the ClO- CL emission through electron transfer. Accordingly, a sensitive and direct CL sensing platform for hypochlorite and titanium ions was constructed. This work provides a neoteric methodology by modulating the surface state of nanoparticles to boost the CL sensitivity.

Prevalence and Subtype Distribution of Blastocystis in Tibetan Sheep in Qinghai Province, Northwestern China.

Blastocystis is one of the most common intestinal protists in humans and a great number of animals, including sheep and goats. High prevalence and multiple subtypes of Blastocystis have been reported in sheep in several regions of China and elsewhere. However, there is a dearth of knowledge about Blastocystis in Tibetan sheep. A total of 761 fecal samples were collected from Tibetan sheep in seven counties of Qinghai Province, northwestern China, and were examined for the prevalence and subtypes of Blastocystis using molecular technology based on the partial small subunit ribosomal RNA gene of Blastocystis. The overall prevalence of Blastocystis in the investigated Tibetan sheep was 7.5% (57/761) using PCR and DNA Sanger sequencing, and differences in prevalence were observed among the ruminants from the seven counties (P < 0.01), and across four seasons (P < 0.01). Sequence analysis revealed five subtypes (ST14 (57.9%), ST10 (26.3%), ST12 (5.3%), ST21 (5.3%), and ST30 (5.3%)) of Blastocystis sp. in these Tibetan sheep, with ST14 as the predominant subtype. To our knowledge, this is the first report of Blastocystis colonization in Tibetan sheep.

Seasonal distribution of Cryptosporidium spp., Giardia duodenalis and Enterocytozoon bieneusi in Tibetan sheep in Qinghai, China.

BACKGROUND: Cryptosporidium spp., Giardia duodenalis and Enterocytozoon bieneusi can cause important intestinal diseases in ruminants. However, data on the distribution of these three protozoan pathogens in Tibetan sheep are limited. METHODS: We collected 761 fecal samples from Tibetan sheep across four seasons in Qinghai Province, China, and screened the samples for Cryptosporidium spp., G. duodenalis and E. bieneusi using PCR-based sequence analysis of the genes encoding 18S ribosomal RNA, triosephosphate isomerase and the internal transcribed spacer, respectively. RESULTS: The positivity rates of Cryptosporidium spp., G. duodenalis and E. bieneusi in Tibetan sheep were 3.68% (28/761 samples), 1.58% (12/761) and 6.44% (49/761), respectively. Four species of Cryptosporidium were identified: C. xiaoi (n = 13 samples), C. ubiquitum (n = 8), C. bovis (n = 6) and C. ryanae (n = 1). Two G. duodenalis assemblages, namely the A (n = 2 samples) and E (n = 10) assemblages, were detected. Five zoonotic E. bieneusi genotypes were found: BEB6 (n = 21 samples), COS-I (n = 14), CHS3 (n = 11) and CGS1 (n = 2) from group 2, and PIGEBITS5 (n = 1) from group 1. Geographic differences in the distribution of E. bieneusi, and seasonal differences for all the three protozoan pathogens were noted. CONCLUSIONS: Our results elucidate the prevalence and genetic diversity of these three pathogens in Tibetan sheep across different regions and seasons, including zoonotic pathogens such as C. ubiquitum, C. ryanae, G. duodenalis assemblage A and five genotypes of E. bieneusi.

Study on the potential mechanism of the active components in YiYiFuZi powder in homotherapy for hetropathy of coronary heart disease and rheumatoid arthritis.

In recent years, the incidence of coronary heart disease and rheumatoid arthritis has been increasing, which has become a common public health problem worldwide. YiYiFuZi (YYFZ ) powder is a classical traditional Chinese prescription, which is commonly used to treat metabolic diseases such as rheumatoid arthritis, with an ideal curative effect, but the therapeutic mechanism is still unclear. In this study, from the perspective of clinical metabolomics, combined with network pharmacology, we sought the comorbidity mechanism and key targets of coronary heart disease and rheumatoid arthritis and the mechanism by which YYFZ powder exerts therapeutic effects, combined with molecular docking and atomic force microscopy to determine the effective components, and found that the higenamine and steroid components in YYFZ powder can bind acid sphingomyelinase enzymes to affect the sphingolipid pathway to produce therapeutic effects, which can bind to sugars existing as a glycoside.

