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In response to the water shortage in Wanzhou North Station (WNS), the authors investigated the stormwater quality characteristics with different underlying surfaces of WNS and carried out stormwater reuse analysis in conjunction with the InfoWorks ICM model. The results show that during heavy, torrential, and moderate rainfall, the road stormwater runoff has the highest concentrations of pollutants, with an average EMC (event mean concentration) value of 206 mg/L for COD. For the square runoff, the average EMC values of COD, SS, TN, and TP are 108 mg/L, 395 mg/L, 2.113 mg/L, and 0.128 mg/L, in comparison, the average EMC values of the corresponding indexes for the roof runoff are 65 mg/L, 212 mg/L, 1.449 mg/L, and 0.086 mg/L, respectively, demonstrating their potential for reuse. The R2 (coefficient of determination) of SS and COD in both roof and square runoff are greater than 0.85, with a good correlation, indicating that SS removal is the key to stormwater purification. InfoWorks ICM analysis shows that the recyclable volume of rainwater from WNS in 2018 is 29,410 m3 , accounting for 61.8% of the total annual rainfall. This study is expected to provide an ideal reference for the stormwater management of public buildings in mountainous areas.

As an emerging environment functional material, biochar has become a research hotspot in environmental fields because of its excellent ecological and environmental benefits. Recently, biochar has been used as an innovative soil ameliorant in bioretention systems (BRS) to effectively enhance pollutant removal efficiency for BRS. This paper summarizes and evaluates the performance and involved mechanisms of biochar amendment in BRS with respect to the removal of nutrients (TN (34–47.55%) and PO43--P (47–99.8%)), heavy metals (25–100%), pathogenic microorganisms (Escherichia coli (30–98%)), and organic contaminants (77.2–100%). For biochar adsorption, the pseudo-second-order and Langmuir models are the most suitable kinetic and isothermal adsorption models, respectively. Furthermore, we analyzed and elucidated some factors that influence the pollutant removal performance of biochar-amended BRS, such as the types of biochar, the preparation process and physicochemical properties of biochar, the aging of biochar, the chemical modification of biochar, and the hydraulic loading, inflow concentration and drying–rewetting alternation of biochar-amended BRS. The high potential for recycling spent biochar in BRS as a soil ameliorant is proposed. Collectively, biochar can be used as an improved medium in BRS. This review provides a foundation for biochar selection in biochar-amended BRS. Future research and practical applications of biochar-amended BRS should focus on the long-term stability of treatment performances under field conditions, chemical modification with co-impregnated nanomaterials in biochar surface, and the durability, aging, and possible negative effects of biochar.

Ovarian aging is associated with depletion of the ovarian follicle reserve, which is the key determinant of fertility potential in females. In this study, we found that the small, secreted protein complement 1Q-like (C1QL1) is involved in the regulation of follicle depletion through intraovarian and endocrine control in a multidimensional collaborative manner. C1ql1 was detected to be conserved in the ovary and showed high transcript levels during folliculogenesis. Blockade of C1QL1 by IP and ovarian intrabursal injection of C1QL1 antiserum into prepubertal mice impaired folliculogenesis accompanied by reductions in body weight, fat mass, and intraovarian lipid accumulation. An elevation of circulating estradiol levels, reduction of hypothalamic KISS1 and GnRH expression, and a decrease in serum FSH levels were found in C1QL1-deficient mice. In C1QL1-deficient ovaries, many primordial follicles were recruited and developed into medium follicles but underwent atresia at the large follicle stages, which resulted in depletion of follicle reserve. Depletion of C1QL1 alleviated the inhibitory effect of C1QL1 on granulosa cell apoptosis and the stimulatory effect of C1QL1 on granulosa cell autophagy, which resulted in accumulation in the preantral and early antral follicles and an increase in the atretic follicles. The abnormal profile of endocrine hormones accelerated the intraovarian effect of C1QL1 deficiency and further led to depletion of ovarian reserve. Altogether, this study revealed the expression patterns and the mechanism of action of C1QL1 during folliculogenesis and demonstrated that deficiency of C1QL1 caused ovarian follicular depletion.

