N6 - Methyladenosine defines a new checkpoint in γδ T cell development.

T cells, which are derived from hematopoietic stem cells (HSCs), are the most important components of adaptive immune system. Based on the expression of αß and γδ receptors, T cells are mainly divided into αß and γδ T cells. In the thymus, they share common progenitor cells, while undergoing a series of well-characterized and different developmental processes. N6 -Methyladenosine (m6 A), one of the most abundant modifications in mRNAs, plays critical roles in cell development and maintenance of function. Recently, we have demonstrated that the depletion of m6 A demethylase ALKBH5 in lymphocytes specifically induces an expansion of γδ T cells through the regulation of Jag1/Notch2 signaling, but not αß T cells, indicating a checkpoint role of ALKBH5 and m6 A modification in the early development of γδ T cells. Based on previous studies, many key pathway molecules, which exert dominant roles in γδ T cell fate determination, have been identified as the targets regulated by m6 A modification. In this review, we mainly summarize the potential regulation between m6 A modification and these key signaling molecules in the γδ T cell lineage commitment, to provide new perspectives in the checkpoint of γδ T cell development.

Simultaneous identification of DNA and RNA pathogens using metagenomic sequencing in cases of severe acute respiratory infection.

Metagenomic next-generation sequencing (mNGS) is a valuable technique for identifying pathogens. However, conventional mNGS requires the separate processing of DNA and RNA genomes, which can be resource- and time-intensive. To mitigate these impediments, we propose a novel method called DNA/RNA cosequencing that aims to enhance the efficiency of pathogen detection. DNA/RNA cosequencing uses reverse transcription of total nucleic acids extracted from samples by using random primers, without removing DNA, and then employs mNGS. We applied this method to 85 cases of severe acute respiratory infections (SARI). Influenza virus was identified in 13 cases (H1N1: seven cases, H3N2: three cases, unclassified influenza type: three cases) and was not detected in the remaining 72 samples. Bacteria were present in all samples. Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii were detected in four influenza-positive samples, suggesting coinfections. The sensitivity and specificity for detecting influenza A virus were 73.33% and 95.92%, respectively. A κ value of 0.726 indicated a high level of concordance between the results of DNA/RNA cosequencing and SARI influenza virus monitoring. DNA/RNA cosequencing enhanced the efficiency of pathogen detection, providing a novel capability to strengthen surveillance and thereby prevent and control infectious disease outbreaks.

Arabidopsis cryptochrome 1 controls photomorphogenesis through regulation of H2A.Z deposition.

Light is a key environmental cue that fundamentally regulates plant growth and development, which is mediated by the multiple photoreceptors including the blue light (BL) photoreceptor cryptochrome 1 (CRY1). The signaling mechanism of Arabidopsis thaliana CRY1 involves direct interactions with CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1)/SUPPRESSOR OF PHYA-105 1 and stabilization of COP1 substrate ELONGATED HYPOCOTYL 5 (HY5). H2A.Z is an evolutionarily conserved histone variant, which plays a critical role in transcriptional regulation through its deposition in chromatin catalyzed by SWR1 complex. Here we show that CRY1 physically interacts with SWC6 and ARP6, the SWR1 complex core subunits that are essential for mediating H2A.Z deposition, in a BL-dependent manner, and that BL-activated CRY1 enhances the interaction of SWC6 with ARP6. Moreover, HY5 physically interacts with SWC6 and ARP6 to direct the recruitment of SWR1 complex to HY5 target loci. Based on previous studies and our findings, we propose that CRY1 promotes H2A.Z deposition to regulate HY5 target gene expression and photomorphogenesis in BL through the enhancement of both SWR1 complex activity and HY5 recruitment of SWR1 complex to HY5 target loci, which is likely mediated by interactions of CRY1 with SWC6 and ARP6, and CRY1 stabilization of HY5, respectively.

Blue light-dependent interactions of CRY1 with GID1 and DELLA proteins regulate gibberellin signaling and photomorphogenesis in Arabidopsis.

