Polarization of Tumor-Associated Macrophages by Chinese Medicine Intervention: Mechanisms and Applications

Macrophage polarization is a spectrum of phenotypes and generally can be classified into two states: (1) classically activated or M1 macrophages, which can be driven by lipopolysaccharide (LPS) alone or in association with Th1 cytokines and produce pro-inflammatory cytokines such as TNF-α, IL-6 and, IL-12, and (2) alternatively activated M2 macrophages, which can be promoted by Th2 mediators IL-4 and IL-13 and produce anti-inflammatory cytokines such as TGF-β and IL-10. Current studies have found that the phenotypic switch between M1 and M2 macrophages governs the fate of an organ in inflammation or injury. The imbalance of M1/M2 polarization is closely involved in various pathological processes and is becoming a potential target for therapeutic strategies. Traditional Chinese medicine is an integrated healthcare system composed of many practices and is characterized by multi-target, multi-level, and coordinated intervention effects. Chinese medicines nowadays are applied to regulate phenotype polarization of macrophages to improve the microenvironment, thus ameliorating or even eliminating the symptoms. In this chapter, we will discuss the molecular mechanisms of macrophage polarization, their roles in health and disease, and the intervention with Chinese medicines to modulate the polarization of macrophages in tumor microenvironment (TME) for therapeutic purpose

Gene Expression Profiles Deciphering Rice Phenotypic Variation between Nipponbare (Japonica) and 93-11 (Indica) during Oxidative Stress

Rice is a very important food staple that feeds more than half the world's population. Two major Asian cultivated rice (Oryza sativa L.) subspecies, japonica and indica, show significant phenotypic variation in their stress responses. However, the molecular mechanisms underlying this phenotypic variation are still largely unknown. A common link among different stresses is that they produce an oxidative burst and result in an increase of reactive oxygen species (ROS). In this study, methyl viologen (MV) as a ROS agent was applied to investigate the rice oxidative stress response. We observed that 93-11 (indica) seedlings exhibited leaf senescence with severe lesions under MV treatment compared to Nipponbare (japonica). Whole-genome microarray experiments were conducted, and 1,062 probe sets were identified with gene expression level polymorphisms between the two rice cultivars in addition to differential expression under MV treatment, which were assigned as Core Intersectional Probesets (CIPs). These CIPs were analyzed by gene ontology (GO) and highlighted with enrichment GO terms related to toxin and oxidative stress responses as well as other responses. These GO term-enriched genes of the CIPs include glutathine S-transferases (GSTs), P450, plant defense genes, and secondary metabolism related genes such as chalcone synthase (CHS). Further insertion/deletion (InDel) and regulatory element analyses for these identified CIPs suggested that there may be some eQTL hotspots related to oxidative stress in the rice genome, such as GST genes encoded on chromosome 10. In addition, we identified a group of marker genes individuating the japonica and indica subspecies. In summary, we developed a new strategy combining biological experiments and data mining to study the possible molecular mechanism of phenotypic variation during oxidative stress between Nipponbare and 93-11. This study will aid in the analysis of the molecular basis of quantitative traits

The genomic and bulked segregant analysis of \u3ci\u3eCurcuma alismatifolia\u3c/i\u3e revealed its diverse bract pigmentation

Compared with most flowers where the showy part comprises specialized leaves (petals) directly subtending the reproductive structures, most Zingiberaceae species produce showy ‘‘flowers’’ through modifications of leaves (bracts) subtending the true flowers throughout an inflorescence. Curcuma alismatifolia, belonging to the Zingiberaceae family, a plant species originating from Southeast Asia, has become increasingly popular in the flower market worldwide because of its varied and esthetically pleasing bracts produced in different cultivars. Here, we present the chromosome-scale genome assembly of C. alismatifolia ‘‘Chiang Mai Pink’’ and explore the underlying mechanisms of bract pigmentation. Comparative genomic analysis revealed C. alismatifolia contains a residual signal of wholegenome duplication. Duplicated genes, including pigment-related genes, exhibit functional and structural differentiation resulting in diverse bract colors among C. alismatifolia cultivars. In addition, we identified the key genes that produce different colored bracts in C. alismatifolia, such as F3\u275’H, DFR, ANS and several transcription factors for anthocyanin synthesis, as well as chlH and CAO in the chlorophyll synthesis pathway by conducting transcriptomic analysis, bulked segregant analysis using both DNA and RNA data, and population genomic analysis. This work provides data for understanding the mechanism of bract pigmentation and will accelerate breeding in developing novel cultivars with richly colored bracts in C. alismatifolia and related species. It is also important to understand the variation in the evolution of the Zingiberaceae family

Room temperature magnetic phase transition in an electrically-tuned van der Waals ferromagnet

Finding tunable van der Waals (vdW) ferromagnets that operate at above room temperature is an important research focus in physics and materials science. Most vdW magnets are only intrinsically magnetic far below room temperature and magnetism with square-shaped hysteresis at room-temperature has yet to be observed. Here, we report magnetism in a quasi-2D magnet Cr1.2Te2 observed at room temperature (290 K). This magnetism was tuned via a protonic gate with an electron doping concentration up to 3.8 * 10^21 cm^-3. We observed non-monotonic evolutions in both coercivity and anomalous Hall resistivity. Under increased electron doping, the coercivities and anomalous Hall effects (AHEs) vanished, indicating a doping-induced magnetic phase transition. This occurred up to room temperature. DFT calculations showed the formation of an antiferromagnetic (AFM) phase caused by the intercalation of protons which induced significant electron doping in the Cr1.2Te2. The tunability of the magnetic properties and phase in room temperature magnetic vdW Cr1.2Te2 is a significant step towards practical spintronic devices.Comment: 18 pages, 4 figure

