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Abstract The dysregulation of pro- and anti-inflammatory processes in the brain has been linked to the pathogenesis of major depressive disorder (MDD), although the precise mechanisms remain unclear. In this study, we discovered that microglial conditional knockout of Pdcd4 conferred protection against LPS-induced hyperactivation of microglia and depressive-like behavior in mice. Mechanically, microglial Pdcd4 plays a role in promoting neuroinflammatory responses triggered by LPS by inhibiting Daxx-mediated PPARγ nucleus translocation, leading to the suppression of anti-inflammatory cytokine IL-10 expression. Finally, the antidepressant effect of microglial Pdcd4 knockout under LPS-challenged conditions was abolished by intracerebroventricular injection of the IL-10 neutralizing antibody IL-10Rα. Our study elucidates the distinct involvement of microglial Pdcd4 in neuroinflammation, suggesting its potential as a therapeutic target for neuroinflammation-related depression.

Abstract Recent findings have shown that fatty acid metabolism is profoundly involved in ferroptosis. However, the role of cholesterol in this process remains incompletely understood. In this work, we show that modulating cholesterol levels changes vulnerability of cells to ferroptosis. Cholesterol alters metabolic flux of the mevalonate pathway by promoting Squalene Epoxidase (SQLE) degradation, a rate limiting step in cholesterol biosynthesis, thereby increasing both CoQ10 and squalene levels. Importantly, whereas inactivation of Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1), the branch point of cholesterol biosynthesis pathway, exhibits minimal effect on ferroptosis, simultaneous inhibition of both CoQ10 and squalene biosynthesis completely abrogates the effect of cholesterol. Mouse models of ischemia-reperfusion and doxorubicin induced hepatoxicity confirm the protective role of cholesterol in ferroptosis. Our study elucidates a potential role of ferroptosis in diseases related to dysregulation of cholesterol metabolism and suggests a possible therapeutic target that involves ferroptotic cell death.

Abstract Emerging evidence reveals that amino acid metabolism plays an important role in ferroptotic cell death. The conversion of methionine to cysteine is well known to protect tumour cells from ferroptosis upon cysteine starvation through transamination. However, whether amino acids‐produced metabolites participate in ferroptosis independent of the cysteine pathway is largely unknown. Here, the authors show that the tryptophan metabolites serotonin (5‐HT) and 3‐hydroxyanthranilic acid (3‐HA) remarkably facilitate tumour cells to escape from ferroptosis distinct from cysteine‐mediated ferroptosis inhibition. Mechanistically, both 5‐HT and 3‐HA act as potent radical trapping antioxidants (RTA) to eliminate lipid peroxidation, thereby inhibiting ferroptotic cell death. Monoamine oxidase A (MAOA) markedly abrogates the protective effect of 5‐HT via degrading 5‐HT. Deficiency of MAOA renders cancer cells resistant to ferroptosis upon 5‐HT treatment. Kynureninase (KYNU), which is essential for 3‐HA production, confers cells resistant to ferroptotic cell death, whereas 3‐hydroxyanthranilate 3,4‐dioxygenase (HAAO) significantly blocks 3‐HA mediated ferroptosis inhibition by consuming 3‐HA. In addition, the expression level of HAAO is positively correlated with lipid peroxidation and clinical outcome. Together, the findings demonstrate that tryptophan metabolism works as a new anti‐ferroptotic pathway to promote tumour growth, and targeting this pathway will be a promising therapeutic approach for cancer treatment.

Bio-based PA56 is as matrix resin, maleic anhydride (MAH), and glycidyl methacrylate (GMA) dual monomer grafted POE (POE-g-MAH/GMA) polyphenyl ether(PPO) are simultaneous as toughening agents. The PA56/POE-g-MAH-GMA/PPO ternary alloys containing 10 wt% POE-g-MAH-GMA with different PPO content prepared by the melt blending method through twin screw extruder. The structure and property of PA56/POE-g-MAH-GMA/PPO ternary alloys were studied. The results showed that the microscopic morphology of each alloy showed an obvious “sea-island” structure. PA56 is a continuous sea phase, and the island phase assumes the “core–shell structure,” the etched POE-g-MAH-GMA particles are as the nucleus, and PPO are as the shell. When the PPO mass fraction is 30%, the relative crystallinity of the alloy is 11.56%, which is 1.68 times lower compared to the pure PA56, the alloy notch impact strength is 42.1 kJ/m2, and reaches 11.7 times of pure PA56; the water absorption rate of 1.22%, which is 3.22 times lower than pure PA56.

