Inhibition of FoxO1 alleviates polycystic ovarian syndrome by reducing inflammation and the immune response.

The aim of this study was to explore the role of forkhead box transcription Factor O1 (FoxO1) in chronic inflammation in polycystic ovary syndrome (PCOS). A PCOS rat model was constructed as an in vivo model by letrozole induction, and granulosa cells (GCs) from PCOS rats were isolated and cultured as an in vitro cellular model. FoxO1 was knocked down by shRNA and siRNA in the PCOS rat model and GCs model, respectively. H&E staining was conducted to evaluate the effect of FoxO1 inhibition on ovarian pathology and dysfunction in PCOS rats. The levels of inflammatory cytokines in the ovaries and uterus of PCOS rats and in GCs were assessed by ELISA. Flow cytometry was used to evaluate the changes in the contents of neutrophils and macrophages in the peripheral blood and spleen of PCOS rats. CCK-8 assays and Annexin V-FITC/PI staining were performed to evaluate the proliferation and apoptosis of GCs. The expression of genes and proteins related to the TLR4/NF-κB/NLRP3 pathway in GCs was determined by RT-qPCR and Western blotting. The results indicated that FoxO1 was highly expressed in PCOS rat model. Inhibition of FoxO1 significantly mitigated the pathological changes and dysfunction in the ovaries of PCOS rats while also suppressing inflammation and fibrosis in the ovaries and uterus. Moreover, knocking down FoxO1 facilitated the restoration of the normal ratio of neutrophils and macrophages in the peripheral blood and spleen of PCOS rats and promoted M2 polarization of macrophages. Additionally, inhibition of FoxO1 promoted the proliferation of GCs and inhibited the inflammatory response in GCs. Furthermore, FoxO1 knockdown inhibited the activation of the NF-κB pathway and the formation of the NLRP3 inflammasome in GCs. In conclusion, inhibition of FoxO1 can alleviate PCOS by inhibiting the TLR4/NF-κB/NLRP3 pathway to reduce inflammation and the immune response.

Iron-Confined CRISPR/Cas9-Ribonucleoprotein Delivery System for Redox-Responsive Gene Editing.

Clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) is a promising gene editing tool to treat diseases at the genetic level. Nonetheless, the challenge of the safe and efficient delivery of CRISPR/Cas9 to host cells constrains its clinical applicability. In the current study, a facile, redox-responsive CRISPR/Cas9-Ribonucleoprotein (RNP) delivery system by combining iron-coordinated aggregation with liposomes (Fe-RNP@L) is reported. The Fe-RNP is formed by the coordination of Fe3+ with amino and carboxyl groups of Cas9, which modifies the lipophilicity and surface charge of RNP and alters cellular uptake from primary endocytosis to endocytosis and cholesterol-dependent membrane fusion. RNP can be rapidly and reversibly released from Fe-RNP in response to glutathione without loss of structural integrity and enzymatic activity. In addition, iron coordination also improves the stability of RNP and substantially mitigates cytotoxicity. This construct enabled highly efficient cytoplasmic/nuclear delivery (≈90%) and gene-editing efficiency (≈70%) even at low concentrations. The high payload content, high editing efficiency, good stability, low immunogenicity, and ease of production and storage, highlight its potential for diverse genome editing and clinical applications.

Identification, biogenesis, and function prediction of a novel circRNA_3238 of chicken.

With the development of high-throughput sequencing, circular RNA has come into people's vision and attracted more and more attention. Many studies have found that circular RNA plays an important role in a variety of biological processes and the occurrence and development of diseases. According to the previous sequencing results, circRNA_3238 was differentially expressed in ALV-J infected group and the non-infected group was selected for subsequent verification and analysis. We found that circRNA_3238 is a stable, circular transcript, which mainly exists in the cytoplasm. And it is widely expressed in various tissues of chickens, and highly expressed in lung, lymph, and bursa of fabricius. Bioinformatics results show that circRNA_3238 and the predicted target genes enriched MAPK signaling pathway, Notch signaling pathway, and other pathways related to disease or immune, revealing circRNA_3238 may indirectly regulate the process of ALV-J infection by regulating target genes.

Evaluation of non-invasive gene detection in preimplantation embryos: a systematic review and meta-analysis.

