Chemical structure and immunomodulatory activity of a polysaccharide from Saposhnikoviae Radix.

A new polysaccharide, named SP40015A01, was obtained from Saposhnikoviae Radix by water extraction, isolation and purification. SP40015A01 (9.7 × 105 Da) is composed of Rhamnose (Rha), Galacturonic acid (GalA), Galactose (Gal), and Arabinose (Ara) with the proportion of 1.6:85.6:5.8:7.6. The backbone of SP40015A01 is composed of 3-α-GalAp, 2-α-GalAp, 2,3-ß-GalAp and 2,3-ß-Galp, and branched at C3 of 2,3-ß-GalAp, C3 of 2,3-ß-Galp. Zebrafish experiments were used to explore the immunomodulatory activity of SP40015A01. Results showed that SP40015A01 could significantly improve the neutrophils density of immunocompromised zebrafish and reduce the content of nitric oxide (NO) and interleukin-1ß (IL-1ß). This study demonstrated that SP40015A01 has significant immunomodulatory activity, which can improve the neutrophils density and reduce inflammatory factor content, suggesting SP40015A01 may be a potential immunomodulator in Saposhnikoviae Radix (SR) for treatment of hypoimmunity related disease. This study supplemented the research on the polysaccharide components in traditional Chinese medicine and provided a scientific explanation for the development and clinical applications of SR.

Sulfhydryl-Functionalized Amino Group Polymer Microcomposites toward Efficient Adsorption of Aqueous Cr(VI), As(III), Cd(II), and Pb(II).

The development of efficient adsorbents for heavy metal pollution, especially five toxic heavy metals, has attracted great research interest. Polymer-based adsorbents have aroused research value for their abundant functional groups and high porosity to the ability to capture metal ions. We designed a sulfhydryl-functionalized polymer microcomposite to take up Cr(VI), As(III), Cd(II), and Pb(II). The adsorption capacity achieved was 64.2 mg g-1 for Cr(VI), 44.9 mg g-1 for As(III), 35.5 mg g-1 for Cd(II), and 18.2 mg g-1 for Pb(II). Langmuir and Sips isotherm model is dominant for As(III), Cd(II), and Pb(II) adsorption. Pseudo-second-order kinetic models can better describe the adsorption behavior of Cr(VI), implying that chemisorption is accompanied by Cr(VI) adsorption. Cr(VI) simultaneous reduction to Cr(III) through the benzenoid amine oxidate pathway was the dominant mechanism, precipitation for Cd(II) adsorption was convinced, and chelation between As(III)/Pb(II) and─SH group and complexation between Pb(II) and C═O or benzene hydroxyl were a plausible mechanism for As(III) and Pb(II) adsorption.

Collagen code in tumor microenvironment: Functions, molecular mechanisms, and therapeutic implications.

The tumor microenvironment (TME) is crucial in cancer progression, and the extracellular matrix (ECM) is an important TME component. Collagen is a major ECM component that contributes to tumor cell infiltration, expansion, and distant metastasis during cancer progression. Recent studies reported that collagen is deposited in the TME to form a collagen wall along which tumor cells can infiltrate and prevent drugs from working on the tumor cells. Collagen-tumor cell interaction is complex and requires the activation of multiple signaling pathways for biochemical and mechanical signaling interventions. In this review, we examine the effect of collagen deposition in the TME on tumor progression and discuss the interaction between collagen and tumor cells. This review aims to illustrate the functions and mechanisms of collagen in tumor progression in the TME and its role in tumor therapy. The findings indicated collagen in the TME appears to be a better target for cancer therapy.

Optimal postoperative surveillance strategies for cancer survivors with gastric neuroendocrine carcinoma based on individual risk: a multicenter real-world cohort study.

