Therapeutic challenges in peripheral T-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of hematological malignancies. Compared to our knowledge of B-cell tumors, our understanding of T-cell leukemia and lymphoma remains less advanced, and a significant number of patients are diagnosed with advanced stages of the disease. Unfortunately, the development of drug resistance in tumors leads to relapsed or refractory peripheral T-Cell Lymphomas (r/r PTCL), resulting in highly unsatisfactory treatment outcomes for these patients. This review provides an overview of potential mechanisms contributing to PTCL treatment resistance, encompassing aspects such as tumor heterogeneity, tumor microenvironment, and abnormal signaling pathways in PTCL development. The existing drugs aimed at overcoming PTCL resistance and their potential resistance mechanisms are also discussed. Furthermore, a summary of ongoing clinical trials related to PTCL is presented, with the aim of aiding clinicians in making informed treatment decisions.

Physiological and transcriptional mechanisms associated with cadmium stress tolerance in Hibiscus syriacus L.

BACKGROUND: Cadmium (Cd) pollution of soils is a global concern because its accumulation in plants generates severe growth retardation and health problems. Hibiscus syriacus is an ornamental plant that can tolerate various abiotic stresses, including Cd stress. Therefore, it is proposed as a plant material in Cd-polluted areas. However, the molecular mechanisms of H. syriacus tolerance to Cd are not yet understood. RESULTS: This study investigated the physiological and transcriptional response of "Hongxing", a Cd2+-tolerant H. syriacus variety, grown on a substrate containing higher concentration of Cd (400 mg/kg). The Cd treatment induced only 28% of plant mortality, but a significant decrease in the chlorophyll content was observed. Malondialdehyde content and activity of the antioxidant enzymes catalase, peroxidase, and superoxide dismutase were significantly increased under Cd stress. Transcriptome analysis identified 29,921 differentially expressed genes (DEGs), including 16,729 down-regulated and 13,192 up-regulated genes, under Cd stress. Functional enrichment analyses assigned the DEGs mainly to plant hormone signal transduction, transport, nucleosome and DNA processes, mitogen-activated protein kinase signaling pathway, antioxidant process, fatty acid metabolism, and biosynthesis of secondary metabolites. Many MYB, EP2/ERF, NAC, WRKY family genes, and genes containing metal binding domains were up-regulated, implying that they are essential for the Cd-stress response in H. syriacus. The most induced genes were filtered out, providing valuable resources for future studies. CONCLUSIONS: Our findings provide insights into the molecular responses to Cd stress in H. syriacus. Moreover, this study offers comprehensive and important resources for future studies toward improving the plant Cd tolerance and its valorization in phytoremediation.

Transcriptome analysis reveals the key pathways and candidate genes involved in salt stress responses in Cymbidium ensifolium leaves.

BACKGROUND: Cymbidium ensifolium L. is known for its ornamental value and is frequently used in cosmetics. Information about the salt stress response of C. ensifolium is scarce. In this study, we reported the physiological and transcriptomic responses of C. ensifolium leaves under the influence of 100 mM NaCl stress for 48 (T48) and 96 (T96) hours. RESULTS: Leaf Na+ content, activities of the antioxidant enzymes i.e., superoxide dismutase, glutathione S-transferase, and ascorbate peroxidase, and malondialdehyde content were increased in salt-stressed leaves of C. ensifolium. Transcriptome analysis revealed that a relatively high number of genes were differentially expressed in CKvsT48 (17,249) compared to CKvsT96 (5,376). Several genes related to salt stress sensing (calcium signaling, stomata closure, cell-wall remodeling, and ROS scavenging), ion balance (Na+ and H+), ion homeostasis (Na+/K+ ratios), and phytohormone signaling (abscisic acid and brassinosteroid) were differentially expressed in CKvsT48, CKvsT96, and T48vsT96. In general, the expression of genes enriched in these pathways was increased in T48 compared to CK while reduced in T96 compared to T48. Transcription factors (TFs) belonging to more than 70 families were differentially expressed; the major families of differentially expressed TFs included bHLH, NAC, MYB, WRKY, MYB-related, and C3H. A Myb-like gene (CenREV3) was further characterized by overexpressing it in Arabidopsis thaliana. CenREV3's expression was decreased with the prolongation of salt stress. As a result, the CenREV3-overexpression lines showed reduced root length, germination %, and survival % suggesting that this TF is a negative regulator of salt stress tolerance. CONCLUSION: These results provide the basis for future studies to explore the salt stress response-related pathways in C. ensifolium.

Leaf-transcriptome profiles of phoebe bournei provide insights into temporal drought stress responses.

