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In this study, adlay rice bran-zinc chelate (ABP-Zn) was prepared as a novel and effective zinc supplement to mitigate environmental pollution and reduce the wastage of protein resources during adlay rice production. Under optimal conditions, i.e. time = 60 min, peptide-to-zinc mass ratio = 3:1, pH = 6.0, temperature = 60°C, the Zn content of the ABP-Zn chelate reached 53.52 ± 3.32 mg/g. The ABP-Zn chelate was formed as a result of the bonding of the carbonyl, amino, and carboxyl groups with Zn2+. This was demonstrated by fluorescence spectra, X-ray diffraction, ultra-violet spectroscopy, Fourier transform infrared spectroscopy, surface elemental composition, amino acid composition, multiangle analyses, and physical attributes, such as microstructure and particle size. Compared to zinc gluconate and zinc sulfate, the ABP-Zn chelate exhibited increased stability under various temperatures, pH, and simulated digestive digestion conditions. Furthermore, ABP-Zn significantly promoted the transport of zinc in the Caco-2 cell model. These findings suggest that zinc-binding peptide derived from adlay rice protein has great potential to be used as an ingredient in zinc supplements.

Natural products are one of the essential sources of innovative drugs. Trigothysoid N, a natural daphnane diterpenoid obtained from Trigonostemon thyrsoideus, possessed the strong ability to inhibit the proliferation of A549 cells. Besides interrupting the cell cycle, the mechanism examination revealed that trigothysoid N can inhibit tumor proliferation and migration by targeting mitochondria, regulating the STAT3/FAK signal pathway, and suppressing angiogenesis. In addition to the possible mechanism, in vivo antitumor experiments were performed to explore the potential of trigothysoid N for treating non-small cell lung cancer (NSCLC). Collectively, these findings supported the great potential of trigothysoid N as a hopeful therapeutic agent against NSCLC.

Nanoparticles have been found to possess unique advantages in many fields, especially in the field of cancer treatment. Herein, based on the unique physical and chemical properties of natural polysaccharides, the polysaccharide from the edible and medicinal fruits of Chaenomeles speciosa was prepared, and the complex nanoparticles constructed by combining C. speciosa polysaccharide with selenium have been successfully developed by a chemical method. Monodisperse spherical nanoparticles with the particle size of 80.5 nm were characterized by various methods, which exhibited ideal size distribution and prominent stability under physiological conditions and alkaline conditions. Cellular studies demonstrated the nanoparticles significantly inhibited the growth of MCF-7 cells with an IC50 value of 8.37 ± 0.97 μg/mL through inducing the apoptosis and arresting the cell circle at S phase. Moreover, the zebrafish assays confirmed the antitumor effects of the nanoparticles, which suppressed the proliferation and migration of tumor and blocked the angiogenesis of transgenic zebrafish. Collectively, the results suggested that the nanoparticles may be considered as a candidate agent to treat breast cancer.

To discover phytochemicals as lead compounds for cancer treatment, cratoxylumxanthone C, a natural xanthone, was obtained from Cratoxylum cochinchinense (Lour.) Bl., for which there have been no reports on the biological effects against cancer. Our study revealed that cratoxylumxanthone C had significant anti-tumor activity by inducing apoptosis, augmenting cellular reactive oxygen species (ROS), and arresting cell circle. The mechanistic examination showed the inhibition of A549 cell proliferation and metastasis by cratoxylumxanthone C was coupled with the signal transducer and activator of transcription 3 (STAT3) and focal adhesion kinase (FAK) signaling pathways. Furthermore, the zebrafish models confirmed its significant in vivo anti-tumor activity, in which cratoxylumxanthone C inhibited tumor proliferation and metastasis and suppressed the angiogenesis. Comprehensively, these cellular and zebrafish experiments implied that cratoxylumxanthone C may have the potential to become an anti-tumor agent for lung cancer, especially non-small cell lung cancer (NSCLC).

