Advancements in the study of synaptic plasticity and mitochondrial autophagy relationship.

Synapses serve as the points of communication between neurons, consisting primarily of three components: the presynaptic membrane, synaptic cleft, and postsynaptic membrane. They transmit signals through the release and reception of neurotransmitters. Synaptic plasticity, the ability of synapses to undergo structural and functional changes, is influenced by proteins such as growth-associated proteins, synaptic vesicle proteins, postsynaptic density proteins, and neurotrophic growth factors. Furthermore, maintaining synaptic plasticity consumes more than half of the brain's energy, with a significant portion of this energy originating from ATP generated through mitochondrial energy metabolism. Consequently, the quantity, distribution, transport, and function of mitochondria impact the stability of brain energy metabolism, thereby participating in the regulation of fundamental processes in synaptic plasticity, including neuronal differentiation, neurite outgrowth, synapse formation, and neurotransmitter release. This article provides a comprehensive overview of the proteins associated with presynaptic plasticity, postsynaptic plasticity, and common factors between the two, as well as the relationship between mitochondrial energy metabolism and synaptic plasticity.

Histone lysine demethylase KDM5B facilitates proliferation and suppresses apoptosis in human acute myeloid leukemia cells through the miR-140-3p/BCL2 axis.

The histone lysine demethylase KDM5B is frequently up-regulated in various human cancer cells. However, its expression and functional role in human acute myeloid leukemia (AML) cells remain unclear. Here, we found that the expression level of KDM5B is high in primary human AML cells. We have demonstrated that knocking down KDM5B leads to apoptosis and impairs proliferation in primary human AML and some human AML cell lines. We further identified miR-140-3p as a downstream target gene of KDM5B. KDM5B expression was inversely correlated with the miR-140-3p level in primary human AML cells. Molecular studies showed that silencing KDM5B enhanced H3K4 trimethylation (H3K4me3) at the promoter of miR-140-3p, leading to high expression of miR-140-3p, which in turn inhibited B-cell CLL/lymphoma 2 (BCL2) expression. Finally, we demonstrate that the defective proliferation induced by KDM5B knockdown (KD) can be rescued with the miR-140-3p inhibitor or enhanced by combining KDM5B KD with a BCL2 inhibitor. Altogether, our data support the conclusion that KDM5B promotes tumorigenesis in human AML cells through the miR-140-3p/BCL2 axis. Targeting the KDM5B/miR-140-3p/BCL2 pathway may hold therapeutic promise for treating human AML.

PABP-driven secondary condensed phase within RSV inclusion bodies activates viral mRNAs for ribosomal recruitment.

Inclusion bodies (IBs) of respiratory syncytial virus (RSV) are formed by liquid-liquid phase separation (LLPS) and contain internal structures termed "IB-associated granules" (IBAGs), where anti-termination factor M2-1 and viral mRNAs are concentrated. However, the mechanism of IBAG formation and the physiological function of IBAGs are unclear. Here, we found that the internal structures of RSV IBs are actual M2-1-free viral messenger ribonucleoprotein (mRNP) condensates formed by secondary LLPS. Mechanistically, the RSV nucleoprotein (N) and M2-1 interact with and recruit PABP to IBs, promoting PABP to bind viral mRNAs transcribed in IBs by RNA-recognition motif and drive secondary phase separation. Furthermore, PABP-eIF4G1 interaction regulates viral mRNP condensate composition, thereby recruiting specific translation initiation factors (eIF4G1, eIF4E, eIF4A, eIF4B and eIF4H) into the secondary condensed phase to activate viral mRNAs for ribosomal recruitment. Our study proposes a novel LLPS-regulated translation mechanism during viral infection and a novel antiviral strategy via targeting on secondary condensed phase.

