Intervention of hypertension by acupuncture-related therapies: A network meta-analysis.

BACKGROUND: The prevalence of essential hypertension contributed significantly to morbidity and mortality rates. Acupuncture-related therapies were commonly employed in hypertension treatment. Nevertheless, a lack of conclusive evidence left uncertainties regarding the optimal strategies for managing hypertensive populations. OBJECTIVES: Conduct a comprehensive systematic review to evaluate the existing clinical evidence about the effectiveness of acupuncture and moxibustion-related therapies in managing hypertension, by employing network meta-analysis techniques. METHODS: A comprehensive electronic search was conducted across n of databases. This search covered studies available up to October 2022. Randomized controlled trials assessing acupuncture and moxibustion-related therapies in managing hypertension based on traditional Chinese medicine were screened. Primary outcome measures included the antihypertensive effectiveness rate, variations in blood pressure and the incorporation of Traditional Chinese Medicine (TCM) syndrome manifestations. The review follows the guidelines outlined in the PRISMA statement. RESULTS: We identified a total of 24 trials with 1867 patients, which evaluated the efficacy of various acupuncture-related therapies for hypertension management. Network meta-analysis showed that moxibustion and auricular point sticking combined with medication therapy had the best effect in terms of antihypertensive effective rate (medication + moxibustion + auricular pressure vs. medication = 1.29 [1.09, 1.54]; sucra = 85.9, p < .05) and hypertension symptom improvement (medication + moxibustion + auricular pressure vs. medication = -1.55 [-2.98, -0.13]; sucra = 96.1, p < .05). Acupuncture combined with moxibustion combined with medication therapy had the best effect in reducing systolic pressure (medication + moxibustion + acupuncture vs. medication = -8.50 [-10.19, -6.80]; sucra = 100, p < .05) and diastolic blood pressure (medication + moxibustion + acupuncture versus medication = -4.72 [-6.71, -2.72]; sucra = 99.71, p < 0.05). CONCLUSIONS: Network meta-analysis suggested that the combined use of moxibustion and auricular point application in conjunction with drug therapy showed the highest likelihood of being the most effective treatment in terms of antihypertensive efficiency rates and improvement in hypertension symptoms. Furthermore, the combination of acupuncture and moxibustion alongside drug treatment emerged as the most promising approach for reducing systolic blood pressure and diastolic blood pressure. Limited by the methodological quality and quantity of the included studies, the results need to be interpreted with caution. It is necessary to conduct more high-quality randomized controlled trials of acupuncture-related therapies for the adjuvant treatment of hypertension in the future. IMPLICATIONS FOR PRACTICE: Clinicians can use acupuncture-related therapies to inform their treatment decisions and potentially incorporate acupuncture-related therapies into their hypertension management protocols.

In Situ Hydrogel Modulates cDC1-Based Antigen Presentation and Cancer Stemness to Enhance Cancer Vaccine Efficiency.

Effective presentation of antigens by dendritic cells (DC) is essential for achieving a robust cytotoxic T lymphocytes (CTLs) response, in which cDC1 is the key DC subtype for high-performance activation of CTLs. However, low cDC1 proportion, complex process, and high cost severely hindered cDC1 generation and application. Herein, the study proposes an in situ cDC1 recruitment and activation strategy with simultaneous inhibiting cancer stemness for inducing robust CTL responses and enhancing the anti-tumor effect. Fms-like tyrosine kinase 3 ligand (FLT3L), Poly I:C, and Nap-CUM (NCUM), playing the role of cDC1 recruitment, cDC1 activation, inducing antigen release and decreasing tumor cell stemness, respectively, are co-encapsulated in an in situ hydrogel vaccine (FP/NCUM-Gel). FP/NCUM-Gel is gelated in situ after intra-tumoral injection. With the near-infrared irradiation, tumor cell immunogenic cell death occurred, tumor antigens and immunogenic signals are released in situ. cDC1 is recruited to tumor tissue and activated for antigen cross-presentation, followed by migrating to lymph nodes and activating CTLs. Furthermore, tumor cell stemness are inhibited by napabucasin, which can help CTLs to achieve comprehensive tumor killing. Collectively, the proposed strategy of cDC1 in situ recruitment and activation combined with stemness inhibition provides great immune response and anti-tumor potential, providing new ideas for clinical tumor vaccine design.

