Heat shock protein 90 inhibitors induce cell differentiation via the ubiquitin-dependent aurora kinase A degradation in a MPLW515L mouse model of primary myelofibrosis.

Primary myelofibrosis (PMF) is characterized by immature megakaryocytic hyperplasia, splenomegaly, extramedullary hematopoiesis and bone marrow fibrosis. Our preclinical study had demonstrated that aurora kinase A (AURKA) inhibitor MLN8237 reduced the mutation burden of PMF by inducing differentiation of immature megakaryocytes. However, it only slightly alleviated splenomegaly, reduced tissue fibrosis, and normalized megakaryocytes in PMF patients of the preliminary clinical study. So enhancing therapeutic efficacy of PMF is needed. In this study, we found that AURKA directly interacted with heat shock protein 90 (HSP90) and HSP90 inhibitors promoted the ubiquitin-dependent AURKA degradation. We demonstrated that HSP90 inhibitors 17-allylamino-17-demethoxygeldanamycin (17-AAG) and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), normalized peripheral blood counts, improved splenomegaly, attenuated extramedullary hematopoiesis, decreased tissue fibrosis and reduced mutant burden in a MPLW515L mouse model of PMF. Importantly, both 17-AAG and 17-DMAG treatment at effective doses in vivo did not influence on hematopoiesis in healthy mice. Collectively, the study demonstrates that HSP90 inhibitors induce cell differentiation via the ubiquitin-dependent AURKA and also are safe and effective for the treatment of a MPLW515L mouse model of PMF, which may provide a new strategy for PMF therapy. Further, we demonstrate that combined therapy shows superior activity in acute megakaryocytic leukemia mouse model than single therapy.

Estimation of Wideband Multi-Component Phasors Considering Signal Damping.

Harmonic and interharmonic content in power system signals is increasing with the development of renewable energy generation and power electronic devices. These multiple signal components can seriously degrade power quality, trip thermal generators, cause oscillations, and threaten system stability, especially the interharmonic tones with positive damping factors. The first step to mitigate these adverse effects is to accurately and quickly monitor signal features, including frequency, damping factor, amplitude, and phase. This paper proposes a concise and robust index to identify the number of modes present in the signal using the singular values of the Hankel matrix and discusses the scope of its application by testing the influence of various factors. Next, the simplified matrix pencil theory is employed to estimate the signal component frequency and damping factor. Then their estimates are considered in the modified least-squares algorithm to extract the wideband multi-component phasors accurately. Finally, this paper designs a series of scenarios considering varying signal frequency, damping factor, amplitude, and phase to test the proposed algorithm thoroughly. The results verify that the proposed method can achieve a maximum total vector error of less than 1.5%, which is more accurate than existing phasor estimators in various signal environments. The high accuracy of the proposed method is because it considers both the estimation of the frequency number and the effect of signal damping.

[Efficacy, safety, and mechanism of Huangkui Capsules in treating chronic kidney disease: Meta-analysis and integrative bioinformatics].

