Optimization of braided stent design for cerebral aneurysms: the role of wire cross-sectional geometry

Flow-diverting stents are crucial for aneurysm treatment, with their structural design significantly impacting post-implantation hemodynamics. While clinically effective, opportunities remain to enhance their flexibility, flow diversion capability, and long-term safety through ongoing structural optimization. In this study, with Pipeline Embolization Device (PED) as a reference, four kinds of flow-diverting stents with different braided cross-section shapes (quadrilateral, hexagon, octagon, and decagon) were designed under the condition of keeping the amount of material constant. Firstly, pure bending loads are applied to each stent through finite element analysis, and its flexibility is evaluated by analyzing the torque-angle curve. Secondly, the computational fluid dynamics method was utilized to simulate the hemodynamic characteristics after the implantation of each stent. The results show that: (1) Under the condition of bending 60°, the decagonal stent has the best flexibility, followed by the quadrilateral one. (2) The overall blood flow distribution of stents with different cross-sections is similar, but there are differences in the local average flow velocity of the tumor cavity: the circular one is the highest, and the quadrilateral one is the lowest. (3) The wall pressure gradient change of the polygonal stent is gentler than that of the circular one. Among them, the wall pressure of the hexagonal and decagonal stents is the maximum and the average pressure in the cavity is the lowest. (4) The area of the low WSS region on the aneurysm wall is the largest in quadrilaterals and the smallest in circles. On the maternal artery segment, the hexagon is the largest and the quadrilateral is the smallest. Comprehensive comparison shows that quadrilateral and decagonal cross-section stents exhibit better comprehensive performance. Through the above research, theoretical support can be provided for the optimal design of flow-diverting stents structures

Nanoparticle-based drug delivery systems to enhance cancer immunotherapy in solid tumors

Immunotherapy has developed rapidly in solid tumors, especially in the areas of blocking inhibitory immune checkpoints and adoptive T-cell transfer for immune regulation. Many patients benefit from immunotherapy. However, the response rate of immunotherapy in the overall population are relatively low, which depends on the characteristics of the tumor and individualized patient differences. Moreover, the occurrence of drug resistance and adverse reactions largely limit the development of immunotherapy. Recently, the emergence of nanodrug delivery systems (NDDS) seems to improve the efficacy of immunotherapy by encapsulating drug carriers in nanoparticles to precisely reach the tumor site with high stability and biocompatibility, prolonging the drug cycle of action and greatly reducing the occurrence of toxic side effects. In this paper, we mainly review the advantages of NDDS and the mechanisms that enhance conventional immunotherapy in solid tumors, and summarize the recent advances in NDDS-based therapeutic strategies, which will provide valuable ideas for the development of novel tumor immunotherapy regimen

Spontaneous rotational symmetry breaking in KTaO3_3 interface superconductors

Strongly correlated electrons could display intriguing spontaneous broken symmetries in the ground state. Understanding these symmetry breaking states is fundamental to elucidate the various exotic quantum phases in condensed matter physics. Here, we report an experimental observation of spontaneous rotational symmetry breaking of the superconductivity at the interface of YAlO$_3$/KTaO$_3$ (111) with a superconducting transition temperature of 1.86 K. Both the magnetoresistance and upper critical field in an in-plane field manifest striking twofold symmetric oscillations deep inside the superconducting state, whereas the anisotropy vanishes in the normal state, demonstrating that it is an intrinsic property of the superconducting phase. We attribute this behavior to the mixed-parity superconducting state, which is an admixture of $s$-wave and $p$-wave pairing components induced by strong spin-orbit coupling. Our work demonstrates an unconventional nature of the pairing interaction in the KTaO$_3$ interface superconductor, and provides a new platform to clarify a delicate interplay of electron correlation and spin-orbit coupling.Comment: 7 pages, 4 figure

Genetic variants in the genes encoding rho GTPases and related regulators predict cutaneous melanoma-specific survival

