Precision Loading and Delivery of Molecular Cargo by Size-Controlled Coacervation of Gold Nanoparticles Functionalized with Elastin-like Peptides.

Thermoresponsive elastin-like peptides (ELPs) have been extensively investigated in biotechnology and medicine, but little attention has been paid to the process by which coacervation causes ELP-decorated particles to aggregate. Using gold nanoparticles (AuNPs) functionalized with a cysteine-terminated 96-repeat of the VPGVG sequence (V96-Cys), we show that the size of the clusters that reversibly form above the ELP transition temperature can be finely controlled in the 250 to 930 nm range by specifying the concentration of free V96-Cys in solution and using AuNPs of different sizes. We further find that the localized surface plasmon resonance peak of the embedded AuNPs progressively red-shifts with cluster size, likely due to an increase in particle-particle contacts. We exploit this fine control over size to homogeneously load precise amounts of the dye Nile Red and the antibiotic Tetracycline into clusters of different hydrodynamic diameters and deliver cargos near-quantitatively by deconstructing the aggregates below the ELP transition temperature. Beyond establishing a key role for free ELPs in the agglomeration of ELP-functionalized particles, our results provide a path for the thermally controlled delivery of precise quantities of molecular cargo. This capability might prove useful in combination photothermal therapies and theranostic applications, and to trigger spatially and temporally uniform responses from biological, electronic, or optical systems.

Towards predictive control of reversible nanoparticle assembly with solid-binding proteins.

Although a broad range of ligand-functionalized nanoparticles and physico-chemical triggers have been exploited to create stimuli-responsive colloidal systems, little attention has been paid to the reversible assembly of unmodified nanoparticles with non-covalently bound proteins. Previously, we reported that a derivative of green fluorescent protein engineered with oppositely located silica-binding peptides mediates the repeated assembly and disassembly of 10-nm silica nanoparticles when pH is toggled between 7.5 and 8.5. We captured the subtle interplay between interparticle electrostatic repulsion and their protein-mediated short-range attraction with a multiscale model energetically benchmarked to collective system behavior captured by scattering experiments. Here, we show that both solution conditions (pH and ionic strength) and protein engineering (sequence and position of engineered silica-binding peptides) provide pathways for reversible control over growth and fragmentation, leading to clusters ranging in size from 25 nm protein-coated particles to micrometer-size aggregate. We further find that the higher electrolyte environment associated with successive cycles of base addition eventually eliminates reversibility. Our model accurately predicts these multiple length scales phenomena. The underpinning concepts provide design principles for the dynamic control of other protein- and particle-based nanocomposites.

Bamboo Inspired Silicon Anodes with Ultrahigh Initial Coulombic Efficiency and High Capacity for the Li-Ion Batteries.

Silicon is regarded as the most promising candidate due to its ultrahigh theoretical energy density (4200 mAh g-1). However, the large volume expansion of silicon nanoparticles would result in the destruction of electrodes and a shortened cycle lifetime. Here, inspired by the natural structure of bamboo, the silicon anode with vascular bundle-like structure is proposed to improve the electrochemical performance for the first time. The dense channel wall in the silicon anode can accommodate the volume change of silicon nanoparticles and the transport of ions and electrons is also enhanced. The obtained silicon anodes display excellent mechanical properties (50% compression resilience and the average peel force of 4.34 N) and good wettability. What more, the silicon anodes exhibit high initial coulombic efficiency (94.5%), excellent cycle stability (2100 mAh g-1 after 300 cycles) which stands out among the silicon anodes. Specially, the silicon anode with impressive areal capacity of 36.36 mAh cm-2 and initial coulombic efficiency of 84% is also achieved. This work offers a novel and efficient strategy for the preparation of the flexible electrodes with outstanding performance.

Comparison of the C-TIRADS, ACR-TIRADS, and ATA guidelines in malignancy risk stratification of thyroid nodules.

