Structural heterogeneity in tetra-armed gels revealed by computer simulation: Evidence from a graph theory assisted characterization.

Designing homogeneous networks is considered one typical strategy for solving the problem of strength and toughness conflict of polymer network materials. Experimentalists have proposed the hypothesis of obtaining a structurally homogeneous hydrogel by crosslinking tetra-armed polymers, whose homogeneity was claimed to be verified by scattering characterization and other methods. Nevertheless, it is highly desirable to further evaluate this issue from other perspectives. In this study, a coarse-grained molecular dynamics simulation coupled with a stochastic reaction model is applied to reveal the topological structure of a polymer network synthesized by tetra-armed monomers as precursors. Two different scenarios, distinguished by whether internal cross-linking is allowed, are considered. We introduce the Dijkstra algorithm from graph theory to precisely characterize the network structure. The microscopic features of the network structure, e.g., loop size, dispersity, and size distribution, are obtained via the Dijkstra algorithm. By comparing the two reaction scenarios, Scenario II exhibits an overall more idealized structure. Our results demonstrate the feasibility of the Dijkstra algorithm for precisely characterizing the polymer network structure. We expect this work will provide a new insight for the evaluation and description of gel networks and further help to reveal the dynamic process of network formation.

Patient-specific warning of epileptic seizure upon shapelets features.

Epilepsy is an intractable chronic neurological disease attached to extensive attention. Due to the fact that unpredictable seizure attacks result in serious physical injuries, early warning before seizure occurrence can help patients to get timely treatment and intervention. This paper presents a novel patient-specific method to predict epileptic seizures by learning shapelets of scalp electroencephalogram (EEG) signals recorded from different channels. In the proposed method, EEG signals are preprocessed to raise the Signal to Noise Rate (SNR). Multichannel shapelets space is constructed by the learning-near-to-optimal shapelets method. EEG signals are converted to distance matrices by projecting them on the shapelets' space. Bi-LSTM, SVM, CNN, and an ensemble of them are used to classify the feature set. Based on the prediction results then raise alarms. The proposed methodology is applied to the CHB-MIT scalp EEG dataset of 10 cases. The proposed method achieves a sensitivity of 91.33% and a false prediction rate of 0.16 h-1.

H3.3-G34R Mutation-Mediated Epigenetic Reprogramming Leads to Enhanced Efficacy of Immune Stimulatory Gene Therapy in Pediatric High-Grade Gliomas.

Pediatric high-grade gliomas (pHGGs) are diffuse and highly aggressive CNS tumors which remain incurable, with a 5-year overall survival of less than 20%. Within glioma, mutations in the genes encoding the histones H3.1 and H3.3 have been discovered to be age-restricted and specific of pHGGs. This work focuses on the study of pHGGs harboring the H3.3-G34R mutation. H3.3-G34R tumors represent the 9-15% of pHGGs, are restricted to the cerebral hemispheres, and are found predominantly in the adolescent population (median 15.0 years). We have utilized a genetically engineered immunocompetent mouse model for this subtype of pHGG generated via the Sleeping Beauty-transposon system. The analysis of H3.3-G34R genetically engineered brain tumors by RNA-Sequencing and ChIP-Sequencing revealed alterations in the molecular landscape associated to H3.3-G34R expression. In particular, the expression of H3.3-G34R modifies the histone marks deposited at the regulatory elements of genes belonging to the JAK/STAT pathway, leading to an increased activation of this pathway. This histone G34R-mediated epigenetic modifications lead to changes in the tumor immune microenvironment of these tumors, towards an immune-permissive phenotype, making these gliomas susceptible to TK/Flt3L immune-stimulatory gene therapy. The application of this therapeutic approach increased median survival of H3.3-G34R tumor bearing animals, while stimulating the development of anti-tumor immune response and immunological memory. Our data suggests that the proposed immune-mediated gene therapy has potential for clinical translation for the treatment of patients harboring H3.3-G34R high grade gliomas.

ROS signaling-induced mitochondrial Sgk1 expression regulates epithelial cell renewal.

