Functional Identification of Malus halliana MhbZIP23 Gene Demonstrates That It Enhances Saline-Alkali Stress Tolerance in Arabidopsis thaliana.

Saline-alkali stress is a significant abiotic stress that restricts plant growth globally. Basic region leucine zipper (bZIP) transcription factor proteins are widely involved in plants in response to abiotic stress such as saline-alkali stress. Based on transcriptome and quantitative real-time PCR (qRT-PCR), we found that the MhbZIP23 gene could respond to saline-alkali stress. Despite this discovery, the underlying mechanism by which the MhbZIP23 transcription factor responds to saline-alkaline stress remains unexplored. To address this gap in knowledge, we successfully cloned the MhbZIP23 (MD05G1121500) gene from Malus halliana for heterologous expression in Arabidopsis thaliana, facilitating the investigation of its functional role in stress response. Compared to the wild type (WT), Arabidopsis plants demonstrated enhanced growth and a lower degree of wilting when subjected to saline-alkali stress. Furthermore, several physiological indices of the plants altered under such stress conditions. The transgenic Arabidopsis plants (OE-5, 6, and 8), which grew normally, exhibited a higher chlorophyll content and had greater root length in comparison to the control check (CK). MhbZIP23 effectively regulated the levels of the osmoregulatory substance proline (Pro), enhanced the activities of antioxidant enzymes such as peroxidase (POD) and superoxide dismutase (SOD), and reduced the levels of malondialdehyde (MDA) and relative conductivity (REC). These actions improved the ability of plant cells in transgenic Arabidopsis to counteract ROS, as evidenced by the decreased accumulation of O2- and hydrogen peroxide (H2O2). In summary, the MhbZIP23 gene demonstrated effectiveness in alleviating saline-alkali stress in M. halliana, presenting itself as an outstanding resistance gene for apples to combat saline-alkali stress.

Rapid Detection of Total Petroleum Hydrocarbons in Soil Using Advanced Fluorescence Imaging Techniques.

Chemical methods for measuring soil organic content are often slow and yield inaccurate results due to significant errors. Simple summation of components may not accurately determine total organic content. In contrast, fluorescence imaging techniques offer rapid, in situ monitoring without complex pretreatment and demonstrate rapid and accurate assessment of soil organic content. Utilizing a soil organic pollutant fluorescence imaging in situ monitoring system that we independently developed, we conducted laboratory experiments to explore methods for acquiring fluorescence signals of petroleum hydrocarbons in soil and extracting image features. We used this monitoring system to obtain fluorescence images of crude oil in standard soil (soil properties are shown in Table S1) samples at concentrations ranging from 0 to 100 g/kg, and the coefficient of determination of the total amount inversion model reached 0.999. Simultaneously, we applied the system to a deserted petroleum storage area, and the relative standard deviation values of 16 of the 18 groups of tests were less than 1%, indicating that the monitoring system is highly stable when applied in the field. This study provides both theoretical foundation and technical support for the rapid and nondestructive detection of total petroleum hydrocarbons in soil at field sites.

