Anopheles sinensis is a major vector of malaria and among the dominant species in Shandong province of China. Insecticide resistance is an important threat to vector-borne disease control. However, there are only few reports about insecticide resistance of An. sinensis populations from Shandong province.

Extensive utilization increases the exposure of humans to Ag nanoparticles (NPs) via the oral pathway. To comprehensively address the action of Ag NPs to the gastrointestinal systems in real situations, i.e., the long-term low-dose exposure, we evaluated and compared the toxicity of three Ag NPs (20-30 nm with different surface coatings) to the human intestine cell Caco-2 after 1-day and 21-day exposures, using various biological assays. In both the short- and long-term exposures, the variety of surface coating predominated the toxicity of Ag NPs in a descending order of citrate-coated Ag NP (Ag-CIT), bare Ag NP (Ag-B), and poly (N-vinyl-2-pyrrolidone)-coated Ag NP (Ag-PVP). The short-term exposure induced cell growth inhibition and death. The cell viability loss appeared after cells were exposed to 0.7 μg/mL Ag-CIT, 0.9 μg/mL Ag-B or >1.0 μg/mL Ag-PVP for 24 h. The short-term and higher-dose exposure also induced reactive oxygen species (ROS) generation, mitochondrial damage, cell membrane leakage, apoptosis, and inflammation (IL-8 level). The long-term exposure only inhibited the cell proliferation. After 21-day exposure to 0.4 μg/mL Ag-CIT, the cell viability dropped to less than 50%, while cells exposed to 0.5 μg/mL Ag-PVP remained normal as the control. Generally, 0.3 μg/mL is the non-toxic dose for the long-term exposure of Caco-2 cells to Ag NPs in this study. However, cells presented inflammation after exposure to Ag NPs with the non-toxic dose in the long-term exposure.

RNA-specific adenosine deaminase ADAR1 is ubiquitously expressed in a variety of mammalian cells and tissues. Although its physiological importance in non-nervous tissues has been confirmed by analysis of null mutation phenotypes, few endogenous editing substrates have been identified in numerous peripheral tissues and biological function of ADAR1 has not been fully understood.

Circadian rhythm exerts its influence on animal physiology and behavior by regulating gene expression at various levels. Here we systematically explored circadian long non-coding RNAs (lncRNAs) in mouse liver and examined their circadian regulation. We found that a significant proportion of circadian lncRNAs are expressed at enhancer regions, mostly bound by two key circadian transcription factors, BMAL1 and REV-ERBα. These circadian lncRNAs showed similar circadian phases with their nearby genes. The extent of their nuclear localization is higher than protein coding genes but less than enhancer RNAs. The association between enhancer and circadian lncRNAs is also observed in tissues other than liver. Comparative analysis between mouse and rat circadian liver transcriptomes showed that circadian transcription at lncRNA loci tends to be conserved despite of low sequence conservation of lncRNAs. One such circadian lncRNA termed lnc-Crot led us to identify a super-enhancer region interacting with a cluster of genes involved in circadian regulation of metabolism through long-range interactions. Further experiments showed that lnc-Crot locus has enhancer function independent of lnc-Crot's transcription. Our results suggest that the enhancer-associated circadian lncRNAs mark the genomic loci modulating long-range circadian gene regulation and shed new lights on the evolutionary origin of lncRNAs.

The effects of revascularization by percutaneous coronary intervention (PCI) on cardiac function and clinical outcomes in patients with confirmed coronary artery disease (CAD) and heart failure (HF), on the basis of the optimal medical treatment recommended by current guidelines, remain to be determined.A cohort study was performed to evaluate the efficacy of PCI on the basis of optimal medical treatment in patients with CAD and HF. Patients who received PCI were subsequently grouped according to partial and complete revascularization (CR) depending on the PCI outcome. The primary outcome was defined as a composite outcome of major adverse cardiovascular events (MACEs). Changes in left ventricular ejection fraction (LVEF) also were compared.A total of 69 patients (12 who received medical treatment and 57 who received PCI) were included. Patients in the PCI group showed significantly improved LVEF (P < .001), but patients in the medical treatment group did not (P > .05) after 3 months of follow-up. MACEs occurred in 50% patients in the medical treatment group and 19.3% patients of the PCI group, with this difference almost reaching statistical significance (P = .06). Compared with patients who received medical therapy only, patients who received PCI experienced better survival (P = .02). Moreover, survival seemed to be better in patients who achieved CR with PCI of the coronary arteries than in those who had partial revascularization of the coronary arteries (P = .06).PCI may be effective for improving survival in patients with CAD and HF.