Cryptochromes are blue light photoreceptors that mediate various light responses in plants and mammals. In Arabidopsis (Arabidopsis thaliana), cryptochrome 1 (CRY1) mediates blue light-induced photomorphogenesis, which is characterized by reduced hypocotyl elongation and enhanced anthocyanin production, whereas gibberellin (GA) signaling mediated by the GA receptor GA-INSENSITIVE DWARF1 (GID1) and DELLA proteins promotes hypocotyl elongation and inhibits anthocyanin accumulation. Whether CRY1 control of photomorphogenesis involves regulation of GA signaling is largely unknown. Here, we show that CRY1 signaling involves the inhibition of GA signaling through repression of GA-induced degradation of DELLA proteins. CRY1 physically interacts with DELLA proteins in a blue light-dependent manner, leading to their dissociation from SLEEPY1 (SLY1) and the inhibition of their ubiquitination. Moreover, CRY1 interacts directly with GID1 in a blue light-dependent but GA-independent manner, leading to the inhibition of the interaction between GID1 with DELLA proteins. These findings suggest that CRY1 controls photomorphogenesis through inhibition of GA-induced degradation of DELLA proteins and GA signaling, which is mediated by CRY1 inhibition of the interactions of DELLA proteins with GID1 and SCFSLY1, respectively.

[Nature-effect transformation mechanism of mulberry leaves and silkworm droppings based on chemical composition analysis].

Starting with the relationship between mulberry leaves and silkworm droppings as food and metabolites, this study systematically compared the chemical components, screened out differential components, and quantitatively analyzed the main differential components based on ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and UPLC-Q-TRAP-MS combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). Moreover, the in vitro enzymatic transformation of the representative differential components was studied. The results showed that(1) 95 components were identified from mulberry leaves and silkworm droppings, among which 27 components only exist in mulberry leaves and 8 components in silkworm droppings. The main differential components were flavonoid glycosides and chlorogenic acids.(2) Nineteen components with significant difference were quantitatively analyzed, and the components with significant differences and high content were neochlorogenic acid, chlorogenic acid, and rutin.(3) The crude protease in the mid-gut of silkworm significantly metabolized neochlorogenic acid and chlorogenic acid, which may be an important reason for the efficacy change in mulberry leaves and silkworm droppings. This study lays a scientific foundation for the development, utilization, and quality control of mulberry leaves and silkworm droppings. It provides references for clarifying the possible material basis and mechanism of the pungent-cool and dispersing nature of mulberry leaves transforming into the pungent-warm and dampness-resolving nature of silkworm droppings, and offers a new idea for the study of nature-effect transformation mechanism of traditional Chinese medicine.

Using Wool Keratin Derived Metallo-Nanozymes as a Robust Antioxidant Catalyst to Scavenge Reactive Oxygen Species Generated by Smoking.

Self-assembled nanostructures based on biomolecules (e.g., proteins and amino acids) and metal ions have promising applications in mimicking the nanostructure, properties, and functions of natural enzymes. Herein, a metal ion-mediated self-assembly method for constructing catalytically active Cu-wool-keratin (CuWK) two-dimensional nanozymes is presented. Specifically, by introducing copper ions as abiological cofactors, WK can serve as a protein scaffold to design and create Cu catalytic sites. The optimized hybrids with Cu-WK coordination framework exhibit significant superoxide dismutases-like activity, catalase-like activity, and hydroxyl radical scavenging ability. These combined antioxidant activities make CuWK a robust nanozyme to effectively remove various reactive oxygen species (ROS). In this work, the as-prepared CuWK as a new additive can be integrated into a cigarette filter system to effectively remove the produced ROS from the burning of tobacco. More importantly, the CuWK nanozymes as a critical element can be further utilized to construct a recycling cigarette holder. Therefore, the present work shows that nanozymes with advanced catalytic capabilities can be constructed by self-assembly of metal ions and proteins, thus facilitating the rational design and discovery of this kind of artificial metalloenzymes.