BACKGROUND: Genetic abnormalities in embryos are responsible for most miscarriages and repeated embryo implantation failures, so a reliable preimplantation genetic screening method is urgently needed. Non-invasive preimplantation genetic testing (niPGT) is a potential method for embryo genetic diagnosis. However, the value of its application is controversial. This meta-analysis aimed to investigate and validate the diagnostic value of niPGT in patients undergoing in vitro fertilization (IVF). METHODS: This review used the "Preferred Reporting Items" as a systematic review and meta-analysis of the diagnostic test accuracy (PRISMA-DTA) statement. We searched PubMed, Embase, Web of Science Core Collection, and Cochrane Library up to May 2022 to retrieve non-invasive preimplantation gene detection studies. The eligible research quality was evaluated following the quality assessment study-2 system for diagnostic accuracy. The pooled receiver operator characteristic curve (SROC) and the area under SROC (AUC) were used to evaluate diagnostic performance quantitatively. Threshold effect, subgroup analysis, and meta-regression analysis were used to explore the source of heterogeneity. Deeks' funnel plots and sensitivity analyses were used to test the publication bias and stability of the meta-analysis, respectively. FINDINGS: Twenty studies met the inclusion criteria. The pooled sensitivity, specificity, and AUC were 0.84 (95% CI 0.72-0.91), 0.85 (95% CI 0.74-0.92), and 0.91 (95% CI 0.88-0.93), respectively. Subgroup analysis showed that the spent culture medium (SCM) subgroup had higher sensitivity and lower specificity than the SCM combined with the blastocoel fluid (BF) subgroup. Subgroup analysis showed that the study sensitivity and specificity of < 100 cases were higher than those of ≥ 100. Heterogeneity (chi-square) analysis revealed that sample size might be a potential source of heterogeneity. Sensitivity analysis and Deeks' funnel plots indicated that our results were relatively robust and free from publication bias. INTERPRETATION: The present meta-analysis indicated that the pooled sensitivity, specificity, and AUC of niPGT in preimplantation genetic testing were 0.84, 0.85, and 0.91, respectively. niPGT may have high detection accuracy and may serve as an alternative model for embryonic analysis. Additionally, by subgroup analysis, we found that BF did not improve the accuracy of niPGT in embryos. In the future, large-scale studies are needed to determine the detection value of niPGT.

Identification, biogenesis and function prediction of novel circRNA during the chicken ALV-J infection.

Circular RNA (circRNA) is a new non-coding RNA with a highly conserved and stable covalently closed loop structure, and it plays an important role in a variety of biological processes and the occurrence of diseases. Based on the sequencing results, circRNA_3079 had the most significant difference between the infected group and normal group, up to about 8 times. It has attracted our attention and was selected for further verification and analysis. Though the characteristics analysis of circRNA_3079 in chicken, we found circRNA_3079 is a stable, circular transcript, which mainly exists in the cytoplasm. And it is widely expressed in various tissues of chickens, and highly expressed in lung, spleen, lymph and bursa of fabricius. Bioinformatics analysis results showed that circRNA_3079 and the predicted target genes are enriched in many pathways related to immunity or tumors, such as p53 signaling pathway, Jak-STAT signaling pathway and NOD-like receptor signaling pathway, which revealed that circRNA_3079 may indirectly regulate the ALV-J infection process through the regulation of target genes.HIGHLIGHTSCircRNA_3079 is an abundant and stable circular RNA expressed in different tissues and cells in chicken.The circularization of circRNA_3079 does not depend on the reverse complementary repetitive sequence of the flanking sequence.CircRNA_3079 may indirectly regulate the ALV-J infection process.

piRNA-19128 regulates spermatogenesis by silencing of KIT in chicken.