Phoebe bournei (Hemsl.) Yang is used as a commercial wood in China and is enlisted as a near-threatened species. Prolonged droughts pose a serious threat to young seedlings (1-2 years old). A transcriptome sequencing approach, together with the measurement of growth parameters and biochemical analyses were used to understand P. bournei's drought responses on 15d, 30d, and 45d of drought stress treatment. The stem and root dry weights decreased significantly with drought stress duration. Activities of antioxidative enzymes i.e., peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) increased significantly with the increase in drought stress duration. A total of 13,274, 15,648, and 9,949 genes were differentially expressed in CKvs15d, CKvs30d, and CKvs45d, respectively. The differential expression analyses showed that photosystem I and II underwent structural changes, chlorophyll biosynthesis, and photosynthesis were reduced. The genes annotated as POD, SOD, and CAT were upregulated in drought-treated leaves as compared to control. Additionally, plant-hormone signal transduction, MAPK signaling-plant, phenylpropanoid biosynthesis, flavonoid biosynthesis, and starch and sucrose metabolism pathways showed large-scale expression changes in major genes. We also found that members of 25 transcription factor families were differentially expressed. Our study presents and discusses these transcriptome signatures. Overall, our findings represent key data for breeding towards drought stress tolerance in P. bournei.

The effect of high-fructose corn syrup vs. sucrose on anthropometric and metabolic parameters: A systematic review and meta-analysis.

High-fructose corn syrup (HFCS) has been speculated to have stronger negative metabolic effects than sucrose. However, given the current equivocality in the field, the aim of the present study was to determine the impact of HFCS use compared to sucrose on anthropometric and metabolic parameters. We searched PubMed, Scopus, Cochrane Central and web of sciences, from database inception to May 2022. A random effects model and the generic inverse variance method were applied to assess the overall effect size. Heterogeneity analysis was performed using the Cochran Q test and the I2 index. Four articles, with 9 arms, containing 767 participants were included in this meta-analysis. Average HFCS and sucrose usage equated to 19% of daily caloric intake. Combined data from three studies indicated that HFCS intake does not significantly change the weight (weighted mean difference (WMD): -0.29 kg, 95% CI: -1.34, 0.77, I2 = 0%) when compared to the sucrose group. Concordant results were found for waist circumstance, body mass index, fat mass, total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Moreover, overall results from three studies indicated a significant increase in CRP levels (WMD: 0.27 mg/l, 95% CI: 0.02, 0.52, I2 = 23%) in the HFCS group compared to sucrose. In conclusion, analysis of data from the literature suggests that HFCS consumption was associated with a higher level of CRP compared to sucrose, whilst no significant changes between the two sweeteners were evident in other anthropometric and metabolic parameters.

Macrophage-Derived Exosomes in TLR9-/- Mice Ameliorate Sepsis-Induced Mitochondrial Oxidative Stress and Apoptosis in Cardiomyocytes.

Objective: To explore the mechanisms of TLR9 from macrophages on mitochondrial apoptosis in cardiomyocytes at early stage of sepsis. Methods: The in vivo and in vitro sepsis mice were bone marrow transplantation (BMT) with wild type (WT) or (toll-like receptor 9) TLR9 knockout (-/- or KO) myeloid cells and then constructed by cecum ligation and puncture (CLP) as vivo experiment and cardiomyocytes cocultured with WT or TLR9-deficient macrophages treated with LPS as vitro experiment, respectively. Sepsis model were performed by CLP. The expression levels of exosome, PI3K/AKT, and ERK1/2, inflammatory factors, and apoptotic proteins were tested by western blot in vivo. Besides, associated apoptotic proteins and JC-1 fluorescence assay were tested in vitro. Results: The expressions of p-PI3K, p-AKT, exosome markers (CD9, CD63, and TSG101), p-ERK1/2, TNF-α, IFN-γ, IL-1ß, and cleaved-caspase-3/-9 were significantly increased in septic mice vs. control mice, and these proteins were declined dramatically in TLR9-/- BMT mice vs. WT BMT mice in sepsis mice models. Meanwhile, the protein expression of cytochrome C, cleaved-caspase-3, and cleaved-caspase-9 increased significantly in primary mouse myocardial cells cocultured with TLR9-/- or WT macrophages stimulated with LPS, and these mitochondrial apoptotic proteins as well as the green 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolcarbocyanine iodide (JC-1) fluorescence were dramatically lower in LPS-stimulated cardiomyocytes cocultured with TLR9-/- than with WT macrophages. Conclusion: TLR9-/- in macrophages suppressed the inflammatory reaction as well as the exosome secretion and resulted in the inhibition of apoptosis and oxidative stress in sepsis-induced cardiomyopathy.

Xiao'er Xiaoji Zhike Oral Liquid Combined with Azithromycin for Mycoplasma pneumoniae Pneumonia in Children: A Systematic Review and Meta-Analysis.