Arabidopsis cryptochrome 1 undergoes COP1 and LRBs-dependent degradation in response to high blue light.

Arabidopsis cryptochrome 1 (CRY1) is an important blue light photoreceptor that promotes photomorphogenesis under blue light. The blue light photoreceptors CRY2 and phototropin 1, and the red/far-red light photoreceptors phytochromes B and A undergo degradation in response to blue and red light, respectively. This study investigated whether and how CRY1 might undergo degradation in response to high-intensity blue light (HBL). We demonstrated that CRY1 is ubiquitinated and degraded through the 26S proteasome pathway in response to HBL. We found that the E3 ubiquitin ligase constitutive photomorphogenic 1 (COP1) is involved in mediating HBL-induced ubiquitination and degradation of CRY1. We also found that the E3 ubiquitin ligases LRBs physically interact with CRY1 and are also involved in mediating CRY1 ubiquitination and degradation in response to HBL. We further demonstrated that blue-light inhibitor of cryptochromes 1 interacts with CRY1 in a blue-light-dependent manner to inhibit CRY1 dimerization/oligomerization, leading to the repression of HBL-induced degradation of CRY1. Our findings indicate that the regulation of CRY1 stability in HBL is coordinated by COP1 and LRBs, which provides a mechanism by which CRY1 attenuates its own signaling and optimizes photomorphogenesis under HBL.

Hybrid FSK-PSK Waveform Optimization for Radar Based on Alternating Direction Method of Multiplier (ADMM).

In this paper, a new radar signal modulated with a hybrid of the frequency shift keying (FSK) and the phase shift keying (PSK) signal-i.e., the FSK-PSK signal-is studied. Different phase encoding sequences are used to modulate the sub-pulses to obtain lower sidelobe levels and ensure signal orthogonality. In addition, to counter intra-pulse slice repeater jamming of specific length generated by the enemy jammer, an orthogonal waveform made of sub-pulses of equal length based on the FSK-PSK modulation scheme is designed. The simulation results show that the optimized discrete phase encoding sequence can significantly enhance the orthogonality of the sub-pulse in the FSK-PSK signal and effectively suppress the slice repeater jamming. Two algorithms are proposed: (1) the low sidelobe waveform optimization algorithm based on ADMM (LSW-ADMM); and (2) the anti-slice-repeater-jamming algorithm based on ADMM (ASRJ-ADMM). Both algorithms exhibit fast convergence speed and low computational complexity.

[Literature-based analysis of conversion of components in fermentation process of Sojae Semen Praeparatum].

Based on the systematic retrieval and the reported components of Sojae Semen Nigrum and Sojae Semen Praeparatum, this study conducted in-depth analysis of conversion of components in the fermentation process, and discussed types and possible mec-hanisms of conversion of chemical components, so as to provide the basis for studying technology, medicinal ingredients and quality standards. According to the analysis, there is a certain degree of conversion of nutrients(like protein, sugar, lipid), bioactive substances(like isoflavones, saponins, γ-aminobutyric acid) and other substances(like nucleosides, melanoids, biamines, etc) in the process of fermentation.

An outbreak of acute respiratory infection at a training base in Beijing, China due to human adenovirus type B55.