Background: To compare the diagnostic performance in determining the malignancy of thyroid nodules and the fine needle aspiration (FNA) recommendations of the guidelines set forth by the Superficial Organ and Vascular Ultrasound Group of the Society of Ultrasound in Medicine of the Chinese Medical Association in 2020 [2020 Chinese Thyroid Imaging Reporting and Data System (C-TIRADS)], the American College of Radiology in 2017 (2017 ACR-TIRADS) and the American Thyroid Association in 2015 (2015 ATA guidelines). Methods: From January 2021 to December 2021, 1,228 thyroid nodules with definitive postoperative histopathology and ultrasound (US) examination within 3 months before surgery in Shantou Central Hospital were enrolled in this study. We collected the data in 2022. The participants formed a consecutive series. The clinical and US features of the nodules were retrospectively reviewed and categorized according to the 2020 C-TIRADS, the 2017 ACR-TIRADS and the 2015 ATA guidelines. The diagnostic performance and unnecessary FNA rates of the three guidelines were calculated. Results: The 2017 ACR-TIRADS had the highest diagnostic performance [area under the receiver operating characteristic curve (AUROC) 0.938], followed by the 2020 C-TIRADS (AUROC 0.933) and the 2015 ATA guidelines (AUROC 0.928). The ATA guidelines had the highest specificity (93.38%), accuracy (92.10%) and positive predictive value (PPV) (80.56%) among the three guidelines. There were no significant differences in the sensitivity and negative predictive value (NPV) among the three guidelines. The sensitivity, specificity, PPV, NPV and accuracy of the FNA recommendations based on the C-TIRADS were 84.25%, 58.76%, 38.92%, 92.28% and 64.82%, respectively, which were higher than those of the ACR-TIRADS (57.53%, 42.94%, 23.93%, 76.43% and 46.42%, respectively) and the ATA guidelines (62.67%, 13.25%, 18.39%, 53.22% and 25.00%, respectively). Compared with the ACR-TIRADS (76.07%) and the ATA guidelines (81.61%), the C-TIRADS showed advantages in the unnecessary FNA rate (61.08%), especially in nodules larger than 20 mm. Conclusions: The 2020 C-TIRADS, the 2017 ACR-TIRADS and the 2015 ATA guidelines can effectively predict the malignancy risk of thyroid nodules. Compared with the 2017 ACR-TIRADS and the 2015 ATA guidelines, the 2020 C-TIRADS may offer a meaningful reduction in FNA recommendations with the highest efficacy in distinguishing thyroid carcinoma.

[Effect of Scutellarin on Proliferation of Acute Myeloid Leukemia Cells and Its Related Mechanism].

OBJECTIVE: To investigate the effect of scutellarin (SCU) on proliferation, cell cycle and apoptosis of acute myeloid leukemia (AML) cells and its related molecular mechanism. METHODS: Human AML HL-60 cells were cultured in vitro. The cells were treated with SCU at the concentration of 0, 2, 4, 8, 16, 32, 64 µmol/L, and the inhibition rate of cell proliferation was detected by CCK-8 method. Then HL-60 cells were treated with SCU at the concentration of 4, 8, 16 µmol/L, and the negative control group (NC group) was set. The cell cycle distribution and apoptosis were detected by flow cytometry, and the expression of cell cycle, apoptosis and JAK2/STAT3 pathway related proteins were detected by Western blot. RESULTS: SCU significantly inhibited the proliferation of HL-60 cells in a concentration- and time-dependent manner(r =0.958,r =0.971). Compared with NC group, the proportion of cells in G0/G1 phase and apoptosis rate of HL-60 cells in 4, 8, 16 µmol/L SCU group were significantly increased, and the proportion of cells in S phase was significantly decreased (P <0.05). The relative protein expression levels of p21, p53, caspase-3 and Bax were significantly increased, while the relative protein expression levels of CDK2, cyclin E and Bcl-2 were significantly decreased (P <0.05). The ratio of p-JAK2/JAK2 and p-STAT3/STAT3 were significantly decreased (P <0.05). The changes of above-mentioned indexes were concentration dependent. CONCLUSION: SCU can inhibit the proliferation of AML cells, induce cell cycle arrest and apoptosis, and its mechanism may be related to the regulation of JAK2/STAT3 signaling pathway.

