IgG antibody response to SARS-CoV-2 infection and its influencing factors in lymphoma patients.

BACKGROUND: The ability of generating effective humoral immune responses to SARS-CoV-2 infection has not been clarified in lymphoma patients. The study aimed to investigate the antibody (Ab) production after SARS-Cov-2 infection and clarify the factors affecting the Ab generation in these patients. PATIENTS & METHODS: 80 lymphoma patients and 51 healthy controls were included in this prospective observational study. Clinical factors and treatment regimens affecting Ab positive rate (APR) and Ab levels were analyzed by univariate and multivariate methods. RESULTS: The anti-SARS-CoV-2 IgG APR and Ab levels in lymphoma patients were significantly lower than those in healthy controls. Lymphoma patients with COVID-19 vaccination had significantly higher APR and Ab levels compared with those without vaccination. Additionally, the use of dexamethasone for COVID-19 treatment had a negative impact on Ab levels. For the impact of treatment regimens on the APR and Ab levels, the results showed that patients treated with ≥ 6 times CD20 monoclonal Ab (mAb) and patients treated with autologous hematopoietic stem cell transplantation (ASCT) prior to infection produced a statistically lower APR and Ab levels compared with those treated with 1-5 times CD20 mAb and those treated without ASCT, respectively. Furthermore, multiple regression analysis indicated that the number of anti-CD20 treatment was an independent predictor for both APR and Ab levels. CONCLUSIONS: Humoral immune response to SARS-CoV-2 infection was impaired in lymphoma patients partly due to anti-CD20 and ASCT treatment. COVID-19 vaccination may be more needed for these patients.

Slow-light silicon modulator with 110-GHz bandwidth.

Silicon modulators are key components to support the dense integration of electro-optic functional elements for various applications. Despite numerous advances in promoting the modulation speed, a bandwidth ceiling emerges in practices and becomes an obstacle toward Tbps-level throughput on a single chip. Here, we demonstrate a compact pure silicon modulator that shatters present bandwidth ceiling to 110 gigahertz. The proposed modulator is built on a cascade corrugated waveguide architecture, which gives rise to a slow-light effect. By comprehensively balancing a series of merits, the modulators can benefit from the slow light for better efficiency and compact size while remaining sufficiently high bandwidth. Consequently, we realize a 110-gigahertz modulator with 124-micrometer length, enabling 112 gigabits per second on-off keying operation. Our work proves that silicon modulators with 110 gigahertz are feasible, thus shedding light on its potentials in ultrahigh bandwidth applications such as optical interconnection and photonic machine learning.

Interoceptive regulation of skeletal tissue homeostasis and repair.

Recent studies have determined that the nervous system can sense and respond to signals from skeletal tissue, a process known as skeletal interoception, which is crucial for maintaining bone homeostasis. The hypothalamus, located in the central nervous system (CNS), plays a key role in processing interoceptive signals and regulating bone homeostasis through the autonomic nervous system, neuropeptide release, and neuroendocrine mechanisms. These mechanisms control the differentiation of mesenchymal stem cells into osteoblasts (OBs), the activation of osteoclasts (OCs), and the functional activities of bone cells. Sensory nerves extensively innervate skeletal tissues, facilitating the transmission of interoceptive signals to the CNS. This review provides a comprehensive overview of current research on the generation and coordination of skeletal interoceptive signals by the CNS to maintain bone homeostasis and their potential role in pathological conditions. The findings expand our understanding of intersystem communication in bone biology and may have implications for developing novel therapeutic strategies for bone diseases.

Sprayed PAA-CaO2 nanoparticles combined with calcium ions and reactive oxygen species for antibacterial and wound healing.

