One-Step Dual-Color Labeling of Viral Envelope and Intraviral Genome with Quantum Dots Harnessing Virus Infection.

Labeling the genome and envelope of a virus with multicolor quantum dots (QDs) simultaneously enables real-time monitoring of viral uncoating and genome release, contributing to our understanding of virus infection mechanisms. However, current labeling techniques require genetic modification, which alters the virus's composition and infectivity. To address this, we utilized the CRISPR/Cas13 system and a bioorthogonal metabolic method to label the Japanese encephalitis virus (JEV) genome and envelopes with different-colored QDs in situ. This technique allows one-step two-color labeling of the viral envelope and intraviral genome with QDs harnessing virus infection. In combination with single-virus tracking, we visualized JEV uncoating and genome release in real time near the endoplasmic reticulum of live cells. This labeling strategy allows for real-time visualization of uncoating and genome release at the single-virus level, and it is expected to advance the study of other viral infection mechanisms.

Allosteric Activator-Regulated CRISPR/Cas12a System Enables Biosensing and Imaging of Intracellular Endogenous and Exogenous Targets.

Sensors designed based on the trans-cleavage activity of CRISPR/Cas12a systems have opened up a new era in the field of biosensing. The current design of CRISPR/Cas12-based sensors in the "on-off-on" mode mainly focuses on programming the activator strand (AS) to indirectly switch the trans-cleavage activity of Cas12a in response to target information. However, this design usually requires the help of additional auxiliary probes to keep the activator strand in an initially "blocked" state. The length design and dosage of the auxiliary probe need to be strictly optimized to ensure the lowest background and the best signal-to-noise ratio. This will inevitably increase the experiment complexity. To solve this problem, we propose using AS after the "RESET" effect to directly regulate the Cas12a enzymatic activity. Initially, the activator strand was rationally designed to be embedded in a hairpin structure to deprive its ability to activate the CRISPR/Cas12a system. When the target is present, target-mediated strand displacement causes the conformation change in the AS, the hairpin structure is opened, and the CRISPR/Cas12a system is reactivated; the switchable structure of AS can be used to regulate the degree of activation of Cas12a according to the target concentration. Due to the advantages of low background and stability, the CRISPR/Cas12a-based strategy can not only image endogenous biomarkers (miR-21) in living cells but also enable long-term and accurate imaging analysis of the process of exogenous virus invasion of cells. Release and replication of virus genome in host cells are indispensable hallmark events of cell infection by virus; sensitive monitoring of them is of great significance to revealing virus infection mechanism and defending against viral diseases.

Focus on Upper Urinary Tract Stones Combined with Parenchymal Infiltrative Renal Pelvis Cancer.

INTRODUCTION: Upper urinary tract stones combined with parenchymal infiltrative renal pelvic cancer are challenging to detect on imaging and to evaluate the differential diagnosis. CASE PRESENTATION: The symptoms and diagnoses in three cases of parenchymal infiltrative renal pelvic cancer and upper urinary tract stones that occurred between June 2019 and June 2022 were reviewed. Primary symptoms of lumbar discomfort and hematuria were evident in all 3 patients. Preoperative computed tomography (CT) abdominal imaging revealed that all three cases had hydronephrosis along with renal stones, while the other two cases only had localized hypoenhancement of the renal parenchyma, which was only thought to be limited inflammatory changes in the renal cortex as a result of the combination of renal pelvis infection. After percutaneous nephrolithotomy or ureteroscopic lithotripsy, a combined renal pelvis tumor was discovered in all of these instances. Radical tumor surgery was later performed. One patient who had several tumor metastases passed away 6 months after surgery. A case with multiple metastases was discovered 15 months after surgery and survived with the help of the current chemotherapy. A case with a bladder tumor recurrence was discovered 16 months after surgery and had transurethral bladder tumor electrosurgery and routine bladder perfusion chemotherapy. CONCLUSION: Upper urinary tract stones and parenchymal infiltrative pyel carcinoma have atypical imaging, easily confused with infectious diseases. CT or computed tomography urography (CTU) must be considered by urologists. Patients who have a CT with local renal parenchyma density should be suspected of having parenchymal invasive renal pelvis carcinoma; a needle biopsy ought to be performed; and repeat biopsies may be performed if necessary. High-risk individuals need multiple, sufficient biopsies as needed and a comprehensive intraoperative assessment of the renal pelvic mucosa.

