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Fulltext Evidence of Sex Differentiation Based on Morphological Traits During the Early Development Stage of Mud Crab Scylla paramamosain

Cui W, Fang S, Lv L, Huang Z, Lin F, Wu Q, et al.

Front Vet Sci, 2021;8:712942.
PMID: 34395579 DOI: 10.3389/fvets.2021.712942

In order to uncover the sexual difference in morphology and how early they appear during the development stage of mud crab Scylla paramamosain, we measured, observed, and biostatistically analyzed morphological traits related to sex. For unveiling the morphological differences between sexes, morphological traits involving abdomen width (AW), carapace length (CL), and carapace width (CW) were first measured during the crablet development stage of S. paramamosain in the present study. The correlation analyses and path analyses exhibited that sexual dimorphism in the third abdomen width (AW3) and fourth abdomen width (AW4) could be used for sex identification from stage C VI (stage VI of crablet). Based on the stepwise discriminant analysis and standardized traits, a sex discriminant equation was constructed, which is capable for sex identification in crablets from stage C VI. Observations for secondary sexual traits and abdomen morphology (shape and pleopods) using a dissecting microscope or scanning electron microscope indicated that sexes are easily identified at stage C VIII according to the abdomen shape; meanwhile, at stage C II based on pleopod difference, and at stage C I by the presence or absence of gonopores. The findings in this study contribute greatly to the accuracy of sex identification of S. paramamosain during the early development stage, which promotes the understanding of the morphological differentiation mechanism of sex.
Deletion of Plasma Membrane Malate Transporters Increased Lipid Accumulation in the Oleaginous Fungus Mucor circinelloides WJ11

Yang J, Cánovas-Márquez JT, Li P, Li S, Niu J, Wang X, et al.

J Agric Food Chem, 2021 Aug 25;69(33):9632-9641.
PMID: 34428900 DOI: 10.1021/acs.jafc.1c03307

Malate as an important intermediate metabolite, its subcellular location, and concentration have a significant impact on fungal lipid metabolism. Previous studies showed that the mitochondrial malate transporter plays an important role in lipid accumulation in Mucor circinelloides by manipulating intracellular malate concentration. However, the role of plasma membrane malate transporters in oleaginous fungi remains unexplored. Therefore, in this work, two plasma membrane malate transporters "2-oxoglutarate:malate antiporters" (named SoDIT-a and SoDIT-b) of M. circinelloides WJ11 were deleted, and the consequences in growth capacity, lipid accumulation, and metabolism were analyzed. The results showed that deletion of sodit-a or/and sodit-b reduced the extracellular malate, confirming that the products of both genes participate in malate transportation. In parallel, the lipid contents in mutants increased approximately 10-40% higher than that in the control strain, suggesting that the defect in plasma membrane malate transport results in an increase of malate available for lipid biosynthesis. Furthermore, transcriptional analysis showed that the expression levels of multiple key genes involved in the lipid biosynthesis were also increased in the knockout mutants. To the best of our knowledge, this is the first report that demonstrated the association between plasma membrane malate transporters and lipid accumulation in M. circinelloides.
Fulltext Author Correction: Novel Hybrid Evolutionary Algorithms for Spatial Prediction of Floods

Bui DT, Panahi M, Shahabi H, Singh VP, Shirzadi A, Chapi K, et al.

Sci Rep, 2021 Jul 20;11(1):15152.
PMID: 34285263 DOI: 10.1038/s41598-021-93957-4
Fulltext Role of Snf-β in lipid accumulation in the high lipid-producing fungus Mucor circinelloides WJ11

Nosheen S, Naz T, Yang J, Hussain SA, Fazili ABA, Nazir Y, et al.

