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The thymus is one of the most crucial immunological organs, undergoing visible age-related shrinkage. Thymic epithelial cells (TECs) play a vital role in maintaining the normal function of the thymus, and their degeneration is the primary cause of age-induced thymic devolution. Thymosin β4 (Tβ4) serves as a significant important G-actin sequestering peptide. The objective of this study was to explore whether Tβ4 influences thymocyte differentiation by regulating the cytoskeletal rearrangement and mitochondrial transfer of TECs. A combination of H&E staining, immunofluorescence, transmission electron microscopy, RT-qPCR, flow cytometry, cytoskeletal immunolabeling, and mitochondrial immunolabeling were employed to observe the effects of Tβ4 on TECs' skeleton rearrangement, mitochondrial transfer, and thymocyte differentiation. The study revealed that the Tβ4 primarily regulates the formation of microfilaments and the mitochondrial transfer of TECs, along with the formation and maturation of double-negative cells (CD4−CD8−) and CD4 single-positive cells (CD3+TCRβ+CD4+CD8−) thymocytes. This study suggests that Tβ4 plays a crucial role in thymocyte differentiation by influencing the cytoskeletal rearrangement and mitochondrial transfer of TECs. These effects may be associated with Tβ4's impact on the aggregation of F-actin. This finding opens up new avenues for research in the field of immune aging. [ABSTRACT FROM AUTHOR]

Thymosin α1 (Tα1) is an immunostimulatory peptide that is commonly used as an immune enhancer in viral infectious diseases such as hepatitis B, hepatitis C, and acquired immune deficiency syndrome (AIDS). Tα1 can influence the functions of immune cells, such as T cells, B cells, macrophages, and natural killer cells, by interacting with various Toll-like receptors (TLRs). Generally, Tα1 can bind to TLR3/4/9 and activate downstream IRF3 and NF-κB signal pathways, thus promoting the proliferation and activation of target immune cells. Moreover, TLR2 and TLR7 are also associated with Tα1. TLR2/NF-κB, TLR2/p38MAPK, or TLR7/MyD88 signaling pathways are activated by Tα1 to promote the production of various cytokines, thereby enhancing the innate and adaptive immune responses. At present, there are many reports on the clinical application and pharmacological research of Tα1, but there is no systematic review to analyze its exact clinical efficacy in these viral infectious diseases via its modulation of immune function. This review offers an overview and discussion of the characteristics of Tα1, its immunomodulatory properties, the molecular mechanisms underlying its therapeutic effects, and its clinical applications in antiviral therapy. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has remarkably affected the business processes and performance of micro-, small-, and medium-sized enterprises (MSMEs) across the world. MSMEs have had to adopt and implement numerous strategies to sustain their businesses, and their financial and sustainability performance has been impacted by their choice of e-commerce (EC) platforms and digital marketing (DM) strategies. The objective of this research was to explore the effects of EC and DM platforms and strategies on facilitating MSMEs' financial and sustainability performance amid the devastating COVID-19 pandemic. This study gathered data from 212 MSMEs from three districts of Bangladesh. A partial least squares structural equation modeling (PLS-SEM) approach was undertaken, to test the hypothesized model. The findings revealed that e-commerce had a significant association with MSMEs' financial performance and sustainability amid the pandemic. It was also observed that digital marketing strategies had a substantial impact on MSMEs' financial performance. However, the linkage between DM strategies and MSMEs' sustainability was found to be insignificant. Furthermore, it was found that the financial performance of MSMEs mediated the relationship between e-commerce adoption and their sustainability performance. These findings contribute to the extant technology adoption literature, by exploring the role of e-commerce and digital marketing on firms' financial outcomes amid a global pandemic. Managers and policymakers of small businesses can learn several things from this study, and understand how crucial digital commerce and digital marketing are to their success and long-term survival. [ABSTRACT FROM AUTHOR]