Effects of Dihuang Yinzi Decoction on Alzheimer's Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this study was to systematically evaluate the therapeutic effects of Dihuang Yinzi decoction on Alzheimer's disease (AD) and provide a medical evidence-based clinical application of traditional Chinese medicine (TCM). METHODS: A comprehensive search was conducted across multiple databases, including PubMed, Embase, Cochrane Library, China National Journals Full-text Database, VIP Database for Chinese Technical Periodicals, Wan Fang database, and SinoMed database, to collect clinical randomized controlled trials of Dihuang Yinzi decoction in the treatment of AD. Strict literature screening was performed based on predefined inclusion and exclusion criteria. The Cochrane Collaboration risk of bias assessment tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system recommendation-level method was used to assess the quality of the included studies. Review Manager 5.4 and Stata 17 software were used for data synthesis and processing, while GRADE Profiler 3.6 software was used to evaluate the quality of evidence for outcome indicators (risk ratio, standardized mean difference, and weighted mean difference). RESULTS: A total of 11 studies involving 798 patients met the inclusion criteria. Dihuang Yinzi decoction, whether used alone or in combination with conventional Western medicine, demonstrated superior efficacy compared to conventional Western medicine alone in improving the clinical effective rate, TCM syndrome score, activity of daily living score, Mini-Mental State Examination score, and Hasegawa Dementia Scale score in AD treatment. Furthermore, it exhibited a favorable safety profile. However, the GRADE evidence quality rating for the included studies was low. CONCLUSIONS: Dihuang Yinzi decoction, either used alone or in combination with conventional Western medicine, shows promising results in enhancing cognitive and memory functions as well as the self-care ability of patients with AD. However, the low GRADE evidence quality rating highlights the need for focused advancements in the planning and execution of clinical randomized controlled trials during future research attempts.Ziel dieser Studie ist es, die therapeutischen Effekte von Dihuang Yinzi-Dekokt auf die Alzheimer-Krankheit systematisch zu bewerten und eine evidenzbasierte klinische Anwendung der traditionellen chinesischen Medizin (TCM) bereitzustellen.Es wurde eine umfassende Suche in mehreren Datenbanken, darunter PubMed, Embase, Cochrane Library, China National Journals Volltext-Datenbank, VIP Database for Chinese Technical Periodicals, Wan Fang Datenbank und SinoMed-Datenbank durchgeführt, um randomisierte, kontrollierte klinische Studien zu Dihuang Yinzi-Dekokt in der Behandlung der Alzheimer-Krankheit zu erfassen. Die strenge Literatursuche erfolgte auf Grundlage von vordefinierten Ein-und Ausschlusskriterien. Zur Bewertung der Qualität der eingeschlossenen Studien wurden das Risk-of-Bias-Tool von Cochrane und das GRADE (Grading of Recommendations Assessment, Development, and Evaluation)-System zur Beurteilung der Empfehlungsgrade herangezogen. Die Datensynthese und -verarbeitung erfolgten mithilfe der Review Manager 5.4- und der Stata 17-Software, während für die Bewertung der Evidenzqualität der Outcome-Indikatoren (Risikoverhältnis, standardisierte Mittelwertdifferenz und gewichtete Mittelwertdifferenz) die Software GRADE Profiler 3.6 verwendet wurde.Insgesamt erfüllten 11 Studien, an denen 798 Patienten teilnahmen, die Einschlusskriterien. Dihuang Yinzi-Dekokt zeigte allein oder in Kombination mit konventioneller westlicher Medizin eine überlegene Wirksamkeit gegenüber der alleinigen Verwendung von konventioneller westlicher Medizin in Bezug auf die klinische Gesamtwirksamkeitsrate, den TCM-Syndrom-Score, den Score für die Alltagsaktivitäten, den Mini-Mental State Examination-Score und den Score der Hasegawa-Demenz-Skala in der Behandlung der Alzheimer-Krankheit. Darüber hinaus wies es ein günstiges Sicherheitsprofil auf. Die Evidenzqualität der eingeschlossenen Studien gemäß GRADE wurde jedoch als gering eingestuft.Dihuang Yinzi-Dekokt zeigt allein oder in Kombination mit konventioneller westlicher Medizin vielversprechende Ergebnisse in Bezug auf die Verbesserung der kognitiven und Gedächtnisfunktionen sowie die Selbstversorgungsfähigkeit von Alzheimer-Patienten. Die niedrige Bewertung der Evidenzqualität gemäß GRADE unterstreicht jedoch die Notwendigkeit von zielgerichteten Weiterentwicklungen bei der Planung und Durchführung von randomisierten, kontrollierten klinischen Studien in zukünftigen Forschungsunternehmungen.