BACKGROUND: The best follow-up strategy for cancer survivors after treatment should balance the effectiveness and cost of disease detection while detecting recurrence as early as possible. Due to the low incidence of gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma [G-(MA)NEC], high-level evidence-based follow-up strategies is limited. Currently, there is a lack of consensus among clinical practice guidelines regarding the appropriate follow-up strategies for patients with resectable G-(MA)NEC. MATERIALS AND METHODS: The study included patients diagnosed with G-(MA)NEC from 21 centers in China. The random forest survival model simulated the monthly probability of recurrence to establish an optimal surveillance schedule maximizing the power of detecting recurrence at each follow-up. The power and cost-effectiveness were compared with the National Comprehensive Cancer Network, European Neuroendocrine Tumor Society, and European Society for Medical Oncology Guidelines. RESULTS: A total of 801 patients with G-(MA)NEC were included. The patients were stratified into four distinct risk groups utilizing the modified TNM staging system. The study cohort comprised 106 (13.2%), 120 (15.0%), 379 (47.3%), and 196 cases (24.5%) for modified groups IIA, IIB, IIIA, and IIIB, respectively. Based on the monthly probability of disease recurrence, the authors established four distinct follow-up strategies for each risk group. The total number of follow-ups 5 years after surgery in the four groups was 12, 12, 13, and 13 times, respectively. The risk-based follow-up strategies demonstrated improved detection efficiency compared to existing clinical guidelines. Further Markov decision-analytic models verified that the risk-based follow-up strategies were better and more cost-effective than the control strategy recommended by the guidelines. CONCLUSIONS: This study developed four different monitoring strategies based on individualized risks for patients with G-(MA)NEC, which may improve the detection power at each visit and were more economical, effective. Even though our results are limited by the biases related to the retrospective study design, we believe that, in the absence of a randomized clinical trial, our findings should be considered when recommending follow-up strategies for G-(MA)NEC.

RNA-Seq Analysis Demystify the Pathways of UV-A Supplementation in Different Photoperiods Integrated with Blue and Red Light on Morphology and Phytochemical Profile of Kale.

As an indispensable element in the morphology and phytochemical profile of plants, UV-A has proved to help promote the growth and quality of kale. In this study, UV-A supplementation in different photoperiods (light period supplemental UVA = LS, dark period supplemental UVA = DS, and light-dark period supplemental UVA = LDS) contributed to yielding greater biomass production (fresh weight, dry weight, and plant moisture content), thus improving morphology (plant height, stem diameter, etc.) and promoting higher phytochemicals content (flavonoids, vitamin c, etc.), especially glucosinolates. To fathom its mechanisms, this study, using RNA-seq, verified that UV-A supplementation treatments signally generated related DEGs of plant hormone signal pathway, circadian rhythm plant pathway, glucosinolate pathway, etc. Moreover, 2047 DEGs were obtained in WGCNA, illustrating the correlations between genes, treatments, and pathways. Additionally, DS remarkedly up-regulated related DEGs of the key pathways and ultimately contributed to promoting the stem diameter, plant height, etc., thus increasing the pigment, biomass, vitamin c, etc., enhancing the antioxidant capacity, and most importantly, boosting the accumulations of glucosinolates in kale. In short, this study displayed new insights into UV-A supplementation affected the pathways related to the morphology and phytochemical profile of kale in plant factories.

Advancements in materials, manufacturing, propulsion and localization: propelling soft robotics for medical applications.

Soft robotics is an emerging field showing immense potential for biomedical applications. This review summarizes recent advancements in soft robotics for in vitro and in vivo medical contexts. Their inherent flexibility, adaptability, and biocompatibility enable diverse capabilities from surgical assistance to minimally invasive diagnosis and therapy. Intelligent stimuli-responsive materials and bioinspired designs are enhancing functionality while improving biocompatibility. Additive manufacturing techniques facilitate rapid prototyping and customization. Untethered chemical, biological, and wireless propulsion methods are overcoming previous constraints to access new sites. Meanwhile, advances in tracking modalities like computed tomography, fluorescence and ultrasound imaging enable precision localization and control enable in vivo applications. While still maturing, soft robotics promises more intelligent, less invasive technologies to improve patient care. Continuing research into biocompatibility, power supplies, biomimetics, and seamless localization will help translate soft robots into widespread clinical practice.