Dual Roles of Azide: Dearomative Dimerization of Furfuryl Azides.

A dearomative dimerization of furfuryl azides for the construction of furfuryl triazoles is developed. As a rare leaving group, azide is capable of initiating the generation of a furfuryl cation under the Lewis acid-catalyzed conditions, followed by reacting with the other azide to realize an intermolecular [3 + 2] cycloaddition/furan ring-opening cascade. By extending the reaction time, a fragmentation reaction of resulting furfuryl triazoles occurs to afford 1H-triazoles in high yield. Control studies demonstrated that key furfuryl cations also can be obtained from furfuryl triazoles. Furthermore, a chemoselective cross-cycloaddition can be achieved between furfuryl azides and a benzyl azide.

The construction of phosphonate triazolyl by copper(II)-catalyzed furan dearomatized [3 + 2] cycloaddition.

Triazole phosphonates are valuable structural motifs in chemical biology and the subject of growing recent interest. A novel methodology to synthesize triazolyl phosphonates starting from furfuryl phosphonate alcohols and organo-azides was developed. This method involved an intermolecular copper-catalyzed dearomatized [3 + 2] cycloaddition/furan ring-opening cascade reaction. A strategy involving a three-component reaction was realized for quick access to triazole phosphonates.

Europium functionalized black phosphorus quantum dots as a CRET platform for synergistically enhanced chemiluminescence.

In this work, we synthesize stable europium ion modified black phosphorus quantum dots (Eu-BPQDs) using a microwave irradiation technique, which can react with organic amines exhibiting unique chemiluminescence (CL). The mechanism of the Eu-BPQDs/organic amines CL system accounting for the efficient CRET is induced by the chelation of organic amines with the surface functionalized europium.

Kinsenoside attenuates liver fibro-inflammation by suppressing dendritic cells via the PI3K-AKT-FoxO1 pathway.

Kinsenoside (KD) exhibits anti-inflammatory and immunosuppressive effects. Dendritic cells (DCs) are critical regulators of the pathologic inflammatory milieu in liver fibrosis (LF). Herein, we explored whether and how KD repressed development of LF via DC regulation and verified the pathway involved in the process. Given our analysis, both KD and adoptive transfer of KD-conditioned DCs conspicuously reduced hepatic histopathological damage, proinflammatory cytokine release and extracellular matrix deposition in CCl4-induced LF mice. Of note, KD restrained the LF-driven rise in CD86, MHC-II, and CCR7 levels and, simultaneously, upregulated PD-L1 expression on DCs specifically, which blocked CD8+T cell activation. Additionally, KD reduced DC glycolysis, maintained DCs immature, accompanied by IL-12 decrease in DCs. Inhibiting DC function by KD disturbed the communication of DCs and HSCs with the expression or secretion of α-SMA and Col-I declined in the liver. Mechanistically, KD suppressed the phosphorylation of PI3K-AKT driven by LF or PI3K agonist, followed by enhanced nuclear transport of FoxO1 and upregulated interaction of FoxO1 with the PD-L1 promoter in DCs. PI3K inhibitor or si-IL-12 acting on DC could relieve LF, HSC activation and diminish the effect of KD. In conclusion, KD suppressed DC maturation with promoted PD-L1 expression via PI3K-AKT-FoxO1 and decreased IL-12 secretion, which blocked activation of CD8+T cells and HSCs, thereby alleviating liver injury and fibro-inflammation in LF.

Regenerating islet-derived protein 3 gamma (Reg3g) ameliorates tacrolimus-induced pancreatic ß-cell dysfunction in mice by restoring mitochondrial function.