Computational Insights into the Catalysis of the pH Dependence of Bromite Decomposition Catalyzed by Chlorite Dismutase from Dechloromonas aromatica (DaCld).

The heme-containing chlorite dismutases catalyze the rapid and efficient decomposition of chlorite (ClO2-) to yield Cl- and O2, and the catalytic efficiency of chlorite dismutase from Dechloromonas aromatica (DaCld) in catalyzing the decomposition of bromite (BrO2-) was dependent on pH, which was supposed to be caused by the conversion of active Cpd I to the inactive Cpd II by proton-coupled electron transfer (PCET) from the pocket Tyr118 to the propionate side chain of heme at high pH. However, the direct evidence of PCET and how the pH affects the efficiency of DaCld, as well as whether Cpd II is really inactive, are still poorly understood. Here, on the basis of the high-resolution crystal structures, the computational models in both acidic (pH 5.0) and alkaline (pH 9.0) environments were constructed, and a series of quantum mechanical/molecular mechanical calculations were performed. On the basis of our calculation results, the O-Br bond cleavage of BrO2- always follows the homolytic mode to generate Cpd II rather than Cpd I. It is different from the O-O cleavage of O2/H2O2 or peracetic acid catalyzed by the other heme-containing enzymes. Thus, in the subsequent O-O rebound reaction, it is the Fe(IV)═O in Cpd II that combines with the O-Br radical. Because the porphyrin ring in Cpd II does not bear an unpaired electron, the previously suggested PCET from Tyr118 to the propionate side chain of heme was not theoretically recognized in an alkaline environment. In addition, the O-O rebound step in an alkaline solution corresponds to an energy barrier that is larger than that in an acidic environment, which can well explain the pH dependence of the activity of DaCld. In addition, the protonation state of the propionic acid side chains of heme and the surrounding hydrogen bond networks were calculated to have a significant impact on the barriers of the O-O rebound step, which is mainly achieved by affecting the reactivity of the Fe(IV)═O group in Cpd II. In an acidic environment, the relatively weaker coordination of the O2 atom to Fe leads to its higher reactivity toward the O-O rebound reaction. These observations may provide useful information for understanding the catalysis of chlorite dismutases.

Advances in molecularly imprinted materials for selective adsorption of phenolic pollutants from the water environment: Synthesis, applications, and improvement.

The application of molecularly imprinted material (MIM) is widely employed as a material for removing phenolic pollutants from the water environment, owing to its exceptional capacity for selective adsorption and high sensitivity. In this paper, the preparation principle, bonding types, and preparation methods of MIM have been comprehensively introduced. Meanwhile, according to the binding type of MIM with phenolic pollutants, three categories of hydroxyl bonding, hydroxyl carboxyl bonding, and hydroxyl nitro bonding were carried out to explain its application to phenolic pollutants. Strategies for addressing the challenges of selective instability, high regeneration costs, and template leakage in MIM applications were summarized. These strategies encompassed the introduction of superior carriers, enhancements in preparation processes, and the utilization of molecular dynamics simulation-assisted technology. Finally, the prospects in the three aspects of material preparation, process coupling, and recycling. In summary, this paper has demonstrated the potential of utilizing MIM for the selective treatment of phenolic pollutants from the water environment.

Optimizing carbon sources regulation in the biochemical treatment systems for coal chemical wastewater: Aromatic compounds biodegradation and microbial response strategies.