Influenza A viruses are a major threat to human health and inflict a significant public health challenge worldwide. Hemagglutinin (HA) is the main contributor to the infectivity of the virus and is a potential target for the development of antiviral therapeutic agents. The stem region of HA, which has been shown to be conserved, is the primary target in the development of antibody-based therapeutic strategies and preventive tools. Here, we confirmed the neutralizing activity and prophylactic efficacy of murine monoclonal antibody PR8-25 as well as Western blot analysis of different influenza virus strains. Then, we identified the epitope of PR8-25, 328-LRMVTGLRNIPS-339, by phage-displayed 12-mer random peptide library. The identified epitope targeted in the stem region of HA, specifically at the C-terminal of the HA1 fragment. This result suggest that the identified epitope may be a potential basis for antiviral drugs and stem-based universal influenza vaccines.

The role of metabolomics in autoimmune diseases has been a rapidly expanding area in researches over the last decade, while its pathophysiologic impact on systemic lupus erythematosus (SLE) remains poorly elucidated. In this study, we analyzed the metabolic profiling of fecal samples from SLE patients and healthy controls based on ultra-high-performance liquid chromatography equipped with mass spectrometry for exploring the potential biomarkers of SLE. The results showed that 23 differential metabolites and 5 perturbed pathways were identified between the two groups, including aminoacyl-tRNA biosynthesis, thiamine metabolism, nitrogen metabolism, tryptophan metabolism, and cyanoamino acid metabolism. In addition, logistic regression and ROC analysis were used to establish a diagnostic model for distinguishing SLE patients from healthy controls. The combined model of fecal PG 27:2 and proline achieved an area under the ROC curve of 0.846, and had a good diagnostic efficacy. In the present study, we analyzed the correlations between fecal metabolic perturbations and SLE pathogenesis. In summary, we firstly illustrate the comprehensive metabolic profiles of feces in SLE patients, suggesting that the fecal metabolites could be used as the potential non-invasive biomarkers for SLE.

The Saiga antelope (Saiga tatarica) is a critically endangered species, and there has been limited success in restoring the population by captive breeding. This study assessed the biochemical and physiological parameters of newborn Saiga antelope to provide reference information that can be used to evaluate their health. Comparisons have been made with parameters for horses and closely related members of the Bovidae family but there are no reference values for the newborn Saiga antelope.

The circadian clock is a cell-autonomous time-keeping mechanism established gradually during embryonic development. Here, we generated a transgenic zebrafish line carrying a destabilized fluorescent protein driven by the promoter of a core clock gene, nr1d1, to report in vivo circadian rhythm at the single-cell level. By time-lapse imaging of this fish line and 3D reconstruction, we observed the sequential initiation of the reporter expression starting at photoreceptors in the pineal gland, then spreading to the cells in other brain regions at the single-cell level. Even within the pineal gland, we found heterogeneous onset of nr1d1 expression, in which each cell undergoes circadian oscillation superimposed over a cell type-specific developmental trajectory. Furthermore, we found that single-cell expression of nr1d1 showed synchronous circadian oscillation under a light-dark (LD) cycle. Remarkably, single-cell oscillations were dramatically dampened rather than desynchronized in animals raised under constant darkness, while the developmental trend still persists. It suggests that light exposure in early zebrafish embryos has significant effect on cellular circadian oscillations.

