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2,4,6,8,10,12-Hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (HNIW) was bonded by fluorine rubber and then desensitized by paraffin wax (PW), stearic acid (SA), and a PW/SA composite system using an aqueous suspension method. The coating and desensitization effects of the composite systems on HNIW and the influence of the addition of SA on the mechanical properties of the coated HNIW samples were studied. In addition, the PW/SA composite solution was simulated using a molecular dynamics method, and the relationship between the desensitization effect on HNIW and the properties of the composite solution was investigated. The results showed that the PW/SA composite system, of which the desensitization effect on HNIW was between those of the two desensitizers, could effectively coat HNIW and that the composite solution had the most stable and well-distributed state when using benzene as solvent with the mass ratio of PW/SA equal to 7/3 or 3/7, thus resulting in the best desensitization effect on HNIW. Moreover, the addition of stearic acid was successful in enhancing the mechanical properties of the coated HNIW samples. [ABSTRACT FROM PUBLISHER]

Additives are one of the most important factors that greatly affect the crystal characteristics of the high energy compound hexahydro-1,3,5-trinitro-1,3,5-s-triazine (RDX, C3H6N6O6) and they have an influence on impact sensitivity. In this article, a growth morphology method was applied to obtain the crystal habit of RDX in a vacuum as well as the morphologically important faces, and molecular dynamics simulations were applied to calculate the interaction energy between these crystal faces and additive molecules for prediction of the additive-effect crystal habits of RDX. On this basis, crystal characteristics including crystal morphology, aspect ratio, and total surface charge were investigated. Then the particle size and surface electrostatic voltage of the samples from recrystallization were analyzed experimentally. The impact sensitivity test indicated that acrylamide, which could enhance the regularity and degree of sphericity of RDX crystals and effectively reduce the surface static electricity of RDX, was successful in reducing the impact sensitivity of RDX as an additive for crystallization. The above experimental results were in good agreement with the conclusions based on the theoretical calculations. [ABSTRACT FROM PUBLISHER]

Objectives: Here, we reported our experience over 28 years with 133 cases of patients with Wilson's disease (WD) in order to illustrate the diverse clinical presentation and to improve understanding and early diagnosis of WD. Methods: We reviewed the medical records of patients with WD at Shengjing Hospital of China Medical University from 1993 to 2011. The clinical manifestations and laboratory findings were analyzed. The diagnosis was based on the presence of Kayser-Fleisher (K-F) rings, low serum copper levels, low serum ceruloplasmin levels, increased urinary copper concentrations before or after penicillamine challenge. Results: Among them, 93 patients mainly presented with hepatic manifestations, 27 with neural abnormalities, and 13 presented with others. Age range at diagnosis was wide (3-74 years, average 13.2 years), and five patients were over 40 years. The oldest one was aged 74 years and presented with neuropsychiatric disorder. The positive rate of K-F rings was 93.0%. The serum ceruloplasmin decreased in 83.6% patients, 24-hour urinary copper increased in 88.1% patients, and serum copper decreased in 68.9% patients. About 79.7% of patients were diagnosed within 6 months, but only 33.1% were diagnosed at their initial medical consultation. There was a substantial delay of up to 15 years. Conclusions: The clinical manifestation of WD is very diverse and no one feature is completely reliable. Doctors in many fields have opportunities to encounter this disease, and the most important thing is to be aware of the possibility of WD. [ABSTRACT FROM AUTHOR]

Taking complex shape arch dam geometry as an example, a model was established with HyperMesh technology. By means of the strong HyperMesh's pre-processing functions, a systematic study was done on the formation of model, geometry clean-up and sub-mesh partitioning. Especially, in meshing the complicated boundary of arch dam, a variety of meshing techniques were employed in completing the high-quality grids, which provides a new idea for meshing different material partitions and dam sections. The results show that HyperMesh software is highly efficient for repairing and optimizing the 3D model, and it can be better compatible with Abaqus. [ABSTRACT FROM AUTHOR]

The article presents a study which constructs the SPRN recombinant prokaryotic expression vector and prepares the rabbit polyclonal antibody against Shadoo protein in New Zealand.