The complex composition of coal chemical wastewater (CCW), marked by numerous highly toxic aromatic compounds, induces the destabilization of the biochemical treatment system, leading to suboptimal treatment efficacy. In this study, a biochemical treatment system was established to efficiently degrade aromatic compounds by quantitatively regulating the dosage of co-metabolized substrates (specifically, the chemical oxygen demand (COD) Glucose: COD Sodium acetate = 3:1, 1:3, and 1:1). The findings demonstrated that the system achieved optimal performance under the condition that the ratio of COD Glucose to COD Sodium acetate was 3:1. When the co-metabolized substrate was added to the system at an optimal ratio, examination of pollutant removal and cumulative effects revealed that the removal efficiencies for COD and total organic carbon (TOC) reached 94.61 % and 86.40 %, respectively. The removal rates of benzene series, nitrogen heterocyclic compounds, polycyclic aromatic hydrocarbons, and phenols were 100 %, 100 %, 63.58 %, and 94.12 %, respectively. Research on the physiological response of microbial cells showed that, under optimal ratio regulation, co-metabolic substrates led to a substantial rise in microbial extracellular polymeric substances (EPS) secretion, particularly extracellular proteins. When the system reached the end of its operation, the contents of loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS) for proteins in the optimal group were 7.12 mg/g-SS and 152.28 mg/g-SS, respectively. Meanwhile, the ratio of α-Helix / (ß-Sheet + Random coil) and the proportion of intermolecular interaction forces were also increased in the optimal group. At system completion, the ratio of α-Helix / (ß-Sheet + Random coil) reached 0.717 (LB-EPS) and 0.618 (TB-EPS), respectively. Additionally, the proportion of intermolecular interaction forces reached 74.83 % (LB-EPS) and 55.03 % (TB-EPS). An in-depth analysis of the metabolic regulation of microorganisms indicated that the introduction of optimal ratios of co-metabolic substrates contributed to a noteworthy upregulation in the expression of Catechol 2,3-dioxygenase (C23O) and Dehydrogenase (DHA). The expression levels of C23O and DHA were measured at 0.029 U/mg Pro·g MLSS and 75.25 mg TF·(g MLSS·h)-1 (peak value), respectively. Correspondingly, enrichment of aromatic compound-degrading bacteria, including Thauera, Saccharimonadales, and Candidatus_Competibacter, occurred, along with the upregulation of associated functional genes such as Catechol 1,2-dioxygenase, Catechol 2,3-dioxygenase, Protocatechuate 3,4-dioxygenase, and Protocatechuate 4,5-dioxygenase. Considering the intricate system of multiple coexisting aromatic compounds in real CCW, this study not only obtained an optimal ratio for carbon source addition but also enhanced the efficient utilization of carbon sources and improved the capability of the system to effectively degrade aromatic compounds. Additionally, this paper established a theoretical foundation for metabolic regulation and harmless treatment within the biochemical treatment of intricate systems, exemplified by real CCW.

Vertical differences in carbon metabolic diversity and dominant flora of soil bacterial communities in farmlands.

The carbon cycle in soil is significantly influenced by soil microbes. To investigate the vertical distribution of the dominant groups in agricultural soil and the carbon metabolic diversity of soil bacteria, 45 soil samples from the 0 ~ 50 cm soil layer in Hunan tobacco-rice multiple cropping farmland were collected in November 2017, and the carbon diversity of the soil bacterial community, bacterial community composition and soil physical and chemical properties were determined. The results showed that the carbon metabolic capabilities and functional diversity of the soil bacterial community decreased with depth. The three most widely used carbon sources for soil bacteria were carbohydrates, amino acids, and polymers. The dominant bacterial groups in surface soil (such as Chloroflexi, Acidobacteriota, and Bacteroidota) were significantly positively correlated with the carbon metabolism intensity. The alkali-hydrolysable nitrogen content, soil bulk density and carbon-nitrogen ratio were the key soil factors driving the differences in carbon metabolism of the soil bacterial communities in the different soil layers.

Computational insights into the binding modes, keto-enol tautomerization and stereo-electronically controlled decarboxylation of oxaloacetate in the active site of macrophomate synthase.