BACKGROUND: Twelve students experienced symptoms of acute respiratory infection (ARI) at a training base in Beijing from August 26 to August 30, 2015. We investigated the cause of this ARI outbreak. METHODS: In partnership with the local center for disease control, we collected a total of twelve pharyngeal swab specimens as well as demographic information for the affected patients. We used multiplex real-time PCR to screen for sixteen common respiratory viruses in these samples. To isolate HAdV, we inoculated Hep-2 cells with the human adenovirus (HAdV)-positive samples and then carried out sequencing and phylogenetic analysis of the hexon, fiber, and penton genes of the isolated adenoviruses. In addition, we analyzed the entire genome of one strain isolated from the index case to identify single-nucleotide substitutions. RESULTS: We identified ten HAdV-positive students using multiplex real-time PCR. None of the students were co-infected with other viruses. We successfully isolated seven HAdV strains from the pharyngeal swab specimens. The coding sequences of the hexon, fiber, and penton genes of these seven HAdV strains were identical, suggesting that they represented seven strains from a single virus clone. One HAdV isolate obtained from the index case, BJDX-01-2015, was selected for whole genome analysis. From this isolate, we obtained a 34,774-nucleotide sequence. The genome of BJDX-01-2015 clustered with HAdV-B55 in phylogenetic analyses and had 99.97% identity with human adenovirus 55 isolate HAdV-B/CHN/BJ01/2011/55 (GenBank accession no. JX491639). CONCLUSIONS: We identified HAdV-B55 as the strain associated with the August 2015 ARI outbreak at a training base in Beijing. This was the first reported outbreak in Beijing due to HAdV-B55. Continuous surveillance of respiratory adenoviruses is urgently needed to understand the epidemiological and evolutionary features of HAdV-B55, and an epidemiological modeling approach may provide further insights into this emerging public health threat. Furthermore, the clinical laboratory data from this outbreak provides important reference for the clinical diagnosis and may ultimately aid in informing the development of strategies to control and prevent respiratory tract infections caused by HAdV-B55.

[Textual research on Bupleuri Radix in Chinese classical prescriptions].

Through consulting the herbs and medical books of past dynasties, combining with modern literature and field investigation, this paper made textual research on the name, origin, producing area, harvesting and processing of Bupleuri Radix used in the Catalogue of Ancient Classical Prescriptions(the first batch).From Han to the Southern and Northern Dynasties, the source of Bupleuri Radix was a mixture of Bupleurum and Peucedanum, it's hard to define the origin of authentic products.In Tang Dynasty, Caryophyllaceae had been used as Bupleuri Radix. In Song Dynasty, it was clear that the genuine production area of Bupleuri Radix was Yinzhou, its origin was B. corzonerifolium and B. yinchowense.After the Ming Dynasty, B. chinense gradually became the mainstream. It has been confirmed that there were differences in the efficacy between Stellaria dichotoma in Caryophyllaceae and Bupleurum in Umbelliferae, however, the use of S. dichotoma is still attributed to Bupleuri Radix. In the Qing Dynasty, S. dichotoma was distinguished from Bupleuri Radix as another medicine. Among the prescriptions containing Bupleuri Radix included in the Catalogue of Classical Prescriptions in Ancient China(the first batch), the mainstream of genuine Bupleuri Radix should be B. scorzonerifolium and B. chinense. It is suggested that the genuine base of Bupleuri Radix should be selected according to the current resources and industrial development of Bupleuri Radix, and it should conform to the Chinese Pharmacopoeia.

[Textual research on "Gui" in Chinese classical prescriptions].

Through consulting the ancient herbs and medical books, combining with modern literature, this paper makes textual research on herbal medicine, and textual research on the name, origin, position and harvest and processing changes of the medicinal herbs in ancient classical prescriptions. According to research, Cinnamon medicinal materials were first listed in the Shennong's Herbal Classic, as the name of "Jungui" and "Mugui". Among them, Jungui has undergone the evolution of "Qungui-Jungui-Tonggui-Jungui". After the Northern and Southern Dynasties, a half-volume fatty "Gui" was added, but the usage of the three was no different. The names of Cinnamomi Ramulus and Cinnamomi Cortex did not appear until the Tang Dynasty, and they were preferably thick-skinned and with no cork cambium, and they were mostly used in the name of "Guixin"; Since the Song and Yuan Dynasties, the medicinal parts of cassia have gradually separated. Cinnamomi Cortex is the trunk bark of sapling or branch bark, the twig is Cinnamomi Ramulus, and the tenderest twig is Liugui, Song Dynasty unified the name as "Guizhi"; After the Ming and Qing Dynasties, Cinnamomi Cortex was used as the trunk bark, and Cinnamomi Ramulus was used as the tender twig; In modern times, the Chinese Pharmacopoeia stipulates that the Cinnamomi Ramulus is the young branch of C. cassia, which is Cinnamomum, and Cinnamomi Cortex was the dried trunk bark. From the plant morphology recorded in the previous herbals and the drawings, combined with the distribution of the origins described in the previous herbals, the mainstream plant used as a medicine in the past generations should be C. cassia, but there are other sect. Cinnamomum plants that are also used in medicine everywhere, such as C. chekiangensis, C. bejolghota, C. wilsonii, etc. Throughout the ages, different plant morphologies and medicinal traits have been used to distinguish different categories. The origins of the past dynasties are mostly present in Guangdong, Guangxi province and Vietnam, and are regarded as authentic. The methods for the harvest and processing of cinnamon medicinal materials are basically the same from ancient to modern times.