[Correlation between PAFAH1B3 Expression Level and Risk of Disease Progression After Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients].

OBJECTIVE: To investigate the association between the expression level of platelet-activating factor acetylhydrolase 1B3 (PAFAH1B3 ) gene in bone marrow CD138+ cells of patients with multiple myeloma (MM) treated with autologous hematopoietic stem cell transplantation (AHSCT) and the prognosis within 2 years. METHODS: 147 MM patients treated with AHSCT in The First and The Second Affiliated Hospital of Nantong University from May 2014 to May 2019 were included in the study. Expression level of PAFAH1B3 mRNA in bone marrow CD138+ cells of the patients was detected. Patients with disease progression or death during 2 years of follow-up were included in progression group, and the rest were included in good prognosis group. After comparing the clinical data and PAFAH1B3 mRNA expression levels of the two groups, the patients were divided into high PAFAH1B3 expression group and low PAFAH1B3 expression group based on the median PAFAH1B3 mRNA expression level of the enrolled patients. Progression-free survival rate (PFSR) between the two groups was compared by the Kaplan-Meier method. The related factors of prognosis within 2 years were analyzed by univariate analysis and multivariate COX regression analysis. RESULTS: At the end of follow-up, there were 13 patients lost to follow-up. Finally, 44 patients were included in the progression group and 90 patients were included in the good prognosis group. Age in the progression group was higher than that in the good prognosis group, the proportion of patients with CR+VGPR after transplantation in the progression group was lower than that in the good prognosis group, and there was a statistical difference between two groups in the cases distribution of ISS stage (all P<0.05). PAFAH1B3 mRNA expression level and the proportion of patients with LDH>250U/L in the progression group were higher than those in the good prognosis group, and platelet count in the progression group was lower than that in the good prognosis group (all P<0.05). Compared with the low PAFAH1B3 expression group, the 2-year PFSR of the high PAFAH1B3 expression group was significantly lower (log-rank χ2=8.167, P=0.004). LDH>250U/L (HR=3.389, P=0.010), PAFAH1B3 mRNA expression (HR=50.561, P=0.001) and ISS stage Ⅲ(HR=1.000, P=0.003) were independent risk factors for prognosis in MM patients, and ISS stage Ⅰ (HR=0.133, P=0.001) was independent protective factor. CONCLUSION: The expression level of PAFAH1B3 mRNA in bone marrow CD138+ cells is related to the prognosis of MM patients treated with AHSCT, and detecting PAFAH1B3 mRNA expression can bring some information for predicting PFSR and prognostic stratification of patients.

Therapeutic Efficacy of Platelet Transfusion and Analysis of Influencing Factors in 364 patients.

INTRODUCTION: The aims of this study were to observe the therapeutic effect of platelet (PLT) transfusion and to analyze influencing factors for the sake of providing useful clues for improving the efficacy of PLT transfusion. METHODS: Included in this study were patients who received PLT transfusion in the affiliated hospital of Nantong University. Patients' sex, age, height, weight, PLT transfusion status, and 20-24-h PLT count before and after PLT transfusion were collected to calculate the PLT corrected count increment values before and after PLT transfusion. Solid-phase red cell adherence assay was used to determine PLT antibody. Statistical analysis was performed using SPSS25.0 Software. RESULTS: A total of 364 patients received 1,060 PLT transfusions, including 728 successful transfusions and 332 unsuccessful transfusions. When the patients were grouped according to different etiologies, significant differences in PLT transfusion effectiveness were observed between these groups (χ2 = 15.070, p < 0.05). Grouping of the 364 patients according to sex, blood type, and PLT transfusion frequency showed no significant difference in PLT transfusion refractoriness (PTR) between different age-groups and sexes (p > 0.05). With the number of PLT transfusions increasing, PTR increased gradually. PLT antibodies were detected of 364 patients, 67 of them were positive. Among them, 63 cases (94.02%) were positive for HLA class I antibody. CONCLUSION: To reduce PTR, multiple factors should be considered comprehensively when PLT transfusion therapy is to be implemented in clinical practice. PLT antibody is the main immune factor causing PTR.