Efficient radical-based light-emitting diodes with doublet emission.

Organic light-emitting diodes (OLEDs)1-5, quantum-dot-based LEDs6-10, perovskite-based LEDs11-13 and micro-LEDs14,15 have been championed to fabricate lightweight and flexible units for next-generation displays and active lighting. Although there are already some high-end commercial products based on OLEDs, costs must decrease whilst maintaining high operational efficiencies for the technology to realise wider impact.  Here we demonstrate efficient action of radical-based OLEDs16, whose emission originates from a spin doublet, rather than a singlet or triplet exciton. While the emission process is still spin-allowed in these OLEDs, the efficiency limitations imposed by triplet excitons are circumvented for doublets. Using a luminescent radical emitter, we demonstrate an OLED with maximum external quantum efficiency of 27 per cent at a wavelength of 710 nanometres-the highest reported value for deep-red and infrared LEDs. For a standard closed-shell organic semiconductor, holes and electrons occupy the highest occupied and lowest unoccupied molecular orbitals (HOMOs and LUMOs), respectively, and recombine to form singlet or triplet excitons. Radical emitters have a singly occupied molecular orbital (SOMO) in the ground state, giving an overall spin-1/2 doublet. If-as expected on energetic grounds-both electrons and holes occupy this SOMO level, recombination returns the system to the ground state, giving no light emission. However, in our very efficient OLEDs, we achieve selective hole injection into the HOMO and electron injection to the SOMO to form the fluorescent doublet excited state with near-unity internal quantum efficiency.

Identification and Fungicide Screening of Fungal Species Associated with Walnut Anthracnose in Shaanxi and Liaoning Provinces, China.

Walnut is cultivated around the world for its precious woody nut and edible oil. Recently, walnut infected by Colletotrichum spp. resulted in a great yield and quality loss. In August and September 2014, walnut fruits with anthracnose were sampled from two commercial orchards in Shaanxi and Liaoning provinces, and five representative isolates were used in this study. To identify the pathogen properly, four genes per region (internal transcribed spacer, glyceraldehyde-3-phosphate dehydrogenase, actin, and chitin synthase) were sequenced and used in phylogenetic studies. Based on multilocus phylogenetic analysis, five isolates clustered with Colletotrichum fioriniae, including its ex-type, with 100% bootstrap support. The results of multilocus phylogenetic analyses, morphology, and pathogenicity confirmed that C. fioriniae was one of the walnut anthracnose pathogens in China. All 13 fungicides tested inhibited mycelial growth and spore germination. Flusilazole, fluazinam, prochloraz, and pyraclostrobin showed the strongest suppressive effects on the mycelial growth than the others, the average EC50 values ranged from 0.09 to 0.40 µg/ml, and there was not any significant difference (P < 0.05). Pyraclostrobin, thiram, and azoxystrobin were the most effective fungicides on spore germination (P < 0.05), and the EC50 values ranged from 0.01 to 0.44 µg/ml. Pyraclostrobin, azoxystrobin, fluazinam, flusilazole, mancozeb, thiram, and prochloraz exhibited a good control effect on walnut anthracnose caused by C. fioriniae, and preventive activities were greater than curative activities. Pyraclostrobin at 250 a.i. µg/ml and fluazinam at 500 a.i. µg/ml provided the highest preventive and curative efficacy, and the values ranged from 81.3 to 82.2% and from 72.9 to 73.6%, respectively. As a consequence, mancozeb and thiram could be used at the preinfection stage, and pyraclostrobin, azoxystrobin, flusilazole, fluazinam, and prochloraz could be used at the early stage for effective prevention and control of walnut anthracnose caused by C. fioriniae. The results will provide more significant instructions for controlling the disease effectively in northern China.

Pulmonary Transit Time Assessment by CEUS in Healthy Rabbits: Feasibility, and the Effects of UCAs Dilution Concentration.

