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In this paper, we study the uniqueness of nodal radial solutions to nonlinear elliptic equations in the unit ball in ℝ3$$ {\mathrm{\mathbb{R}}}^3 $$. Under suitable conditions, we prove that, for any given positive integer k$$ k $$, the problem we considered has at most one solution possessing exactly k−1$$ k-1 $$ nodes. Together with the results presented by Nagasaki [J. Fac. Sci. Univ. Tokyo Sect. IA Math. 36 (2): 211–232, 1989] and Tanaka [Proc. Roy. Soc. Edinburgh Sect. A. 138 (6): 1331–1343, 2008], we can prove that more types of nonlinear elliptic equations have the uniqueness of nodal radial solutions. [ABSTRACT FROM AUTHOR]

Introduction: Cadonilimab (AK104) is a first-in-class tetravalent bispecific antibody that targets both PD-1 and CTLA-4, showing a manageable safety profile and favorable clinical benefits. This study aimed to identify the biomarkers of clinical response and explore the immune response within the tumor microenvironment upon the AK104 therapy in advanced solid tumors. Material and methods: Gene expression profiles of paired pre- and post-treatment tumor tissues from twenty-one patients were analyzed. The association of gene expression levels with either clinical efficacy or prognosis was evaluated and subsequently validated with published datasets using log-rank for Kaplan–Meier estimates. Comparative immune profile analyses of tumor microenvironment before and after AK104 treatment were conducted. The visualization of tumor-infiltrating lymphocytes was performed using multiplex immunohistochemistry. The predictive value of CD74 was further validated with protein expression by immunohistochemistry. Results: Baseline CD74 gene expression was associated with favorable patient outcomes (overall survival [OS], HR = 0.33, 95% CI 0.11–1.03, p = 0.0463), which was further confirmed with the published datasets. Tumors with high CD74 gene expression at baseline were more likely to exhibit an immune-inflamed microenvironment. AK104 efficiently enhanced the infiltration of immune cells in the tumor microenvironment. Additionally, high CD74 protein expression (≥ 10% of the tumor area occupied by CD74 stained immune cells) at baseline was associated with better progressive-free survival (HR = 0.21, 95% CI 0.06–0.68, p = 0.0065) and OS (HR = 0.35, 95% CI 0.12–1.08, p = 0.0615). Conclusions: Our findings demonstrate that CD74 is a promising predictive biomarker for AK104 therapeutic response in advanced solid tumors. Trial registration number NCT03261011. [ABSTRACT FROM AUTHOR]

Natural compounds are rich in pharmacological properties that are a hot topic in pharmaceutical research. The quinoline ring plays important roles in many biological processes in heterocycles. Many pharmacological compounds, including saquinavir and chloroquine, have been marketed as quinoline molecules with good anti-viral and anti-parasitic properties. Therefore, in this review, we summarize the medicinal chemistry of quinoline-modified natural product quinoline derivatives that were developed by several research teams in the past 10 years and find that these compounds have inhibitory effects on bacteria, viruses, parasites, inflammation, cancer, Alzheimer's disease, and others. [ABSTRACT FROM AUTHOR]

Background: The molecular subtypes of endometrial carcinoma are significantly correlated with survival outcomes and can guide surgical methods and postoperative adjuvant therapy. Among them, the TP53mut subtype has the worst prognosis and can only be determined by detection after surgery. Therefore, identifying preoperative noninvasive clinical parameters for early prediction of the TP53mut subtype would provide important guidance in choosing the appropriate surgical method and early warning for clinicians. Our study aimed to establish a model for the early prediction of the TP53mut subtype by using preoperative noninvasive parameters of endometrial cancer and screen out potential TP53mut patients. Methods: Information and pathological specimens of 376 patients who underwent surgery for FIGO stage I-IV endometrial cancer in the Department of Gynecology, Peking University Cancer Hospital, from June 2011 to July 2020 were collected, and 178 cases were finally included in the study as the training dataset (part A). Thirty-six cases from January 2022 to March 2023 were collected as the validation dataset (part B). Molecular subtyping was performed using a one-stop next-generation sequencing (NGS) approach. Compared with the TP53mut subtype, the POLE EDM, MSI-H and TP53 wild-type subtypes were defined as non-TP53mut subtypes. Univariate Cox regression analysis and multivariate logistic analysis were performed to determine the preoperative clinical parameters associated with the TP53mut subtype. A nomogram prediction model was established using preoperative noninvasive parameters, and its efficacy in predicting TP53mut subtype and survival outcomes was verified. Results: The TP53mut subtype was identified in 12.4% of the part A and 13.9% of the part B. Multivariate logistic regression analysis showed that HDL-C/LDL-C level, CA125 level, and cervical or lower uterine involvement were independent influencing factors associated with the TP53mut subtype (p = 0.016, 0.047, <0.001). A TP53mut prognostic model (TPMM) was constructed based on the factors identified in the multivariate analysis, namely, TPMM = -1.385 × HDL-C/LDL-C + 1.068 × CA125 + 1.89 × CI or LUI, with an AUC = 0.768 (95% CI, 0.642 to 0.893) in the part A. The AUC of TPMM for predicting TP53mut subtype in the part B was 0.781(95% CI, 0.581 to 0.980). The progression-free survival (PFS) and overall survival (OS) of patients with the TP53mut subtype were significantly worse than those of patients with the non-TP53mut subtype, as predicted by the model in the part A. Conclusions: TP53mut prediction model (TPMM) had good diagnostic accuracy, and survival analysis showed the model can identify patients with different prognostic risk. [ABSTRACT FROM AUTHOR]

• This meta-analysis focuses on patients aged over 60 years. • Intensive blood pressure control reduces major adverse cardiovascular events (MACEs) by 20.1 % and stroke by 30.3 %. • Intensive treatment is linked to the risks of hypotension and syncope. • The results support intensive blood pressure control for patients aged over 60. To evaluate the effects of intensive treatment to lower blood pressure (BP) on the risk of cardiovascular disease (CVD) among patients aged over 60 years. We extracted individual-level data of participants aged over 60 years from the SPRINT study and ACCORD study first, and then conducted a meta-analysis of major adverse cardiovascular events (MACEs) and other adverse events (hypotension and syncope) and renal outcomes across the SPRINT, STEP, ACCORD BP trials, which included 18,806 participants over 60 years of age. Participants were randomized to receive standard BP treatment or intensive BP treatment. Hazard ratios (HRs) were used to calculate summary statistics. In this meta-analysis, intensive treatment did not decrease either the all-cause mortality rate (HR: 0.98; 95 % confidence interval [CI]: 0.76–1.26; p = 0.87) or the cardiovascular mortality rate (HR: 0.77; 95 % CI: 0.54–1.08; p = 0.13). The incidence of MACEs (HR: 0.83; 95 % CI: 0.74–0.94; p = 0.003) and stroke (HR: 0.70; 95 % CI: 0.56–0.88; p = 0.002) was reduced, however. Intensive treatment had no effect on acute coronary syndrome (HR: 0.87; 95 % CI: 0.69–1.10; p = 0.24) or heart failure (HR: 0.70; 95 % CI: 0.40–1.22; p = 0.21). Intensive treatment increased the risk of hypotension (HR: 1.46; 95 % CI: 1.12–1.91; p = 0.006) and syncope (HR: 1.43; 95 % CI: 1.06–1.93; p = 0.02). Intensive treatment did not increase the risk of impaired kidney function among patients with chronic kidney disease (HR: 0.98; 95 % CI: 0.41–2.34; p = 0.96) or without chronic kidney disease (HR: 1.77; 95 % CI: 0.48–6.56; p = 0.40) at baseline. Intensive BP goals reduced the incidence of MACEs and increased the risk of other adverse events without significant changes in mortality or renal outcome. ACCORD: Action to Control Cardiovascular Risk in Diabetes; SPRINT: Systolic Blood Pressure Intervention Trial; STEP: Strategy of Blood Pressure Intervention in Elderly Hypertensive Patients; MACEs: major adverse cardiovascular events; Pts: patients; BP: blood pressure; SBP: systolic blood pressure; HR: hazard ratio; CKD: chronic kidney disease. [Display omitted] [ABSTRACT FROM AUTHOR]