Meta-analysis and integrative bioinformatics were employed to comprehensively study the efficacy, safety, and mechanism of Huangkui Capsules in treating chronic kidney disease(CKD). CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed, EMbase, and Web of Science were searched for randomized controlled trial(RCT) of Huangkui Capsules for CKD from inception to January 3, 2023. The outcome indicators included urine protein, serum creatinine(Scr), and blood urea nitrogen(BUN) levels, and Cochrane Handbook 5.1 and RevMan 5.3 were employed to perform the Meta-analysis of the included RCT. The active ingredients of Huangkui Capsules were retrieved from CNKI, and the targets of CKD from GeneCards, OMIM, and TTD. Cytoscape 3.8.0 was used to build a "component-disease" network and a protein-protein interaction(PPI) network for the screening of core components and targets. Next, a differential analysis of the core targets of Huangkui Capsules for treating CKD was conducted with the clinical samples from GEO to identify the differentially expressed core targets, and correlation analysis and immune cell infiltration analysis were then performed for these targets. A total of 13 RCTs were included for the Meta-analysis, involving 2 372 patients(1 185 in the observation group and 1 187 in the control group). Meta-analysis showed that the Huangkui Capsules group and the losartan potassium group had no significant differences in reducing the urinary protein levels after 12(MD=19.60, 95%CI[-58.66, 97.86], P=0.62) and 24 weeks(MD=-66.00, 95%CI[-264.10, 132.11], P=0.51) of treatment. Huangkui Capsules in combination with conventional treatment was superior to conventional treatment alone(MD=-0.55, 95%CI[-0.86,-0.23], P=0.000 6). Huangkui Capsules combined with conventional treatment was superior to conventional treatment alone in recovering Scr(MD=-9.21, 95%CI[-15.85,-2.58], P=0.006) and BUN(MD=-1.02, 95%CI[-1.83,-0.21], P=0.01). Five patients showed clear adverse reactions, with abdominal or gastrointestinal discomfort. Huangkui Capsules had 43 active ingredients and 393 targets, and the core ingredients were myricetin, quercetin, gossypin, elaidic acid, dihydromyricetin, isochlorogenic acid B, and caffeic acid. CKD and Huangkui Capsules shared 247 common targets, including 25 core targets. The GEO differential analysis predicted 18 differentially expressed core targets, which were mainly positively correlated with immune cell expression and involved in immune inflammation, oxidative stress, pyroptosis, lipid metabolism, sex hormone metabolism, and cell repair. Conclusively, Huangkui Capsules combined with conventional treatment significantly reduced urine protein, Scr, and BUN. Huangkui Capsules alone and losartan potassium had no significant difference in reducing urine protein. This efficacy of Huangkui Capsules may be associated with the multi-component, multi-target, and multi-pathway responses to immune inflammation and oxidative stress. The included RCT had small sample sizes and general quality. More clinical trial protocols with large sample sizes and rigorous design and in line with international norms are needed to improve the evidence quality, and the results of bioinformatics analysis remain to be confirmed by further studies.

Chemical reactions of a CL-20 crystal under heat and shock determined by ReaxFF reactive molecular dynamics simulations.

Studying the chemical reactions of hexanitrohexaazaisowurtzitane (CL-20) under heat and shock is helpful to understand its sensitivity and shock initiation mechanism. In this work, several molecular dynamics simulations were performed under three different conditions: high temperature, high temperature and pressure, and shock. The formation and breakage of chemical bonds, changes of bond lengths, and initial reactions were analysed. It was found that the main small-molecule product of CL-20 during initial decomposition under the three different conditions was always NO2, but the generation pathways were different. At high temperatures, NO2 was generated by the direct cleavage of N-NO2 bonds. In contrast, high pressure and shock promoted the transfer of O atoms to N atoms connected to NO2, leading to the breakage of N-NO2 bonds. Almost all NO2 originated from the transfer of O atoms under the shock conditions.

Effect of density on the thermal decomposition mechanism of ε-CL-20: a ReaxFF reactive molecular dynamics simulation study.

The explosive detonation reaction occurs when explosives are compressed by different shock strengths, and the degree of compression affects the chemical reaction of the detonation process. The thermal decomposition mechanism of explosives under different compression densities has thus attracted significant research interest, and a better understanding of this mechanism would be helpful for determining the mechanism of the detonation reaction of explosives. In this study, a ε-CL-20 supercell was constructed, and the thermal decomposition was calculated at different compression densities and temperatures using molecular dynamics simulations based on the ReaxFF-lg reactive force field. We analyzed the effect of density on the main elementary reaction, which consists of the initial reaction and the formation of final products. In addition, we studied the effect of density on the generation of clusters and the reaction kinetics of the thermal decomposition. The results indicate that the initial reaction pathway of the CL-20 molecule is the cleavage of the N-NO2 bond at different densities and that the frequency of N-NO2 bond breakage decreases at high density. As the density increases, clusters easily form and are resistant to decomposition at the later stage of thermal decomposition, which eventually leads to a decrease in the number of final products. Increasing the initial density of CL-20 significantly increases the reaction rate of the initial decomposition but hardly changes the activation energy of the decomposition.

Thermal Decomposition Mechanism of CL-20 at Different Temperatures by ReaxFF Reactive Molecular Dynamics Simulations.