Oxaloacetic acid (OAA) is a ß-ketocarboxylic acid, which plays an important role as an intermediate in some metabolic pathways, including the tricarboxylic acid cycle, gluconeogenesis and fatty acid biosynthesis. Animal studies have indicated that supplementing oxaloacetic acid shows an increase of lifespan and other substantial health benefits including mitochondrial DNA protection, and protection of retinal, neural and pancreatic tissues. Most of the chemical transformations of OAA in the metabolic pathways have been extensively studied; however, the understanding of decarboxylation of OAA at the atomic level is relatively lacking. Here, we carried out MD simulations and combined quantum mechanical/molecular mechanical (QM/MM) calculations as an example to systematically elucidate the binding modes, keto-enol tautomerization and decarboxylation of OAA in the active site of macrophomate synthase (MPS), which is a Mg(II)-dependent bifunctional enzyme that catalyzes both the decarboxylation of OAA and [4+2] cycloaddition of 2-pyrone with the decarboxylated intermediate of OAA (pyruvate enolate). On the basis of our calculations, it was found that the Mg2+-coordinated oxaloacetate may exist in enol forms and keto forms. The four keto forms can be transformed into each other by simply rotating the C2-C3 single bond, nevertheless, the keto-enol tautomerization strictly requires the assistance of pocket water molecules. In addition, the decarboxylation is stereo-electronically controlled, i.e., it is the relative orientation of the terminal carboxyl anion that determines the rate of decarboxylation. As such, the chemistry of oxaloacetate in the active site of MPS is complex. On one hand, the most stable binding mode (K-I) may undergo enol-keto tautomerization to isomerize to the enol form, which may further react with the second substrate; on the other hand, K-I may isomerize to another binding mode K-II to proceed decarboxylation to generate pyruvate enolate and CO2. Starting from K-I, the enol-keto tautomerization corresponds to a barrier of 16.2 kcal mol-1, whereas the decarboxylation is associated with an overall barrier of 19.7 kcal mol-1. These findings may provide useful information for understanding the chemistry of OAA and the catalysis of related enzymes, and they are basically in agreement with the available experimental kinetic data.

Self-delivery photothermal-boosted-nanobike multi-overcoming immune escape by photothermal/chemical/immune synergistic therapy against HCC.

Immune checkpoint inhibitors (ICIs) combined with antiangiogenic therapy have shown encouraging clinical benefits for the treatment of unresectable or metastatic hepatocellular carcinoma (HCC). Nevertheless, therapeutic efficacy and wide clinical applicability remain a challenge due to "cold" tumors' immunological characteristics. Tumor immunosuppressive microenvironment (TIME) continuously natural force for immune escape by extracellular matrix (ECM) infiltration, tumor angiogenesis, and tumor cell proliferation. Herein, we proposed a novel concept by multi-overcoming immune escape to maximize the ICIs combined with antiangiogenic therapy efficacy against HCC. A self-delivery photothermal-boosted-NanoBike (BPSP) composed of black phosphorus (BP) tandem-augmented anti-PD-L1 mAb plus sorafenib (SF) is meticulously constructed as a triple combination therapy strategy. The simplicity of BPSP's composition, with no additional ingredients added, makes it easy to prepare and presents promising marketing opportunities. (1) NIR-II-activated BPSP performs photothermal therapy (PTT) and remodels ECM by depleting collagen I, promoting deep penetration of therapeutics and immune cells. (2) PTT promotes SF release and SF exerts anti-vascular effects and down-regulates PD-L1 via RAS/RAF/ERK pathway inhibition, enhancing the efficacy of anti-PD-L1 mAb in overcoming immune evasion. (3) Anti-PD-L1 mAb block PD1/PD-L1 recognition and PTT-induced ICD initiates effector T cells and increases response rates of PD-L1 mAb. Highly-encapsulated BPSP converted 'cold' tumors into 'hot' ones, improved CTL/Treg ratio, and cured orthotopic HCC tumors in mice. Thus, multi-overcoming immune escape offers new possibilities for advancing immunotherapies, and photothermal/chemical/immune synergistic therapy shows promise in the clinical development of HCC.

Discovery of anti-inflammatory agents from 3, 4-dihydronaphthalene-1(2H)-one derivatives by inhibiting NLRP3 inflammasome activation.