The prevalence and mortality of hepatocellular carcinoma (HCC) are still increasing. This study aimed to identify potential therapeutic targets related to patient prognosis. Data were downloaded from TCGA, GSE25097, GSE36376, and GSE76427 datasets. Differential analysis and enrichment analysis were performed in HCC. Cell deaths were evaluated, and least absolute shrinkage and selection operator regression (LASSO) regression was analyzed to screen candidate genes. Additionally, immune cell infiltration in HCC was assessed. We identified 4088 common DEGs with the same direction of differential expression in all four datasets, they were mainly enriched in immunoinflammation and cell cycle pathways. Apoptosis was significantly suppressed in HCC in GSEA and GSVA. After LASSO regression analysis, we screened CD69, CDC25B, MGMT, TOP2A, and TXNIP as candidate genes. Among them, CD69 significantly influenced the overall survival of HCC patients in both TCGA and GSE76427. CD69 may be a protective factor for outcome of HCC patients. In addition, CD69 was positive correlation with T cells and CD3E. CD69, CDC25B, MGMT, TOP2A, and TXNIP were potential diagnostic and prognostic target for HCC, especially CD69. [ABSTRACT FROM AUTHOR]

"VP/AP + (dek)le + AP/VP" is a predicative complement construction in Shanghai Wu Chinese (SWC) with (dek)le being the complement marker. In everyday SWC conversation, the terminal complement is often dropped, forming the Truncated Predicative Complement Construction (TPCC): "AP + (dek)le". The data for the present study are approximately 4.5 h of naturalistic SWC face-to-face conversations. Adopting the methodology of conversation analysis and interactional linguistics, we explore the interactional functions of the TPCC in the SWC conversational data. We find that TPCCs after the possible closure of a topic are deployed to initiate a new topic in two ways: initiating a disjunctive topic shift, and changing to a topic that is connected to a prior one. The findings demonstrate that TPCCs are routinized grammatical patterns accomplishing the conversational action of initiating new topics in SWC conversation. [ABSTRACT FROM AUTHOR]

We report for the first time the complete genome sequence of a novel amalgavirus, tentatively designated as 'lily amalgavirus 1' (LAV-1), isolated from Lilium spp. in China. LAV-1 is a 3448-nt double-stranded RNA virus that encodes two putative proteins. Open reading frame 1 (ORF1) encodes a 394-aa protein with unknown function. ORF2 encodes a putative RNA-dependent RNA polymerase (RdRp) of 895 aa. The two ORFs putatively encode a '1 + 2' fusion protein generated by a '+1' programmed ribosomal frameshift (PRF). BLASTp analysis revealed that the complete genome sequence of LAV-1 shares 48.23–59.80% sequence identity (query sequence coverage > 77%) with those of members of the genus Amalgavirus, with the highest nucleotide sequence identity of 59.80% with that of Allium cepa amalgavirus 1 (query sequence coverage, 87%). The genome structure, phylogenetic relationships, and sequence similarities to other plant amalgaviruses suggest that LAV-1 is a new member of the genus Amalgavirus. [ABSTRACT FROM AUTHOR]

Alcohol consumption is regarded as one of the leading risk factors for secondary osteopenia. Angiogenesis and osteogenesis coupled by type-H vessels coordinate the biological process of bone homeostasis to prevent osteopenia. This study aimed to determine whether chronic alcohol inhibits type-H vessel-dependent bone formation. Two-month-old mice were fed with 5% (v/v) alcohol liquid diet (28% of calories) or normal liquid diet every day for 2 months. The tibias were isolated and detected with X-ray and microcomputed tomography. Paraffin-embedded or frozen tibial sections were prepared and used for immunohistochemical or immunofluorescence staining, respectively. Human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of alcohol, including 0 mM (0%), 8.7 mM (0.5%), 52 mM (3%), or 87 mM (5%) alcohol for 12 h. The conditioned medium of the above HUVEC cells was collected to culture human bone marrow-mesenchymal stem cells (BM-MSCs), which were induced to differentiate into osteoblasts in vitro. The alcoholic diet retarded the bone growth and led to osteoporosis, impaired bone formation of osteoblasts, and decreased CD31hiEMCNhi type-H vessel formation through inhibiting proliferation and promoting aging of endothelial cells in mice. Alcohol treatment obviously increased the expression of p16, while significantly decreased the expression of Bmi-1, CDK6, Cyclin D, E2F1, and bone morphogenetic protein (BMP)2 compared with vehicle. Alcohol inhibited the differentiation of BM-MSCs into osteoblasts through reducing the BMP2 secretion of endothelial cells in type-H vessels. Alcoholic diet impaired CD31hiEMCNhi type-H vessel formation through inhibiting proliferation and promoting aging of endothelial cells through Bmi-1/p16 signaling, and inhibited the differentiation of BM-MSCs into osteoblasts through reducing the BMP2 secretion of endothelial cells in type-H vessels. This study provides a basis for developing a new treatment strategy targeting aging endothelial cells of type-H vessel to prevent alcoholic osteopenia. [ABSTRACT FROM AUTHOR]

Background: The cultivated peanut (Arachis hypogaea L., AABB) is an allotetraploid hybrid between two diploid peanuts, A. duranensis (AA genome) and A. ipaensis (BB genome). Miniature inverted-repeat transposable elements (MITEs), some of which are known as active nonautonomous DNA transposons with high copy numbers, play important roles in genome evolution and diversification. AhMITE1, a member of the MITE family of transposons, but information on the peanut genomes is still limited. Here, we analyzed AhMITE1, AuMITE1 and ApMITE1 in the cultivated (A. hypogaea) and two wild peanut (A. duranensis and A. ipaensis) genomes. Results: The cultivated and the two wild peanut genomes harbored 142, 14 and 21 AhMITE1, AuMITE1 and ApMITE1 family members, respectively. These three family members exhibited highly conserved TIR sequences, and insertions preferentially occurred within 2 kb upstream and downstream of gene-coding and AT-rich regions. Phylogenetic and pairwise nucleotide diversity analysis showed that AhMITE1 and ApMITE1 family members have undergone one round of amplification bursts during the evolution of the peanut genome. PCR analyses were performed in 23 peanut varieties and demonstrated that AhMITE1 is an active transposon and that hybridization or chemical mutagenesis can promote the mobilization of AhMITE1. Conclusions: AhMITE1, AuMITE1 and ApMITE1 family members were identified based on local BLAST search with MAK between the cultivated and the two wild peanut genomes. The phylogenetic, nucleotide diversity and variation copy numbers of AhMITE1, AuMITE1 and ApMITE1 members provides opportunities for investigating their roles during peanut evolution. These findings will contribute to knowledge on diversity of AhMITE1, provide information about the potential impact on the gene expression and promote the development of DNA markers in peanut. [ABSTRACT FROM AUTHOR]

Background: The cultivated peanut (Arachis hypogaea L., AABB) is an allotetraploid hybrid between two diploid peanuts, A. duranensis (AA genome) and A. ipaensis (BB genome). Miniature inverted-repeat transposable elements (MITEs), some of which are known as active nonautonomous DNA transposons with high copy numbers, play important roles in genome evolution and diversification. AhMITE1, a member of the MITE family of transposons, but information on the peanut genomes is still limited. Here, we analyzed AhMITE1, AuMITE1 and ApMITE1 in the cultivated (A. hypogaea) and two wild peanut (A. duranensis and A. ipaensis) genomes. Results: The cultivated and the two wild peanut genomes harbored 142, 14 and 21 AhMITE1, AuMITE1 and ApMITE1 family members, respectively. These three family members exhibited highly conserved TIR sequences, and insertions preferentially occurred within 2 kb upstream and downstream of gene-coding and AT-rich regions. Phylogenetic and pairwise nucleotide diversity analysis showed that AhMITE1 and ApMITE1 family members have undergone one round of amplification bursts during the evolution of the peanut genome. PCR analyses were performed in 23 peanut varieties and demonstrated that AhMITE1 is an active transposon and that hybridization or chemical mutagenesis can promote the mobilization of AhMITE1. Conclusions: AhMITE1, AuMITE1 and ApMITE1 family members were identified based on local BLAST search with MAK between the cultivated and the two wild peanut genomes. The phylogenetic, nucleotide diversity and variation copy numbers of AhMITE1, AuMITE1 and ApMITE1 members provides opportunities for investigating their roles during peanut evolution. These findings will contribute to knowledge on diversity of AhMITE1, provide information about the potential impact on the gene expression and promote the development of DNA markers in peanut. [ABSTRACT FROM AUTHOR]