Hexanitrohexaazaisowurtzitane (CL-20) has a high detonation velocity and pressure, but its sensitivity is also high, which somewhat limits its applications. Therefore, it is important to understand the mechanism and characteristics of thermal decomposition of CL-20. In this study, a ε-CL-20 supercell was constructed and ReaxFF-lg reactive molecular dynamics simulations were performed to investigate thermal decomposition of ε-CL-20 at various temperatures (2000, 2500, 2750, 3000, 3250, and 3500 K). The mechanism of thermal decomposition of CL-20 was analyzed from the aspects of potential energy evolution, the primary reactions, and the intermediate and final product species. The effect of temperature on thermal decomposition of CL-20 is also discussed. The initial reaction path of thermal decomposition of CL-20 is N-NO2 cleavage to form NO2, followed by C-N cleavage, leading to the destruction of the cage structure. A small number of clusters appear in the early reactions and disappear at the end of the reactions. The initial reaction path of CL-20 decomposition is the same at different temperatures. However, as the temperature increases, the decomposition rate of CL-20 increases and the cage structure is destroyed earlier. The temperature greatly affects the rate constants of H2O and N2, but it has little effect on the rate constants of CO2 and H2.

Enhanced Interpolated Dynamic DFT Synchrophasor Estimator Considering Second Harmonic Interferences †.

In the future, phasor measurement units are expected to be applied in distribution networks (DNs) for their control and monitoring. Because of the widely used power electronic devices in DNs, harmonics are widely present in a voltage/current signal. Particularly, second harmonics have the most significant uncertainty contributions to synchrophasor estimation, which is especially true when a short cycle observation window is used for a fast response. Based on the interpolated dynamic discrete Fourier transform (IpD 2 FT), this paper introduces an enhanced IpD 2 FT (e-IpD 2 FT) synchrophasor estimator that considers second harmonic interferences. First, the adaptive equivalent filters of the IpD 2 FT are given. Based on these, the optimal frequencies where the IpD 2 FT has the least second harmonic interferences are then searched using an enumeration method, and the e-IpD 2 FT synchrophasor estimator is accordingly proposed. Instantaneous frequency responses and several simulation tests show that the e-IpD 2 FT performs much better than the IpD 2 FT in second harmonic suppression, and can meet the P-class response time requirements and most of the M-class accuracy requirements of the IEEE standard C37.118.1 only over a three-cycle window.

HMGB1-induced autophagy: a new pathway to maintain Treg function during chronic hepatitis B virus infection.

High-mobility group box-1 (HMGB1) protein, as one of the well-known damage-associated molecular pattern molecules (DAMPs), is enriched in chronic hepatitis B virus (HBV) infection and has a context-dependent role in autophagy, a highly conserved self-digestive process in response to environmental stress. Recent mouse studies indicate that autophagy is highly active in regulatory T (Treg)-cells. In the present study, we evaluated spontaneous and induced autophagy of peripheral Treg cells from 98 patients with chronic hepatitis B (CHB), by measuring levels of lipidated form of microtubule-associated light chain 3 (LC3-II, marker for closed autophagosomes) and observing autophagic vacuoles (AV) with transmission electron microscope. No significant difference was found in spontaneous autophagy of either Treg or CD4+ naive cells when comparing CHB patients with healthy subjects, apart from CHB-Treg showed significantly higher autophagic activity after activation by anti-CD3-CD28 beads. Besides, incubation of CHB-Treg cells with CHB-serum greatly maintained their autophagic behaviour, which could be significantly diminished by blocking HMGB1 with the neutralizing antibody. Further, we characterized time- and dose-dependent effects by recombinant HMGB1 protein on autophagy of CHB-Treg cells. We also documented a significant up-regulation of HMGB1 and its receptors [toll-like receptor (TLR4), receptor for advanced glycation end-product (RAGE)] in both peripheral and intra-hepatic microenvironments of CHB patients. Moreover, the RAGE-extracellular regulated protein kinases (ERK) axis and rapamycin-sensitive components of mammalian target of rapamycin (mTOR) pathways were demonstrated in vitro to be involved in HMGB1-induced autophagy of Treg cells. Additionally, HMGB1-induced autophagy could maintain cell survival and functional stability of CHB-Treg cells. Our findings could open new perspectives in developing therapeutic strategies to activate specific anti-HBV immunity by diminishing Treg autophagy.

Virulence and Molecular Diversity of the Puccinia striiformis f. sp. tritici Population in Xinjiang in Relation to Other Regions of Western China.

