Spatiotemporal trends of hemorrhagic fever with renal syndrome (HFRS) in China under climate variation.

Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease caused by the rodent-transmitted orthohantaviruses (HVs), with China possessing the most cases globally. The virus hosts in China are Apodemus agrarius and Rattus norvegicus, and the disease spread is strongly influenced by global climate dynamics. To assess and predict the spatiotemporal trends of HFRS from 2005 to 2098, we collected historical HFRS data in mainland China (2005-2020), historical and projected climate and population data (2005-2098), and spatial variables including biotic, environmental, topographical, and socioeconomic. Spatiotemporal predictions and mapping were conducted under 27 scenarios incorporating multiple integrated representative concentration pathway models and population scenarios. We identify the type of magistral HVs host species as the best spatial division, including four region categories. Seven extreme climate indices associated with temperature and precipitation have been pinpointed as key factors affecting the trends of HFRS. Our predictions indicate that annual HFRS cases will increase significantly in 62 of 356 cities in mainland China. Rattus regions are predicted to be the most active, surpassing Apodemus and Mixed regions. Eighty cities are identified as at severe risk level for HFRS, each with over 50 reported cases annually, including 22 new cities primarily located in East China and Rattus regions after 2020, while 6 others develop new risk. Our results suggest that the risk of HFRS will remain high through the end of this century, with Rattus norvegicus being the most active host, and that extreme climate indices are significant risk factors. Our findings can inform evidence-based policymaking regarding future risk of HFRS.

Reactive Oxygen-Correlated Photothermal Imaging of Smart COF Nanoreactors for Monitoring Chemodynamic Sterilization and Promoting Wound Healing.

Chemodynamic therapy (CDT) has emerged as a promising approach for treating infected diabetic wounds, while reliable imaging technology for simultaneous monitoring of ROS and therapeutic processes is still a formidable challenge. Herein, smart covalent organic framework (COF) nanoreactors (COF NRs) are constructed by hyaluronic acid (HA) packaged glucose oxidase (GOx) covalently linked Fe-COF for diabetic wound healing. Upon the breakdown of the HA protective layer, GOx consumes glucose to produce gluconic acid and hydrogen peroxide (H2O2), resulting in decreased local pH and H2O2 supplementation. Density functional theory (DFT) calculations show that Fe-COF has high catalytic activity towards H2O2, leading to in situ generation of hydroxyl radicals (·OH) for sterilization, and the localized downregulation of glucose effectively improved the microenvironment of diabetic wounds. Meanwhile, based on the near-infrared photothermal imaging of oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB), the authors showed that TMB can be applied for the point-of-care testing of ·OH and glucose, and assessing the sterilization progress in vivo. More significantly, the facile photothermal signaling strategy can be extended to monitor various ROS-mediated therapeutic systems, enabling accurate prediction of treatment outcomes.

Elevated unphosphorylated STAT1 and IRF9 in T and B cells of primary sjögren's syndrome: Novel biomarkers for disease activity and subsets.

OBJECTIVES: Autoreactive B cells and interferon (IFN) signature are hallmarks of primary sjögren's syndrome (pSS), but how IFN signaling pathways influence autoantibody production and clinical manifestations remain unclear. More detailed studies hold promise for improved diagnostic methodologies and personalized treatment. METHODS: We analyzed peripheral blood T and B cell subsets from 34 pSS patients and 38 healthy donors (HDs) at baseline and upon stimulation regarding their expression levels of type I and II IFN signaling molecules (STAT1/2, IRF1, IRF9). Additionally, we investigated how the levels of these molecules correlated with serological and clinical characteristics and performed ROC analysis. RESULTS: Patients showed elevated IFN pathway molecules, including STAT1, STAT2 and IRF9 among most T and B cell subsets. We found a reduced ratio of phosphorylated STAT1 and STAT2 in patients in comparison to HDs, although B cells from patients were highly responsive by increased phosphorylation upon IFN stimulation. Correlation matrices showed further interrelations between STAT1, IRF1 and IRF9 in pSS. Levels of STAT1 and IRF9 in T and B cells correlated with the IFN type I marker Siglec-1 (CD169) on monocytes. High levels of STAT1 and IRF9 within pSS B cells were significantly associated with hypergammaglobulinemia as well as anti-SSA/anti-SSB autoantibodies. Elevated STAT1 levels were found in patients with extraglandular disease and could serve as a biomarker for this subgroup (p < 0.01). Notably, IRF9 levels in T and B cells correlated with EULAR Sjögren's syndrome disease activity index (ESSDAI). CONCLUSION: Here, we provide evidence that in active pSS patients, enhanced IFN signaling incl. unphosphorylated STAT1 and STAT2 with IRFs entertain chronic T and B cell activation. Furthermore, increased STAT1 levels candidate as biomarker of extraglandular disease, while IRF9 levels can serve as biomarker for disease activity.