To evaluate the inter-observer variability and the intra-observer repeatability of pulmonary transit time (PTT) measurement using contrast-enhanced ultrasound (CEUS) in healthy rabbits, and assess the effects of dilution concentration of ultrasound contrast agents (UCAs) on PTT. Thirteen healthy rabbits were selected, and five concentrations UCAs of 1:200, 1:100, 1:50, 1:10, and 1:1 were injected into the right ear vein. Five digital loops were obtained from the apical 4-chamber view. Four sonographers obtained PTT by plotting the TIC of right atrium (RA) and left atrium (LA) at two time points (T1 and T2). The frame counts of the first appearance of UCAs in RA and LA had excellent inter-observer agreement, with intra-class correlations (ICC) of 0.996, 0.988, respectively. The agreement of PTT among four observers was all good at five different concentrations, with an ICC of 0.758-0.873. The reproducibility of PTT obtained by four observers at T1 and T2 was performed well, with ICC of 0.888-0.961. The median inter-observer variability across 13 rabbits was 6.5% and the median variability within 14 days for 4 observers was 1.9%, 1.7%, 2.2%, 1.9%, respectively; The PTT of 13 healthy rabbits is 1.01 ± 0.18 second. The difference of PTT between five concentrations is statistically significant. The PTT obtained by a concentration of 1:200 and 1:100 were higher than that of 1:1, while there were no significantly differences in PTT of a concentration of 1:1, 1:10, and 1:50. PTT measured by CEUS in rabbits is feasible, with excellent inter-observer and intra-observer reliability and reproducibility, and dilution concentration of UCAs influences PTT results.

A Genome-Wide Analysis of the Jasmonic Acid Biosynthesis Gene Families in Peanut Reveals Their Crucial Roles in Growth and Abiotic Stresses.

Abiotic stress is a limiting factor in peanut production. Peanut is an important oil crop and cash crop in China. Peanut yield is vulnerable to abiotic stress due to its seeds grown underground. Jasmonic acid (JA) is essential for plant growth and defense against adversity stresses. However, the regulation and mechanism of the jasmonic acid biosynthesis pathway on peanut defense against abiotic stresses are still limitedly understood. In this study, a total of 64 genes encoding key enzymes of JA biosynthesis were identified and classified into lipoxygenases (AhLOXs), alleno oxide synthases (AhAOSs), allene oxide cyclases (AhAOCs), and 12-oxo-phytodienoic acid reductases (AhOPRs) according to gene structure, conserved motif, and phylogenetic feature. A cis-regulatory element analysis indicated that some of the genes contained stress responsive and hormone responsive elements. In addition to proteins involved in JA biosynthesis and signaling, they also interacted with proteins involved in lipid biosynthesis and stress response. Sixteen putative Ah-miRNAs were identified from four families targeting 35 key genes of JA biosynthesis. A tissue expression pattern analysis revealed that AhLOX2 was the highest expressed in leaf tissues, and AhLOX32 was the highest expressed in shoot, root, and nodule tissues. AhLOX16, AhOPR1, and AhOPR3 were up-regulated under drought stress. AhLOX16, AhAOS3, AhOPR1, and AhAOC4 had elevated transcript levels in response to cold stress. AhLOX5, AhLOX16, AhAOC3, AhOPR1, and AhOPR3 were up-regulated for expression under salt stress. Our study could provide a reference for the study of the abiotic stress resistance mechanism in peanut.

Phenyl Derivatives Modulate the Luminescent Properties and Stability of CzBTM-Type Radicals.

The distinctive electron structures of luminescent radicals offer considerable potential for a diverse array of applications. Up to now, the luminescent properties of radicals have been modulated through the introduction of electron-donating substituents, predominantly derivatives of carbazole and polyaromatic amines with more and more complicated structures and redshifted luminescent spectra. Herein, four kinds of (N-carbazolyl)bis(2,4,6-tirchlorophenyl)-methyl (CzBTM) radicals, Ph2CzBTM, Mes2CzBTM, Ph2PyIDBTM, and Mes2PyIDBTM, were synthesized and characterized by introducing simple phenyl and 2,4,6-trimethylphenyl groups to CzBTM and PyIDBTM. These radicals exhibit rare blueshifted emission spectra compared to their parent radicals. Furthermore, modifications to CzBTM significantly enhanced the photoluminescence quantum yields (PLQYs), with a highest PLQY of 21% for Mes2CzBTM among CzBTM-type radicals. Additionally, the molecular structures, photophysical properties of molecular orbitals, and stability of the four radicals were systematically investigated. This study provides a novel strategy for tuning the luminescent color of radicals to shorter wavelengths and improving thermostability.