The discovery of ancestral RAG transposons in early deuterostomia reveals the origin of vertebrate V(D)J recombination. Here, we analyze the functional regulation of a RAG transposon, ProtoRAG, in lancelet. We find that a specific interaction between the cis-acting element within the TIR sequences of ProtoRAG and a trans-acting factor, lancelet YY1-like (bbYY1), is important for the transcriptional regulation of lancelet RAG-like genes (bbRAG1L and bbRAG2L). Mechanistically, bbYY1 suppresses the transposition of ProtoRAG; meanwhile, bbYY1 promotes host DNA rejoins (HDJ) and TIR-TIR joints (TTJ) after TIR-dependent excision by facilitating the binding of bbRAG1L/2 L to TIR-containing DNA, and by interacting with the bbRAG1L/2 L complex. Our data thus suggest that bbYY1 has dual functions in fine-tuning the activity of ProtoRAG and maintaining the genome stability of the host., Lancelet expresses an ancestral RAG transposon, ProtoRAG, which predates human RAGgenes that are responsible for V(D)J recombination and adaptive immunity repertoire generation. Here the authors show that ProtoRAG is functionally regulated by a trans-acting factor, bbYY1, for tuning transposon activity and maintaining genome stability.

The discovery of ProtoRAG in amphioxus indicated that vertebrate RAG recombinases originated from an ancient transposon. However, the sequences of ProtoRAG terminal inverted repeats (TIRs) were obviously dissimilar to the consensus sequence of mouse 12/23RSS and recombination mediated by ProtoRAG or RAG made them incompatible with each other. Thus, it is difficult to determine whether or how 12/23RSS persisted in the vertebrate RAG system that evolved from the TIRs of ancient RAG transposons. Here, we found that the activity of ProtoRAG is highly dependent on its asymmetric 5′TIR and 3′TIR, which are composed of conserved TR1 and TR5 elements and a partially conserved TRsp element of 27/31 bp to separate them. Similar to the requirements for the recombination signal sequences (RSSs) of RAG recombinase, the first CAC in TR1, the three dinucleotides in TR5 and the specific length of the partially conserved TRsp are important for the efficient recombination activity of ProtoRAG. In addition, the homologous sequences flanking the signal sequences facilitate ProtoRAG- but not RAG-mediated recombination. In addition to the diverged TIRs, two differentiated functional domains in BbRAG1L were defined to coordinate with the divergence between TIRs and RSSs. One of these is the CTT* domain, which facilitates the specific TIR recognition of the BbRAGL complex, and the other is NBD*, which is responsible for DNA binding and the protein stabilization of the BbRAGL complex. Thus, our findings reveal that the functional requirement for ProtoRAG TIRs is similar to that for RSS in RAG-mediated recombination, which not only supports the common origin of ProtoRAG TIRs and RSSs from the asymmetric TIRs of ancient RAG transposons, but also reveals the development of RAG and RAG-like machineries during chordate evolution.

In the past two decades, emerging studies have suggested that DExD/H box helicases belonging to helicase superfamily 2 (SF2) play essential roles in antiviral innate immunity. However, the antiviral functions of helicase SF1, which shares a conserved helicase core with SF2, are little understood. Here we demonstrate that zinc finger NFX1-type containing 1 (ZNFX1), a helicase SF1, is an interferon (IFN)-stimulated, mitochondrial-localised dsRNA sensor that specifically restricts the replication of RNA viruses. Upon virus infection, ZNFX1 immediately recognizes viral RNA through its Armadillo-type fold and P-loop domain and then interacts with mitochondrial antiviral signalling protein to initiate the type I IFN response without depending on retinoic acid-inducible gene I-like receptors (RLRs). In short, as is the case with interferon-stimulated genes (ISGs) alone, ZNFX1 can induce IFN and ISG expression at an early stage of RNA virus infection to form a positively regulated loop of the well-known RLR signalling. This provides another layer of understanding of the complexity of antiviral immunity.