Robust, Reproducible, and Scalable Synthesis of Silver Nanocubes.

It remains a challenge to accomplish colloidal synthesis of noble-metal nanocrystals marked by high quality, large quantity, and batch-to-batch consistency. Here we report a self-airtight setup for achieving robust, reproducible, and scalable production of Ag nanocubes with uniform and controlled sizes from 18 to 60 nm. Different from the conventional open-to-air setup, the self-airtight system makes it practical to stabilize the reaction condition by minimizing the loss of volatile reagents. The new setup also allows us to easily optimize the amount of O2 (from air) trapped in the system, ensuring burst nucleation of single-crystal seeds, followed by their slow growth into nanocubes. Most significantly, the new setup allows for the production of Ag nanocubes at gram quantities without sacrificing uniformity, corner/edge sharpness, controlled size, and high purity across different batches. The availability of high-quality Ag nanocubes in such a large quantity is anticipated to substantially boost their use in applications related to plasmonics, catalysis, and biomedicine.

Ambient Synthesis of Porphyrin-Based Fe-Covalent Organic Frameworks for Efficient Infected Skin Wound Healing.

Reactive oxygen species (ROS) have emerged as a promising treatment option for antibacterial and biofilm eradication. However, their therapeutic efficacy is significantly hampered by the unique microenvironments of diabetic wounds. In this study, we designed and synthesized porphyrin-based Fe covalent organic frameworks (Fe-COF) through a Schiff base condensation reaction. Subsequently, Fe-COF were encapsulated with hyaluronic acid (HA) through electrostatic adsorption, resulting in a novel formulation named HA-Fe-COF for diabetic wound healing. HA-Fe-COF were engineered to respond to hyaluronidase in the infected wound, leading to the controlled release of Fe-COF. Those released Fe-COF served a dual role as photosensitizers, generating singlet oxygen and localized heating when exposed to dual light sources. Additionally, they acted as peroxidase-like nanozymes, facilitating the production of ROS through enzymatic reactions. This innovative approach enabled a synergistic therapeutic effect combining photodynamic, photothermal, and chemodynamic modalities. Furthermore, the sustained release of HA from HA-Fe-COF promoted angiogenesis, collagen deposition, and re-epithelialization during the diabetic wound healing process. This "all-in-one" strategy offers a novel approach for the development of antimicrobial and biofilm eradication strategies that minimize damage to healthy tissues in vivo.

Nischarin inhibits the epithelial-mesenchymal transition process and angiogenesis in breast cancer cells by inactivating FAK/ERK signaling pathway via EGF like repeats and discoidin domains 3.

BACKGROUND: Our previous study has demonstrated that Nischarin (NISCH) exerts its antitumor effects in breast cancer (BC) by suppressing cell migration and invasion. This study aims to explore the underlying mechanism through which NISCH functions in BC. METHODS AND RESULTS: The relevance between EGF Like Repeats and Discoidin Domains 3 (EDIL3) mRNA expression and the overall survival of tumor patients was depicted by the Kaplan-Meier curve. The findings revealed that overexpressed NISCH attenuated cell motility and colony-forming capacities of Hs578T cells, yet silenced NISCH in MDA-MB-231 cells led to contrasting results. Western blot (WB) analysis indicated that overexpression of NISCH significantly down-regulated the Vimentin and Slug expression, and inactivated the FAK/ERK signaling pathway. RNA sequencing (RNA-seq) was performed in NISCH-overexpressed Hs578T cells and the control cells to analyze differentially expressed genes (DeGs), and the results showed a significant down-regulation of EDIL3 mRNA level upon overexpression of NISCH. Subsequent functional analyses demonstrated that overexpression of EDIL3 attenuated the inhibitory effect of NISCH on cell migration, invasion, colony formation, and tube formation. CONCLUSION: In summary, our finding preliminarily revealed that NISCH inhibits the epithelial-mesenchymal transition (EMT) process and angiogenesis in BC cells by down-regulating EDIL3 to inactivate the FAK/ERK signaling pathway, thereby suppressing the progression of BC. Our results hold promise for contributing to the deep understanding of BC pathogenesis and identifying new therapeutic strategies for clinical application.