[Combination of shikonin and gefitinib reverses drug resistance in human non-small cell lung cancer and its mechanism].

The occurrence and development of tumors are associated with the cell energy metabolism. Inhibiting energy metabolism of lung cancer cells is an important strategy to overcome drug resistance. Based on the cellular energy metabolism pathway, this study observed the effect of combination of shikonin(SKN) and gefitinib(GFB) on the drug resistance in non-small cell lung cancer and explored the underlying mechanism. The human non-small cell lung cancer line HCC827/GR resistant to gefitinib was used as the cell model in vitro. The CCK-8 assay and flow cytometry were employed to investigate the cell viability and apoptosis, respectively. The high performance liquid chromatography was employed to measure the intracellular accumulation of GFB. A Seahorse XFe96 Analyzer was used to detect the changes of cellular energy metabolism. Western blot was employed to determine the expression of the proteins involved in the drug resistance. The tumor-bearing nude mouse model was used to verify the efficacy of SKN+GFB in overcoming drug resistance in vivo. The results showed that SKN+GFB significantly reduced the IC_(50) of GFB on HCC827/GR cells, with the combination index of 0.628, indicating that the combination of the two drugs had a synergistic effect and promoted cell apoptosis. SKN increased the intracellular accumulation of GFB. SKN+GFB lowered the oxygen consumption rate(OCR) and glycolytic proton efflux rate(GlycoPER) in cell energy metabolism, and down-regulated the overexpression of PKM2, p-EGFR, P-gp, and HIF-1α in drug resistance. The results of reversing drug resistance test in vivo showed that GFB or SKN alone had no significant antitumor effect, while the combination at different doses induced the apoptosis of the tumor tissue and inhibited the expression of PKM2 and P-gp, demonstrating a significant antitumor effect. Moreover, the tumor inhibition rate in the high-dose combination group reached 64.01%. In summary, SKN+GFB may interfere with the energy metabolism to limit the function of HCC827/GR cells, thus reversing the GFB resistance in non-small cell lung cancer.

Dual Channel Emissions of Kasha and Anti-Kasha from a Single Radical Molecule.

Stable open-shell luminescent radicals have recently attracted much attention due to their unique luminescence properties. However, a radical molecule with both Kasha and anti-Kasha doublet emission properties has not been reported. Herein, we have successfully synthesized a stable chlorine-substituted Chichibabin's hydrocarbon, TTM-TTM, along with its mono-radical counterpart, TTM-HTTM. The emission of TTM-TTM follows Kasha's rule in the near infrared region. However, TTM-HTTM shows dual channel doublet emissions of Kasha and anti-Kasha. Remarkably, these two types of emission compete dynamically in both solution and condensed states. Our findings provide valuable insights into the rational design and discovery of stable radicals that possess distinctive luminescent properties, thus broadening the horizons of luminescent materials research.

Immunotherapy as a later-line option for HER2-altered advanced non-small-cell lung cancer: taxane might be a favorable partner.

Aim: To assess the effectiveness of different types of taxanes, including nab-paclitaxel, paclitaxel and docetaxel, and further compare the effectiveness of taxane-based chemotherapy, taxane-based chemotherapy plus angiogenesis inhibitors or taxane-based chemotherapy plus immune checkpoint inhibitors in HER2-altered non-small-cell lung cancer in the second- or third-line setting. Materials & methods: A total of 52 patients were included in the study. Progression-free survival was compared between subgroups. Results: A clinically meaningful improvement in progression-free survival was observed among patients in the nab-paclitaxel group compared with the docetaxel group. Taxane-based chemotherapy plus immune checkpoint inhibitors achieved longer progression-free survival than taxane-based chemotherapy. There was no difference between taxane-based chemotherapy plus immune checkpoint inhibitors and taxane-based chemotherapy plus angiogenesis inhibitors. Conclusion: Nab-paclitaxel appears to be a reasonable alternative to docetaxel. Chemotherapy plus immune checkpoint inhibitors might yield more survival benefits than chemotherapy alone.

