Effect of Axial Clearance Variation on Dual-Rotor Flowmeter Performance.

This study examines the impact of axial clearance variations on the performance characteristics of a dual-rotor flowmeter (DRT-FM) through numerical simulations, with the validity of the numerical results verified by calibration experiments. The results indicate that within the range of 200 L/h to 1600 L/h, the K factors of different groups increase as clearance increases. The K factor of the 0.80 mm group is the largest, showing an average increase of around 6% compared to that of the 0.50 mm group. Additionally, Linearity E also decreased, with a minimum of 1.07% in the 0.65 mm group, significantly lower than the 3.33% in the 0.50 mm group. Furthermore, the pressure loss increased slightly, with the 0.65 mm group having the largest pressure loss; however, at a flow rate of 1600 L/h, the pressure loss only increases by 0.186 kPa compared to that of the 0.50 mm group. Flow field analysis reveals that changes in axial clearance predominantly affect pressure distribution. Larger clearances reduce low-pressure regions on upstream and downstream transition surfaces, thereby reducing energy loss due to pressure changes. Entropy analysis further demonstrates that higher axial clearance decreases energy loss in the upstream and downstream stationary domains, optimizing the DRT-FM's energy characteristics.

Microbiological profile of diabetic foot infections in China and worldwide: a 20-year systematic review.

Introduction: Pathogens causing diabetic foot infections (DFIs) vary by region globally; however, knowledge of the causative organism is essential for effective empirical treatment. We aimed to determine the incidence and antibiotic susceptibility of DFI pathogens worldwide, focusing on Asia and China. Methods: Through a comprehensive literature search, we identified published studies on organisms isolated from DFI wounds from January 2000 to December 2020. Results: Based on our inclusion criteria, we analyzed 245 studies that cumulatively reported 38,744 patients and 41,427 isolated microorganisms. DFI pathogens varied according to time and region. Over time, the incidence of Gram-positive and Gram-negative aerobic bacteria have decreased and increased, respectively. America and Asia have the highest (62.74%) and lowest (44.82%) incidence of Gram-negative bacteria, respectively. Africa has the highest incidence (26.90%) of methicillin-resistant Staphylococcus aureus. Asia has the highest incidence (49.36%) of Gram-negative aerobic bacteria with species infection rates as follows: Escherichia coli, 10.77%; Enterobacter spp., 3.95%; and Pseudomonas aeruginosa, 11.08%, with higher local rates in China and Southeast Asia. Linezolid, vancomycin, and teicoplanin were the most active agents against Gram-positive aerobes, while imipenem and cefoperazone-sulbactam were the most active agents against Gram-negative aerobes. Discussion: This systematic review showed that over 20 years, the pathogens causing DFIs varied considerably over time and region. This data may inform local clinical guidelines on empirical antibiotic therapy for DFI in China and globally. Regular large-scale epidemiological studies are necessary to identify trends in DFI pathogenic bacteria. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023447645.

Prediction of carbon emissions in China's construction industry using an improved grey prediction model.

As a significant source of global energy consumption and greenhouse gas emissions, the construction industry garners widespread attention due to its high carbon emissions. Anticipating its development trends is crucial for energy conservation and emission reduction. In this paper, we utilize the carbon emission data from China's national and provincial construction sectors from 2012 to 2021, employ the grey prediction model optimized by the particle swarm optimization algorithm, coupled with a metabolic algorithm, to forecast the carbon emissions of the construction industry across China and its provinces. The results demonstrate that: (1) The dynamic grey prediction model combined with the metabolism algorithm has a better prediction effect than the classical model, and the relative error is reduced from 5.103 % to 0.874 %. (2) The carbon emissions of China's construction industry will continue to rise in the next decade, but the growth rate will decrease, and the proportion of indirect carbon emissions continues to increase. (3) There is a marked regional disparity in carbon emissions, with the eastern region exhibiting higher emission levels yet slower growth. In contrast, the western region has lower emission levels but experiences faster growth. These studies provide valuable insights for both the existing approaches to energy conservation and emission reduction, as well as for future policy improvements.