Molecular genetics and management of world health organization defined atypical chronic myeloid leukemia.

Atypical chronic myeloid leukemia (CML) is a rare BCR::ABL1-negative hematopoietic stem cell disease characterized by granulocytic proliferation and granulocytic dysplasia. Due to both the challenging diagnosis and the rarity of atypical CML, comprehensive molecular annotation-based analyses of this disease population have been scarce, and it is currently difficult to identify the optimal treatment for atypical CML. To explore atypical CML genomic landscape and treatment options, we performed a systematic retrospective of the clinical data and outcomes of 31 atypical CML patients. We observed that the molecular landscape of atypical CML was highly heterogeneous, with multiple molecular events driving its pathogenesis. Patients with atypical CML had a low response to current therapies, with an overall response rate (ORR) of 33.3% to hypomethylating agent (HMA)-based therapy. The current treatment strategies, including hematopoietic stem cell transplantation (HSCT), did not improve overall survival (OS) in atypical CML patients, with a median survival of 20 months. Thus, the benefits from HSCT and candidates for HSCT remain to be further evaluated. Acute myeloid leukemia (AML)-like chemotherapy followed by bridging allogeneic HSCT may be an ideal regimen for suitable individuals. The large-scale and prospective clinical studies will help to address the dilemma.

Slidable and Highly Ionic Conductive Polymer Binder for High-Performance Si Anodes in Lithium-Ion Batteries.

Silicon is expected to become the ideal anode material for the next generation of high energy density lithium battery because of its high theoretical capacity (4200 mAh g-1 ). However, for silicon electrodes, the initial coulombic efficiency (ICE) is low and the volume of the electrode changes by over 300% after lithiation. The capacity of the silicon electrode decreases rapidly during cycling, hindering the practical application. In this work, a slidable and highly ionic conductive flexible polymer binder with a specific single-ion structure (abbreviated as SSIP) is presented in which polyrotaxane acts as a dynamic crosslinker. The ionic conducting network is expected to reduce the overall resistance, improve ICE and stabilize the electrode interface. Furthermore, the introduction of slidable polyrotaxane increases the reversible dynamics of the binder and improves the long-term cycling stability and rate performance. The silicon anode based on SSIP provides a discharge capacity of ≈1650 mAh g-1 after 400 cycles at 0.5C with a high ICE of upto 92.0%. Additionally, the electrode still exhibits a high ICE of 87.5% with an ultra-high Si loading of 3.84 mg cm-2 and maintains a satisfying areal capacity of 5.9 mAh cm-2 after 50 cycles, exhibiting the potential application of SSIP in silicon-based anodes.

Severe aplastic anemia patients with infection who received an allogeneic hematopoietic stem cell transplantation had a better chance: Long-term outcomes of a multicenter study.