Abstract In the field of RFID, the reading performance of tags is an important performance indicator for measuring tag. Related studies have shown that the tags’ geometrical distribution has an important influence on the tags’ reading performance. In order to optimize the tags’ geometrical distribution and improve the tags’ reading performance, this paper proposes a tag distribution optimization method based on multi‐level wavelet‐CNN (MWCNN) and extreme learning machine (ELM). First, this paper designs a tag distribution optimization system based on stereo‐vision. Second, the stereo‐cameras are used to capture the images of the tags. Aiming at the degradation phenomenon in the acquired images, MWCNN is used to recover the degraded tag images. On the basis of the image restoration, the template matching method is used to obtain the 3D coordinates of the tags. Then, ELM is used to model and predict the nonlinear relationship between 3D coordinates of the tags and the corresponding reading distance. The results show that the average prediction relative error is 0.56% and the time cost is 2.0 s. The average prediction relative error of ELM is smaller than GA‐BP and PSO‐BP. The time cost of ELM is smaller than the wavelet neural network.

Abstract Depression is one of the most common psychiatric disorders. Recently, studies demonstrate that antidepressants generating BDNF not only maintain synaptic signal transmission but also repress neuroinflammatory cytokines such as IL-6 and IL-1β. Therefore, promoting BDNF expression provides a strategy for the treatment of depression. Our recent research has indicated that programmed cell death 4 (Pdcd4) is a new target for antidepressant treatment by facilitating BDNF. Herein, we modified Pdcd4 specific small interfering RNA (siPdcd4) with the rabies virus glycoprotein peptide (RVG/siPdcd4) which enables it cross the blood-brain barrier (BBB). We found that RVG/siPdcd4 complex was selectively delivered to neurons and microglia and silenced the expression of Pdcd4, thereby up-regulating the level of BDNF and down-regulating IL-6 and IL-1β expression. More importantly, RVG/siPdcd4 injection attenuated synaptic plasticity impairment and protected mice from CRS-induced depressive behavior. These findings suggest that RVG/siPdcd4 complex is a potential therapeutic medicine for depression.

Objective. Chronic low back pain is an overwhelming problem for a wide range of people and leads to tactile acuity deficits. We aimed to investigate the correlations among age, pain severity, disability, and tactile acuity in patients with chronic low back pain by using multiple tactile acuity tests. Methods. A total of 58 participants (36.40 ± 14.95 years) with chronic low back pain were recruited, and two-point discrimination, point-to-point test, and two-point estimation were performed on their painful low back areas. The correlations between age, pain intensity, disability, and tactile acuity were characterized with Pearson’s correlation coefficients. Subgroup analyses according to the median values of age, pain intensity, and disability were used to compare the intergroup difference in tactile acuity. Results. Results illustrated significant negative associations among age, pain intensity, disability, and tactile acuity. Subgroup analyses revealed that patients with below-the-median values of age, pain intensity, and disability had better performance in tactile acuity tests than those with above-the-median values. Conclusion. This study indicated that tactile acuity was negatively associated with age, pain intensity, and disability in young patients with chronic low back pain.

Safety is an eternal issue in the civil aviation transportation. Once a civil aviation accident occurs, it will cause great casualties and economic losses. In order to ensure the civil aviation safety, the hazard identification and prediction of civil aircraft should be effectively and accurately realized. The civil aircraft uses Aircraft Communications Addressing and Reporting System (ACARS) to interact with the ground during flight. The data generated by ACARS has a simple structure and strong timeliness. In view of the advantages of ACARS data, a hazard identification and prediction method based on support vector machine optimized by particle swarm optimization (PSO-SVM) and long short term memory (LSTM) neural networks which uses ACARS report as analysis data is proposed. First, in order to reduce the identification and prediction time cost, the SVM-based recursive feature elimination method with cross-validation algorithm (SVM-RFECV) is used to select the characteristic parameters. Then, the SVM optimized by PSO is used to identify hazard based on the selected parameters. According to the identification results, the LSTM is used to predict the trend of the selected parameters to realize hazard prediction. An A13 report of APU generated by ACARS is selected as analysis data for hazard identification and predication in this paper. The analysis results show that the proposed identification method based on PSO-SVM and SVM-RFECV has high identification speed and accuracy. The proposed prediction method based on LSTM has the best prediction performance. The proposed method can effectively identify hazards and accurately predict the trend of parameters to improve the safety of aircraft.