BACKGROUND Internet hospitals, an innovative approach to outpatient service delivery via the Internet, are rapidly developing in China, especially in the current ongoing COVID-19 epidemic, with adequately fulfilling people’s demands for health services. However, despite a number of studies regarding internet hospitals, there has been little research that further evaluates the effect of internet hospitals on physician-patient relationship during outpatient visits. OBJECTIVE The purpose of our study was to examine whether the use of internet hospitals improves physician-patient relationship and to find out the difference in physician-patient relationship between internet hospital users and nonusers (offline hospital users) during outpatient visits. METHODS We developed a questionnaire based on the patient-doctor relationship questionnaire (PDRQ-9), a widely used tool for measuring the physician-patient relationship, to survey physician-patient relationship. The random sampling technique was used to include respondents who used medical services in offline physical or internet hospitals in the past 12 months. Chi-square tests were employed to compare the different categorical characteristics between internet hospital users and nonusers (offline hospital users). T tests were used to test the significance in continuous variables between user scores and nonuser scores in physician-patient relationship. Multiple linear regression was performed to determine whether the use of internet hospitals during outpatient visits was associated with physician-patient relationship. RESULTS A total of 505 valid responses were received from patients, and 25.7% (130/505) reported that they had sought for medical services in internet hospitals in the past 12 months. Internet hospital users gave significantly lower scores than nonusers in total physician-patient relationship scores (t503=-2.610, P=.010), and the 5 items of “My physician helps me” (t503=-4.176, P CONCLUSIONS The use of internet hospitals could not improve but decrease the physician-patient relationship during outpatient visits. Internet hospitals as an important supplement to conventional physician-patient relationship, policy makers should pay attention to the improvement of physician-patient relationship when devoted to the development of internet hospitals.

N6 -methyladenosine (m6 A) is a chemical modification present in multiple RNA species and is most abundant in mRNAs. Studies on m6 A reveal its comprehensive roles in almost every aspect of mRNA metabolism, as well as in a variety of physiological processes. Although some recent discoveries indicate that m6 A can affect the life cycles of numerous viruses as well as the cellular antiviral immune response, the roles of m6 A modification in type I interferon (IFN-I) signaling are still largely unknown. Here, we reveal that WT1-associated protein (WTAP), one of the m6 A "writers", is degraded via the ubiquitination-proteasome pathway upon activation of IFN-I signaling. With the degradation of WTAP, the m6 A levels of IFN-regulatory factor 3 (IRF3) and interferon alpha/beta receptor subunit 1 (IFNAR1) mRNAs are reduced, leading to translational suppression of IRF3 and instability of IFNAR1 mRNA. Thus, the WTAP-IRF3/IFNAR1 axis may serve as negative feedback pathway to fine-tune the activation of IFN-I signaling, which highlights the roles of m6 A in the antiviral response by dictating the fate of mRNAs associated with IFN-I signaling.

N 6‐methyladenosine (m6A) is a chemical modification present in multiple RNA species and is most abundant in mRNAs. Studies on m6A reveal its comprehensive roles in almost every aspect of mRNA metabolism, as well as in a variety of physiological processes. Although some recent discoveries indicate that m6A can affect the life cycles of numerous viruses as well as the cellular antiviral immune response, the roles of m6A modification in type I interferon (IFN‐I) signaling are still largely unknown. Here, we reveal that WT1‐associated protein (WTAP), one of the m6A “writers”, is degraded via the ubiquitination‐proteasome pathway upon activation of IFN‐I signaling. With the degradation of WTAP, the m6A levels of IFN‐regulatory factor 3 (IRF3) and interferon alpha/beta receptor subunit 1 (IFNAR1) mRNAs are reduced, leading to translational suppression of IRF3 and instability of IFNAR1 mRNA. Thus, the WTAP‐IRF3/IFNAR1 axis may serve as negative feedback pathway to fine‐tune the activation of IFN‐I signaling, which highlights the roles of m6A in the antiviral response by dictating the fate of mRNAs associated with IFN‐I signaling., Proteasome mediated degradation of the m6A writer WTAP upon viral infection reduces m6A levels on IRF3 and IFNAR1 mRNAs and subsequently their protein output, thereby blocking IFN‐I‐mediated antiviral responses.

Natural steroid estrogens (NSEs), including free estrogens (FEs) and conjugated estrogens (CEs), are of emerging concern globally among public and scientific community due to their recognized adverse effects on human and wildlife endocrine systems in recent years. In this review, the properties, occurrence, sorption process, and transformation pathways of NSEs are clarified in the environment. The work comprehensively summarizes the occurrence of both free and conjugated estrogens in different natural and built environments (e.g., river, WWTPs, CAFOs, soil, and sediment). The sorption process of NSEs can be impacted by organic compounds, colloids, composition of clay minerals, specific surface area (SSA), cation exchange capacity (CEC), and pH value. The degradation and transformation of free and conjugated estrogens in the environment primarily involves oxidation, reduction, deconjugation, and esterification reactions. Elaboration about the major, subordinate, and minor transformation pathways of both biotic and abiotic processes among NSEs is highlighted. The moiety types and binding sites also would affect deconjugation degree and preferential transformation pathways of CEs. Notably, some intermediate products of NSEs still remain estrogenic potency during transformation process; the elimination of total estrogenic activity needs to be addressed in further studies. The in-depth researches regarding the behavior of both free and conjugated estrogens are further required to tackle their contamination problem in the ecosystem. Graphical abstract ᅟ.