Microb Cell Fact, 2021 Feb 27;20(1):52.
PMID: 33639948 DOI: 10.1186/s12934-021-01545-y

BACKGROUND: Mucor circinelloides WJ11 is a high-lipid producing strain and an excellent producer of γ-linolenic acid (GLA) which is crucial for human health. We have previously identified genes that encode for AMP-activated protein kinase (AMPK) complex in M. circinelloides which is an important regulator for lipid accumulation. Comparative transcriptional analysis between the high and low lipid-producing strains of M. circinelloides showed a direct correlation in the transcriptional level of AMPK genes with lipid metabolism. Thus, the role of Snf-β, which encodes for β subunit of AMPK complex, in lipid accumulation of the WJ11 strain was evaluated in the present study.
RESULTS: The results showed that lipid content of cell dry weight in Snf-β knockout strain was increased by 32 % (from 19 to 25 %). However, in Snf-β overexpressing strain, lipid content of cell dry weight was decreased about 25 % (from 19 to 14.2 %) compared to the control strain. Total fatty acid analysis revealed that the expression of the Snf-β gene did not significantly affect the fatty acid composition of the strains. However, GLA content in biomass was increased from 2.5 % in control strain to 3.3 % in Snf-β knockout strain due to increased lipid accumulation and decreased to 1.83 % in Snf-β overexpressing strain. AMPK is known to inactivate acetyl-CoA carboxylase (ACC) which catalyzes the rate-limiting step in lipid synthesis. Snf-β manipulation also altered the expression level of the ACC1 gene which may indicate that Snf-β control lipid metabolism by regulating ACC1 gene.
CONCLUSIONS: Our results suggested that Snf-β gene plays an important role in regulating lipid accumulation in M. circinelloides WJ11. Moreover, it will be interesting to evaluate the potential of other key subunits of AMPK related to lipid metabolism. Better insight can show us the way to manipulate these subunits effectively for upscaling the lipid production. Up to our knowledge, it is the first study to investigate the role of Snf-β in lipid accumulation in M. circinelloides.
Fulltext A soft artificial muscle driven robot with reinforcement learning

Yang T, Xiao Y, Zhang Z, Liang Y, Li G, Zhang M, et al.

Sci Rep, 2018 09 28;8(1):14518.
PMID: 30266999 DOI: 10.1038/s41598-018-32757-9

Soft robots driven by stimuli-responsive materials have their own unique advantages over traditional rigid robots such as large actuation, light weight, good flexibility and biocompatibility. However, the large actuation of soft robots inherently co-exists with difficulty in control with high precision. This article presents a soft artificial muscle driven robot mimicking cuttlefish with a fully integrated on-board system including power supply and wireless communication system. Without any motors, the movements of the cuttlefish robot are solely actuated by dielectric elastomer which exhibits muscle-like properties including large deformation and high energy density. Reinforcement learning is used to optimize the control strategy of the cuttlefish robot instead of manual adjustment. From scratch, the swimming speed of the robot is enhanced by 91% with reinforcement learning, reaching to 21 mm/s (0.38 body length per second). The design principle behind the structure and the control of the robot can be potentially useful in guiding device designs for demanding applications such as flexible devices and soft robots.
Modeling flood susceptibility using data-driven approaches of naïve Bayes tree, alternating decision tree, and random forest methods

Chen W, Li Y, Xue W, Shahabi H, Li S, Hong H, et al.

Sci Total Environ, 2020 Jan 20;701:134979.
PMID: 31733400 DOI: 10.1016/j.scitotenv.2019.134979

Floods are one of the most devastating types of disasters that cause loss of lives and property worldwide each year. This study aimed to evaluate and compare the prediction capability of the naïve Bayes tree (NBTree), alternating decision tree (ADTree), and random forest (RF) methods for the spatial prediction of flood occurrence in the Quannan area, China. A flood inventory map with 363 flood locations was produced and partitioned into training and validation datasets through random selection with a ratio of 70/30. The spatial flood database was constructed using thirteen flood explanatory factors. The probability certainty factor (PCF) method was used to analyze the correlation between the factors and flood occurrences. Consequently, three flood susceptibility maps were produced using the NBTree, ADTree, and RF methods. Finally, the area under the curve (AUC) and statistical measures were used to validate the flood susceptibility models. The results indicated that the RF method is an efficient and reliable model in flood susceptibility assessment, with the highest AUC values, positive predictive rate, negative predictive rate, sensitivity, specificity, and accuracy for the training (0.951, 0.892, 0.941, 0.945, 0.886, and 0.915, respectively) and validation (0.925, 0.851, 0.938, 0.945, 0.835, and 0.890, respectively) datasets.
Fulltext Molecular Characteristics of Burkholderia pseudomallei Collected From Humans in Hainan, China

Zhu X, Chen H, Li S, Wang LC, Wu DR, Wang XM, et al.

Front Microbiol, 2020;11:778.
PMID: 32457710 DOI: 10.3389/fmicb.2020.00778

Melioidosis is a common infectious disease in Southeast Asia and Northern Australia. In Hainan, several cases have been reported, but no systematic study has yet been done on the molecular epidemiology profiles of the organism. An investigation of the molecular epidemiology links and population structure of Burkholderia pseudomallei would help to better understand the clonally of the isolates and differences among them. In this study, multilocus variable-number tandem repeat analysis (MLVA), and multilocus sequence typing (MLST) were applied to examine the epidemiological relatedness and population structure of 166 B. pseudomallei isolates obtained during 2002-2014 in Hainan, China. Both the MLVA_4 and MLST approaches had high discriminatory power for this population, with diversity indices of 0.9899 and 0.9457, respectively. However, the MLVA_4 assay showed a higher discriminatory power than the MLST approach, and a variable-number tandem repeat (VNTR3 933) found by the MLVA approach was the most useful in discriminating strains from this province. A total of 166 strains yielded 99 MLVA_4 genotypes, of which 34 genotypes were shared by 101 isolates, for a clustering rate of 60.8% (101/166), which suggested that some cases may have a common source. Additionally, 65 isolates showed distinct genotypes, indicating that more than 39.2% (65/166) of melioidosis cases in Hainan had epidemiologically unrelated or sporadic characteristics. The 166 isolates were resolved into 48 STs, of which five STs (ST55, -70, -46, -50, and -58) were here found to be predominant. Phylogenetic analysis of 116 isolates conducted using the eBURST v3 segregated the 48 STs into eight groups with ST50 as predicted founder, and 21 STs were found to be singletons, which suggest that the strains in the Hainan region represent a high diversity of ST clones, indicating that many B. pseudomallei clone groups are endemic to this region. Moreover, ST50 had 5 SLV, 7 DLV, 6 TLV, and 29 satellite STs and formed a radial expansion pattern, suggesting that the melioidosis epidemic in this study was mainly caused by the clonal expansion of ST 50. Phylogenetic analysis on global scale suggests that China's isolates are closely related to isolates from Southeast Asia, particularly from Thailand and Malaysia.
Fulltext A Novel Benzofuran Derivative Moracin N Induces Autophagy and Apoptosis Through ROS Generation in Lung Cancer

Gao C, Sun X, Wu Z, Yuan H, Han H, Huang H, et al.

Front Pharmacol, 2020;11:391.
PMID: 32477104 DOI: 10.3389/fphar.2020.00391

Introduction: The leaves of Morus alba L is a traditional Chinese medicine widely applied in lung diseases. Moracin N (MAN), a secondary metabolite extracted form the leaves of Morus alba L, is a potent anticancer agent. But its molecular mechanism remains unveiled.
Objective: In this study, we aimed to examine the effect of MAN on human lung cancer and reveal the underlying molecular mechanism.
Methods: MTT assay was conducted to measure cell viability. Annexin V-FITC/PI staining was used to detect cell apoptosis. Confocal microscope was performed to determine the formation of autophagosomes and autolysosomes. Flow cytometry was performed to quantify cell death. Western blotting was used to determine the related-signaling pathway.
Results: In the present study, we demonstrated for the first time that MAN inhibitd cell proliferation and induced cell apoptosis in human non-small-cell lung carcinoma (NSCLC) cells. We found that MAN treatment dysregulated mitochondrial function and led to mitochondrial apoptosis in A549 and PC9 cells. Meanwhile, MAN enhanced autophagy flux by the increase of autophagosome formation, the fusion of autophagsomes and lysosomes and lysosomal function. Moreover, mTOR signaling pathway, a classical pathway regualting autophagy, was inhibited by MAN in a time- and dose-dependent mannner, resulting in autophagy induction. Interestingly, autophagy inhibition by CQ or Atg5 knockdown attenuated cell apoptosis by MAN, indicating that autophagy serves as cell death. Furthermore, autophagy-mediated cell death by MAN can be blocked by reactive oxygen species (ROS) scavenger NAC, indicating that ROS accumulation is the inducing factor of apoptosis and autophagy. In summary, we revealed the molecular mechanism of MAN against lung cancer through apoptosis and autophagy, suggesting that MAN might be a novel therapeutic agent for NSCLC treatment.
Fulltext Exosomal miR-224 contributes to hemolymph microbiota homeostasis during bacterial infection in crustacean

Gong Y, Wei X, Sun W, Ren X, Chen J, Aweya JJ, et al.

PLoS Pathog, 2021 08;17(8):e1009837.
PMID: 34379706 DOI: 10.1371/journal.ppat.1009837

It is well known that exosomes could serve as anti-microbial immune factors in animals. However, despite growing evidences have shown that the homeostasis of the hemolymph microbiota was vital for immune regulation in crustaceans, the relationship between exosomes and hemolymph microbiota homeostasis during pathogenic bacteria infection has not been addressed. Here, we reported that exosomes released from Vibrio parahaemolyticus-infected mud crabs (Scylla paramamosain) could help to maintain the homeostasis of hemolymph microbiota and have a protective effect on the mortality of the host during the infection process. We further confirmed that miR-224 was densely packaged in these exosomes, resulting in the suppression of HSP70 and disruption of the HSP70-TRAF6 complex, then the released TRAF6 further interacted with Ecsit to regulate the production of mitochondrial ROS (mROS) and the expression of Anti-lipopolysaccharide factors (ALFs) in recipient hemocytes, which eventually affected hemolymph microbiota homeostasis in response to the pathogenic bacteria infection in mud crab. To the best of our knowledge, this is the first document that reports the role of exosome in the hemolymph microbiota homeostasis modulation during pathogen infection, which reveals the crosstalk between exosomal miRNAs and innate immune response in crustaceans.
Fulltext Novel Hybrid Evolutionary Algorithms for Spatial Prediction of Floods

Bui DT, Panahi M, Shahabi H, Singh VP, Shirzadi A, Chapi K, et al.

Sci Rep, 2018 Oct 18;8(1):15364.
PMID: 30337603 DOI: 10.1038/s41598-018-33755-7

Adaptive neuro-fuzzy inference system (ANFIS) includes two novel GIS-based ensemble artificial intelligence approaches called imperialistic competitive algorithm (ICA) and firefly algorithm (FA). This combination could result in ANFIS-ICA and ANFIS-FA models, which were applied to flood spatial modelling and its mapping in the Haraz watershed in Northern Province of Mazandaran, Iran. Ten influential factors including slope angle, elevation, stream power index (SPI), curvature, topographic wetness index (TWI), lithology, rainfall, land use, stream density, and the distance to river were selected for flood modelling. The validity of the models was assessed using statistical error-indices (RMSE and MSE), statistical tests (Friedman and Wilcoxon signed-rank tests), and the area under the curve (AUC) of success. The prediction accuracy of the models was compared to some new state-of-the-art sophisticated machine learning techniques that had previously been successfully tested in the study area. The results confirmed the goodness of fit and appropriate prediction accuracy of the two ensemble models. However, the ANFIS-ICA model (AUC = 0.947) had a better performance in comparison to the Bagging-LMT (AUC = 0.940), BLR (AUC = 0.936), LMT (AUC = 0.934), ANFIS-FA (AUC = 0.917), LR (AUC = 0.885) and RF (AUC = 0.806) models. Therefore, the ANFIS-ICA model can be introduced as a promising method for the sustainable management of flood-prone areas.
Fulltext Deacetylation of K481 and K484 on Penaeid Shrimp Hemocyanin Is Critical for Antibacterial Activity

Nie J, Aweya JJ, Yu Z, Zhou H, Wang F, Yao D, et al.

J Immunol, 2022 Aug 01;209(3):476-487.
PMID: 35851542 DOI: 10.4049/jimmunol.2200078

Although invertebrates' innate immunity relies on several immune-like molecules, the diversity of these molecules and their immune response mechanisms are not well understood. Here, we show that Penaeus vannamei hemocyanin (PvHMC) undergoes specific deacetylation under Vibrio parahaemolyticus and LPS challenge. In vitro deacetylation of PvHMC increases its binding capacity with LPS and antibacterial activity against Gram-negative bacteria. Lysine residues K481 and K484 on the Ig-like domain of PvHMC are the main acetylation sites modulated by the acetyltransferase TIP60 and deacetylase HDAC3. Deacetylation of PvHMC on K481 and K484 allows PvHMC to form a positively charged binding pocket that interacts directly with LPS, whereas acetylation abrogates the positive charge to decrease PvHMC-LPS attraction. Besides, V. parahaemolyticus and LPS challenge increases the expression of Pvhdac3 to induce PvHMC deacetylation. This work indicates that, during bacterial infections, deacetylation of hemocyanin is crucial for binding with LPS to clear Gram-negative bacteria in crustaceans.
Fulltext Can egg yolk antibodies terminate the CSBV infection in apiculture?

Li A, Wang Q, Huang Y, Hu L, Li S, Wang Q, et al.

Virus Res, 2023 Apr 15;328:199080.
PMID: 36882131 DOI: 10.1016/j.virusres.2023.199080

Chinese sacbrood virus (CSBV) is the most severe pathogen of Apis cerana, which leads to serious fatal diseases in bee colonies and eventual catastrophe for the Chinese beekeeping industry. Additionally, CSBV can potentially infect Apis mellifera by bridging the species barrier and significantly affect the productivity of the honey industry. Although several approaches, such as feeding royal jelly, traditional Chinese medicine, and double-stranded RNA treatments, have been employed to suppress CSBV infection, their practical applicabilities are constrained due to their poor effectiveness. In recent years, specific egg yolk antibodies (EYA) have been increasingly utilized in passive immunotherapy for infectious diseases without any side effects. According to both laboratory research and practical use, EYA have demonstrated superior protection for bees against CSBV infection. This review provided an in-depth analysis of the issues and drawbacks in this field in addition to provide a thorough summary of current advancements in CSBV studies. Some promising strategies for the synergistic study of EYA against CSBV, including the exploitation of novel antibody drugs, novel TCM monomer/formula determination, and development of nucleotide drugs, are also proposed in this review. Furthermore, the prospects for the future perspectives of EYA research and applications are presented. Collectively, EYA would terminate CSBV infection soon, as well as will provide scientific guidance and references to control and manage other viral infections in apiculture.
Correction of Lying Ear and Aesthetic Modification of Helix and Ear Lobule with Hyaluronic Acid Filler Injection: Experience in Chinese Patients

Li Y, Dong W, Zhang L, Yang Y, Song Y, Shi N, et al.

Aesthet Surg J, 2024 Jan 25.
PMID: 38271268 DOI: 10.1093/asj/sjae010

BACKGROUND: Large and long ears are regarded as symbols of wealth and health in eastern Asian culture, patients with lying ears wish their ears to be more exposed and prominent. Surgeries correcting lying ears have been documented.
OBJECTIVES: We report correction of lying ears and aesthetic modification of helix and ear lobule with HA injections.
METHODS: We performed HA injections at auriculocephalic sulcus (AS) to increase cranioauricular angle (CA) and correct lying ears. The injections at helix and lobule were case-specific. The CA was measured and photographs were taken at baseline and 1-, 3-, 6-, and 10-month follow-ups. Efficacy was assessed using a 5-point global aesthetic improvement scale (GAIS). Adverse events (AEs) were recorded.
RESULTS: Forty-six patients (92 ears) received HA injections and completed follow-ups. Instant correction outcomes were observed. Sixteen (34.8%) patients received one touch-up injection, whose clinical efficacy persisted for 1 to 1.5 years. The GAIS for over 90% of cases with touch-up treatment was "very much improved" or "much improved" at all follow-ups. The GAIS for over 70% of cases without touch-up treatment was "very much improved" or "much improved" at 1, 3, and 6-month follow-ups. CA increased significantly compared with the baseline. Patients also reported "more V-shaped face shape" and "lifted jawline" effects. No serious AEs occurred.
CONCLUSIONS: As an alternative technique to surgeries, HA filler injections at AS effectively corrected lying ears. This technique produced immediate, long-lasting, and aesthetically pleasing results. The side effects and downtime were minimal.
Fulltext Exosomes drive ferroptosis by stimulating iron accumulation to inhibit bacterial infection in crustaceans

Sun Q, Yang J, Zhang M, Zhang Y, Ma H, Tran NT, et al.

J Biol Chem, 2023 Dec;299(12):105463.
PMID: 37977221 DOI: 10.1016/j.jbc.2023.105463

Ferroptosis, characterized by iron-dependent cell death, has recently emerged as a critical defense mechanism against microbial infections. The present study aims to investigate the involvement of exosomes in the induction of ferroptosis and the inhibition of bacterial infection in crustaceans. Our findings provide compelling evidence for the pivotal role of exosomes in the immune response of crustaceans, wherein they facilitate intracellular iron accumulation and activate the ferroptotic pathways. Using RNA-seq and bioinformatic analysis, we demonstrate that cytochrome P450 (CYP) can effectively trigger ferroptosis. Moreover, by conducting an analysis of exosome cargo proteins, we have identified the participation of six-transmembrane epithelial antigen of prostate 4 in the regulation of hemocyte ferroptotic sensitivity. Subsequent functional investigations unveil that six-transmembrane epithelial antigen of prostate 4 enhances cellular Fe2+ levels, thereby triggering Fenton reactions and accelerating CYP-mediated lipid peroxidation, ultimately culminating in ferroptotic cell death. Additionally, the Fe2+-dependent CYP catalyzes the conversion of arachidonic acid into 20-hydroxyeicosatetraenoic acid, which activates the peroxisome proliferator-activated receptor. Consequently, the downstream target of peroxisome proliferator-activated receptor, cluster of differentiation 36, promotes intracellular fatty acid accumulation, lipid peroxidation, and ferroptosis. These significant findings shed light on the immune defense mechanisms employed by crustaceans and provide potential strategies for combating bacterial infections in this species.
Fulltext Redirecting Metabolic Flux towards the Mevalonate Pathway for Enhanced β-Carotene Production in M. circinelloides CBS 277.49

Naz T, Nazir Y, Nosheen S, Ullah S, Halim H, Fazili ABA, et al.

Biomed Res Int, 2020;2020:8890269.
PMID: 33457420 DOI: 10.1155/2020/8890269

Carotenoids produced by microbial sources are of industrial and medicinal importance due to their antioxidant and anticancer properties. In the current study, optimization of β-carotene production in M. circinelloides strain 277.49 was achieved using response surface methodology (RSM). Cerulenin and ketoconazole were used to inhibit fatty acids and the sterol biosynthesis pathway, respectively, in order to enhance β-carotene production by diverting metabolic pool towards the mevalonate pathway. All three variables used in screening experiments were found to be significant for the production of β-carotene. The synergistic effect of the C/N ratio, cerulenin, and ketoconazole was further evaluated and optimized for superior β-carotene production using central composite design of RSM. Our results found that the synergistic combination of C/N ratios, cerulenin, and ketoconazole at different concentrations affected the β-carotene productions significantly. The optimal production medium (std. order 11) composed of C/N 25, 10 μg/mL cerulenin, and 150 mg/L ketoconazole, producing maximum β-carotene of 4.26 mg/L (0.43 mg/g) which was 157% greater in comparison to unoptimized medium (1.68 mg/L, 0.17 mg/g). So, it was concluded that metabolic flux had been successfully redirected towards the mevalonate pathway for enhanced β-carotene production in CBS 277.49.
Exosome-mediated viral nucleic acid presentation in a crustacean expounds innate immunity from a novel perspective

Gong Y, Hu H, Zhao X, Wei W, Zhang M, Tran NT, et al.

J Virol, 2024 Nov 15.
PMID: 39545727 DOI: 10.1128/jvi.01519-24

As an enduring hot topic in the field of innate immunity, apoptosis is widely considered an effective approach to eliminate pathogenic microbes and plays a crucial role during host-pathogen interactions. Recently, researchers have found that the virus-containing host cells could transmit apoptotic signals to the surrounding uninfected cells during infection, but the mechanism remains unclear. Here, we found that exosomes secreted by WSSV-infected mud crab hemocytes contain viral nucleic acid wsv277, which could be transported to the recipient cells and further expressed viral protein with phosphokinase activity. Besides, by using transcriptome, proteome, ChIP-seq, and coIP techniques, the results revealed that wsv277 could activate the transcription and translation of apoptotic genes via interacting with CBF and EF-1α so as to suppress the spread of virus infection by inducing apoptosis of the surrounding cells. Therefore, for the first time, our study proved that the components of DNA virus could be encapsulated into exosomes and elucidated the mechanism of apoptotic signal transduction between cells from the perspective of exosomes.
IMPORTANCE: Our study revealed that the components of DNA virus could be packaged and transmitted through the exosomes of lower invertebrates, which strongly demonstrated the diversity of exosome-mediated viral immunity and its universality in animals. Furthermore, we elucidated the mechanism of apoptotic signal transduction between cells from the perspective of exosomes and revealed a novel strategy for the host to cope with viral infection.
Fulltext Research Trend and Future Perspectives of Traditional Chinese Medicine for Atopic Dermatitis from 2004 to 2023: A Bibliometric Analysis

Feng H, Qin Y, Li Y, Li S, Zheng Y, Yan J, et al.

Clin Cosmet Investig Dermatol, 2024;17:2595-2613.
PMID: 39600528 DOI: 10.2147/CCID.S479632

AIM: The application of bibliometric analysis gives insights into research trend and future perspectives. This paper aims to understand the current status of studies on traditional Chinese medicine (TCM) in the treatment of atopic dermatitis (AD), and to investigate the cooperation network, hotspots and trends in the field.
METHODS: The original data were retrieved from the Web of Science Core Collection by searching for the topic "atopic dermatitis" and "traditional Chinese medicine" with the time span of 2004-2023. Microsoft Excel was used to create statistical tables and charts, whereas CiteSpace and VOSViewer were applied for knowledge mapping.
RESULTS: In total, 252 publications were identified and downloaded. Current research on TCM treating AD is in the steady growth period. China has the largest number of publications, whereas the USA has the greatest international influence. Notably, the Arab Emirates, Malaysia, India and Bangladesh all have a high research impact but with a low amount of publications. Universities in Hong Kong China have the largest number of publications, but their interaction with other institutions is very poor. The top three most productive authors are all from Hong Kong, having a strong collaboration network with each other. The popular research topics in this field are "children" "cell" "activation" "nf kappa b" "inflammation" "asthma" "extract" "management" and "cytokine". According to the analysis of leading co-cited journals and authors, "J ETHNOPHARMACOL" has the largest amount of citations whilst "AM J CHINESE MED" the strongest academic influence. The largest number of co-cited authors comes from "Hon Karn-Lun Ellis", a well-known scholar from Hong Kong.
CONCLUSION: TCM has been widely used in AD treatment, honored for its individualized therapeutic concepts of evidence-based treatment. The academic community must form a continuous and deep-going pattern to achieve higher international influence and a stronger research degree in this field.
Fulltext The kiss/kissr systems are dispensable for zebrafish reproduction: evidence from gene knockout studies

Tang H, Liu Y, Luo D, Ogawa S, Yin Y, Li S, et al.

