Oncogenic and immunological roles of RACGAP1 in pan-cancer and its potential value in nasopharyngeal carcinoma.

A particular GTPase-activating protein called RACGAP1 is involved in apoptosis, proliferation, invasion, metastasis, and drug resistance in a variety of malignancies. Nevertheless, the role of RACGAP1 in pan-cancer was less studied, and its value of the expression and prognostic of nasopharyngeal carcinoma (NPC) has not been explored. Hence, the goal of this study was to investigate the oncogenic and immunological roles of RACGAP1 in various cancers and its potential value in NPC. We comprehensively analyzed RACGAP1 expression, prognostic value, function, methylation levels, relationship with immune cells, immune infiltration, and immunotherapy response in pan-cancer utilizing multiple databases. The results discovered that RACGAP1 expression was elevated in most cancers and suggested poor prognosis, which could be related to the involvement of RACGAP1 in various cancer-related pathways such as the cell cycle and correlated with RACGAP1 methylation levels, immune cell infiltration and reaction to immunotherapy, and chemoresistance. RACGAP1 could inhibit anti-tumor immunity and immunotherapy responses by fostering immune cell infiltration and cytotoxic T lymphocyte dysfunction. Significantly, we validated that RACGAP1 mRNA and protein were highly expressed in NPC. The Gene Expression Omnibus database revealed that elevated RACGAP1 expression was associated with shorter PFS in patients with NPC, and RACGAP1 potentially influenced cell cycle progression, DNA replication, metabolism, and immune-related pathways, resulting in the recurrence and metastasis of NPC. This study indicated that RACGAP1 could be a potential biomarker in pan-cancer and NPC.

Multiresponsive Ti3C2Tx MXene-Based Actuators Enabled by Dual-Mechanism Synergism for Soft Robotics.

Multiresponsive and high-performance flexible actuators with a simple configuration, high mechanical strength, and low-power consumption are highly desirable for soft robotics. Here, a novel mechanically robust and multiresponsive Ti3C2Tx MXene-based actuator with high actuation performance via dual-mechanism synergistic effect driven by the hygroexpansion of bacterial cellulose (BC) layer and the thermal expansion of biaxially oriented polypropylene (BOPP) layer is developed. The actuator is flexible and shows an ultrahigh tensile strength of 195 MPa. Unlike the conventional bimorph-structured actuators based on a single-mechanism, the actuator developed provides a favorable architecture for dual-mechanism synergism, resulting in exceptionally reversible actuation performance under electricity and near-infrared (NIR) light stimuli. Typically, the developed actuator can produce the largest bending angle (∼400°) at the lowest voltage (≤4 V) compared with that reported previously for single mechanism soft actuators. Furthermore, the actuator also can be driven by a NIR light at a 2 m distance, displaying an excellent long-distance photoresponsive property. Finally, various intriguing applications are demonstrated to show the great potential of the actuator for soft robotics.

Focal adhesion kinase-related non-kinase ameliorates liver fibrosis by inhibiting aerobic glycolysis via the FAK/Ras/c-myc/ENO1 pathway.

BACKGROUND: Hepatic stellate cell (HSC) hyperactivation is a central link in liver fibrosis development. HSCs perform aerobic glycolysis to provide energy for their activation. Focal adhesion kinase (FAK) promotes aerobic glycolysis in cancer cells or fibroblasts, while FAK-related non-kinase (FRNK) inhibits FAK phosphorylation and biological functions. AIM: To elucidate the effect of FRNK on liver fibrosis at the level of aerobic glycolytic metabolism in HSCs. METHODS: Mouse liver fibrosis models were established by administering CCl4, and the effect of FRNK on the degree of liver fibrosis in the model was evaluated. Transforming growth factor-ß1 was used to activate LX-2 cells. Tyrosine phosphorylation at position 397 (pY397-FAK) was detected to identify activated FAK, and the expression of the glycolysis-related proteins monocarboxylate transporter 1 (MCT-1) and enolase1 (ENO1) was assessed. Bioinformatics analysis was performed to predict putative binding sites for c-myc in the ENO1 promoter region, which were validated with chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. RESULTS: The pY397-FAK level was increased in human fibrotic liver tissue. FRNK knockout promoted liver fibrosis in mouse models. It also increased the activation, migration, proliferation and aerobic glycolysis of primary hepatic stellate cells (pHSCs) but inhibited pHSC apoptosis. Nevertheless, opposite trends for these phenomena were observed after exogenous FRNK treatment in LX-2 cells. Mechanistically, the FAK/Ras/c-myc/ENO1 pathway promoted aerobic glycolysis, which was inhibited by exogenous FRNK. CONCLUSION: FRNK inhibits aerobic glycolysis in HSCs by inhibiting the FAK/Ras/c-myc/ENO1 pathway, thereby improving liver fibrosis. FRNK might be a potential target for liver fibrosis treatment.