Effects of Pre-Harvest Supplemental UV-A Light on Growth and Quality of Chinese Kale.

The effects of supplemental UV-A (385 nm) period and UV-A intensity for 5 days before harvest (DBH) on growth, antioxidants, antioxidant capacity, and glucosinolates contents in Chinese kale (Brassica oleracea var. alboglabra Bailey) were studied in plant factory. In the experiment of the UV-A period, three treatments were designed with 10 W·m-2 UV-A supplement, T1(5 DBH), T2 (10 DBH), and no supplemental UV-A as control. In the experiment of UV-A intensity, four treatments were designed with 5 DBH, control (0 W·m-2), 5 w (5 W·m-2), 10 w (10 W·m-2), and 15 w (15 W·m-2). The growth light is as follows: 250 µmol·m-2·s-1; red light: white light = 2:3; photoperiod: 12/12. The growth and quality of Chinese kale were improved by supplemental UV-A LED. The plant height, stem diameter, and biomass of Chinese kale were the highest in the 5 W·m-2 treatment for 5 DBH. The contents of chlorophyll a, chlorophyll b, and total chlorophyll were only highly increased by 5 W·m-2 UV-A for 5 DBH, while there was no significant difference in the content of carotenoid among all treatments. The contents of soluble sugar and free amino acid were higher only under 10 DBH treatments than in control. The contents of total phenolic and total antioxidant capacity were the highest in 5 W·m-2 treatment for 5 DBH. There was a significant positive correlation between total phenolic content and DPPH and FRAP value. After 5 DBH treatments, the percentages and contents of total aliphatic glucosinolates, sinigrin (SIN), gluconapin (GNA), and glucobrassicanapin (GBN) were highly increased, while the percentages and contents of glucobrassicin (GBS), 4-methoxyglucobrassicin (4-MGBS), and Progoitrin (PRO) were significantly decreased, especially under 10 W·m-2 treatment. Our results show that UV-A LED supplements could improve the growth and quality of Chinese kale, and 5 W·m-2 UV-A LED with 5 DBH might be feasible for Chinese kale growth, and 10 W·m-2 UV-A LED with 5 DBH was better for aliphatic glucosinolates accumulation in Chinese kale.

Tumor-associated macrophage-derived exosomes transmitting miR-193a-5p promote the progression of renal cell carcinoma via TIMP2-dependent vasculogenic mimicry.

Previous studies have investigated whether tumor-associated macrophages (TAMs) play tumorigenic and immunosuppressive roles to encourage cancer development, but the role of TAMs in regulating vasculogenic mimicry (VM) in clear-cell renal cell carcinoma (ccRCC) cells has not been completely clarified. We conducted immunostaining of the tumor-associated macrophage biomarkers CD68/CD163 and double staining for PAS/CD31 in ccRCC human specimens to find that higher TAM infiltration was positively correlated with VM formation. Then we demonstrated that TAM-derived exosomes downregulate TIMP2 expression in RCC cells to promote VM and invasion by shuttling miR-193a-5p. Mechanistic analysis indicated that HIF-1α upregulation in macrophages could transcriptionally increase miR-193a-5p expression. Exosome-shuttled miR-193a-5p then targeted the 3' untranslated region (UTR) of TIMP2 mRNA to suppress its translation. A preclinical study using an in vivo orthotopic xenograft model of ccRCC in mice substantiated that TAM-derived exosomes enhance VM and enable tumor progression, which confirmed our in vitro data. Suppressing TAM-derived exosomal miR-193a-5p successfully inhibited tumor progression and metastasis. Overall, miR-193a-5p from TAM-derived exosomes downregulates the TIMP2 gene to facilitate the development of RCC, which provides a novel perspective for developing therapeutic strategies for RCC.

Elevation of ADAM12 facilitates tumor progression by enhancing metastasis and immune infiltration in gastric cancer.