Spermatogenesis is a complex process. Some studies have shown that Piwi-interacting RNAs (piRNAs) play an important role in spermatogenesis. To verify the evaluate between piRNAs and PIWI proteins in chicken and its possible role in spermatogenesis and reproductive stem cell proliferation and differentiation, we performed immunoprecipitation and deep sequencing analyses and determined the expression profiles of small RNAs in primordial germ cells (PGCs), spermatogonial stem cells (SSCs), spermatogonia (Sa) cells, and spermatozoa. Length analysis showed that piRNAs bound to PIWIL1 mainly contained 23-30 nt. Base preference analysis showed "1U-10A"; moreover, base preference of piRNAs was obvious in all of germline cells. Here we reported the TE family of gallus gallus, and targeted by piRNA. Target gene of piRNA annotation enrichment analysis identified candidate genes KIT, SRC, WNT4, and HMGB2. Kyoto Encyclopedia of Genes and Genomes analysis showed that these genes were associated with steroid hormone biosynthesis, Notch signaling pathway, and melanogenesis. These results indicate that chicken piRNAs perform important regulatory roles during spermatogenesis similar to mice piRNAs. Chicken piRNAs interacted with PIWI proteins and regulated spermatogenesis and germ cell proliferation and differentiation. Further, we observed a negative correlation between piRNA-19128 and KIT expression. Results of dual-luciferase reporter assay confirmed that piRNA-19128 directly interacted with KIT, suggesting that it plays a key role in the regulation spermatogenesis by inhibiting KIT expression. Thus, the present study provides information on the length and base preference of chicken piRNAs and suggests that piRNA-19128 regulates spermatogenesis in chicken by silencing KIT.

A camel anti-lysozyme CDR3 only domain antibody selected from phage display VHH library acts as potent lysozyme inhibitor.

Mimetics of antibody-binding sites represent particularly interesting targets, however they are difficult to identify. In most cases, naturally derived CDR3 peptides show a much lower activity and affinity. In this study, we identified a CDR3 domain antibody with framework 3 (FR3) and FR4 in the flank by screening a lysozyme-immunized phage display VHH library. This antibody has a potent enzyme inhibiting activity and high thermal stability. With sequence alignment and site-directed mutagenic analysis, we found that the cysteine residue at amino acid position 88 in FR3 might play a key role in maintaining the stability of the CDR3 antibody. The small-sized CDR3 domain antibody might act as a new scaffold for affinity transfer, hence making a useful contribution to the understanding of antigen-antibody interactions.

Analysis of transcriptome in hickory (Carya cathayensis), and uncover the dynamics in the hormonal signaling pathway during graft process.

BACKGROUND: Hickory (Carya cathayensis), a woody plant with high nutritional and economic value, is widely planted in China. Due to its long juvenile phase, grafting is a useful technique for large-scale cultivation of hickory. To reveal the molecular mechanism during the graft process, we sequenced the transcriptomes of graft union in hickory. RESULTS: In our study, six RNA-seq libraries yielded a total of 83,676,860 clean short reads comprising 4.19 Gb of sequence data. A large number of differentially expressed genes (DEGs) at three time points during the graft process were identified. In detail, 777 DEGs in the 7 d vs 0 d (day after grafting) comparison were classified into 11 enriched Gene Ontology (GO) categories, and 262 DEGs in the 14 d vs 0 d comparison were classified into 15 enriched GO categories. Furthermore, an overview of the PPI network was constructed by these DEGs. In addition, 20 genes related to the auxin-and cytokinin-signaling pathways were identified, and some were validated by qRT-PCR analysis. CONCLUSIONS: Our comprehensive analysis provides basic information on the candidate genes and hormone signaling pathways involved in the graft process in hickory and other woody plants.

DNA methylation-mediated transcription factors regulate Piwil1 expression during chicken spermatogenesis.

The P-element induced wimpy testis (Piwi) protein family is responsible for initiating spermatogenesis and maintaining the integrity of germ cells and stem cells, but little is known regarding its transcriptional regulation in poultry. Here, we characterized the methylation status of the Piwil1 promoter in five different spermatogenic cell lines using direct bisulfite pyrosequencing and determined that methylation correlates negatively with germ cell type-specific expression patterns of piwil1. We demonstrated that methylation of the -148 CpG site, which is the predicted binding site for the transcription factors TCF3 and NRF1, was differentially methylated in different spermatogenic cells. This site was completely methylated in PGCs (primordial germ cells), but was unmethylated in round spermatids. A similar result was obtained in the region from +121 to +139 CpG sites of the Piwil1 promoter CpG island, which was predicted to contain SOX2 binding sites. In addition, demethylation assays further demonstrated that DNA methylation indeed regulates Piwil1 expression during chicken spermatogenesis. Combined with transcription factor binding site prediction, we speculate that methylation influences the recruitment of corresponding transcription factors. Collectively, we show the negative correlation between promoter methylation and piwil1 expression and that the spatiotemporal expression of chicken Piwil1 from the PGC stage to the round spermatid stage is influenced by methylation-mediated transcription factor regulation.