Advanced synchrotron radiation sources are major facilities for analyzing the formation and evolution of material structure in multidisciplinary research, owing to their high luminosity, low emittance, wide energy bandwidth and other characteristics. In China, several advanced synchrotron radiation sources are under construction, including the HEPS (High Energy Photon Source) and SHINE (Shanghai high repetition rate X-ray Free Electron Laser and extreme light facility). These facilities are poised to become major multidisciplinary research platforms in China. To meet the requirements of pixel detectors in these facilities, dedicated pixel readout chips are being developed, including HEPS-BPIX and HYLITE. This paper presents a high-speed serializer circuit developed in a commercial 130-nm CMOS technology for the full-scale (128 × 128) pixel readout chip of HYLITE, which requires a data rate of 4 Gbps currently. The serializer consists of a 16-to-1 binary-tree multiplexer, a ring-oscillating-based phase-locked loop (RO-PLL) and a current-mode logic driving stage with a multi-stage pre-amplifier. Test results demonstrate its expected functionality within a wide operating range from 0.52 Gbps to 5.5 Gbps. At 5.12 Gbps, the measured jitter values are about 2 ps for random jitter, 20 ps for deterministic jitter, and 47 ps for total jitter with a 10−12 bit error rate. Additionally, the horizontal and vertical eye openings are 0.84 UI and 72%, respectively. These positive results indicate that the serializer meets the requirements of HYLITE. [ABSTRACT FROM AUTHOR]

Monolithic Active Pixel Sensor is one of the promising candidates for the Circular Electron Positron Collider Vertex detector, due to its good performance and trade-off of granularity, readout speed, material budgets and power consumption. A full-scale TaichuPix chip, including a matrix of 512 × 1024 pixels with a size of 25 × 25 μm2 is developed to provide a spatial resolution better than 5 μm. It requires a raw data rate up to 3.84 Gbps and power consumption less than 100 mA for the serializer circuit. Based on one of the small-scale prototypes, the highest serial data rate is tested to be 3.36 Gbps with a peak-to-peak jitter of about 150 ps and large current consumption. Moreover, the 32-bit parallel data width of the serializer isn't suitable for the 8B10B encoder. Therefore, two 4 Gbps serializers have been designed and optimized to meet these requirements based on the same process node of 180 nm as the TaichuPix, considering the funding and time costs. The serializer consists of a phase locked loop (PLL), several 5:1 sub-multiplexers based on a shift-register chain, a 4:1 or 8:1 sub-multiplexer based on the binary-tree structure, a clock distributor and a high-speed driver. Both ring-oscillating PLL and LC-tank PLL were integrated for performance evaluation. The preliminary tests showed low-jitter characteristics of the two PLLs despite this version's biasing problem, and both serializer circuits functioned correctly. A revision corrected the error and was submitted in October 2023. [ABSTRACT FROM AUTHOR]

Juice sac granulation (a physiological disorder) leads to large postharvest losses of pomelo (Citrus maxima). Previous studies have shown that juice sac granulation is closely related to lignin accumulation, while the molecular mechanisms underlying this disorder remain elusive in pomelo. Our results showed that the lignin content in NC (near the core) and FC (far away from the core) juice sacs overall increased from 157 DPA (days post anthesis) to 212 DPA and reached a maximum at 212 DPA. Additionally, the lignin content of NC juice sacs was higher than that of FC juice sacs. In this study, we used transcriptome-based weighted gene co-expression network analysis (WGCNA) to address how lignin formation in NC and FC juice sacs is generated during the development of pomelo. After data assembly and bioinformatic analysis, we found a most correlated module (black module) to the lignin content, then we used the 11 DEGs in this module as hub genes for lignin biosynthesis. Among these DEGs, PAL (phenylalanine ammonia lyase), HCT (hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferase), 4CL2 (4-coumarate: CoA ligase), C4H (cinnamate 4-hydroxylase), C3′H (p-coumarate 3-hydroxylase), and CCoAOMT1 (caffeoyl CoA 3-Omethyltransferase) were the most distinct DEGs in granulated juice sacs. Co-expression analysis revealed that the expression patterns of several transcription factors such as MYB, NAC, OFP6, and bHLH130 are highly correlated with lignin formation. In addition, the expression patterns of the DEGs related to lignin biosynthesis and transcription factors were validated by qRT-PCR, and the results were highly concordant with the RNA-seq results. These results would be beneficial for further studies on the molecular mechanism of lignin accumulation in pomelo juice sacs and would help with citrus breeding. [ABSTRACT FROM AUTHOR]

Background. As the most common hepatic malignancy, hepatocellular carcinoma (HCC) has a high incidence; therefore, in this paper, the immune-related genes were sought as biomarkers in liver cancer. Methods. In this study, a differential expression analysis of lncRNA and mRNA in The Cancer Genome Atlas (TCGA) dataset between the HCC group and the normal control group was performed. Enrichment analysis was used to screen immune-related differentially expressed genes. Cox regression analysis and survival analysis were used to determine prognostic genes of HCC, whose expression was detected by molecular experiments. Finally, important immune cells were identified by immune cell infiltration and detected by flow cytometry. Results. Compared with the normal group, 1613 differentially expressed mRNAs (DEmRs) and 1237 differentially expressed lncRNAs (DElncRs) were found in HCC. Among them, 143 immune-related DEmRs and 39 immune-related DElncRs were screened out. These genes were mainly related to MAPK cascade, PI3K-AKT signaling pathway, and TGF-beta. Through Cox regression analysis and survival analysis, MMP9, SPP1, HAGLR, LINC02202, and RP11-598F7.3 were finally determined as the potential diagnostic biomarkers for HCC. The gene expression was verified by RT-qPCR and western blot. In addition, CD4 + memory resting T cells and CD8 + T cells were identified as protective factors for overall survival of HCC, and they were found highly expressed in HCC through flow cytometry. Conclusion. The study explored the dysregulation mechanism and potential biomarkers of immune-related genes and further identified the influence of immune cells on the prognosis of HCC, providing a theoretical basis for the prognosis prediction and immunotherapy in HCC patients. [ABSTRACT FROM AUTHOR]

Bacteremia, as a serious infectious disease, has an increasing incidence and a high mortality rate. Early diagnosis and early treatment are crucial for improving the cure rate. In this work, we proposed an inductively coupled plasma mass spectrometry (ICP-MS)-based detection method combined with gold nanoparticle (Au NP) and silver nanoparticle (Ag NP) labeling for the simultaneous detection of Salmonella and Escherichia coli (E. coli O157:H7) in human blood samples. Salmonella and E. coli O157:H7 were captured by magnetic beads coupled with anti-8G3 and anti-7C2, and then specifically labeled by Au NP-anti-5H12 and Ag NP-anti-8B1 respectively, which were used as signal probes for ICP-MS detection. Under the optimal experimental conditions, the limits of detection of 164 CFU mL−1 for Salmonella , 220 CFU mL−1for E. coli O157:H7 and the linear ranges of 400–80,000 CFU mL−1 Salmonella , 400–60,000 CFU mL−1 E. coli O157:H7 were obtained. The proposed method can realize the simultaneous detection of two types of pathogenic bacteria in human whole blood in 3.5 h, showing great potential for the rapid diagnosis of bacteremia in clinic. [Display omitted] • This work combined immunomagnetic separation and ICP-MS with Au NP and Ag NP as elemental tags for bacteremia diagnosis. • Two types of pathogenic bacteria in human blood sample could be simultaneously detected in 3.5 h. • The proposed method improved the sample throughput of the reported ICP-MS based methods for bacteria detection. • This work shows the great potential of ICP-MS based methods for the rapid bacteremia diagnosis in clinic. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is a clinically high mortality disease, which has not yet been effectively treated. The development of anti -ALI drugs is imminent. ALI can be effectively treated by inhibiting the inflammatory cascade and reducing the inflammatory response in the lung. Forsythia suspense is a common Chinese herbal medicine with significant anti-inflammatory activity. Using forsythin as the parent, 27 Forsythin derivatives were designed and synthesized, and the anti-AIL activity of these compounds was evaluated. Among them, compound B5 has the best activity to inhibit the release of IL-6, and the inhibition rate reaches 91.79% at 25 μM, which was 7.5 times that of the parent forsythin. In addition, most of the compounds have no significant cytotoxicity in vitro. Further studies showed that compound B5 had a concentration-dependent inhibitory effect on NO, IL-6 and TNF-α. And the IC 50 values of compound B5 for NO and IL-6 are 10.88 μM and 4.93 μM, respectively. We also found that B5 could significantly inhibit the expression of some immune-related cytotoxic factors, including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, B5 inhibits NF-κB/MAPK signaling pathway. In vivo experiments showed that B5 could alleviate lung inflammation in LPS-induced ALI mice and inhibit IL-6, TNF-α, COX-2 and iNOS. In summary, B5 has anti-inflammatory effects and alleviates ALI by regulating inflammatory mediators and inhibiting MAPK and NF-κB signaling pathways. [Display omitted] • 27 novel forsythin derivatives from 6 series have been designed and synthesized. • In vitro , compound B5 has the strongest anti-inflammatory activity, with an IC 50 value of 4.93 μM for IL-6. • In vivo , compound B5 can alleviate LPS induced acute lung injury in mice. • Compound B5 alleviates ALI by regulating inflammatory mediators and inhibiting MAPK and NF-κB signaling pathways. [ABSTRACT FROM AUTHOR]