Polymer composites with high thermal conductivity have a great potential for applications in modern electronics due to their low cost, easy process, and stable physical and chemical properties. Nevertheless, most polymer composites commonly possess unsatisfactory thermal conductivity, primarily because of the high interfacial thermal resistance between inorganic fillers. Herein, we developed a novel method through silver functionalized graphene nanosheets (GNS) and multiwalled carbon nanotube (MWCNT) composites with excellent thermal properties to meet the requirements of thermal management. The effects of composites on interfacial structure and properties of the composites were identified, and the microstructures and properties of the composites were studied as a function of the volume fraction of fillers. An ultrahigh thermal conductivity of 12.3 W/mK for polymer matrix composites was obtained, which is an approximate enhancement of 69.1 times compared to the polyvinyl alcohol (PVA) matrix. Moreover, these composites showed more competitive thermal conductivities compared to untreated fillers/PVA composites applied to the desktop central processing unit, making these composites a high-performance alternative to be used for thermal management.

Abstract Background The aim of this study is to investigate the relationship between16-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF (vascular endothelial growth factor) expression in patients with benign and malignant pulmonary nodules, and differential diagnosis between benign and malignant pulmonary nodules. Methods Sixty-four patients with benign and malignant pulmonary nodules underwent 16-slice spiral CT perfusion imaging. The CT perfusion imaging was analyzed for TDC (time density curve), perfusion parametric maps, and the respective perfusion parameters. Immunohistochemical findings of MVD (microvessel density) measurement and VEGF expression was evaluated. Results The shape of the TDC of peripheral lung cancer was similar to those of inflammatory nodule. PH (peak height), PHpm/PHa (peak height ratio of pulmonary nodule to aorta), BF (blood flow), BV (blood volume) value of peripheral lung cancer and inflammatory nodule were not statistically significant (all P > 0.05). Both showed significantly higher PH, PHpm/PHa, BF, BV value than those of benign nodule (all P < 0.05). Peripheral lung cancer showed significantly higher PS (permeability surface) value than that of inflammatory nodule and benign nodule (all P < 0.05). BV, BF, PS, MTT, PH, PHpm/PHa, and MVD among three groups of peripheral lung cancers were not significantly (all P > 0.05). In the case of adenocarcinoma, BV, BF, PS, PHpm/PHa, and MVD between poorly and well differentiation and between poorly and moderately differentiation were statistically significant (all P < 0.05). The peripheral lung cancers with VEGF positive expression showed significantly higher PH, PHpm/PHa, BF, BV, PS, and MVD value than those of the peripheral lung cancer with VEGF negative expression, and than those of benign nodule with VEGF positive expression (all P < 0.05). When investigating VEGF negative expression, it is found that PH, PHpm/PHa, and MVD of inflammatory nodule were significantly higher than those of peripheral lung cancer, PS of inflammatory nodule were significantly lower than that of peripheral lung cancer (all P < 0.05). PH, PHpm/PHa, BF, and BV of benign nodule were significantly lower than those of inflammatory nodule (all P < 0.05), rather than PS and MTT (mean transit time) (all P > 0.05). PH, PHpm/PHa, BV, and PS of benign nodule were significantly lower than those of peripheral lung cancer (all P < 0.05). In the case of VEGF positive expression, MVD was positively correlated with PH, PHpm/PHa, BF, BV, and PS of peripheral lung cancer and PS of benign nodule (all P < 0.05). Conclusion Multi-slice spiral CT perfusion imaging closely correlated with tumor angiogenesis and reflected MVD measurement and VEGF expression. It provided not only a non-invasive method of quantitative assessment for blood flow patterns of peripheral pulmonary nodules but also an applicable diagnostic method for peripheral pulmonary nodules.