Background and aims: How to select the treatment is a challenge for the management of acquired patients with infections. This study aimed at comparing the outcomes of SAA with infections who had an allogeneic hematopoietic stem cell transplantation (allo-HSCT)with that of patients who had an infection and received non-HSCT therapy. Methods: We retrospectively compared the outcomes of patients with acquired SAA and infections who had an allo-HSCT (n = 141) with that of patients who had an infection and received non-HSCT therapy (n = 186) between July 2004 and January 2020. Results: The treatment-related mortality (TRM) of grade 1-2 infections in the HSCT and non-HSCT groups was 24.99% and 13.68%, respectively (P = 0.206), while the TRM of grade 3-4 infections was lower in the HSCT group than that observed in the non-HSCT group (18.54% vs. 33.33%, P = 0.036). At 6 months post-treatment, 91.30% patients in the HSCT group and 8.78% patients in the non-HSCT group had achieved a normal blood profile (P < 0.0001). The time required to discontinue transfusions of red blood cells and platelets in the non-HSCT group was longer than in the HSCT group (P < 0.0001). Estimated overall survival (OS) at 6 years was similar in the two groups (75.5% ± 3.9% vs. 76.3% ± 3.1%, P = 0.996), while the estimated failure-free survival (FFS) at 6 years was 75.2% ± 3.8% in the HSCT group and 48.9% ± 3.7% in the non-HSCT group (P < 0.0001). Multivariate analysis showed that younger age, lower grade of infection (grade 1-2), and SAA (vs. very SAA) were favorable factors for OS (P < 0.05), and that the choice of HSCT and younger age were favorable factors for FFS (P < 0.0001). Conclusion: These results suggest that allo-HSCT has a better chance of a successful outcome than non-HSCT in SAA patients with an infection.

Why they willingly complied: Ordinary people, the big environment, and the control of COVID-19 in China.

During the first two years of the COVID-19 pandemic, the Chinese public consistently demonstrated a high level of compliance with some of the most restrictive infection control measures in the world. As a result, as of early 2022 China achieved remarkable control of a virus that had devastating effects in other parts of the world. In this article we take seriously the complexities of a simple question: Why did most urban Chinese citizens so willingly comply with the state's COVID-19 control measures for so long? Based on two years of ethnographic research conducted primarily in Shanghai, China between June 2020 and May 2022, we argue that the strong support the Chinese government enjoyed among China's self-described laobaixing ("ordinary people") in implementing its COVID-19 control measures emerged from a combination of self-interest, nationalistic pride, and "conscious indifference to transparency," rooted in ongoing critical evaluations of governmental competence. With these evaluations changing in the wake of new outbreaks in 2022, the future of China's zero-COVID policy is in jeopardy.

Predictive Theoretical Framework for Dynamic Control of Bioinspired Hybrid Nanoparticle Self-Assembly.

At-will tailoring of the formation and reconfiguration of hierarchical structures is a key goal of modern nanomaterial design. Bioinspired systems comprising biomacromolecules and inorganic nanoparticles have potential for new functional material structures. Yet, consequential challenges remain because we lack a detailed understanding of the temporal and spatial interplay between participants when it is mediated by fundamental physicochemical interactions over a wide range of scales. Motivated by a system in which silica nanoparticles are reversibly and repeatedly assembled using a homobifunctional solid-binding protein and single-unit pH changes under near-neutral solution conditions, we develop a theoretical framework where interactions at the molecular and macroscopic scales are rigorously coupled based on colloidal theory and atomistic molecular dynamics simulations. We integrate these interactions into a predictive coarse-grained model that captures the pH-dependent reversibility and accurately matches small-angle X-ray scattering experiments at collective scales. The framework lays a foundation to connect microscopic details with the macroscopic behavior of complex bioinspired material systems and to control their behavior through an understanding of both equilibrium and nonequilibrium characteristics.

Analysis of the molecular mechanism and pedigree investigation of para-Bombay phenotype caused by combined mutations at position h649 and h768 of FUT1 gene.