In recent years, wheat stripe rust caused severe yield losses in western China, especially the Xinjiang Autonomous Region. The population of the stripe rust fungus Puccinia striiformis f. sp. tritici in the vast region had not been well studied. To determine the population structure and compare it with the populations in the neighboring provinces or autonomous regions, P. striiformis f. sp. tritici isolates from Xinjiang, Qinghai, Gansu, Ningxia, and Tibet in western China were characterized by virulence tests with 19 wheat genotypes that are used to differentiate races of P. striiformis f. sp. tritici in China and by genotyping tests with 15 simple-sequence repeat (SSR) markers. In total, 56 races, including 39 previously known and 17 new races, were identified from 308 isolates obtained from the three epidemiological regions covering five provinces, of which 27 previously known and 8 unknown races were detected in Xinjiang, higher than the numbers in either of the other two regions. The races in Xinjiang consisted of those historically and recently predominant races in other regions of China. The P. striiformis f. sp. tritici population in Xinjiang had a higher genetic diversity than populations in other epidemiological regions. Molecular variation among subpopulations within Xinjiang was higher than in other regions. Both virulence and molecular data indicate that the P. striiformis f. sp. tritici population in Xinjiang is related to but more diverse than those in other epidemiological regions. The results show that Xinjiang is an important stripe rust epidemiological region in China, and the information should be useful for control of the disease in the region as well as in other regions.

Molecular mechanism analysis of apoptosis induced by silk fibroin peptides.

Silk fibroin derived from silkworm cocoons exhibits excellent mechanical properties, good biocompatibility, and low immunogenicity. Previous studies showed that silk fibroin had an inhibitory effect on cells, suppressing proliferation and inducing apoptosis. However, the source of the toxicity and the mechanism of apoptosis induction are still unclear. In this study, we hypothesized that the toxicity of silk fibroin might originate from the crystalline region of the heavy chain of silk fibroin. We then verified the hypothesis and the specific induction mechanism. A target peptide segment was obtained from α-chymotrypsin. The potentially toxic mixture of silk fibroin peptides (SFPs) was separated by ion exchange, and the toxicity was tested by an MTT assay. The results showed that SFPs obtained after 4 h of enzymatic hydrolysis had significant cytotoxicity, and SFPs with isoelectric points of 4.0-6.8 (SFPα II) had a significant inhibitory effect on cell growth. LC-MS/MS analysis showed that SFPα II contained a large number of glycine-rich and alanine-rich repetitive sequence polypeptides from the heavy-chain crystallization region. A series of experiments showed that SFPα II mediated cell death through the apoptotic pathway by decreasing the expression of Bcl-2 protein and increasing the expression of Bax protein. SFPα II mainly affected the p53 pathway and the AMPK signaling pathway in HepG2 cells. SFPα II may indirectly increase the expression of Cers2 by inhibiting the phosphorylation of EGFR, which activated apoptotic signaling in the cellular mitochondrial pathway and inhibited the Akt/NF-κB pathway by increasing the expression of PPP2R2A.

Oral sericin ameliorates type 2 diabetes through passive intestinal and bypass transport into the systemic circulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Boiled silkworm cocoons have been used to treat 'Xiaoke disease' (diabetes mellitus) recorded in Chinese medicine for over 800 years. In recent years, it has been found that the active substance silk sericin (SS) has therapeutic benefits in treating type 2 diabetes mellitus (T2DM). SS promotes pancreatic islet signalling, the proliferation of pancreatic islet cells, and insulin secretion. It is inferred that SS enters the bloodstream after oral administration and plays a role in the body's circulation. As a natural protein, SS needs to resist digestion by proteases in the gastrointestinal tract and cross the gastrointestinal barrier after oral administration. It is currently unclear how SS crosses the gastrointestinal barrier and whether it exerts therapeutic effects on T2DM by entering the circulation. AIM OF THE STUDY: To study how SS crosses the gastrointestinal barrier and whether it enters the body circulation to exert a therapeutic effect on T2DM. MATERIALS AND METHODS: SS was extracted from silkworm cocoons using an alkaline method with sodium carbonate. The antidigestive capacity of SS was detected using SDS-PAGE gel electrophoresis experiments. The mode of uptake and translocation of orally consumed SS in vivo was analysed using the AP-side to BL-side and BL-side-AP-side translocations, apparent Permeability coefficient (Papp), and Exocytosis rates (ER). The study compared the differences between the adSS group and the adSS + EDTA group by using Ethylenediaminetetraacetic acid (EDTA) to separate the tight junctions between Caco-2 cells. The aim was to analyze whether the transport mode of oral filaggrin proteins in vivo could be absorbed by bypass transport. By administering SS through oral and intraperitoneal injection to type 2 diabetic mice, we measured its concentration in the blood, as well as blood glucose and insulin levels, to determine its effectiveness in treating diabetes and its ability to enter the body's circulation for treatment. RESULTS: The molecular weight of SS decreased from 10k∼25 kDa to 10k∼15 kDa after in vitro simulated gastrointestinal fluid digestion, indicating its good antidigestive properties. The apparent Papp was greater than 1 × 10-6 cm·s-1, and the ER was between 0.5 and 1.5, indicating that adSS was well-absorbed and mainly passively transported. The Caco-2 cell model showed that the addition of EDTA promoted the transport of adSS, resulting in significantly larger Papp and ER values, indicating that adSS was absorbed by bypass transport. After oral administration of SS, the concentration of SS in the blood was lower than after intraperitoneal injection, which is 60% of intraperitoneal administration. Mice with a T2DM model who were administered SS for 5 weeks showed significant improvement in insulin resistance and glucose tolerance. Additionally, the pancreatic tissue appeared more regular. In the treatment of T2DM, injections of SS have been shown to be more effective than oral administration. Both oral and intraperitoneal injections have been partially involved in the circulation. CONCLUSIONS: SS is enzymatically cleaved by proteolytic enzymes in the gastrointestinal tract. The smaller molecules are partially absorbed into the body's circulation through passive and paracrine transport, exerting a therapeutic effect on T2DM.

