Characterization and engineering of peroxisome targeting sequences for compartmentalization engineering in Pichia pastoris.

Peroxisomal compartmentalization has emerged as a highly promising strategy for reconstituting intricate metabolic pathways. In recent years, significant progress has been made in the peroxisomes through harnessing precursor pools, circumventing metabolic crosstalk, and minimizing the cytotoxicity of exogenous pathways. However, it is important to note that in methylotrophic yeasts (e.g. Pichia pastoris), the abundance and protein composition of peroxisomes are highly variable, particularly when peroxisome proliferation is induced by specific carbon sources. The intricate subcellular localization of native proteins, the variability of peroxisomal metabolic pathways, and the lack of systematic characterization of peroxisome targeting signals have limited the applications of peroxisomal compartmentalization in P. pastoris. Accordingly, this study established a high-throughput screening method based on ß-carotene biosynthetic pathway to evaluate the targeting efficiency of PTS1s (Peroxisome Targeting Signal Type 1) in P. pastoris. First, 25 putative endogenous PTS1s were characterized and 3 PTS1s with high targeting efficiency were identified. Then, directed evolution of PTS1s was performed by constructing two PTS1 mutant libraries, and a total of 51 PTS1s (29 classical and 22 noncanonical PTS1s) with presumably higher peroxisomal targeting efficiency were identified, part of which were further characterized via confocal microscope. Finally, the newly identified PTS1s were employed for peroxisomal compartmentalization of the geraniol biosynthetic pathway, resulting in more than 30% increase in the titer of monoterpene compared with when the pathway was localized to the cytosol. The present study expands the synthetic biology toolkit and lays a solid foundation for peroxisomal compartmentalization in P. pastoris.

A fungal P450 enzyme from Fusarium equiseti HG18 with 7ß-hydroxylase activity in biosynthesis of ursodeoxycholic acid.

Cytochrome P450 enzyme with 7ß-hydroxylation capacity has attracted widespread attentions due to the vital roles in the biosynthesis of ursodeoxycholic acid (UDCA), a naturally active molecule for the treatment of liver and gallbladder diseases. In this study, a novel P450 hydroxylase (P450FE) was screen out from Fusarium equiseti HG18 and identified by a combination of genome and transcriptome sequencing, as well as heterologous expression in Pichia pastoris. The biotransformation of lithocholic acid (LCA) by whole cells of recombinant Pichia pastoris further confirmed the C7ß-hydroxylation with 5.2% UDCA yield. It was firstly identified a fungal P450 enzyme from Fusarium equiseti HG18 with the capacity to catalyze the LCA oxidation producing UDCA. The integration of homology modeling and molecular docking discovered the substrate binding to active pockets, and the key amino acids in active center were validated by site-directed mutagenesis, and revealed that Q112, V362 and L363 were the pivotal residues of P450FE in regulating the activity and selectivity of 7ß-hydroxylation. Specifically, V362I mutation exhibited 2.6-fold higher levels of UDCA and higher stereospecificity than wild-type P450FE. This advance provided guidance for improving the catalytic efficiency and selectivity of P450FE in LCA hydroxylation, indicative of the great potential in green synthesis of UDCA from biologically toxic LCA.

Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits.

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

Wound microenvironment regulatory poly(L-glutamic acid) composite hydrogels containing metal ion-coordinated nanoparticles for effective hemostasis and wound healing.