Metagenomic Sequencing Analysis Identifies Cross-Cohort Gut Microbial Signatures Associated With Age-Related Macular Degeneration.

Purpose: Alterations in the gut microbiota have been associated with age-related macular degeneration (AMD). However, the dysbiosis shared by different ethnicity and geographic groups, which may associate with the disease pathogenesis, remain underexplored. Here, we characterized dysbiosis of the gut microbiota in patients with AMD from Chinese and Swiss cohorts and identified cross-cohort signatures associated with AMD. Methods: Shotgun metagenomic sequencing was performed on fecal samples from 30 patients with AMD and 30 healthy subjects. Published datasets with 138 samples from Swiss patients with AMD and healthy subjects were re-analyzed. Comprehensive taxonomic profiling was conducted by matching to the RefSeq genome database, metagenome-assembled genome (MAG) database, and Gut Virome Database (GVD). Functional profiling was performed by reconstruction of the MetaCyc pathways. Results: The α-diversity of the gut microbiota was decreased in patients with AMD according to taxonomic profiles generated using MAG but not RefSeq database as reference. The Firmicutes/Bacteroidetes ratio was also decreased in patients with AMD. Among AMD-associated bacteria shared between Chinese and Swiss cohorts, Ruminococcus callidus, Lactobacillus gasseri, and Prevotellaceae (f) uSGB 2135 were enriched in patients with AMD, whereas Bacteroidaceae (f) uSGB 1825 was depleted in patients with AMD and was negatively associated with hemorrhage size. Bacteroidaceae was one of the major hosts of phages associated with AMD. Three degradation pathways were reduced in AMD. Conclusions: These results demonstrated that dysbiosis of the gut microbiota was associated with AMD. We identified cross-cohort gut microbial signatures involving bacteria, viruses, and metabolic pathways, which potentially serve as promising targets for the prevention or treatment of AMD.

Morphogenesis and functional organization of viral inclusion bodies.

Eukaryotic viruses are obligate intracellular parasites that rely on the host cell machinery to carry out their replication cycle. This complex process involves a series of steps, starting with virus entry, followed by genome replication, and ending with virion assembly and release. Negative strand RNA and some DNA viruses have evolved to alter the organization of the host cell interior to create a specialized environment for genome replication, known as IBs, which are precisely orchestrated to ensure efficient viral replication. The biogenesis of IBs requires the cooperation of both viral and host factors. These structures serve multiple functions during infection, including sequestering viral nucleic acids and proteins from innate immune responses, increasing the local concentration of viral and host factors, and spatially coordinating consecutive replication cycle steps. While ultrastructural and functional studies have improved our understanding of IBs, much remains to be learned about the precise mechanisms of IB formation and function. This review aims to summarize the current understanding of how IBs are formed, describe the morphology of these structures, and highlight the mechanism of their functions. Given that the formation of IBs involves complex interactions between the virus and the host cell, the role of both viral and cellular organelles in this process is also discussed.

Rapid Identification of Pathogens in Severe Pneumonia by Species-specific Bacterial Detector (SSBD).