Autophagy is a homeostatic process which degrades cytoplasmic constituents to maintain the balance of organs when they were challenged with nutrient stress. It also participates in cancer, neurodegenerative disorders, aging and innate immune defense. In order to reveal how autophagy participates in innate immune response when invertebrates evolved into vertebrates. Firstly, we performed a systematic analysis of Atg genes and found that they are highly conserved among lancelet, lamprey and zebrafish. Then, we observed autophagosomes upon starvation by TEM in lancelet, lamprey and zebrafish and found that the morphology of autophagosome is similar to that was observed in yeast and mammals. In addition, rapamycin can induce autophagy in lamprey leukocytes and the deficiency of human Beclin1 protein can be rescued by lancelet and lamprey Beclin1 proteins. When lamprey leukocytes were treated with polyI:C and LPS, autophagy was induced. Moreover, when lamprey leukocytes were challenged with live E. coli, phagocytosis along with autophagy was triggered to degrade pathogenic bacteria. In all, our study here indicated that autophagy is highly conserved during evolution and plays a key role in innate defense when invertebrates evolved into vertebrates.

Abstract Nitrogen migration and transformation in the stormwater bioretention system were studied in laboratory experiments, in which the effects of drying-rewetting were particularly investigated. The occurrence and distribution of nitrogen in the plants, the soil, and the pore water were explored under different drying-rewetting cycles. The results clearly showed that bioretention system could remove nitrogen efficiently in all drying-rewetting cycles. The incoming nitrogen could be retained in the topsoil (0–10 cm) and accumulated in the planted layer. However, the overlong dry periods (12 and 22 days) cause an increase in nitrate in the pore water. In addition, nitrogen is mostly stored in the plants’ stem tissues. Up to 23.26% of the inflowing nitrogen can be immobilized in plant organ after a dry period of 22 days. In addition, the relationships between nitrogen reductase activity in the soil and soil nitrogen content were explored. The increase of soil TN content could enhance the activity of nitrate reductase. Meanwhile, the activity of hydroxylamine reductase (HyR) could be enhanced with the increase of soil NO3− content. These results provide a reference for the future development of nitrogen transformation mechanism and the construction of stormwater bioretention systems.

In the past decades, the environmental presence and ecological risks of chlorinated paraffins (CPs), an emerging class of organic halogen compounds, have been receiving increasing attention worldwide. Short-chain CPs (SCCPs) and medium-chain CPs (MCCPs) constitute the important CPs of considerable concern. In this review article, the state-of-the-art research status on the environmental transformation of CPs, including thermal decomposition, photolytic and photocatalytic degradation, biological metabolism, and atmospheric transformation, was summarized and integrated in detail. The degradation efficiency and transformation products of CPs in these environmental processes were evaluated, in which dechlorination was considered as the major reaction pathway. Notably, waste incineration of CPs has been demonstrated to generate a variety of persistent chlorinated aromatic hydrocarbons such as polychlorinated biphenyls and polychlorinated naphthalenes, which have more significant environmental impacts. Additionally, photodegradation and photocatalysis are suggested as the feasible techniques for efficient removal of SCCPs from water matrices. Overall, the current transformation studies of CPs could facilitate the comprehensive understanding of their environmental behaviors and fate as well as the development of promising remediation strategies for pollution control.