Harnessing microbial metabolomics for industrial applications.

Metabolome defines a set of metabolites present in a biological sample, which provides an immediate and dynamic recording of microbes in response to genetic and/or environmental perturbations. In recent years, metabolomics in combination with other omics diagnostic tools such as genomics, transcriptomics and proteomics is focused on addressing open biological questions that accelerate our understanding of the system as a whole and boost the use of systems metabolic engineering tools in industrial settings. In this review article, we summarize the applications of metabolomics to industrial microbial fermentations with respect to the bulk production of organic acids, amino acids, enzymes, antibiotics and therapeutic proteins. In addition, future prospects regarding metabolomics-assisted research are provided.

[Textual research on "Zhu" in Chinese classical prescriptions].

Through consulting the ancient herbs and medical books,combining with modern literature and field investigation,this paper makes textual research on herbal medicine,and makes textual research on the name,origin,position and changes of collection and processing of the medicinal herbs in Ancient Classical Prescriptions. " Zhu" wasn't distinguished before the Northern and Southern Dynasties,but the efficacy of the techniques recorded in the documents at that time was similar to that of today's Atractylodis Rhizoma.Tao Hongjing put forward the theory of " red and white" in the Northern and Southern Dynasties. " Cangzhu" and " Baizhu" gradually differentiated,but there was no clear distinction between them. Since Song and Yuan Dynasties, " Baizhu" has been respected and classified in the literature. In Ming Dynasty, " Baizhu" was cultivated and differentiated into different quality specifications according to its growth pattern and origin. Maoshan is the genuine production area of " Cangzhu". The quality of wild " Baizhu" produced in Yuqian city is the best. In modern times,the origins of " Cangzhu" and " Baizhu" were defined according to plant taxonomy. " Zhu" before Song Dynasty was close to Atractylodes lancea, " Baishu" had been respected since the Song Dynasty. So when Song people revised the previous literature,they unified " Zhu" into " Baizhu" and used it for later generations. Its safety and effectiveness have been confirmed,and the wild resources of modern atractylodes are scarce. Therefore,it is suggested that when classical famous prescriptions are developed,the prescription recorded as " Baizhu" does not need to be changed in its origin,that is,A. macrocephala at present or can choose the appropriate basis according to the principle of local righteousness.Textual research shows that the origin of " Cangzhu" in the classical prescription should be A. lancea.

[Textual research on classical prescription of Acorus tatarinowii].

Based on the prescription books of herbs and medical books of all dynasties,this article makes a textual research on the name,origin,position,quality,collection,processing and concocting of Acorus tatarinowii used in the classical prescription,and clarifies the relationship between ancient and modern,so as to provide reference and basis for the development and utilization of the classical famous prescription.According to research,A. tatarinowii has many aliases and is often remembered as " Chang pu" when use as medicine; It has a wide distribution of resources in our country,all over the country have produced and mostly wild,its producing areas there is a trend of migration to the southeast; It is recorded in the ancient books of Chinese herbs that most of its medicinal parts are roots,and to root thin,solid quality,dense,aromatic smell,full taste,chewing less slag of high quality; It is harvested in February,May,August and December,and dried in the shade after harvesting; Its concocting methods are more than 20 species have been recorded; Before the Tang Dynasty,the basis of the medicinal A. tatarinowii was relatively chaotic,through textual research,it is concluded that A. tatarinowii should be the mainstream in all dynasties,and that its quality is superior to that of other species in the same genus.It is recommended to be used in " Kaixin san" and " rehmannia drink".