Fast and accurate detection of pathogenic bacterial infection in patients with severe pneumonia is significant to its treatment. The traditional culture method currently used by most medical institutions relies on a time-consuming culture process (over two days) that is unable to meet clinical needs. Rapid, accurate, and convenient species-specific bacterial detector (SSBD) has been developed to provide timely information on pathogenic bacteria. The SSBD was designed based on the fact that Cas12a indiscriminately cleaves any DNA following the binding of the crRNA-Cas12a complex to the target DNA molecule. SSBD involves two processes, starting with PCR of the target DNA using primers specific for the pathogen, followed by detection of the existence of pathogen target DNA in the PCR product using the corresponding crRNA and Cas12a protein. Compared to the culture test, the SSBD can obtain accurate pathogenic information in only a few hours, dramatically shortening the detection time and allowing more patients to benefit from timely clinical treatment.

[Visual analysis of research on traditional Chinese medicine treatment of Alzheimer's disease in recent ten years].

This study employed bibliometrics tools to review the studies of traditional Chinese medicine(TCM) treatment of Alzheimer's disease(AD) in recent ten years, aiming to explore the research status, hotspots, and future trends in this field at home and abroad. The relevant literature published from January 1, 2012 to August 15, 2022 was retrieved from Web of Science and CNKI. CiteSpace 6.1R2 and VOSviewer 1.6.15 were used for the visual analysis of authors, countries, institutions, keywords, journals, etc. A total of 2 254 Chinese articles and 545 English articles were included. The annual number of articles published showed a rising trend with fluctuations. The country with the largest number of relevant articles published and the largest centrality was China. SUN Guo-jie and WANG Qi were the authors publishing the most Chinese articles and English articles, respectively. Hubei University of Chinese Medicine and Beijing University of Chinese Medicine published the most articles in Chinese and English, respectively. Journal of Ethnopharmacology and Neuroscience Letters published the articles with the highest cited frequency and the highest centrality. According to the keywords, the research on TCM treatment of AD mainly focused on the mechanism of action and treatment methods. Metabolomics, intestinal flora, oxidative stress, tau hyperphosphorylation, ß-amyloid(Aß), inflammatory cytokines, and autophagy were the focuses of the research on mechanism of action. Acupuncture, clinical effect, kidney deficiency and phlegm stasis, and dredging governor vessel to revitalize mind were the hotspots of clinical research. This research field is still in the stage of exploration and development. Exchanges and cooperation among institutions should be encouraged to carry out more high-quality basic research on TCM treatment of AD, obtain high-level evidence, and clarify the pathogenesis and prescription mechanism.

Coronavirus subverts ER-phagy by hijacking FAM134B and ATL3 into p62 condensates to facilitate viral replication.

ER-phagy is a form of autophagy that is mediated by ER-phagy receptors and selectively degrades endoplasmic reticulum (ER). Coronaviruses have been shown to use the ER as a membrane source to establish their double-membrane vesicles (DMVs). However, whether viruses modulate ER-phagy to drive viral DMV formation and its underlying molecular mechanisms remains largely unknown. Here, we demonstrate that coronavirus subverts ER-phagy by hijacking the ER-phagy receptors FAM134B and ATL3 into p62 condensates, resulting in increased viral replication. Mechanistically, we show that viral protein ORF8 binds to and undergoes condensation with p62. FAM134B and ATL3 interact with homodimer of ORF8 and are aggregated into ORF8/p62 liquid droplets, leading to ER-phagy inhibition. ORF8/p62 condensates disrupt ER-phagy to facilitate viral DMV formation and activate ER stress. Together, our data highlight how coronavirus modulates ER-phagy to drive viral replication by hijacking ER-phagy receptors.

Isl1 promotes gene transcription through physical interaction with Set1/Mll complexes.