Peri-ovarian adipose tissue (POAT) is a kind of intra-abdominal white adipose tissue that is present surrounding the ovaries in rodents. Recent studies demonstrated that POAT-deficient mice displayed a phenotype of delayed antral follicular development, for which decreases in serum estrogen, serum FSH and FSHR levels were responsible. However, folliculogenesis is regulated by endocrine signals and also modulated by a number of locally produced intraovarian factors whose acts are both autocrine and paracrine. Here, we used a model of surgical removal of POAT unilaterally and contralateral ovaries as controls, as both were under the same endocrine control, to assess the paracrine effect of the POAT on folliculogenesis. Surgical removal of unilateral POAT resulted in delayed antral follicular development and the increased number of atretic follicles, accompanied by decreased levels of intraovarian adipokines and growth factors, lipid accumulation and steroidogenic enzyme expression. POAT-deficient ovaries displayed compensatory increased expressions of intraovarian genes, such asVegfandAdpnfor angiogenesis,Acc,Fasn, andGapdhinvolved in lipogenesis andFshrin response to FSH stimulation. Furthermore, we demonstrated that removal of POAT promoted follicular apoptosis, caused retention of cytoplasmic YAP and inhibited PTEN-AKT-mTOR activation. These alterations were observed only in the POAT-deficient ovaries but not in the contralateral ovaries (with POAT), which suggests that a paracrine interaction between POAT and ovaries is important for normal folliculogenesis.

The literature on mining community preferences for mineral development, which is the basis for engaging local communities, mainly focuses on rural communities, and may not provide enough insight into an urban community's needs, concerns, and preferences. To bridge this gap, this work uses Salt Lake City, Utah in the United States of America (USA) as a case study to understand an urban population's preferences for mineral resource development. The work considered 16 mining project attributes and four demographic factors (gender, age, education, and income), which have previously been identified as important for explaining individual preferences for mining projects in the USA. The study recruited 628 participants from Salt Lake City to participate in a survey and used a discrete choice model to examine their preferences. The results show that 15 of the 16 attributes have statistically significant influence on the preferences of these urban dwellers. The probability of the respondents preferring mineral development increases with job opportunities, availability of independent information, income increase, infrastructure improvement, and mine buffer but decreases with noise pollution, air pollution, increase in housing costs, and crime increase. Older, male respondents with higher levels of income and education are more likely to prefer mineral development. The issues that drive the preferences of these urban dwellers are generally similar to those of rural dwellers. However, the study finds that job and housing cost are more important for our urban dwellers than for rural dwellers in other studies. The results suggests that our respondents prefer mines with longer lives.

Current extensive research on aerobic granular sludge (AGS) largely focuses on improving its microbial biodiversity, settlement behavior, nitrogen and phosphorus removal efficiency, and shock load resistance. Great challenges that have to be faced are the bottleneck of slow-speed granulation and easy disintegration after granulation, which are key to the extended application of AGS technology. In the present review, the typical morphological structures of AGS are firstly summarized as well as the granulation model hypotheses, and then, we analyze the dominant microflora and their spatial distribution features. The influencing factors on particle structure stability are discussed thereafter on a macro and micro scale. Prospects and future research trends are also discussed based on the current study results for AGS technology.

In the past two decades, emerging studies have suggested that DExD/H box helicases belonging to helicase superfamily 2 (SF2) play essential roles in antiviral innate immunity. However, the antiviral functions of helicase SF1, which shares a conserved helicase core with SF2, are little understood. Here we demonstrate that zinc finger NFX1-type containing 1 (ZNFX1), a helicase SF1, is an interferon (IFN)-stimulated, mitochondrial-localised dsRNA sensor that specifically restricts the replication of RNA viruses. Upon virus infection, ZNFX1 immediately recognizes viral RNA through its Armadillo-type fold and P-loop domain and then interacts with mitochondrial antiviral signalling protein to initiate the type I IFN response without depending on retinoic acid-inducible gene I-like receptors (RLRs). In short, as is the case with interferon-stimulated genes (ISGs) alone, ZNFX1 can induce IFN and ISG expression at an early stage of RNA virus infection to form a positively regulated loop of the well-known RLR signalling. This provides another layer of understanding of the complexity of antiviral immunity.

