Serum amyloid A and interleukin -1ß facilitate LDL transcytosis across endothelial cells and atherosclerosis via NF-κB/caveolin-1/cavin-1 pathway.

BACKGROUND AND AIMS: Inflammatory molecules play important roles in atherosclerosis. We aimed to illustrate the roles of serum amyloid A (SAA), and interleukin (IL)-1ß in low density lipoproteins (LDL) transcytosis and atherosclerosis. METHODS: Effects of SAA and IL-1ß on transcytosis of LDL were measured by an in vitro LDL transcytosis model. NF-κB/caveolin-1/cavin-1 pathway activation was investigated by Western blots and ELISA. Effects of SAA and IL-1ß on the retention of LDL in aorta of C57BL/6J mice were detected by IVIS spectrum. Effects of SAA and IL-1ß on atherosclerosis in Apoe-/- mice were examined by Oil Red O staining. RESULTS: SAA and IL-1ß stimulated LDL transcytosis across endothelial cells (ECs), which was accompanied by an increase in LDL uptake by ECs. SAA and IL-1ß enhanced the activity of nuclear factor (NF)-κB, consequently facilitating an up-regulation of proteins involved in caveolae formation, including caveolin-1 and cavin-1, along with an assembly of NLRP3 inflammasome. Furthermore, SAA- and IL-1ß-induced effects were blocked by NF-κB subunit p65 siRNA. Meanwhile, SAA- and IL-1ß-induced LDL transcytosis were effectively blocked by caveolin-1 siRNA or cavin-1 siRNA. Interestingly, SAA and IL-1ß facilitated LDL entering into the aorta of C57BL/6J mice. In Apoe-/- mice, SAA and IL-1ß increased the areas of lipid-rich atherosclerotic lesions in the both ascending and root of aorta. Furthermore, a significant increase in the NLRP3 inflammasome, accompanied by accumulation of cavin-1 and caveolin-1, was observed in the aortic endothelium of Apoe-/- mice. CONCLUSIONS: SAA and IL-1ß accelerated LDL transcytosis via the NF-κB/caveolin-1/cavin-1 axis.

[Mechanism of Xiaoer Chiqiao Qingre Granules in clearing heat and removing food stagnation in suckling rats with fever and food accumulation based on metabolomics].

Children's fever is often accompanied by food accumulation. Traditional Chinese medicine believes that removing food stagnation while clearing heat of children can effectively avoid heat damage. To systematically evaluate the efficacy of Xiaoer Chiqiao Qingre Granules(XRCQ) in clearing heat and removing food accumulation and explore its potential mechanism, this study combined suckling SD rats fed with high-sugar and high-fat diet with injection of carrageenan to induce rat model of fever and food accumulation. This study provided references for the study on the pharmacodynamics and mechanism of XRCQ. The results showed that XRCQ effectively reduced the rectal temperature of suckling rats, improved the inflammatory environment such as the content of interleukin-1ß(IL-1ß), interleukin-2(IL-2), interferon-γ(IFN-γ), white blood cells, and monocytes. XRCQ also effectively repaired intestinal injury and enhanced intestinal propulsion function. According to the confirmation of its efficacy of clearing heat, the thermolytic mechanism of XRCQ was further explored by non-targeted and targeted metabolomics methods based on LTQ-Orbitrap MS/MS and UPLC-QQQ-MS/MS. Non-target metabolomics analysis of brain tissue samples was performed by QI software combined with SIMCA-P software, and 22 endogenous metabolites that could be significantly regulated were screened out. MetaboAnalyst pathway enrichment results showed that the intervention mechanism was mainly focused on tyrosine metabolism, tricarboxylic acid cycle, inositol phosphate metabolism, and other pathways. At the same time, the results of targeted metabolomics of brain tissue samples showed that XRCQ changed the vitality of digestive system, and inhibited abnormal energy metabolism and inflammatory response, playing a role in clearing heat and removing food stagnation from multiple levels.