Depression and cancer are both prevalent diseases worldwide. Numerous cancer patients experience psychological illnesses, especially depression, following a malignancy's dismal prognosis. Although some research has suggested that caffeine may be protective against depressive symptoms, it is still unclear how caffeine and cancer patients are related. Thus, we hypothesized that moderate daily caffeine intake may reduce the risk of depression in both the cancer and noncancer populations. Data were extracted and combined from the National Health and Nutrition Examination Survey from 2007 to 2016. After controlling for potential confounding factors, interaction effects analysis was used to clarify the interaction between caffeine and cancer on depressive symptoms. Linear regression analysis and restricted cubic splines were used to further analyze the relationship between caffeine and depression in cancer and noncancer populations. A total of 24,145 participants were included in the analysis. In the noncancer population, the quartile 3 group of caffeine intake showed a negative association between caffeine intake and Patient Health Questionnaire-9 (PHQ-9) scores (β = –0.23, 95% confidence interval, –0.45 to –0.01; P =.041). No association between caffeine intake and PHQ-9 scores was observed in the cancer population. In both cancer and noncancer populations, restricted cubic splines indicated a nonlinear trend between caffeine and PHQ-9 scores, with the lowest PHQ-9 scores when caffeine intake was 119.52 mg. In the noncancer population, moderate daily caffeine intake (quartile 3 group; range, 119.5-236.5 mg) was associated with reduced depressive symptoms, whereas in the cancer population, no association was found between caffeine intake and depression. Our study included 24,145 participants in NHANES. In the noncancer population, moderate caffeine intake (119.5-236.5 mg) is associated with less severe depressive symptoms. In the cancer population, however, caffeine intake bears no relationship to depression severity. NHANES, National Health and Nutrition Examination Survey. [Display omitted] [ABSTRACT FROM AUTHOR]

The introduction of immune checkpoint inhibitors (ICIs) has reshaped the therapy of hepatocellular carcinoma (HCC). ICIs are a novel therapy with frequent adverse events (AEs), including treatment-related adverse events (trAEs) and immune-related adverse events (irAEs). However, no comprehensive overview of the toxicity spectrum of ICIs in HCC patients has been provided. Electronic databases were searched to identify eligible studies. A meta-analysis of the incidence rate of AEs in HCC patients treated with ICIs was performed. Lastly, the prognostic value of irAEs in HCC patients treated with ICIs was verified. Forty-seven studies with 6472 participations met the inclusion criteria. The pooled all-grade trAEs incidence rate was 83.4% (95% confidence interval [95% CI] 77.0–89.1%), ≥ grade 3 trAEs incidence rate was 33.0% (95% CI 26.9–39.5%), all-grade irAEs incidence rate was 34% (95% CI 22–47%), and ≥ grade 3 irAEs incidence rate was 9% (95% CI 5–14%). Aspartate aminotransferase (AST) increase (38%, 95% CI 35–40%) is the most common trAEs. Fatigue (14%, 95% CI 7–23%) is the most common irAEs. The pooled results also showed that 18.8% (95% CI 13.2–25.2%) of patients required systemic steroid therapy due to AEs, while 6.6% (95% CI 4.6–9.0%) of patients withdrew from treatment due to AEs. Additionally, patients experiencing irAEs may have a better progression-free survival (PFS) (multivariate analysis: hazard ratio [HR] = 0.41, 95% CI 0.27–0.61, I2 = 36.3%) but not overall survival (OS) (multivariate analysis: HR = 0.54, 95% CI 0.22–1.36, I2 = 83.2%) than those with no irAEs. Our study presents a systemic assessment of the AEs profile in HCC patients receiving ICIs, providing important reference for clinicians on toxicity profile. Besides, patients with irAEs may have a better PFS. More large-scale and prospective studies are needed to confirm our conclusions. [ABSTRACT FROM AUTHOR]

Background: The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to play a vital role in the occurrence and development of various tumors. However, the underlying mechanism of MALAT1 in hepatocellular carcinoma (HCC) has not been thoroughly elucidated. Methods: The expression levels of MALAT1 in HCC tissues and different cell lines were detected by qRT-PCR. Antisense oligonucleotides (ASO)-MALAT1 transfected cells were used to explore the biological effects of MALAT1 in HCC cells by cell counting kit 8 (CCK-8), colony formation, transwell, wound healing, and flow cytometry analysis. Western blotting was performed to measure AMPK and apoptosis-related protein levels. Dual-luciferase reporter assay was performed to verify the relationship between MALAT1 and its specific targets. Results: We found that MALAT1 was upregulated in HCC, and MALAT1 knockdown in HCC cells inhibited cell proliferation, migration, and invasion and inhibited apoptosis in vitro. Further studies demonstrated that MALAT1 positively regulated the expression of transcription factor II B‑related factor 2 (BRF2), which was associated with tumor recurrence, large tumor size, and poor prognosis in HCC. Mechanistically, MALAT1 was found to act as a competitive endogenous RNA to sponge has-miR-1-3p, which upregulated BRF2 expression. Knockdown of BRF2 inhibited the progression of HCC by activating the LKB1/AMPK signaling pathway. Overexpression of BRF2 reversed the inhibitory effect of MALAT1 knockdown on HCC cell viability. Moreover, ASO targeting MALAT1 inhibited the growth of xenograft tumors. Conclusions: Our results demonstrate a novel MALAT1/miR-1-3p/BRF2/LKB1/AMPK regulatory axis in HCC, which may provide new molecular therapeutic targets for HCC in the future. [ABSTRACT FROM AUTHOR]