NLRP3 inflammatory vesicles are a polymer of cellular innate immunity composed of a pair of proteins. The continuous activation of NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammatory vesicles induces the occurrence and enhancement of inflammatory response. In this study, a series of 3, 4-dihydronaphthalene-1(2H)-one derivatives (DHNs, 6a-u, 7a-e, 8a-n) were synthesized and characterized by NMR and HRMS. We evaluated the cytotoxicity and anti-inflammatory activity of all compounds in vitro, and selected 7a substituted by 7-Br in A-ring and 2-pyridylaldehyde in C-ring as effective lead compounds. Specifically, 7a can block the assembly and activation of NLRP3 inflammasome by down-regulating the expression of NLPR3 and apoptosis-associated speck-like protein containing a CARD (ASC), and inhibiting the production of reactive oxygen species (ROS) and other inflammatory mediators. In addition, 7a inhibits the phosphorylation of inhibitor kappa B alpha (IκBα) and NF-κB/p65 and the nuclear translocation of p65, thereby inhibiting nuclear factor kappa-B (NF-κB) signaling. Molecular docking analysis confirmed that 7a could reasonably bind the active sites of NLRP3, ASC and p65 proteins. Therefore, 7a is predicted as a potential NLRP3 inflammatory vesicle inhibitor and deserves further research and development.

Population pharmacokinetics of cyclosporine A in pediatric patients with thalassemia undergoing allogeneic hematopoietic stem cell transplantation.

PURPOSE: To establish the population pharmacokinetics (PPK) model of cyclosporine A(CsA) in pediatric patients with thalassemia undergoing allogeneic hematopoietic stem cell transplantation (HSCT), aiming at providing a reference for clinical dose individualization of CsA. METHODS: Children with thalassemia who underwent allogeneic HSCT were enrolled retrospectively. The PPK structural model and the random variable model of CsA were established on NONMEN. And goodness of fit plots (GOFs), visual predictive check (VPC), and bootstrap and normalized prediction distribution errors (NPDE) were used to evaluate the final model. RESULTS: A one-compartment model with first-order absorption was employed to fit the base model. A total of 74 pediatric patients and 600 observations of whole blood concentration were included. The final model included weight (WT) in clearance (CL), alongside post-operative day (POD), fluconazole (FLUC), voriconazole (VORI), posaconazole (POSA), and red blood cell count (RBC) significantly. All the model evaluations were passed. CONCLUSION: In the PPK model based on the pediatric cohort on CsA with thalassemia undergoing allogeneic HSCT, WT, POD, FLUC, VORI, POSA, and RBC were found to be the significant factors influencing CL of CsA. The reliability and robustness of the final model were excellent. It is expected that the PPK model can assist in individualizing dosing strategy clinically.

Multiscale Study on the Intramolecular C-S Bond Formation Catalyzed by P450 Monooxygenase CxnD Involved in the Biosynthesis of Chuangxinmycin: The Critical Roles of Noncrystal Water Molecule and Conformational Change.

Cytochrome P450 monooxygenase CxnD catalyzes intramolecular C-S bond formation in the biosynthesis of chuangxinmycin, which is representative of the synthesis of sulfur-containing natural heterocyclic compounds. The intramolecular cyclization usually requires the activation of two reaction sites and a large conformational change; thus, illuminating its detailed reaction mechanism remains challengeable. Here, the reaction pathway of CxnD-catalyzed C-S bond formation was clarified by a series of calculations, including Gaussian accelerated molecular dynamics simulations and quantum mechanical-molecular mechanical calculations. Our results revealed that the C-S formation follows a diradical coupling mechanism. CxnD first employs Cpd I to abstract the hydrogen atom from the imino group of the indole ring, and then, the resulted Cpd II further extracts another hydrogen atom from the thiol group of the side chain to afford a diradical intermediate, in which a noncrystal water molecule entering into the active site after the formation of Cpd I was proved to play an indispensable role. Moreover, the diradical intermediate cannot directly perform the coupling reaction. It should first undergo a series of conformational changes leading to the proximity of two reaction sites. It is the flexibility of the active site of the enzyme and the side chain of the substrate that makes the diradical coupling to be successful.

Multiplex Aptamer-Based Fluorescence Assay Using Magnetism-Encoded Nanoparticles for Simultaneous Detection of Multiple Pathogenic Bacteria.