Magnetic-field modulation of topological electronic state and emergent magneto-transport in a magnetic Weyl semimetal.

The modulation of topological electronic state by an external magnetic field is highly desired for condensed-matter physics. Schemes to achieve this have been proposed theoretically, but few can be realized experimentally. Here, combining transverse transport, theoretical calculations, and scanning tunneling microscopy/spectroscopy (STM/S) investigations, we provide an observation that the topological electronic state, accompanied by an emergent magneto-transport phenomenon, was modulated by applying magnetic field through induced non-collinear magnetism in the magnetic Weyl semimetal EuB6. A giant unconventional anomalous Hall effect (UAHE) is found during the magnetization re-orientation from easy axes to hard ones in magnetic field, with a UAHE peak around the low field of 5 kOe. Under the reasonable spin-canting effect, the folding of the topological anti-crossing bands occurs, generating a strong Berry curvature that accounts for the observed UAHE. Field-dependent STM/S reveals a highly synchronous evolution of electronic density of states, with a dI/dV peak around the same field of 5 kOe, which provides evidence to the folded bands and excited UAHE by external magnetic fields. This finding elucidates the connection between the real-space non-collinear magnetism and the k-space topological electronic state and establishes a novel manner to engineer the magneto-transport behaviors of correlated electrons for future topological spintronics.

Stem cell-assisted enzyme/prodrug therapy makes drug-resistant ovarian cancer cells vulnerable to natural killer cells through upregulation of NKG2D ligands.

Cancer stem-like cells (CSCs) are believed to be responsible for cancer recurrence and metastasis. Therefore, a therapeutic approach is needed to eliminate both rapidly proliferating differentiated cancer cells and slow-growing drug-resistant CSCs. Using established ovarian cancer cells lines as well as ovarian cancer cells isolated from a patient with high-grade drug-resistant ovarian carcinoma, we demonstrate that ovarian CSCs consistently express lower levels of NKG2D ligands (MICA/B and ULBPs) on their surfaces, a mechanism by which they evade natural killer (NK) cells' surveillance. Here, we discovered that exposure of ovarian cancer (OC) cells to SN-38 followed by 5-FU not only acts synergistically to kill the OC cells, but also makes the CSCs vulnerable to NK92 cells through upregulation of NKG2D ligands. Since systemic administration of these two drugs is marred by intolerance and instability, we engineered and isolated an adipose-derived stem cell (ASC) clone, which stably expresses carboxylesterase-2 and yeast cytosine deaminase enzymes to convert irinotecan and 5-FC prodrugs into SN-38 and 5-FU cytotoxic drugs, respectively. Co-incubation of ASCs and prodrugs with drug-resistant OC cells not only led to the death of the drug-resistant OC cells but also made them significantly vulnerable to NK92 cells. This study provides proof of principle for a combined ASC-directed targeted chemotherapy with NK92-assisted immunotherapy to eradicate drug-resistant OC cells.

Corrigendum: Clinical outcomes following surgical mitral valve plasty or replacement in patients with infectious endocarditis: A meta-analysis.

[This corrects the article DOI: 10.3389/fsurg.2022.1048036.].

Nonsebaceous Lymphadenoma of the Salivary Glands: A Potential Overdiagnosis Pitfall.

Nonsebaceous lymphadenoma is a rare benign salivary tumor. It is easily misdiagnosed as lymphoepithelial carcinoma, leading to overtreatment. Some patients experience sequelae after undergoing cervical lymph node resection and adjuvant treatment, so it is critical to distinguish these entities. We describe the histopathological and immunohistochemical features of this rare entity in 3 cases and discuss the differential diagnosis and histogenesis. Nonsebaceous lymphadenoma can be distinguished from lymphoepithelial carcinoma by the following histological features: There is a lymph node-like form at low magnification, with prominent proliferating epithelial nests but no destructive growth pattern; variable numbers of tubuloglandular components are always seen in proliferating epithelial nests, which transition to cystically dilated salivary ducts; no lesion necrosis exists; and mitotic figures are absent or rare. No patients experienced recurrence during the 8- to 69-month (mean, 29 months) follow-up.