Casearlucin A, a diterpenoid obtained from Casearia graveolens, has been reported to possess strong cytotoxic activity. However, the in vivo anti-tumor effects and the action mechanism of casearlucin A remain poorly understood. Our study revealed that casearlucin A arrested cell cycle at G0/G1 stage and induced cell apoptosis in cell level. Additionally, casearlucin A inhibited HepG2 cell migration via regulating a few of metastasis-related proteins. Furthermore, it inhibited tumor angiogenesis in zebrafish in vivo. More importantly, casearlucin A significantly inhibited cell proliferation and migration in an in vivo zebrafish xenograft model. Collectively, these results are valuable for the further development and application of casearlucin A as an anticancer agent.

Abstract TNF inhibitors have been used to treat autoimmune and autoinflammatory diseases. Here we report an unexpected mechanism underlying the therapeutic effects of TNF inhibitors in Behçet’s disease (BD), an autoimmune inflammatory disorder. Using serum metabolomics and peripheral immunocyte transcriptomics, we find that polymorphonuclear neutrophil (PMN) from patients with BD (BD-PMN) has dysregulated mevalonate pathway and subsequently increased farnesyl pyrophosphate (FPP) levels. Mechanistically, FPP induces TRPM2-calcium signaling for neutrophil extracellular trap (NET) and proinflammatory cytokine productions, leading to vascular endothelial inflammation and damage. TNF, but not IL-1β, IL-6, IL-18, or IFN-γ, upregulates TRPM2 expression on BD-PMN, while TNF inhibitors have opposite effects. Results from mice with PMN-specific FPP synthetase or TRPM2 deficiency show reduced experimental vasculitis. Meanwhile, analyses of public datasets correlate increased TRPM2 expressions with the clinical benefits of TNF inhibitors. Our results thus implicate FPP-TRPM2-TNF/NETs feedback loops for inflammation aggravation, and novel insights for TNF inhibitor therapies on BD.

Abstract Aims This study was performed to identify and summarize systematic reviews focusing on the prevention of unplanned endotracheal extubation in the intensive care unit. Design Overview of systematic reviews. Methods This overview was conducted according to the Preferred Reporting Items for Overviews of Systematic Reviews, including the harms checklist. A literature search of PubMed, the Cochrane Library, CINAH, Embase, Web of Science, SINOMED and PROSPERO was performed from January 1, 2005–June 1, 2021. A systematic review focusing on unplanned extubation was included, resulting in an evidence summary. Results Thirteen systematic reviews were included. A summary of evidence on unplanned endotracheal extubation was developed, and the main contents were risk factors, preventive measures and prognosis. The most important nursing measures were restraint, fixation of the tracheal tube, continuous quality improvement, psychological care and use of a root cause analysis for the occurrence of unplanned endotracheal extubation. Conclusions This overview re‐evaluated risk factors and preventive measures for unplanned endotracheal extubation in the intensive care unit, resulting in a summary of evidence for preventing unplanned endotracheal extubation and providing direction for future research. Trial registration details The study was registered on the PROSPERO website.

BackgroundPatients with diabetes mellitus often suffer from diabetes distress. Social support and certain psychological factors potentially influence diabetes distress, but studies exploring the mechanisms underlying these relationships are scarce.ObjectivesTo reveal the associations between social support, diabetes stigma, diabetes self-efficacy, and diabetes distress among patients with type 2 diabetes and the underlying mechanisms linking these variables.Design and methodsA multicenter cross-sectional study was adopted and a sample of 431 patients with type 2 diabetes was investigated. Social support, diabetes stigma, diabetes self-efficacy, and diabetes distress were surveyed with the Perceived Social Support Scale, Type 2 Diabetes Stigma Assessment Scale, Self-Efficacy for Diabetes Scale, and Diabetes Distress Scale, respectively. The hypothesized model was verified using structural equation modeling.ResultsSocial support and diabetes stigma had direct associations with diabetes distress. Diabetes stigma mediated the association between social support and diabetes distress, and the association between diabetes self-efficacy and diabetes distress. Diabetes stigma and self-efficacy exerted a chain mediation effect on the association between social support and diabetes distress.ConclusionSocial support and diabetes stigma were significant predictors of diabetes distress. Diabetes stigma and self-efficacy play essential mediating roles in relieving diabetes distress. This can provide guidance for the development of evidence- and theory-based interventions. Culturally sensitive interventions that aim to provide ongoing social support, decrease diabetes stigma, and enhance self-efficacy have the potential to relieve diabetes distress.