Multiplex assay has emerged as a robust and versatile method for the simultaneous detection of multiple analytes in a single test. However, challenges in terms of poor accuracy and complexity remained. In this work, we developed a multiplex aptamer-based fluorescence assay using magnetism-encoded nanoparticles for the simultaneous detection of multiple pathogenic bacteria. The encapsulation of different amounts of Fe3O4 nanoparticles in zeolitic imidazolate framework-90 (ZIF-90) leads to the formation of Fe3O4@ZIF-90 (FZ) composites with distinct magnetism strengths. By functionalizing a specific aptamer on the surface of the FZ composites, target bacteria can be specifically and precisely separated from a mixed sample in a sequential manner. This property allows for the simultaneous quantitative analysis of multiple target bacteria by using a single-color fluorescence label, thereby resulting in minimal spectral crosstalk interference and improved accuracy. The successful determination of multiple bacteria in contaminated milk samples demonstrates the applicability of this multiplex assay in complex biological matrices. Compared to conventional multiplex fluorescence assays, this approach offers distinct advantages of simplicity, efficiency, and implementation. We believe that this study can provide valuable insights into the development of the multiplex assay while introducing a new method for the simultaneous detection of multiple bacteria.

Quantitative Analysis of Resistance to Deformation of the DNA Origami Framework Supported by Struts.

Nanostructures with controlled shapes are of particular interest due to their consistent physical and chemical properties and their potential for assembly into complex superstructures. The use of supporting struts has proven to be effective in the construction of precise DNA polyhedra. However, the influence of struts on the structure of DNA origami frameworks on the nanoscale remains unclear. In this study, we developed a flexible square DNA origami (SDO) framework and enhanced its structural stability by incorporating interarm supporting struts (SDO-s). Comparing the framework with and without such struts, we found that SDO-s demonstrated a significantly improved resistance to deformation. We assessed the deformability of these two DNA origami structures through the statistical analysis of interior angles of polygons based on atomic force microscopy and transmission electron microscopy data. Our results showed that SDO-s exhibited more centralized interior angle distributions compared to SDO, reducing from 30-150° to 60-120°. Furthermore, molecular dynamics simulations indicated that supporting struts significantly decreased the thermodynamic fluctuations of the SDO-s, as described by the root-mean-square fluctuation parameter. Finally, we experimentally demonstrated that the 2D arrays assembled from SDO-s exhibited significantly higher quality than those assembled from SDO. These quantitative analyses provide an understanding of how supporting struts can enhance the structural integrity of DNA origami frameworks.

Distribution characteristics, source analysis and risk assessment of polycyclic aromatic hydrocarbons in sediments of Kuye River: a river in a typical energy and chemical industry zone.

This study systematically analyzed the distribution characteristics, sources, and ecological risk of polycyclic aromatic hydrocarbons (PAHs) in Kuye River sediments, located in an energy and chemical industry base in northern Shaanxi, China. The results that revealed the concentrations of 16 PAHs in the sediment ranged from 1090.04 to 32,175.68 ng∙g-1 dw, with the four-ring PAHs accounting for the highest proportion. Positive matrix factorization analysis (PMF) revealed the main sources of PAHs as incomplete fossil fuel combustion, biomass combustion, and traffic emissions. The total toxic equivalent concentration of BaP, risk quotient, and lifetime carcinogenic risk of PAHs suggested moderate to high contamination of PAHs in the area. The higher incremental lifetime carcinogenic risk (ILCR) indicated that PAH ingestion was the primary route of impact on public health, with children potentially being more susceptible to PAH exposure. This study can provide valuable theoretical support for implementing pollution prevention measures and ecological restoration strategies for rivers in energy and chemical industry areas.

Phosphatase, Mg2+/Mn2+ dependent 1B regulates the hematopoietic stem cells homeostasis via the Wnt/ß-catenin signaling.