[Display omitted] • Twenty-nine 20(R)-Panaxadiol derivatives with carbamate structures were designed and synthesized and characterized. • In vitro neuroprotective activity was assessed using an Aβ 25-35 -induced PC12 cell injury model. • Molecular docking studies revealed a stronger binding affinity of compound Q4 for β-secretase. • In vivo experiments, Q4 significantly alleviated learning and memory deficits in mice. • Q4 is a potential multifunctional neuroprotective agent. It is reported that panaxadiol has neuroprotective effects. Previous studies have found that compound with carbamate structure introduced at the 3-OH position of 20 (R) -panaxadiol showed the most effective neuroprotective activity with an EC 50 of 13.17 μM. Therefore, we designed and synthesized a series of ginseng diol carbamate derivatives with ginseng diol as the lead compound, and tested their anti-AD activity. It was found that the protective effect of compound Q4 on adrenal pheochromocytoma was 80.6 ± 10.85 % (15 μM), and the EC 50 was 4.32 μM. According to the ELISA results, Q4 reduced the expression of Aβ 25-35 by decreasing β-secretase production. Molecular docking studies revealed that the binding affinity of Q4 to β-secretase was −49.67 kcal/mol, indicating a strong binding affinity of Q4 to β-secretase. Western blotting showed that compound Q4 decreased IL-1β levels, which may contribute to its anti-inflammatory effect. Furthermore, compound Q4 exhibits anti-AD activities by reducing abnormal phosphorylation of tau protein and activation of the mitogen activated protein kinase pathway. The learning and memory deficits in mice treated with Q4 in vivo were significantly alleviated. Therefore, Q4 may be a promising multifunctional drug for the treatment of AD, providing a new way for anti-AD drugs. [ABSTRACT FROM AUTHOR]

This study proposes an analytical framework for explaining how national IR (international relations) can keep exceptionalism at bay and join global IR in promoting common understanding. Building on the premise that dialogue is key to bridging the self–other divide, it stresses that self-reflection lies at the heart of a true "dialogic spirit," which urges the self to recognize its own shortcomings by learning from the other's point of view. By embracing the dialogic spirit and self-reflection, therefore, national IR can distance itself from exceptionalist claims that the "national self" is intrinsically superior to others and so its preferences and interests must outweigh those of the latter. Applying this framework to the nascent Chinese IR theory, this study finds that its leading exponents do try to avoid identifying with such exceptionalist claims, though the complications of their work further illustrate the promise and difficulty of self-reflection in the shadow of rising power. [ABSTRACT FROM AUTHOR]

In this paper, the synthesis of miniaturized filtering coupled‐line trans‐directional (CL‐TRD) coupler with wide suppression band is presented. This coupler is formed by two parallel coupled lines, one capacitor‐loaded coupled line, and four sub‐circuits. With the introduction of the sub‐circuits, extra transmission poles located at the cut‐off frequency are generated, resulting in high frequency selectivity. Size reduction is also achieved. Design equations of the filtering CL‐TRD coupler are derived using the even‐odd mode decomposition analysis and design procedures are provided for guidance. For demonstration, a 3 dB prototype with a size of 0.46 λg × 0.21 λg is designed, fabricated and measured. The measured results validate the 32% bandwidth centered at 1 GHz with more than 10 dB return loss/isolation, less than 0.5 dB amplitude imbalance and 5° phase error. Besides, a 15 dB wide stopband from 1.18 to 5.07 GHz (5.07f0) is obtained with a sharped skirt selectivity. [ABSTRACT FROM AUTHOR]

With Zn substitution to the three-dimensional antiferromagnetically ordered barlowite Cu4(OH)6FBr, Cu3Zn(OH)6FBr shows no magnetic phase transition down to 50 mK, and the system is suggested to be a two-dimensional kagomé quantum spin liquid [Chin. Phys. Lett. 34 077502 (2017)]. A key issue to identify such phase diagram is the exact chemical formula of the substituted compound. With Cu L-edge x-ray absorption spectrum (XAS) combined with the MultiX XAS calculations, we evaluate the Cu concentration in a nominal Cu3Zn(OH)6FBr sample. Our results show that although the Cu concentration is 2.80, close to the expected value, there is 34% residual Cu occupation in intersite layers between kagomé layers. Thus the Zn substitution of the intersite layers is not complete, and likely it intrudes the kagomé layers. [ABSTRACT FROM AUTHOR]

Summary This paper addresses the issue of distributed finite‐time attitude coordination control of spacecraft formations with multiple constraints on angular velocities and control torques. First, the multiple constrained problem is transformed into a bounded issue by virtue of the nonlinear transformation technique and an input saturation model. Next, the nearest neighbor rule is applied to deal with the problem of the unavailability of the leader's information to all followers. Then, a distributed attitude coordination control algorithm is derived to enforce that all attitude tracking errors can converge to a neighborhood around the origin in finite time even when there exist multiple constraints and external disturbances imposed on spacecraft systems. Finally, several numerical simulation examples are presented to illustrate the efficiency of the derived method. [ABSTRACT FROM AUTHOR]

Sorghum bicolor is widely cultivated in arid and semi-arid areas. This paper reports the chemical profiles of cuticular waxes on adaxial and abaxial sides of common leaf, flag leaf, sheath and stem from six sorghum cultivars and the variations of leaf cuticular waxes at seedling, jointing and filling stages. Then, the bioassay of leaf and sheath wax were evaluated against Penicillium sp and Alternaria alternata. The six sorghum cultivars had similar wax profiles. In total, eight wax compounds were identified, including fatty acids, aldehydes, primary alcohols, alkanes, secondary alcohols, ketones, sterols and minor triterpenoids. Leaf wax coverage increased from 2.2 to 3.1 μg/cm2 at seedling stages to 6.5–14.0 μg/cm2 at jointing and filling stages, respectively. The relative abundance of primary alcohols decreased from 51 to 62% at seedling stage to 17–33% at jointing stage whereas alkanes increased from 5-9% to 19–33%. Leaf was dominated with alkanes (28.4%) and aldehydes (28.4%), sheath with acids (42.8%), and stem with aldehydes (80.8%). Epicuticular wax of leaf and sheath contained higher proportions of alkanes whereas the intracuticular waxes contained higher proportions of sterols. The leaf wax improved the growth of Penicillium but reduced that of A. alternaria , whereas sheath wax reduced the growth of Penicillium but unchanged A. alternaria. The detailed sorghum wax profiles improve our understanding of the physiological roles of these waxes and their diversified potential usages in industries. Image 1 • The total wax coverage varied between growing stages and organs. • Sheath wax was dominated by acids whereas leaf wax was dominated with alkanes and aldehydes. • The total coverage of intracuticular wax was higher than that of epicuticular wax. • Leaf and sheath wax had different effects on growth of Penicillium sp and Alternaria alternatea. [ABSTRACT FROM AUTHOR]