Many types of differentiated cells can reenter the cell cycle upon injury or stress. The underlying mechanisms are still poorly understood. Here, we investigated how quiescent cells are reactivated using a zebrafish model, in which a population of differentiated epithelial cells are reactivated under a physiological context. A robust and sustained increase in mitochondrial membrane potential was observed in the reactivated cells. Genetic and pharmacological perturbations show that elevated mitochondrial metabolism and ATP synthesis are critical for cell reactivation. Further analyses showed that elevated mitochondrial metabolism increases mitochondrial ROS levels, which induces Sgk1 expression in the mitochondria. Genetic deletion and inhibition of Sgk1 in zebrafish abolished epithelial cell reactivation. Similarly, ROS-dependent mitochondrial expression of SGK1 promotes S phase entry in human breast cancer cells. Mechanistically, SGK1 coordinates mitochondrial activity with ATP synthesis by phosphorylating F1Fo-ATP synthase. These findings suggest a conserved intramitochondrial signaling loop regulating epithelial cell renewal.

FK506-binding protein 5 regulates cell quiescence-proliferation decision in zebrafish epithelium.

Using a zebrafish ionocyte model, transcriptomics and genetic analyses were performed to identify pathways and genes involved in cell quiescence-proliferation regulation. Gene ontology and Kyoto encyclopedia of genes and genomes pathway analyses revealed that genes involved in transcription regulation, cell cycle, Foxo signalling and Wnt signalling pathway are enriched among the up-regulated genes while those involved in ion transport, cell adhesion and oxidation-reduction are enriched among the down-regulated genes. Among the top up-regulated genes is FK506-binding protein 5 (Fkbp5). Genetic deletion and pharmacological inhibition of Fkbp5 abolished ionocyte reactivation and impaired Akt signalling. Forced expression of a constitutively active form of Akt rescued the defects caused by Fkbp5 inhibition. These results uncover a key role of Fbkp5 in regulating the quiescence-proliferation decision via Akt signalling.

The application of new complex indicators in the detection of urine.

BACKGROUND: Accurate diagnosis and assessment of hematuria is crucial for the early detection of chronic kidney disease(CKD). As instability of urinary RBC count (URBC) often results with clinical uncertainty, therefore new urinary indexes are demanded to improve the accuracy of diagnosis of hematuria. In this study, we aimed to investigate the benefit of applying new complex indicators based on random urine red blood cell counts confirmed in hematuric kidney diseases. METHODS: All patients enrolled underwent renal biopsy, and their clinical information was collected. Urinary and blood biomedical indexes were implemented with red blood cell counts to derive complex indicators. Patients were divided into two groups (hematuria-dominant renal histologic lesions and non-hematuria-dominant renal histologic lesions) based on their renal pathological manifestations. The target index was determined by comparing the predictive capabilities of the candidate parameters for hematuric kidney diseases. Hematuria stratification was divided into four categories based on the scale of complex indicators and distributional features. The practicality of the new complex indicators was demonstrated by fitting candidate parameters to models comprising demographic information. RESULTS: A total of 1,066 cases (678 hematuria-dominant renal histologic lesions) were included in this study, with a mean age of 44.9 ± 15 years. In differentiating hematuria-dominant renal histologic lesion from the non-hematuria-dominant renal histologic lesion, the AUC value of "The ratio of the random URBC to 24-h albumin excretion" was 0.76, higher than the standard approach of Lg (URBC) [AUC = 0.744] (95% Confidence interval (CI) 0.712 ~ 0.776). The odds ratio of hematuria-dominant renal histologic lesion (Type I) increased from Q2 (3.81, 95% CI 2.66 ~ 5.50) to Q4 (14.17, 95% CI 9.09 ~ 22.72). The predictive model, composed of stratification of new composite indexes, basic demographic characteristics, and biochemical parameters, performed best with AUC value of 0.869 (95% CI 0.856-0.905). CONCLUSION: The new urinary complex indicators improved the diagnostic accuracy of hematuria and may serve as a useful parameter for screening hematuric kidney diseases.

High-Speed Shift Register with Dual-Gated Thin-Film Transistors for a 31-Inch 4K AMOLED Display.

In this work, a promising dual-gated thin film transistor (TFT) structure has been proposed and introduced in the shift register (SR)-integrated circuits to reduce the rising time. The threshold voltage can be simultaneously changed by the top gate and the bottom gate in the proposed dual-gated TFTs. When the SR circuits start to export the scan signals in the displays, the driving currents in the SR circuits are increased by switching the working station of driving TFTs from the enhancement characterization to the depletion characterization. Subsequently, the detailed smart spice simulation has been used to study the function of the proposed SR circuits. In the next step, the proposed SR circuits have been fabricated in a G4.5 active-matrix organic light-emitting diode manufacture factory. The simulated and experimental results indicate that the shift register pulses with the full swing amplitude can be obtained in the SR circuits. Moreover, in contrast to the conventional SR circuits employing with the single-gated TFTs, it has been found that the rising time of the output signals can be reduced from 3.75 µs to 1.23 µs in the proposed SR circuits with the dual-gated TFTs, thus exhibiting the significant improvement of the driving force in the proposed SR circuits. Finally, we demonstrated a 31-inch 4K AMOLED display with the proposed SR circuits.

GCAF(TMEM251) regulates lysosome biogenesis by activating the mannose-6-phosphate pathway.

The mannose-6-phosphate (M6P) biosynthetic pathway for lysosome biogenesis has been studied for decades and is considered a well-understood topic. However, whether this pathway is regulated remains an open question. In a genome-wide CRISPR/Cas9 knockout screen, we discover TMEM251 as the first regulator of the M6P modification. Deleting TMEM251 causes mistargeting of most lysosomal enzymes due to their loss of M6P modification and accumulation of numerous undigested materials. We further demonstrate that TMEM251 localizes to the Golgi and is required for the cleavage and activity of GNPT, the enzyme that catalyzes M6P modification. In zebrafish, TMEM251 deletion leads to severe developmental defects including heart edema and skeletal dysplasia, which phenocopies Mucolipidosis Type II. Our discovery provides a mechanism for the newly discovered human disease caused by TMEM251 mutations. We name TMEM251 as GNPTAB cleavage and activity factor (GCAF) and its related disease as Mucolipidosis Type V.

Disulfiram ameliorates ischemia/reperfusion-induced acute kidney injury by suppressing the caspase-11-GSDMD pathway.

Acute kidney injury (AKI) is a serious condition with high mortality. The most common cause is kidney ischemia/reperfusion (IR) injury, which is thought to be closely related to pyroptosis. Disulfiram is a well-known alcohol abuse drug, and recent studies have shown its ability to mitigate pyroptosis in mouse macrophages. This study investigated whether disulfiram could improve IR-induced AKI and elucidated the possible molecular mechanism. We generated an IR model in mouse kidneys and a hypoxia/reoxygenation (HR) injury model with murine tubular epithelial cells (MTECs). The results showed that IR caused renal dysfunction in mice and triggered pyroptosis in renal tubular epithelial cells, and disulfiram improved renal impairment after IR. The expression of proteins associated with the classical pyroptosis pathway (Nucleotide-binding oligomeric domain (NOD)-like receptor protein 3 (NLRP3), apoptosis-related specific protein (ASC), caspase-1, N-GSDMD) and nonclassical pyroptosis pathway (caspase-11, N-GSDMD) were upregulated after IR. Disulfiram blocked the upregulation of nonclassical but not all classical pyroptosis pathway proteins (NLRP3 and ASC), suggesting that disulfiram might reduce pyroptosis by inhibiting the caspase-11-GSDMD pathway. In vitro, HR increased intracellular ROS levels, the positive rate of PI staining and LDH levels in MTECs, all of which were reversed by disulfiram pretreatment. Furthermore, we performed a computer simulation of the TIR domain of TLR4 using homology modeling and identified a small molecular binding energy between disulfiram and the TIR domain. We concluded that disulfiram might inhibit pyroptosis by antagonizing TLR4 and inhibiting the caspase-11-GSDMD pathway.

The truncated form of flagellin (tFlic) provides the 2dCap subunit vaccine with better immunogenicity and protective effects in mice.

Porcine circovirus type 2 (PCV2) is the main causative agent of porcine circovirus-associated diseases, and it causes substantial economic losses in the swine industry each year. It is crucial to develop an effective vaccine against the circulating strain PCV2d, which is prone to substantial degrees of mutation. In this study, a truncated form of flagellin (tFlic: 85-111 aa) was inserted into the C-terminal sequence of 2dCap, and Western blotting results showed that recombinant Cap-tFlic VLPs were successfully expressed. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) data indicated that purified recombinant Cap-tFlic fusion proteins existed in the form of polymers and that tFlic could not affect the formation and internalization of VLPs. Integrated Cap-tFlic VLPs induced the expression of antigen presentation-related factors (MHC-II and CD86) by bone marrow-derived dendritic cells (BM-DCs), and the expression of TLR5-related factors (TNF-α) was dramatically elevated. Mice intramuscularly immunized with Cap-tFlic VLPs exhibited significantly higher levels of Cap-specific antibodies and neutralizing antibodies than mice immunized with wild-type Cap VLPs. The data obtained in the current study indicate that Cap-tFlic may be a candidate for a subunit vaccine against PCV2 in the future.

MicroRNA-382 Promotes M2-Like Macrophage via the SIRP-α/STAT3 Signaling Pathway in Aristolochic Acid-Induced Renal Fibrosis.

Aristolochic acid nephropathy (AAN) is a type of drug-induced nephropathy and is correlated with a potentially progression of kidney fibrosis. However, whether miR-382 is implicated in macrophage activation in AA-induced kidney fibrosis remains elusive. Here, cell-sorting experiments defined a significant miR-382 enrichment in renal macrophage after AAN 14 days. Then, we found that treatment of AA induced a significant switch in the phenotype of macrophage both in vivo and in vitro. Furthermore, miR-382 knockout (KO) mice and miR-382-/- bone marrow-derived macrophage (BMDM) were subjected to AA induction. We found that both systemic KO and macrophage-specific miR-382 depletion notably suppressed M2-like macrophage activation as well as kidney interstitial fibrosis. Additionally, adoptive transfer of miR-382 overexpression BMDMs into mice promoted AA-induced kidney injury. Moreover, in cultured macrophage, upregulation of miR-382 promoted M2-related gene expression, accompanied by downregulation of signal regulatory protein α (SIRP-α) and activation of signal transducer and activator of transcription 3 (STAT3). The interaction between miR-382 and SIRP-α was evaluated via dual-luciferase assay. Knockdown of SIRP-α upregulated phosphorylated STAT3 at S727 and Y705. Pharmacological inhibition of STAT3 was performed both in vivo and in vitro. Inhibition of STAT3 attenuated AA-induced kidney fibrosis, in parallel to lesser macrophage M2 polarization. Coculture experiments further confirmed that overexpressed miR-382 in macrophage promoted injuries of tubular cells. Luminex bio-chip detection suggested that IL-4 and CCL-5 were critical in the cross talk between macrophages and tubular cells. Taken together, our data suggest that miR-382 is a critical mediator in M2-like macrophage polarization and can be a promising therapeutic target for kidney fibrosis.

Targeted Delivery of Nanovaccine to Dendritic Cells via DC-Binding Peptides Induces Potent Antiviral Immunity in vivo.

Background: Dendritic cell (DC) targeted antigen delivery is a promising strategy to enhance vaccine efficacy and delivery of therapeutics. Self-assembling peptide-based nanoparticles and virus-like particles (VLPs) have attracted extensive interest as non-replicating vectors for nanovaccine design, based on their unique properties, including molecular specificity, biodegradability and biocompatibility. DCs are specialized antigen-presenting cells involved in antigen capture, processing, and presentation to initiate adaptive immune responses. Using DC-specific ligands for targeted delivery of antigens to DCs may be utilized as a promising strategy to drive efficient and strong immune responses. Methods: In this study, several candidates for DC-binding peptides (DCbps) were individually integrated into C-terminal of porcine circovirus type 2 (PCV2) Cap, a viral protein that could self-assemble into icosahedral VLPs with 60 subunits. The immunostimulatory adjuvant activity of DC-targeted VLPs was further evaluated in a vaccine model of PCV2 Cap. Results: With transmission electron microscopy (TEM), E. coli expressed Cap-DCbp fusion proteins were observed self-assembled into highly ordered VLPs. Further, in dynamic light scattering (DLS) analysis, chimeric VLPs exhibited similar particle size uniformity and narrow size distribution as compared to wild type Cap VLPs. With a distinctly higher targeting efficiency, DCbp3 integrated Cap VLPs (Cap-DCbp3) displayed enhanced antigen uptake and increased elicitation of antigen presentation-related factors in BM-DCs. Mice subcutaneously immunized with Cap-DCbp3 VLPs exhibited significantly higher levels of Cap-specific antibodies, neutralizing antibodies and intracellular cytokines than those with other DCbp integrated or wild type Cap VLPs without any DCbp. Interestingly, Cap-DCbp3 VLPs vaccine induces robust cellular immune response profile, including the efficient production of IFN-γ, IL-2 and IL-10. Meanwhile, the improved proliferation index in lymphocytes with Cap-DCbp3 was also detected as compared to other VLPs. Conclusion: This study described the potential of DC-binding peptides for further improved antigen delivery and vaccine efficacy, explainning nanovaccine optimization in relation to a range of emerging and circulating infectious pathogens.

Broad antiviral peptides against PRRSV based on novel linear epitopes on porcine CD163.

PRRSV causes major economic losses to swine industry world-wide, which requires innovative antiviral agents. Porcine scavenger receptor CD163 has been identified as an essential fusion receptor for Porcine reproductive and respiratory Syndrome Virus (PRRSV) infection. In this study, novel antiviral peptides from pCD163 against PRRSV were developed based on broad neutralizing monoclonal antibodies. SRCR-5-9 of pCD163 from baculovirus efficiently binds to PRRSVs of lineage 8 and lineage 1, blocking infection in PAMs. A batch of monoclonal antibodies targeting SRCR-5-9 were generated and characterized. 8H2 and 4H7 block PRRSV infection by the disruption in viral attachment to PAMs. Virus titer reduced 100-1000 folds in average and the virus copy number decreased about 104 folds with these antibodies. Linear epitopes of 8H2 and 4H7 were individually localized in SRCR6 (1-30 aa) and PSTI(1-15aa) of pCD163. Mutations of SRCR6 NI1718KT and PST SS1314AA abolished the recognition of 8H2 and 4H7 to the corresponding region individually. Peptides derived from the linear epitopes displayed a broad inhibitory effect on PRRSVs of different lineages in a dose-dependent manner and further modulated PRRSV-related NF-κB pathway. In conclusion, these findings deepen the understanding in the interaction between PRRSV and pCD163 receptor and provide alternative universal antiviral strategies against PRRSV.

Limb development genes underlie variation in human fingerprint patterns.

Fingerprints are of long-standing practical and cultural interest, but little is known about the mechanisms that underlie their variation. Using genome-wide scans in Han Chinese cohorts, we identified 18 loci associated with fingerprint type across the digits, including a genetic basis for the long-recognized "pattern-block" correlations among the middle three digits. In particular, we identified a variant near EVI1 that alters regulatory activity and established a role for EVI1 in dermatoglyph patterning in mice. Dynamic EVI1 expression during human development supports its role in shaping the limbs and digits, rather than influencing skin patterning directly. Trans-ethnic meta-analysis identified 43 fingerprint-associated loci, with nearby genes being strongly enriched for general limb development pathways. We also found that fingerprint patterns were genetically correlated with hand proportions. Taken together, these findings support the key role of limb development genes in influencing the outcome of fingerprint patterning.

Regulation of cell quiescence-proliferation balance by Ca2+-CaMKK-Akt signaling.

Compared with our extensive understanding of the cell cycle, we have limited knowledge of how the cell quiescence-proliferation decision is regulated. Using a zebrafish epithelial model, we report a novel signaling mechanism governing the cell quiescence-proliferation decision. Zebrafish Ca2+-transporting epithelial cells, or ionocytes, maintain high cytoplasmic Ca2+ concentration ([Ca2+]c) due to the expression of Trpv6. Genetic deletion or pharmacological inhibition of Trpv6, or reduction of external Ca2+ concentration, lowered the [Ca2+]c and reactivated these cells. The ionocyte reactivation was attenuated by chelating intracellular Ca2+ and inhibiting calmodulin (CaM), suggesting involvement of a Ca2+ and CaM-dependent mechanism. Long-term imaging studies showed that after an initial decrease, [Ca2+]c gradually returned to the basal levels. There was a concomitant decease in endoplasmic reticulum (ER) Ca2+ levels. Lowering the ER Ca2+ store content or inhibiting ryanodine receptors impaired ionocyte reactivation. Further analyses suggest that CaM-dependent protein kinase kinase (CaMKK) is a key molecular link between Ca2+ and Akt signaling. Genetic deletion or inhibition of CaMKK abolished cell reactivation, which could be rescued by expression of a constitutively active Akt. These results suggest that the quiescence-proliferation decision in zebrafish ionocytes is regulated by Trpv6-mediated Ca2+ and CaMKK-Akt signaling.

Perilipin 2 Impacts Acute Kidney Injury via Regulation of PPARα.

Renal ischemia-reperfusion (I/R) can induce oxidative stress and injury via the generation of reactive oxygen species (ROS). Renal proximal tubular cells are susceptible to oxidative stress, and the dysregulation of renal proximal tubular cellular homeostasis can damage cells via apoptotic pathways. A recent study showed that the generation of ROS can increase perilipin 2 (Plin2) expression in HepG2 cells. Some evidence has also demonstrated the association between Plin2 expression and renal tumors. However, the underlying mechanism of Plin2 in I/R-induced acute kidney injury (AKI) remains elusive. Here, using a mouse model of I/R-induced AKI, we found that ROS generation was increased and the expression of Plin2 was significantly upregulated. An in vitro study further revealed that the expression of Plin2, and the generation of ROS were significantly upregulated in primary tubular cells treated with hydrogen peroxide. Accordingly, Plin2 knockdown decreased apoptosis in renal proximal tubular epithelial cells treated with hydrogen peroxide, which depended on the activation of peroxisome proliferator-activated receptor α (PPARα). Overall, the present study demonstrated that Plin2 is involved in AKI; knockdown of this marker might limit apoptosis via the activation of PPARα. Consequently, the downregulation of Plin2 could be a novel therapeutic strategy for AKI.

Flow-driven competition between two capsules passing through a narrow pore.

By incorporating a distance function into the finite element simulation, we investigate the flow-driven competition between two soft capsules passing through a narrow pore, employing the arbitrary Lagrangian-Eulerian formulation to satisfy the boundary conditions for fluid flow and capsule deformation. In our simulations, the motion and deformation of the capsules can be described in an intuitive manner, and the order in which capsules of different sizes pass through a pore can be clearly determined. Meanwhile, when the capsules are near the narrow pore, the change of the flow field is also very interesting and can be expressed intuitively. It is shown that, driven by the Poiseuille flow, the larger capsule has a stronger tendency to pass through the pore than the small one, which can be attributed to the greater resistance and the volume advantage of the larger capsule. In addition, we demonstrate that this tendency can be reversed by changing the inlet velocity and setting the initial position of the smaller capsule closer to the axis of the pore. And as long as the large one passes through first, the small one will offset the axis to the same orientation as the initial, while the large one always moves along the axis.

Relationship between rice farming and polygenic scores potentially linked to agriculture in China.

Following domestication in the lower Yangtze River valley 9400 years ago, rice farming spread throughout China and changed lifestyle patterns among Neolithic populations. Here, we report evidence that the advent of rice domestication and cultivation may have shaped humans not only culturally but also genetically. Leveraging recent findings from molecular genetics, we construct a number of polygenic scores (PGSs) of behavioural traits and examine their associations with rice cultivation based on a sample of 4101 individuals recently collected from mainland China. A total of nine polygenic traits and genotypes are investigated in this study, including PGSs of height, body mass index, depression, time discounting, reproduction, educational attainment, risk preference, ADH1B rs1229984 and ALDH2 rs671. Two-stage least-squares estimates of the county-level percentage of cultivated land devoted to paddy rice on the PGS of age at first birth (b = -0.029, p = 0.021) and ALDH2 rs671 (b = 0.182, p < 0.001) are both statistically significant and robust to a wide range of potential confounds and alternative explanations. These findings imply that rice farming may influence human evolution in relatively recent human history.

Observations from Wuhan: An Adaptive Risk and Crisis Communication System for a Health Emergency.

PURPOSE: With the rapid spread of COVID-19 across the world, the consideration of effective communication strategies from Wuhan can provide valuable insight to other countries in how to manage their risk response. This study analyzes the building of a risk communication system in Wuhan, China, to aid cross-country comparison from a policy and academic perspective. METHODS: We use complex adaptive systems theory (CAS) to theorize the communication strategy adopted by the government - led by the Hubei Province COVID-19 Epidemic Prevention and Control Headquarters. Using ethnographic fieldwork and discourse analysis, we observed and analyzed the online and offline communication process to formulate an overview of the communications platforms used in Wuhan. RESULTS: Wuhan's adaptive crisis communication system was backed by digital and offline infrastructure, human resources support, policy development, as well as access to scientific and technological expertize. The Wuhan municipal government adapted its communication strategy in response to public feedback, and created mechanisms to ensure that two-way communication was used to drive policy and integrate feedback from the government, enterprises, social organizations and the public. Wuhan's risk and crisis communication strategy aimed to meet emergency commitments, recover trust, regulate the public's emotions and build consensus, operating within a complex adaptive system (CAS). CONCLUSION: By using complex adaptive system (CAS) theory, we argue that Wuhan quickly built an adaptive communication system consisting of five elements: 1) non-linear information output, 2) online and offline continuous support systems, 3) a public emotional support system, 4) multi-subject information interaction platforms and 5) a context-based approach.

Significant East Asian Affinity of the Sichuan Hui Genomic Structure Suggests the Predominance of the Cultural Diffusion Model in the Genetic Formation Process.

The ancestral origin and genomic history of Chinese Hui people remain to be explored due to the paucity of genome-wide data. Some evidence argues that an eastward migration of Central Asians gave rise to modern Hui people, which is referred to as the demic diffusion hypothesis; other evidence favors the cultural diffusion hypothesis, which posits that East Asians adopted Muslim culture to form the modern culturally distinct populations. However, the extent to which the observed genetic structure of the Huis was mediated by the movement of people or the assimilation of Muslim culture also remains highly contentious. Analyses of over 700 K SNPs in 109 western Chinese individuals (49 Sichuan Huis and 60 geographically close Nanchong Hans) together with the available ancient and modern Eurasian sequences allowed us to fully explore the genomic makeup and origin of Hui and neighboring Han populations. The results from PCA, ADMIXTURE, and allele-sharing-based f-statistics revealed a strong genomic affinity between Sichuan Huis and Neolithic-to-modern Northern East Asians, which suggested a massive gene influx from East Asians into the Sichuan Hui people. Three-way admixture models in the qpWave/qpAdm analyses further revealed a small stream of gene influx from western Eurasians into the Sichuan Hui people, which was further directly confirmed via the admixture event from the temporally distinct Western sources to Sichuan Hui people in the qpGraph-based phylogenetic model, suggesting the key role of the cultural diffusion model in the genetic formation of the Sichuan Huis. ALDER-based admixture date estimation showed that this observed western Eurasian admixture signal was introduced into the Sichuan Huis during the historic periods, which was concordant with the extensive western-eastern communication along the Silk Road and historically documented Huis' migration history. In summary, although significant cultural differentiation exists between Hui people and their neighbors, our genomic analysis showed their strong genetic affinity with modern and ancient Northern East Asians. Our results support the hypothesis that the Sichuan Huis arose from a mixture of minor western Eurasian ancestry and predominant East Asian ancestry.