High-Performance Bamboo Steel Derived from Natural Bamboo.

It is highly desirable to develop green and renewable structural materials from biomaterials to replace synthetic materials involved from civil engineering to aerospace industries. Herein, we put forward a facile but effective top-down strategy to convert natural bamboo into bamboo steel. The fabrication process of bamboo steel involves the removal of lignin and hemicellulose, freeze-drying followed by epoxy infiltration, and densification combined with in situ solidification. The prepared bamboo steel is a super-strong composite material with a high specific tensile strength (302 MPa g-1 cm3), which is higher than that (227 MPa g-1 cm3) of conventional high specific strength steel. The bamboo steel demonstrates a high tensile strength of 407.6 MPa, a record flexural strength of 513.8 MPa, and a high toughness of 14.08 MJ/m3, which is improved by 360, 290, and 380% over those of natural bamboo, respectively. Particularly, the mechanical properties of the bamboo steel are the highest among the biofiber-reinforced polymer composites reported previously. The well-preserved bamboo scaffolds assure the integrity of bamboo fibers, while the densification under high pressure results in a high-fiber volume fraction with an improved hydrogen bonding among the adjacent bamboo fibers, and the epoxy resin impregnated enhances the stress transfer because of its chemical crosslinking with cellulose molecules. These endow the bamboo steel with superior mechanical performance. Furthermore, the bamboo steel demonstrates an excellent thermal insulating capability with a low thermal conductivity (about 0.29 W/mK). In addition, the bamboo steel shows a low coefficient of thermal expansion (about 6.3 × 10-6 K-1) and a very high-dimensional stability to moisture attack. The strategy of fabricating high-performance bamboo steel with green and abundant natural bamboo as raw materials is highly attractive for the sustainable development of structural engineering materials.

Dual-Mode Carbon Aerogel/Iron Rubber Sensor.

Nowadays, the integration of easy production, simple structure, high sensitivity, and multifunctionality is the developing tendency for flexible sensors. Herein we report a facile manufacture of a highly flexible, sensitive, and multifunctional dual-mode sensor with an ultrasimple structure by directly attaching magnetic iron rubber (IR) onto the surface of carbon aerogel (CA) derived from melamine foam. The dual-mode CA/IR sensor exhibits high sensitivities of 5.6 kPa-1 and 1.6·10-3 Oe-1, respectively, toward pressure and magnetic field in a wide frequency ranging from 0.1 to 10 Hz, which are higher than those of the existing flexible pressure/magnetism sensors. The multifunctionality of the dual-mode CA/IR sensor is demonstrated by monitoring blood pulse, human breath, balloon volume, and thoracic volume via pressure and magnetism sensing or their combination. Due to its simple structure and high sensitivities, the dual-mode sensor is employed as the building block to create a direction-recognizable sensor for identifying the directions of pressure and magnetic field for the awareness of surrounding barriers that are of practical importance in sophisticated situations such as autonomous artificial intelligence, autodriving and robotics, and so on.

High serum IgA/C3 ratio better predicts a diagnosis of IgA nephropathy among primary glomerular nephropathy patients with proteinuria ≤ 1 g/d: an observational cross-sectional study.

BACKGROUND: The serum immunoglobulin A (IgA)/C3 ratio is considered to be an effective predictor of IgA nephropathy (IgAN). This study sought to explore the diagnostic value of the IgA/C3 ratio in IgAN among primary glomerular nephropathy patients in China. METHODS: We recruited 1095 biopsy-diagnosed primary glomerular nephropathy patients, including 757 IgAN patients and 338 non-IgAN patients. Patient demographics, serum immunological indices, and other clinical examinations were measured. IgAN cases were propensity score matched (PSM) to non-IgAN cases on the logit of the propensity score using nearest neighbor matching in a 1:1 fashion, with a caliper of 0.02 with no replacements, according to age, gender, BMI, proteinuria level, and estimated glomerular filtration rate (eGFR). RESULTS: We found that in both the full cohort and PSM cohort, the IgA/C3 ratio in the IgAN group was significantly higher than that of the non-IgAN group. The same results were also obtained with stratification by different levels of proteinuria and renal function. In the PSM cohort, there was no difference in IgA/C3 ratio in patients with IgAN between different proteinuria groups and different chronic kidney disease (CKD) groups. The area under the ROC curve (AUROC) of the IgA/C3 ratio in distinguishing IgAN among primary glomerular disease was 0.767 in the full cohort, and 0.734 in the PSM cohort. The highest AUROC of the IgA/C3 ratio was in the ≤1 g/d proteinuria group (0.801 in the full cohort, and 0.803 in the PSM cohort); however, there was no difference between all CKD groups. Meanwhile, the diagnostic accordance rate for the diagnosis of IgAN among all patients with an IgA/C3 ratio > 3.5304 was as high as 92.02% in the full cohort. IgAN was independently correlated with IgA/C3 ratio in the full cohort by multivariate logistic regression analysis. CONCLUSIONS: The present study provides clear evidence that the IgA/C3 ratio is an effective predictor of IgA diagnosis, especially in patients with proteinuria ≤1 g/d. In order to study the effectiveness of this biomarker, and to determine a standardized cut-off value, additional multicenter large-scale studies are needed.