The most common socioeconomic healthcare issues in clinical are burns, surgical incisions and other skin injuries. Skin lesion healing can be achieved with nanomedicines and other drug application techniques. This study developed a nano-spray based on cross-linked amorphous calcium peroxide (CaO2) nanoparticles of polyacrylic acid (PAA) for treating skin wounds (PAA-CaO2 nanoparticles). CaO2 serves as a 'drug' precursor, steadily and continuously releasing calcium ions (Ca2+) and hydrogen peroxide (H2O2) under mildly acidic conditions, while PAA-CaO2 nanoparticles exhibited good spray behavior in aqueous form. Tests demonstrated that PAA-CaO2 nanoparticles exhibited low cytotoxicity and allowed L929 cells proliferation and migration in vitro. The effectiveness of PAA-CaO2 nanoparticles in promoting wound healing and inhibiting bacterial growth in vivo was assessed in SD rats using full-thickness skin defect and Staphylococcus aureus (S.aureus)-infected wound models based thereon. The results revealed that PAA-CaO2 nanoparticles demonstrated significant advantages in both aspects. Notably, the infected rats' skin defects healed in 12 days. The benefits are linked to the functional role of Ca2+ coalesces with H2O2 as known antibacterial and healing-promoted agents. Therefore, we developed nanoscale PAA-CaO2 sprays to prevent bacterial development and heal skin lesions.

ARHGAP4 promotes leukemogenesis in acute myeloid leukemia by inhibiting DRAM1 signaling.

Rho GTPase-activating protein 4 (ARHGAP4) is an important Rho family GTPase-activating protein that is strongly associated with the onset and progression of some tumors. We found that ARHGAP4 mRNA and protein are overexpressed in human acute myeloid leukemia (AML) patients and are associated with a poor prognosis. ARHGAP4 knockdown significantly impairs viability and colony formation capacity and induces apoptosis in AML cells. Further results demonstrate that ARHGAP4 deletion impairs AML progression in vivo. Interestingly, DRAM1 signaling is significantly activated in AML cells with ARHGAP4 knockdown. Our results also indicated that ARHGAP4 might function in AML cells by binding with p53 to inhibit DRAM1. Moreover, knockdown of DRAM1 rescues the defects of ARHGAP4 in AML cells. This newly described role of the ARHGAP4/DRAM1 axis in regulating AML progression may have important therapeutic implications.

Long noncoding RNA SENCR facilitates the progression of acute myeloid leukemia through the miR-4731-5p/IRF2 pathway.

BACKGROUND: Acute myeloid leukemia (AML) is a type of hematological tumor caused by malignant clone hematopoietic stem cells. The relationship between lncRNAs and tumor occurrence and progression has been gaining attention. Research has shown that Smooth muscle and endothelial cell-enriched migration/differentiation-associated lncRNA (SENCR) is abnormally expressed in various diseases, whereas its role in AML is still poorly understood. METHODS: The expression of SENCR, microRNA-4731-5p (miR-4731-5p) and Interferon regulatory factor 2 (IRF2) were measured using qRT-PCR. The proliferation, cycle and apoptosis of AML cells with or without knockdown of SENCR were detected by CCK-8 assay, EdU assay, flow cytometry, western blotting and TUNEL assay, respectively. Consistently, SENCR knockdown was impaired the AML progression in immunodeficient mice. In addition, the binding of miR-4731-5p to SENCR or IRF2 was confirmed by luciferase reporter genes assay. Finally, rescue experiments were conducted to confirm the role of SENCR/miR-4731-5p/IRF2 axis in AML. RESULTS: SENCR is highly expressed in AML patients and cell lines. The patients with high SENCR expression had poorer prognosis compared with those with low SENCR expression. Interestingly, knockdown of SENCR inhibits the growth of AML cells. Further results demonstrated that the reduction of SENCR slows the progression of AML in vivo. SENCR could function as a competing endogenous RNA (ceRNA) to negatively regulate miR-4731-5p in AML cells. Furthermore, IRF2 was validated as a direct target gene of miR-4731-5p in AML cells. CONCLUSIONS: Our findings underscore the important role of SENCR in regulating the malignant phenotype of AML cells by targeting the miR-4731-5p/IRF2 axis.

Oxymatrine boosts hematopoietic regeneration by modulating MAPK/ERK phosphorylation after irradiation-induced hematopoietic injury.