Diindoles produced from commensal microbiota metabolites function as endogenous CAR/Nr1i3 ligands.

Numerous studies have demonstrated the correlation between human gut bacteria and host physiology, mediated primarily via nuclear receptors (NRs). Despite this body of work, the systematic identification and characterization of microbe-derived ligands that regulate NRs remain a considerable challenge. In this study, we discover a series of diindole molecules produced from commensal bacteria metabolites that act as specific agonists for the orphan constitutive androstane receptor (CAR). Using various biophysical analyses we show that their nanomolar affinities are comparable to those of synthetic CAR agonists, and that they can activate both rodent and human CAR orthologues, which established synthetic agonists cannot. We also find that the diindoles, diindolylmethane (DIM) and diindolylethane (DIE) selectively up-regulate bona fide CAR target genes in primary human hepatocytes and mouse liver without causing significant side effects. These findings provide new insights into the complex interplay between the gut microbiome and host physiology, as well as new tools for disease treatment.

Quantifying forms and functions of intestinal bile acid pools in mice.

Bile acids (BAs) are gastrointestinal metabolites that serve dual functions in lipid absorption and cell signaling. BAs circulate actively between the liver and distal small intestine (i.e., ileum), yet the dynamics through which complex BA pools are absorbed in the ileum and interact with intestinal cells in vivo remain ill-defined. Through multi-site sampling of nearly 100 BA species in individual wild type mice, as well as mice lacking the ileal BA transporter, Asbt/Slc10a2, we calculate the ileal BA pool in fasting C57BL/6J mice to be ~0.3 µmoles/g. Asbt-mediated transport accounts for ~80% of this pool and amplifies size, whereas passive absorption explains the remaining ~20%, and generates diversity. Accordingly, ileal BA pools in mice lacking Asbt are ~5-fold smaller than in wild type controls, enriched in secondary BA species normally found in the colon, and elicit unique transcriptional responses in cultured ileal explants. This work quantitatively defines ileal BA pools in mice and reveals how BA dysmetabolism can impinge on intestinal physiology.

Efficiency evaluation of China's transportation system considering carbon emissions: Evidence from big data analytics methods.

China's transportation sector is a vital link between production and consumption, but it also has issues with low efficiency, high carbon emissions, and technological bottlenecks. To improve efficiency and provide actionable recommendations and strategies, this study first constructs a comprehensive evaluation index system to gauge the transportation sector's inputs using panel data from different Chinese provinces from 2007 to 2021. Within the assessment system, the principal component analysis (PCA) method is used to reduce the dimension of the indexes, thereby yielding a set of adjusted inputs. Subsequently, the transportation system efficiency (TSE) is evaluated using the super-efficiency SBM-DEA model, which includes unexpected outputs such as carbon emissions, and three-stage DEA modifies the efficiency. Then, we calculate the Malmquist-Luenberger index (TML) and its components: technological change (TTC) and technological efficiency change (TEC). Lastly, the influential factors impacting TSE are analyzed via a truncated regression Tobit model. The following are the conclusions: (1) The transportation industry in China exhibits inefficiency, and the average TSE in Stage I and III is 0.91 and 0.93, respectively. TSE is underestimated due to the influence of external environmental factors and inefficiencies in management in Stage I. (2) TSE in the eastern area also produces significant carbon emissions that surpass the national average. At the same time, other regions face efficiency limitations due to geographical constraints and management obstacles. (3) Insufficient technical capacity is a major cause of inefficiency in the transport sector and is prevalent in the northeast, west, and central regions. (4) Population growth and income per capita advancements foster transportation industry development, while increased GDP, fiscal revenues, and traffic accidents contribute to declining efficiency. The study above findings serve as a foundation for regional and national management initiatives and policies to enhance transportation effectiveness.

Multilevel Pedicle Subtraction Osteotomy for Correction of Thoracolumbar Kyphosis in Ankylosing Spondylitis: Clinical Effect and Biomechanical Evaluation.