International audience; Co-option of RAG1 and RAG2 for antigen receptor gene assembly by V(D)J recombination was a crucial event in the evolution of jawed vertebrate adaptive immunity. RAG1/2 are proposed to have arisen from a transposable element, but definitive evidence for this is lacking. Here, we report the discovery of ProtoRAG, a DNA transposon family from lancelets, the most basal extant chordates. A typical ProtoRAG is flanked by 5-bp target site duplications and a pair of terminal inverted repeats (TIRs) resembling V(D) J recombination signal sequences. Between the TIRs reside tail-to-tail-oriented, intron-containing RAG1-like and RAG2-like genes. We demonstrate that ProtoRAG was recently active in the lancelet germ-line and that the lancelet RAG1/2-like proteins can mediate TIR-dependent transposon excision, host DNA recombination, transposition, and low-efficiency TIR rejoining using reaction mechanisms similar to those used by vertebrate RAGs. We propose that ProtoRAG represents a molecular "living fossil" of the long-sought RAG transposon.

The IFN regulatory factor (IRF) family encodes transcription factors that play important roles in immune defense, stress response, reproduction, development, and carcinogenesis. Although the origin of the IRF family has been dated back to multicellular organisms, invertebrate IRFs differ from vertebrate IRFs in genomic structure and gene synteny, and little is known about their functions. Through comparison of multiple amphioxus genomes, in this study we suggested that amphioxus contains nine IRF members, whose orthologs are supposed to be shared among three amphioxus species. As the orthologs to the vertebrate IRF1 and IRF4 subgroups, Branchiostoma belcheri tsingtauense (bbt)IRF1 and bbtIRF8 bind the IFN-stimulated response element (ISRE) and were upregulated when amphioxus intestinal cells were stimulated with poly(I:C). As amphioxus-specific IRFs, both bbtIRF3 and bbtIRF7 bind ISRE. When activated, they can be phosphorylated by bbtTBK1 and then translocate into nucleus for target gene transcription. As transcriptional repressors, bbtIRF2 and bbtIRF4 can inhibit the transcriptional activities of bbtIRF1, 3, 7, and 8 by competing for the binding of ISRE. Interestingly, amphioxus IRF2, IRF8, and Rel were identified as target genes of bbtIRF1, bbtIRF7, and bbtIRF3, respectively, suggesting a dynamic feedback regulation among amphioxus IRF and NF-κB. Collectively, to our knowledge we present for the first time an archaic IRF signaling framework in a basal chordate, shedding new insights into the origin and evolution of vertebrate IFN-based antiviral networks.

The sustainable development of the Yangtze River will affect the lives of the people who live along it as well as the development of cities beside it. This study investigated the relationship between shipping development and the water environment of the Yangtze River. Canonical correlation analysis is a multivariate statistical method used to study the correlation between two groups of variables, this study employed it to analyze data relevant to shipping and the water environment of the Yangtze River from 2006 to 2016. Furthermore, the Yangtze River Shipping Prosperity Index and Yangtze River mainline freight volume were used to characterize the development of Yangtze River shipping. The water environment of the Yangtze River is characterized by wastewater discharge, ammonia nitrogen concentration, biochemical oxygen demand, the potassium permanganate index, and petroleum pollution. The results showed that a significant correlation exists between Yangtze River shipping and the river&rsquo, s water environment. Furthermore, mainline freight volume has a significant impact on the quantity of wastewater discharged and petroleum pollution in the water environment.

As an emerging class of silica-based mesoporous materials with incorporation of active components (e.g., transition metals/metal oxides and nanocarbons), SBA-15-based composites (X@SBA-15) have been attracting increasing attention in the field of water treatment owing to their unique characteristics and excellent remediation performance. This paper reviews recent advances in catalytic applications of X@SBA-15 to remove organic contaminants from water. Emphasis is made on the use of X@SBA-15 in four advanced oxidation processes (AOPs) (i.e., photocatalysis, Fenton-like oxidation, catalytic ozonation, and sulfate radical-based oxidation). Impregnation and hydrothermal methods are two most widely used synthetic approaches to combine the active composites with SBA-15, obtaining a synergistic effect with significant improvement in their individual catalytic activity for pollution remediation. The enhanced generation of highly reactive hydroxyl radicals from the surface of X@SBA-15 was widely recognized as being responsible for water decontamination using these AOPs, while sulfate radicals were also involved during activation of persulfate or peroxymonosulfate. Especially, X@SBA-15 could significantly enhance the light harvest and reduce the recombination of photo-induced electrons and holes during photocatalytic treatment, which also played the critical role in oxidizing the organics. The superior catalytic performance of X@SBA-15 without leaching metal ions during successive runs demonstrated the excellent reusability and structural stability. Together with the reduced toxicity of the treated solutions and the cost-effective characteristics of X@SBA-15 nanohybrids reported in the published literature, their great potential as the efficient and environmentally friendly heterogeneous catalysts in a real use scenario is suggested. Finally, the future perspectives on the development and practical utilization of X@SBA-15 are addressed.