The thymus is the most sensitive organ under various pathophysiological conditions, such as aging, starvation, and infection. As a key stromal cell for T cell development, it is well-known that thymic epithelial cells (TECs) play an important role in the thymus response to the external environment. Thymosin beta 15 (Tβ15) is a G-actin binding protein secreted by TECs, it plays an important role in maintaining the dynamic balance of actin, angiogenesis, axonal formation, and wound healing, but the relationship between Tβ15 and TECs is not clear yet. Here, we show the impact of Tβ15 on the TEC's spatial development, as well as the T-cell differentiation and thymic output. As a result, TEC is the main effector cell of Tβ15 in the thymus. Tβ15 OX inhibits the chemotaxis of TECs to the medulla and subsequently blocks the positive selection of thymocytes from CD3+TCRβ+CD4+CD8+ double positive cells to CD3+TCRβ+CD4+CD8− single-positive (CD4SP) cells. Tβ15-knockdown accelerates the reticular differentiation of astral TECs and medullary TECs. Importantly, mice implanted with Tβ15-knockdown iTECs show high thymic output but low peripheral T cell maturity and activity. In a word, our results explain the role of Tβ15 on the differentiation and function of TECs and provide a new perspective for understanding the process of thymus development and degeneration. [ABSTRACT FROM AUTHOR]

Abstract The main purpose of this paper is using the analytic method to study the convergent properties of the Jozse Sandor's function, and obtain some interesting results. Keywords Riemann zeta-function, [...]

Highly nonlinear systems exist in many real-world applications. The control design of such systems is challenging even for existing advanced control theory. Besides, when there is uncertainty in the nonlinear system and networked control strategy is considered, the problem will become even more complicated. To confront the problem, for the first time, this article provides a solution for the tracking control design of the nonlinear networked control systems (NCSs) subject to uncertainty under the polynomial event-triggered mechanism (PETM). In the proposed tracking control scheme, the nonlinearity in the NCSs is effectively represented by a polynomial fuzzy model while the uncertainty is handled by the interval type-2 (IT2) fuzzy sets. The tracking control objective is to properly design the event-triggered IT2 polynomial controller, which drives the states of the plant to track those of the stable reference system under the PETM. Different from the existing works in the literature, the event-triggering condition can be varied according to the state to improve the flexibility and capacity of event-triggered mechanism. Furthermore, in some works reported in the literature, the perfect match of premise variables is assumed. However, this assumption is extremely difficult to be fulfilled in the event-triggered control applications. To address the long-standing challenge of an intrinsic mismatch issue of the premise variables due to event-triggering mechanism, in the proposed analysis, the imperfect premise matching (IPM) concept is adopted along with the membership-function-dependent (MFD) approach to facilitate the stability analysis and control synthesis. The stability conditions are summarized as sum-of-squares (SOS). The H∞ index is utilized to evaluate the tracking control performance, and the performance can be improved through minimizing the H∞ index. A detailed simulation example is provided to verify the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

As one of the most abundant immune cell populations in the tumor microenvironment (TME), tumor‐associated macrophages (TAMs) play important roles in multiple solid malignancies, including breast cancer, prostate cancer, liver cancer, lung cancer, ovarian cancer, gastric cancer, pancreatic cancer, and colorectal cancer. TAMs could contribute to carcinogenesis, neoangiogenesis, immune‐suppressive TME remodeling, cancer chemoresistance, recurrence, and metastasis. Therefore, reprogramming of the immune‐suppressive TAMs by pharmacological approaches has attracted considerable research attention in recent years. In this review, the promising pharmaceutical targets, as well as the existing modulatory strategies of TAMs were summarized. The chemokine–chemokine receptor signaling, tyrosine kinase receptor signaling, metabolic signaling, and exosomal signaling have been highlighted in determining the biological functions of TAMs. Besides, both preclinical research and clinical trials have suggested the chemokine–chemokine receptor blockers, tyrosine kinase inhibitors, bisphosphonates, as well as the exosomal or nanoparticle‐based targeting delivery systems as the promising pharmacological approaches for TAMs deletion or reprogramming. Lastly, the combined therapies of TAMs‐targeting strategies with traditional treatments or immunotherapies as well as the exosome‐like nanovesicles for cancer therapy are prospected. [ABSTRACT FROM AUTHOR]

Based on DEA - Tobit model, the efficiency of occupational training for rural migrant workers of 30 provinces and cities was studied in this paper. The results indicated that there are significant differences among these 30 provinces and cities. Technical efficiency of East areas is lower than average level. Moreover, there is a significant negative correlation between the efficiency and Average education attainment, and a significant positive correlation between the efficiency and proportion of rural population. [ABSTRACT FROM AUTHOR]

Ruyong Formula (RYF) is a famous Chinese herbal formula composed of 10 traditional Chinese herbs. It has been used as a therapeutic agent for breast cancer patients with depressive symptoms in China. However, its underlying pharmacological mechanism remains unclear. This study aimed to explore the mechanism of RYF on the changes of thymus immune function in breast cancer body under mood disorders such as depression/anxiety. The chronic unpredictable mild stress (CUMS) was used to stimulate 4T1 breast cancer mice. The behavioral changes, 5-hydroxytryptamine (5-HT) level in brain, cytokeratin 5 (CK5) and 8 (CK8) expression in thymus, the proportion of T cell subsets, the thymic output, phenotypic changes of thymus epithelial cells (TECs), the expression levels of immune-related factors and downstream proteins of TSLP were analyzed after RYF treatment. In CUMS stimulated group, the level of 5-HT in brain was significantly increased after RYF treatment. The output function of the thymus was improved, and the number of TECs in the medulla (CK5+), the proportion of CD3+CD4−CD8− (Double negative) and CD3+CD4+CD8+ (Double positive) T cells were all increased. The mRNA level of TSLP in mouse thymus was significantly decreased, but increased for IL-7. The protein levels of TSLP and Vimentin were decreased, but increased for p-STAT3, p-JAK2, E-cadherin, and p-PI3K p55 in vivo. In vitro study was showed the levels of Snail 1, Zeb 1 and Smad increased significantly in TGF-β1 group, and RYF could reverse their expression. RYF could restore the structure and function of the thymus in depressed breast cancer mice by reversing the phenotypic changes of TECs and activating the JAK2/STAT3/PI3K pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Danshen (Salvia miltiorrhiza) is a well-known herb in Traditional Chinese Medicine (TCM) for treating cardiovascular diseases, but the underlying mechanism remains to be fully elucidated. Here, we showed that Danshen and its active ingredient rosmarinic acid exhibited antiplatelet effects through the inhibition of ERp57, a member of protein disulfide isomerase (PDI) with potential roles in platelet aggregation. Danshen extract (DSE) exhibited potent inhibitory effects on the platelet aggregation induced by arachidonic acid- (AA-) induced platelet aggregation and the enzymatic activity of ERp57. Rosmarinic acid was identified by virtual screening and molecular docking as one of the hit compounds for ERp57. In line with this, rosmarinic acid displayed significant inhibitory effect on ERp57 activity and inhibited AA-induced platelet aggregation. Taken together, we demonstrated for the first time that DSE and rosmarinic acid displayed inhibitory effects on the catalytic activity of ERp57, providing evidence of the regulatory role of ERp57 underlying the antiplatelet effects of Danshen. [ABSTRACT FROM AUTHOR]

Weierning tablet (WEN) is a traditional Chinese patent medicine widely used in clinical for chronic atrophic gastritis (CAG) therapy for years. However, the underlying mechanisms of WEN on anti-CAG are still unveiled. The present study aimed to elucidate the characteristic function of WEN on anti-CAG and to illuminate its potential mechanism. The CAG model was established by gavage rats with a modeling solution (consisting of 2% sodium salicylate and 30% alcohol) with irregular diets and free access to 0.1% ammonia solution for two months on end. An enzyme-linked immunosorbent assay was used to measure the serum levels of gastrin, pepsinogen, and inflammatory cytokines. qRT-PCR was applied to measure mRNA expressions of IL-6 , IL-18, IL-10, TNF-α, and γ-IFN in gastric tissue. Pathological changes and the ultrastructure of gastric mucosa were examined by hematoxylin and eosin staining and transmission electron microscopy, respectively. AB-PAS staining was applied to observe the intestinal metaplasia of gastric mucosa. Immunohistochemistry and Western blot were used to measure the expression levels of mitochondria apoptosis-related proteins and Hedgehog pathway-related proteins in gastric tissues. Expressions of Cdx2 and Muc2 protein were determined by immunofluorescent staining. WEN could dose-dependently lower the serum level of IL-1β and the mRNA expressions of IL-6, IL-8, IL-10, TNF-α, and γ-IFN in gastric tissue. Also, WEN significantly alleviated the collagen deposition in gastric submucosa, regulated the expressions of Bax, Cleaved-caspase9, Bcl2, and Cytochrome c to reduce the apoptosis of gastric mucosa epithelial cells, and maintained the integrity of the gastric mucosal barrier. Moreover, WEN could reduce protein expressions of Cdx2, Muc2, Shh, Gli1, and Smo, and reverse intestinal metaplasia of gastric mucosa to block the progress of CAG. This study demonstrated a positive effect of WEN on improving CAG and reverse intestinal metaplasia. These functions were related to the suppression of gastric mucosal cells' apoptosis and the inhibition of Hedgehog pathways' activation. [Display omitted] • Weierning tablet inhibited gastric mucosal cells apoptosis and reversed intestinal metaplasia. • Weierning tablet inhibited the inflammation of gastric tissue. • Mitochondrial apoptotic pathway was down-regulated by Weierning tablet. [ABSTRACT FROM AUTHOR]