Hematopoietic stem cells (HSCs) are primarily dormant in a cell-cycle quiescence state to preserve their self-renewal capacity and long-term maintenance. How HSCs maintain the balance between activation and quiescence remains largely unknown. Herein, we found that Phosphatase, Mg2+/Mn2+ Dependent 1B (Ppm1b) is required for the expansion of phenotypic HSCs in vitro. By using a conditional knockout mouse model in which Ppm1b was specifically depleted in hematopoietic cells, we demonstrated that loss of Ppm1b impaired the HSC homeostasis and hematopoietic reconstitution. Ppm1b deficiency mice also exhibited B-cell leukocytopenia, which is due to the compromised commitment and proliferation of B-biased lymphoid progenitor cells from CLPs. With the aid of a small molecular inhibitor, we confirmed the roles of Ppm1b in adult hematopoiesis that phenocopied the effects with loss of Ppm1b. Furthermore, transcriptome profiling of Ppm1b-deficient HSCs revealed the disruptive quiescence of HSC. Mechanistically, Ppm1b interacted with ß-catenin and mediated its dephosphorylation. Loss of Ppm1b led to the decrease of the active ß- catenin (non-phosphorylated) that interrupted the Wnt/ß-catenin signaling in HSC, which consequently suppressed HSC expansion. Together, our study identified an indispensable role of Ppm1b in regulating HSC homeostasis via Wnt/ß-catenin pathway.

Spacer-Programmed Two-Dimensional DNA Origami Assembly.

Two-dimensional (2D) DNA origami assembly represents a powerful approach to the programmable design and construction of advanced 2D materials. Within the context of hybridization-mediated 2D DNA origami assembly, DNA spacers play a pivotal role as essential connectors between sticky-end regions and DNA origami units. Here, we demonstrated that programming the spacer length, which determines the binding radius of DNA origami units, could effectively tune sticky-end hybridization reactions to produce distinct 2D DNA origami arrays. Using DNA-PAINT super-resolution imaging, we unveiled the significant impact of spacer length on the hybridization efficiency of sticky ends for assembling square DNA origami (SDO) units. We also found that the assembly efficiency and pattern diversity of 2D DNA origami assemblies were critically dependent on the spacer length. Remarkably, we realized a near-unity yield of ∼98% for the assembly of SDO trimers and tetramers via this spacer-programmed strategy. At last, we revealed that spacer lengths and thermodynamic fluctuations of SDO are positively correlated, using molecular dynamics simulations. Our study thus paves the way for the precision assembly of DNA nanostructures toward higher complexity.

A Rapid and Safe Minimally Invasive Procedure for Percutaneous Pedicle Screw Removal: A Case-Control Study and Technical Description.

Purpose: Percutaneous pedicle screw fixation is a common minimally invasive treatment for traumatic thoracolumbar and lumbar fractures; however, research on hardware removal after successful healing is limited. We aimed to introduce a rapid, safe, minimally invasive, and cost-effective method for percutaneous pedicle screw removal. Patients and Methods: We conducted a retrospective analysis of demographic (age, sex, body mass index, alcohol use, and current smoking), clinical (hypertension and diabetes mellitus), surgical (affected levels, number of screws, time of surgery, and blood loss), and treatment cost characteristics of 92 patients who had undergone percutaneous pedicle screw removal between May 2016 and February 2023. The first 57 patients underwent the conventional method, and the remaining 35 underwent the modified method. Independent-sample t-tests and chi-square tests were used to compare continuous and categorical variables, respectively, between the two groups. Results: No significant differences were observed in the demographic parameters, complications, or affected levels between the groups. However, the average surgical time (P=0.000) was significantly shorter, and the average blood loss volume (P=0.002) and total cost (P=0.000) were significantly lower in the modified group than in the conventional group. Conclusion: Compared with the conventional method, our modified method can shorten the surgical time, reduce blood loss, and reduce the total cost of treatment. It is a quick and safe minimally invasive method that does not require additional surgical instruments and is suitable for implementation in primary hospitals.

Catalytic Ozonation of Air toward Direct Nitric Acid Production Using Hierarchical Co3O4 with a Tunable Microstructure.