C2H2-type zinc-finger protein BCL11B suppresses avian Leukosis virus subgroup J replication by regulating apoptosis.

Apoptosis plays a crucial role in host antiviral defense. The avian leukosis virus subgroup J (ALV-J), an avian oncogenic retrovirus, has been shown to suppress apoptosis while promoting its own replication. ALV-J induces myeloid tumors and hemangiomas in chickens resulting in significant economic losses for commercial layer and meat-type chicken production. B-cell lymphoma/leukemia 11B (Bcl11b) encodes a C2H2-type zinc finger protein-BCL11B, that exerts critical functions in cell proliferation, differentiation, and plays an essential role in the immune system. Previous study has been shown that Bcl11b is associated with ALV-J infection. In this study, we further investigated the pathological changes in ALV-J infected cells and examined the role and expression regulation of chicken Bcl11b. Our results demonstrate that Bcl11b, as an interferon-stimulated gene (ISG), encodes C2H2-type zinc finger protein BCL11B that promotes apoptosis to inhibit ALV-J infection. Additionally, gga-miR-1612 and gga-miR-6701-3p regulate apoptosis and are involved in ALV-J infection by targeting Bcl11b, thus revealing immune response strategies between the host and ALV-J. Although the underlying mechanisms require further validation, Bcl11b and its regulatory miRNAs are the first to demonstrate inhibition of ALV-J replication via apoptosis. BCL11B can a valuable target for treating diseases triggered by ALV-J infection.

Diffusion-weighted MRI in the assessment of split renal function: comparison of navigator-triggered prospective acquisition correction and breath-hold acquisition.

OBJECTIVE: The purpose of this study was to ascertain whether prospective acquisition correction (PACE) diffusion-weighted MRI (DWI) is superior to conventional breath-hold DWI in assessment of split renal function. SUBJECTS AND METHODS: Fifty-four subjects underwent coronal breath-hold DWI and PACE DWI with the b value set at 0 and 800 s/mm(2). Isotope renographic glomerular filtration rate (GFR) was used as the reference standard for assessing split renal function. A GFR of 40 mL/min or greater indicated normal and a GFR less than 40 mL/min indicated reduced split renal function. Reduced split renal function was further divided into a mild reduction group (GFR ≥ 20 mL/min) and a moderate-to-severe reduction group (GFR < 20 mL/min). Various comparisons between the imaging methods were conducted. RESULTS: The signal-to-noise and contrast-to-noise ratios of the PACE DW images were greater than those of the breath-hold DW images (p < 0.001). The correlation between the apparent diffusion coefficient (ADC) value and GFR was stronger when the ADC was measured with PACE DWI than with breath-hold DWI (p = 0.033). Area under the receiver operator curve (AUC) analysis revealed that PACE DWI (AUC, 0.790 ± 0.045; p < 0.001) but not breath-hold DWI (AUC, 0.616 ± 0.060; p = 0.053) had diagnostic value in predicting a reduction in split renal function. ADC value assessed with PACE DWI was lower in the groups with mild and moderate-to-severe reduction in split renal function than in the group with normal function (p < 0.01). CONCLUSION: Preliminary results imply that PACE DWI is superior to breath-hold DWI in the assessment of split renal function.

Prevalence, risk factors, and clinical outcomes of remote intracerebral hemorrhage after intravenous thrombolysis in acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Hemorrhagic transformation (HT) is a common complication of alteplase treatment. However, the prevalence rate, risk factors, and clinical outcomes of remote intracerebral hemorrhage (rICH) after intravenous thrombolysis in acute ischemic stroke are not well understood. METHODS: Following a previously registered protocol, the PubMed, Web of Science, and Embase databases were systematically searched to identify relevant literature up to June 2022. Cohort studies reporting thrombolysis-related rICH in patients with acute ischemic stroke were included. Random effects models were used to calculate pooled prevalence rate, mean difference (MD) or odds ratio (OR) with corresponding 95% confidence interval (CI). RESULTS: Fourteen studies with 52,610 patients were included in this meta-analysis. The pooled rICH prevalence was 3.2% (95% CI 3.1-3.4%). Compared to patients without intracerebral hemorrhage (ICH), those with rICH were older, more likely to be female, and had a higher proportion of prior stroke, chronic heart failure and cardioembolism, and higher diastolic blood pressure. Small vessel disease markers (e.g., white matter hyperintensities and cerebral microbleeds) were strongly associated with rICH. The presence of rICH decreased the likelihood of favorable outcomes (OR 0.36, 95% CI 0.31-0.41) and increased the risk of mortality (OR 4.37, 95% CI 2.86-6.67). CONCLUSIONS: Although rICH is uncommon after intravenous thrombolysis, its presence can lead to worse functional outcomes and higher mortality in acute ischemic stroke. Patients at high risk of rICH must be identified based on potential risk factors.