Inflammation-related molecular signatures involved in the anticancer activities of brigatinib as well as the prognosis of EML4-ALK lung adenocarcinoma patient.

Although ALK tyrosine kinase inhibitors (ALK-TKIs) have shown remarkable benefits in EML4-ALK positive NSCLC patients compared to conventional chemotherapy, the optimal sequence of ALK-TKIs treatment remains unclear due to the emergence of primary and acquired resistance and the lack of potential prognostic biomarkers. In this study, we systematically explored the validity of sequential ALK inhibitors (alectinib, lorlatinib, crizotinib, ceritinib and brigatinib) for a heavy-treated patient with EML4-ALK fusion via developing an in vitro and in vivo drug testing system based on patient-derived models. Based on the patient-derived models and clinical responses of the patient, we found that crizotinib might inhibit proliferation of EML4-ALK positive tumors resistant to alectinib and lorlatinib. In addition, NSCLC patients harboring the G1269A mutation, which was identified in alectinib, lorlatinib and crizotinib-resistant NSCLC, showed responsiveness to brigatinib and ceritinib. Transcriptomic analysis revealed that brigatinib suppressed the activation of multiple inflammatory signaling pathways, potentially contributing to its anti-tumor activity. Moreover, we constructed a prognostic model based on the expression of IL6, CXCL1, and CXCL5, providing novel perspectives for predicting prognosis in EML4-ALK positive NSCLC patients. In summary, our results delineate clinical responses of sequential ALK-TKIs treatments and provide insights into the mechanisms underlying the superior effects of brigatinib in patients harboring ALKG1269A mutation and resistant towards alectinib, lorlatinib and crizotinib. The molecular signatures model based on the combination of IL6, CXCL1 and CXCL5 has the potential to predict prognosis of EML4-ALK positive NSCLC patients.

miRTarBase update 2022: an informative resource for experimentally validated miRNA-target interactions.

MicroRNAs (miRNAs) are noncoding RNAs with 18-26 nucleotides; they pair with target mRNAs to regulate gene expression and produce significant changes in various physiological and pathological processes. In recent years, the interaction between miRNAs and their target genes has become one of the mainstream directions for drug development. As a large-scale biological database that mainly provides miRNA-target interactions (MTIs) verified by biological experiments, miRTarBase has undergone five revisions and enhancements. The database has accumulated >2 200 449 verified MTIs from 13 389 manually curated articles and CLIP-seq data. An optimized scoring system is adopted to enhance this update's critical recognition of MTI-related articles and corresponding disease information. In addition, single-nucleotide polymorphisms and disease-related variants related to the binding efficiency of miRNA and target were characterized in miRNAs and gene 3' untranslated regions. miRNA expression profiles across extracellular vesicles, blood and different tissues, including exosomal miRNAs and tissue-specific miRNAs, were integrated to explore miRNA functions and biomarkers. For the user interface, we have classified attributes, including RNA expression, specific interaction, protein expression and biological function, for various validation experiments related to the role of miRNA. We also used seed sequence information to evaluate the binding sites of miRNA. In summary, these enhancements render miRTarBase as one of the most research-amicable MTI databases that contain comprehensive and experimentally verified annotations. The newly updated version of miRTarBase is now available at https://miRTarBase.cuhk.edu.cn/.

Genomic insights into biased allele loss and increased gene numbers after genome duplication in autotetraploid Cyclocarya paliurus.