Alternative polyadenylation (APA) is an important regulatory mechanism of gene functions in many biological processes. However, the extent of 3′ UTR variation and the function of APA during the innate antiviral immune response are unclear. Here, we show genome-wide poly(A) sites switch and average 3′ UTR length shortens gradually in response to vesicular stomatitis virus (VSV) infection in macrophages. Genes with APA and mRNA abundance change are enriched in immune-related categories such as the Toll-like receptor, RIG-I-like receptor, JAK-STAT and apoptosis-related signalling pathways. The expression of 3′ processing factors is down-regulated upon VSV infection. When the core 3′ processing factors are knocked down, viral replication is affected. Thus, our study reports the annotation of genes with APA in antiviral immunity and highlights the roles of 3′ processing factors on 3′ UTR variation upon viral infection., RNA processing by alternative polyadenylation (APA) can result in 3′UTR diversity and regulation of target RNA function. Here the authors survey APA in viral infection of macrophages.

Animals exploit different germ-line-encoded proteins with various domain structures to detect the signature molecules of pathogenic microbes. These molecules are known as pathogen-associated molecular patterns (PAMPs), and the host proteins that react with PAMPs are called pattern recognition proteins (PRPs). Here, we present a novel type of protein domain structure capable of binding to bacterial peptidoglycan (PGN) and the minimal PGN motif muramyl dipeptide (MDP). This domain is designated as apextrin C-terminal domain (ApeC), and its presence was confirmed in several invertebrate phyla and subphyla. Two apextrin-like proteins (ALP1 and ALP2) were identified in a basal chordate, the Japanese amphioxus Branchiostoma japonicum (bj). bjALP1 is a mucosal effector secreted into the gut lumen to agglutinate the Gram-positive bacterium Staphylococcus aureus via PGN binding. Neutralization of secreted bjALP1 by anti-bjALP1 monoclonal antibodies caused serious damage to the gut epithelium and rapid death of the animals after bacterial infection. bjALP2 is an intracellular PGN sensor that binds to TNF receptor-associated factor 6 (TRAF6) and prevents TRAF6 from self-ubiquitination and hence from NF-κB activation. MDP was found to compete with TRAF6 for bjALP2, which released TRAF6 to activate the NF-κB pathway. BjALP1 and bjALP2 therefore play distinct and complementary functions in amphioxus gut mucosal immunity. In conclusion, discovery of the ApeC domain and the functional analyses of amphioxus ALP1 and ALP2 allowed us to define a previously undocumented type of PRP that is represented across different animal phyla.

In the past decade, ubiquitination has been well documented to have multifaceted roles in regulating NF-κB activation in mammals. However, its function, especially how deubiquitinating enzymes balance the NF-κB activation, remains largely elusive in invertebrates. Investigating bbtA20 and its binding proteins, bbt A20-binding inhibitor of NF-κB (bbtABIN1) and bbtABIN2, in Chinese amphioxus Branchiostoma belcheri tsingtauense, we found that bbtABIN2 can colocalize and compete with bbt TNF receptor-associated factor 6 to connect the K63-linked polyubiquitin chains, whereas bbtABIN1 physically links bbtA20 to bbt NF-κB essential modulator (bbtNEMO) to facilitate the K48-linked ubiquitination of bbtNEMO. Similar to human A20, bbtA20 is a dual enzyme that removes the K63-linked polyubiquitin chains and builds the K48-linked polyubiquitin chains on bbt receptor-interacting serine/threonine protein kinase 1b, leading to the inhibition of NF-κB signaling. Our study not only suggests that ubiquitination is an ancient strategy in regulating NF-κB activation but also provides the first evidence, to our knowledge, for ABINs/A20-mediated inhibition of NF-κB via modifying the ubiquitinated proteins in a basal chordate, adding information on the stepwise development of vertebrate innate immune signaling.