Fatal myocarditis and rhabdomyolysis induced by nivolumab during the treatment of type B3 thymoma.

Immune checkpoint inhibitors including programmed death-1 inhibitors are promising agents for many types of malignancies; however, it is still an off-label choice for type B3 thymoma. We reported for the first time a patient with type B3 thymoma developed fatal myocarditis and rhabdomyolysis after one dose of nivolumab administration. The results from myocardial and muscle biopsies revealed extensive myocyte damage, T-lymphocytic infiltration and strongly expression of PD-L1 which confirmed the nivolumab-related immune-related adverse events (irAEs). The blood tests showed elevated levels of serum AChR-binding antibody and inflammatory cytokines, in addition abnormal lymphocyte subsets were noted. Our report suggested that administration of nivolumab in type B3 thymoma could cause rare but fatal myocarditis and rhabdomyolysis, over-expressed AChR-binding antibody and inflammatory cytokines may be potential biomarkers for irAEs.

Human papillomavirus as a potential risk factor for gastric cancer: a meta-analysis of 1,917 cases.

BACKGROUND: Human papillomaviruses (HPVs) are causally associated with the tumorigenesis of several classes of cancers. However, the prevalence of HPV in gastric cancer (GC) has not yet been systematically reviewed. Hence, a meta-analysis was conducted to estimate the HPV prevalence in patients with GC, and its potential etiologic significance was assessed. METHODS: The pooled HPV prevalence and 95% confidence intervals (CIs) were estimated among all GC patients. Heterogeneity was described by using the I2 statistic. Sources of heterogeneity were explored by meta-regression and stratified analyses. The meta-influence was applied to evaluate the influence of a single study on the pooled estimates. Odds ratios (ORs) and 95% CIs were computed for case-control studies. For research providing clinicopathological parameters of age, sex, pathological, differentiated, and clinical stages, and HPV subtypes, the corresponding pooled ORs and 95% CIs were also calculated. RESULTS: Thirty studies were included in the current meta-analysis, involving 1,917 patients with GC and 576 controls. The pooled HPV prevalence was 28.0% (95% CI: 23.2%, 32.7%) among all the patients with GC, and the I2 was 96.9% (P<0.001). A pooled OR of 7.388 (95% CI: 3.876, 14.082) was achieved based on 15 case-control studies (I2=56.7%, P=0.004). Moreover, the HPV prevalence was significantly higher in patients from China than in those from non-Chinese regions (31% vs 9%, I2=95.0%, P<0.001). The pooled prevalence of HPV16 was 21% in GC tissues, and the pooled prevalence of HPV18 was 7% with an OR of 3.314 (95% CI =1.617, 6.792). HPV16 was 3 times more frequently detected than HPV18. CONCLUSION: HPV could play a potential role in the pathogenesis of GC. A causal relationship can be confirmed only by detecting HPV in the cells of GC precursor lesions (gastric dysplasia or adenoma). In addition, this study might be beneficial for expounding the potential etiologic significance of molecular mechanism of gastric tumorigenesis and providing opinions regarding precautionary measures.

[Prevention and treatment of aromatase inhibitor-associated bone loss by shugan jiangu recipe in postmenopausal women with breast cancer: a clinical study].