Finite element analysis of screw fixation durability under multiple boundary and loading conditions for a custom pelvic implant.

Despite showing promising functional outcomes for pelvic reconstruction after sarcoma resection, custom-made pelvic implants continue to exhibit high complication rates due to fixation failures. Patient-specific finite element models have been utilized by researchers to evaluate implant durability. However, the effect of assumed boundary and loading conditions on failure analysis results of fixation screws remains unknown. In this study, the postoperative stress distributions in the fixation screws of a state-of-the-art custom-made pelvic implant were simulated, and the risk of failure was estimated under various combinations of two bone-implant interaction models (tied vs. frictional contact) and four load cases from level-ground walking and stair activities. The study found that the average weighted peak von Mises stress could increase by 22-fold when the bone-implant interactions were modeled with a frictional contact model instead of a tied model, and the likelihood of fatigue and pullout failure for each screw could change dramatically when different combinations of boundary and loading conditions were used. The inclusion of additional boundary and loading conditions led to a more reliable analysis of fixation durability. These findings demonstrated the importance of simulating multiple boundary conditions and load cases for comprehensive implant design evaluation using finite element analysis.

Geodesic path for the optimal nonequilibrium transition: Momentum-independent protocol.

Accelerating controlled thermodynamic processes requires an auxiliary Hamiltonian to steer the system into instantaneous equilibrium states. An extra energy cost is inevitably needed in such finite-time operation. We recently developed a geodesic approach to minimize such energy cost for the shortcut to isothermal process. The auxiliary control typically contains momentum-dependent terms, which are hard to be experimentally implemented due to the requirement of constantly monitoring the speed. In this work, we employ a variational auxiliary control without the momentum-dependent force to approximate the exact control. Following the geometric approach, we obtain the optimal control protocol with variational minimum energy cost. We demonstrate the construction of such protocol via an example of Brownian motion with a controllable harmonic potential.

ZDHHC11 Suppresses Zika Virus Infections by Palmitoylating the Envelope Protein.

Zika virus (ZIKV) is an RNA-enveloped virus that belongs to the Flavivirus genus, and ZIKV infections potentially induce severe neurodegenerative diseases and impair male fertility. Palmitoylation is an important post-translational modification of proteins that is mediated by a series of DHHC-palmitoyl transferases, which are implicated in various biological processes and viral infections. However, it remains to be investigated whether palmitoylation regulates ZIKV infections. In this study, we initially observed that the inhibition of palmitoylation by 2-bromopalmitate (2-BP) enhanced ZIKV infections, and determined that the envelope protein of ZIKV is palmitoylated at Cys308. ZDHHC11 was identified as the predominant enzyme that interacts with the ZIKV envelope protein and catalyzes its palmitoylation. Notably, ZDHHC11 suppressed ZIKV infections in an enzymatic activity-dependent manner and ZDHHC11 knockdown promoted ZIKV infection. In conclusion, we proposed that the envelope protein of ZIKV undergoes a novel post-translational modification and identified a distinct mechanism in which ZDHHC11 suppresses ZIKV infections via palmitoylation of the ZIKV envelope protein.

Distracted driving behavior in patients with insomnia.