OBJECTIVE: To compare the clinical outcomes and biomechanical characteristics of 1-, 2-, and 3-level pedicle subtraction osteotomy (PSO), and establish selection criteria based on preoperative radiographic parameters. METHODS: Patients undergone PSO to treat ankylosing spondylitis from February 2009 to May 2019 in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were enrolled. According to the quantity of osteotomy performed, the participants were divided into group A (1-level PSO, n = 24), group B (2-level PSO, n = 19), and group C (3-level PSO, n = 11). Clinical outcomes were assessed before surgery and at the final follow-up. Comparisons of the radiographic parameters and quality-of-life indicators were performed among and within these groups, and the selection criteria were established by regression. Finite element analysis was conducted to compare the biomechanical characteristics of the spine treated with different quantity of osteotomies under different working conditions. RESULTS: Three-level PSO improved the sagittal parameters more significantly, but resulted in longer operative time and greater blood loss (p < 0.05). Greater stress was found in the proximal screws and proximal junction area of the vertebra in the model simulating 1-level PSO. Larger stress of screws and vertebra was observed at the distal end in the model simulating 3-level PSO. CONCLUSION: Multilevel PSO works better for larger deformity correction than single-level PSO by allowing greater sagittal parameter correction and obtaining a better distribution of stress in the hardware construct, although with longer operation time and greater blood loss. Three-level osteotomy is recommended for the patients with preoperative of global kyphosis > 85.95°, T1 pelvic angle > 62.3°, sagittal vertical alignment > 299.55 mm, and pelvic tilt+ chin-brow vertical angle > 109.6°.

Gold perfusion experiments support the multi-layered, mesoporous nature of intervessel pit membranes in angiosperm xylem.

Fluid transport across intervessel pit membranes of angiosperm xylem plays a major role in plant transpiration, with transport resistance largely depending on pore constriction sizes. Traditionally, fluid particles traversing pit membranes are assumed to cross a single instead of multiple pore constrictions. We tested a multi-layered pit membrane model in xylem of eight angiosperm species by estimating the size frequency of pore constrictions in relation to pit membrane thickness and compared modelled data with perfusion characteristics of nanoscale gold particles based on transmission electron microscopy. The size frequency of modelled pore constrictions showed similar patterns to the measured number of perfused particle sizes inside pit membranes, although frequency values measured were 10-50 times below modelled data. Small particles enter pit membranes most easily, especially when injected in thin pit membranes. The trapping of gold particles by pore constrictions becomes more likely with increasing pore constriction number and pit membrane thickness. While quantitative differences between modelled and experimental data are due to various practical limitations, their qualitative agreement supports a multi-layered pit membrane model with multiple pore constrictions. Pore constrictions between 5 and 50 nm are realistic, and confirm the mesoporous nature of pit membranes.

MicroRNA-18a regulates the Pyroptosis, Apoptosis, and Necroptosis (PANoptosis) of osteoblasts induced by tumor necrosis factor-α via hypoxia-inducible factor-1α.

BACKGROUND: Tumor necrosis factor-α (TNF-α) is involved in inflammatory responses and promotes cell death and the inhibition of osteogenic differentiation. MicroRNA (miRNA) plays a crucial role in the infected bone diseases, however, the biological role of miRNAs in inflammation-induced impaired osteogenic differentiation remains unclear. This study aimed to explore the role of miRNA-18a-5p (miR-18a) in regulating PANoptosis and osteogenic differentiation in an inflammatory environment via hypoxia-inducible factor-1α (HIF1-α). METHODS: The expression of miR-18a in MC3T3-E1 cells was analyzed using quantitative reverse transcription-polymerase chain reaction in an inflammatory environment induced by TNF-α. The expression of HIF1-α and NLRP3 in LV-miR-18a or sh-miR-18a cells was analyzed using western blotting. Fluorescence imaging for cell death, flow cytometry, and alkaline phosphatase activity analysis were used to analyze the role of miR-18a in TNF-α-induced PANoptosis and the inhibition of osteogenic differentiation. An animal model of infectious bone defect was established to validate the regulatory role of miR-18a in an inflammatory environment. RESULTS: The expression of miRNA-18a in the MC3T3-E1 cell line was significantly lower under TNF-α stimulation than in the normal environment. miR-18a significantly inhibited the expression of HIF1-α and NLRP3, and inhibition of HIF1-α expression further inhibited NLRP3 expression. Furthermore, inhibition of miR-18a expression promoted the TNF-α-induced PANoptosis and inhibition of osteogenic differentiation, whereas miR-18a overexpression and the inhibition of both HIF1-α and NLRP3 reduced the effects of TNF-α. These findings are consistent with those of the animal experiments. CONCLUSION: miRNA-18a negatively affects HIF1-α/NLRP3 expression, inhibits inflammation-induced PANoptosis, and impairs osteogenic differentiation. Thus, it is a potential therapeutic candidate for developing anti-inflammatory strategies for infected bone diseases.