Background and aims: The impacts of macrovascular invasion (MVI) or extrahepatic spread (EHS) on the efficacy and safety of immune checkpoint inhibitors (ICIs) among hepatocellular carcinoma (HCC) patients remain unclear. Thus, we conducted a systematic review and meta-analysis to clarify whether ICI therapy is a feasible treatment option for HCC with MVI or EHS. Methods: Eligible studies published before September 14, 2022, were retrieved. In this meta-analysis, the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and occurrence of adverse events (AEs) were outcomes of interest. Results: Fifty-four studies involving 6187 individuals were included. The findings indicated that the presence of EHS in ICI-treated HCC patients may indicate an inferior ORR (OR 0.77, 95% CI 0.63–0.96), but may not significantly affect the PFS (multivariate analyses: HR 1.27, 95% CI 0.70–2.31) and OS (multivariate analyses: HR 1.23, 95% CI 0.70–2.16). Additionally, the presence of MVI in ICI-treated HCC patients may not have significant prognostic impact on ORR (OR 0.84, 95% CI 0.64–1.10), but may indicate inferior PFS (multivariate analyses: HR 1.75, 95% CI 1.07–2.84) and OS (multivariate analyses: HR 2.03, 95% CI 1.31–3.14). The presence of EHS or MVI in ICI-treated HCC patients may not significantly impact the occurrence of any serious immune-related adverse events (irAEs) (grades ≥ 3) (EHS: OR 0.44, 95% CI 0.12–1.56; MVI: OR 0.68, 95% CI 0.24–1.88). Conclusion: The presence of MVI or EHS in ICI-treated HCC patients may not significantly impact the occurrence of serious irAEs. However, the presence of MVI (but not EHS) in ICI-treated HCC patients may be a significant negative prognostic factor. Therefore, ICI-treated HCC patients with MVI warrant more attention. [ABSTRACT FROM AUTHOR]

Adiposity is associated with an increased risk of primary liver cancer (PLC). As the most commonly used indicator of adiposity, the body mass index (BMI) has been questioned for its limitations in reflecting visceral fat. This study aimed to investigate the role of different anthropometric indicators in identifying the risk of PLC by accounting for potential non-linear associations. Systematic searches were conducted in the PubMed, Embase, Cochrane Library, Sinomed, Web of Science, and CNKI databases. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to assess the pooled risk. The dose-response relationship was assessed using a restricted cubic spline model. Sixty-nine studies involving more than 30 million participants were included in the final analysis. Regardless of the indicator used, adiposity was strongly associated with an increased risk of PLC. When comparing the HRs per 1-standard deviation increment across indicators of adiposity, the association was strongest for waist-to-height ratio (WHtR) (HR = 1.39), followed by waist-to-hip ratio (WHR) (HR = 1.22), BMI (HR = 1.13), waist circumference (WC) (HR = 1.12), and hip circumference (HC) (HR = 1.12). A strong non-linear association was observed between each anthropometric parameter and the risk of PLC, regardless of whether the original or decentralised value was used. The positive association between WC and PLC risk remained substantial after adjusting for BMI. The incidence of PLC was higher with central adiposity (52.89 per 100,000 person-years, 95% CI = 50.33–55.44) than general adiposity (39.01 per 100,000 person-years, 95% CI = 37.26–40.75). Central adiposity seems to contribute more to the development of PLC than general adiposity. A larger WC, independent of BMI, was strongly associated with the risk of PLC and might be a more promising predictive indicator than BMI. [Display omitted] • BMI, WC, WHR, WHtR, and HC were, respectively, positively associated with the risk of PLC. • Elevated WC, independent of BMI, was associated with an increased risk of PLC. • The incidence of PLC was higher in central adiposity than that in general adiposity. • WC might be a more promising predictive indicator for PLC beyond BMI. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibitors (ICIs) have been explored as first-line treatment in various types of previously untreatable malignancies, while limited evidence is available on the management of hepatitis B virus (HBV) in patients undergoing immunotherapy. We systematically reviewed data concerning challenges of hepatic adverse events including HBV reactivation and hepatitis in patients with chronic HBV infection undergoing immunotherapy. Methods: A systematic search was conducted in Medline, web of science, Embase and Cochrane library up to May 31, 2022. Studies reporting the safety profile of ICIs in patients with HBV infection were eligible. Meta-analyses were conducted to generate odds ratios (ORs) with 95% confidence intervals (CIs). Results: A total of 13 studies including 2561 patients were included for meta-analysis. The overall incidence rates of HBV reactivation in patients with chronic HBV infection and past HBV infection were 1.0% (95% CI 0–3%) and 0% (95% CI 0–0%), respectively. Among patients with chronic HBV infection, the incidence rates of HBV reactivation were 1.0% (95% CI 0–2%) and 10.0% (95% CI 4–18%) for patients with and without antiviral prophylaxis, respectively. Patients with chronic HBV infection were at a higher risk of HBV reactivation compared with those with past HBV infection [OR = 8.69, 95% CI (2.16–34.99)]. Antiviral prophylaxis significantly reduced the risk of HBV reactivation [OR = 0.12, 95% CI (0.02–0.67)] and HBV-associated hepatitis [OR = 0.05, 95% CI (0.01–0.28)] in patients with chronic HBV infection. Conclusions: Prophylactic antiviral therapy should be administered to patients with chronic HBV infection undergoing anticancer immunotherapy. Patients with past HBV infection are at lower risk of HBV reactivation compared with those with chronic HBV infection, they could be initiated with antiviral prophylaxis or monitored with the intent of on-demand antiviral therapy. [ABSTRACT FROM AUTHOR]