Da-Chai-Hu-Tang Formula inhibits the progression and metastasis in HepG2 cells through modulation of the PI3K/AKT/STAT3-induced cell cycle arrest and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Da-Chai-Hu-Tang (DCHT), a Chinese traditional herbal compound, has been utilized for the treatment of Hepatic diseases in China for over 1800 years. The DCHT formula contains eight herbals: Bupleurum chinense DC. (chaihu), Scutellaria baicalensis Georgi (huangqin), Paeonia lactiflora Pall. (baishao), Pinellia ternata (Thunb.) Makino (banxia), Rheum officinale Baill. (dahuang), Citrus × aurantium L. (zhishi), Zingiber officinale Roscoe (shengjiang), Ziziphus jujuba Mill. (dazao). Clinical studies have demonstrated the effectiveness of DCHT in hepatocellular carcinoma (HCC) and its ability to enhance the immunity of patients with hepatocellular carcinoma. A total of 20 Chinese articles have been published on the use of DCHT in treating HCC. AIM OF THE STUDY: The study aimed to validate the effect of DCHT in HCC cells and to identify related targets (TP53, AKT1, BCL2, STAT3) in treating HCC by DCHT in vitro experiments. MATERIALS AND METHODS: Cell proliferation and migration were investigated in vitro. Flow cytometry analysis was used to evaluate the cell cycle and apoptosis. Apoptotic bodies in HepG2 cells were observed using a confocal microscope. Biochemical detection was employed to analyze LDH release, MDA levels, and SOD levels. Bioinformatics analysis was used to predict core targets between DCHT and HCC, as well as potential signaling pathways. The protein levels of metastasis-associated, apoptosis, and PI3K, AKT, p-AKT, and STAT3 were further determined through Western blotting. RESULTS: Following treatment with DCHT, the inhibition of viability, migration, and G2/M arrest was observed in HepG2 cells. Flow cytometry analysis and Morphological apoptosis studies provided evidence that DCHT could induce apoptosis in HepG2 cells. Biochemical detection revealed that DCHT could increase LDH release and the level of MDA, and inhibit the viability of the SOD. Bioinformatics analysis identified key targets such as TP53, AKT1, BCL2, STAT3. The PI3K/AKT/STAT3 signaling pathway emerged as a critical pathway in the KEGG enrichment analysis. Western blotting results indicated that DCHT could enhance the expression of E-cadherin, p53, and Bax, while reducing the content of N-cadherin, Bcl-2, PI3K, p-AKT, AKT1, and STAT3. CONCLUSIONS: The results proved that DCHT could inhibit the progression and metastasis of HCC by regulating the expression of E-cadherin, N-cadherin, p53, Bax, Bcl-2, PI3K, p-AKT, AKT, and STAT3 through the PI3K/AKT/STAT3 signaling pathway.

[Pseudo-targeted metabolomics for differential components of Rhei Radix et Rhizoma from three plant species].

Rhei Radix et Rhizoma is common traditional Chinese medicine with multiple original plants. The content and proportion of the active components in Rhei Radix et Rhizoma from different plant species were compared to accurately evaluate the medicine qua-lity and provide a theoretical basis for precise use of this medicine in clinical practice. In this study, fresh Rhei Radix et Rhizoma samples were collected from the four-year-old plants of Rheum palmatum, R. tanguticum, and R. officinale. The relative content of 220 anthraquinones, anthrones, and tannins in the samples were determined by pseudo-targeted metabolomics, and the differential components were screened by multivariate statistical methods. The principal component analysis classified the samples into three clusters according to the original plants. The orthogonal partial least squares-discriminant analysis(OPLS-DA) screened out 117 differential components, including 8 free anthraquinones, 18 anthraquinone glycosides, 80 anthrones, and 11 tannins. Twenty-eight components had the highest content in R. tanguticum, mainly including sennosides, anthraquinone glycosides, and procyanidins. Thirty-five components showed the highest content in R. officinale, mainly including free anthraquinones and catechines. Fifty-four components showed the highest content in R. palmatum, mainly including dianthrones, while the structures of most of them cannot be determined temporarily. The content distribution of differential components in the three original plants indicates that R. tanguticum has the strongest effect of purging, while R. officinale has the strongest effect of clearing heat and purging fire, and both have stronger effects of resolvong stasis and dredging meridians than R. palmatum.

Effects of CYP2D6 gene polymorphism on plasma concentration and therapeutic effect of olanzapine.

This study aimed to evaluate the relationship between gene polymorphisms of metabolic enzymes, particularly the CYP2D6 gene, and the plasma concentration of olanzapine, as well as treatment response in patients with chronic schizophrenia. We recruited olanzapine-treated patients and examined their plasma olanzapine levels. Additionally, a common mutation site within each of the nine exons of the full-length CYP2D6 sequence was assayed. The Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, and Overall Clinical Impression were used to assess schizophrenic symptoms, whereas the Barnes Akathisia Scale and Extrapyramidal Symptom Rating Scale were used to evaluate adverse effects. The results showed no significant differences in plasma olanzapine concentrations, treatment response, or the occurrence of adverse effects among different CYP2D6 genotypes. However, an association between olanzapine concentrations and improvement in clinical symptoms and adverse reactions was observed. In conclusion, the CYP2D6 genotype did not significantly impact plasma olanzapine concentrations, treatment response, or the occurrence of adverse effects.

A Load-Adaptive Driving Method for a Quasi-Continuous-Wave Laser Diode.