BACKGROUND AND PURPOSE: Tacrolimus a first-line medication used after transplantation can induce ß-cell dysfunction, causing new-onset diabetes mellitus (NODM). Regenerating islet-derived protein 3 gamma (Reg3g), a member of the pancreatic regenerative gene family, has been reported to improve type 1 diabetes by promoting ß-cell regeneration. We aim to investigate the role of Reg3g in reversing tacrolimus-induced ß-cell dysfunction and NODM in mice. EXPERIMENTAL APPROACH: Circulating REG3A (the human homologue of mouse Reg3g) in heart transplantation patients treated with tacrolimus was detected. The glucose-stimulated insulin secretion and mitochondrial functions, including mitochondria membrane potential (MMP), mitochondria calcium, ATP production, oxygen consumption rate and mitochondrial morphology were investigated in ß-cells. Additionally, effects of Reg3g on tacrolimus-induced NODM in mice were analysed. KEY RESULTS: Circulating REG3A level in heart transplantation patients with NODM significantly decreased compared with those without diabetes. Tacrolimus down-regulated Reg3g via inhibiting STAT3-mediated transcription activation. Moreover, Reg3g restored glucose-stimulated insulin secretion suppressed by tacrolimus in ß-cells by improving mitochondrial functions, including increased MMP, mitochondria calcium uptake, ATP production, oxygen consumption rate and contributing to an intact mitochondrial morphology. Mechanistically, Reg3g increased accumulation of pSTAT3(Ser727) in mitochondria by activating ERK1/2-STAT3 signalling pathway, leading to restoration of tacrolimus-induced mitochondrial impairment. Reg3g overexpression also effectively mitigated tacrolimus-induced NODM in mice. CONCLUSION AND IMPLICATIONS: Reg3g can significantly ameliorate tacrolimus-induced ß-cell dysfunction by restoring mitochondrial function in a pSTAT3(Ser727)-dependent manner. Our observations identify a novel Reg3g-mediated mechanism that is involved in tacrolimus-induced NODM and establish the novel role of Reg3g in reversing tacrolimus-induced ß-cell dysfunction.

Hemecitones A and B: two phenanthrenes with cytotoxicity from Hemerocallis fulva (L.) L.

Two new phenanthrenes, Hemecitones A and B, were isolated from Hemerocallis fulva (L.) L. Their structures were determined by UV, IR, HR-ESI-MS, 1D and 2D NMR analysis. The in vitro cytotoxic activities of compounds 1 and 2 were studied against breast carcinoma MDA-MB-231, hepatocellular carcinoma HepG2 and lung carcinoma A549 cell lines. And compounds 1 and 2 exhibited anti-proliferative effects against these least one of the three types of cell lines with IC50 ranging from 12.57 ± 2.34 to 31.22 ± 1.36 µM.[Formula: see text].

Taxonomic description of Pseudomonas rhizovicinus sp. nov., isolated from the rhizosphere of a desert shrub Haloxylon ammodendron.

A Gram-negative aerobic bacterium, strain M30-35 T, was isolated from the rhizosphere of Haloxylon ammodendron in Tengger desert, Gansu province, northwest China. Our previous research indicated that strain M30-35 T can promote the growth of ryegrass (Lolium perenne L.). In this study, strain M30-35 T was subjected to a polyphasic taxonomic study. Phylogenetic analysis of the 16S rRNA gene and two other housekeeping genes (gyrB, rpoD) showed that strain M30-35 T is a member of Pseudomonas anguilliseptica group. The average nucleotide identity (ANI) scores for strains KMM 3042 T and FR1439T were 76.5% and 83.7%, respectively, and DNA-DNA hybridization (DDH) were 21.6% and 26.6%, respectively, and the rates were less than the threshold range for species determination. The dominant cellular fatty acids of strain M30-35 T were C16:0 (22.7%), summed feature 3 (C16:1ω7c and/or C16:1ω6c; 18.5%), summed feature 8 (C18:1ω7c and/or C18:1ω6c; 23.1%). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phospholipid and aminophospholipid and the predominant respiratory quinone was ubiquinone (Q9). On the basis of above data, it can be concluded that strain M30-35 T represents a novel species in the genus Pseudomonas, for which the name Pseudomonas rhizovicinus sp. nov. is proposed. The type strain is M30-35 T (= MCCC 1K03247T = KCTC 52664 T).

Manganese-Catalyzed Achmatowicz Rearrangement Using Green Oxidant H2O2.

Oxidation reactions have been extensively studied in the context of the transformations of biomass-derived furans. However, in contrast to the vast literature on utilizing the stoichiometric oxidants, such as m-CPBA and NBS, catalytic methods for the oxidative furan-recyclizations remain scarcely investigated. Given this, we report a means of manganese-catalyzed oxidations of furan with low loading, achieving the Achmatowicz rearrangement in the presence of hydrogen peroxide as an environmentally benign oxidant under mild conditions with wide functional group compatibility.

Dual Passivation of Perovskite and SnO2 for High-Efficiency MAPbI3 Perovskite Solar Cells.