[Textual research on Chinese herbaceous peony in Chinese classical prescriptions].

In this paper,the name,origin,producing area,harvesting and processing changes of Paeonia lactiflora used in classical prescriptions were studied by textual research of herbal medicine and field investigation. Chinese herbaceous peony wasn' t distinguished before the Northern and Southern Dynasties; Tao Hongjing proposed that there were two kinds of P. lactiflora in the Northern and Southern Dynasties,but they were not clearly defined; since the Song and Yuan Dynasties,the method of distinguishing P. lactiflora by flower color and root color was proposed. In the Ming Dynasty,people put forward the criteria similar to modern ones,that is,to divide red peony and white peony by means of harvesting and processing,and to continue for future generations. Since modern times,different growth patterns and processing methods have been used to classify red peony and white peony. Paeoniae Radix Alba has gradually formed three major cultivation genuine producing areas: Hangzhou,Sichuan and Bozhou,while Paeoniae Radix Rubra in modern times has praised the wild medicinal materials produced in Inner Mongolia,Toronto and other places. According to textual research,Paeoniae Radix Alba was highly praised in Song Dynasty. When people in Song Dynasty revised the previous literature,they changed " Shaoyao" into " Baishao" and continued to use Paeoniae Radix Alba for future generations. Therefore,the origin of P. lactiflora in classical prescriptions before the Song Dynasty should be determined by the combination of prescription function and prescription meaning evolution; After the Song Dynasty,the origins of " Red Paeonia Root" and " White Paeonia Root" in prescriptions are basically the same as those in today's prescriptions,which should be recorded in ancient prescriptions. For the medicinal flavor of " Paeonia Root" recorded in prescriptions after the Song Dynasty,the origins can be determined by functional domination and the evolution of prescriptions.

Genetic variation in the hemagglutinin of A(H1N1) 09pdm and A(H3N2) influenza viruses in the Beijing area from 2009 to 2014.

BACKGROUND: A(H1N1) 09pdm and A(H3N2) influenza viruses are the main cause of occasional influenza pandemics and seasonal influenza epidemics around the world. Unfortunately, the understanding of long-term genetic variation in these viruses remains limited. METHODS: In this study, hemagglutinin genes from 90 A(H1N1) 09pdm and 48 A(H3N2) influenza viruses in the Beijing area from 2009 to 2014 were sequenced and analyzed. RESULTS: The hemagglutinin genes in A(H1N1) 09pdm and A(H3N2) shared nucleotide similarity that ranged from 93.06% - 99.88% and 98.68% - 99.29%, respectively, compared with current vaccine strains. 10 and 7 amino acid mutations in antigenic sites were identified in these two strains, respectively. In addition, a new site 177 glycosylation, which did not exist in previous circulating strains, was identified in 3 A(H1N1) 09pdm isolates. CONCLUSIONS: This study demonstrated the continued evolution of seasonal influenza viruses in the Beijing area, indicating that an update of the vaccine is needed, especially for A(H1N1) 09pdm influenza virus.

[Study on the superantigen gene profiles of group A Streptococcus isolated from children in Beijing, 2014].