Background and Aim: The purpose of the present study was to evaluate the effect of direct‐acting antivirals (DAAs) therapy on the clinical outcomes of hepatitis C virus (HCV) patients with hepatocellular carcinoma (HCC). Methods: We searched multiple electronic databases from database inception to June 14, 2021. Meta‐analyses were performed separately for HCC recurrence and overall survival (OS). Results: A total of 23 studies were identified for the primary analysis. Compared with no intervention, pooled data showed significant benefit from DAAs therapy in reducing recurrence (adjusted HR = 0.55, 95% CI 0.41–0.74, P < 0.001; I2 = 66.6%, P < 0.001) and improving OS (adjusted HR = 0.36, 95% CI 0.16–0.83, P = 0.017; I2 = 90.7%, P < 0.001) of HCV‐related HCC patients. Compared with non‐responders, patients with sustained virologic response (SVR) had greater benefit from DAAs therapy in reducing recurrence (HR = 0.37, 95% CI 0.16–0.84, P = 0.017; I2 = 58.8%, P = 0.088) and improving OS (HR = 0.17; 95% CI 0.06–0.50; P = 0.001; I2 = 56.4%, P = 0.130). Though DAAs did not show significant advantages over IFN in reducing recurrence (adjusted HR = 0.96, 95% CI 0.72–1.28, P = 0.784; I2 = 0.0%, P = 0.805), there seems to be a trend toward OS benefit from DAAs therapy (adjusted HR = 0.11, 95% CI 0.01–1.19, P = 0.059). Conclusion: DAAs therapy can prevent recurrence and improve OS of HCV‐related HCC patients, especially for patients with SVR. Further prospective randomized controlled trial is warranted to validate these results. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma is one of the most lethal malignancies, having a significantly poor prognosis. Immunotherapy, as an emerging tumor treatment option, provides new hope for many cancer patients. However, a large proportion of patients do not benefit from immunotherapy. As a critical cell-to-cell communication mediator in the tumor immune microenvironment, exosomes may play a unique role in hepatocellular carcinoma immune response and thus affect the efficiency of immunotherapy. In this review, we discuss related research on the roles of exosomes in the current immunotherapy resistance mechanism of hepatocellular carcinoma. Furthermore, we also clarify the excellent predictive value of exosomes and the roles they play in improving immunotherapy efficacy for hepatocellular carcinoma patients. We hope that our review can help readers to gain a more comprehensive understanding of exosomes' roles in hepatocellular carcinoma immunotherapy. Hepatocellular carcinoma (HCC) is one of the most lethal malignancies, having a significantly poor prognosis and no sufficiently efficient treatments. