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Biomedical subjects

Gang Yan

Publications and source records attributed to Gang Yan.

12 recordsLinked to original sources

In vivo CRISPR screening identifies metastasis suppressors in triple-negative breast cancer.

Metastatic cancer remains the leading cause of cancer-related mortality, yet tumor cell-intrinsic mechanisms restraining metastatic dissemination remain incompletely defined. Here, we perform an unbiased in vivo genome-wide CRISPR/Cas9 loss-of-function screen in a breast cancer xenograft model to identify regulators of metastatic progression. This approach uncovers clinically relevant metastasis suppressor genes (MSGs), including VPS45, CMTR2, RBSN, and NF2, whose loss enhances lung colonization. Functional validation demonstrates that depletion of these genes promotes epithelial-to-mesenchymal transition, migration, invasion, intravasation, and angiogenesis, whereas CRISPR-mediated activation suppresses metastatic spread. Integration with patient datasets reveals reduced expression in tumors and associations with advanced disease, with higher expression trending toward improved outcomes. Notably, CMTR2 loss induces vascular remodeling and intratumoral heterogeneity, supporting a role in tumor-vascular interactions. Collectively, this study identifies a network of MSGs that constrain tumor dissemination and highlights the power of in vivo CRISPR functional genomics to uncover regulators of metastatic disease.

Humans↗

Integrating local static and dynamic information for routing traffic.

The efficiency of traffic routing on complex networks can be reflected by two key measurements, i.e., the network capacity and the average travel time of data packets. In this paper we propose a mixing routing strategy by integrating local static and dynamic information for enhancing the efficiency of traffic on scale-free networks. The strategy is governed by a single parameter. Simulation results show that maximizing the network capacity and reducing the packet travel time can generate an optimal parameter value. Compared with the strategy of adopting exclusive local static information, the new strategy shows its advantages in improving the efficiency of the system. The detailed analysis of the mixing strategy is provided for explaining its effects on traffic routing. The work indicates that effectively utilizing the larger degree nodes plays a key role in scale-free traffic systems.

Journal Article↗

Efficient routing on complex networks.

We propose a routing strategy to improve the transportation efficiency on complex networks. Instead of using the routing strategy for shortest path, we give a generalized routing algorithm to find the so-called efficient path, which considers the possible congestion in the nodes along actual paths. Since the nodes with the largest degree are very susceptible to traffic congestion, an effective way to improve traffic and control congestion, as our strategy, can be redistributing traffic load in central nodes to other noncentral nodes. Simulation results indicate that the network capability in processing traffic is improved more than 10 times by optimizing the efficient path, which is in good agreement with the analysis.

Journal Article↗

Mutual attraction model for both assortative and disassortative weighted networks.

For most complex networks, the connection between a pair of nodes is the result of their mutual affinity and attachment. In this letter, we will propose a mutual attraction model to characterize weighted evolving networks. By introducing the initial attractiveness A and the general mechanism of mutual attraction (controlled by parameter m), our model can naturally reproduce scale-free distributions of degree, weight, and strength, as found in many real systems. Also, simulation results are consistent with theoretical predictions. Interestingly, we obtain nontrivial clustering coefficient C and tunable degree assortativity r, depending on the values of m and A. Our model appears as a more general one that unifies the characterization of both assortative and disassortative weighted networks.

Journal Article↗

[An adaptive criterion for cluster number estimation and the optimal algorithm for image segmentation].

In the algorithms for image segmentation, the number of clusters (NOC), which impacts on the segmentation results, should be first solved, and its correct estimation both theoretically and in application is of much importance. The authors propose an adaptive total energy criterion (ATEC) based on Markov random fields (MRF). The correct NOC of different images can be obtained by minimizing the ATEC and the parameters in the criterion are estimated by expectation maximization algorithm and maximum pseudo-likelihood method. The experiments show that the NOC can be automatically detected by adjusting the parameters, and the segmentation with the estimated NOC can be obtained by the maximum a posteriori at the same time.

Algorithms↗

General dynamics of topology and traffic on weighted technological networks.

For most technical networks, the interplay of dynamics, traffic, and topology is assumed crucial to their evolution. In this Letter, we propose a traffic-driven evolution model of weighted technological networks. By introducing a general strength-coupling mechanism under which the traffic and topology mutually interact, the model gives power-law distributions of degree, weight, and strength, as confirmed in many real networks. Particularly, depending on a parameter W that controls the total weight growth of the system, the nontrivial clustering coefficient C, degree assortativity coefficient r, and degree-strength correlation are all consistent with empirical evidence.

Journal Article↗

Maximal planar networks with large clustering coefficient and power-law degree distribution.

In this article, we propose a simple rule that generates scale-free networks with very large clustering coefficient and very small average distance. These networks are called random Apollonian networks (RANs) as they can be considered as a variation of Apollonian networks. We obtain the analytic results of power-law exponent gamma=3 and clustering coefficient C= (46/3)-36 ln 3/2 approximately 0.74, which agree with the simulation results very well. We prove that the increasing tendency of average distance of RANs is a little slower than the logarithm of the number of nodes in RANs. Since most real-life networks are both scale-free and small-world networks, RANs may perform well in mimicking the reality. The RANs possess hierarchical structure as C(k) approximately k(-1) that are in accord with the observations of many real-life networks. In addition, we prove that RANs are maximal planar networks, which are of particular practicability for layout of printed circuits and so on. The percolation and epidemic spreading process are also studied and the comparisons between RANs and Barabási-Albert (BA) as well as Newman-Watts (NW) networks are shown. We find that, when the network order N (the total number of nodes) is relatively small (as N approximately 10(4)), the performance of RANs under intentional attack is not sensitive to N , while that of BA networks is much affected by N. And the diseases spread slower in RANs than BA networks in the early stage of the susceptible-infected process, indicating that the large clustering coefficient may slow the spreading velocity, especially in the outbreaks.