Insomnia is one of the most common sleep disorders and is characterized by a subjective perception of difficulty falling asleep. Drivers with insomnia are vulnerable to distraction and exhibit higher levels of risk while driving. This study investigated the effect of two sources of in-vehicle distractions on the driving performance of drivers with insomnia and good sleepers by analyzing different driving behavior measures. Twenty-one drivers with insomnia and twenty-one healthy volunteers were recruited to complete simulated driving dual tasks. The primary task required the participants to perform: (a) a lane-keeping task, and (b) a lane-change task. The secondary task required the participants to deal with: (a) baseline (non-task), (b) internal distraction task, and (c) external distraction task. The internal distraction task required participants to complete quantitative reasoning tasks, while the external distraction task was a 0-back test. The relationship between distracted driving ability and cognitive function was also investigated. The results demonstrate that for lane-keeping tasks, drivers with insomnia had significantly higher standard deviations (SD) for speed, throttle position, acceleration, and lateral position than healthy drivers under internal distraction, but the driving performance did not differ significantly between groups under internal distraction or baseline. In the lane-change task, drivers with insomnia had higher SDs for steering wheel angle, steer angular velocity, lateral acceleration, and lateral speed than healthy drivers under external distraction. Moreover, external distraction impaired driving behavior in the healthy group, while internal distraction impaired driving ability in both groups. Healthy drivers with cognitive impairment displayed impaired lane-keeping abilities under internal distractions and impaired lane-changing abilities under external distractions. Driving performance in the insomnia group was not significantly associated with cognitive function. The results demonstrate that insomnia and distraction impair driving ability, and driver performance is affected differently by the distraction source (internal or external). The driving ability of healthy drivers with decreased cognition was impaired, but not that of insomniacs.The findings of this study provide new insights for preventing and estimating the potential influence of distracted driving behavior in individuals with insomnia.

ZDHHC11 Suppresses Zika Virus Infections by Palmitoylating the Envelope Protein.

Zika virus (ZIKV) is an RNA-enveloped virus that belongs to the Flavivirus genus, and ZIKV infections potentially induce severe neurodegenerative diseases and impair male fertility. Palmitoylation is an important post-translational modification of proteins that is mediated by a series of DHHC-palmitoyl transferases, which are implicated in various biological processes and viral infections. However, it remains to be investigated whether palmitoylation regulates ZIKV infections. In this study, we initially observed that the inhibition of palmitoylation by 2-bromopalmitate (2-BP) enhanced ZIKV infections, and determined that the envelope protein of ZIKV is palmitoylated at Cys308. ZDHHC11 was identified as the predominant enzyme that interacts with the ZIKV envelope protein and catalyzes its palmitoylation. Notably, ZDHHC11 suppressed ZIKV infections in an enzymatic activity-dependent manner and ZDHHC11 knockdown promoted ZIKV infection. In conclusion, we proposed that the envelope protein of ZIKV undergoes a novel post-translational modification and identified a distinct mechanism in which ZDHHC11 suppresses ZIKV infections via palmitoylation of the ZIKV envelope protein.

Ultrasensitive, Fast-Responsive, Directional Airflow Sensing by Bioinspired Suspended Graphene Fibers.

The development of high-performance miniaturized and flexible airflow sensors is essential to meet the need of emerging applications. Graphene-based airflow sensors are hampered by the sluggish response and recovery speed and low sensitivity. Here we employ laser-induced graphene (LIG) with poststructural biomimicry for fabricating high-performance, flexible airflow sensors, including cotton-like porous LIG, caterpillar fluff-like vertical LIG fiber, and Lepidoptera scale-like suspended LIG fiber (SLIGF) structures. The structural engineering changes the deformation behavior of LIGs under stress, among which the synchronous propagation of the scale-like structure of SLIGF is the most conducive to airflow sensing. The SLIGF achieves the shortest average response time of 0.5 s, the highest sensitivity of 0.11 s/m, and a record-low detection threshold of 0.0023 m/s, benchmarked against the state-of-the-art airflow sensors. Furthermore, we showcase the SLIGF airflow sensors in weather forecasting, health, and communications applications. Our study will help develop next-generation waterflow, sound, and motion sensors.

Proteomic analysis of protein lysine 2-hydroxyisobutyrylation (Khib) in soybean leaves.