BACKGROUND: The para-Bombay phenotype is a rare red blood cell phenotype characterised by the lack of ABH antigens on red blood cells, but ABH substances can be found in saliva. The aim of this research was to study the mechanism of mutation of FUT1 and FUT2 genes and the pedigree of a family with the para-Bombay phenotype. MATERIAL AND METHODS: The blood group was detected by a conventional serological method, H antigen adsorption-elution test, and testing saliva for A, B, and H antigens. We amplified and sequenced the ABO, FUT1, and FUT2 genes of the proband and her family using a polymerase chain reaction method, and performed TA cloning and sequencing on the amplified products of the FUT1 gene to determine its genotype. RESULTS: With the conventional serological method, it was found that the red blood cell phenotype of the proband and her sister lacked H antigen, while the adsorption-elution test of H antigen could detect weak H antigen. Through FUT1 cloning and sequencing, it was found that the proband had a compound heterozygous mutation of c.649G>T and c.768delC, and the genotype was FUT1*01W.24/FUT1*01N.20; the proband's father and mother had heterozygous mutations of c.768delC and c.649G>T, and their genotypes were FUT1*01N.20/FUT1*01 and FUT1*01W.24/FUT1*01. The sister's FUT1 mutation site and genotype were the same as the those of the proband. FUT2 gene sequencing revealed that the proband and sister had a synonymous mutation of c.357C>T, while their parents both had a synonymous mutation of c.357C>T and a missense mutation of c.385A>T. The Lewis blood types of the four samples all showed Le (a-b+), all of which were secretory. CONCLUSION: Blood group serology and molecular diagnostic techniques showed that the compound heterozygous mutations of the proband and her sister were inherited from their father and mother.

Inefficacy of Immunosuppressive Therapy for Severe Aplastic Anemia Progressing From Non-SAA: Improved Outcome After Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND AND AIMS: This study aimed at comparing the efficacy and safety of severe aplastic anemia (SAA) cases that had met the criteria for SAA at the time of diagnosis (group A) with SAA that had progressed from non-SAA (NSAA) (group B), both undergoing first-line immunosuppressive therapy (IST). Additionally, group B was compared with SAA that had progressed from NSAA and who had been treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) (group C). METHODS: We retrospectively compared 608 consecutive patients in group A (n = 232), group B (n = 229) and group C (n = 147) between June 2002 and December 2019. Six months after treatment, the rate of overall response and the fraction of patients who had achieved normal blood values, treatment-related mortality (TRM), secondary clonal disease, 5-year overall survival (OS) and failure-free survival (FFS) were indirectly compared between group A and group B, group B and group C. RESULTS: Six months after treatment, the rate of overall response and the fraction of patients who had achieved normal blood values in group A was higher than in group B (65.24% vs. 40.54%, P < 0.0001; 23.33% vs. 2.25%, P < 0.0001); the same was true for group C (92.50% vs. 2.25%, P < 0.0001). The rate of relapse in group B was higher than in group C (P < 0.0001), but there were no differences in TRM and secondary clonal disease (P > 0.05). There were no differences in estimated 5-year OS between groups A and B (83.8% ± 2.6% vs. 85.8% ± 2.6%, P = 0.837), or between B and C (85.8% ± 2.6% vs. 77.9% ± 3.4%, P = 0.051). The estimated 5-year FFS in groups A and C was higher than for group B (57.1% ± 3.3% vs. 39.7% ± 3.4%, P < 0.001; 76.7% ± 3.5% vs. 39.7% ± 3.4%, P < 0.0001). CONCLUSION: These results indicate that IST is less effective in SAA progressing from non-SAA but allo-HSCT can improve outcomes.

Diagnosis and Treatment of Myeloproliferative Neoplasms With PCM1-JAK2 Rearrangement: Case Report and Literature Review.

Myeloproliferative neoplasm (MPN) with PCM1-JAK2 rearrangement is a rare disease with poor prognosis and lacks uniform treatment guidelines. Several studies confirmed the efficacy of ruxolitinib in hematological malignancies with PCM1-JAK2 fusion, but the efficacy is variable. Here, we report two patients diagnosed with MPN with PCM1-JAK2 fusion who were treated with ruxolitinib-based regimen, including the first case of ruxolitinib combined with pegylated interferon (Peg-IFN), and we conduct a literature review. We found that ruxolitinib combined with Peg-IFN is an effective treatment option in the case of poor efficacy of ruxolitinib monotherapy.