Cannabinoid receptors type 1 (CB1) and 2 (CB2) are widely expressed in the human body, and are attractive drug targets in the prevention and management of central nervous system (CNS) and immune system dysfunction, respectively. Recent breakthroughs in the structural elucidation of cannabinoid receptors and their signaling complexes with G proteins, provide the important molecular basis of ligand–receptor interactions, activation and signaling mechanism, which will facilitate the next-generation drug design and the precise modulation of the endocannabinoid system. Here, we provide an overview on the structural features of cannabinoid receptors in different functional states and the diverse ligand binding modes. The major challenges and new strategies for future therapeutic applications targeting the endocannabinoid system (ECS) are also discussed. Cannabinoid receptors as key components of the endocannabinoid system are involved in regulating a variety of physiological and pathological activities, and their ligands are regarded as potential drug candidates for the treatment of many diseases. Ligands of cannabinoid receptors with functional and subtype receptor selectivity may provide more desired therapeutic benefits with fewer on/off-target adverse effects. Rapid progress in structural studies of cannabinoid receptors reveals their inactive, active-like, and active signaling states and provides valuable insights into ligand–receptor interactions, activation and signaling of cannabinoid receptors. The structural information will facilitate the specific drug/probe design for precise modulation of the endocannabinoid system. [ABSTRACT FROM AUTHOR]

This study examines the uses of interpersonal touch in everyday interaction. An examination of everyday interactions among adult Mandarin Chinese speakers shows that sustained touch recurs in conversational jokings in two interactional and sequential environments: sequentially disaligned jokings (i.e., jokings that disrupt the speaker's ongoing turn- and activity-in-progress) and jokings after extended disagreement. Sustained touch seems to perform several functions in the two environments. In sequentially disaligned jokings, the initiation of touch displays the speaker's orientation to the concurrent talk as disaligned with the projected talk- and activity-in-progress. Sustained touch secures the recipient's continuous participation in the sequentially disaligned jokings and requests the recipient's appreciation of the jokings. After extended disagreement, sustained touch displays intimacy and invites the recipient into intimate interaction with the speaker. In both environments, sustained touch seems to delimit the boundaries of a joking. The data are in Mandarin Chinese with English translation. [ABSTRACT FROM AUTHOR]

FoxO3a is a well-defined tumor suppressor gene in the forkhead transcription factor O subfamily (FoxO), and its reduction is related to the occurrence of various tumors. It was found that the expression of miR-155 is abnormally elevated in oral cancer tissues, suggesting that miR-155 may be a tumor-promoting gene for oral cancer. Bioinformatics analysis revealed a targeted complementary binding site between miR-155 and FoxO3a. In this study, we established a cisplatin-resistant cell line of oral cancer to compare the expression of miR-155 and FoxO3a in parental oral cancer cells, and explore whether miR-155 regulates the expression of FoxO3a and affects the proliferation and apoptosis of oral cancer cells. Dual luciferase reporter gene assay validated the targeted regulatory role between miR-155 and FoxO3a. The DDP-resistant oral cancer cell line KB/DDP was established, and the expressions of miR-155 and FoxO3a were compared. The CCK-8 assay was used to calculate the resistance index (RI). KB/DDP cells were divided into miR-NC group and miR-155 inhibitor group. Cell apoptosis was detected by flow cytometry. Cell proliferation ability was detected by EdU staining. There is a targeted regulatory relationship between miR-155 and FoxO3a mRNA. The expression of miR-155 was significantly higher, while the expression of Foxo3a mRNA and protein was obviously lower in KB/DDP cells than that in KB cells. CCK-8 experiments showed that the same concentration of DDP exhibited apparently lower proliferation inhibition in KB/DDP cells than KB cells. Compared with the miR-NC group, transfection of miR-155 inhibitor markedly increased the expression of Foxo3a in KB/DDP cells, which significantly attenuated cell proliferation and enhanced apoptosis in DDP-treated cells. Increased expression of miR-155 and decreased expression of Foxo3a were associated with DDP resistance in oral cancer cells. Inhibition of miR-155 expression upregulated Foxo3a expression, restrained oral cancer cell proliferation, promoted cell apoptosis, and enhanced DDP sensitivity in oral cancer cells. [ABSTRACT FROM AUTHOR]

Background: The status of axillary lymph nodes (ALNs) is one of the important factors in decision‐making for breast cancer treatment. Physical examination (PE) has long been the main, or even the only, means of clinical staging for ALNs in breast cancer. However, the sensitivity and accuracy of PE remains unsatisfactory. The results from this study suggest that axillary ultrasonography (US) should replace PE as a standard method for the clinical staging of ALNs in breast cancer. Methods: Consecutive and nonselective breast cancer patients treated between September 2018 and November 2018 in our center were enrolled in the study. Comparisons of ALN results between PE/US and pathological results were conducted and the difference in sensitivity, specificity and accuracy between PE and US were tested by McNemar chi‐square test. Results: A total of 123 patients were enrolled into the study. Their ages ranged from 28 to 76 years with a median age of 53 ± 10. There were 83 ALN positive cases and 40 ALN negative cases confirmed pathologically. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of PE and US were 54.2%, 90.0%, 65.9%, 91.8%, 48.7% versus 86.8%, 72.5%, 82.1%, 86.8%, 72.5%, respectively. The sensitivity and accuracy of US was significantly higher than that of PE (P = 0.004 and P = 0.002). Conclusion: The results of this study demonstrated that US is superior in evaluating ALNs when compared with PE and that US should replace PE as the standard method for the clinical staging of ALNs in breast cancer. [ABSTRACT FROM AUTHOR]

Clicks are velarically initiated ingressive stops. This study investigates the interactional uses of clicks in approximately 12 hours of Mandarin face-to-face conversations. It focuses on the TCU-medial clicks that occur in a type of action repair: a syntactically incomplete TCU followed by a click and the start of a new TCU. The click-initiated action repair changes the projected trajectories of actions-in-progress. It seems to be used to deal with two types of problems: the social and interactional inappositeness and sensitivity of the speaker's ongoing action shown through coparticipants' visually displayed orientations, and the speaker's own change of state. This study adds to our knowledge about the types of practices that may be used to accomplish repair and the types of problems that the action repair may be mobilized to deal with. Data are in Mandarin Chinese with English translation. [ABSTRACT FROM AUTHOR]

Background: Our study sought to investigate the therapeutic effects and mechanisms of miR-326-5p-overexpressing endothelial progenitor cells (EPCs) on acute myocardial infarction (AMI). Methods: Mouse EPCs were isolated, purified, and identified by flow cytometry and uptake of DiI-ac-LDL. The target gene of miR-326-5p was predicted using target prediction algorithms and verified by dual-luciferase reporter assay, RT-qPCR, and Western blot. After EPCs were transfected with the agomir or antagomir of miR-326-5p, tube formation assay and Matrigel plug angiogenesis assay were conducted in four groups (NC, miR-326-5p agomir, miR-326-5p antagomir, and miR-326-5p agomir+Wnt1 agonist). In addition, a mouse model of MI was established and treated with the injection of miR-326-5p-EPCs, miR-326-5p-EPCs+ Wnt1 agonist, EPCs-NC, or PBS/control into the peri-infarcted myocardium. Subsequently, cardiac function was monitored by echocardiography at 7 and 28 days postoperatively. Finally, the infarcted hearts were collected at 28 days, and the size of myocardial infarction was measured by Masson's trichrome staining and the neovascularization in the peri-infarcted area was examined through immunofluorescence staining. Results: Luciferase reporter assay indicated that Wnt1 was a direct target of miR-326-5p. Using RT-qPCR and Western blot analysis, we further demonstrated that the expression level of Wnt1 was negatively correlated with miR-326-5p expression in EPCs. Both in vitro study of tube formation assay and in vivo investigation of subcutaneous Matrigel plug assay revealed that the miR-326-5p agomir could significantly enhance the angiogenic capacity of EPCs, and this effect was partially inhibited by Wnt1 agonist. Meanwhile, miR-326-5p antagomir could obviously reduce the the angiogenic capacity of EPCs in vivo compared with that in the NC group. Moreover, the transplantation of miR-326-5p-overexpressing EPCs in the ischemic hearts of mice significantly enhanced the angiogenesis in the peri-infarcted zone and improved the cardiac function. However, the enhanced capacity of angiogenesis of miR-326-5p-overexpressing EPCs was remarkably neutralized by Wnt1 agonist, accompanied by the decreased improvement in cardiac function. Conclusion: miR-326-5p significantly enhanced the angiogenic capacity of EPCs. Transplantation of miR-326-5p-overexpressing EPCs improved cardiac function for AMI therapy, which can be a novel strategy for enhancing therapeutic angiogenesis in ischemic heart diseases. [ABSTRACT FROM AUTHOR]