In vitro safety signals for potential clinical development of the anti-inflammatory pregnane X receptor agonist FKK6.

Based on the mimicry of microbial metabolites, functionalized indoles were demonstrated as the ligands and agonists of the pregnane X receptor (PXR). The lead indole, FKK6, displayed PXR-dependent protective effects in DSS-induced colitis in mice and in vitro cytokine-treated intestinal organoid cultures. Here, we report on the initial in vitro pharmacological profiling of FKK6. FKK6-PXR interactions were characterized by hydrogen-deuterium exchange mass spectrometry. Screening FKK6 against potential cellular off-targets (G protein-coupled receptors, steroid and nuclear receptors, ion channels, and xenobiotic membrane transporters) revealed high PXR selectivity. FKK6 has poor aqueous solubility but was highly soluble in simulated gastric and intestinal fluids. A large fraction of FKK6 was bound to plasma proteins and chemically stable in plasma. The partition coefficient of FKK6 was 2.70, and FKK6 moderately partitioned into red blood cells. In Caco2 cells, FKK6 displayed high permeability (A-B: 22.8 × 10-6 cm.s-1) and no active efflux. These data are indicative of essentially complete in vivo absorption of FKK6. The data from human liver microsomes indicated that FKK6 is rapidly metabolized by cytochromes P450 (t1/2 5 min), notably by CYP3A4. Two oxidized FKK6 derivatives, including DC73 (N6-oxide) and DC97 (C19-phenol), were detected, and these metabolites had 5-7 × lower potency as PXR agonists than FKK6. This implies that despite high intestinal absorption, FKK6 is rapidly eliminated by the liver, and its PXR effects are predicted to be predominantly in the intestines. In conclusion, the PXR ligand and agonist FKK6 has a suitable pharmacological profile supporting its potential preclinical development.

Muscone ameliorates myocardial ischemia‒reperfusion injury by promoting myocardial glycolysis.

Objective: The incidence of acute myocardial infarction (AMI) is increasing yearly. With the use of thrombolysis or percutaneous coronary intervention (PCI), the mortality rate of acute myocardial infarction has been significantly reduced. However, reperfusion can cause additional myocardial injury. There is still a lack of effective drugs to treat I/R injury, and it is urgent to find new therapeutic drugs. Methods: In this study, network pharmacology was used to predict potential targets and biological processes involved in Muscone-mediated treatment of acute myocardial infarction. To model ischemia‒reperfusion injury, a hypoxia-reoxygenation model and in vivo ischemia‒reperfusion injury C57BL/6 mice model was constructed. Mice were treated with Muscone i.p. for 4 weeks. We detected the cardiac function on day 28.The expression levels of the apoptotic proteins Caspase-3 and Bax and the anti-apoptotic protein Bcl-2 were detected by immunoblotting after Muscone treatment of AC16 cells and in vivo. Additionally, the gene expression levels of the PUMA and p53 were analyzed by qRT‒PCR. Molecular docking was used to evaluate the binding energy between Muscone and NLRP3-related proteins. Immunoblotting and qRT‒PCR were used to assess the expression levels of NLRP3 signaling pathway-related proteins (NLRP3, ASC, and Caspase-1) and the NLRP3 gene, respectively. Moreover, the extracellular acidification rate of AC16 cells was measured using the Seahorse system to evaluate glycolysis levels after Muscone treatment. The expression of the key glycolytic enzyme PKM2 was analyzed by immunoblotting and qRT‒PCR. Finally, ChIP‒qPCR was performed to determine the levels of histone modifications (H3K4me3, H3K27me3, and H2AK119Ub) in the PKM2 promoter region. Results: GO functional enrichment analysis revealed that muscone was involved in regulating the biological processes (BP) of AMI, which mainly included negative regulation of the apoptosis signaling pathway, the response to lipopolysaccharide, and blood pressure regulation. The cellular components (CC) involved in muscone-mediated regulation of AMI mainly included lipid rafts, membrane microdomains, and membrane regions. The molecular functions (MF) involved in muscone-mediated regulation of AMI mainly included oxidoreductase activity, nuclear receptor activity, and transcription factor activity. In vitro results indicated that muscone treatment could inhibit the expression levels of Bax and Caspase-3 in AC16 cells after ischemia‒reperfusion while increasing the expression level of the antiapoptotic protein Bcl-2. Muscone significantly suppressed the transcription levels of p53 and PUMA in AC16 cells. Molecular docking suggested that muscone could bind well with the Cryo-EM structure of NEK7(PDB ID:6NPY). Further investigation of inflammatory pathways revealed that muscone could inhibit the expression level of NLRP3 in AC16 cells and reduce the expression levels of Caspase-1 and Caspase recruitment domain. Fluorescent quantitative PCR experiments showed that muscone significantly inhibited the transcription of NLRP3. Moreover, we found that muscone could enhance the glycolytic efficiency of AC16 cells, which may be related to the increased protein expression of PKM2 in AC16 cells. Fluorescent quantitative PCR showed that muscone could increase the transcription level of PKM2. Chromatin immunoprecipitation assays showed that muscone treatment increased the expression level of H3K4me3 in the PKM2 promoter region and inhibited the levels of H3K27me3 and H2AK119Ub in the PKM2 promoter region. Conclusion: Muscone promoted myocardial glycolysis and inhibited NLRP3 pathway activation to improve myocardial ischemia‒reperfusion injury.

The impact of population agglomeration on ecological resilience: Evidence from China.

Due to climate change and human activities, ecological and environmental issues have become increasingly prominent and it is crucial to deeply study the coordinated development between human activities and the ecological environment. Combining panel data from 31 provinces in China spanning from 2011 to 2020, we employed a fixed-effects model, a threshold regression model, and a spatial Durbin model to empirically examine the intricate impacts of population agglomeration on ecological resilience. Our findings indicate that population agglomeration can have an impact on ecological resilience and this impact depends on the combined effects of agglomeration and crowding effects. Also, the impact of population agglomeration on ecological resilience exhibits typical dual-threshold traits due to differences in population size. Furthermore, population agglomeration not only directly impacts the ecological resilience of the local area, but also indirectly affects the ecological resilience of surrounding areas. In conclusion, we have found that population agglomeration does not absolutely impede the development of ecological resilience. On the contrary, to a certain extent, reasonable population agglomeration can even facilitate the progress of ecological resilience.

[Effects of Mirror Therapy Combined With Task-Oriented Training on Limb Function Recovery in Stroke Patients With Hemiplegia].

Objective: To explore the effects of mirror therapy combined with task-oriented training on limb function recovery in stroke patients with hemiplegia. Methods: A total of 304 older patients with post-stroke hemiplegia who received treatment in Nanyang Third People's Hospital between March 2020 and March 2022 were enrolled as the subjects. They were assigned to the intervention group and the control group through a systematic randomization method, with 152 patients in each group. The control group was treated with conventional medication and task-oriented training, while the intervention group received a combined mirror therapy in addition to the treatment given to the control group. Both groups received continuous treatment for 3 months. The pre-treatment findings and those obtained after 3 month of treatment were compared between the two groups in the following areas, the neurological functions, including the levels of neuron-specific enolase (NSE) and S100ß, a central nervous system specific protein, upper and lower limb motor function as reflected by Fugl-Meyer Assessment (FMA) score, balance ability as measured by Berg Balance Scale (BBS), and the integrated electromyography (iEMG) values of quadriceps femoris, gastrocnemius, and tibialis anterior muscles, three-dimensional gait spatiotemporal parameters, and quality of life as reflected by the assessment results for the National Institute of Stroke Scale (NIHSS) and Stroke-Specific Quality of Life Scale (SS-QOL). The findings were compared to identify changes. Results: After 3 months of treatment, the FMA and BBS scores and three-dimensional gait spatio-temporal parameters in the intervention group were significantly better than those in the control group (all P<0.05). Conclusion: Mirror therapy combined with task-oriented training promotes the function recovery of the affected limbs in older patients with post-stroke hemiplegia, effectively improves their motor function and quality of life, and helps improve patient prognosis.