Abstract Background Cervical cancer (CC) is one of the most common malignancies affecting female worldwide. Long non-coding RNAs (lncRNAs) are increasingly indicated as crucial participants and promising therapeutic targets in human cancers. The main objective of this study was to explore the functions and mechanism of LINC00885 in CC. Methods RT-qPCR and western blot were used to detect RNA and protein levels. Functional and mechanism assays were respectively done for the analysis of cell behaviors and molecular interplays. Results Long intergenic non-coding RNA 885 (LINC00885) was discovered to be upregulated in CC tissues and cell lines through bioinformatics analysis and RT-qPCR. Overexpression of LINC00885 promoted proliferation and inhibited apoptosis, whereas its silence exerted opposite effects. The cytoplasmic localization of LINC00885 was ascertained and furthermore, LINC00885 competitively bound with miR-3150b-3p to upregulate BAZ2A expression in CC cells. Rescue assays confirmed that LINC00885 regulated CC proliferation and apoptosis through miR-3150b-3p/BAZ2A axis. Finally, we confirmed that LINC00885 aggravated tumor growth through animal experiments. Conclusions LINC00885 exerted oncogenic function in CC via regulating miR-3150b-3p/BAZ2A axis. These findings suggested LINC00885 might serve as a potential promising therapeutic target for CC patients.

The water discharge and sediment load have been increasingly altered by climate change and human activities in recent decades. For the Pearl River, however, long-term variations in the sediment regime, especially in the last decade, remain poorly known. Here we updated knowledge of the temporal trends in the sediment regime of the Pearl River at annual, seasonal and monthly time scales from the 1950s to 2020. Results show that the annual sediment load and suspended sediment concentration (SSC) exhibited drastically decreased, regardless of water discharge. Compared with previous studies, we also found that sediment load and SSC reached a conspicuous peak in the 1980s, and showed a significant decline starting in the 2000s and 1990s, respectively. In the last decade, however, water discharge and sediment load showed slightly increasing trends. At the seasonal scale, the wet-season water discharge displays a decreasing trend, while the dry-season water discharge is increasing. At the monthly scale, the flood seasons in the North and East Rivers typically occur one month earlier than that in the West River due to the different precipitation regimes. Precipitation was responsible for the long-term change of discharge, while human activities (e.g. dam construction and land use change) exerted different effects on the variations in sediment load among different periods. Changes in the sediment regime have exerted substantial influences on downstream channel morphology and saltwater intrusion in the Greater Bay Area. Our study proposes a watershed-based solution, and provides scientific guidelines for the sustainable development of the Greater Bay Area.

BackgroundThe information on medication literacy among Chinese caregivers of discharged children with Kawasaki disease (KD) is unknown. We aimed to investigate the status of medication literacy among caregivers of discharged children with KD and evaluate the influencing factors of medication literacy.MethodsFrom March 2020 to February 2021, 106 caregivers with a KD child were recruited for the present study. We collected the sociodemographic characteristics of the KD caregivers using structured interviews. The medication literacy of the KD caregivers was assessed by the Chinese version of Medication Literacy Assessment. KD patients' demographic and clinical data were obtained from the medical records. The multiple logistic regression was performed to identify factors associated with medication literacy.Results(1) The average medication literacy score was 4.91 ± 1.51. (2) Most of the Chinese KD caregivers had insufficient medication literacy (≤ 5 scores), and only 39.2% of the caregivers had adequate medication literacy (>5 scores). (3) The multiple logistic regression shows that education level, monthly income, and duration of hospitalization are the independent influencing factors on the medication literacy of KD caregivers.ConclusionThere is preliminary evidence that medication literacy among KD caregivers is low and needs improvement. A higher level of education, higher income, and longer duration of hospitalization were influencing factors of adequate medication literacy.