INHBA-encoded inhibin β A is a member of the transforming growth factor-β (TGF-β) superfamily. INHBA has been reported to be implicated in the progression of multiple types of cancer including ovarian cancer (OC). However, the mechanisms by which INHBA affects OC progression are not well-characterized. The aim of our study was to explore the prognostic value of INHBA for different stages and grades of OC and to identify the possible mechanisms by which INHBA promotes OC progression. Our results demonstrated that INHBA was specifically expressed in OC epithelium, and higher expression was associated with higher risk of mortality in patients with advanced and higher-grade serous OC (SOC). In addition, knockdown of INHBA in cancer cells impaired cancer xenograft growth through reducing OC stromal fibroblast activation in vivo. Further results confirmed that Smad2 signaling pathway was involved in INHBA-induced stromal fibroblast activation, and inhibiting this pathway could effectively reverse activation of stromal fibroblasts. In summary, our results showed that blocking INHBA in cancer cells may be a potential therapeutic strategy to inhibit SOC progression. [ABSTRACT FROM AUTHOR]

Based on streptavidin coated nanospheres and T7 exonuclease assisted dual-cycle signal amplification, we developed a novel sensitive fluorescence polarization detection method for miRNA. When target miRNA was present in the system, hairpin probe hybridized with miRNA, forming a double-stranded structure. The 5′ end of hairpin probe was then recognized and digested by T7 exonuclease, releasing the non-degraded single strand DNA fragments and miRNA. The released target miRNA could trigger the next cycle of hybridization and digestion, releasing more non-degraded fragments from hairpin probe. The fragments could hybridize with a signal probe (with carboxyfluorescein modification at 5′-end and biotin modification at 3′-end). The formed blunt 5′-end of signal probe was then recognized and degraded by T7 exonuclease, releasing the fragments and the fluorophore carboxyfluorescein. The next cycle of hybridization and digestion of signal probe was triggered by the released fragment at the same time. The free carboxyfluorescein cannot connect with streptavidin coated nanospheres which were used as the fluorescence polarization signal amplifier. So, there was a big change of fluorescence polarization signal after adding miRNA into the detection system, due to the different fluorescence polarization signal between nanospheres-captured intact signal probe and free carboxyfluorescein. The detection limit of this method is about 0.001 nM, and it has a good selectivity. In addition, it was also applicable to determine target miRNA in total miRNA extracts and compare the expression level of target miRNA in different cells. Consequently, the proposed method is expected to be used for the potential cancer diagnosis and the related biomedical research. Image 1 • A simple fluorescence polarization assay for sensitive and selective detection of miRNA was developed. • Dual-cycle signal amplification based on T7 Exo was designed. • Using streptavidin-modified nanospheres as mass amplifiers, there was a big difference in FP signal with a low LOD. • It could be used to determine target miRNA in total miRNA extracts and compare the expression level in different cells. [ABSTRACT FROM AUTHOR]

• Minimum temperature played a dominant role in controlling the green-up date of alpine grassland on the Tibetan Plateau. • Minimum temperature in spring had greater impact on the GUD than that in winter. • Difference in minimum temperature between winter and spring may be a novel indicator for spring onset in alpine grassland. Temperature increases in spring can advance vegetation green-up date (GUD) due to the increased heat accumulations. However, temperature increases in winter will delay the GUD due to the postponed fulfilment of chilling requirements. Such contrasting impacts of temperature changes in spring and winter on the GUD have been documented from many ecosystems in the Northern Hemisphere. However, the combined effects of temperature variations in winter and spring on the GUD remained unclear, especially in the cold Tibetan Plateau. To advance our understanding of how alpine grassland GUD responds to climate warming, this study evaluated 14 years of field GUD observations of sedge species Kobresia humilis on the Tibetan Plateau. The results showed that January and March-April were two critical periods in determining the long-term GUD variations. The minimum temperatures (T min) during these two critical periods played the dominant roles in controlling the GUD. Increases in the T min significantly shifting the GUD by −3.9 days °C−1 and 1.7 days °C−1 in the spring and winter, respectively. Moreover, T min in March-April played a more important role in determining the GUD than did T min in January. In addition, the difference in minimum temperature (ΔT min) between these two critical periods of January and March-April might be a novel indicator for vegetation GUD. This study provides novel insights into the differential impacts of minimum temperatures in winter and spring on the GUD and how they should be explicitly considered to better understand the effects of climate change on vegetation phenology. [ABSTRACT FROM AUTHOR]

Bacterial detection is a daily work closely related to human health. Although many detection methods can achieve rapid and sensitive bacterial detection, they usually focus on detecting small-volume samples. Due to the uneven distribution of bacterial particles in the liquid, the total bacterial content calculated based on small-volume samples may deviate significantly from the actual state. Here, a simple visual assay for the detection of bacteria in large-volume samples was reported, and the Gram-positive bacteria detection was taken as an example to verify its practicability. By using a composite filter membrane with a hydrophobic layer and an adjustable interception area to filter the sample, the bacteria can be confined to a small detection area. After the obvious chromogenic reaction was catalyzed by antibiotic-modified nanoparticles specifically bound to bacteria, the naked eye can more easily perceive the highly concentrated color molecules, thus realizing more sensitive bacterial detection. As a result, samples containing more than 20 Staphylococcus aureus cells (2 cfu/mL) can be easily identified by naked eyes within 30 min, and show reasonable specificity and practicability. Given the advantages of easy preparation, simple operation, and low dependence on instruments, the visual assay is worthy of being widely used. [Display omitted] • Deal with the challenge of bacterial detection in large-volume samples. • Realize sensitive and rapid visual detection of Gram-positive bacteria. • Easy preparation, simple operation, and low dependence on instruments. [ABSTRACT FROM AUTHOR]

A novel mono-quaternary phosphorus salt functionalized fiber (PAN QPS F) was developed as the multifunctional material to simultaneously realize selective removal of sodium dodecyl benzene sulfonate (SDBS) from water and green conversion of CO 2. Compared with other adsorption materials and functionalized fibers, PAN QPS F exhibits the eminent adsorption performance for SDBS due to its high polarization and hydrophobicity, and the adsorption capacity can reach 5.1 mol mol−1, equivalenting to 1066 mg g−1. And the synergistic adsorption mechanism of electrostatic interaction and lipophilic interaction between PAN QPS F and SDBS is proposed. Furthermore, the PAN QPS F still keeps excellent adsorption capacity even after 10 cycles. More satisfactorily, PAN QPS F is used to catalyze the cycloaddition reaction of CO 2 and epoxy compounds. The catalytic mechanism based on the nucleophilicity of Br− and the stabilizing effect of electrostatic interaction is promoted. In summary, the adsorption and catalytic performance prove that PAN QPS F is an outstanding material with multi-dimensional applications. [Display omitted] • A novel mono-quaternary phosphorus salt functionalized polyacrylonitrile fiber (PAN QPS F) was developed. • PAN QPS F can be used to selective removal of sodium dodecyl benzene sulfonate (SDBS) and green conversion of CO 2. • The adsorption capacity for SDBS can reach 1066 mg g−1 and it still keeps excellent adsorption capacity after 10 cycles. [ABSTRACT FROM AUTHOR]