Atorvastatin improves bone marrow endothelial progenitor cell function from patients with immune-related hemocytopenia.

BACKGROUND: Immune-related hemocytopenia (IRH) is a type of autoimmune disease that targets bone marrow hematopoietic cells. This study investigated the influence of atorvastatin on the functional aspects of bone marrow endothelial progenitor cells (BM EPCs) in IRH patients. METHODS: BM EPCs were isolated from 15 patients with IRH and 20 normal controls. The isolated BM EPCs were characterized by flow cytometry. Cell counting kit-8, flow cytometry, and Transwell migration assays were used to determine the proliferation, apoptosis, and migration of BM EPCs, respectively. Protein levels were determined by western blot assay. RESULTS: The BM EPCs isolated from IRH patients showed reduced proliferation, increased apoptosis, and attenuated migratory ability compared to those from normal controls. Western blot analysis showed that the protein level of p-p38 was significantly increased, while that of Phosphorylated protein kinase B (p-AKT) was significantly decreased in the BM EPCs from IRH patients, compared to BM EPCs from healthy subjects. Cell proliferation and migration were significantly enhanced by atorvastatin, recombinant human thrombopoietin, and SB20358 compared to the untreated BM EPCs from IRH patients. Atorvastatin, Recombinant human thrombopoietin (TPO), and SB20358 treatment significantly suppressed the protein levels of p-p38 protein, but increased those of p-AKT in BM EPCS from IRH patients. CONCLUSIONS: In summary, atorvastatin increases the number and function of BM EPCs in IRH patients by regulating the p38 and AKT signaling pathways.

Protective effect of teprenone on gastric mucosal injury induced by dual antiplatelet therapy in rats.

OBJECTIVE: To investigate the protective effect of teprenone on gastric mucosal injury induced by dual antiplatelet therapy in rats. METHODS: Healthy, specifically pathogen free SD, rats were selected and divided into 4 groups: Normal group (normal rats, without any treatment), Model group (rats received dual antiplatelet therapy: aspirin and clopidogrel), Teprenone group (rats received dual antiplatelet therapy and teprenone) and Pantoprazole group (rats received dual antiplatelet therapy and pantoprazole). The gastric mucosal blood flow, ulcer index, gastric gel mucus thickness, the levels of gastrin (Gas), prostaglandin (PG), prostaglandin E2 (PGE2), endothelin-1 (ET-1) tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IL-10 in serum, the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and myeloperoxidase (MPO) in the gastric mucosa, as well as the expression of vascular endothelial growth factor (VEGF) in the rat's stomach were measured. RESULTS: Compared with the Normal group, the other groups showed more severe gastric injury, elevated levels of inflammatory factors (TNF-α, IL-1ß, IL-6 and IL-10), elevated levels of MDA and MPO, as well as reduced levels of GSH, SOD and VEGF (all P<0.05). Compared with the Model group, the gastric mucosal lesions in the Teprenone group and the Pantoprazole group were improved significantly (both P<0.05). Compared with the Pantoprazole group, the Teprenone group had reduced levels of ET-1 and elevated levels of PG and PGE2 (all P<0.05). CONCLUSION: Teprenone protects against gastric mucosal injury induced by dual antiplatelet therapy through inhibiting gastric mucosal inflammation inhibiting oxidative stress and improving gastric mucosa indices.

Solid-Binding Proteins: Bridging Synthesis, Assembly, and Function in Hybrid and Hierarchical Materials Fabrication.