BACKGROUND: Autopolyploidy is a valuable model for studying whole-genome duplication (WGD) without hybridization, yet little is known about the genomic structural and functional changes that occur in autopolyploids after WGD. Cyclocarya paliurus (Juglandaceae) is a natural diploid-autotetraploid species. We generated an allele-aware autotetraploid genome, a chimeric chromosome-level diploid genome, and whole-genome resequencing data for 106 autotetraploid individuals at an average depth of 60 × per individual, along with 12 diploid individuals at an average depth of 90 × per individual. RESULTS: Autotetraploid C. paliurus had 64 chromosomes clustered into 16 homologous groups, and the majority of homologous chromosomes demonstrated similar chromosome length, gene numbers, and expression. The regions of synteny, structural variation and nonalignment to the diploid genome accounted for 81.3%, 8.8% and 9.9% of the autotetraploid genome, respectively. Our analyses identified 20,626 genes (69.18%) with four alleles and 9191 genes (30.82%) with one, two, or three alleles, suggesting post-polyploid allelic loss. Genes with allelic loss were found to occur more often in proximity to or within structural variations and exhibited a marked overlap with transposable elements. Additionally, such genes showed a reduced tendency to interact with other genes. We also found 102 genes with more than four copies in the autotetraploid genome, and their expression levels were significantly higher than their diploid counterparts. These genes were enriched in enzymes involved in stress response and plant defense, potentially contributing to the evolutionary success of autotetraploids. Our population genomic analyses suggested a single origin of autotetraploids and recent divergence (~ 0.57 Mya) from diploids, with minimal interploidy admixture. CONCLUSIONS: Our results indicate the potential for genomic and functional reorganization, which may contribute to evolutionary success in autotetraploid C. paliurus.

Putting Hybrid Nanomaterials to Work for Biomedical Applications.

Hybrid nanomaterials have found use in many biomedical applications. This article provides a comprehensive review of the principles, techniques, and recent advancements in the design and fabrication of hybrid nanomaterials for biomedicine. We begin with an introduction to the general concept of material hybridization, followed by a discussion of how this approach leads to materials with additional functionality and enhanced performance. We then highlight hybrid nanomaterials in the forms of nanostructures, nanocomposites, metal-organic frameworks, and biohybrids, including their fabrication methods. We also showcase the use of hybrid nanomaterials to advance biomedical engineering in the context of nanomedicine, regenerative medicine, diagnostics, theranostics, and biomanufacturing. Finally, we offer perspectives on challenges and opportunities.

Novel Antioxidant Peptides Identified from Arthrospira platensis Hydrolysates Prepared by a Marine Bacterium Pseudoalteromonas sp. JS4-1 Extracellular Protease.

Crude enzymes produced by a marine bacterium Pseudoalteromonas sp. JS4-1 were used to hydrolyze phycobiliprotein. Enzymatic productions showed good performance on DPPH radical and hydroxyl radical scavenging activities (45.14 ± 0.43% and 65.11 ± 2.64%, respectively), especially small peptides with MWCO <3 kDa. Small peptides were fractioned to four fractions using size-exclusion chromatography and the second fraction (F2) had the highest activity in hydroxyl radical scavenging ability (62.61 ± 5.80%). The fraction F1 and F2 both exhibited good antioxidant activities in oxidative stress models in HUVECs and HaCaT cells. Among them, F2 could upregulate the activities of SOD and GSH-Px and reduce the lipid peroxidation degree to scavenge the ROS to protect Caenorhabditis elegans under adversity. Then, 25 peptides total were identified from F2 by LC-MS/MS, and the peptide with the new sequence of INSSDVQGKY as the most significant component was synthetized and the ORAC assay and cellular ROS scavenging assay both illustrated its excellent antioxidant property.

Multi-scroll attractor and its broken coexisting attractors in cyclic memristive neural network.

This paper proposes a simple-structured memristive neural network, which incorporates self-connections of memristor synapses alongside both unidirectional and bidirectional connections. Different from other multi-scroll chaotic systems, this network structure has a more concise three-neuron structure. This simple memristive neural network can generate a number of multi-scroll attractors in manageable quantities and shows the characteristics of the coexisting attractors and amplitude control. In particular, when the parameters are changed, the coexisting attractors break up around the center of gravity into two centrosymmetric chaotic attractors. Abundant dynamic behaviors are studied through phase portraits, bifurcation diagrams, Lyapunov exponents, and attraction basins. The feasibility of the system is demonstrated by building a circuit realization platform.