Background: The measurement of the coping difficulties of parents of premature infants after discharge provides objective data for nurses to prepare infants for discharge. However, no Chinese scale has been developed to measure parents' coping difficulties after their premature infants are discharged., Aim: To translate the parent version of the Post-Discharge Coping Difficulty Scale (Ped-PDCDS) from English to Chinese and test the reliability and validity of the Chinese version in parents of premature infants., Methods: A multicenter cross-sectional study of 356 parents of premature infants was conducted. The scale was symmetrically translated. Validity was evaluated in terms of content, construct, discriminant, and convergent validities. Reliability was assessed in terms of internal consistency, split-half reliability, and test-retest reliability., Results: The Chinese Ped-PDCDS finally contained 11 items. Exploratory and confirmatory factor analyses results showed that the Chinese Ped-PDCDS had three dimensions, and the convergent and discriminant validities of the scale was satisfactory. The overall reliability, split-half reliability, and test-retest reliability of the scale was 0.85, 0.92, and 0.84, respectively., Conclusion: The Chinese Ped-PDCDS has adequate psychometric properties, and is an easy and appropriate instrument for measuring parents' difficulty in coping with premature infants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Gong, Shen, Si, Gao, Xu, Liu, Song and Li.)

Objectives: To investigate the mechanism of Xuanhusuo powder (XHSP) inhibiting the differentiation of spleen myeloid-derived suppressor cells (MDSCs) in breast cancer mice., Methods: Forty-eight BALB/c female mice aged 4-5 weeks were selected, 6 of them were in normal control group, while others were in tumor-bearing models established by orthotopic injection of 4T1 cells into the subcutaneous fat pad of the second pair of left mammary glands. The tumor-bearing mice were divided into granulocyte colony stimulating factor (G-CSF) control group, G-CSF knock-down group, model control group, XHSP small dose group, XHSP medium dose group, XHSP high dose group, and cyclophosphamide (CTX) group, with 6 mice in each group. G-CSF control group and G-CSF knock-down group were constructed by stably transfecting 4T1 cells established by shRNA lentivirus combined with puromycin selection. 48 h after the model was established, XHSP small, medium, high dose group were given 2, 4, 8 g·kg －1 ·d －1 intragastric administration once a day, respectively. CTX was given 30 mg/kg by intraperitoneal injection, once every other day. The other groups were given an equal volume of 0.5% hydroxymethylcellulose sodium. The drugs in each group were continuously administered for 25 d. Histological changes in spleen were observed by HE staining, the proportion of MDSCs subsets in the spleen were detected by flow cytometry, the co-expression of CD11b and Ly6G in the spleen was detected by immunofluorescence, and the concentration of G-CSF in peripheral blood was detected by ELISA. The spleen of tumor-bearing mice was co-cultured with 4T1 stably transfected cell lines in vitro , treated with XHSP (30 μg/mL) for 24 h, and the co-expression of CD11b and Ly6G in the spleen was detected by immunofluorescence. 4T1 cells were treated by XHSP (10, 30, 100 μg/mL) for 12 h. The mRNA level of G - CSF was detected by realtime RT-PCR., Results: Compared with normal mice, the red pulp of the spleen in tumor-bearing mice was widened with megakaryocyte infiltration. The proportion of spleen polymorphonucleocyte-like MDSCs (PMN-MDSCs) was significantly increased ( P <0.01) and the co-expression of CD11b and Ly6G was increased, and the concentration of G-CSF in peripheral blood was significantly increased ( P <0.01). However, XHSP could significantly reduce the proportion of PMN-MDSCs ( P <0.05) and the co-expression of CD11b and Ly6G in the spleen, down-regulate the mRNA level of G - CSF in 4T1 cells ( P <0.01). The concentration of G-CSF in peripheral blood of tumor-bearing mice also decreased ( P <0.05) and tumor volume was reduced and splenomegaly was improved (all P <0.05)., Conclusions: XHSP may play an anti-breast cancer role by down-regulating G-CSF, negatively regulating the differentiation of MDSCs, and reconstruct the spleen myeloid microenvironment.