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

Study on the effeets of hypoxia on the level of OCN in nucleus pulposus cells

In order to studing the effects of hypoxia on the level of OCN in nucleus pulposus cells.Human nucleus pulposus cell were line cultured in vitro.The growth morphological of nucleus pulposus cells were observed under a microscope.Two groups of cells were collected respectively from 24,48,72 h in culture.Immunohistochemical SABC method was used in the OCN expression.Then IPP image analysis system was used in the semi quantitative detection results of which were expressed by optical density value.Results suggested that expression of hypoxia group of nucleus pulposus cells OCN levels were significantly higher than the normal oxygen group at 48,72 h in vitro.The average optical density values were 180.50+8.76 vs 169.29+3.04,190.87+7.06 vs 166.33+4.44,PP<0.01).There is no significant difference on between different time groups the expression level of OCN in normal oxygen nucleus pulposus cells OCN between each time group.Hypoxia can induce nucleus pulposus cells overexpress OCN.Hypoxia may contribute to intervertebral disc endplate cartilage mineralization

Complete Chloroplast Genome Sequences of Four Species in the Caladium Genus: Comparative and Phylogenetic Analyses

Caladiums are promising colorful foliage plants due to their dazzling colors of the leaves, veins, stripes, and patches, which are often cultivated in pots or gardens as decorations. Four wild species, including C. bicolor, C. humboldtii, C. praetermissum, and C. lindenii, were employed in this study, where their chloroplast (cp) genomes were sequenced, assembled, and annotated via high-throughput sequencing. The whole cp genome size ranged from 162,776 bp to 168,888 bp, and the GC contents ranged from 35.09% to 35.91%. Compared with the single large copy (LSC) and single small copy (SSC) regions, more conserved sequences were identified in the inverted repeat regions (IR). We further analyzed the different region borders of nine species of Araceae and found the expansion or contraction of IR/SSC regions might account for the cp genome size variation. Totally, 131 genes were annotated in the cp genomes, including 86 protein-coding genes (PCGs), 37 tRNAs, and eight rRNAs. The effective number of codons (ENC) values and neutrality plot analyses provided the foundation that the natural selection pressure could greatly affect the codon preference. The GC3 content was significantly lower than that of GC1 and GC2, and codons ending with A/U had higher usage preferences. Finally, we conducted phylogenetic relationship analysis based on the chloroplast genomes of twelve species of Araceae, in which C. bicolor and C. humboldtii were grouped together, and C. lindenii was furthest from the other three Caladium species occupying a separate branch. These results will provide a basis for the identification, development, and utilization of Caladium germplasm

Using 3D finite element models verified the importance of callus material and microstructure in biomechanics restoration during bone defect repair

<p><b>Background:</b> There is lack of further observations on the microstructure and material property of callus during bone defect healing and the relationships between callus properties and the mechanical strength. <b>Methods:</b> Femur bone defect model was created in rabbits and harvested CT data to reconstruct finite element models at 1 and 2 months. Three types of assumed finite element models were compared to study the callus properties, which assumed the material elastic property as heterogeneous (R-model), homogenous (H-model) or did not change from 1 to 2 months (U-model). <b>Results:</b> The apparent elastic moduli increased at 2 months (from 355.58 ± 132.67 to 1139.30 ± 967.43 MPa) in R-models. But there was no significant difference in apparent elastic moduli between R-models (355.58 ± 132.67 and 1139.30 ± 967.43 MPa) and H-models (344.79 ± 138.73 and 1001.52 ± 692.12 MPa) in 1 and 2 months. A significant difference of apparent elastic moduli was found between the R-model (1139.30 ± 967.43 MPa) and U-model group (207.15 ± 64.60 MPa) in 2 months. <b>Conclusions:</b> This study showed that the callus structure stability remodeled overtime to achieve a more effective structure, while the material quality of callus tissue is a very important factor for callus strength. At the meantime, this study showed an evidence that the material heterogeneity maybe not as important as it is in bone fracture model.</p

Applying Queuing Theory and Mixed Integer Programming to Blood Center Nursing Schedules of a Large Hospital in China

Blood centers in large hospitals in China are facing serious problems, including complex patient queues and inflexible nursing schedules. This study is aimed at developing a flexible scheduling method for blood center nurses. By systematically analyzing the constraints that affect scheduling, a flexible scheduling model is established based on queuing theory and mixed integer programming. This combined model can reasonably determine the number of nurses required during a given working period and flexibly arrange nursing schedules while ensuring sufficient rest periods for individual nurses. Results of numerical studies conducted using data from a large hospital in China show a significant improvement in patient waiting time performance metrics over the hospital’s current practice. In addition, the nurses’ workloads and rest periods are well balanced, indicating that the proposed method can effectively and flexibly arrange nursing shifts in blood centers