Journal Article↗

An optimal model and its application for the management of municipal solid waste from regional small cities in China.

Based on the basic characteristics of municipal solid waste (MSW) from regional small cities in China, some optimal management principles have been put forward: regional optimization, long-term optimization, and integrated treatment/disposal optimization. According to these principles, an optimal MSW management model for regional small cities is developed and provides a useful method to manage MSW from regional small cities. A case study application of the optimal model is described and shows that the optimal management scenarios in the controlling region can be gained, adequately validating and accounting for the advantages of the optimal model.

China↗

Impaired processing and presentation by MHC class II proteins in human diabetic cells.

The biochemical processing of and Ag presentation by MHC class II molecules were examined in B cell lines derived from pairs of identical twins discordant for type 1 diabetes. MHC class II defects detected exclusively in cells derived from the twins with autoimmunity included increased rates of transport to and subsequent turnover at the cell surface, inadequate glycosylation, and a reduced display at the cell surface of antigenic peptides. These defects appeared to be secondary to a decreased abundance of the p35 isoform of the invariant chain (Ii), a human-specific chaperone protein for MHC class II normally generated by use of an alternative translation start site. Stable transfection of diabetic B cell lines with an Ii p35 expression vector corrected the defects in MHC class II processing and peptide presentation. A defect in the expression of Ii p35 may thus result in impairment of Ag presentation by MHC class II molecules and thereby contribute to the development of type 1 diabetes in at-risk genotypes.

Amino Acid Sequence↗

Polymorphisms of human TAP2 detected by denaturing gradient gel electrophoresis.

The human transporter associated with antigen processing (TAP1 and TAP2) genes are located in the human leukocyte antigen (HLA) class II region of the genome and encode proteins that form a heterodimer essential for the transport of endogenous peptides into the endoplasmic reticulum for assembly with HLA class I molecules. Type 1 diabetes is an autoimmune disease that is associated with the HLA region of the genome, with HLA class II genes conferring the greatest statistical risk. The presentation of self-peptides by HLA class I molecules is defective in individuals with this disease, and both TAP1 and TAP2 are potential contributors to this defect. Denaturing gradient gel electrophoresis (DGGE) was applied to screen all 11 exons and the 3' flanking region of TAP2 for polymorphisms in individuals with type 1 diabetes patients and controls. Seventy polymorphisms, including 51 in introns, 4 in the 3' flanking region, and 15 in exons, were identified. Sequencing of polymorphic DNA fragments revealed several new polymorphisms, including a Gln --> Arg substitution at codon 611 and a GT --> GC polymorphism affecting the donor splice site of intron 4, that might be of functional significance. None of the polymorphisms examined differed in frequency between individuals with type 1 diabetes and controls.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Application of optimization management model of municipal solid waste from medium or small city of China].

According to the basic characteristics of municipal solid waste generated from medium or small city of China, the optimal management principles and programs for optimization management model suitable to them were put forward. By application of the model in case study, the optimal scenarios for the disposal of municipal solid waste from the planning system in 1999, 2005 and 2010 were calculated, which adequately validated and accounted for the advantages of optimization model by comparison of costs between optimization scenarios and former scenarios.

China↗

[An experimental study on the apoptosis of rabbit small intestinal cells during early postburn stage].

OBJECTIVE: To explore the significance of apoptosis of rabbit small intestinal mucosal epithelial cells and lymphocytes, and lymphocytes of lumbrical process at early postburn stage. METHODS: Twenty-five Japanese white rabbits were randomly divided into 5 groups with 5 in each group, i.e. normal control (N), 3-postburn-hour group (3 PBH), 6 PBH, 12 PBH and 24 PBH groups. The rabbits in all PBH groups were inflicted with 30% TBSA III degree of flame burn on the back. The intestinal tissue samples were harvested from 5 anatomical sites for HE staining, electron microscopic examination and the detection of apoptosis in situ by TUNEL method at all the postburn time points. The results of TUNEL slides were analyzed statistically. RESULTS: HE staining revealed that there were relatively abundant apoptotic cells scattering solitarily in the lymph nodules and diffuse lymphatic tissue in the mucosal epithelial and mucosal lamina propria (and partially extended into the submucosal layer) of the intestine and lumbrical process in all burn groups. There were some disruption of intestinal mucosa in 24 PBH group. But no obvious inflammatory reaction and signs of necrosis were observed in all the slides. Apoptotic body formation could be identified by EM. Large number of blue-black positive cellular nuclei were revealed by TUNEL method with their distribution as similar to that found by HE staining. When comparing with those in control group, the apoptotic cells in small intestine and lumbrical process were increased obviously (P < 0.01) in 3 PBH group and reached the top level in 6 and 12 PBH groups (P < 0.01), declining thereafter to near value of 3 PBH in 24 PBH group, though it was still higher than control (P < 0.05). The number of apoptotic epithelial cells in middle distal portions of small intestinal mucosa in burn groups was much higher than that in proximal intestine (P < 0.05). CONCLUSION: There was a large number of apoptotic cells in rabbit small intestinal mucosal epithelium, gut associated lymphoid tissue and lymphocytes in the lumbrical process, especially in the middle and distal portions of the intestine. These change might be the cellular basis of postburn intestinal translocation of bacteria and endotoxin.

Animals↗