Animal immune systems can be classified into those of innate immunity and those of adaptive immunity. It is generally thought that the former are universal for all animals and depend on germline-encoded receptors that recognize highly conserved pathogen-associated molecular patterns (PAMPs), whereas the latter are vertebrate specific and are mediated primarily by lymphocytes bearing a unique antigen receptor. However, novel adaptive or adaptive-like immunities have been found in invertebrates and jawless vertebrates, and extraordinarily complex innate immunities, created through huge expansions of many innate gene families, have recently been found in the cephalochordate amphioxus and the echinoderm sea urchin. These studies not only inspire immunologists to seek novel immune mechanisms in invertebrates but also raise questions about the origin and evolution of vertebrate immunities.

This chapter introduces the immune-related transcription factors in amphioxus, including NF-κB, IRFs, and STATs. It starts by introducing the architecture, evolution, and transcriptional mechanism of two amphioxus NF-κB family members. It then introduces the phylogeny and transcriptional activities of nine amphioxus IRFs, which shed light on the evolution of IFN-based antiviral mechanisms. By the end of the chapter the JAK-STAT pathway among species and introduction of the amphioxus STAT family are compared. The composition of transcriptional factors in amphioxus remains in a simple form compared with the great expansion in pattern recognition receptors and their adaptors, suggesting a tight regulation of amphioxus innate immune signaling at the transcriptional level.

This chapter introduces the putative apoptosis mechanism in amphioxus. It starts by presenting general information about apoptosis in mammals. It then introduces the apoptosis-related genes in amphioxus, including Apaf-1 and Bcl2 homolog, the caspase family, and the TRAIL-DR apoptosis-related genes. DFD shuffling is discussed to shed lights on the emergence of extrinsic apoptosis in basal chordates. At the end of the chapter, it is postulated that the expanded DFD genes may involve two interfaces in regulating amphioxus apoptosis and pattern recognition systems.

This chapter introduces the pattern recognition system in amphioxus. It starts by giving an overview of pattern recognition and its related signaling in vertebrates and then introduces the TLR signaling pathway, innate antiviral immunity, and NLR signaling pathway in amphioxus. In this chapter, by summarizing recent studies on TLRs and NLRs, as well as by discussing the evolution of antiviral mechanisms, an extraordinary and complex innate immune system in basal chordate amphioxus is presented and compared with that in other species.

Tandem 3′ untranslated regions (UTRs), produced by alternative polyadenylation (APA) in the terminal exon of a gene, could have critical roles in regulating gene networks. Here we profiled tandem poly(A) events on a genome-wide scale during the embryonic development of zebrafish (Danio rerio) using a recently developed SAPAS method. We showed that 43% of the expressed protein-coding genes have tandem 3′ UTRs. The average 3′ UTR length follows a V-shaped dynamic pattern during early embryogenesis, in which the 3′ UTRs are first shortened at zygotic genome activation, and then quickly lengthened during gastrulation. Over 4000 genes are found to switch tandem APA sites, and the distinct functional roles of these genes are indicated by Gene Ontology analysis. Three families of cis-elements, including miR-430 seed, U-rich element, and canonical poly(A) signal, are enriched in 3′ UTR-shortened/lengthened genes in a stage-specific manner, suggesting temporal regulation coordinated by APA and trans-acting factors. Our results highlight the regulatory role of tandem 3′ UTR control in early embryogenesis and suggest that APA may represent a new epigenetic paradigm of physiological regulations.

Whole-genome shotgun assembly has been a long-standing issue for highly polymorphic genomes, and the advent of next-generation sequencing technologies has made the issue more challenging than ever. Here we present an automated pipeline, HaploMerger, for reconstructing allelic relationships in a diploid assembly. HaploMerger combines a LASTZ-ChainNet alignment approach with a novel graph-based structure, which helps to untangle allelic relationships between two haplotypes and guides the subsequent creation of reference haploid assemblies. The pipeline provides flexible parameters and schemes to improve the contiguity, continuity, and completeness of the reference assemblies. We show that HaploMerger produces efficient and accurate results in simulations and has advantages over manual curation when applied to real polymorphic assemblies (e.g., 4%–5% heterozygosity). We also used HaploMerger to analyze the diploid assembly of a single Chinese amphioxus (Branchiostoma belcheri) and compared the resulting haploid assemblies with EST sequences, which revealed that the two haplotypes are not only divergent but also highly complementary to each other. Taken together, we have demonstrated that HaploMerger is an effective tool for analyzing and exploiting polymorphic genome assemblies.