Background: Observational studies analyzing the risk of prostate cancer in schizophrenia patients have generated mixed results. We performed a meta-analysis and a Mendelian randomization (MR) analysis to evaluate the relationship and causality between schizophrenia and the risk of prostate cancer. Methods: A comprehensive and systematic search of cohort studies was conducted, and a random-effects model meta-analysis was performed to calculate the standardized incidence ratios (SIRs) for prostate cancer incidence among schizophrenia patients versus the general population. To investigate the correlation between genetically-predicted schizophrenia and prostate cancer risk, we used summary statistics from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium (61,106 controls and 79,148 cases), and 75 schizophrenia-associated single nucleotide polymorphisms (SNP) from European descent as the instrumental variable. Results: In the meta-analysis of 13 cohort studies with 218,076 men involved, a decreased risk of prostate cancer was observed among schizophrenia patients [SIR 0.610; 95% confidence interval (CI) 0.500–0.740; p

We collected flying fish (Exocoetus volitans) from the South China Sea to determine whether fish scale isotope values correlate with those from muscle, and discuss relevant eco-environmental implications. A significant positive correlation was determined between fish scales and muscle δ13C and δ15N, rendering a fish scale an alternative to muscle tissue for stable isotope analysis. However, muscle and scale isotopic offsets should be fully considered when using δ13C and δ15N to analyze the actual trophic level of fish and their food source. The average offsets of δ13C and δ15N between muscles and scales are -2.1 ± 0.5‰ and 2.3 ± 0.6‰, respectively, though these values vary slightly with fish mass. Weak correlations were found between δ13C and δ15N, both in the flying fish muscle and scales, suggesting that other factors are influencing δ13C and δ15N. Fish δ15N also correlates with the size of individuals, while δ13C reflects the marine habitat. Based on our data, it appears that more eco-environmental processes can be revealed from modern or ancient flying fish scales. [ABSTRACT FROM AUTHOR]

Sensitive detection methods for T4 polynucleotide kinase/phosphatase (T4 PNKPP) are urgently required to obtain information on malignancy and thereby to provide better guidance in PNKP-related diagnostics and drug screening. Although the CRISPR/Cas12a system shows great promise in DNA-based signal amplification protocols, its guide RNAs with small molecular weight often suffer nuclease degradation during storage and utilization, resulting in reduced activation efficiency. Herein, we proposed a self-supplying guide RNA-mediated CRISPR/Cas12a system for the sensitive detection of T4 PNKP in cancer cells, in which multiple copies of guide RNA were generated by in situ transcription. In this assay, T4 PNKP was chosen as a model, and a dsDNA probe with T7 promoter region and the transcription region of guide RNA were involved. Under the action of T4 PNKP, the 5′-hydroxyl group of the dsDNA probe was converted to a phosphate group, which can be recognized and digested by Lambda Exo, resulting in dsDNA hydrolysis. The transcription template was destroyed, which resulted in the failure to generate guide RNA by the transcription pathway. Therefore, the CRISPR/Cas12a system could not be activated to effectively cleavage the F-Q-reporter, and the fluorescence signal was turned off. In the absence of T4 PNKP, the 5′-hydroxyl group of the substrate DNA cannot be digested by Lambda Exo. The intact dsDNA acts as the transcription template to generate a large amount of guide RNA. Finally, the formed Cas12a/gRNA complex triggered the reverse cleavage of Cas12a on the F-Q-reporter, resulting in a “turn-on” fluorescence signal. This strategy displayed sharp sensitivity of T4 PNKP with the limit of detection (LOD) down to 0.0017 mU/mL, which was mainly due to the multiple regulation effect of transcription amplification. In our system, the dsDNA simultaneously serves as the T4 PNKP substrate, transcription template, and Lambda Exo substrate, avoiding the need for multiple probe designs and saving costs. By integrating the target recognition, Lambda Exo activity, and trans-cleavage activity of Cas12a, CRISPR/Cas12a catalyzed the cleavage of fluorescent-labeled short-stranded DNA probes and enabled synergetic signal amplification for sensitive T4 PNKP detection. Furthermore, the T4 PNKP in cancer cells has been evaluated as a powerful tool for biomedical research and clinical diagnosis, proving a good practical application capacity.