Impact of Visceral Obesity on Structural and Functional Alterations of Gut Microbiota in Polycystic Ovary Syndrome (PCOS): A Pilot Study Using Metagenomic Analysis.

Objective: We aimed to identify structural and functional alterations of gut microbiota associated with visceral obesity in adult women with polycystic ovary syndrome (PCOS). Methods: Twenty-seven adults with PCOS underwent stool and fasting blood collection, oral glucose tolerance testing, and visceral fat area (VFA) measurement via dual-bioimpedance technique. Metagenomic analysis was used to analyze gut microbiota. Results: PCOS patients were divided into three groups: visceral obesity group (PCOS-VO, n=9, age 28.33±5.68 years, BMI 37.06±4.27 kg/m2, VFA 128.67±22.45 cm2), non-visceral obesity group (PCOS-NVO, n=10, age 25.40±4.53, BMI 30.74±3.95, VFA 52.00±24.04), normal BMI group (PCOS-NB, n=8, age 27.88±2.53, BMI 21.56±2.20, VFA 27.00±21.18), with no statistical difference in age (P>0.05) and significantly statistical differences in BMI and VFA (P<0.05). The groups showed a significant difference in microbial ß-diversity between PCOS-VO and PCOS-NVO (P=0.002) and no difference between PCOS-NVO and PCOS-NB (P=0.177). Bacteroidetes was the phylum with the highest relative abundance among all patients, followed by Firmicutes. Those with visceral obesity had a higher abundance of Prevotella, Megamonas, and Dialister genera, positively correlated with metabolic markers (r>0.4, P<0.05), and lower abundance of Phascolarctobacterium and Neisseria genera, negatively correlated with metabolic markers (r<-0.4, P<0.05). Functional annotation analysis showed significant differences in relative abundance of ribosome pathway, fatty acid biosynthesis pathway, and sphingolipid signaling pathway between groups, affecting lipid homeostasis and visceral fat accumulation. Conclusion: Alteration in ß-diversity of gut microbiota exists in PCOS with visceral obesity versus those without visceral obesity and relates to functional differences in ribosomes, fatty acid biosynthesis, and sphingolipid signaling pathways.

Combine with RNA-seq Reveals the Effect of Melatonin in the Synthesis of Melanin in Primary Melanocytes of Silky Fowls Black-Bone Chicken.

(1) Background: It was found that the melanin of black-bone chicken has various effects such as scavenging DPPH free radicals and anti-oxidation, and the synthesis of melanin is affected by various factors including hormones. In addition, several studies have found that melatonin affects the melanoma cell synthesis of melanin, which has not been reported in chicken primary melanocytes; so, relevant studies were conducted. (2) Methods: In this study, chicken primary melanocytes were isolated and characterized, and then melanocytes were treated with different concentrations of melatonin to investigate the effects of melatonin on melanin synthesis in chicken melanocytes in terms of melanin synthesis-related genes, melanin content, and tyrosinase activity, and combined with RNA seq to detect the change in gene expression level of chicken melanocytes after melatonin treatment. (3) Results: We isolated and characterized primary melanocytes, and indirect immunofluorescence assay results showed positive melanocyte marker genes. RT-qPCR results showed that melatonin decreased the expression of melanin synthesis-related genes. In addition, melatonin reduced the melanin content and decreased the tyrosinase activity of melanocytes in the treated group. A total of 1703 differentially expressed genes were screened by RNA-seq, and in addition, in the KEGG results, the signaling pathway associated with melanin synthesis, and the mTOR signaling pathway were enriched. (4) Conclusions: Melatonin could decrease the synthesis of melanin in chicken primary melanocytes.