OBJECTIVE: To investigate superantigen gene profiles of group A Streptococcus (GAS) isolated in Beijing pediatric patients in 2014, and to explore the the relationship between superantigen gene profiles with emm types, and GAS infections with diseases. METHODS: A total of 259 GAS strains were isolated from pediatric patients clinically who diagnosed with scarlet fever and pharyngitis from 36 hospitals in Beijing from May to July, 2014.The Superantigens genes of strains were performed by Real-time PCR (speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ, ssa). PCR amplification of GAS strain M protein N gene segments were carried ort; products after sequencing comparison were analyzed to determine the GAS types of emm. The differences in distributions of superantigen genes and emm types of GAS isolates were compared between subgroups. RESULTS: Among the 259 GAS strains, the detection rates of 13 superantigens were as the following: speA 48.6% (126), speB 99.2% (257), speC 99.2% (257), speF 98.8% (256), speG 98.5% (255), speH 43.6% (113), speI 46.3% (120), speJ 49.0% (127), smeZ 99.2% (257) and ssa 98.5% (255), respectively, however, speK, speL, and speM were not found. Eleven superantigen gene profiles in all were observed (A-K). The percentage of emm1 strains harbored spe A and speJ were 94.2% (113/120), 95.0% (114/120), respectively, which were significantly higher than those of emm12 strains (5.6% (7/124), 5.6% (7/124), respectively; χ(2) = 191.20, 194.80, P < 0.001). The percentage of emm12 strains harbored speH and speI were 83.9% (104/124), 88.7% (110/124), respectively, which were significantly higher than those of emm1 strains (3.3% (4/120), 4.2% (5/120), respectively; χ(2) = 160.30, 174.90, P < 0.001).The superantigen genotypes of GAS strains and emm types, which were isolated from scarlet fever and pharyngitis cases, were not significant different (P > 0.05). CONCLUSION: The GSA strains isolated in Beijing pediatric patients in 2014, the relevance ratio of speB, speC, speF, smeZ, speG, ssa were higher than others, while speK, speL, and speM were no detected in any GAS strains. The superantigen genes appeared to be associated with the emm type. Furthermore, emm type distribution and superantigen genes were not different between scalet fever and pharyngitis.

Developing rational scale-down simulators for mimicking substrate heterogeneities based on cell lifelines in industrial-scale bioreactors.

The influence of extracellular variations on the cellular metabolism and thereby the process performance at large-scale can be evaluated using the so-called scale-down simulators. Nevertheless, the major challenge is to design an appropriate scale-down simulator, which can accurately mimic the cell lifelines that record the flow paths and experiences of cells circulating in large-scale bioreactors. To address this, a dedicated SDSA (scale-down simulator application) was purposedly developed on the basis of black box model and process reaction model established for Penicillium chrysogenum strain as well as cell lifelines or trajectories information in an industrial-scale fermentor. Guided by the SDSA, the industrial-relevant metabolic regimes for substrate availability, i.e., excess, limitation and starvation, were successfully reproduced at laboratory-scale three-compartment scale-down (SD) system. In addition, such SDSA can also display individual process dynamics in each compartment, and demonstrate how individual factors influence the entire bioprocess performance, thus serving both educational and research purposes.

Adaptive Fusion of Deep Learning With Statistical Anatomical Knowledge for Robust Patella Segmentation From CT Images.

Kneeosteoarthritis (KOA), as a leading joint disease, can be decided by examining the shapes of patella to spot potential abnormal variations. To assist doctors in the diagnosis of KOA, a robust automatic patella segmentation method is highly demanded in clinical practice. Deep learning methods, especially convolutional neural networks (CNNs) have been widely applied to medical image segmentation in recent years. Nevertheless, poor image quality and limited data still impose challenges to segmentation via CNNs. On the other hand, statistical shape models (SSMs) can generate shape priors which give anatomically reliable segmentation to varying instances. Thus, in this work, we propose an adaptive fusion framework, explicitly combining deep neural networks and anatomical knowledge from SSM for robust patella segmentation. Our adaptive fusion framework will accordingly adjust the weight of segmentation candidates in fusion based on their segmentation performance. We also propose a voxel-wise refinement strategy to make the segmentation of CNNs more anatomically correct. Extensive experiments and thorough assessment have been conducted on various mainstream CNN backbones for patella segmentation in low-data regimes, which demonstrate that our framework can be flexibly attached to a CNN model, significantly improving its performance when labeled training data are limited and input image data are of poor quality.