A disintegrin and metalloprotease 12 (ADAM12), an essential transmembrane protein with metalloprotease, cell binding and intracellular signal­regulating capabilities, has been reported to play a crucial role in various types of cancers. However, the biological function of ADAM12 in gastric cancer (GC) remains unclear. Bioinformatic and experimental analyses were used to determine the expression level and prognostic value of ADAM12 in GC. The level of DNA methylation and the competing endogenous RNA (ceRNA) network was identified using MethSurv, Starbase3.0, miRNet2.0 and experimental analyses. Then, the co­expression profiles of ADAM12 were determined and subjected to enrichment analysis using the LinkedOmics database. The protein­protein interaction network and the docking model of ADAM12 were constructed using the GeneMANIA, STRING, and HDOCK webservers. The role of ADAM12 in tumor metastasis and immune infiltration was investigated using in vitro assays and TIMER database exploration. It was found that ADAM12 was overexpressed and was correlated with a poor prognosis of GC patients. In addition, the aberrant DNA methylation status and ceRNA regulation may contribute to the upregulation of ADAM12 in GC. Moreover, the enrichment analysis revealed that ADAM12 is involved in multiple vital biological functions and pathways, such as 'macrophage activation', 'extracellular matrix binding' and 'ECM­receptor interaction'. Subsequently, the protein­protein interaction network and molecular docking model demonstrated that follistatin like 3 (FSTL3) is a potential binding partner of ADAM12. Finally, it was demonstrated that ADAM12 promotes tumor metastasis, immune infiltration and M2 macrophage polarization in GC. In summary, these results highlight the potential of ADAM12 to be used as a therapeutic target for GC.

Preoperative prediction for lymph node metastasis in early gastric cancer by interpretable machine learning models: A multicenter study.

BACKGROUND: The presence of lymph node metastasis plays a decisive role in the selection of treatment options in patients with early gastric cancer. However, there is currently no established protocol to predict the risk of lymph node metastasis before/after endoscopic resection. The aim of this study was to develop and validate several machine learning algorithms for clinical practice. METHODS: A total of 2,348 patients with early gastric cancer were selected from 5 major tertiary medical centers. We applied 6 machine learning algorithms to develop lymph node metastasis prediction models for clinical feature variables. The partial dependence plots were used to explain the prediction of the models. The area under the receiver operating characteristic curve and area under the precision recall curve were measured to assess the detection performance. The R shiny interactive web application was used to translate the prediction model in a clinical setting. RESULTS: The incidence of lymph node metastasis in patients with early gastric cancer was 13.63% (320/2348) and significantly higher in young women, in the lower third of the stomach, with a size >2 cm, depressed type, poorly/nondifferentiated, lymphovascular invasion, nerve invasion, and submucosal infiltration. In terms of age, there is a nonlinear and younger trend. XGBOOST displayed the best predictive performance at the initial and postendoscopy evaluation. In addition, the machine learning algorithm was converted to a user-friendly web tool for patients and clinicians. CONCLUSION: XGBOOST can predict the risk of lymph node metastasis with best accuracy in patients with early gastric cancer. Our online web application may help determine the optimal best surgical option for patients with early gastric cancer.

Stretchable Thermoelectric-Based Self-Powered Dual-Parameter Sensors with Decoupled Temperature and Strain Sensing.

Thermoelectric-based sensors with multifunctional sensing properties that can recognize different stimulations in a self-powered environment by converting low-grade heat into electrical energy have attracted increasing attention. However, the current thermoelectric-based multifunctional sensors are faced with issues such as limited preparation methods, complex structural designs, and hard decoupling, which greatly hinder their further development in the field of wearable electronics. Herein, we have fabricated novel free-standing self-powered temperature-strain sensors based on poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS)/carbon nanotube (CNT)/waterborne polyurethane (WPU) composite films through a simple drop-casting method. The composite films can maintain stable thermoelectric performance after washing 1000 times and withstand repeated bending and stretching. More importantly, based on the Seebeck effect arising from PEDOT:PSS/CNT composites, the assembled sensor successfully detects temperature changes and strain deformations under a self-powered condition. The decoupling of strain stimulation and temperature stimulation is mainly attributed to the good conductive network inside the composite film and the conductive bridge formed by PEDOT:PSS particles between CNTs when the composite film is stretched. Thus, the designed self-powered sensor with dual-parameter sensing prepared by a simple strategy has shown great potential in wearable electronics.