Regulating the wound microenvironment to promote proliferation, vascularization, and wound healing is challenging for hemostats and wound dressings. Herein, polypeptide composite hydrogels have been simply fabricated by mixing a smaller amount of metal ion-coordinated nanoparticles into dopamine-modified poly(L-glutamic acid) (PGA), which had a microporous size of 10-16 µm, photothermal conversion ability, good biocompatibility, and multiple biological activities. In vitro scratch healing of fibroblast L929 cells and the tube formation of HUVECs provide evidence that the PGA composite hydrogels could promote cell proliferation, migration, and angiogenesis with the assistance of mild photothermia. Moreover, these composite hydrogels plus mild photothermia could effectively eliminate reactive oxygen species (ROS), alleviate inflammation, and polarize the pro-inflammatory M1 macrophage phenotype into the pro-healing M2 phenotype to accelerate wound healing, as assessed by means of fluorescent microscopy, flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR). Meanwhile, a rat liver bleeding model illustrates that the composite hydrogels reduced the blood loss ratio to about 10% and shortened the hemostasis time to about 25 s better than commercial chitosan-based hemostats. Furthermore, the full-thickness rat skin defect models showcase that the composite hydrogels plus mild photothermia could proheal wounds completely with a fast healing rate, optimal neovascularization, and collagen deposition. Therefore, the biodegradable polypeptide PGA composite hydrogels are promising as potent wound hemostats and dressings.

The ecological suitability area of Cirsium lineare (Thunb.) Sch.-Bip. under future climate change in China based on MaxEnt modeling.

Many kinds of medicinal ingredients occur in Cirsium lineare that have good clinical efficacy, conferring on this species its high medicinal development value. However, with a rapidly changing global climate, it is increasingly imperative to study the factors affecting the habitat distribution and survival of species. We predicted the current and future distribution areas of suitable habitats for C. lineare, analyzed the importance of environmental variables in influencing habitat shifts, and described the alterations to suitable habitats of C. lineare in different periods (modern, 2050s, and 2070s) and scenarios (RCP2.6, RCP4.5, and RCP8.5). The results show that, under the current climate, the total suitable area of C. lineare is about 2,220,900 km2, of which the highly suitable portion amounts to ca. 292,600 km2. The minimum temperature of the coldest month, annual precipitation, and mean daily temperature range are the chief environmental variables affecting the distribution of habitat for C. lineare. In the same period, with rising greenhouse gas emission concentrations, the total suitable area will increase. In general, under future climate change, the suitable habitat for C. lineare will gradually migrate to the west and north, and its total suitable area will also expand. The results of this experiment can be used for the conservation and management of the wild resources of C. lineare. We can choose suitable growth areas to protect the medicinal resources of C. lineare through in situ conservation and artificial breeding.

Application of five risk stratification tools for syncope in older adults.

OBJECTIVE: Treatment of syncope in older adults places a burden on healthcare systems. We used five risk stratification tools to predict short-term adverse outcomes in older patients with syncope. METHODS: This was a retrospective analysis of patients with syncope (age ≥60 years) in the emergency department of an urban academic hospital. The data were evaluated using the Risk Stratification of Syncope in the Emergency Department (ROSE), San Francisco Syncope Rule (SFSR), FAINT, Canadian Syncope Risk Score (CSRS), and Boston Syncope Criteria (BSC) tools. Sensitivity, specificity, accuracy, positive and negative predictive value (NPV), and positive and negative likelihood ratios of each tool were calculated and compared for adverse events within 1 month. RESULTS: In total, 221 patients (average age 75.6 years) were analyzed. Fifty-nine patients (26.7%) had experienced an adverse event within 1 month. For the ROSE, SFSR, FAINT, CSRS and BSC tools, sensitivities were 81.3%, 76.3%, 93.2%, 71.2%, and 94.9%, specificities were 88.3%, 87.7%, 56.8%, 71.6%, and 67.3%, and NPVs were 92.9%, 91.0%, 95.8%, 87.2%, and 97.3%, respectively. CONCLUSION: The five assessed tools could be useful for physicians in screening older patients with syncope for the risk of short-term adverse events, according to the patient's actual situation.

Evaluation of retinal structural and functional changes after silicone oil removal in patients with rhegmatogenous retinal detachment: a retrospective study.