The nitrogen oxidation reaction (NOR) to form nitric acid by applying natural air and H2O under ambient conditions is a sustainable approach to achieving efficient and selective N2 fixation for industrial applications. In this study, four kinds of Co3O4 catalysts with a controllable microstructure were prepared to catalyze the direct NOR of N2 in the air. At the same time, the reaction mechanism of the conversion of N2 to nitric acid under catalytic ozonation was explored through experimental research and density functional theory (DFT) calculation. The results showed that the prepared porous nanosheets self-assembled into microflower-structured samples. The HCOF showed extraordinary catalytic performance for direct NOR to produce a high concentration of nitric acid. The maximum rate of nitric acid formation could be as high as 6.67 mmol/(h·gcat), which was higher than those of most reported photocatalytic or electrocatalytic N2 fixation processes for direct NOR to produce NO3-. Furthermore, the 15N isotopic-labeling experiment confirmed that the produced NO3- originated from N2 in the air by the direct NOR process. In the direct NOR mechanism, inert N2 molecules were captured at the Co3+ active sites by the acceptance-donation electron conduction mode, and the oxygen vacancies boosted the chemical adsorption of N2 molecules and greatly reduced the activation energy barrier of N2 molecules. The active free radicals •OH and •O2- generated by the decomposition of O3 molecules oxidized N2 to the intermediate *NO, which was the rate-determining step, and it was then absorbed by water to form nitric acid. The air catalytic ozonation method in this study was proposed as a facile pathway for efficient nitrogen fixation. This research provides a new method for environmental protection and efficient production of nitric acid at distributed sources.

Towards precision oncology discovery: four less known genes and their unknown interactions as highest-performed biomarkers for colorectal cancer.

The goal of this study was to use a new interpretable machine-learning framework based on max-logistic competing risk factor models to identify a parsimonious set of differentially expressed genes (DEGs) that play a pivotal role in the development of colorectal cancer (CRC). Transcriptome data from nine public datasets were analyzed, and a new Chinese cohort was collected to validate the findings. The study discovered a set of four critical DEGs - CXCL8, PSMC2, APP, and SLC20A1 - that exhibit the highest accuracy in detecting CRC in diverse populations and ethnicities. Notably, PSMC2 and CXCL8 appear to play a central role in CRC, and CXCL8 alone could potentially serve as an early-stage marker for CRC. This work represents a pioneering effort in applying the max-logistic competing risk factor model to identify critical genes for human malignancies, and the interpretability and reproducibility of the results across diverse populations suggests that the four DEGs identified can provide a comprehensive description of the transcriptomic features of CRC. The practical implications of this research include the potential for personalized risk assessment and precision diagnosis and tailored treatment plans for patients.

Construction of aldehyde-based, ester-based hyper-cross-linked polar resin and its selective adsorption mechanism for phenol in coal chemical wastewater.

Efficient and precise recovery of phenol from coal chemical wastewater (CCW) poses a significant challenge, prompting the development of a novel aldehyde-based, ester-based hyper-cross-linked polar resin (DES-COOC-CHO) in this study. Two distinct functional group modification methods were employed to enhance the screening effect of the resin. SEM, FT-IR, NMR, XPS, and BET characterizations confirmed the successful construction of the hyper-cross-linked polar resin, incorporation aldehyde and ester groups, exhibiting a special surface area of 627.2 m2/g and a microporous specific surface area percentage of 29.94%. DES-COOC-CHO adhered to the pseudo-second-order kinetic model and Langmuir model (maximum adsorption capacity of 118.0 mg/g). Its adsorption of phenol was spontaneous chemisorption, monolayer adsorption. Notably, even after undergoing 20 adsorption-desorption cycles, the resin maintained a stable adsorption capacity, showcasing excellent recoverability. In the presence of phenols sharing similar properties, DES-COOC-CHO exhibited superior selectivity for phenol. In real CCW, it achieved a remarkable 90% selective removal rate of phenol. The primary selective mechanism relied on the hydrogen bonding effect facilitated by aldehyde and ester groups, coupled with microporous sieving of appropriate size. In comparison with other adsorbent materials, DES-COOC-CHO exhibited superior adsorption properties, coupled with a cost-effective preparation process, presenting significant potential for practical applications.