BACKGROUND: Protein lysine 2-hydroxyisobutyrylation (Khib) is a novel post-translational modification (PTM) discovered in cells or tissues of animals, microorganisms and plants in recent years. Proteome-wide identification of Khib-modified proteins has been performed in several plant species, suggesting that Khib-modified proteins are involved in a variety of biological processes and metabolic pathways. However, the protein Khib modification in soybean, a globally important legume crop that provides the rich source of plant protein and oil, remains unclear. RESULTS: In this study, the Khib-modified proteins in soybean leaves were identified for the first time using affinity enrichment and high-resolution mass spectrometry-based proteomic techniques, and a systematic bioinformatics analysis of these Khib-modified proteins was performed. Our results showed that a total of 4251 Khib sites in 1532 proteins were identified as overlapping in three replicates (the raw mass spectrometry data are available via ProteomeXchange with the identifier of PXD03650). These Khib-modified proteins are involved in a wide range of cellular processes, particularly enriched in biosynthesis, central carbon metabolism and photosynthesis, and are widely distributed in subcellular locations, mainly in chloroplasts, cytoplasm and nucleus. In addition, a total of 12 sequence motifs were extracted from all identified Khib peptides, and a basic amino acid residue (K), an acidic amino acid residue (E) and three aliphatic amino acid residues with small side chains (G/A/V) were found to be more preferred around the Khib site. Furthermore, 16 highly-connected clusters of Khib proteins were retrieved from the global PPI network, which suggest that Khib modifications tend to occur in proteins associated with specific functional clusters. CONCLUSIONS: These findings suggest that Khib modification is an abundant and conserved PTM in soybean and that this modification may play an important role in regulating physiological processes in soybean leaves. The Khib proteomic data obtained in this study will help to further elucidate the regulatory mechanisms of Khib modification in soybean in the future.

Magnetic-field-induced simultaneous charge separation and oxygen transfer in photocatalytic oxygen activation for algae inactivation.

Photocatalytic oxygen activation is an excellent strategy for algae control in water. However, the fast recombination of photogenerated charge and slow rate of oxygen transfer limit the reactive oxygen species generation efficiency for algae inactivation. Herein, to solve above issues, magnetic field was introduced to the BiO2-x/Bi3NbO7 system to effectively covert oxygen into reactive radicals. The electrochemical experiment and DFT calculation results indicated the charge separation could be accelerated by the Lorentz force generated by the magnetic field, resulting in increase of electron concentration. Meanwhile, the value of volumetric gas-liquid mass transfer coefficient was increased by 59.79 % with magnetic field, thus more oxygen could be reduced to superoxide radical. Photocatalytic algae inactivation rate by BiO2-x/Bi3NbO7 with magnetic field could be increased by 2.07 times than that without magnet filed. This work further extends the strategy of using magnetic field to simultaneously facilitate the charge separation and oxygen transfer rate.

Transcriptomic reveals the ferroptosis features of host response in a mouse model of Zika virus infection.

Zika virus (ZIKV) is a neurotropic flavivirus. The outbreak of ZIKV in 2016 created a global health emergency. However, the underlying pathogenic mechanisms remain elusive. We investigated the host response features of in vivo replication in a mouse model of ZIKV infection, by performing a series of transcriptomic and bioinformatic analyses of ZIKV and mock-infected brain tissue. Tissue damage, inflammatory cells infiltration and high viral replication were observed in the brain tissue of ZIKV infected mice. RNA-Seq of the brain indicated the activation of ferroptosis pathways. Enrichment analysis of ferroptosis regulators revealed their involvement in pathways such as mineral absorption, fatty acid biosynthesis, fatty acid degradation, PPAR signaling pathway, peroxidase, and adipokinesine signalling pathway. We then identified 12 interacted hub ferroptosis regulators (CYBB, HMOX1, CP, SAT1, TF, SLC39A14, FTL, LPCAT3, FTH1, SLC3A2, TP53, and SLC40A1) that were related to the differential expression of CD8+ T cells, microglia and monocytes. CYBB, HMOX1, SALT, and SLAC40A1 were selected as potential biomarkers of ZIKV infection. Finally, we validated our results using RT-qPCR and outside available datasets. For the first time, we proposed a possible mechanism of ferroptosis in brain tissue infected by ZIKV in mice and identified the four key ferroptosis regulators.