Thymosin β4 (Tβ4) is the β-thymosin (Tβs) with the highest expression level in human cells; it makes up roughly 70-80% of all Tβs in the human body. Combining the mechanism and activity studies of Tβ4 in recent years, we provide an overview of the subtle molecular mechanism, pharmacological action, and clinical applications of Tβ4. As a G-actin isolator, Tβ4 inhibits the polymerization of G-actin by binding to the matching site of G-actin in a 1:1 ratio through conformational and spatial effects. Tβ4 can control the threshold concentration of G-actin in the cytoplasm, influence the balance of depolymerization and polymerization of F-actin (also called Tread Milling of F-actin), and subsequently affect cell's various physiological activities, especially motility, development and differentiation. Based on this, Tβ4 is known to have a wide range of effects, including regulation of inflammation and tumor metastasis, promotion of angiogenesis, wound healing, regeneration of hair follicles, promotion of the development of the nervous system, and improving bone formation and tooth growth. Tβ4 therefore has extensive medicinal applications in many fields, and serves to preserve the kidney, liver, heart, brain, intestine, and other organs, as well as hair loss, skin trauma, cornea repairing, and other conditions. In this review, we focus on the mechanism of action and clinical application of Tβ4 for its main biological functions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To analyze the characteristics of abnormal granulocytic differentiation in breast cancer patients and explore the role of TGF-β1 in granulocytic differentiation of hematopoietic stem cells (HSCs) and tumor development., Methods: Blood samples were collected from 52 patients with invasive ductal carcinoma and 47 healthy donors. The distribution of granulocytes was compared between the two groups and the effects of surgery and radiotherapy on granulocytes were analyzed. The relationship between granulocyte abnormalities and the clinicopathological characteristics of the patients was analyzed. Spleen hematopoietic stem cells isolated from normal and tumor-bearing mice were cultured and treated with TGF-β1, and colony formation of the myeloid cells was compared and the proportion of granulocytes was analyzed with flow cytometry., Results: The white blood cell (WBC) count, neutrophils, total granulocytes, granulocyte ratio in the total WBCs, and neutrophil/lymphocyte ratio (NLR) were significantly increased ( P < 0.05), while the eosinophils and its subpopulations were obviously decreased ( P < 0.05) in breast cancer patients. Clone formation experiments showed that the numbers of CFU-GM, BFU-E and CFU-M colonies were significantly greater in the spleen cells from tumor-bearing mice than in those from normal mice ( P < 0.05). TGF- β1 treatment obviously suppressed clone formation in spleen HSCs from normal mice but significantly promoted the proliferation and granulocyte differentiation of the spleen HSCs from tumor-bearing mice., Conclusions: Breast cancer patients have obvious abnormalities in granulocytic differentiation possibly as a result of hematopoietic stem cell differentiation imbalance induced by TGF-β1 and other growth factors produced by the tumor cells. TGF-β1 highlights a paradoxical shift in the regulation of clone formation and granulocytic differentiation of spleen hematopoietic stem cells.

In this study, three commercially available nanodiamonds (NDs) of similar size (about 5 nm in diameter) but with different surface chemistry (-COOH, -NH2 and -poly(ethylene glycol)) were used to study the toxicity and immune activation of Raw264.7 cells. Only ND-PEG is well dispersed in water and cell culture medium (about 10 nm in diameter), while ND-COOH and ND-NH2 only showed some aggregation, about 50 nm in water and about 100 nm in cell culture medium. The three NDs showed different zeta potentials in water but the difference disappeared in cell culture medium due to the surface adsorption of the proteins. The ND-PEG did not show any obvious signs of cytotoxicity or activation on Raw264.7 cells under tested conditions. The ND-COOH and ND-NH2 caused dose-dependent toxicity, with the amino group capped NDs being much more toxic compare to those of the carboxylic acid group at the same exposure conditions. ND-COOH induced a certain immune response in Raw264.7 cells, leading to a higher expression of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), especially with a significantly longer incubation time. ND-NH2 also induced significant expression of TNF-α and IL-6 in Raw264.7 cells at first, but this expression was reduced with a longer incubation time due to cell death.