Advances of phytotherapy in ischemic stroke targeting PI3K/Akt signaling.

The pathogenesis of ischemic stroke is complex, and PI3K/Akt signaling is considered to play a crucial role in it. The PI3K/Akt pathway regulates inflammation, oxidative stress, apoptosis, autophagy, and vascular endothelial homeostasis after cerebral ischemia; therefore, drug research targeting the PI3K/Akt pathway has become the focus of scientists. In this review, we analyzed the research reports of antiischemic stroke drugs targeting the PI3K/Akt pathway in the past two decades. Because of the rich sources of natural products, increasing studies have explored the value of natural compounds, including Flavonoids, Quinones, Alkaloids, Phenylpropanoids, Phenols, Saponins, and Terpenoids, in alleviating neurological impairment and achieved satisfactory results. Herbal extracts and medicinal formulas have been applied in the treatment of ischemic stroke for thousands of years in East Asian countries. These precious clinical experiences provide a new avenue for research of antiischemic stroke drugs. Finally, we summarize and discuss the characteristics and shortcomings of the current research and put forward prospects for further in-depth exploration.

Intermittent versus continuous control of tracheal cuff pressure in patients undergoing mechanical ventilation: A systematic review and meta-analysis.

AIMS AND OBJECTIVES: To evaluate the effects and safety of intermittent versus continuous control of cuff pressure in patients with mechanical ventilation. BACKGROUND: Tracheal cuff pressure management is vital to the prognosis of patients with mechanical ventilation. DESIGN: A meta-analysis. METHODS: This meta-analysis was conducted and reported according to the PRISMA checklist. We searched Pubmed, Embase, The Cochrane Library, BMJ Best Practice, Web of Science, ProQuest Dissertations, as well as the Chinese Biomedical Literature Database, Wanfang, and China national knowledge infrastructure databases up to 5 August 2022 for randomised controlled trials (RCTs) on the intermittent versus continuous control of cuff pressure. Review Manager 5.3 software was used for relevant data analysis. RESULTS: A total of 18 RCTs involving 1998 patients with mechanical ventilation were included. The synthesised outcomes indicated that continuous control of cuff pressure is beneficial to reduce the incidence of ventilator-associated pneumonia (VAP) [RR = 0.41, 95%CI (0.35, 0.49)], aspiration [RR = 0.36, 95%CI (0.21, 0.63)], duration of mechanical ventilation [MD = -3.23, 95%CI (-4.66, -1.79)], length of ICU stay [MD = -4.12, 95%CI (-5.40, -2.83)], and increase the volume of subglottic drainage [MD = 18.54, 95%CI (16.50, 20.58)]. There was no significant difference in the mortality between two groups [RR = 1.01, 95%CI (0.84, 1.21)]. Egger regression analyses showed that there were no obvious publication biases in the synthesised results (all p > .05). CONCLUSIONS: Existing evidence shows that compared with intermittent monitoring of cuff pressure, continuous monitoring of cuff pressure can reduce the occurrence of aspiration and VAP, shorten the patient's duration of mechanical ventilation and length of ICU stay. RELEVANCE TO CLINICAL PRACTICE: Continuous monitoring of cuff pressure is more beneficial and should be promoted in clinical nursing care of patients undergoing mechanical ventilation.

Characteristics and Application of a Novel Cold-Adapted and Salt-Tolerant Protease EK4-1 Produced by an Arctic Bacterium Mesonia algae K4-1.

Mesonia algae K4-1 from the Arctic secretes a novel cold-adapted and salt-tolerant protease EK4-1. It has the highest sequence similarity with Stearolysin, an M4 family protease from Geobacillus stearothermophilus, with only 45% sequence identity, and is a novel M4 family protease. Ek4-1 has a low optimal catalytic temperature (40 °C) and is stable at low temperatures. Moreover, EK4-1 is still active in 4 mol/L NaCl solution and is tolerant to surfactants, oxidizing agents and organic solvents; furthermore, it prefers the hydrolysis of peptide bonds at the P1' position as the hydrophobic residues, such as Leu, Phe and Val, and amino acids with a long side chain, such as Phe and Tyr. Mn2+and Mg2+ significantly promoted enzyme activity, while Fe3+, Co+, Zn2+ and Cu2+ significantly inhibited enzyme activity. Amino acid composition analysis showed that EK4-1 had more small-side-chain amino acids and fewer large-side-chain amino acids. Compared with a thermophilic protease Stearolysin, the cold-adapted protease EK4-1 contains more random coils (48.07%) and a larger active pocket (727.42 Å3). In addition, the acidic amino acid content of protease EK4-1 was higher than that of the basic amino acid, which might be related to the salt tolerance of protease. Compared with the homologous proteases EB62 and E423, the cold-adapted protease EK4-1 was more efficient in the proteolysis of grass carp skin, salmon skin and casein at a low temperature, and produced a large number of antioxidant peptides, with DPPH, ·OH and ROO· scavenging activities. Therefore, cold-adapted and salt-tolerant protease EK4-1 offers wide application prospects in the cosmetic and detergent industries.