Relationship between atmospheric pollution and polycyclic aromatic hydrocarbons in fresh snow during heavy pollution episodes in a cold city, northeast China.

Air quality index (AQI) and air pollutants during two typical pollution episodes, and polycyclic aromatic hydrocarbons (PAHs) in fresh snow after each episode in the winter 2019 across Harbin City in northeast China were investigated to explore the co-environmental behaviors. Significantly greater values of AQI and PAHs were found in the more serious atmospheric pollution episode (episode Ⅱ), demonstrating that PAHs in fresh snow is a robust indicator. PM2.5 was the primary air pollutant in both episodes based on PM2.5/PM10 ratios, which might be attributed to fine particulate converted from gas-to-particle process. PM2.5 and 4-ring PAHs significantly positive correlated, indicating that airborne particulate PAHs were co-emitted and co-transported with atmospheric fine particles released from coal combustion and vehicular emission under low temperature and high relative humidity. 3- and 4- rings PAHs were dominant in episode Ⅱ, while 5- and 6- rings PAHs were found the lowest in both episodes. These characteristics reflected that long-range transportation of coal and biomass burning were from the surrounding areas, while vehicle exhausts were mainly from local emissions. Except for the impact of local pollution source emissions, the regional transport could make a greater contribution in a more serious pollution event.

Curcumin alleviates bisphenol AF-induced oxidative stress and apoptosis in caprine endometrial epithelial cells via the Nrf2 signaling pathway.

Bisphenol AF (BPAF), a BPA-substitute, has been widely used in industrial compounds throughout the world. Several studies have shown that BPAF has endocrine interference and reproductive toxicity. However, the toxic effects of BPAF on pregnancy and placenta of goats are still unclear. Therefore, the objective of this study was to reveal the toxic effect of BPAF by using an in vitro culture model of caprine endometrial epithelial cells (EECs) and further attempted to alleviate the toxicity by curcumin pretreatment. The results showed that BPAF induces significant effects on EECs, including decreased cell viability and mitochondrial membrane potential (△ψm), elevating intracellular reactive oxygen species (ROS), promoting cell apoptosis through upregulating the expression of Bax, Cytochrome c, and downregulating the expression of Bcl-2. Meanwhile, BPAF induced dysregulation of oxidative stress by increasing the levels of malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) but decreasing the activities of superoxide dismutase (SOD). However, curcumin pretreatment could significantly attenuate BPAF-induced toxic effects in EECs. Further study revealed that BPAF treatment could activate mitogen-activated protein kinase (MAPK) pathway and nuclear factor-erythroid 2-related factor 2 (Nrf2) expression, but curcumin pretreatment significantly inhibited the activation of MAPK signal pathway and Nrf2 expression induced by BPAF. Overall, this study indicated that curcumin could prevent BPAF-induced EECs cytotoxicity, which provides a potential therapeutic strategy for female infertility associated with BPAF exposure.

High-dose synthetic phenolic antioxidant propyl gallate impairs mouse oocyte meiotic maturation through inducing mitochondrial dysfunction and DNA damage.

Propyl gallate (PG) is one of the most widely used antioxidants in food products, cosmetics and pharmaceutical industries. Increased research has suggested that exposure to PG influences reproductive health in humans and animals. However, until now, it has not yet been confirmed whether PG would impact oocyte quality. In this study, the hazardous effects of PG on oocyte meiotic maturation were investigated in mice. The findings showed that PG exposure compromises oocyte meiosis by inducing mitochondrial stress which activates apoptosis to trigger oocyte demise. Moreover, DNA damage was significantly induced in PG-treated oocytes, which might be another cause of oocyte developmental arrest and degeneration. Besides, the level of histone methylation (H3K27me2 and H3K27me3) in oocyte was also significantly increased by PG exposure. Furthermore, PG-induced oxidative stress was validated by the increased level of reactive oxygen species (ROS), which might be the underlying reason for these abnormities. In conclusion, the foregoing findings suggested that PG exposure impaired oocyte meiotic maturation by yielding mitochondrial stress to activate apoptosis, inducing DNA damage and oxidative stress, and altering histone methylation level.