Hydroxyl silicone oil grafting onto a rough thermoplastic polyurethane surface created durable super-hydrophobicity.

Indwelling medical catheters are frequently utilized in medical procedures, but they are highly susceptible to infection, posing a vital challenge for both health workers and patients. In this study, the superhydrophobic micro-nanostructure surface was constructed on the surface of thermoplastic polyurethane (TPU) membrane using heavy calcium carbonate (CaCO3) template. To decrease the surface free energy, hydroxyl silicone oil was grafted onto the surface, forming a super-hydrophobic surface. The water contact angle (WCA) increased from 91.1° to 143 ± 3° when the concentration of heavy calcium CaCO3 was 20% (weight-to-volume (w/v)). However, the increased WCA was unstable and tended to decrease over time. After grafting hydroxyl silicone oil, the WCA rose to 152.05 ± 1.62° and remained consistently high for a period of 30 min. Attenuated total reflection infrared spectroscopy (ATR-FTIR) analysis revealed a chemical crosslinking between silicone oil and the surface of TPU. Furthermore, Scanning electron microscope (SEM) image showed the presence of numerous nanoparticles on the micro surface. Atomic force microscope (AFM) testing indicated a significant improvement in surface roughness. This method of creating a hydrophobic surface demonstrated several advantages, including resistance to cell, bacterial, protein, and platelet adhesion and good biosecurity. Therefore, it holds promising potential for application in the development of TPU-based medical catheters with antibacterial properties.

Regulatory effects of stress release from decellularized periosteum on proliferation, migration, and osteogenic differentiation of periosteum-derived cells.

Bone injury is often associated with tears in the periosteum and changes in the internal stress microenvironment of the periosteum. In this study, we investigated the biological effects of periosteal prestress release on periosteum-derived cells (PDCs) and the potential mechanisms of endogenous stem cell recruitment. Decellularized periosteum with natural extracellular matrix (ECM) components was obtained by a combination of physical, chemical, and enzymatic decellularization. The decellularized periosteum removed immunogenicity while retaining the natural network structure and composition of the ECM. The Young's modulus has no significant difference between the periosteum before and after decellularization. The extracted PDCs were further composited with the decellularized periosteum and subjected to 20% stress release. It was found that the proliferative capacity of PDCs seeded on decellularized periosteum was significantly enhanced 6 h after stress release of the periosteum. The cell culture supernatant obtained after periosteal prestress release was able to significantly promote the migration ability of PDCs within 24 h. Enzyme-linked immunosorbnent assay (ELISA) experiments showed that the expression of stroma-derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF) in the supernatant increased significantly after 3 h and 12 h of stress release, respectively. Furthermore, periosteal stress release promoted the high expression of osteogenic markers osteocalcin (OCN), osteopontin (OPN), and collagen type I of PDCs. The change in stress environment caused by the release of periosteal prestress was sensed by integrin ß1, a mechanoreceptor on the membrane of PDCs, which further stimulated the expression of YAP in the nucleus. These investigations provided a novel method to evaluate the importance of mechanical stimulation in periosteum, which is also of great significance for the design and fabrication of artificial periosteum with mechanical regulation function.

Fine-Scale Genetic Structure of Curculio chinensis (Coleoptera: Curculionidae) Based on Mitochondrial COI: The Role of Host Specificity and Spatial Distance.

The Camellia weevil, Curculio chinensis (Chevrolat, 1978), is a dominant oligophagous pest that bores into the fruit of oil-tea Camellia. Genetic differentiation among populations in various hosts can easily occur, which hinders research on pest management. In this study, the genetic structure, genetic diversity, and phylogenetic structure of local C. chinensis populations were examined using 147 individuals (from 6 localities in Jiangxi), based on 2 mitochondrial COI markers. Results indicated that the C. chinensis population in Jiangxi exhibits a high haplotype diversity, especially for the populations from Cam. meiocarpa plantations. Structural differentiation was observed between Haplogroup 1 (73 individuals from Ganzhou, Jian, and Pingxiang) in the monoculture plantations of Cam. meiocarpa and Haplogroup 2 (75 individuals from Pingxiang and Jiujiang) in Cam. oleifera. Two haplogroups have recently undergone a demographic expansion, and Haplogroup 1 has shown a higher number of effective migrants than Haplogroup 2. This suggests that C. chinensis has been spreading from Cam. meiocarpa plantations to other oil-tea Camellia, such as Cam. oleifera. The increased cultivation of oil-tea Camellia in Jiangxi has contributed to a unique genetic structure within the C. chinensis population. This has, in turn, expanded the distribution of C. chinensis and increased migration between populations.

Population genetic diversity of Puccinia striiformis f. sp. tritici on different wheat varieties in Tianshui, Gansu Province.

Population genetic diversity in Tianshui city was analyzed with SSR markers in 605 single-pustule isolates of the stripe rust pathogen, Puccinia striiformis f. sp. tritici (Pst), obtained from 19 varieties of wheat. Significant differences in genetic diversity among populations were defected. Genetic diversity was highest in population on Tian 863-13, a highly resistant variety, whereas genetic diversity was lowest in population on Huixianhong, a highly susceptible variety. Seven populations from seven varieties that carried the common Yr18 resistance gene were clustered as one sub-group at 0.88 similarity coefficient, which showed that resistance gene selection had close relation with pathogen's component. The results of present study can provide a theoretical basis for integrated management of wheat stripe rust and effective deployment of resistance genes in Pst over-summering zones in China.

Mechanism of the Impact-Sensitivity Reduction of Energetic CL-20/TNT Cocrystals: A Nonequilibrium Molecular Dynamics Study.

High-energy low-sensitivity explosives are research objectives in the field of energetic materials, and the formation of cocrystals is an important method to improve the safety of explosives. However, the sensitivity reduction mechanism of cocrystal explosives is still unclear. In this study, CL-20/TNT, CL-20 and TNT crystals were taken as research objects. On the basis of the ReaxFF-lg reactive force field, the propagation process of the wave front in the crystals at different impact velocities was simulated. The molecular dynamics data were used to analyze the molecular structure changes and initial chemical reactions, and to explore the sensitivity reduction mechanism of the CL-20/TNT cocrystal. The results showed that the chemical reaction of the CL-20/TNT cocrystal, compared with the CL-20 single crystal, is different under different impact velocities. At an impact velocity of 2 km/s, polymerization and separation of the component molecules weakened the decomposition of CL-20. At an impact velocity of 3 km/s, the decay rates of CL-20 and TNT in the cocrystal decreased, and the intermediate products were enhanced, such as nitrogen oxides. At an impact velocity of 4 km/s, the cocrystal had little effect on the decay rates of the molecules and formation of CO2, but it enhanced formation of N2 and H2O. This may explain the reason for the impact-sensitivity reduction of the CL-20/TNT cocrystal.

Cell Transdifferentiation: A Challenging Strategy with Great Potential.

With the discovery and development of somatic cell nuclear transfer, cell fusion, and induced pluripotent stem cells, cell transdifferentiation research has presented unique advantages and stimulated a heated discussion worldwide. Cell transdifferentiation is a phenomenon by which a cell changes its lineage and acquires the phenotype of other cell types when exposed to certain conditions. Indeed, many adult stem cells and differentiated cells were reported to change their phenotype and transform into other lineages. This article reviews the differentiation of stem cells and classification of transdifferentiation, as well as the advantages, challenges, and prospects of cell transdifferentiation. This review discusses new research directions and the main challenges in the use of transdifferentiation in human cells and molecular replacement therapy. Overall, such knowledge is expected to provide a deep understanding of cell fate and regulation, which can change through differentiation, dedifferentiation, and transdifferentiation, with multiple applications.