Histone H3 lysine 4 (H3K4) methylation is generally recognized as a prominent marker of gene activation. While Set1/Mll complexes are major methyltransferases that are responsible for H3K4 methylation, the mechanism of how these complexes are recruited into the target gene promotor is still unclear. Here, starting with an affinity purification-mass spectrometry approach, we have found that Isl1, a highly tissue-specific expressed LIM/homeodomain transcription factor, is physically associated with Set1/Mll complexes. We then show that Wdr5 directly binds to Isl1. And this binding is likely mediated by the homeodomain of Isl1. Functionally, using mouse ß-cell and human neuroblastoma tumor cell lines, we show that both Wdr5 binding and H3K4 methylation level at promoters of some Isl1 target genes are significantly reduced upon depletion of Isl1, suggesting Isl1 is required for efficient locus-specific H3K4 methylation. Taken together, our results establish a critical role of Set1/Mll complexes in regulating the target gene expression of Isl1.

Comparative transcriptome analysis of non-germinated and germinated spores of Enterocytozoon hepatopenaei (EHP) in vitro.

Enterocytozoon hepatopenaei (EHP), an obligate intracellular parasite classified as microsporidia, is an emerging pathogen with a significant impact on the global shrimp aquaculture industry. The understanding of how microsporidia germinate has been a key factor in exploring its infection process. However, the germination process of EHP was rarely reported. To gain insight into the germination process, we conducted a high-throughput sequencing analysis of purified EHP spores that had undergone in vitro germination treatment. This analysis revealed 137 differentially expressed genes, with 84 up-regulated and 53 down-regulated genes. While the functions of some of the genes remain unknown, this study provides important data on the transcriptomic changes before and after EHP germination, which can aid in further studies on the EHP infection mechanism.

Isolation and purification of antibacterial lipopeptides from Bacillus velezensis YA215 isolated from sea mangroves.

The increasing burden and health risks of antimicrobial resistance (AMR) pose a great threat to society overall. Lipopeptides exhibit great potential as novel and safe alternatives to traditional antibiotics. In this study, the strain YA215, which was isolated from the mangrove area in Beibu Gulf, Guangxi, China, was identified as Bacillus velezensis. Then, YA215 lipopeptide extracts (YA215LE) from B. velezensis was found to exhibit a wide spectrum of antibacterial and antifungal activities. Additionally, YA215LE was identified and found to contain three groups of lipopeptides (surfactin, iturin, and fengycin). Furthermore, one separation fraction (BVYA1) with significant antibacterial activity was obtained. Additionally, liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of BVYA1 showed three molecular ion peaks ([M + H]+: m/z 980.62; 994.66; 1008.66) corresponding to conventional surfactin homologs. By MS/MS analysis, BVYA1 was identified as sufactin with the precise amino acid sequence Glu-Leu/Ile-Leu-Val-Asp-Leu-Leu/Ile and hydroxyl fatty acids with 11-13 carbons. [M + H]+ at m/z 980.62 was detected for the first time in B. velezensis, which demonstrates that the strain corresponds to a new surfactin variant. In particular, BVYA1 showed antibacterial activity with the minimum inhibitory concentration (MIC) values of 7.5-15 µg/ml. Finally, the preliminary mechanism of inhibiting E. coli treated with BVYA1 showed that BVYA1 effectively permeabilized the cytoplasmic membrane and disrupted the morphology of targeted bacterial cells. In conclusion, this study suggests that the YA215LE from B. velezensis YA215 might be a potential candidate for a bactericide.

N6-methyladenosine-associated prognostic pseudogenes contribute to predicting immunotherapy benefits and therapeutic agents in head and neck squamous cell carcinoma.