BACKGROUND: To evaluate retinal structural and functional changes after silicone oil (SO) removal in eyes with macula-off rhegmatogenous retinal detachment (RRD). METHODS: Best-corrected visual acuity (BCVA) testing, microperimetry, and optical coherence tomography angiography were performed in 48 eyes with macula-off RRD before and 3 months after SO removal. The values of healthy contralateral eyes were used as control data. Correlations between retinal vessel density (VD), retinal nerve fiber layer thickness (RNFLT), the interval between retinal detachment and surgery, the duration of SO tamponade, the follow-up time after SO removal, and visual function were analyzed. RESULTS: Significant increases in 2˚ fixation rate (FR), 4˚ FR, 2˚ mean retinal sensitivity (MRS), 6˚ MRS, parafoveal superficial capillary plexus VD and RNFLT were observed after SO removal (all P < 0.05). The increase of 2˚ MRS and 6˚ MRS were correlated with the duration of SO tamponade and the follow-up time after SO removal respectively (all P < 0.05). The last 2˚ MRS and 6˚ MRS were correlated with the duration of SO tamponade, the interval between retinal detachment and surgery, and the follow-up time after SO removal (all P < 0.01). The last FR in RRD eyes was close to that of contralateral eyes (P > 0.05). CONCLUSION: Retinal structure and function improved to different degrees after SO removal. Fixation stability and retinal sensitivity increased more than BCVA postoperatively. Retinal sensitivity, which was affected by the interval between retinal detachment and surgery and the duration of SO tamponade, gradually recovered after SO removal.

Maternal uniparental disomy for chromosome 6 in 2 prenatal cases with IUGR: case report and literature review.

BACKGROUND: Uniparental disomy (UPD) is a rare genetic condition leading to potential disease risks. Maternal UPD of chromosome 6 upd(6)mat is exceptionally rare, with limited cases reported. This study reported two new cases of upd(6)mat and reviewed the literature of previous cases. CASE PRESENTATION: Both cases exhibited intrauterine growth restriction (IUGR), and genetic analysis confirmed upd(6)mat in each case. The literature review identified a total of 19 cases. IUGR and preterm labor were the most common two symptoms observed, and additional anomalies and genetic variations were also reported in some cases. CONCLUSION: upd(6)mat is potentially associatied with IUGR, but the precise genotype-phenotype relationship remains unclear. The cases with upd(6)mat may present clinical features due to imprinting disorders.

Venous Thromboembolism Prophylaxis After Spontaneous Intracerebral Hemorrhage: A Review.

BACKGROUND: Patients with spontaneous intracerebral hemorrhage (sICH) are at high risk for venous thromboembolism (VTE). The administration of mechanical and pharmacological VTE prophylaxis after sICH is important but challenging. The safety and efficacy of the optimal anticoagulant dose, timing, and type of VTE chemoprophylaxis in cases of sICH are still unclear, and clinicians are concerned that it may lead to cerebral hematoma expansion, which is associated with poor prognosis. Through this literature review, we aim to summarize the latest guidelines, recommendations, and clinical research progress to support evidence-based treatment strategies. REVIEW SUMMARY: It has been proven that intermittent pneumatic compression can effectively reduce the risk of VTE and should be used at the time of hospital admission, whereas gradient compression stockings or lack of prophylaxis in sICH cases are not recommended by current guidelines. Studies regarding pharmacological VTE prophylaxis in patients with ICH were reviewed and summarized. Prophylactic anticoagulation for VTE in patients with ICH seems to be safe and was not associated with cerebral hematoma expansion. Meanwhile, the prophylactic efficacy of anticoagulation for pulmonary embolism seems to be more obvious than that of deep vein thrombosis in patients with ICH. CONCLUSIONS: Clinicians should pay attention to the prevention and management of VTE after sICH. Intermittent pneumatic compression should be applied to patients with sICH on the day of hospital admission. After documentation of bleeding cessation, early initiation of pharmacological VTE prophylaxis (24 h to 48 h from sICH onset) seems to be safe and effective in pulmonary embolism prophylaxis.

Summary of the application value of ultrasound imaging features in the clinical differential diagnosis of intramuscular capillary-type hemangioma and fibro-adipose vascular anomaly.