Surface grafting of sericin onto thermoplastic polyurethanes to improve cell adhesion and function.

Thermoplastic polyurethane (TPU) membrane has super physical-mechanical properties and biocompatibility, but the surface is inert and lack of active groups which limit its application in cell culture. Silk sericin (SS) can improve cell adhesion, proliferation, growth and metabolism. In this paper, SS was grafted onto the surface of TPU membrane by -NH2 bridge to build a high efficiency cell culture membrane. The FT-IR spectrum results indicated SS was grafted by chemical bond. According to the SEM and AFM results, we found that the grafting of SS reduced the water contact angle by 43.31% and increased the surface roughness by about four times. When TPU-SS was used for HepG2 cell culture, the cell adhesion rate of TPU-SS was significantly higher than that of the general TCPS cell culture plate, and the cell proliferation rate was close to that of TCPS. FDA/EB staining showed that HepG2 cells remained a better cellular growth behavior. HepG2 cells had higher cell vitality including the albumin secretion and the intracellular total protein synthesis. Grafting SS maintained the stability of cell and significantly decreased the cytotoxicity by decreased LDH release. In conclusion, SS grafting is beneficial to cell culture in vitro, and provides a key material for bioartificial liver culture system.

Postbiotics as potential new therapeutic agents for sepsis.

Sepsis is the main cause of death in critically ill patients and gut microbiota dysbiosis plays a crucial role in sepsis. On the one hand, sepsis leads to the destruction of gut microbiota and induces and aggravates terminal organ dysfunction. On the other hand, the activation of pathogenic gut flora and the reduction in beneficial microbial products increase the susceptibility of the host to sepsis. Although probiotics or fecal microbiota transplantation preserve gut barrier function on multiple levels, their efficacy in sepsis with intestinal microbiota disruptions remains uncertain. Postbiotics consist of inactivated microbial cells or cell components. They possess antimicrobial, immunomodulatory, antioxidant and antiproliferative activities. Microbiota-targeted therapy strategies, such as postbiotics, may reduce the incidence of sepsis and improve the prognosis of patients with sepsis by regulating gut microbial metabolites, improving intestinal barrier integrity and changing the composition of the gut microbiota. They offer a variety of mechanisms and might even be superior to more conventional 'biotics' such as probiotics and prebiotics. In this review, we present an overview of the concept of postbiotics and summarize what is currently known about postbiotics and their prospective utility in sepsis therapy. Overall, postbiotics show promise as a viable adjunctive therapy option for sepsis.

Preparation of a modified silk-based gel/microsphere composite as a potential hepatic arterial embolization agent.

Transcatheter arterial chemoembolization (TACE) is an effective method for treating hepatocellular carcinoma (HCC). In this study, chitosan (CS), sodium glycerophosphate (GP), and sodium alginate (SA) were used as the main raw materials to develop clinically non-degradable embolization microspheres (Ms). Chitosan/sodium alginate embolization Ms. were generated using an emulsification cross-linking method. The Ms. were then uniformly dispersed in CS/GP temperature-sensitive gels to produce Gel/Ms. composite embolic agents. The results showed that Gel/Ms. had good morphology and a neatly arranged three-dimensional structure, and the Ms. dispersed in the Gel as evidenced by SEM. Furthermore, Gel/Ms. has good blood compatibility, with a hemolysis rate of ≤5 %. The cytotoxicity experiments have also proven its excellent cell compatibility. The degradation rate of Gel/Ms. was 58.869 ± 1.754 % within 4 weeks, indicating that Gel/Ms. had good degradation performance matching its drug release purpose. The Gel/Ms. adheres better at the target site than Ms. alone and releases the drug steadily over a long period, and the maximum release rate of Gel/Ms. within 8 h was 38.33 ± 1.528 %, and within 168 h was 81.266 ± 1.193 %. Overall, Gel/Ms. demonstrate better slow drug release, reduced sudden drug release, prolonged drug action time at the target site, and reduced toxic side effects on the body compared to Gel alone.