Rationale: N6-methyladenosine (m6A) is involved in critical cancerous processes. Pseudogenes play various roles in carcinogenesis and progression. However, the functional roles of m6A-associated pseudogenes in head and neck squamous cell carcinoma (HNSCC) are largely unknown. Methods: We systematically analyzed the mRNA profile of 24 m6A regulators and 13931 pseudogenes from The Cancer Genome Atlas HNSCC dataset and ultimately identified 10 m6A-associated prognostic pseudogenes, which were validated in the Gene Expression Omnibus and our hospital datasets. Based on the risk score of m6A-associated pseudogenes, comprehensive analytical frameworks and experimental validation were implemented among pseudogene-defined low-/high-risk subtypes. Results: Here, we found expression pattern of m6A-associated pseudogenes was significantly associated with infiltrating immune cell compositions, and the expression of antitumor immune response markers, including T cell exhaustion, antigen presentation, interferon, and kinase genes. The m6A-associated pseudogenes, which had dramatic m6A peaks and higher m6A levels, could regulate the expression of targeted immune-involved genes through miRNAs. We experimentally validate the oncogene PDIA3P1, and tumor-suppressor RRN3P3, which promote the RNA and protein expression of their targeted immune-involved genes AKT1 and EZH2 via miR-34a-5p and miR-26b-5p, respectively. Moreover, HNSCC patients in the high-risk subtype could benefit more from immune checkpoint inhibitors therapy. Furthermore, doxorubicin and topotecan were considered to hold the most promising therapeutic potential robustly in silico evidence and in vitro experiments for HNSCC patients in the high-risk subtype. Conclusions: Our discovery revealed that the 10 m6A-associated prognostic pseudogenes significantly contribute to predicting immunotherapy benefits and therapeutic agents, which might bring some potential implications for both immunotherapy and chemotherapy in HNSCC.

Periodic evolution of the out-of-phase dipole and the single-charged vortex solitons in periodic photonic moiré lattice with saturable self-focusing nonlinearity media.

We survey the propagation properties of the out-of-phase (OOP) dipole solitons and the single-charged vortex (SCV) soliton in a periodic photonic moiré lattice with θ=arctan⁡(3/4) under self-focusing nonlinearity media. Since the rotation angle, periodic photonic moiré lattices have peculiar energy band structures, with highly flat bands and the bandgaps being much more extensive, which is very favorable for the realization and stability of the solitons. When exciting a single point on-site with the OOP dipole beam, its evolution shows a periodic rollover around the lattice axis. Whereas, when exciting a single point on-site with the SCV beam, it transmits counterclockwise rotating periodically. Both the OOP dipole solitons and the SVC soliton maintain the local state, but their phase exhibits different variations. The phase of the OOP dipole solitons is flipped, while that of the SCV is rotated counterclockwise. Our work further complements the exploration of solitons in photonic moiré lattice with nonlinearity.

Vimentin inhibits α-tubulin acetylation via enhancing α-TAT1 degradation to suppress the replication of human parainfluenza virus type 3.

We previously found that, among human parainfluenza virus type 3 (HPIV3) proteins, the interaction of nucleoprotein (N) and phosphoprotein (P) provides the minimal requirement for the formation of cytoplasmic inclusion bodies (IBs), which are sites of RNA synthesis, and that acetylated α-tubulin enhances IB fusion and viral replication. In this study, using immunoprecipitation and mass spectrometry assays, we determined that vimentin (VIM) specifically interacted with the N-P complex of HPIV3, and that the head domain of VIM was responsible for this interaction, contributing to the inhibition of IB fusion and viral replication. Furthermore, we found that VIM promoted the degradation of α-tubulin acetyltransferase 1 (α-TAT1), through its head region, thereby inhibiting the acetylation of α-tubulin, IB fusion, and viral replication. In addition, we identified a 20-amino-acid peptide derived from the head region of VIM that participated in the interaction with the N-P complex and inhibited viral replication. Our findings suggest that VIM inhibits the formation of HPIV3 IBs by downregulating α-tubulin acetylation via enhancing the degradation of α-TAT1. Our work sheds light on a new mechanism by which VIM suppresses HPIV3 replication.

Characterization and functional of four mutants of hydroxy fatty acid dehydrogenase from Lactobacillus plantarump-8.