Objective: To investigate the value of ultrasonography as a diagnostic aid in differentiating intramuscular capillary-type hemangioma (ICTH) from fibro-adipose vascular anomaly (FAVA). Methods: A retrospective analysis was conducted of the clinical and ultrasound imaging data of 20 patients with ICTH and 45 patients with FAVA who were admitted to and pathologically confirmed in hospital between January 2013 and April 2023. The clinical and ultrasonographic appearances of the lesions in the two groups were compared and analyzed. A stepwise regression analysis was performed, and a joint diagnostic equation was constructed using the final variables selected. The receiver operating characteristic (ROC) curve and indicators, including sensitivity and specificity, were used to evaluate the efficacy of the joint diagnostic model. Results: The two groups of patients suffering from ICTH and FAVA presented a statistically significant difference (P< 0.05) in terms of 'age', 'lesion size', 'fascial tail sign', 'presence of a fatty-tissue-like hyperecho around the lesion', 'blood flow' and 'presence of straight blood capillaries within the lesion'. Finally, the variables 'fascial tail sign' and 'presence of straight blood capillaries within the lesion' were selected to construct the model. The constructed joint diagnostic model had a sensitivity value of 70.0% (95% CI: 59.00-81.00), a specificity value of 98.0% (95% CI: 94.70-100.00) and a ROC curve value of 0.908, indicating the high efficacy of the combined diagnosis method. Conclusions: Ultrasonography can be utilized to differentiate ICTH from FAVA, and the combined diagnosis method can further improve the technique's diagnostic efficacy.

GDU-952, a novel AhR agonist ameliorates skin barrier abnormalities and immune dysfunction in DNFB-induced atopic dermatitis in mice.

The aryl hydrocarbon receptor (AhR) is widely expressed in the skin. It controls immune-mediated skin responses to various external environmental signals, promote terminal differentiation of epidermal keratinocytes and participates the maintenance of the skin barrier function. As a therapeutic target, AhR activation modulates many diseases progression driven by immune/inflammatory processes such as atopic dermatitis (AD) and psoriasis. In this study, we revealed that GDU-952 is a novel AhR agonist, which is able to decreases IgE serum levels, to inhibit pro-inflammatory cytokines such as IL-6 and TNF-α and to induce immunoregulatory effects through restoring Th1/Th2 immune balance and promoting CD4+FOXP3+regulatory T (Treg) populations in AD skin lesions. Furthermore, GDU-952 can strengthen the skin barrier function through upregulating epidermal differentiation-related and tight junction proteins. This may alleviate AD symptoms, such as dermatitis scores, epidermal hyperplasia and mast cell infiltration. These results offer a rationale for further preclinical/clinical studies to evaluate the possible use of GDU-952 in the management of AD.

Occurrence and health risk assessment of phthalates in a typical estuarine soil: A case study of the various functional areas of the Yellow River Delta.

In recent years, the extensive distribution of phthalates (PAEs) in soils has attracted increasing attention. In this study, the concentrations of six types of PAEs were measured in five dissimilar regions of the Yellow River Delta (YRD), and regional differences, pollution characteristics and health risks of PAEs pollution were investigated. The detection rate of PAEs was 100 %, and the concentration range of Σ6PAEs was 0.709-9.565 mg/kg, with an average of 3.258 ± 2.031 mg/kg. There were different spatial distribution differences of PAEs in soils of the YRD, with residential living, chemical industrial, and crop growing areas being the main areas of PAEs distribution. It was worth noting that di (2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) are prominent contributors to PAEs in soils of the YRD. Correlation analyses showed that soils physicochemical properties such as SOM, TN and CEC were closely correlated to the transport and transformation of PAEs. Use by petrochemical industries, accumulation of plasticizers, additives (derived from cosmetics, food, pharmaceutical), fertilizers, pesticides, plastics, and atmospheric deposition are the principal sources of PAEs in the YRD. A health risk assessment showed that the health risk caused by non-dietary intake of PAEs was low and considered acceptable. PAEs pollution in the YRD soil is particularly noteworthy, especially for the prevention and control of DEHP and DBP pollution. This study provides basic data for an effective control of soil PAEs pollution in the YRD, which is conducive to the sustainable development of the region.

Design, synthesis and evaluation of novel pyrimidinylaminothiophene derivatives as FGFR1 inhibitors against human glioblastoma multiforme.

Vascular endothelial growth factor receptors (VEGFRs) have emerged as the most promising anti-angiogenic therapeutic targets for the treatment of recurrent glioblastomas (GBM). However, anti-VEGF treatments led to the high proportion of non-responder patients or non lasting clinical response and the tumor progression to the greater malignant stage. To overcome these problems, there is an utmost need to develop innovative anti-angiogenic therapies. In this study, we report the development of a series of new FGFR1 inhibitors. Among them, compound 4i was able to potently inhibit FGFR1 kinase activities both in vitro and in vivo. This compound displayed strong anti-angiogenic activity in HUVECs and anti-tumor growth and anti-invasion effects in U-87MG cell line. These results emphasize the importance of FGFR1-mediated signaling pathways in GBM and reveal that pharmacological inhibition of FGFR1 can enhance the anti-tumoral, anti-angiogenic and anti-metastatic efficiency against GBM. These data support targeting of FGFR1 as a novel anti-angiogenic strategy and highlight the potential of compound 4i as a promising anti-angiogenic and anti-metastatic candidate for GBM therapy.

Pigment Epithelium-Derived Factor, a Novel Adipokine, Contributes to Gestational Diabetes Mellitus.

CONTEXT: Excessive insulin resistance, inadequate insulin compensation, or both could result in gestational diabetes mellitus (GDM). Levels of pigment epithelium-derived factor (PEDF), a novel adipokine that could induce insulin resistance, are high in patients with obesity and diabetes. However, the impact of PEDF in pregnancy remains unknown. OBJECTIVE: This study aimed to elucidate the role of PEDF on insulin resistance and compensatory elevation of insulin levels during normal pregnancy and in patients with GDM. METHODS: In this population-based and cohort study, logistic regression analysis was performed to determine the association of PEDF/adiponectin/leptin levels with the risk of developing GDM and to predict postpartum prediabetes. PEDF protein, PEDF transgenic mice, PEDF knockout mice, and PEDF-neutralized antibodies were used to observe changes in insulin resistance and insulin levels with pregnancy. RESULTS: Plasma PEDF levels were increased in normal pregnancy and higher in GDM women. Higher PEDF levels were associated with the increased risk of developing GDM and emerged as a significant independent determinant of postpartum prediabetes in GDM women. Mechanistically, in vivo and in vitro experiments revealed that PEDF induced insulin resistance by inhibiting the insulin signaling pathway. CONCLUSION: In addition to insulin resistance and upregulated insulin levels in normal pregnancy and GDM, aberrant PEDF levels can serve as a "fingerprint" of metabolic abnormalities during pregnancy. Thus, PEDF is a valuable biomarker but could interfere with the time course for early diagnosis and prognosis of GDM.

Boosting the mono-axial crystal field in stable high-coordinate Dy(III) single-ion magnets by substitution of the phenoxy axial ligand.

Synthesis of air-stable and high-performance single-molecule magnets (SMMs) is challenging. Here, a heptadentate pentapyridyldiamine (BPA-TPA) ligand and fine-tuned axial phenoxy ligands are used to synthesize two triangular dodecahedral Dy(III) complexes [Dy(BPA-TPA)(4-methoxy-PhO)](BPh4)2·3CH2Cl2 (4) and [Dy(BPA-TPA)(2,4-dimethyl-PhO)](BPh4)2·0.85CH2Cl2 (5). Both complexes have high effective barriers exceeding 400 K and magnetic hysteresis up to 8 K, which is ascribed to one strong and short Dy-O bond combined with seven weak Dy-N bonds. Ab initio calculations reveal the thermally activated quantum tunneling of magnetization through the first excited Kramers doublet, due to the presence of a strong axial Dy-O crystal ligand. Substitution of the phenoxy ligand leads to more constrained vibrations, improving the magnetic hysteresis behavior for 5.

Several potential serum proteomic biomarkers for diagnosis of osteoarticular tuberculosis based on mass spectrometry.