Study for Some Eccentricity-based Topological Indices of Second Type of Dominating David-derived Network.

BACKGROUND: Dominating David-derived networks are widely studied due to their fractal nature, with applications in topology, chemistry, and computer sciences. The use of molecular structure descriptors is a standard procedure that is used to correlate the biological activity of molecules with their chemical structures, which can be useful in the field of pharmacology. OBJECTIVE: This article's goal is to develop analytically closed computing formulas for eccentricity-based descriptors of the second type of dominating David-derived derived network. Thermodynamic characteristics, physicochemical properties, and chemical and biological activities of chemical graphs are just a few of the many properties that may be determined using these computation formulas. METHODS: Vertex sets were initially divided according to their degrees, eccentricities, and cardinalities of occurrence. The eccentricity-based indices are then computed using some combinatorics and these partitions. RESULTS: Total eccentricity, average eccentricity, and the Zagreb index are distance-based topological indices utilized in this study for the second type of dominating David-derived network, denoted as D_2 (m). CONCLUSION: These calculations will assist the readers in estimating the fractal and difficult-to-handle thermodynamic and physicochemical aspects of chemical structure. Apart from configuration and impact resistance, the D_2 (m) design has been used for fundamental reasons in a variety of technical and scientific advancements.

Degree Descriptors and Graph Entropy Quantities of Zeolite ACO.

BACKGROUND: Cheminformatics is a fascinating emerging subfield of chemical graph theory that studies quantitative structure-activity and property relationships of molecules and, in turn, uses these to predict the physical and chemical properties, which are extremely useful in drug discovery and optimization. Knowledge discovery can be put to use in pharmaceutical data matching to help in finding promising lead compounds. METHOD: Topological descriptors are numerical quantities corresponding to the chemical structures that are used in the study of these phenomena. RESULT: This paper is concerned with developing the generalized analytical expression of topological descriptors for zeolite ACO structures with underlying degree and degree-sum parameters. CONCLUSION: To demonstrate improved discrimination power between the topological descriptors, we have further modified Shannon's entropy approach and used it to calculate the entropy measures of zeolite ACO structures.

Disclosing Environmental Ligands of L-FABP and PPARγ: Should We Re-evaluate the Chemical Safety of Hydrocarbon Surfactants?

Chemical contaminants can cause adverse effects by binding to the liver-fatty acid binding protein (L-FABP) and peroxisome proliferator-activated nuclear receptor γ (PPARγ), which are vital in lipid metabolism. However, the presence of numerous compounds in the environment has hindered the identification of their ligands, and thus only a small portion have been discovered to date. In this study, protein Affinity Purification with Nontargeted Analysis (APNA) was employed to identify the ligands of L-FABP and PPARγ in indoor dust and sewage sludge. A total of 83 nonredundant features were pulled-out by His-tagged L-FABP as putative ligands, among which 13 were assigned as fatty acids and hydrocarbon surfactants. In contrast, only six features were isolated when His-tagged PPARγ LBD was used as the protein bait. The binding of hydrocarbon surfactants to L-FABP and PPARγ was confirmed using both recombinant proteins and reporter cells. These hydrocarbon surfactants, along with >50 homologues and isomers, were detected in dust and sludge at high concentrations. Fatty acids and hydrocarbon surfactants explained the majority of L-FABP (57.7 ± 32.9%) and PPARγ (66.0 ± 27.1%) activities in the sludge. This study revealed hydrocarbon surfactants as the predominant synthetic ligands of L-FABP and PPARγ, highlighting the importance of re-evaluating their chemical safety.