AIM: To evaluate the clinical effects and safety of Loratadine combined with Diclofenac sodium eye drops in the treatment of allergic conjunctivitis by system review.METHODS:Using “Loratadine” “Diclofenac sodium” and “allergic conjunctivitis” as keywords, a randomized controlled trial of Loratadine combined with diclofenac sodium in the treatment of allergic conjunctivitis was searched in Embase, Cochrane library, Pubmed, CNKI, Wanfang database, VIP and SionMed. The retrieval time is from the establishment of the database to July 2021. The risk bias tool provided by the Cochrane cooperation scale was used to assess the risk bias of included studies of RCTs. The publication bias of the included studies was assessed by the Egger's test. Meta-analysis of clinical efficiency, incidence of adverse effects, ocular itch score, and discharge score were using RevMan 5.3. Descriptive analysis were performed on the results with high heterogeneity.RESULTS:A total of 19 articles were included, all of which were Chinese literatures, including 1 931 patients(2 044 eyes). The control group was treated with Loratadine, and the experimental group was treated with Loratadine combined with Diclofenac sodium eye drops. The Meta-analysis showed that the clinical effect of experimental group was better than control group(OR=4.43, 95%CI:3.26-6.03,P

This study explored the relations between the social support network of mothers of children with autism spectrum disorder (ASD), perceived social support, and their subjective wellbeing. The participants were mothers of children with ASD in Shanghai. Their social support network structure was explored via the nomination method. Perceived social support was measured using the Revised Social Provisions Scale for Autism (R-SPS-A), and the mothers’ subjective wellbeing was assessed using the Index of Wellbeing, Index of General Affect. A significant correlation was observed between the subjective wellbeing of mothers of children with ASD and perceived social support. Meanwhile, perceived social support was significantly correlated with the effectiveness of overall social support. Finally, perceived social support was also significantly correlated with the network size of social support. Moreover, the effectiveness of social support was significantly associated with the network size of social support and was highly significantly associated with the degree of intimacy of social support. Furthermore, the network size of instrumental support has a significant influence on all perceived social support subdimensions. Overall, social support effectiveness plays an important role in the social support network mechanism on perceived social support and subjective wellbeing in China.

Abstract The function of natural killer (NK) cells has previously been implicated in hematopoietic-related diseases. Killer immunoglobulin-like receptors (KIR) play an important role in NK cells after hematopoietic stem cell transplantation. To explore the immunogenetic predisposition of hematological-related diseases, herein, a multi-center retrospective study in China was conducted, analyzing and comparing 2519 patients with hematopathy (mainly, acute lymphoblastic leukemia, acute myeloid leukemia, aplastic anemia, and myelodysplastic syndrome) to 18,108 individuals without known pathology. Genotyping was performed by polymerase chain reaction with specific sequence primers (PCR-SSP). As a result, we discovered four genes including KIR2DL5 (OR: 0.74, 95% CI 0.59–0.93; Pc = 0.0405), 2DS1 (OR: 0.74, 95% CI 0.59–0.93; Pc = 0.0405), 2DS3 (OR: 0.58, 95% CI 0.41–0.81; Pc = 0.0180), and 3DS1 (OR: 0.74, 95% CI 0.58–0.94; Pc = 0.0405) to be protective factors that significantly reduce the risk of aplastic anemia. Our findings offer new approaches to immunotherapy for hematological-related diseases. As these therapies mature, they are promising to be used alone or in combination with current treatments to help to make blood disorders a manageable disease.

AIM: To systematically evaluate the efficacy and safety of olopatadine combined with pranoprofen in the treatment of allergic conjunctivitis.METHODS: Using “olopatadine eye drops”, “pranoprofen eye drops” and “allergic conjunctivitis” as keywords, the controlled clinical trials of olopatadine combined with pranoprofen in the treatment of allergic conjunctivitis were searched from Embase, Cochrane library, PubMed, CNKI, Wanfang and VIP database, with an retrieval time from the establishment of the database to January 1, 2022; The Cochrane Risk of Bias Assessment Tool was used to assess the quality of the included studies, and the Egger's test was performed for publication bias of the included literatures. Meta-analysis was performed by using RevMan 5.3.RESULTS: A total of 24 eligible Chinese literatures were included, with 2 443 patients(2 547 eyes)in total. The test group was administrated olopatadine combined with pranoprofen, and the control group was treated with olopatadine monotherapy; The results of Meta-analysis showed that the clinical efficiency of the test group was better than that of the control group(OR=4.42, 95%CI:3.37-5.80,P