BACKGROUND: Osteoarticular tuberculosis is one of the extrapulmonary tuberculosis (EPTB) diseases, which is mainly caused by infection of Mycobacterium tuberculosis (MTB) in bone and joints. The limitation of current clinical test methods is leading to a high misdiagnosis rate and affecting the treatment and prognosis. This study aims to search serum biomarkers that can assist in the diagnosis of osteoarticular tuberculosis. METHODS: Proteomics can serve as an important method in the discovery of disease biomarkers. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze proteins in 90 serum samples, which were collected from June 2020 to December 2021, then evaluated by statistical analysis to screen potential biomarkers. After that, potential biomarkers were validated by enzyme-linked immunosorbent assay (ELISA) and diagnostic models were also established for observation of multi-index diagnostic efficacy. RESULTS: 118 differential expressed proteins (DEPs) were obtained in serum after statistical analysis. After the diagnostic efficacy evaluation and clinical verification, inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2), complement factor H-related protein 2 (CFHR2), complement factor H-related protein 3 (CFHR3), and complement factor H-related protein 5 (CFHR5) were found as potential biomarkers, with 0.7167 (95 %CI: 0.5846-0.8487), 0.8600 (95 %CI: 0.7701-0.9499), 0.8150 (95 %CI: 0.6998-0.9302), and 0.9978 (95 %CI: 0.9918-1.0040) AUC value, respectively. The remaining DEPs except CFHR5 were constructed as diagnostic models, the diagnostic model contained CFHR2 and CFHR3 had good diagnostic efficacy with 0.942 (95 %CI: 0.872-0.980) AUC value compared to other models. CONCLUSION: This study provides a reference for the discovery of serum protein markers for osteoarticular tuberculosis diagnosis, and the screened DEPs can also provide directions for subsequent pathogenesis research.

Venous thromboembolism after spontaneous intracerebral hemorrhage and the status quo of anticoagulation in this population: A retrospective casecontrol study from a tertiary hospital in China.

OBJECTIVE: Patients with spontaneous intracerebral hemorrhage (sICH) are susceptible to venous thromboembolism (VTE) including pulmonary embolism (PE) and deep venous thrombosis (DVT) due to a variety of risk factors. There are few studies regarding the predictive value of D-dimer for VTE in patients with sICH, and the anticoagulation therapy for these patients are still controversial. The objective of this study is to study the independent predictors of VTE in sICH patients. The rates of anticoagulation therapy and hemorrhagic evens were also investigated. METHODS: Retrospective review of patients with sICH admitted to the First Affiliated Hospital of Dalian Medical University from 2012 to 2022 and who developed VTE (PE and/or DVT) during hospitalization. A similar number of sICH patients without VTE were randomly selected into the control group. A variety of clinical characteristics were compared between groups. Univariate and multivariate analyses were performed to identify independent predictors of VTE in patients with sICH. RESULTS: A total of 270 sICH patients were enrolled in this study, including 132 patients with VTE and 138 patients without VTE. After adjusting for other confounders, the maximum level of D-dimer during hospitalization (odds ratio [OR] 1.061, 95 % confidence interval (CI) 1.014-1.110), Glasgow coma scale (GCS) on admission (OR 1.347, 95 % CI 1.110-1.634), modified Rankin Scale (mRS) at discharge (OR 2.578, 95 % CI 1.546-4.298), neutrophil count (OR 1.056, 95 % CI 1.025-1.088) and hospitalization time (OR 1.089, 95 % CI 1.018-1.164) were independently associated with the sICH patients who developed VTE. The maximum D-dimer plasma level of 5.655 mg/L during hospitalization was the optimal threshold to indicate sICH patients developing VTE with a sensitivity of 83.3 % and a specificity of 67.4 %. No patients with sICH received prophylactic anticoagulation therapy against VTE in the present study. A total of 57.6 % (76/132) of the sICH patients with VTE were administered anticoagulant therapy and the rate of hemorrhagic complication was 9.2 %. CONCLUSIONS: sICH patients with increased levels of D-dimer, higher GCS scores, higher mRS scores, increased neutrophil counts and longer hospitalization time are more likely to develop VTE complications. Routine and serial monitoring of the D-dimer values may be useful in patients with sICH, and VTE should be considered when the plasma level of D-dimer increases to 5.655 mg/L during hospitalization. In tertiary hospitals in China, the rate of sICH patients with VTE receiving anticoagulation treatment is low. Further studies are necessary to explore the safety and efficacy of VTE therapeutic anticoagulation in patients with sICH.