Characteristics and potential functional effects of long insertions in Asian butternuts.

BACKGROUND: Structural variants (SVs) play important roles in adaptation evolution and species diversification. Especially, in plants, many phenotypes of response to the environment were found to be associated with SVs. Despite the prevalence and significance of SVs, long insertions remain poorly detected and studied in all but model species. RESULTS: We used whole-genome resequencing of paired reads from 80 Asian butternuts to detect long insertions and further analyse their characteristics and potential functional effects. By combining of mapping-based and de novo assembly-based methods, we obtained a multiple related species pangenome representing higher taxonomic groups. We obtained 89,312 distinct contigs totaling 147,773,999 base pair (bp) of new sequences, of which 347 were putative long insertions placed in the reference genome. Most of the putative long insertions appeared in multiple species; in contrast, only 62 putative long insertions appeared in one species, which may be involved in the response to the environment. 65 putative long insertions fell into 61 distinct protein-coding genes involved in plant development, and 105 putative long insertions fell into upstream of 106 distinct protein-coding genes involved in cellular respiration. 3,367 genes were annotated in 2,606 contigs. We propose PLAINS ( https://github.com/CMB-BNU/PLAINS.git ), a streamlined, comprehensive pipeline for the prediction and analysis of long insertions using whole-genome resequencing. CONCLUSIONS: Our study lays down an important foundation for further whole-genome long insertion studies, allowing the investigation of their effects by experiments.

Association of anti-TNF-α treatment with gut microbiota of patients with ankylosing spondylitis.

OBJECTIVE: Gut dysbiosis contributes to multiple autoimmune diseases, including ankylosing spondylitis, which is commonly treated with tumor necrosis factor (TNF)-α inhibitors (TNFis). Because host TNF-α levels are considered to interact with gut microbiota, we aimed to systematically investigate the microbiota profile of ankylosing spondylitis patients with anti-TNF-α-based treatment and identify potential key bacteria. METHODS: Fecal samples were collected from 11 healthy controls and 24 ankylosing spondylitis patients before/after anti-TNF-α treatment, the microbiota profiles of which were evaluated by 16S ribosomal DNA amplicon sequencing and subsequent bioinformatic analysis. RESULTS: Significantly different microbial compositions were observed in samples from ankylosing spondylitis patients compared with healthy controls, characterized by a lower abundance of short-chain fatty acid (SCFA)-producing bacteria. All patients exhibited a positive response after anti-TNF-α treatment, accompanied by a trend of restoration in the microbiota compositions and functional profile of ankylosing spondylitis patients to healthy controls. In particular, the abundance of SCFA-producing bacteria (e.g. Megamonsa and Lachnoclostridium ) was not only significantly lower in ankylosing spondylitis patients than in healthy controls and restored after anti-TNF-α treatment but also negatively correlated with disease severity (e.g. cor = -0.52, P = 8 × 10 -5 for Megamonsa ). In contrast, Bacilli and Haemophilus may contribute to ankylosing spondylitis onset and severity. CONCLUSIONS: Microbiota dysbiosis in ankylosing spondylitis patients can be restored after anti-TNF-α treatment, possibly by impacting SCFA-producing bacteria.

The effect of prophylactic balloon occlusion in patients with placenta accreta spectrum: a Bayesian network meta-analysis.