A quasi-continuous-wave (QCW) laser diode (LD) driver is commonly used to drive diode bars and stacks designed specifically for QCW operations in solid-state lasers. Such drivers are optimized to deliver peak current and voltage pulses to LDs while maintaining low average power levels. As a result, they are widely used in laser processing devices and laser instruments. Traditional high-energy QCW LD drivers primarily use capacitors as energy storage components and pulsed constant-current sources with op-amps and power metal-oxide-semiconductor field-effect transistors (MOSFETs) as their core circuits for generating repeated constant-current pulses. The drawback of this type of driver is that the driver's output voltage needs to be manually adjusted according to the operating voltage of the load before use to maximize driver efficiency while providing a sufficient current. Another drawback is its inability to automatically adjust the output voltage to maintain high efficiency when the load changes during the driver operation. Drastic changes in the load can cause the driver to fail to function properly in extreme cases. Based on the above traditional circuit structure, this study designed a stability compensation circuit and realized a QCW LD driver for driving a GS20 diode stack with a maximum repetition rate of 100 Hz, a constant current of approximately 300 A, a load voltage of approximately 10 V, and a pulse width of approximately 300 µs. In particular, a high-efficiency, load-adaptive driving method was used with the MOSFETs in the critical saturation region (i.e., between the linear and saturated regions), controlling its power loss effectively while achieving maximum output current of the driver. The experiments demonstrated that the driver efficiency could be maintained at more than 80% when the load current varied from 50 to 300 A.

Near-cognate tRNAs increase the efficiency and precision of pseudouridine-mediated readthrough of premature termination codons.

Programmable RNA pseudouridylation has emerged as a new type of RNA base editor to suppress premature termination codons (PTCs) that can lead to truncated and nonfunctional proteins. However, current methods to correct disease-associated PTCs suffer from low efficiency and limited precision. Here we develop RESTART v3, which uses near-cognate tRNAs to improve the readthrough efficiency of pseudouridine-modified PTCs. We show an average of ~5-fold (range: 2.1- to 9.5-fold) higher editing efficiency than RESTART v2 in cultured cells and achieve functional PTC readthrough in disease cell models of cystic fibrosis and Hurler syndrome. Furthermore, RESTART v3 enables accurate incorporation of the original amino acid for nearly half of the PTC sites, considering the naturally occurring frequencies of sense-to-nonsense codons, without affecting normal termination codons. Although off-target sites were detected, we did not observe changes to the coding information or the expression level of transcripts, and the overall natural tRNA abundance remained constant.

Molecular characterization, antibacterial and immunoregulatory activities of liver-expressed antimicrobial peptide 2 in black rockfish, Sebastes schlegelii.

LEAP2 (liver expression antimicrobial peptide 2), is an antimicrobial peptide widely found in vertebrates and mainly expressed in liver. LEAP2 plays a vital role in host innate immunity. In teleosts, a number of LEAP2 homologs have been reported, but their in vivo effects on host defense are still limited. In this study, a LEAP2 homolog (SsLEAP2) was identified from black rockfish, Sebastes schlegelii, and its structure, expression as well as biological functions were analyzed. The results showed that the open reading frame of SsLEAP2 is 300 bp, with a 5'- untranslated region (UTR) of 375 bp and a 3' - UTR of 238 bp. The deduced amino acid sequence of SsLEAP2 shares the highest overall identity (96.97%) with LEAP2 of Sebastes umbrosus. SsLEAP2 possesses conserved LEAP2 features, including a signal peptide sequence, a prodomain and a mature peptide, in which four well-conserved cysteines formed two intrachain disulphide domain. The expression of SsLEAP2 was highest in liver and could be induced by experimental infection with Listonella anguillarum, Edwardsiealla piscicida and Rock bream iridovirus C1 (RBIV-C1). Recombinant SsLEAP2 (rSsLEAP2) purified from Escherichia coli was able to bind with various Gram-positive and Gram-negative bacteria. Further analysis showed that rSsLEAP2 could enhance the respiratory burst activity, and induce the expression of immune genes including interleukin 1-ß (IL-1ß) and serum amyloid A (SAA) in macrophages; additionally, rSsLEAP2 could also promote the proliferation and chemotactic of peripheral blood lymphocytes (PBLs). In vivo experiments indicated that overexpression of SsLEAP2 could inhibit bacterial infection, and increase the expression level of immune genes including IL-1ß, tumor necrosis factor ligand superfamily member 13B (TNF13B) and haptoglobin (HP); conversely, knock down of SsLEAP2 promoted bacterial infection and decreased the expression level of above genes. Taken together, these results suggest that SsLEAP2 is a novel LEAP2 homolog that possesses apparent antibacterial activity and immunoregulatory property, thus plays a critical role in host defense against pathogens invasion.