Lanthanide-doped upconversion nanoparticles can convert long wavelength excitation radiation to short wavelength emission. They have great potential in biomedical applications, such as bioimaging, biodetection, drug delivery, and theranostics. However, there is little information available on their bioavailability and biological effects after oral administration. In this study, we systematically investigated the bioavailability, biodistribution, and toxicity of silica-coated upconversion nanoparticles administrated by gavage. Our results demonstrate that these nanoparticles can permeate intestinal barrier and enter blood circulation by microstructure observation of Peyer's patch in the intestine. Comparing the bioavailability and the biodistribution of silica-coated upconversion nanoparticles with oral and intravenous administration routes, we found that the bioavailability and biodistribution are particularly dependent on the administration routes. After consecutive gavage for 14 days, the body weight, pathology, Zn and Cu level, serum biochemical analysis, oxidative stress, and inflammatory cytokines were studied to further evaluate the potential toxicity of the silica-coated upconversion nanoparticles. The results suggest that these nanoparticles do not show overt toxicity in mice even at a high dose of 100 mg/kg body weight.

The knowledge of genetic variation in Chinese patients with non-small-cell lung cancer (NSCLC) is still limited. We aimed to profile this genetic variation in 206 Chinese patients with NSCLC using next-generation sequencing. Tumor tissues or whole-blood samples were collected and subjected to whole-exome targeted next-generation sequencing, which included 565 tumor-associated genes, for somatic gene mutation screening and copy number variation (CNV) detection. Potential functions of most commonly mutated genes and genes with CNV were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Atotal of 18,749 mutations were identified using targeted next-generation sequencing, and 85.3% of them were missense mutations. Among the mutation, conversions between pyrimidine and purine were predominant, and C> T/G > A was the most common substitution type. High frequencies of mutations were noted in TP53 (47.6%), EGFR (41.7%), CREBBP (23.1%), KMT2C (16.9%), MUC2 (16.6%), DNMT3A (15.5%), LRP1B (15.5%), MUC4 (15.5%), CDC27 (15.2%), and KRAS (12.8%). EGFR and KRAS mutations were mutually exclusive. The tumor mutation load showed differences depending on gender and tumor type. CNV analysis showed that BCORL1 and ARAF have the highest copy number amplification, whereas KDM6A and RBM10 showed the highest copy number deletion. GO and KEGG analyses indicated that high-frequency mutations and CNV genes were concentrated in tumor-related PI3K-Akt, FoxO, and Ras signaling pathway. Cumulatively, we studied somatic gene mutations involved in NSCLC and predicted their clinical significance in Chinese population. These findings may provide clues for etiology and drug target of NSCLC.

In this work, a novel ternary nanocomposite of PEI/RuSi-MWCNTs was designed and synthesized for the first time, which an ultrasensitive and self-enhanced electrochemiluminescent (ECL) aptasensor was developed for the detection of profenofos residues in vegetables. The self-enhanced complex PEI-Ru (II) enhanced the emission and stability of ECL, and the multi-walled carbon nanotubes (MWCNTs) acted as an excellent carrier and signal amplification. The PEI/RuSi-MWCNTs were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM) and energy dispersive spectrometer (EDS). The incorporation of gold nanoparticles (AuNPs) improved the performance of the sensor and provided a platform for the immobilization of the aptamer. The results of the experiment showed that the presence of profenofos significantly suppressed the electrochemiluminescence intensity of the sensor. The detection sensitivity of the aptamer sensor was in the range of 1 × 10-2 to 1 × 103 ng/mL. Under optimal conditions, the limit of detection (LOD) of the sensor for profenofos was 1.482 × 10-3 ng/mL. The sensor had excellent stability, reproducibility and specificity. The recoveries of the sensor ranged from 92.29 % to 106.47 % in real sample tests.