Redox-responsive self-assembled podophyllotoxin twin drug nanoparticles for enhanced intracellular drug delivery.

Podophyllotoxin (PPT) is an active natural pharmaceutical component with potent anticancer activity. However, due to its poor water solubility and serious side effects, its medical applications are limited. In this work, we synthesized a series of PPT dimers, which can be self-assembled into stable nanoparticles of 124-152 nm in aqueous solution and can significantly increase the solubility of PPT in aqueous solution. In addition, PPT dimer nanoparticles exhibited high drug loading capacity (>80%) and could store at 4 °C in aqueous state with good stability for at least 30 d.In vitrorelease studies showed that nanoparticles with disulfide bonds (SS NPs) can quickly release (about 96.5% drug released within 24 h) the conjugated drug in PBS buffer (pH = 7.4) in the presence of DTT. Cell endocytosis experiments showed that SS NPs enhanced cell uptake (18.56 times higher than PPT for Molm-13, 10.29 times for A2780S and 9.81 times for A2780T) and maintained antitumor effect against human ovarian tumor cells (A2780S and resistant A2780T) and human breast cancer cells (MCF-7). In addition, the endocytosis mechanism of SS NPs was revealed that these nanoparticles were mainly up-taken by macropinocytosis-mediated endocytosis. We believe that these PPT dimer-based nanoparticles will become an alternative formula for PPT, moreover the assembly behavior of PPT dimer can be extended to other therapeutic drugs.

The Bcr-Abl inhibitor DCC-2036 inhibits necroptosis and ameliorates osteoarthritis by targeting RIPK1 and RIPK3 kinases.

Osteoarthritis (OA) is a chronic progressive degenerative joint disease. Owing to its complex pathogenesis, OA treatment is typically challenging. Necroptosis is a form of programmed cell death mainly mediated by the serine/threonine kinases, RIPK1 and RIPK3, and mixed lineage kinase-like domain (MLKL). In this study, we found that the multi-targeted kinase inhibitor DCC-2036 can inhibit TSZ (TNF-α, Smac mimetic, and z-VAD-FMK)-induced necroptosis of chondrocytes and synovial fibroblast cells (SFs). In addition, we found that oral DCC-2036 inhibited chondrocyte damage in a rat model of OA induced by intra-articular injection of monosodium iodoacetate (MIA). A mechanistic study showed that DCC-2036 directly inhibited the activities of RIPK1 and RIPK3 kinases to block necroptosis, inhibiting the inflammatory response and protecting chondrocytes. In summary, our research suggests that DCC-2036, a new necroptosis inhibitor targeting RIPK1 and RIPK3 kinase activity, may be useful for the clinical treatment of OA and provides a new direction for the research and treatment of OA.

Entropy Related to K-Banhatti Indices via Valency Based on the Presence of C6H6 in Various Molecules.

Entropy is a measure of a system's molecular disorder or unpredictability since work is produced by organized molecular motion. Shannon's entropy metric is applied to represent a random graph's variability. Entropy is a thermodynamic function in physics that, based on the variety of possible configurations for molecules to take, describes the randomness and disorder of molecules in a given system or process. Numerous issues in the fields of mathematics, biology, chemical graph theory, organic and inorganic chemistry, and other disciplines are resolved using distance-based entropy. These applications cover quantifying molecules' chemical and electrical structures, signal processing, structural investigations on crystals, and molecular ensembles. In this paper, we look at K-Banhatti entropies using K-Banhatti indices for C6H6 embedded in different chemical networks. Our goal is to investigate the valency-based molecular invariants and K-Banhatti entropies for three chemical networks: the circumnaphthalene (CNBn), the honeycomb (HBn), and the pyrene (PYn). In order to reach conclusions, we apply the method of atom-bond partitioning based on valences, which is an application of spectral graph theory. We obtain the precise values of the first K-Banhatti entropy, the second K-Banhatti entropy, the first hyper K-Banhatti entropy, and the second hyper K-Banhatti entropy for the three chemical networks in the main results and conclusion.