Statins: a repurposed drug to fight cancer.

As competitive HMG-CoA reductase (HMGCR) inhibitors, statins not only reduce cholesterol and improve cardiovascular risk, but also exhibit pleiotropic effects that are independent of their lipid-lowering effects. Among them, the anti-cancer properties of statins have attracted much attention and indicated the potential of statins as repurposed drugs for the treatment of cancer. A large number of clinical and epidemiological studies have described the anticancer properties of statins, but the evidence for anticancer effectiveness of statins is inconsistent. It may be that certain molecular subtypes of cancer are more vulnerable to statin therapy than others. Whether statins have clinical anticancer effects is still an active area of research. Statins appear to enhance the efficacy and address the shortcomings associated with conventional cancer treatments, suggesting that statins should be considered in the context of combined therapies for cancer. Here, we present a comprehensive review of the potential of statins in anti-cancer treatments. We discuss the current understanding of the mechanisms underlying the anti-cancer properties of statins and their effects on different malignancies. We also provide recommendations for the design of future well-designed clinical trials of the anti-cancer efficacy of statins.

MiR-450a-5p Inhibits Gastric Cancer Cell Proliferation, Migration, and Invasion and Promotes Apoptosis via Targeting CREB1 and Inhibiting AKT/GSK-3ß Signaling Pathway.

Gastric cancer seriously affects human health and research on gastric cancer is attracting more and more attentions. In recent years, molecular targets have become the research focus. Accumulating evidence indicates that miR-450a-5p plays a critical role in cancer progression. However, the biological role of miR-450a-5p in gastric carcinogenesis remains largely unknown. In this study, we explore the effects and mechanisms of miR-450a-5p on the development and progression of gastric cancer. We used gain-of-function approaches to investigate the role of miR-450a-5p on gastric cancer cell proliferation, migration, invasion, and apoptosis using biological and molecular techniques including real-time quantitative PCR (RT-qPCR), CCK-8, colony formation, flow cytometry, Western blot, wound healing, transwell chamber, dual luciferase reporter, and tumor xenograft mouse model. We found that gastric cancer cells have low expression of miR-450a-5p and overexpression of miR-450a-5p inhibited gastric cancer cell proliferation, migration and invasion, and induced apoptosis in vitro. Moreover, we demonstrated that ectopic expression of miR-450a-5p inhibited gastric cancer growth in vivo. At the molecular level, overexpression of miR-450a-5p significantly increased the expression of pro-apoptotic proteins, including caspase-3, caspase-9, and Bax, and inhibited the expression of anti-apoptotic protein Bcl-2. Luciferase reporter experiment suggested that camp response element binding protein 1 (CREB1) had a negative correlation with miR-450a-5p expression, and knockdown of CREB1 alleviated gastric cancer growth. Furthermore, we also found that miR-450a-5p inhibited the activation of AKT/GSK-3ß signaling pathway to inhibit the progression of gastric cancer. Collectively, miR-450a-5p repressed gastric cancer cell proliferation, migration and invasion and induced apoptosis through targeting CREB1 by inhibiting AKT/GSK-3ß signaling pathway. MiR-450a-5p could be a novel molecular target for the treatment of gastric cancer.

Comparative study of laparoscopic versus open radical gastrectomy in advanced gastric neuroendocrine carcinoma: Analysis from a high-volume institution.