BackgroundPreterm birth is one of the leading causes of perinatal morbidity and mortality. Gut microbiome dysbiosis is closely related to adverse pregnancy outcomes. However, the role of the gut microbiome in the pathogenesis of preterm birth remains poorly studied.MethodWe collected fecal samples from 41 women (cases presenting with threatened preterm labor =19, 11 of which delivered preterm; gestational age-matched no-labor controls, all of which delivered at term = 22) were recruited for the study. We performed 16S rRNA amplicon sequencing to compare the composition of the gut microbiome in threatened preterm labor cases and controls and among women who delivered preterm and at term. By annotating taxonomic biomarkers with the Human Oral Microbiome Database, we observed an increased abundance of potential oral-to-gut bacteria in preterm patients.ResultsPatients with preterm birth showed a distinct gut microbiome dysbiosis compared with those who delivered at term. Opportunistic pathogens, particularly Porphyromonas, Streptococcus, Fusobacterium, and Veillonella, were enriched, whereas Coprococcus and Gemmiger were markedly depleted in the preterm group. Most of the enriched bacteria were annotated oral bacteria using the Human Oral Microbiome Database. These potential oral-to-gut bacteria were correlated with clinical parameters that reflected maternal and fetal status.ConclusionsThis study suggests that patients who deliver preterm demonstrate altered gut microbiome that may contain higher common oral bacteria.

The risk of metabolic abnormalities in menopausal women increases significantly due to the decline in estrogen level. Nuclear factor E2-related factor 2 (NRF2) is an important oxidative stress sensor that plays regulatory role in energy metabolism. Therefore, an ovariectomized menopausal model in Nrf2-knockout (KO) mice was applied to evaluate the effect of Nrf2 deficiency on metabolism in menopausal females. The mice were divided into four groups according to their genotypes and treatments. Blood samples and bodyweights were obtained preoperatively and in the first to ninth postoperative weeks after overnight fasting. Serum levels of triglycerides (TG), total cholesterol (T-CHO), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and glucose (GLU) were measured at postoperative weeks 0, 1, 3, 5, 7, and 9. Neurotransmitter dopamine (DA) and serotonin (5-HT) was analyzed in brain tissues after sacrifice at postoperative week 9. The results demonstrated that, compared with the corresponding wild-type (WT) mice, KO ovariectomized mice had a greater bodyweight gain (P

While the CuBi2O4-based photocathode has emerged as an ideal candidate for photoelectrochemical water splitting, it is still far from its theoretical values due to poor charge carrier transport, poor electron–hole separation, and instability caused by self-photoelectric-corrosion with electrolytes. Establishing synthesis methods to produce a CuBi2O4 photocathode with sufficient cocatalyst sites would be highly beneficial for water splitting. Here, the platinum-enriched porous CuBi2O4 nanofiber (CuBi2O4/Pt) with uniform coverage and high surface area was prepared as a photocathode through an electrospinning and electrodeposition process for water splitting. The prepared photocathode material was composed of a CuBi2O4 nanofiber array, which has a freestanding porous structure, and the Pt nanoparticle is firmly embedded on the rough surface. The highly porous nanofiber structures allow the cocatalyst (Pt) better alignment on the surface of CuBi2O4, which can effectively suppress the electron–hole recombination at the electrolyte interface. The as-fabricated CuBi2O4 nanofiber has a tetragonal crystal structure, and its band gap was determined to be 1.8 eV. The self-supporting porous structure and electrocatalytic activity of Pt can effectively promote the separation of electron–hole pairs, thus obtaining high photocurrent density (0.21 mA/cm2 at 0.6 V vs. RHE) and incident photon-to-current conversion efficiency (IPCE, 4% at 380 nm). This work shows a new view for integrating an amount of Pt nanoparticles with CuBi2O4 nanofibers and demonstrates the synergistic effect of cocatalysts for future solar water splitting.