Improving the Luminescence and Stability of Carbon-Centered Radicals by Kinetic Isotope Effect.

The kinetic isotope effect (KIE) is beneficial to improve the performance of luminescent molecules and relevant light-emitting diodes. In this work, the influences of deuteration on the photophysical property and stability of luminescent radicals are investigated for the first time. Four deuterated radicals based on biphenylmethyl, triphenylmethyl, and deuterated carbazole were synthesized and sufficiently characterized. The deuterated radicals exhibited excellent redox stability, as well as improved thermal and photostability. The appropriate deuteration of relevant C-H bonds would effectively suppress the non-radiative process, resulting in the increase in photoluminescence quantum efficiency (PLQE). This research has demonstrated that the introduction of deuterium atoms could be an effective pathway to develop high-performance luminescent radicals.

Uncovering the F-Actin-Based Nuclear Egress Mechanism of Newly Synthesized Influenza A Virus Ribonucleoprotein Complexes by Single-Particle Tracking.

Nuclear trafficking of viral genome is an essential cellular process in the life cycles of viruses. Despite substantial progress in uncovering a wide variety of complicated mechanisms of virus entry, intracellular transport of viral components, virus assembly, and egress, the temporal and spatial dynamics of viral genes trafficking within the nucleus remains poorly understood. Herein, using single-particle tracking, we explored the real-time dynamic nuclear trafficking of influenza A virus (IAV) genes packaged as the viral ribonucleoprotein complexes (vRNPs) by combining a four-plasmid DNA transfection system for the reconstruction of green fluorescent protein (GFP)-labeled vRNPs and a spinning disk super-resolution fluorescence microscope. We found that IAV infection significantly induced the formation of actin microfilaments (F-actin) in the nucleus. In combination with the fluorescent protein-tagged nuclear F-actin probe, we visualized the directed movement of GFP-labeled vRNPs foci along the nuclear F-actin with a speed of 0.18 µm/s, which is similar to the microfilaments-dependent slow directed motion of IAVs in the cytoplasm. The disruption of nuclear F-actin after treatment with microfilament inhibitors caused a considerable decrease in vRNPs motility and suppressed the nuclear export of newly produced vRNPs, indicating that the slow, directed movement plays a crucial role in facilitating the nuclear egress of vRNPs. Our findings identified a nuclear F-actin-dependent pathway for IAV vRNPs transporting from the nucleus into the cytoplasm, which may in turn uncover a novel target for antiviral treatment.

Comparative physiological and coexpression network analyses reveal the potential drought tolerance mechanism of peanut.

BACKGROUND: Drought stress has negative effects on plant growth and productivity. In this study, a comprehensive analysis of physiological responses and gene expression was performed. The responses and expressions were compared between drought-tolerant (DT) and drought-sensitive (DS) peanut varieties to investigate the regulatory mechanisms and hub genes involved in the impact of drought stress on culture. RESULTS: The drought-tolerant variety had robust antioxidative capacities with higher total antioxidant capacity and flavonoid contents, and it enhanced osmotic adjustment substance accumulation to adapt to drought conditions. KEGG analysis of differentially expressed genes demonstrated that photosynthesis was strongly affected by drought stress, especially in the drought-sensitive variety, which was consistent with the more severe suppression of photosynthesis. The hub genes in the key modules related to the drought response, including genes encoding protein kinase, E3 ubiquitin-protein ligase, potassium transporter, pentatricopeptide repeat-containing protein, and aspartic proteinase, were identified through a comprehensive combined analysis of genes and physiological traits using weighted gene co-expression network analysis. There were notably differentially expressed genes between the two varieties, suggesting the positive roles of these genes in peanut drought tolerance. CONCLUSION: A comprehensive analysis of physiological traits and relevant genes was conducted on peanuts with different drought tolerances. The findings revealed diverse drought-response mechanisms and identified candidate genes for further research.

Proanthocyanidins inhibit the apoptosis and aging of nucleus pulposus cells through the PI3K/Akt pathway delaying intervertebral disc degeneration.