In this study, the hydroxy fatty acid dehydrogenase CLA-DH from Lactobacillus plantarump-8 and its four mutant variants were expressed in Escherichia coli Rosetta (DE3). UV spectrophotometry was employed to verify the catalytic power of the purified CLA-DH to convert ricinoleic acid into 12-oxo-cis-9-octadecenoic acid in the presence of oxidized nicotinamide adenine dinucleotide (NAD+). The optimum reaction temperature for CLA-DH was 45°C, with a maintained stability between 20°C and 40°C. The optimal pH for CLA-DH catalytic activity was 6.0-7.0, with a maintained stability at a pH range of 6.0-8.0. In addition, Fe3+ promoted enzyme activity, whereas Cu2+, Zn2+, and Fe2+ inhibited enzyme activity (P < 0.05). The Km, Vmax, Kcat, and Kcat/Km of CLA-DH were determined as 2.19 ± 0.34 µM, 2.06 ± 0.28 µM min-1, 2.00 ± 0.27 min-1, and 0.92 ± 0.02 min-1µM-1, respectively. Site-directed mutagenesis and molecular dynamics simulations demonstrated that both Tyr156 and Ser143 residues play significant roles in the catalysis of CLA-DH, and its solubility is affected by Lys160 and Asp63. Moreover, Gas chromatography determined that recombinant CLA-DH could be successfully applied to Conjugated linoleic acids production.

Changes in the intestinal microbiota of Pacific white shrimp (Litopenaeus vannamei) with different severities of Enterocytozoon hepatopenaei infection.

The intestinal microbiota of the Pacific white shrimp Litopenaeus vannamei during Enterocytozoon hepatopenaei (EHP) infection was investigated by 16S rRNA gene-based analysis. The results showed that bacterial diversity in the intestine of L. vannamei was high, but it decreased with increasing severity of EHP infection. The relative abundances of the phyla Planctomycetes, Actinobacteria and Acidobacteria decreased significantly with a decrease in body size or EHP infection severity (P < 0.05). The most abundant genera were Pseudomonas, Methylobacterium, Bradyrhizobium, Bacteroides, Vibrio, Prevotella and so on. In addition, the relative abundances of some bacteria, such as Pseudomonas, Bradyrhizobium, Bacteroides and Vibrio, increased significantly with a decrease in body size or EHP infection severity (P < 0.05). These findings suggest that changes in the intestinal microbiota occur depending on the severity of EHP infection.

Brillouin Frequency Shift Extraction Based on AdaBoost Algorithm.

The Brillouin Optical Time-Domain Analyzer assisted by the AdaBoost Algorithm for Brillouin frequency shift (BFS) extraction is proposed and experimentally demonstrated. The Brillouin gain spectrum classification under different BFS is realized by iteratively updating the weak classifier in the form of a decision tree, forming several base classifiers and combining them into a strong classifier. Based on the pseudo-Voigt curve training set with noise, the performance of the AdaBoost Algorithm is studied, and the influence of different signal-to-noise ratio (SNR), frequency range, and frequency step is also studied. Results show that the performance of BFS extraction decreases with the decrease in SNR, the reduction in frequency range, and the increase in frequency step.

SLC35B2 Acts in a Dual Role in the Host Sulfation Required for EV71 Infection.