Continuous risky decisions refer to decisions that involve trade-offs among options with persistent risks. People can use the probability of occurrence per unit time (e.g., ‘the probability of occurrence is 1% per month’) or the average time of risk occurrence (e.g., ‘the average occurrence time is 100 months’) to represent continuous risky options. In this study, we examined the effect of the presentation format (i.e., the probability of occurrence per unit time vs. the average time of risk occurrence) on continuous risky decisions in the gain domain and further explored the underlying mechanism. In Study 1 (N = 122), we demonstrated the effect of presentation format on continuous risky decisions and the moderating effect of the magnitude of probabilities. Specifically, when the probabilities were relatively low, compared with the probability of occurrence per unit time, using the average time of risk occurrence to present the continuous risky options led to more risk-averse decisions. However, when the probabilities were relatively high, compared with the probability of occurrence per unit time, the presentation format of the average time occurrence led to more risk-seeking decisions. In Study 2 (N = 136), we found that the moderating effect of the option probabilities on continuous risky decisions was mediated by the subjective attribute-wise difference judgment. In Study 3 (N = 221), we replicated the effect of presentation format on continuous risky decisions in more natural scenarios. The study offered a deep understanding of the mechanism of continuous risky decision-making, and the results were conducive to further developing theories in relevant fields.

AIM: To compare the clinical efficacy and safety of gatifloxacin eye drops and levofloxacin eye drops in the treatment of acute bacterial conjunctivitis using Meta-analysis.METHODS: According to the Cochrane systematic evaluation method, “gatifloxacin” “levofloxacin” and “acute bacterial conjunctivitis” were used as keywords for literature search in Embase, Cochrane library, Pubmed, Medline, CNKI, Wanfang, VIP and CBMdisc from the establishment of the database to March 1, 2021. Randomized controlled trials(RCTs)gatifloxacin eye drops and levofloxacin eye drops in the treatment of acute bacterial conjunctivitis were included. Cochrane bias risk assessment tool was used to evaluate the quality of the included studies. RevMan5.3 software was used for combined analysis. Egger's test in Stata12 was used to assess publication bias, and the level of evidence was evaluated according to the GRADE system.RESULTS: A total of 10 RCTs were included in this study with 1 149 patients. The control group was treated with levofloxacin and the experimental group was treated with gatifloxacin. The results of Meta-analysis showed that the clinical effective rate of acute bacterial conjunctivitis in gatifloxacin group was higher than that in levofloxacin group(OR=3.75, 95%CI: 2.52-5.58, P

AIM: To evaluate the clinical effects of subconjunctival injection of vitamin C in the treatment of corneal ulcer by using Meta-analysis.METHODS: Using “vitamin C” and “corneal ulcer” as keywords, the randomized controlled trials(RCT)of subconjunctival injection of vitamin C in Embase, Cochrane library, Pubmed, CNKI and Wanfang database in the treatment of corneal ulcer was searched. Relevant reference published before February 2021. The risk bias tool provided by the Cochrane cooperation scale was used to assess the risk bias of included studies of RCTs. The publication bias of the included studies were assessed by the Egger's test with Stata software. Meta-analysis was performed with RevMan 5.3.RESULTS: A total of 32 eligible articles were included, all of which were Chinese literatures, with a total of 4 514 patients. The control group was treated with routine treatment, and the experimental group was treated with subconjunctival injection of vitamin C combined with routine treatment. The Meta-analysis showed that the experimental group was better than control group(OR=4.61, 95%CI:3.70, 5.74). The recurrence rate was lower than control group(OR=0.24, 95%CI: 0.18, 0.31). The cure time in experimental group was shorter than control group(MD= -6.29, 95%CI: -7.08, -5.51), 32 studies do not adequately report adverse drug reactions(ADR). Egger's test was performed on the total effective rate, recurrence rate and cure time. The results showed that there was publication bias in the total effective rate and cure time. Trim and fill method showed that the publication bias did not affect the results.CONCLUSION: Subconjunctival injection of vitamin C is feasible in the treatment of corneal ulcer. The clinical effect, cure time and recurrence rate were better than routine treatment. However, due to the low intensity of the included research evidence, more multicenter, randomized double-blind clinical trials are needed to improve the evidence intensity of vitamin C in the treatment of corneal ulcer.

From a biodiversity survey of a subterranean habitat near Sinan County, Guizhou Province, southwestern China, a new atyid shrimp of the genus Caridina H. Milne Edwards, 1837, C. sinanensis sp. nov. was discovered. The new species can be separated from other congeners based on a combination of characters including depigmentation in body and reduction of eyes, small pigment spot at the centre of the cornea, the shape of rostrum and the endopod of the 1st male pleopod, and the relatively longer appendix interna on the appendix masculina of the 2nd pleopod. Mitochondrial COI and 16S rRNA gene sequences also support the establishment of the new species. Information on the habitat, and the levels of threat are discussed to guide the conservation of C. sinanensis sp. nov.