There is considerable interest in the development of hybrid organic-inorganic materials because of the potential for harvesting the unique capabilities that each system has to offer. Proteins are an especially attractive organic component owing to the high amount of chemical information encoded in their amino acid sequence, their amenability to molecular and computational (re)design, and the many structures and functions they specify. Genetic installation of solid-binding peptides (SBPs) within protein frameworks affords control over the position and orientation of adhesive and morphogenetic segments, and a path toward predictive synthesis and assembly of functional materials and devices, all while harnessing the built-in properties of the host scaffold. Here, we review the current understanding of the mechanisms through which SBPs bind to technologically relevant interfaces, with an emphasis on the variables that influence the process, and highlight the last decade of progress in the use of solid-binding proteins for hybrid and hierarchical materials synthesis.

Thrombopoietin Promotes Cell Proliferation and Attenuates Apoptosis of Aplastic Anemia Serum-Treated 32D Cells via Activating STAT3/STAT5 Signaling Pathway and Modulating Apoptosis-Related Mediators.

The present study aimed to investigate the effect and possible mechanism of recombinant human thrombopoietin (rhTPO) on mouse 32D cells (a mouse myeloid progenitor cell line) treated with serum from patients with aplastic anemia and to elucidate the potential mechanism of rhTPO in the treatment of aplastic anemia. After treatment with aplastic anemia serum, the apoptotic rate of 32D cells was increased and the proliferation of 32D cells was significantly inhibited. rhTPO reduced the apoptotic rate and promoted the proliferation of 32D cells, while rhTPO failed to restore the cell proliferation of 32D cells from aplastic anemia serum group to the normal level as compared to that from the normal serum group. The phosphorylation level of STAT3 protein was higher, and the phosphorylation level of STAT5 protein was lower in 32D cells from aplastic anemia serum group than that in normal serum group. After rhTPO treatment, the phosphorylation level of STAT3 protein in aplastic anemia serum group was decreased and the phosphorylation level of STAT5 protein was increased. The expression levels of Survivin and Bcl-2 were significantly decreased in 32D cells from aplastic anemia serum group, which were significantly increased after rhTPO treatment. The expression level of Bax protein in 32D cells from the normal serum group after rhTPO treatment was significantly decreased; while the mRNA expression level of Bax was not affected by rhTPO. The expression levels of Bax mRNA and protein were significantly up-regulated in 32D cells from aplastic anemia serum group, which was significantly decreased by rhTPO treatment. In conclusion, our results indicated that aplastic anemia serum impaired proliferative potential and enhanced apoptosis of 32D cells. Further mechanistic studies revealed that rhTPO promoted cell proliferation and attenuated apoptosis of aplastic anemia serum-treated 32D cells via activating STAT3/STAT5 signaling pathway and modulating apoptosis-related mediators.

Pegylated Interferon Alpha-2b in Patients With Polycythemia Vera and Essential Thrombocythemia in the Real World.

Several clinical trials have shown promising efficacy of pegylated interferon (Peg-IFN) in the first- and second-line polycythemia vera (PV) and essential thrombocythemia (ET). However, the efficacy and safety of Peg-IFN in the real world have rarely been reported. Hence, we conducted a prospective, single-center, single-arm, open exploratory study, which aimed to explore the hematologic response, molecular response, safety, and tolerability of patients with PV and ET treated with Peg-IFN in the real world. This study included newly diagnosed or previously treated patients with PV and ET, aged 18 years or older, admitted to the Department of Hematology of the First Affiliated Hospital of Soochow University from November 2017 to October 2019. The results revealed that complete hematological response (CHR) was achieved in 66.7% of patients with PV and 76.2% of patients with ET, and the molecular response was obtained in 38.5% of patients with PV and 50% of patients with ET after 48 weeks of Peg-IFN treatment. Peg-IFN is safe, effective and well tolerated in most patients. In the entire cohort, 4 patients (9.1%) discontinued treatment due to drug-related toxicity. In conclusion, Peg-IFN is a promising strategy in myeloproliferative neoplasms (MPNs), and Peg-IFN alone or in combination with other drugs should be further explored to reduce treatment-related toxicity and improve tolerability.