Circ_PIAS1 Promotes the Apoptosis of ALV-J Infected DF1 Cells by Up-Regulating miR-183.

(1) Background: circRNAs are closed circular molecules with covalent bonds generated by reverse shearing, which have high stability and have different manifestations in different tissues, cells, or physiological conditions and play important roles in various disease processes and physiological processes. In addition, circ_PIAS1 has been screened out and verified, and the bioinformatics analyzed in previous studies. In this study, we investigated the function of circ_PIAS1 and studied its role in ALV-J infection to provide a basis for the role of circRNA in ALV-J infection. (2) Methods: the effect of circ_PIAS1 on apoptosis during ALV-J infection was studied by flow cytometry and detection of apoptotic gene expression, and miR-183 was screened by a biotin-labeled RNA pull-down technique. After overexpression and inhibition of miR-183, the effect of miR-183 on apoptosis in the process of ALV-J infection was studied by flow cytometry and detection of apoptotic gene expression. (3) Results: after overexpression of circ_PIAS1, flow cytometry and apoptotic gene expression showed that circ_PIAS1 promoted apoptosis. The results of RNA pull-down showed that 173 miRNAs could bind to circ_PIAS1, and circ_PIAS1 up-regulated the expression of miR-183. On the other hand, the same results were obtained whether miR-183 was overexpressed or inhibited that miR-183 affected ALV-J infection by promoting cell apoptosis. (4) Conclusions: circ_PIAS1 up-regulated the expression of miR-183 and influenced ALV-J infection by promoting cell apoptosis.

Clinical characteristics, risk factors, and outcomes of patients with polymicrobial Pseudomonas aeruginosa bloodstream infections.

BACKGROUND: Previous studies on polymicrobial Pseudomonas aeruginosa bloodstream infections (Pa-BSIs) are dated, and it is necessary to reanalyze polymicrobial Pa-BSIs. The aim of this study was to investigate clinical characteristics and risk factors for polymicrobial Pa-BSI in comparison with monomicrobial Pa-BSI. METHODS: A double-center retrospective observational study was performed between January 1, 2013 and June 30, 2022, in two tertiary hospitals. All patients with Pa-BSI were enrolled, and their clinical data were collected by reviewing electronic medical records. RESULTS: A total of 278 patients with Pa-BSI were enrolled, including 77 patients (27.7%) with polymicrobial Pa-BSI. Compared with monomicrobial Pa-BSI, the main source of polymicrobial Pa-BSI was pneumonia (49.4% vs 31.3%, p < 0.01), whereas the main source of monomicrobial Pa-BSI was primary BSIs (21.9% vs 2.6%, p = 0.04). In multivariate analysis, a history of cerebrovascular accident (CVA) (adjusted odds ratio [OR], 3.62; 95% CI, 1.46-8.92) was independently associated with polymicrobial Pa-BSI. Primary BSI was associated with monomicrobial Pa-BSI (OR, 0.08; 95% CI, 0.02-0.38). Patients with polymicrobial Pa-BSI had a longer intensive care unit (ICU) length of stay after onset of BSI than those with monomicrobial Pa-BSI (2 [2, 16] vs 13 [3.75, 29], p = 0.02). CONCLUSION: Patients with Pa-BSI and the presence of CVA need to be alert to the possibility of polymicrobial BSI occurrence. Prolonged ICU stay and pneumonia as a source of BSI warrant clinician attention for polymicrobial Pa-BSI, and primary BSIs are likely associated with monomicrobial BSIs.

Histidine modulates amyloid-like assembly of peptide nanomaterials and confers enzyme-like activity.

Amyloid-like assembly is not only associated with pathological events, but also leads to the development of novel nanomaterials with unique properties. Herein, using Fmoc diphenylalanine peptide (Fmoc-F-F) as a minimalistic model, we found that histidine can modulate the assembly behavior of Fmoc-F-F and induce enzyme-like catalysis. Specifically, the presence of histidine rearranges the ß structure of Fmoc-F-F to assemble nanofilaments, resulting in the formation of active site to mimic peroxidase-like activity that catalyzes ROS generation. A similar catalytic property is also observed in Aß assembled filaments, which is correlated with the spatial proximity between intermolecular histidine and F-F. Notably, the assembled Aß filaments are able to induce cellular ROS elevation and damage neuron cells, providing an insight into the pathological relationship between Aß aggregation and Alzheimer's disease. These findings highlight the potential of histidine as a modulator in amyloid-like assembly of peptide nanomaterials exerting enzyme-like catalysis.