Colon cancer is one of the most common malignancies causing the majority of cancer-related deaths. Gelsolin (GSN) has been found to be dysregulated in various cancers. However, the secreted GSN in colon cancer remains largely unknown. In the present study, we explored the expression profile of GSN in colon cancer tissues and the diagnostic value of serum GSN in colon cancer. In addition, the effects of secreted GSN in colon cancer cells were studied. We thus found that immunoreactive GSN levels were significantly lower in colon cancer tissues than those in non-tumor colon tissues. Functional studies demonstrated that secreted GSN could restrain cell invasion and migration in vitro. Mechanistically, dose dependent recombinant GSN down-regulated the expression of MMP2 and MMP9, which might restrain the process of cell invasion and migration. Furthermore, serum levels of GSN were significantly lower in colon cancer patients than those in healthy volunteers, and ROC curves showed serum level of GSN had a better diagnostic value for colon cancer (AUC=0.932) than the traditional tumor biomarker Carcinoembryonic Antigen (CEA) or Carbohydrate Antigen 19-9 (CA199). In conclusion, our results suggest that the secreted GSN restrains the invasion and migration of colon cancer cells. Meanwhile, the serum GSN may be a new biomarker for the diagnosis of colon cancer.

To impart biomedical functions to nanoparticles (NPs), the common approach is to conjugate functional groups onto NPs by dint of the functions of those groups per se. It is still beyond current reach to create protein-like specific interactions and functions on NPs by conformational engineering of nonfunctional groups on NPs. Here, we develop a conformational engineering method to create an NP-based artificial antibody, denoted "Goldbody," through conformational reconstruction of the complementary-determining regions (CDRs) of natural antibodies on gold NPs (AuNPs). The seemingly insurmountable task of controlling the conformation of the CDR loops, which are flexible and nonfunctional in the free form, was accomplished unexpectedly in a simple way. Upon anchoring both terminals of the free CDR loops on AuNPs, we managed to reconstruct the "active" conformation of the CDR loops by tuning the span between the two terminals and, as a result, the original specificity was successfully reconstructed on the AuNPs. Two Goldbodies have been created by this strategy to specifically bind with hen egg white lysozyme and epidermal growth factor receptor, with apparent affinities several orders of magnitude stronger than that of the original natural antibodies. Our work demonstrates that it is possible to create protein-like functions on NPs in a protein-like way, namely by tuning flexible surface groups to the correct conformation. Given the apparent merits, including good stability, of Goldbodies, we anticipate that a category of Goldbodies could be created to target different antigens and thus used as substitutes for natural antibodies in various applications.

Nanoplastics, one component of plastic pollution, can enter human bodies via inhalation and thus threaten human health. However, the knowledge about the uptake and exocytosis of nanoplastics in cells of human lung organs is still very limited. Herein, we investigated the endocytosis, distribution, and exocytosis of polystyrene nanoparticles (PS NPs) of 50 nm (G50PS) and 100 nm (R100PS) in A549 cells and BEAS-2B cells. We found that both the cellular uptake of PS NPs increased positively with exposure time and dose, and A549 cells ingested more PS NPs than BEAS-2B cells did. In addition, the intracellular content of G50PS was higher than that of R100PS except at a higher dose and longer time. The ingested PS NPs were distributed mainly in lysosomes, while many G50PS appeared around the cell membrane, and R100PS also accumulated in mitochondria in BEAS-2B cells. As for the exocytosis, R100PS was more difficult to excrete than G50PS. Lysosomes in A549 cells and actin and microtubule in BEAS-2B cells were involved in the exocytosis of the PS NPs. These findings provide detailed information about the translocation of nanoplastics in lung cells, which is valuable for the safety assessment of nanoplastics in the environment.

The extensive use of chemical insecticides for public health and agricultural purposes has increased the occurrence and development of insecticide resistance. This study used transcriptome sequencing to screen 10 upregulated metabolic detoxification enzyme genes from Aedes albopictus resistant strains. Of these, CYP6A14 and CYP6N6 were found to be substantially overexpressed in the deltamethrin-induced expression test, indicating their role in deltamethrin resistance in Ae. albopictus. Furthermore, the corresponding 60-kDa recombinant proteins, CYP6A14 and CYP6N6, were successfully expressed using the Escherichia coli expression system. Enzyme activity studies revealed that CYP6A14 (5.84 U/L) and CYP6N6 (6.3 U/L) have cytochrome P450 (CYP450) enzyme activity. In vitro, the metabolic analysis revealed that the recombinant proteins degraded deltamethrin into 1-oleoyl-sn-glycero-3-phosphoethanolamine and 2',2'-dibromo-2'-deoxyguanosine. Subsequently, the CYP450 genes in larvae of Ae. albopictus were silenced by RNA interference technology to study deltamethrin resistance in vivo. The silencing of CYP6A14 and CYP6N6 increased the mortality rate of mosquitoes without affecting their survival time, spawning quantity, hatching rate, and other normal life activities. Altogether, CYP6A14 and CYP6N6 belong to the CYP6 family and mutually increase deltamethrin resistance in Ae. albopictus.