So far, most techniques for modifying perovskite solar cells (PSCs) focus on either the perovskite or electron transport layer (ETL). For the sake of comprehensively improving device performance, a dual-functional method of simultaneously passivating trap defects in both the perovskite and ETL films is proposed that utilizes guidable transfer of Eu3+ in SnO2 to perovskite. Europium ions are distributed throughout the SnO2 film during the formation process of SnO2, and they can diffuse directionally through the SnO2/perovskite interface into the perovskite, while most of the europium ions remain at the interface. Under the synergistic effect of distributed Eu3+ in the SnO2 and aggregated Eu3+ at the interface, the electron mobilities of ETLs are evidently improved. Meanwhile, diffused Eu3+ ions passivate the perovskite to reduce trap densities at the grain boundaries, which can dramatically elevate the open-circuit voltage (V oc) of PSCs. Finally, the mainly PSCs coated on SnO2:Eu3+ ETL achieve a power conversion efficiency of 20.14%. Moreover, an unsealed device degrades by only 13% after exposure to ambient atmosphere for 84 days.

First Detection and Molecular Identification of Entamoeba in Yaks from China.

BACKGROUND: Yak, a predominant livestock of plateau areas, is known as a host to many parasites. And the genus Entamoeba, the third-common cause of the mortality worldwide from parasitic diseases, was discovered in yaks once. METHODS: We investigated the distribution and species of Entamoeba spp. from yaks in Qinghai province, northwestern China, by collecting 1027 yak fecal samples. All samples were divided according to seven geographical sites, four seasons, and two age groups of yaks. After extracting DNA, polymerase chain reaction (PCR) was performed to amplify the 18S rRNA gene, and sequences were analyzed with phylogenetic method. RESULTS: We observed an overall Entamoeba positive rate of 36.32% (373/1027) in yaks from Qinghai province. The common species included Entamoeba bovis (284/373), Entamoeba sp. MG107/BEL (79/373), Entamoeba sp. ribosomal lineage (RL) two (8/373), and Entamoeba sp. RL9 (2/373). According to the result of statistical analysis, Entamoeba infection rate was the highest in summer and significantly differed from that observed during other seasons (P < 0.05). The yaks from Golog had the highest prevalence of Entamoeba among all geographical origins in Qinghai province (P < 0.05). However, no significant difference was observed (P > 0.05) among different age groups, as evident from a positive rate of 39.58% in ≤ 6-month and 36.16% in > 6-month yaks. CONCLUSION: These results indicate the prevalence and predominant species of Entamoeba in yaks. To our knowledge, this is the first study to report E. bovis, Entamoeba sp. RL2, and Entamoeba sp. RL9 in Chinese yaks.

Knee Joint Swelling at Presentation: A Case of Pediatric Crohn Disease With a TNFAIP3 Mutation.

Crohn disease (CD) is a chronic inflammatory disease, and its incidence in children is rising. Despite extensive reports and investigations, the pathogenesis of CD has not been clearly elucidated, particularly in regard to triggering factors. A genetic predisposition is considered important when investigating the mechanism leading to CD, and the discovery of new CD-associated genes has increased our understanding of its immunopathogenesis and improved the efficacy of its treatment of CD. Early detection and treatment (eg, as children) with gene-based precision therapy can effectively prevent complications related to CD. In this case, a Chinese Han boy with CD associated with a mutation of tumor necrosis factor α-induced protein 3 was treated with recombinant human tumor necrosis factor-a receptor II:IgG Fc fusion protein. We suspected the boy had CD because of chronic abdominal pain, aphthous stomatitis, moderate anemia, a high erythrocyte sedimentation rate (36-79 mm/h), multiple intestinal ulcers, knee joint swelling, and a tumor necrosis factor α-induced protein 3 mutation. After total enteral nutrition and hormone therapy for 5 months, his abdominal pain and joint symptoms did not improve, so we started gene-based precision therapy with recombinant human tumor necrosis factor-a receptor II: IgG Fc fusion protein, which may play an important role in restricting TNF-α-induced NF-κB signaling. After 3 weeks, inflammation indicators were within the normal range, and multiple ulcers and joint symptoms were relieved. The present case demonstrates a safe therapeutic schedule that leads to rapid improvements in the clinical and biochemical status of patients with CD.