Germline specific genes increase DNA double-strand break repair and radioresistance in lung adenocarcinoma cells.

In principle, germline cells possess the capability to transmit a nearly unaltered set of genetic material to infinite future generations, whereas somatic cells are limited by strict growth constraints necessary to assure an organism's physical structure and eventual mortality. As the potential to replicate indefinitely is a key feature of cancer, we hypothesized that the activation of a "germline program" in somatic cells can contribute to oncogenesis. Our group recently described over one thousand germline specific genes that can be ectopically expressed in cancer, yet how germline specific processes contribute to the malignant properties of cancer is poorly understood. We here show that the expression of germ cell/cancer (GC) genes correlates with malignancy in lung adenocarcinoma (LUAD). We found that LUAD cells expressing more GC genes can repair DNA double strand breaks more rapidly, show higher rates of proliferation and are more resistant to ionizing radiation, compared to LUAD cells that express fewer GC genes. In particular, we identified the HORMA domain protein regulator TRIP13 to be predominantly responsible for this malignant phenotype, and that TRIP13 inhibition or expression levels affect the response to ionizing radiation and subsequent DNA repair. Our results demonstrate that GC genes are viable targets in oncology, as they induce increased radiation resistance and increased propagation in cancer cells. Because their expression is normally restricted to germline cells, we anticipate that GC gene directed therapeutic options will effectively target cancer, with limited side effects besides (temporary) infertility.

Phosphorus-doped synergy of phase change in heterogeneous catalysts of NiS-NiS2 for efficient electrocatalysis of Pb(II).

A fundamental understanding of the electroanalytical activity of transition metal sulfide electrocatalysts, especially the origin of the electrocatalytic reactivity on the surface sites of heterostructures with multiple crystalline phases, is essential for the design of low-cost and highly efficient nonprecious metal electrocatalysts for further scientific and technological achievements. Herein, we injected P into NiS and occupied the S sites through a doping strategy. The redistributed electronic structure induced the construction of heterostructures, which significantly improved the structure and chemical state of electrochemically inert NiS. The phase-change mechanism between NiS and NiS2 synergistically catalyzes Pb(II), while the P and S sites jointly lose electrons. Moreover, the constructed heterojunction sensor shows the a sensitivity of 83.43 µA µM-1 to Pb(II) with a theoretical limit of detection of 48 nM, as well as excellent stability, reproducibility, and anti-interference ability. The accurate detection in real water further reveals the potential of this sensor for practical applications. This study provides a guiding strategy for improving electrochemically inert materials to design highly active electrocatalytic interfaces, which has important implications for the development of highly efficient electrode-sensitive materials similar to precious metals to achieve accurate electrical analysis.

Biodegradation enhancement of high concentrations formaldehyde waste gas and verification of the metabolic mechanism.

The enhanced effects of formaldehyde biodegradation in a biofilm packing tower are investigated in this study. Three experimental groups were established: a blank control group, a biochar addition group, and a lanthanum addition group. The inlet gas flow rate, the inlet gas concentration, and the structural succession characteristics of the microbial community in the tower were investigated by regular sampling. The intracellular metabolites and key enzymes of the dominant functional bacteria, Pseudomonas P1 and Methylobacterium Q1, in the tower were analyzed. The results indicated that with the biochar addition, the formaldehyde purification efficiency increased significantly from 91.67-94.67 % to 94.12 96.85 %, and the bio-elimination capacity increased with an increase in the inlet gas flow rate from 2.314 to 13.988 mg L-1h-1 to 2.697-15.051 mg L-1h-1. With the addition of lanthanum, the purification efficiency increased significantly from 90.80-93.98 % to 94.36-96.78 %, and the bio-elimination capacity increased with an increase in the inlet gas concentration from 1.099-11.284 mg L-1h-1 to 1.266-11.961 mg L-1h-1. The microbial community structure in the tower changed with system operation, and the formaldehyde degrading functional bacteria formed the dominant bacteria. It was verified that P1 and Q1 metabolized high concentrations of formaldehyde by the serine cycle and the ribulose monophosphate (RuMP) cycle.