A faunistic and ecological survey was conducted to document the diversity of freshwater atyid shrimps of Dawanshan Island. Two species of Caridina that occur on this island were documented and discussed. One of these, Caridina tetrazona sp. nov. is described and illustrated as new to science. It can be easily distinguished from its congeners based on a combination of characters, which includes a short rostrum, the shape of the endopod of the male first pleopod, the segmental ratios of antennular peduncle and third maxilliped, the slender scaphocerite, and the absence of a median projection on the posterior margin. Live individuals of the new species display a unique coloration pattern with four dark blue transverse bands on the body, and can be easily recognized in the field. So far, despite considerable surveying efforts made on neighboring islands, this species has only been found from a small stream on Dawanshan Island, which suggests that it may have a very limited range, probably endemic to Dawanshan Island. Molecular characteristics of the mitochondrial cytochrome c oxidase subunit I (COI) demonstrate that this species shows sufficient interspecific divergence from its congeners, including C. serrata Stimpson, 1860, which was found in four streams on Dawanshan Island, and has been previously reported on the neighboring islands of Hong Kong, Dong’ao, Wailingding, and Guishan.

ABSTRACT: Lithium ore (mineralized) bodies in the area A of central Yunnan Province belong to a sedimentary-type, which are controlled by stratum. The studied ore (mineralized) body mainly occurs in the Middle Permian Liangshan Formation. This work described the morphology, structures, main ore types and geochemical characteristics of this ore body in detail, and discussed the ore-forming material source, occurrence state of lithium and the formation mechanism of lithium ores to clarify the prospecting marks. In the further exploration, comprehensive evaluation of the lithium resources of known bauxite ore bodies in central Yunnan Province should be strengthened, and the exploration of hidden lithium ore bodies should be intensified in order to discover more large and super-large lithium orebodies, which will fill the gap of the national demand for lithium resources, and promote the national defense construction and new energy industry development.

Evidence-based information is the foundation for addressing urgent global challenges in conservation and sustainable management of the freshwater biodiversity. The present study expands current knowledge of the genus Macrobrachium in Zaomu Mountain Forest Park, Guangdong Province based on the morphology, colouration, distribution, and molecular characteristics of Macrobrachium maculatum, M. inflatum, M. nipponense, and an undescribed new species, M. laevis. Macrobrachium laevis sp. nov. can be distinguished from its congeners by a combination of characters, which includes the shape of rostrum, smooth carapace, and male second pereiopod. Macrobrachium laevis sp. nov. displays striking colour pattern, which could help to distinguish this species from other congeneric species in living specimen. Furthermore, the molecular characteristics of mitochondrial cytochrome c oxidase subunit I (COI) showed that this species has a sufficient interspecific divergence from its congeners.

Abstract Background The CRISPR/dCas9 system is a powerful tool to activate the transcription of target genes in eukaryotic or prokaryotic cells, but lacks assays in complex conditions, such as the biosynthesis of secondary metabolites. Results In this study, to improve the transcription of the heterologously expressed biosynthetic genes for the production of epothilones, we established the CRISPR/dCas9-mediated activation technique in Myxococcus xanthus and analyzed some key factors involving in the CRISPR/dCas9 activation. We firstly optimized the cas9 codon to fit the M. xanthus cells, mutated the gene to inactivate the nuclease activity, and constructed the dCas9-activator system in an epothilone producer. We compared the improvement efficiency of different sgRNAs on the production of epothilones and the expression of the biosynthetic genes. We also compared the improvement effects of different activator proteins, the ω and α subunits of RNA polymerase, and the sigma factors σ54 and CarQ. By using a copper-inducible promoter, we determined that higher expressions of dCas9-activator improved the activation effects. Conclusions Our results showed that the CRISPR/dCas-mediated transcription activation is a simple and broadly applicable technique to improve the transcriptional efficiency for the production of secondary metabolites in microorganisms. This is the first time to construct the CRISPR/dCas9 activation system in myxobacteria and the first time to assay the CRISPR/dCas9 activations for the biosynthesis of microbial secondary metabolites.