BACKGROUND: This study was aimed at systematically evaluating the clinical effect and safety of Xiao'er Xiaoji Zhike oral liquid in the treatment of Mycoplasma pneumoniae pneumonia (MPP) in children and providing evidence-based references for clinical application. METHODS: The databases like Chinese Biomedical Literature Database, China Network Knowledge Infrastructure, Wan Fang Database, Chinese Scientific Journal Database, PubMed, EmBase, and the Cochrane Library were systematically investigated via searching clinical trials about Xiao'er Xiaoji Zhike oral liquid in treating MPP from the establishment of these databases to Jun 8, 2020, the valid data from which were entered meta-analysis. The quality of evidence was assessed by GRADE criteria. RESULTS: Totally, 15 trials and 1500 patients were involved in this review. It showed that clinical efficacy of trial group was more superior than control group at the outcome measures of cough disappearance time, lung rale disappearance time, fever subsidence time, total effective rate, lung X-ray infiltrates disappearing time, reduction of hospital stay, immunological indexes, and some other measures. And the differences between groups were statistically significant. There was no statistical difference in the adverse effects between two groups. Lung X-ray infiltrates disappearing time and cough disappearance time were separately high- and moderate-quality evidences while lung rale disappearance time and fever subsidence time were all low in accordance with GRADE criteria. CONCLUSIONS: In accordance with trials with low methodological quality, Xiao'er Xiaoji Zhike oral liquid combined with azithromycin seems to be safe and superior to azithromycin alone for the treatment of MPP in children. However, further trials with rigorous methodology need to be implemented for these potential benefits.

Interfacial water intercalation-induced metal-insulator transition in NbS2/BN heterostructure.

Interfacial engineering, such as molecule intercalation, can modify properties and optimize performance of van der Waals heterostructures and their devices. Here, we investigated the pristine and water molecule intercalated heterointerface of niobium disulphide (NbS2) on hexagonal boron nitride (h-BN) (NbS2/BN) using advanced atomic force microscopy (AFM), and observed the metal-insulator transition (MIT) of first layer (1L-) of NbS2 induced by water molecule intercalation. In pristine sample, interfacial charge transfers were confirmed by the direct detection of trapped static charges at the post-exposed h-BN surface, produced by mechanically peeling off the 1L-NbS2 from the substrate. The interfacial charge transfers facilitate the intercalation of water molecules at the heterointerface. The intercalated water layers make a MIT of 1L-NbS2, while the pristine metallic state of the following NbS2 layers remains preserved. This work is of great significance to help understand the interfacial properties of 2D metal/insulator heterostructures and can pave the way for further preparation of an ultrathin transistor.

Dynamic interfacial mechanical-thermal characteristics of atomically thin two-dimensional crystals.

Owing to the flexible nanoelectronic applications of two-dimensional (2D) materials, further exploration of their nanoscale local mechanical properties and their coupled physical characteristics becomes extremely significant. The puckering effect is a typical micro/nanoscale local frictional characteristic generally in the tip-film-substrate system, which is simultaneously expected to be coupled with a dynamic thermal interfacial response. Here, applying scanning thermal microscopy (SThM), we observed a novel mechanical-thermal coupling effect in monolayer/bilayer MoS2 and WS2 films: puckering deformation can induce the enhancement of interfacial thermal resistance (TR). By the SThM method, the puckering effect was further proved to depend on the film thickness and the scan velocity. More importantly, the crystallographic orientation-dependent anisotropy of the puckering effect in atomically thin two-dimensional crystals was demonstrated by SThM. It is inferred that the puckering deformation of the film redistributes the in-plane stress, resulting in the isotropy breaking of the in-plane stiffness. Such new findings are of great significance to help optimize the nanoscale tribological/thermal design and dynamic mechanical-thermal management of 2D-materials in nanoelectronics.

Nanoscale charge transfer and diffusion at the MoS2/SiO2 interface by atomic force microscopy: contact injection versus triboelectrification.

Understanding the process of charge generation, transfer, and diffusion between two-dimensional (2D) materials and their supporting substrates is very important for potential applications of 2D materials. Compared with the systematic studies of triboelectric charging in a bulk sample, a fundamental understanding of the triboelectrification of the 2D material/insulator system is rather limited. Here, the charge transfer and diffusion of both the SiO2 surface and MoS2/SiO2 interface through contact electrification and frictional electrification are investigated systematically in situ by scanning Kelvin probe microscopy and dual-harmonic electrostatic force microscopy. Different from the simple static charge transfer between SiO2 and the PtSi alloy atomic force microscope (AFM) tip, the charge transfer between the tip and the MoS2/SiO2 system is complicated. Triboelectric charges, generated by contact or frictional electrification with the AFM tip, are trapped at the MoS2/SiO2 interface and act as floating gates. The local charge discharge processes can be obtained by monitoring the surface potential. The charge decay time (τ) of the MoS2/SiO2 interface is one (or two) orders of magnitude larger than the decay time τ of the SiO2 surface. This work facilitates an understanding of the triboelectric and de-electrification of the interface between 2D materials and substrates. In addition to the charge transfer and diffusion, we demonstrate the nanopatterns of surface and interfacial charges, which have great potential for the application of self-assembly of charged nanostructures.