OBJECTIVES: Placenta accreta spectrum (PAS) can induce severe life-threatening obstetric hemorrhage. Herein, we conducted a Bayesian network meta-analysis of previous studies to evaluate the relative benefits of different prophylactic balloon occlusion (PBO) procedures. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to July 2021. Blood loss volume, blood transfusion volume, and hysterectomy rate were regarded as the primary endpoints. The data were pooled using a Bayesian network and traditional pairwise meta-analysis. RESULTS: Fifty-nine articles with a total sample size of 5150 patients were included. Compared with no PBO (non-PBO) intervention, PBO of the abdominal aorta (PBOAA, mean difference(MD) - 1.02, 95% credible interval (CrI) - 1.4 to - 0.67), common iliac artery (PBOCIA, MD - 0.84; 95%CrI - 1.36 to - 0.06) and internal iliac artery (PBOIIA, MD - 0.42; 95%CrI - 0.72 to - 0.13) significantly lowered blood loss volume, with PBOAA being more effective than PBOIIA (MD - 0.60; 95%CrI - 1.05 to - 0.17). PBOAA and PBOIIA also significantly decreased blood loss volume (MD - 2.33; 95%CrI - 3.74 to - 0.94, MD - 1.57; 95%CrI - 2.77 to - 0.47 respectively) and hysterectomy rate (OR 0.31; 95%CrI 0.16 to 0.54, OR 0.53; 95%CrI 0.29 to 0.92 respectively). PBOAA has the highest probability of being more effective in reducing the blood loss volume, blood transfusion volume, and hysterectomy rate. CONCLUSIONS: Performing PBOAA, PBOCIA, or PBOIIA in PAS patients is an effective way to minimize blood loss volume, while PBOAA and PBOIIA also reduce blood transfusion volume and hysterectomy rate. PBOAA is a notably more effective strategy to reduce blood loss volume than PBOIIA. KEY POINTS: • PBOAA, PBOCIA, and PBOIIA procedures can significantly reduce the blood loss volume compared to non-PBO intervention in PAS patients, of which PBOAA was more effective than the PBOIIA procedure. • PBOAA and PBOIIA could significantly reduce the blood transfusion volume and hysterectomy rate in contrast to the non-PBO intervention in patients with PAS. • According to our statistical treatment ranking, PBOAA was statistically superior in reducing blood transfusion volume, blood transfusion volume, and hysterectomy rate than other PBO procedures.

Homochiral Chemistry Strategy To Trigger Dielectric Switching and Second-Harmonic Generation Response on Spirocyclic Derivatives.

Organic-inorganic hybrid materials with switchable properties have significant potential applications in intelligent devices. There are some conventional ways to obtain optical and/or electric multiple responses, such as asymmetric design, chirality, doping, and structural dimension in hybrid materials. Among them, the homochirality strategy is one of the best ways to regulate the molecular structure and symmetry, thereby ensuring second-harmonic generation (SHG) and dielectric dual response characteristics. Here, we report a homochiral design strategy to obtain noncentrosymmetric [R-(HASD)][Cd(SCN)3] (HASD = 7-hydroxy-5-azaspiro[4.5]decan) and [S-(HASD)][Cd(SCN)3]; [Rac-(HASD)][Cd(SCN)3] was also synthesized as a comparative experiment to illustrate the relationship between structural chirality and physical properties. With the help of homochiral regulation, the SHG response is excited and dielectric phase transition temperature (Tc) is also highly improved. In addition, both the optical SHG and dielectric phase change show an optical/electric switchable response. This work is of great significance for the further exploration of multifunctional molecular switching materials through homochiral chemistry.

Solid lipid nanoparticles as a drug delivery system to across the blood-brain barrier.

Solid lipid nanoparticles (SLNs) were prepared by biocompatible and biodegradable solid-phase lipids. ß-elemene is a safe natural essential oil with broad-spectrum anti-tumor activity. However, its clinical application has been adversely affected by its poor water solubility and limited bioavailability. SLN incorporation is a potential strategy to bypass the blood-brain barrier, the most important factor limiting the bioactivity of neurotherapeutics. The SLNs-ß has the same efficacy as commercially available elemene in vitro and an enhanced brain drug accumulation in vivo. The survival rate data was promising and acute toxicity experiment proved its safety. All these data suggested that SLN-ß is a safe and effective drug delivery system, especially for brain tumor therapy, and warrants further development.