As an important neurotropic enterovirus, enterovirus 71 (EV71) is occasionally associated with severe neurological diseases and high mortality rates in infants and young children. Understanding the interaction between host factors and EV71 will play a vital role in developing antivirals and optimizing vaccines. Here, we performed a genome-wide CRISPR-Cas9 knockout screen and revealed that scavenger receptor class B member 2 (SCARB2), solute carrier family 35 member B2 (SLC35B2), and beta-1,3-glucuronyltransferase 3 (B3GAT3) are essential in facilitating EV71 replication. Subsequently, the exploration of molecular mechanisms suggested that the knockout of SLC35B2 or B3GAT3, not SCARB2, led to a remarkable decrease in the binding of EV71 to cells and internalization into cells. Furthermore, we found that the infection efficiency for EV71 was positively correlated with the level of host cell sulfation, not simply with the amount of heparan sulfate, suggesting that an unidentified sulfated protein(s) must contribute to EV71 infection. In support of this idea, we screened possible sulfated proteins among the proteinous receptors for EV71 and confirmed that SCARB2 could uniquely interact with both tyrosyl protein sulfotransferases in humans. We then performed mass spectrometric analysis of SCARB2, identifying five sites with tyrosine sulfation. The function verification test indicated that there were more than five tyrosine-sulfated sites on SCARB2. Finally, we constructed a model for EV71 entry in which both heparan sulfate and SCARB2 are regulated by SLC35B2 and act cooperatively to support viral binding, internalization, and uncoating. Taken together, this is the first time that we performed the pooled CRISPR-Cas9 genetic screening to investigate the interplay of host cells and EV71. Furthermore, we found that a novel host factor, SLC35B2, played a dual role in regulating the overall sulfation comprising heparan sulfate sulfation and protein tyrosine sulfation, which are critical for EV71 entry. IMPORTANCE As the most important nonpolio neurotropic enterovirus lacking specific treatments, EV71 can transmit to the central nervous system, leading to severe and fatal neurological complications in infants and young children. The identification of new factors that facilitate or inhibit EV71 replication is crucial to uncover the mechanisms of viral infection and pathogenesis. To date, only a few host factors involved in EV71 infection have been characterized. Herein, we conducted a genome-wide CRISPR-Cas9 functional knockout (GeCKO) screen for the first time to study EV71 in HeLa cells. The screening results are presented as a ranked list of candidates, including 518 hits in the positive selection that facilitate EV71 replication and 1,044 hits in the negative selection that may be essential for cell growth and survival or for suppressing EV71 infection. We subsequently concentrated on the top three hits in the positive selection: SCARB2, SLC35B2, and B3GAT3. The knockout of any of these three genes confers strong resistance against EV71 infection. We confirmed that EV71 infection is codependent on two receptors, heparan sulfate and SCARB2. We also identified a host entry factor, SLC35B2, indirectly facilitating EV71 infection through regulation of the host cell sulfation, and determined a novel posttranslational modification, protein tyrosine sulfation existing in SCARB2. This study revealed that EV71 infectivity exhibits a significant positive correlation with the level of cellular sulfation regulated by SLC35B2. Due to the sulfation pathway being required for many distinct viruses, including but not limited to EV71 and respiratory syncytial virus (RSV), which were tested in this study, SLC35B2 represents a target of broad-spectrum antiviral therapy.

Novel method based on inherent connection between absorption and fluorescence spectra for water contaminant analysis.

Multi-source spectroscopy is increasingly applied in water contaminant analysis, and general existing spectral features are based on direct mathematical statistics rather than revealing inherent connection between multisource spectra, which has restricted the accuracy and robustness performance. Here in, a novel method is proposed and it is based on the inherent connection between fluorescence and absorption spectra, which can reflect deeper information than conventional methods. The relevant theory was analyzed based on energy level transition and the symmetry between absorption and fluorescence spectra, and then three features were extracted related to internal molecular properties and dependent on two sources of spectral information simultaneously. The three features include the width of the fluorescence emission peak, Stokes shift and symmetry axis between absorption peak and fluorescent emission peak, that correspond to bandwidth of the ground state, vibrational relaxations and conjugate systems respectively. Their significant change of values in monitoring can reflect richer and deeper information in pollution events for contamination tracing and subsequent processing, such as the category, common properties and functional groups of contaminants. The effectiveness of this feature extraction method was assessed by conducting experiments with sample mixtures of typical chemicals and four real water samples. The results highlight the potential of these features in water pollution early warning and contaminant analysis with richer information and stronger robustness.