Hematopoietic toxicity due to ionizing radiation (IR) is a leading cause of death in nuclear incidents, occupational hazards, and cancer therapy. Oxymatrine (OM), an extract originating from the root of Sophora flavescens (Kushen), possesses extensive pharmacological properties. In this study, we demonstrate that OM treatment accelerates hematological recovery and increases the survival rate of mice subjected to irradiation. This outcome is accompanied by an increase in functional hematopoietic stem cells (HSCs), resulting in enhanced hematopoietic reconstitution abilities. Mechanistically, we observed significant activation of the MAPK signaling pathway, accelerated cellular proliferation, and decreased cell apoptosis. Notably, we identified marked increases in the cell cycle transcriptional regulator Cyclin D1 (Ccnd1) and the anti-apoptotic protein BCL2 in HSCs after OM treatment. Further investigation revealed that the expression of Ccnd1 transcript and BCL2 levels were reversed upon specific inhibition of ERK1/2 phosphorylation, effectively negating the rescuing effect of OM. Moreover, we determined that targeted inhibition of ERK1/2 activation significantly counteracted the regenerative effect of OM on human HSCs. Taken together, our results suggest a crucial role for OM in hematopoietic reconstitution following IR via MAPK signaling pathway-mediated mechanisms, providing theoretical support for innovative therapeutic applications of OM in addressing IR-induced injuries in humans.

Recent Progress in Silicon-Based Slow-Light Electro-Optic Modulators.

As an important optoelectronic integration platform, silicon photonics has achieved significant progress in recent years, demonstrating the advantages on low power consumption, low cost, and complementary metal-oxide-semiconductor (CMOS) compatibility. Among the different silicon photonics devices, the silicon electro-optic modulator is a key active component to implement the conversion of electric signal to optical signal. However, conventional silicon Mach-Zehnder modulators and silicon micro-ring modulators both have their own limitations, which will limit their use in future systems. For example, the conventional silicon Mach-Zehnder modulators are hindered by large footprint, while the silicon micro-ring modulators have narrow optical bandwidth and high temperature sensitivity. Therefore, developing a new structure for silicon modulators to improve the performance is a crucial research direction in silicon photonics. Meanwhile, slow-light effect is an important physical phenomenon that can reduce the group velocity of light. Applying slow-light effect on silicon modulators through photonics crystal and waveguide grating structures is an attractive research point, especially in the aspect of reducing the device footprint. In this paper, we review the recent progress of silicon-based slow-light electro-optic modulators towards future communication requirements. Beginning from the principle of slow-light effect, we summarize the research of silicon photonic crystal modulators and silicon waveguide grating modulators in detail. Simultaneously, the experimental results of representative silicon slow-light modulators are compared and analyzed. Finally, we discuss the existing challenges and development directions of silicon-based slow-light electro-optic modulators for the practical applications.

Activation of 5-Hydroxytryptamine 4 Receptor Improves Colonic Barrier Function by Triggering Mucin 2 Production in a Mouse Model of Type 1 Diabetes.

Diabetes leads to intestinal barrier dysfunction. 5-Hydroxytryptamine 4 receptor (5-HT4R) is distributed in the colonic mucosa, but little is known about the role of its activation in diabetes-evoked colonic barrier dysfunction. This study investigates whether activation of 5-HT4Rs on goblet cells (GCs) protects the colon from commensal bacterial translocation in diabetic mice. Expression of 5-HT4R detected inside the colonic epithelium by RNAscope in situ hybridization was further observed within the mucin 2 (MUC2)-immunoreactive GCs. In diabetic mice, neither 5-HT4R transcription nor protein levels were altered compared with those in nondiabetic mice. Bacterial translocation was characterized by 16S rRNA RNAscope in situ hybridization and manifested in both crypts and lamina propria of the colon in diabetic mice. Mucin production and MUC2 expression were significantly decreased in diabetic mice. Furthermore, the loss of mitochondrial cristae of GCs and the down-regulation of mitofilin, the core protein maintaining mitochondrial homeostasis, were observed in diabetic mice. Long-term treatment with 5-HT4R agonist in diabetic mice not only prevented bacterial penetration of the whole colonic mucosa but also promoted mucin production and MUC2 expression. Markedly, 5-HT4R agonist also restored the mitochondrial cristae of GCs and up-regulated mitofilin. However, co-administration of 5-HT4R antagonist abolished the effects of 5-HT4R agonist on diabetic mice. These findings indicate that 5-HT4R in colonic mucosa is an effective target for the treatment of diabetes-induced colonic mucous barrier dysfunction.

Photocrosslinking silver nanoparticles-aloe vera-silk fibroin composite hydrogel for treatment of full-thickness cutaneous wounds.