BACKGROUND: Gastric neuroendocrine carcinomas (G-NECs) are rare. This study aimed to explore the feasibility and clinical efficacy of laparoscopic surgery in patients with advanced G-NECs. METHODS: The clinicopathological data of 175 G-NECs patients who underwent radical gastrectomy in a high-volume centre were collected. One hundred fifty-one cases with advanced G-NECs (laparoscopic gastrectomy [LG] = 30, open gastrectomy [OG] = 121) were finally selected for comparison of the short-term outcomes and oncologic efficacy. RESULTS: In the postoperative recovery, when comparing the OG group, the time to ambulation (3.2 d vs. 2.6 d, respectively, p = 0.049), the time to first flatus (4.1 d vs. 3.6 d, respectively, p = 0.050), the time to first soft diet (7.9 d vs. 6.7 d, respectively, p = 0.007), and the postoperative hospital stay (13.1 d vs. 11.4 d, respectively, p = 0.047) of the LG group were shorter. There was no significant difference in the postoperative complication rates between the OG and LG groups (19.8% vs. 23.3%, p = 0.671). The 3-year overall survival (OS) rate was 57.0% in the OG group and 64.4% in the LG group (p = 0.349). The 3-year disease-free survival (DFS) rate was 51.7% in the OG group and 57.4% in the LG group (p = 0.357). There was no significant difference in the 3-year OS and DFS rates between the LG and OG groups at each stage. The recurrence rate was 35.5% in the OG group and 33.0% in the LG group (p = 0.821). CONCLUSIONS: The short-term outcomes and oncologic efficacy of laparoscopic gastrectomy and open gastrectomy for advanced G-NECs are comparable.

High Expression of Retinoic Acid Induced 14 (RAI14) in Gastric Cancer and Its Prognostic Value.

BACKGROUND To explore the expression level of retinoic acid induced 14 (RAI14) in gastric cancer (GC) patients and its potentially clinical prognostic value. MATERIAL AND METHODS Initially, The Cancer Genome Atlas (TCGA) and Oncomine databases were mined to examine the differential expression levels and clinical prognostic significance of RAI14 mRNA in GC patients. Subsequently, 68 cases of GC and paired adjacent normal tissues were collected retrospectively, and the expression level of RAI14 protein was detected by immunohistochemical staining. In addition, Kaplan-Meier univariate and Cox multivariate survival analyses were used to verify the correlation between RAI14 expression and clinicopathological parameters in GC patients and its clinical prognostic significance. RESULTS TCGA and GEO (from Oncomine database) data mining results found that RAI14 mRNA level was remarkably higher in GC than normal gastric tissues (All P<0.05). Besides, immunohistochemical results detected that RAI14 protein level in GC was dramatically higher (P=0.004) compared to that in the matched normal tissues. Moreover, TCGA database and Kaplan-Meier Plotter mining results showed that compared to those with RAI14 low mRNA expression levels, GC patients with RAI14 high mRNA expression levels had remarkably lower time of both overall survival and disease-free survival (All P<0.05). Additionally, based on the immunohistochemical results, Kaplan-Meier univariate and Cox multivariate survival analyses indicated that high expression of RAI14 was the only independent predictor of unfavorable prognosis in patients with gastric cancer (P=0.000). CONCLUSIONS RAI14 was highly expressed in GC, and the high expression of RAI14 could be an independent predictor of poor prognosis in GC patients.

Effect of reorganized-human growth hormone on cell cycle kinetics in liver cancer in vitro.

OBJECTIVE: To study the effect of reorganized-human growth hormone (r-hGH) on cycle kinetics and apoptosis of liver cancer cells or 7402 cells. METHODS: Liver cancer cells were cultured for 24 hours with r-hGH at different concentrations with or without cisplatin (DDP). Cells undergoing apoptosis and differentiation were determined by flow cytometry (FCM). RESULTS: Comparison of the results in culture with and without r-hGH showed that the percentage of cells in G0-G1 phase dropped (P<0.05), whereas in S phase increased (P<0.05). Adding of r-hGH and DDP to the culture medium increased the apoptosis of liver cancer cells more significantly than adding DDP only (P<0.05). CONCLUSIONS: Liver cancer cells might express the hGH receptor. In vitro r-hGH might induce the differentiation of liver cancer cells, stimulate the combination of DNA, and reduce the cells in G0-G1 phases. These improve the sensibility of tumors to the special-staged chemical treatment. Chemotherapy together with r-hGH may increase the apoptosis of liver cancer cells.