The C-Terminal 300 Amino Acid Residues of the G Protein and Putative Open Reading Frame X of the G Gene of Tailam Paramyxovirus (TlmPV) Are Not Required for Replication in Tissue Culture Cells.

Tailam paramyxovirus (TlmPV) was identified in Sikkim Rats in Hong Kong, China in 2011. Its negative sense RNA genome is similar to J paramyxovirus (JPV) and Beilong paramyxovirus (BeiPV), the prototypes of the recently established genus Jeilongvirus. TlmPV genome is predicted to have eight genes in the order 3'-N-P/V/C-M-F-SH-TM-G/X-L-5'. The predicted size of the TlmPV G protein is 1,052 amino acid (aa) residues and much larger than G proteins of typical paramyxoviruses, which are often less than 800 aa. In addition to G open reading frame (ORF) in the G gene, another ORF, termed ORF-X exists in the G gene transcript. Similar ORF-X exists in JPV and BeiPV G gene, but their expression in virus-infected cells has not been confirmed. In this study, we generated infectious TlmPV using a newly developed reverse genetics system. We have found that the G protein of TlmPV is truncated in cultured cells: stop codons emerged in the G open reading frame, resulting in deletions of amino acid residues beyond residue 732. We have obtained infectious TlmPV lacking the C-terminal 307 aa (rTlmPV-G745) and TlmPV lacking the C-terminal 306 aa and the ORF-X (rTlmPV-GΔ746-X). The recombinant TlmPVs lacking the C-terminal 300 aa reach a higher peak viral titer and have improved genome stability in tissue cultured cells. The work indicates that the C-terminal of the G protein of TlmPV and ORF-X are not required for replication in tissue culture cells, and the deletion of the C-terminal confers a growth advantage in tissue culture cells. IMPORTANCE TlmPV is a member of the recently established genus Jeilongvirus. TlmPV encodes a large G protein and its G gene contains ORF-X. In this work, infectious TlmPV was recovered using reverse genetics. Using this system, we have demonstrated that 300 aa of C-terminal of G and the ORF-X are not required for viral replication in tissue culture cells.

Generation of innervated cochlear organoid recapitulates early development of auditory unit.

Functional cochlear hair cells (HCs) innervated by spiral ganglion neurons (SGNs) are essential for hearing, whereas robust models that recapitulate the peripheral auditory circuity are still lacking. Here, we developed cochlear organoids with functional peripheral auditory circuity in a staging three-dimensional (3D) co-culture system by initially reprogramming cochlear progenitor cells (CPCs) with increased proliferative potency that could be long-term expanded, then stepwise inducing the differentiation of cochlear HCs, as well as the outgrowth of neurites from SGNs. The function of HCs and synapses within organoids was confirmed by a series of morphological and electrophysiological evaluations. Single-cell mRNA sequencing revealed the differentiation trajectories of CPCs toward the major cochlear cell types and the dynamic gene expression during organoid HC development, which resembled the pattern of native HCs. We established the cochlear organoids with functional synapses for the first time, which provides a platform for deciphering the mechanisms of sensorineural hearing loss.

Metal Anodes with Ultrahigh Reversibility Enabled by the Closest Packing Crystallography for Sustainable Batteries.