Damage to the skin causes physiological and functional issues. The most effective treatment approach is the use of wound dressings. Silk fibroin (SF) is a promising candidate biomaterial for regulating wound healing; however, its antibacterial properties and biological activity must be further improved. In this study, a photocrosslinking hydrogel was developed to treat full-thickness cutaneous wounds. The composite hydrogel (Ag-AV-SF hydrogel) was prepared by introducing the silver nanoparticles (AgNPs) and aloe vera (AV) as the modifiers. In vitro study exhibited great antibacterial ability, biocompatibility and cell-proliferation and -migration-promoting capacities. It also showed the pH-response releasing properties which release more AgNPs in a simulated chronic infection environment. The healing effect evaluation in vivo showed the healing-promoting ability of the Ag-AV-SF hydrogel was stronger than the single-modifiers groups, and the healing rate of it reached 97.02% on Day 21, higher than the commercial wound dressing, silver sulfadiazine (SS) cream on sale. Additionally, the histological and protein expression results showed that the Ag-AV-SF hydrogel has a greater effect on the pro-healing regenerative phenotype with M2 macrophages at the early stage, reconstructing the blood vessels networks and inhibiting the formation of scars. In summary, the Ag-AV-SF hydrogel developed in this study had good physical properties, overwhelming antibacterial properties, satisfactory biocompatibility and significantly promoting effect on cell proliferation, migration and wound healing. Overall, our results suggest that the Ag-AV-SF hydrogel we developed has great potential for improving the wound healing in clinical treatment.

Vascular Endothelial Growth Factor Mediates the Sprouted Axonogenesis of Breast Cancer in Rat.

Nerve infiltration into the tumor is a common feature of the tumor microenvironment. The mechanisms of axonogenesis in breast cancer remain unclear. We hypothesized that vascular endothelial growth factor (VEGF), as well as nerve growth factor (NGF), is involved in the axonogenesis of breast cancer. A N-methyl-N-nitrosourea (MNU)-induced rat model of breast cancer was used to explore the presence of axonogenesis in breast tumor and the involvement of VEGF, as well as NGF, in the axonogenesis of breast tumor. Nerve infiltration into the tumor was found in MNU-induced rat model of breast cancer including the sensory and sympathetic nerve fibers. Nerve density was increased following the growth of tumor. The sensory neurons innervating the thoracic and abdominal mammary tumors peaked at T5 to T6 and L1 to L2 dorsal root ganglions, respectively. Either VEGF receptor inhibitor or antibody against VEGF receptor 2, as well as NGF receptor inhibitor, apparently decreased both the nerve density and vascular density of breast tumor. The reduced nerve density was correlated with the decreased vascular density induced by these treatments. In cultured dorsal root ganglion neurons, phosphatidylinositol 3 (PI3K)/Akt, extracellular signal-regulated protein kinase (ERK), and p38 inhibitors significantly attenuated VEGF-induced neurite elongation. These findings provide direct evidence that VEGF, as well as NGF, may control the axonogenesis of breast cancer.

Curcumin ameliorates rat experimental autoimmune neuritis.

Experimental autoimmune neuritis (EAN) is a helper T cell-mediated autoimmune demyelinating inflammatory disease of the peripheral nervous system that serves as an animal model for human Guillain-Barre syndrome. Curcumin, a naturally occurring polyphenolic phytochemical isolated from the medicinal plant Curcuma longa, has anti-inflammatory activities. Here we investigated the therapeutic effects and potential mechanisms of curcumin in EAN rats. Exogenous curcumin treatment (100 mg/kg/day) significantly delayed the onset of EAN neurological signs, ameliorated EAN neurological severity, and reduced body weight loss of EAN rats. In EAN sciatic nerves, curcumin treatment suppressed the inflammatory cell accumulation and the expression of interferon (IFN)-γ, tumor necrosis factor-α, interleukin (IL)-1ß, and IL-17. Furthermore, curcumin treatment significantly decreased the percentage of CD4(+) T helper cells in EAN spleen and suppressed concanavalin A-induced lymphocyte proliferation in vitro. In addition, curcumin altered helper T cell differentiation by decreasing IFN-γ(+) CD4(+) Th1 cells in EAN lymph node and spleen. In summary, our data demonstrate that curcumin could effectively suppress EAN by attenuating inflammation, indicating that curcumin might be a candidate for treatment of autoimmune neuropathies.