BACKGROUND: Low back pain is a common symptom of intervertebral disc degeneration (IDD), which seriously affects the quality of life of patients. The abnormal apoptosis and senescence of nucleus pulposus (NP) cells play important roles in the pathogenesis of IDD. Proanthocyanidins (PACs) are polyphenolic compounds with anti-apoptosis and anti-aging effects. However, their functions in NP cells are not yet clear. Therefore, this study was performed to explore the effects of PACs on NP cell apoptosis and aging and the underlying mechanisms of action. METHODS: Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. The apoptosis rate was determined TUNEL assays. Levels of apoptosis-associated molecules (Bcl-2, Bax, C-caspase-3 and Caspase-9) were evaluated via western blot. The senescence was observed through SA-ß-gal staining and western blotting analysis was performed to observe the expression of senescence-related molecules (p-P53, P53, P21 and P16). RESULTS: Pretreatment with PACs exhibited protective effects against IL-1ß-induced NP cell apoptosis including apoptosis rate, expressions of proapoptosis and antiapoptosis related genes and protein. PACs could also alleviate the increase of p-p53, P21, and P16 in IL-1ß-treated NP cells. SA-ß-gal staining showed that IL-1ß-induced senescence of NP cells was prevented by PACs pertreatment. In addition, PACs activated PI3K/Akt pathway in IL-1ß-stimulated NP cells. However, these protected effects were inhibited after LY294002 treatment. CONCLUSION: The results of the present study showed that PACs inhibit IL-1ß-induced apoptosis and aging of NP cells by activating the PI3K/Akt pathway, and suggested that PACs have therapeutic potential for IDD.

LncRNA-mediated ceRNA networks provide novel potential biomarkers for peanut drought tolerance.

Drought stress has been the major constraint on peanut yield and quality, and an understanding of the function of long non-coding (lncRNAs) in the peanut drought stress response is still in its infancy. In this study, two peanut varieties with contrasting drought tolerance were used to explore the functions of lncRNAs in the peanut drought response, and the results showed that the drought-tolerant variety presented greater antioxidant enzyme activity, osmotic adjustment ability, and photosynthesis under drought conditions. There were 4329 lncRNAs identified in the two varieties, of which 535 and 663 lncRNAs were differentially expressed in NH5 and FH18, respectively. The cis targets of the differentially expressed lncRNAs were putatively involved in secondary metabolite biosynthesis and other basic metabolic processes. A total of 673 competing endogenous RNA (ceRNA) pairs were selected specifically in NH5, and the associated ceRNA network revealed six lncRNAs, MSTRG.70535.2, MSTRG.86570.2, MSTRG.86570.1, MSTRG.100618.1, MSTRG.81214.2, and MSTRG.30931.1were considered as hub nodes. They were speculated to contribute to enhancing peanut drought tolerance, such as regulating transcription and plant growth processes, thereby improving the drought stress response. In this study, lncRNAs and mRNAs interaction networks were constructed to aid a comprehensive understanding of the peanut drought stress response and form a basis for future research.

Health-related quality of life questionnaires used in primary biliary cholangitis: a systematic review.

OBJECTIVE: The purpose of this systematic review was to assess the suitability of health-related quality of life (HRQOL) questionnaires in patients with primary biliary cholangitis. METHODS: Relevant studies were compiled from a search of five electronic databases. The properties under investigation included the validity of the translated questionnaires, floor and ceiling effects, internal consistency and test-retest reliability. RESULTS: Forty-four studies were included, from which fifteen HRQOL questionnaires were identified. The most frequently used instruments were the PBC-40 (n = 22), the SF-36 (n = 19), the PBC-27 (n = 4), the CLDQ (n = 3) and the NIDDK-QA (n = 2). The remaining instruments were used only once. Twenty-six studies used a translated HRQOL questionnaire, but only six reported or referenced validating the translated questionnaire. CONCLUSIONS: PBC-specific HRQOL questionnaires generally have good psychometric properties. However, many studies have directly applied HRQOL tools without verifying their validity and reliability in PBC patients. There was no clear indication that one HRQOL tool was superior to another, although the PBC-40 is the most well-studied. Thus, more robust psychometric studies are needed to investigate the measurement properties of HRQOL questionnaires.