Highlights • Mixotrophic microalga showed better growth and stronger tolerance to high ammonium. • The synthesis of microalgal carbohydrates was inhibited by higher ammonium. • Ammonium increased microalgal lipids in mixotrophic cultivation. • Inhibition to the photosynthetic activity was intensified by elevated ammonium. Abstract To enhance microalgal growth and optimize ammonium utilization, the effect of ammonium on microalgal growth, biochemical composition and photosynthetic performance were investigated by mixotrophic cultivation of microalga Spirulina platensis comparing with autotrophic cultivation. The results indicated that elevated ammonium significantly affected the microalgal growth, but the microalga in mixotrophic cultivation showed better growth and stronger tolerance to higher ammonium. The microalgal proteins were increased by increasing nitrogen concentration. The synthesis of microalgal carbohydrates was inhibited by higher ammonium, especially in mixotrophic cultivation. The addition of ammonium decreased the microalgal lipids in autotrophic cultivation but increased microalgal lipids in mixotrophic cultivation. Ammonium negatively affected the microalgal photosynthetic performance. The inhibition was intensified by elevated ammonium, inducing stronger photosystem protection mechanism, particularly in mixotrophic cultivation. The rate of ammonium inhibition to the microalgal photosystem was quick in the early stage by decreasing electron transport rate of PS II. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Magnesium Isoglycyrrhizinate (MgIG), a novel molecular compound extracted from licorice root, has exhibited greater anti-inflammatory activity and hepatic protection than glycyrrhizin and β-glycyrrhizic acid. In this study, we investigated the anti-inflammatory effect and the potential mechanism of MgIG on Lipopolysaccharide (LPS)-treated RAW264.7 cells. MgIG down-regulated LPS-induced pro-inflammatory mediators and enzymes in LPS-treated RAW264.7 cells, including TNF-α, IL-6, IL-1β, IL-8, NO and iNOS. The generation of reactive oxygen species (ROS) in LPS-treated RAW264.7 cells was also reduced. MgIG attenuated NF-κB translocation by inhibiting IKK phosphorylation and IκB-α degradation. Simultaneously, MgIG also inhibited LPS-induced activation of MAPKs, including p38, JNK and ERK1/2. Taken together, these results suggest that MgIG suppresses inflammation by blocking NF-κB and MAPK signaling pathways, and down-regulates ROS generation and inflammatory mediators. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Dual-functional probe for quantification and imaging of intracellular telomerase was designed. • ICP-MS quantification and fluorescence imaging of intracellular telomerase were realized. • ICP-MS with Tb-DOTA labeling could quantify intracellular telomerase without extraction. • It is potential for studying mechanism of cancer and other telomerase-related life processes. Abstract The analysis of telomerase is of great significance for the study and diagnosis of cancer. In this work, a dual-functional Au NP probe for the quantification and imaging of intracellular telomerase was prepared. The probe contained an elemental tag (1,4,7,10-tetraazacyclododecane-1,4,7-tris-acetic acid (Tb-DOTA)) for accurate quantification using inductively coupled plasma mass spectrometry (ICP-MS) and a fluorescent tag (FAM) which constructed the fluorescence resonance energy transfer (FRET) system with Au NPs for fluorescence imaging. After the probe entered into the Hela cells, the telomerase primer was extended with TTAGGG repeats in the presence of the intracellular telomerase, resulting in turning on the fluorescence of FAM and releasing the Tb-DOTA. Thus, the intracellular telomerase could be in situ visualized by the released FAM with fluorescence imaging and quantified by the released Tb-DOTA with ICP-MS detection. The average amount of telomerase in one Hela cell was quantified to be 3.1 × 10−11 IU. The proposed method was demonstrated with good potential in the study of telomerase and the cancer diagnosis, providing a new strategy for the analysis of intracellular biomarkers by ICP-MS. [ABSTRACT FROM AUTHOR]

Abstract Bioequivalence study is highly prized to piroxicam (PIRO), since its generic products have been widely used worldwide. The present work was undertaken to explore the pharmacokinetic behaviors and bioequivalence of two branded PIRO tablets in beagle dogs using the supercritical fluid chromatography tandem mass spectrometry (SFC-MS/MS) method. Here, a fast evaporation-free liquid-liquid extraction (EF-LLE) method using ethyl acetate was developed for extracting PIRO from beagle dog plasma. To improve the response as well as peaks elution and symmetry of analytes, several key factors were investigated including post-column compensation, stationary phase, mobile phase, column temperature, back pressure and flow rate, and finally the analytes were eluted on an ACQUITY UPC2™ BEH 2-EP column (100 × 3 mm, 1.7 μm) within only 2.5 min in optimal conditions. The performance of the established method was evaluated, good linearity was found over the concentration range of 5–5000 ng/mL (R2 ≥ 0.994) with a lower limit of quantification (LLOQ) of 5 ng/mL. Accuracy of all quality control (QC) samples were between 96.6% and 99.6% with a satisfactory intra and inter-day precision (RSD values < 6.6%). The proposed rapid, sensitive, user-friendly and high throughput method will be an alternative way for PIRO analysis in biological samples. Highlights • A rapid and straightforward analytical method was exploited using SFC-MS/MS. • An evaporation-free LLE method was firstly used in PIRO biological sample preparation. • A satisfied sensitivity (LLOQ 5 ng/mL) and short elution time (2.5 min) were achieved. • Less plasma usage is more consistent with animal ethical requirements. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights: • 74 benzenesulfonyl derivatives were designed and synthesized. • A5.7 and B5.7 showed promising insecticidal activities. • Isothermal Titration Calorimetry data supported the activity studies. Abstract Two lead compounds with benzenesulfonamide were found through virtual screening based on the 3D structure of the subunit H of V-ATPase in previous study. 74 benzenesulfonyl derivatives were synthesized and their insecticidal activities were evaluated. The derivatives with propargyl substituents exhibit excellent insecticidal activities against Mythimna separata Walker. The LD 50 values of compounds A5.7 (28.0 μg·g−1) and B5.7 (36.4 μg·g−1) were significantly less than that of Celangulin V (344.0 μg·g−1). Furthermore, Isothermal Titration Calorimetry (ITC) data indicate there is a strong binding affinity between A5.7 and V-ATPase Subunit H. These results demonstrate that it is a practical way to develop pesticides targeting at H subunit of V-ATPase. [ABSTRACT FROM AUTHOR]

Purpose: Distinct subgroup of the Ras family member 3 (DIRAS3), also called Aplasia Ras homolog member I, is a tumor suppressor gene that induces autophagy in several cancer cell lines.Methods: This study analyzed DIRAS3, and markers of autophagy (p62, and LC3B-II) in surgically resected GC samples from 420 patients. The promotion of autophagy by DIRAS3 in gastric cancer (GC) cells was explored, which might explain its inhibitory role in gastric cancer cells.Results: DIRAS3 expression in GC was positively correlated with LC3B-II amount, and negatively with metastasis; DIRAS3 and p62 levels were independent prognostic factors in GC. Overexpression of DIRAS3 in BGC-823 cells induced autophagy, led to decreased proliferation, cell cycle arrest in G0/G1 phase, increased apoptosis, and impaired migration and invasion. While knockdown of DIRAS3 promoted proliferation and migration in MKN-45 cells. Overexpression of DIRAS3 in BGC-823 cells elevated autophagy levels in subcutaneous xenograft and inhibited tumor growth in mice; the hematogenous liver and lung metastasis of cancer cells were also suppressed.Conclusions: In conclusion, the results suggest DIRAS3 may play a role in affecting proliferation and metastatic potential of GC cells, which may be associated with its involvement in autophagy regulation. [ABSTRACT FROM AUTHOR]

In this study, the effect of nitrogen limitation on microalgal growth, biochemical composition and photosynthetic performance was investigated in fed-batch mixotrophic cultivation of microalga Spirulina platensis , compared with that in autotrophic cultivation. The microalgal biomass productivity was greatly enhanced by mixotrophic cultivation. With nitrogen limitation, the mixotrophic culture accelerated the degradation of microalgal pigments and proteins to supply intracellular nitrogen for maintaining higher biomass productivity, simultaneously accumulating more carbohydrates. The mixotrophic cultivation amplified the adverse effect of nitrogen limitation on the microalgal photosynthetic performance in comparison with autotrophic cultivation. This fed-batch mixotrophic cultivation is an effective strategy for enhancing biomass productivity and total carbohydrates yield under nitrogen limited conditions. [ABSTRACT FROM AUTHOR]