Rho GTPases control cell division, motility, adhesion, vesicular trafficking and phagocytosis, which may affect progression and/or prognosis of cancers. Here, we investigated associations between genetic variants of Rho GTPases-related genes and cutaneous melanoma-specific survival (CMSS) by re-analyzing a published melanoma genome-wide association study (GWAS) and validating the results in another melanoma GWAS. In the single-locus analysis of 36,018 SNPs in 129 Rho-related genes, 427 SNPs were significantly associated with CMSS (p  C, ARHGAP22 rs3851552 T > C, ARHGAP44 rs72635537 C > T and ARHGEF10 rs7826362 A > T) were independently predictive of CMSS (a meta-analysis derived p = 9.04 × 10-4 , 9.58 × 10-4 , 1.21 × 10-4 and 8.47 × 10-4 , respectively). Additionally, patients with an increasing number of unfavorable genotypes (NUGs) of these loci had markedly reduced CMSS in both discovery dataset and validation dataset (ptrend =1.47 × 10-7 and 3.12 × 10-5 ). The model including the NUGs and clinical variables demonstrated a significant improvement in predicting the five-year CMSS. Moreover, rs10916352C and rs3851552C alleles were significantly associated with an increased mRNA expression levels of RHOU (p = 1.8 × 10-6 ) and ARHGAP22 (p = 5.0 × 10-6 ), respectively. These results may provide promising prognostic biomarkers for CM personalized management and treatment

Experimental investigation on the reverse mechano-electrical effect of porcine articular cartilage

IntroductionThe electric signals within the cartilage tissue are essential to biological systems and play a significant role in cartilage regeneration. Therefore, this study analyzed and investigated the reverse mechano-electrical effect in porcine articular cartilage and its related influencing factors.MethodsThe deflection of cartilage samples in an electric field was measured to analyze the mechanisms of different factors affecting the reverse mechano-electrical effect in articular cartilage.ResultsThe results showed that the cartilage thickness, water content, and externally applied voltage all impacted the deflection of the cartilage. The reduction in cartilage water content resulted in a decrease in cartilage thickness, following the same influencing mechanism as thickness. On the other hand, an increase in the externally applied voltage led to an increase in the electric field force within the cartilage space, consequently increasing the deflection of the cartilage in the electric field. Additionally, the externally applied voltage also caused a slight temperature rise in the vicinity of the cartilage specimens, and the magnitude of the temperature increase was proportional to the externally applied voltage.DiscussionThe fitting results of the experimental data indicated that cartilage thickness influenced the dielectric constant and moment of inertia of the cartilage in the electric field, thereby affecting the magnitude of the electric field force and deflection of the cartilage. This may provide valuable insights for further investigation into the microscopic mechanisms of cell proliferation, differentiation, and cartilage regeneration induced by electrical stimulation

Biomechanical design of titanium-PEEK combined fusion cage based on PLIF surgical model

Fusion devices play a critical role in lumbar fusion surgery. Titanium alloy fusion devices offer good biocompatibility and stability, but their mechanical properties far exceed those of bone, leading to stress shielding effects after implantation, which can reduce spinal fusion rates and cause endplate collapse. On the other hand, fusion devices made of polyether ether ketone (PEEK), which has a lower elastic modulus, are not conducive to bone ingrowth and fusion stability due to their material properties. Personalized fusion devices that can precisely adapt to a patient’s physiological condition are not widely used due to their lengthy design cycle. This study proposes an optimized design method based on a titanium alloy-PEEK composite structure. By constructing three composite structure models—PEEK core and Ti frame (square hole type, circular hole type, plate type)—and combining finite element compression simulation with machine learning algorithms, the structural parameters are intelligently optimized. The machine learning algorithm used in this study is Back Propagation Neural Network. The aim of this study is to match the equivalent elastic modulus of the fusion device with that of cortical bone. The three optimized fusion devices, along with the Ti fusion device and PEEK fusion device as control groups, were implanted into a traditional PLIF postoperative model for static and transient dynamic analysis. The biomechanical responses of the lumbar spine at various locations after implantation of the five fusion devices were analyzed and compared. The results indicate that all three optimized fusion devices effectively reduce the risk of device settlement, thereby mitigating stress shielding effects, improving fusion rates, and enhancing postoperative lumbar stability. Among them, the circular hole inner core fusion device (M2) demonstrated the best overall performance. The peak von Mises stress of L4 lower endplate and L5 upper endplate in M2 model were 54.2% and 27.7% respectively lower than those in Ti fusion device. Compared with Ti fusion device, the strain energy of M2 model increased by 49.7%. The development framework of this study which integrated “finite element simulation-machine learning-postoperative model biomechanical validation and evaluation” can effectively reduce the design cycle and cost of personalized orthopedic implants

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Safety of hypomagnetic field and its effects on the skeletal system