Due to the high similarity in their requirements for space and food, close bacterial relatives may be each other's strongest competitors. Close bacterial relatives often form visible boundaries to separate their swarming colonies, a phenomenon termed colony-merger incompatibility. While bacterial species are known to have many incompatible strains, it is largely unclear which traits lead to multiple incompatibilities and the interactions between multiple incompatible siblings. To investigate the competitive interactions of closely related incompatible strains, we mutated Myxococcus xanthus DK1622, a predatory bacterium with complex social behavior. From 3392 random transposon mutations, we obtained 11 self-identification (SI) deficient mutants that formed unmerged colony boundaries with the ancestral strain. The mutations were at nine loci with unknown functions and formed nine independent SI mutants. Compared with their ancestral strain, most of the SI mutants showed reduced growth, swarming and development abilities, but some remained unchanged from their monocultures. When pairwise mixed with their ancestral strain for co-cultivation, these mutants exhibited improved, reduced or unchanged competitive abilities compared with the ancestral strain. The sporulation efficiencies were affected by the DK1622 partner, ranging from almost complete inhibition to 360% stimulation. The differences in competitive growth between the SI mutants and DK1622 were highly correlated with the differences in their sporulation efficiencies. However, the competitive efficiencies of the mutants in mixture were inconsistent with their growth or sporulation abilities in monocultures. We propose that the colony-merger incompatibility in M. xanthus is associated with multiple independent genetic loci, and the incompatible strains hold competitive interaction abilities, which probably determine the complex relationships between multiple incompatible M. xanthus strains and their co-existence strategies.

Objectives: This study aimed to review etiological and epidemiological data for hand, foot, and mouth disease (HFMD) cases that occurred between 2008 and 2010 in Guangzhou City, to help develop and implement precautionary measures applicable for future outbreaks. Methods: The characteristics of 4,753 HFMD episodes were retrospectively reviewed in 4,636 patients reported between 2008 and 2010 by the Guangdong Women and Children's Hospital, which is the national enterovirus monitoring agent and the designated hospital in China for treating severe HFMD. Results: Out of 4,753 incident episodes reviewed, 525 patients were hospitalized; 60% were males. Most patients (93.8%) were children under 5 years old, with a median age at onset of 2.4 years. HFMD incidence peaked in April/May and September/October. From the total, 1,067 (22.4%) infections were positive for human enterovirus 71 (HEV71), 1,094 (23.0%) were positive for coxsackievirus A16 (CA16), and 941 (19.8%) were positive for other common enteroviruses. In contrast, 1,666 (35.0%) cases were negative to HEV71, CA16, and other common enteroviruses. Cross-correlation coefficients demonstrated associations between the number of cases, seasonal temperatures, and humidity. Among hospitalized cases, HEV71 was positive in 261 (24.5%), and 42 (3.9%) critical cases were positive for HEV71. Conclusion: Seasonal fluctuations and HEV71 and CA16 were the two key factors influencing the Guangzhou HFMD epidemic. The infection predominantly affected children younger than 5 years old. Keywords: Epidemic, Hand, foot and mouth disease, Coxsackie virus A16, Human enterovirus 71

OBJECTIVES: This study aimed to review etiological and epidemiological data for hand, foot, and mouth disease (HFMD) cases that occurred between 2008 and 2010 in Guangzhou City, to help develop and implement precautionary measures applicable for future outbreaks. METHODS: The characteristics of 4,753 HFMD episodes were retrospectively reviewed in 4,636 patients reported between 2008 and 2010 by the Guangdong Women and Children's Hospital, which is the national enterovirus monitoring agent and the designated hospital in China for treating severe HFMD. RESULTS: Out of 4,753 incident episodes reviewed, 525 patients were hospitalized; 60% were males. Most patients (93.8%) were children under 5 years old, with a median age at onset of 2.4 years. HFMD incidence peaked in April/May and September/October. From the total, 1,067 (22.4%) infections were positive for human enterovirus 71 (HEV71), 1,094 (23.0%) were positive for coxsackievirus A16 (CA16), and 941 (19.8%) were positive for other common enteroviruses. In contrast, 1,666 (35.0%) cases were negative to HEV71, CA16, and other common enteroviruses. Cross-correlation coefficients demonstrated associations between the number of cases, seasonal temperatures, and humidity. Among hospitalized cases, HEV71 was positive in 261 (24.5%), and 42 (3.9%) critical cases were positive for HEV71. CONCLUSION: Seasonal fluctuations and HEV71 and CA16 were the two key factors influencing the Guangzhou HFMD epidemic. The infection predominantly affected children younger than 5 years old.