[Display omitted] • Based on aggregation of Y-shaped DNA for FP assay is reported for the first time. • It combined DSN-assisted target recycling and CHA for dual amplification. • This method could distinguish single-base mismatch with high selectivity. • The result for the expression level of miRNA in different cell lines is satisfactory. MicroRNAs (miRNAs) have emerged as one of the promising biomarkers. Their aberrant levels are intimately connected to various diseases. However, Sensitive assay of low-abundance miRNAs remain a grand challenge. Herein, a novel sensitive cascade-amplified fluorescence polarization (FP) sensing platform for miRNA detection was developed based on aggregation strategy of Y-shaped DNA via streptavidin (SA). The miRNA-155 was employed as the model target analyte. In the presence of miRNA-155, the duplex-specific nuclease (DSN) cycling amplification and catalytic hairpin assembly (CHA) cycling amplification were triggered successively. Owing to the target-triggering dual cyclic amplification, numerous Y-shaped DNA nanostructure could be easily generated according to the assembly order of hairpin probes. Then, SA was added to the system, inducing the aggregation of Y-shaped DNA nanostructure to form a large-size of DNA/SA complexes. Taking advantages of cascade-amplified strategy, a significant enhancement of the FP signal was achieved and a sensitive assay for miRNA detection was realized with the detection limit of 1 × 10-13 M. Beyond that, the proposed method could distinguish single-base mismatch and achieved satisfactory result for the expression level assay of miRNA-155 in different cell lines, holding great potential in the applications in miRNA-related clinical diagnosis and biochemical researches. [ABSTRACT FROM AUTHOR]

[Display omitted] • The pore size of the ZIF-67 was enlarged by thermal annealing treatment. • The intercrystalline cracks in ZIF-67 layer were eliminated. • The permeance of the annealed ZIF-67 membrane was enhanced by two times. • The annealed ZIF-67 membrane had high rejection for pharmaceutical molecule. • The annealed ZIF-67 membrane exhibited stable separation performance. Zeolitic imidazolate frameworks (ZIFs) have been attracting intensive attention in membrane separation fields because of their ultrahigh specific surface areas, well-defined apertures, and variable topological characteristics. However, the aperture sizes of ZIFs are smaller than the kinetic diameters of most organic solvent molecules, which impedes their applications in organic solvent separation. Herein, we develop a thermal annealing-derived methodology for defect engineering on the ZIF-67 membrane. This post-synthetic modification not only expanded the aperture size of ZIF-67 but also repaired intercrystalline cracks in the polycrystalline ZIF-67 layer. By controlling the thermal annealing conditions, the permeability of the polycrystalline ZIF-67 membrane toward organic solvent nanofiltration was enhanced by two times. Moreover, the annealed ZIF-67 membrane showed a high rejection of more than 99.6% for dyes (Evans blue) and pharmaceutical molecules (tetracycline, vitamin B12). This work provides an avenue for the controllable modification of ZIFs membranes to broaden their applications. [ABSTRACT FROM AUTHOR]

Objective: This retrospective study aimed to investigate the association between TNs and the systemic immune-inflammation index (SII) and the aggregate index of systemic inflammation (AISI) in patients with T2DM. Methods: A total of 370 T2DM patients, who were admitted to Dongzhimen Hospital between January 2020 and March 2023, were included in this retrospective study. Binary logistic regression models with multivariable adjustment were employed to assess the relationship between SII, AISI quartiles, and TNs. Furthermore, receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic accuracy of SII and AISI in identifying T2DM patients with TNs. Results: Age, diabetes duration, diabetic nephropathy (DN), SII, and AISI demonstrated significant positive associations with TNs. Compared to the first quartile of SII, the second, third, and fourth quartiles showed increased risks of TNs with hazard ratios (HRs) of 1.578 (0.883–2.820), 2.279 (1.257–4.131), and 3.626 (1.931–6.810), respectively (P < 0.001). Similar results were observed for AISI and TNs. ROC curve analysis revealed that SII and AISI exhibited a high discriminatory capability for identifying TNs in the overall and male participant group, whereas the significance among females was not discernible. Conclusions: This study provides evidence that SII and AISI are independent risk factors for TNs, suggesting that elevated SII and AISI levels may contribute to the development of TNs in patients with T2DM particularly among male individuals. [ABSTRACT FROM AUTHOR]

Lactic acid bacteria are of interest to the food industry due to their antimicrobial properties. In this study, five strains of Lactobacillus plantarum were isolated from traditional fermented dairy food in Inner Mongolia; the strains displayed antifungal characteristics. Lactobacillus plantarum ALAC‐4 was selected for further study due to its strong inhibitory effect on fungal development. The antifungal substances produced by L. plantarum ALAC‐4 were characterised based on treatments with heat, pH and enzymes. The antifungal metabolites were analysed using gel‐filtration chromatography and SDS‐PAGE. The results showed that the antifungal substances were heat stable and active against most of the tested fungi, and maximal activity was observed at pH values from 4.0 to 4.5. The antifungal activity was decreased by protease treatments, which indicated the proteinaceous nature of the antifungal substances. Enhanced antifungal activity occurred after 28 h of incubation in de Man, Rogosa, Sharpe (MRS) broth with a 4% inoculum level at 34 °C and initial pH of 7.0, which resulted in an increase from baseline data. The molecular mass of the antifungal substance determined by SDS‐PAGE was approximately 40.32 kDa. This study demonstrated that L. plantarum ALAC‐4 produces a peptide with a remarkable antifungal activity, which can be potentially used as a biopreservative in dairy products. [ABSTRACT FROM AUTHOR]

In this work, we developed an immunoassay based on tyramide signal amplification (TSA) and gold nanoparticles (Au NPs) labeling for highly sensitive detection of alpha fetoprotein (AFP) by inductively coupled plasma mass spectrometry (ICP-MS). AFP was captured by anti-AFP1 coating on the 96-well plate and labeled by anti-AFP2-horseradish peroxidase (HRP), in which the HRP can catalyze the deposition of biotinylated tyramine on the nearby protein. Then the streptavidin (SA)-Au NPs was labeled on the deposited biotinylated tyramine as the intensive signal probe for ICP-MS measurement. Under the optimal experimental conditions, the limit of detection of the developed method for AFP was 1.85 pg/mL and the linear range was 0.005–2 ng/mL. The relative standard deviation for seven replicate detections of 0.01 ng/mL AFP was 5.2%. The proposed method was successfully applied to the detection of AFP in human serum with good recoveries. This strategy is highly sensitive and easy to operate, and can be extended to the sensitive detection of other biomolecules in human serum. [ABSTRACT FROM AUTHOR]

Interferon-γ (IFN-γ), a cytokine produced by activated natural killer cells and T lymphocytes, is an important regulator of innate and adaptive immunity. Interleukin (IL)-18, also known as IFN-γ-inducing factor, is a cytokine that induces T and natural killer cells to produce IFN-γ. In this study, the chicken IL-18 (ChIL-18) and chicken IFN-γ (ChIFN-γ) genes were inserted into the pET28a prokaryotic expression vector, resulting in pET28a-IL-18 and pET28a-IFN-γ, respectively. These plasmids were transformed into Escherichia coli strain BL21, and the ChIL-18 and ChIFN-γ proteins were expressed and purified. To determine their antiviral activities, 200 ng/mL of ChIL-18 and/or ChIFN-γ were inoculated into chicken embryonic fibroblast cells. After 24 h, one 50% tissue culture infective dose (TCID50) of infectious bursal disease virus (IBDV) was inoculated into the chicken embryonic fibroblast cells. The results showed that the antiviral effect of ChIL-18 and ChIFN-γ in combination was better than that of ChIL-18 or ChIFN-γ alone. Next, 14-day-old chicken were injected with 200 µg of ChIL-18 and/or ChIFN-γ and then were challenged with 10³ TCID50 of IBDV via intraperitoneal injection. The results showed that the proliferation of IBDV was inhibited by the injection of the recombinant proteins, especially the combination of ChIL-18 and ChIFN-γ, as evidenced by cytokine detection, quantitative PCR, and pathology analyses. These results indicate that ChIL-18 and ChIFN-γ could inhibit IBDV infection and the combination of ChIL-18 and ChIFN-γ has a better inhibitory effect than either cytokine alone. [ABSTRACT FROM AUTHOR]