&amp;lt;p&amp;gt;&amp;amp;#160; &amp;amp;#160;&amp;amp;#160;All organisms survive and multiply under the geomagnetic magnetic field (GMF) &amp;lt;sup&amp;gt;[1]&amp;lt;/sup&amp;gt;. With the launch of the Moon and Mars space program, during long-distance space mission, astronauts will inevitably be exposed to an environment with a hypomagnetic field (HyMF), which several thousand times weaker than GMF&amp;lt;sup&amp;gt;[2]&amp;lt;/sup&amp;gt;. Spatial hypomagnetic field exists on the surface of the moon or in the deep space of the solar system, and its magnetic intensity is less than 5 &amp;amp;#956;T&amp;lt;sup&amp;gt;[3]&amp;lt;/sup&amp;gt;. At present, the research on the effects of HyMF on the health of astronauts is mainly focused on the conditions of ground simulation experiments, including the central nervous system, blood system and brain cognition &amp;lt;sup&amp;gt;[4,5]&amp;lt;/sup&amp;gt;. However, relevant safety of the skeletal system studies about HyMF are deficient. Our recent research indicated that the effects of HyMF on bone cannot be overlooked. In vivo, our study found that HyMF aggravated bone loss induced by hindlimb unloading (HLU) in rats and mice, which related to the changes in iron metabolism&amp;lt;sup&amp;gt;[6,7]&amp;lt;/sup&amp;gt;. In addition, HyMF also inhibited the recovery of simulated microgravity-induced osteoporosis of mice, probably by restraining elevated iron return to normal levels&amp;lt;sup&amp;gt;[8]&amp;lt;/sup&amp;gt;. Meanwhile, we found that HyMF can inhibit osteoblast differentiation and mineralization&amp;lt;sup&amp;gt;[9]&amp;lt;/sup&amp;gt;, promote osteoclast formation and bone resorption in vitro&amp;lt;sup&amp;gt;[10]&amp;lt;/sup&amp;gt;. The research results have significant academic values in the field of magneto-biology and the potential application values in space activities for the manned moon landing exploration.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Key words:&amp;lt;/strong&amp;gt;&amp;amp;#160;&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Hypomagnetic field, geomagnetic field, safety management, iron storage.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;References&amp;lt;/strong&amp;gt;&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;[1]Dubrov A P. The Geomagnetic Field and Life: Geomagnetobiology. Bioscience. 1978. 978-1-4757-1610-8.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;[2]Belyavskaya N. Biological effects due to weak magnetic field on plants. Advances in space Research, 2004,&amp;amp;#160;34(7): 1566-1574.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;[3]Mo W C, Ying L &amp;amp; He R Q. Hypomagnetic field, an ignorable environmental factor in space? Science China -Life Sciences, 2014. 57(7): 726-728.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;[4]Mo WC, Liu Y &amp;amp; He RQ. A biological perspective of the hypomagnetic field: from definition towards mechanism. Prog Biochem Biophys, 2012, 39: 835&amp;amp;#8211;842&amp;amp;#160;&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;[5]Jia B, Zhang WJ, Xie L, Zheng&amp;amp;#160; Q, Tian ZC &amp;amp; Shang P&amp;lt;em&amp;gt;. &amp;lt;/em&amp;gt;Effects of hypomagnetic field environment on hematopoietic system in mice. Space Medicine &amp;amp;Medical Engineering, 2011.24(5): 318-322.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;[6]&amp;amp;#160;Jia B, Xie L, Zheng Q, Yang P F, Zhang W J &amp;amp; Shang P. A hypomagnetic field aggravates bone loss induced by hindlimb unloading in rat femurs. PloS one, 2014, 9(8): e105604.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;[7]&amp;amp;#160;Yang J, Meng X, Dong D, Xue Y, Chen X &amp;amp; Shang P. Iron overload involved in the enhancement of unloading-induced bone loss by hypomagnetic field. Bone, 2018 Sep;114:235-245.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;[8]Xue YR, Yang JC, Luo J, Ren L, Shen Y &amp;amp; Shang P, Disorder of iron metabolism inhibits the recovery of unloading-induced bone loss in hypomagnetic field. Journal of bone and mineral research.2020. DOI: 10.1111/JBMR.3949.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;[9]Yang J, Zhang J, Ding C, Dong D &amp;amp; Shang P. Regulation of Osteoblast Differentiation and Iron Content in MC3T3-E1 Cells by Static Magnetic Field with Different Intensities. Biological trace element research, 2017, 184(7): 1-12.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;[10]Zhang J, Meng X, Ding C, Xie L, Yang P &amp;amp; Shang P. Regulation of osteoclast differentiation by static&amp;amp;#160;magnetic fields. Electromagnetic biology and medicine, 2017, 36(1): 8-19.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;&amp;amp;#160;&amp;lt;/p&amp;gt; </jats:p