OBJECTIVE: To study the effect of Shugan Jiangu Recipe (SJR) on bone mineral density (BMD) and serum bone metabolic biochemical markers in postmenopausal breast cancer patients with osteopenia. METHODS: Totally 38 patients of postmenopausal women with breast cancer, who received aromatase inhibitors (AIs), were assigned to the treatment group (21 cases) and the control group (17 cases) by using random digit table. All patients took Caltrate D Tablet (containing Ca 600 mg and Vit D3 125 IU), one tablet daily. Patients in the treatment group took SJR, 6 g each time, twice daily for 6 successive months. The bone mineral density (BMD) level was detected before treatment and at months 6 after treatment. Levels of bone alkaline phosphatase (BALP), bone gla protein (BGP), tartrate-resistant acid phosphatase (TRAP), and C-terminal telopeptide of type II collagen (CTX-II) were detected by enzyme linked immunosorbent assay (ELISA). The drug safety was also assessed. RESULTS: Compared with before treatment, BMD of L2-4 and femur neck obviously increased in the treatment group at month 6 after treatment (P < 0.01), serum BALP and TRAP decreased (P < 0.05). Compared with before treatment, BMD of L2-4 and femur neck obviously decreased in the control group at month 6 after treatment (P < 0.05), serum BALP and TRAP increased (P < 0.01). Compared with the control group, lumbar and femur neck BMD obviously increased, serum levels of BGP and BALP obviously decreased, and serum levels of CTX-II and TRAP obviously increased in the treatment group at month 6 after treatment (P < 0.01). No serious adverse event occurred during the treatment period. Bone fracture occurred in one case of the control group (5.8%). CONCLUSION: SJR could attenuate bone loss of postmenopausal women with breast cancer who received AIs, increase BMD and improve abnormal bone metabolism.

A severe dermatologic adverse effect related with gefitinib: case report and review of the literature.

Gefitinib, a selective inhibitor of the epidermal growth factor receptor-tyrosine kinase, it's one of the most frequent drug-related adverse effects (AEs) reported in literature is dermatologic AEs. We report, a case of severe cutaneous adverse reactions induced by gefitinib as second-line treatment in a male patient with advanced non-small cell lung cancer after 1 month of treatment. Although tumor shrunk and patient got benefit from the treatment, gefitinib had to be stopped right away. We managed the symptoms of rash with a variety of treatments, including topical ethacridine lactate, antihistamine and so on. After the rash improved, we found his tumor were progress. Then he took gefitinib again without severe skin toxicity or disease progression. We think the development of gefitinib-induced rash may be a sign of effective and administrating it again maybe relieves the degree of rash.

[Effects of Fuzheng Yiliu Granule-medicated serum on apoptosis of liver cancer cells from mice and its mechanism].

OBJECTIVE: To study the effects of Fuzheng Yiliu Granule (FZYLG)-medicated serum on apoptosis of liver cancer cells H22 from mice and its mechanism. METHODS: Liver cancer cells H22 from mice were incubated in culture media containing sera from rabbits medicated with different doses of FZYLG. Flow cytometry was used to examine the cell cycle and analyze the apoptotic rate of the H22 cells. The morphological changes of the H22 cells were observed by transmission electron microscope and the apoptosis related proteins Bcl-2 and Bax were examined by streptavidin-biotin peroxidase complex (SABC) method. RESULTS: FZYLG-medicated serum could influence the cell cycle and stop the proliferation of H22 cells at the G(1)/G(0) phase with apoptotic peak being detected. In culture media with FZYLG-medicated sera, the expression of Bcl-2 decreased while that of Bax increased as compared with that in culture medium with non-medicated serum (P<0.05). CONCLUSION: FZYLG-medicated serum can induce apoptosis of the liver cancer cells H22 by influencing the cell cycle, down-regulating the expression of Bcl-2 and up-regulating the expression of Bax.

Are depressive symptoms a risk factor for mortality in elderly Japanese American men?: the Honolulu-Asia Aging Study.

OBJECTIVE: This study determined the influence of depressive symptoms on subsequent mortality of all causes. METHOD: The Honolulu Heart Program, established in 1965, is a prospective, community-based cohort of Japanese American men living in Hawaii. The analysis was based on 3,196 Japanese American men aged 71-93 at the time of the fourth examination in 1991-1993. Depressive symptoms were measured by use of an 11-question version of the Centers for Epidemiologic Studies Depression Scale questionnaire. All-cause mortality data were available for 6 years of follow up. Data were analyzed on the basis of presence or absence of chronic diseases. RESULTS: The overall prevalence of frequent depressive symptoms was 9.9%. Age-adjusted mortality rates at 3 years were 48.0 and 30.3 per 1,000 person-years for the depressed and nondepressed groups, respectively. At 6 years, the rates were 54.1 (depressed) and 41.5 (nondepressed) per 1,000 person-years. After adjustment for age, marital status, and antidepressant use, the relative risk for all-cause mortality associated with depressive symptoms was 1.53 for 3-year and 1.27 for 6-year mortality. Among participants who were healthy (without cognitive impairment, coronary heart disease, stroke, diabetes, or cancer), the association between depressive symptoms and mortality was greater (relative risk of 2.30 and 1.57 for 3- and 6-year mortality, respectively). Among participants with chronic disease, there were no significant associations between depressive symptoms and mortality. CONCLUSIONS: Depressive symptoms are a risk factor for mortality in elderly people, particularly in physically healthy individuals.