The ever-growing annual electricity generated from sustainable and intermittent energy such as wind and solar power requires cost effective and reliable electrochemical energy storage. Rechargeable batteries based on multivalent metal anodes such as Zn, Al, and Fe, taking advantage of large-scale production and affordable cost, have emerged as promising candidates. However, the uncontrollable dendrite-like metal deposition on regular substrate caused by disordered metal crystallization usually leads to premature failure of batteries and even safety concerns when the dendrite bridges the electrodes. Here it is reported that a series of metal anodes (Zn, Co, Al, Ni, and Fe) with multiple crystal structures (hexagonal close-packed, face-centered cubic, and body-centered cubic) can achieve dendrite-free and epitaxial deposition on single-crystal Cu(111) substrates enabled by the closest packing crystallography. Moreover, the closest packed facets are aligned horizontally with the substrates, resulting in compact planar construction and excellent chemical stability even at an unprecedented current density of 1 A cm-2 . The full cells under a practical anode-to-cathode capacity ratio of 2.3 show a cycling life span of over 800 cycles with Coulombic efficiency of > 99.9%. The universal approach of regulating metal electrodeposition in this work is expected to boost the development of emerging sustainable energy storage/conversion devices.

A computational method for estimating trunk muscle activations during gait using lower extremity muscle synergies.

One of the surgical treatments for pelvic sarcoma is the restoration of hip function with a custom pelvic prosthesis after cancerous tumor removal. The orthopedic oncologist and orthopedic implant company must make numerous often subjective decisions regarding the design of the pelvic surgery and custom pelvic prosthesis. Using personalized musculoskeletal computer models to predict post-surgery walking function and custom pelvic prosthesis loading is an emerging method for making surgical and custom prosthesis design decisions in a more objective manner. Such predictions would necessitate the estimation of forces generated by muscles spanning the lower trunk and all joints of the lower extremities. However, estimating trunk and leg muscle forces simultaneously during walking based on electromyography (EMG) data remains challenging due to the limited number of EMG channels typically used for measurement of leg muscle activity. This study developed a computational method for estimating unmeasured trunk muscle activations during walking using lower extremity muscle synergies. To facilitate the calibration of an EMG-driven model and the estimation of leg muscle activations, EMG data were collected from each leg. Using non-negative matrix factorization, muscle synergies were extracted from activations of leg muscles. On the basis of previous studies, it was hypothesized that the time-varying synergy activations were shared between the trunk and leg muscles. The synergy weights required to reconstruct the trunk muscle activations were determined through optimization. The accuracy of the synergy-based method was dependent on the number of synergies and optimization formulation. With seven synergies and an increased level of activation minimization, the estimated activations of the erector spinae were strongly correlated with their measured activity. This study created a custom full-body model by combining two existing musculoskeletal models. The model was further modified and heavily personalized to represent various aspects of the pelvic sarcoma patient, all of which contributed to the estimation of trunk muscle activations. This proposed method can facilitate the prediction of post-surgery walking function and pelvic prosthesis loading, as well as provide objective evaluations for surgical and prosthesis design decisions.

Isolation, complete genome sequencing and in silico genome mining of Burkholderia for secondary metabolites.

Recent years, Burkholderia species have emerged as a new source of natural products (NPs) with increasing attractions. Genome mining suggests the Burkholderia genomes include many natural product biosynthetic gene clusters (BGCs) which are new targets for drug discovery. In order to collect more Burkholderia, here, a strain S-53 was isolated from the soil samples on a mountain area in Changde, P.R. China and verified by comparative genetic analysis to belong to Burkholderia. The complete genome of Burkholderia strain S-53 is 8.2 Mbps in size with an average G + C content of 66.35%. Its taxonomy was both characterized by 16S rRNA- and whole genome-based phylogenetic trees. Bioinformatic prediction in silico revealed it has a total of 15 NP BGCs, some of which may encode unknown products. It is expectable that availability of these BGCs will speed up the identification of new secondary metabolites from Burkholderia and help us understand how sophisticated BGC regulation works.