Biocompatible Polymer-Modified Nanoplatform for Ferroptosis-Enhanced Combination Cancer Therapy.

Ferroptosis is a novel type of iron-dependent non-apoptotic pathway that regulates cell death and shows unique mechanisms including causing lipid peroxide accumulation, sensitizing drug-resistant cancers, priming immunity by immunogenic cell death, and cooperatively acting with other anticancer modalities for eradicating aggressive malignancies and tumor relapse. Recently, there has been a great deal of effort to design and develop anticancer biocompatible polymeric nanoplatforms including polypeptide and PEGylated ones to achieve effective ferroptosis therapy (FT) and synergistic combination therapies including chemotherapy (CT), photodynamic therapy (PDT), sonodynamic therapy (SDT), photothermal therapy (PTT), gas therapy (GT) including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2 S), and immunotherapy (IT). To be noted, the combo therapies such as FT-CT, FT-PTT, FT-GT, and FT-IT are attracting much efforts to fight against intractable and metastatic tumors as they can generate synergistic antitumor effects and immunogenic cell death (ICD) effects or modulate immunosuppressive tumor microenvironments to initiate strong antitumor immunity and memory effects. The polymeric Fenton nano-agents with good biosafety and high anticancer efficacy will provide a guarantee for their applications. In this review, various biocompatible polymer-modified nanoplatforms designed for FT and combo treatments are summarized for anticancer therapies and discussed for potential clinical transitions.

Deformable hard tissue with high fatigue resistance in the hinge of bivalve Cristaria plicata.

The hinge of bivalve shells can sustain hundreds of thousands of repeating opening-and-closing valve motions throughout their lifetime. We studied the hierarchical design of the mineralized tissue in the hinge of the bivalve Cristaria plicata, which endows the tissue with deformability and fatigue resistance and consequently underlies the repeating motion capability. This folding fan-shaped tissue consists of radially aligned, brittle aragonite nanowires embedded in a resilient matrix and can translate external radial loads to circumferential deformation. The hard-soft complex microstructure can suppress stress concentration within the tissue. Coherent nanotwin boundaries along the longitudinal direction of the nanowires increase their resistance to bending fracture. The unusual biomineral, which exploits the inherent properties of each component through multiscale structural design, provides insights into the evolution of antifatigue structural materials.

Association between Interactions among ACE Gene Polymorphisms and Essential Hypertension in Patients in the Hefei Region, Anhui, China.

Objective: Essential hypertension (EH) is a common cardiovascular disease that endangers human health. Its pathogenesis is complex and has not been fully elucidated. We explore the association between EH and interactions among polymorphisms of the angiotensin converting enzyme (ACE) gene in the Hefei region, Anhui, China. Methods: A total of 500 participants (400 hypertensive and 100 normotensive) were included in this study. The polymorphisms were detected via improved multiple ligase detection reaction (iMLDR). To improve the accuracy of prediction, multifactor dimensionality reduction (MDR) was used to analyze the overall effect of interactions among seven loci on the incidence of EH. Results: The frequencies of polymorphisms in the ACE genes rs12709426, rs4291, rs4309, rs4331, rs4343, rs4459609, and rs4461142 in the EH group were not statistically significantly different from those in the control group. We also found that the single nucleotide polymorphism (SNP) rs12709426 only had a homozygous AA genotype and no polymorphisms. There were no differences in the frequency of genetic polymorphisms between the EH and control groups. The best model explaining the EH group was the combined effect of ACE genes rs4291, rs4309, and rs4461142. Conclusion: There is an interaction effect among ACE gene loci in EH patients in Hefei region, Anhui, China. Also, the ACE gene SNP rs12709426 only has a homozygous AA genotype and does not show an association with EH.