The First Crested Duck Genome Reveals Clues to Genetic Compensation and Crest Cushion Formation.

The Chinese crested (CC) duck is a unique indigenous waterfowl breed, which has a crest cushion that affects its survival rate. Therefore, the CC duck is an ideal model to investigate the genetic compensation response to maintain genetic stability. In the present study, we first generated a chromosome-level genome of CC ducks. Comparative genomics revealed that genes related to tissue repair, immune function, and tumors were under strong positive selection, indicating that these adaptive changes might enhance cancer resistance and immune response to maintain the genetic stability of CC ducks. We also assembled a Chinese spot-billed (Csp-b) duck genome, and detected the structural variations (SVs) in the genome assemblies of three ducks (i.e., CC duck, Csp-b duck, and Peking duck). Functional analysis revealed that several SVs were related to the immune system of CC ducks, further strongly suggesting that genetic compensation in the anti-tumor and immune systems supports the survival of CC ducks. Moreover, we confirmed that the CC duck originated from the mallard ducks. Finally, we revealed the physiological and genetic basis of crest traits and identified a causative mutation in TAS2R40 that leads to crest formation. Overall, the findings of this study provide new insights into the role of genetic compensation in adaptive evolution.

[Screening based on response surface methodology of multi-fractions traditional Chinese medicine with anti-influenza virus neuraminidase activity: take shuanghuanglian injection as an example].

This study aimed to establish a novel method to screen out the combined components of multi-fractions traditional Chinese medicine (TCM), so that the internal relationship between multi-ingredients could be objectively assessed and the proportioning ratio could be optimized. Taking antiviral effect on neuraminidase activity of influenza virus as the evaluating indicator and using Box-Behnken response surface methodology, the main effective ingredients of Shuanghuanglian injection (SHL) were screened. Meanwhile, the relationship between active ingredients was discussed. Taking SHL as a comparison, the optimum proportioning ratio was predicted. The results indicated that chlorogenic acid, cryptochlorogenic acid, caffeic acid and baicalin have comparatively strong antiviral activity against influenza virus. Moreover, antagonistic action existed between chlorogenic acid and cryptochlorogenic acid, whereas synergistic action between caffeic acid and other components. The optimum proportioning ratio resulted from fitted model is: chlorogenic acid, cryptochlorogenic acid, caffeic acid and baicalin (107 microg x mL(-1) : 279 microg x mL(-1) : 7.99 microg x mL(-1) : 92 microg x mL(-1)). The antiviral activity of the recombined components is stronger than that of SHL, which was consistent with the experiment results (P < 0.05). Box-Behnken response surface methodology has the advantages of general-screening, high-performance and accurate-prediction etc, which is appropriate for screening the combined components of multi-fractions TCM and the optimization of the proportioning ratio. The proposed method can serve as a technological support for the development of modern multi-fractions TCM.

[Investigation on production process quality control of traditional Chinese medicine--Banlangen granule as an example].

For the quality management system of herbal medicines, intermediate and finished products it exists the " short board" effect of methodologies. Based on the concept of process control, new strategies and new methods of the production process quality control had been established with the consideration of the actual production of traditional Chinese medicine an the characteristics of Chinese medicine. Taking Banlangen granule as a practice example, which was effective and widespread application, character identification, determination of index components, chemical fingerprint and biometrics technology were sequentially used respectively to assess the quality of Banlangen herbal medicines, intermediate (water extraction and alcohol precipitation) and finished product. With the transfer rate of chemical information and biological potency as indicators, the effectiveness and transmission of the above different assessments and control methods had been researched. And ultimately, the process quality control methods of Banlangen granule, which were based on chemical composition analysis-biometric analysis, had been set up. It can not only validly solute the current status that there were many manufacturers varying quality of Banlangen granule, but also ensure and enhance its clinical efficacy. Furthermore it provided a foundation for the construction of the quality control of traditional Chinese medicine production process.