Multidimensional landscapes of regulatory genes in neuronal phenotypes at whole-brain levels in the vertebrate remain elusive. We generated single-cell transcriptomes of ~67,000 region- and neurotransmitter/neuromodulator-identifiable cells from larval zebrafish brains. Hierarchical clustering based on effector gene profiles ('terminal features') distinguished major brain cell types. Sister clusters at hierarchical termini displayed similar terminal features. It was further verified by a population-level statistical method. Intriguingly, glutamatergic/GABAergic sister clusters mostly expressed distinct transcription factor (TF) profiles ('convergent pattern'), whereas neuromodulator-type sister clusters predominantly expressed the same TF profiles ('matched pattern'). Interestingly, glutamatergic/GABAergic clusters with similar TF profiles could also display different terminal features ('divergent pattern'). It led us to identify a library of RNA-binding proteins that differentially marked divergent pair clusters, suggesting the post-transcriptional regulation of neuron diversification. Thus, our findings reveal multidimensional landscapes of transcriptional and post-transcriptional regulators in whole-brain neuronal phenotypes in the zebrafish brain.

Voice training has been proposed as an intervention to improve swallowing function in patients with dysphagia. However, little is known about the effects of voice training on swallowing physiology.

Previous studies on the relationship between the circulating level of interleukin-17 (IL-17) and disease activity in systemic lupus erythematosus (SLE) were contradictory. This study is aimed at quantitatively assessing the correlation between the circulating IL-17 level and disease activity in SLE patients. A systematic search for related literature was conducted via PubMed, Web of Science, EMBASE, and Cochrane Library (up to January 26, 2021). The relationship between circulating IL-17 levels and SLE activity was evaluated using Fisher's z value, which was then converted to r. The standardized mean difference (SMD) and its 95% confidence interval (CI) were used to describe the difference between the circulating IL-17 level in patients with active and inactive SLE. STATA 16.0 was used to perform statistical analysis. Random-effects model was performed to synthesize data. Twenty-six studies involving 1,560 SLE patients were included in this review. The pooled r value was 0.38 (95% CI: 0.25-0.50; I 2 = 83.8%, P < 0.001) between the SLE activity and circulating level of IL-17. Patients with active SLE had higher level of circulating IL-17 than that of inactive (pooled SMD = 0.95, 95% CI: 0.38-1.53; I 2 = 90.5%, P < 0.001). The subgroup analysis suggested that the region and detection method of circulating IL-17 might not be a source of heterogeneity. No significant publication bias was found. In summary, circulating IL-17 level has a low positive relationship with SLE activity. It is necessary to carefully consider the use of circulating IL-17 as a biomarker of the disease activity in SLE patients. The relationship between the circulating level of IL-17 and SLE activity should be further confirmed in randomized controlled studies.

The intestinal symbiotic bacteria of Aedes albopictus play a potential role in host resistance to insecticides. In this study, we sequenced the full-length of 16S rRNA and analyzed the differences in the intestinal microbiota between deltamethrin-resistant and -sensitive Ae. albopictus. Symbiotic bacteria were cultured and analyzed using six types of culture media in aerobic and anaerobic environments. We found significant differences in the diversity and abundance of the intestinal microbiota of the two strains of Ae. albopictus. The symbiotic bacteria cultured in vitro were found to be mainly facultative anaerobes. The cultured bacteria such as Serratia oryzae and Acinetobacter junii may function to promote the development of insecticide resistance. This work indicates that intestinal bacteria may contribute to the enhancement of insecticide resistance of Ae. albopictus It also highlights the analytical advantage of full-length 16S rRNA sequencing to study the intestinal microbiota of mosquitoes.