A three-channel thermal dissociation cavity ring-down spectrometer for simultaneous measurement of ambient total peroxy nitrates, total alkyl nitrates, and NO2.

A newly constructed thermal dissociation cavity ring-down spectrometer (TD-CRDS) for the simultaneous measurement of ambient total peroxy nitrates (ΣPNs, RO2NO2), total alkyl nitrates (ΣANs, RONO2), and NO2 was presented in this work. ΣPNs and ΣANs were detected as NO2 with the CRDS instrument after thermal dissociation. PNs and ANs completely dissociated at 180 °C and 360 °C, with conversion efficiencies of 96 % and 99 %, respectively. The effects of NO2 and NO on measurement in different temperatures and two types of thermal dissociation inlet (TDI) were further explored. The influence of ambient NO2 and NO on PNs and ANs in the improved TDI (TDI-2) was significantly improved. To further enhance the measurement accuracy, the consistency of the observed NO2 in the three channels was tested, which achieved good agreement. The detection limits of the TD-CRDS instrument for NO2, ΣPNs, and ΣANs were determined as 6.5, 6.8, and 8.6 pptv (10 s, 1σ), respectively. Observations of PNs and ANs were conducted in a suburban site in Hefei, China, from September 2-30, 2021, using the TD-CRDS instrument, and the consecutive time series of PNs and ANs were derived, verifying the capability of the TD-CRDS instrument for continuous field observations of ΣPNs and ΣANs.

Regulation of the integrin αVß3- actin filaments axis in early osteogenic differentiation of human mesenchymal stem cells under cyclic tensile stress.

BACKGROUND: Integrins are closely related to mechanical conduction and play a crucial role in the osteogenesis of human mesenchymal stem cells. Here we wondered whether tensile stress could influence cell differentiation through integrin αVß3. METHODS: We inhibited the function of integrin αVß3 of human mesenchymal stem cells by treating with c(RGDyk). Using cytochalasin D and verteporfin to inhibit polymerization of microfilament and function of nuclear Yes-associated protein (YAP), respectively. For each application, mesenchymal stem cells were loaded by cyclic tensile stress of 10% at 0.5 Hz for 2 h daily. Mesenchymal stem cells were harvested on day 7 post-treatment. Western blotting and quantitative RT-PCR were used to detect the expression of alkaline phosphatase (ALP), RUNX2, ß-actin, integrin αVß3, talin-1, vinculin, FAK, and nuclear YAP. Immunofluorescence staining detected vinculin, actin filaments, and YAP nuclear localization. RESULTS: Cyclic tensile stress could increase the expression of ALP and RUNX2. Inhibition of integrin αVß3 activation led to rearrangement of actin filaments and downregulated the expression of ALP, RUNX2 and promoted YAP nuclear localization. When microfilament polymerization was inhibited, ALP, RUNX2, and nuclear YAP nuclear localization decreased. Inhibition of YAP nuclear localization could reduce the expression of ALP and RUNX2. CONCLUSIONS: Cyclic tensile stress promotes early osteogenesis of human mesenchymal stem cells via the integrin αVß3-actin filaments axis. YAP nuclear localization participates in this process of human mesenchymal stem cells. Video Abstract.

Modulating paired Ir-O-Ir via electronic perturbations of correlated Ir single atoms to overcome catalytic selectivity.

Single-atom catalysts have been extensively utilized for electrocatalysis, in which electronic metal-support interactions are typically employed to stabilize single atoms. However, this neglects the metal-metal interactions of adjacent atoms, which are essential for the fine-tuning of selective sites. Herein, the high-loading of Ir single atoms (Ir SAs) (8.9 wt%) were adjacently accommodated into oxygen vacancy-rich Co3O4 nanosheets (Ir SAs/Co3O4). Electronic perturbations for both Ir single atoms and Co3O4 supports were observed under electronic metal-support and metal-metal interactions, thus generating Ir-O-Co/Ir units. Electrons were transferred from Co and Ir to O atoms, inducing the depletion of 3d/5d states in Co/Ir and the occupation of 2p states in O atoms to stabilize the Ir SAs. Moreover, the O atoms of Ir-O-Ir functioned as the main active sites for the electrocatalysis of As(iii), which reduced the energy barrier for the rate-determining step. This was due to the stronger electronic affinities for intermediates from reduction of As(iii), which were completely distinct from other coordinated O atoms of Co3O4 or IrO2. Consequently, the resultant Ir SAs/Co3O4 exhibited far more robust electrocatalytic activities than IrO2/Co3O4 and Co3O4 in the electrocatalysis of As(iii). Moreover, there was a strong orbital coupling effect between the coordinated O atoms of Ir SAs and the -OH of H3AsO3, thus exhibiting superior selectivity for As(iii) in contrast to other common heavy metal cations. This work offers useful insights into the rational design of intriguing SACs with high selectivity and stability for the electrocatalysis and electrochemical analysis of pollutants on an electronic level.

Multifaceted roles of T cells in obesity and obesity-related complications: A narrative review.

Obesity is characterized by chronic low-grade inflammatory responses in the adipose tissue, accompanied by pronounced insulin resistance and metabolic anomalies. It affects almost all body organs and eventually leads to diseases such as fatty liver disease, type 2 diabetes mellitus, and atherosclerosis. Recently, T cells have emerged as interesting therapeutic targets because the dysfunction of T cells and their cytokines in the adipose tissue is implicated in obesity-induced inflammation and their complicated onset. Although several recent narrative reviews have provided a brief overview of related evidence in this area, they have mainly focused on either obesity-associated T cell metabolism or modulation of T cell activation in obesity. Moreover, at present, no published review has reported on the multifaceted roles of T cells in obesity and obesity-related complications, even though there has been a significant increase in studies on this topic since 2019. Therefore, this narrative review aims to comprehensively summarize current advances in the mechanistic roles of T cells in the development of obesity and its related complications. Further, we aim to discuss relevant drugs for weight loss as well as the contradictory role of T cells in the same disease so as to highlight key findings regarding this topic and provide a valid basis for future treatment strategies.

A China-developed adenovirus vector-based COVID-19 vaccine: review of the development and application of Ad5-nCov.

INTRODUCTION: The global spread of COVID-19 has prompted the development of vaccines. A recombinant adenovirus type-5 vectored COVID-19 vaccine (Ad5-nCoV) developed by Chinese scientists has been authorized for use as a prime and booster dose in China and several other countries. AREAS COVERED: We searched published articles as of 4 May 2023, on PubMed using keywords related to Adenovirus vector, vaccine, and SARS-CoV-2. We reported the progress and outcomes of Ad5-nCov, including vaccine efficacy, safety, immunogenicity based on pre-clinical trials, clinical trials, and real-world studies for primary and booster doses. EXPERT OPINION: Ad5-nCoV is a significant advancement in Chinese vaccine development technology. Evidence from clinical trials and real-world studies has demonstrated well-tolerated, highly immunogenic, and efficacy of Ad5-nCoV in preventing severe/critical COVID-19. Aerosolized Ad5-nCoV, given via a novel route, could elicit mucosal immunity and improve the vaccine efficacy, enhance the production capacity and availability, and reduce the potential negative impact of preexisting antibodies. However, additional research is necessary to evaluate the long-term safety and immunogenicity of Ad5-nCoV, its efficacy against emerging variants, its effectiveness in a real-world context of hybrid immunity, and its cost-effectiveness, particularly with respect to aerosolized Ad5-nCoV.

A Mid-Infrared Quantum Cascade Laser Ultra-Sensitive Trace Formaldehyde Detection System Based on Improved Dual-Incidence Multipass Gas Cell.

Formaldehyde (HCHO) is a tracer of volatile organic compounds (VOCs), and its concentration has gradually decreased with the reduction in VOC emissions in recent years, which puts forward higher requirements for the detection of trace HCHO. Therefore, a quantum cascade laser (QCL) with a central excitation wavelength of 5.68 µm was applied to detect the trace HCHO under an effective absorption optical pathlength of 67 m. An improved, dual-incidence multi-pass cell, with a simple structure and easy adjustment, was designed to further improve the absorption optical pathlength of the gas. The instrument detection sensitivity of 28 pptv (1σ) was achieved within a 40 s response time. The experimental results show that the developed HCHO detection system is almost unaffected by the cross interference of common atmospheric gases and the change of ambient humidity. Additionally, the instrument was successfully deployed in a field campaign, and it delivered results that correlated well with those of a commercial instrument based on continuous wave cavity ring-down spectroscopy (R2 = 0.967), which indicates that the instrument has a good ability to monitor ambient trace HCHO in unattended continuous operation for long periods of time.

Identification, expression pattern and functional characterization of IFN-γ involved in activating JAK-STAT pathway in Sebastes schlegeli.

IFN-γ (interferon gamma) is a critical cytokine in the immune system involved both directly and indirectly in antiviral activity, stimulation of bactericidal activity, antigen presentation and activation of macrophages via the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway. The IFN-γ function is best described in cell defense against intracellular pathogens in mammals, but IFN-γ cytokine-induced metabolic change and its role in anti-infection remain unknown in teleost fish. In this study, a novel IFN-γ (SsIFN-γ) was identified from black rockfish (Sebastes schlegeli) by rapid amplification of cDNA ends (RACE). The open reading frame (ORF) of SsIFN-γ encoded a putative protein of 215 amino acids and shares 60.2%-93.5% overall sequence identities with other teleost IFN-γ. SsIFN-γ was distributed ubiquitously in all the detected tissues and immune cells, which was highly expressed in the spleen, gills, head kidney by quantitative real-time PCR. The mRNA expression of SsIFN-γ was significantly upregulated in the spleen, head kidney, head kidney (HK) macrophages and peripheral blood lymphocytes (PBLs) during pathogen infection. Meanwhile, the recombinant protein (rSsIFN-γ) exhibited an immunomodulatory function to enhance respiratory burst activity and nitric oxide response of HK macrophages. Furthermore, rSsIFN-γ could effectively upregulate the expression of macrophage proinflammatory cytokine, the expression of JAK-STAT signaling pathway related genes and interferon-related downstream genes in the head kidney and spleen. Luciferase assays showed ISRE and GAS activity were obviously enhanced after rSsIFN-γ treatment. These results indicated that SsIFN-γ possessed apparent immunoregulatory properties and played a role in fighting pathogen infection which will be helpful to further understanding of the immunologic mechanism of teleosts IFN-γ in innate immunity.

A carbon-11 labeled imidazo[1,2-a]pyridine derivative as a new potential PET probe targeting PI3K/mTOR in cancer.

The PI3K/Akt/mTOR pathway is frequently dysregulated in cancer due to its central role in cell growth, survival, and proliferation. Overactivation of the PI3K/Akt/mTOR pathway may occur through varying mechanisms including mutations, gene amplification, and upstream signaling events, ultimately resulting in cancer. Therefore, PI3K/Akt/mTOR pathway has emerged as an attractive target for cancer therapy and imaging. A promising approach to inhibit this pathway involves a simultaneous inhibition of both PI3K and mTOR using a dual inhibitor. Recently, a potent dual PI3K/mTOR inhibitor, 2,4-difluoro-N-(2-methoxy-5-(3-(5-(2-(4-methylpiperazin-1-yl)ethyl)-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)benzenesulfonamide (7), was discovered and demonstrated excellent kinase selectivity IC50 (PI3K/mTOR) = 0.20/21 nM; good cellular growth inhibition IC50 (HCT-116 cell) = 10 nM, modest plasma clearance, and acceptable oral bioavailability. Expanding on this discovery, here we present the synthesis of the carbon-11 labeled imidazo[1,2-a]pyridine derivative 2,4-difluoro-N-(2-methoxy-5-(3-(5-(2-(4-[11C]methylpiperazin-1-yl)ethyl)-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)benzenesulfonamide (N-[11C]7) as a new potential radiotracer for the biomedical imaging technique positron emission tomography (PET) imaging of PI3K/mTOR in cancer. The reference standard 7 and its N-demethylated precursor, 2,4-difluoro-N-(2-methoxy-5-(3-(5-(2-(piperazin-1-yl)ethyl)-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)benzenesulfonamide (11), were synthesized in 7 and 8 steps with 10% and 7% overall chemical yield, respectively. N-[11C]7 was prepared from 11 using [11C]methyl triflate ([11C]CH3OTf) through N-11C-methylation and isolated by high-performance liquid chromatography (HPLC) and solid-phase extraction (SPE) formulation in 40-50% radiochemical yield decay corrected to end of bombardment (EOB) based on [11C]CO2. The radiochemical purity was > 99% and the molar activity (Am) at EOB was in the range of 296-555 GBq/µmol (n = 5).