Endocrinology, 2015 Feb;156(2):589-99.
PMID: 25406015 DOI: 10.1210/en.2014-1204

The kiss1/gpr54 signaling system is considered to be a critical regulator of reproduction in most vertebrates. However, this presumption has not been tested vigorously in nonmammalian vertebrates. Distinct from mammals, multiple kiss1/gpr54 paralogous genes (kiss/kissr) have been identified in nonmammalian vertebrates, raising the possibility of functional redundancy among these genes. In this study, we have systematically generated the zebrafish kiss1(-/-), kiss2(-/-), and kiss1(-/-);kiss2(-/-) mutant lines as well as the kissr1(-/-), kissr2(-/-), and kissr1(-/-);kissr2(-/-) mutant lines using transcription activator-like effector nucleases. We have demonstrated that spermatogenesis and folliculogenesis as well as reproductive capability are not impaired in all of these 6 mutant lines. Collectively, our results indicate that kiss/kissr signaling is not absolutely required for zebrafish reproduction, suggesting that the kiss/kissr systems play nonessential roles for reproduction in certain nonmammalian vertebrates. These findings also demonstrated that fish and mammals have evolved different strategies for neuroendocrine control of reproduction.
Fulltext Performance of a novel left ventricular lead with short bipolar spacing for cardiac resynchronization therapy: primary results of the Attain Performa quadripolar left ventricular lead study

Crossley GH, Biffi M, Johnson B, Lin A, Gras D, Hussin A, et al.

Heart Rhythm, 2015 Apr;12(4):751-8.
PMID: 25533587 DOI: 10.1016/j.hrthm.2014.12.019

The Medtronic Attain Performa quadripolar leads provide 16 pacing vectors with steroid on every electrode. This includes a short bipolar configuration between the middle 2 electrodes.
Fulltext A 3.4-kb Copy-Number Deletion near EPAS1 Is Significantly Enriched in High-Altitude Tibetans but Absent from the Denisovan Sequence

Lou H, Lu Y, Lu D, Fu R, Wang X, Feng Q, et al.

Am J Hum Genet, 2015 Jul 02;97(1):54-66.
PMID: 26073780 DOI: 10.1016/j.ajhg.2015.05.005

Tibetan high-altitude adaptation (HAA) has been studied extensively, and many candidate genes have been reported. Subsequent efforts targeting HAA functional variants, however, have not been that successful (e.g., no functional variant has been suggested for the top candidate HAA gene, EPAS1). With WinXPCNVer, a method developed in this study, we detected in microarray data a Tibetan-enriched deletion (TED) carried by 90% of Tibetans; 50% were homozygous for the deletion, whereas only 3% carried the TED and 0% carried the homozygous deletion in 2,792 worldwide samples (p < 10(-15)). We employed long PCR and Sanger sequencing technologies to determine the exact copy number and breakpoints of the TED in 70 additional Tibetan and 182 diverse samples. The TED had identical boundaries (chr2: 46,694,276-46,697,683; hg19) and was 80 kb downstream of EPAS1. Notably, the TED was in strong linkage disequilibrium (LD; r(2) = 0.8) with EPAS1 variants associated with reduced blood concentrations of hemoglobin. It was also in complete LD with the 5-SNP motif, which was suspected to be introgressed from Denisovans, but the deletion itself was absent from the Denisovan sequence. Correspondingly, we detected that footprints of positive selection for the TED occurred 12,803 (95% confidence interval = 12,075-14,725) years ago. We further whole-genome deep sequenced (>60×) seven Tibetans and verified the TED but failed to identify any other copy-number variations with comparable patterns, giving this TED top priority for further study. We speculate that the specific patterns of the TED resulted from its own functionality in HAA of Tibetans or LD with a functional variant of EPAS1.

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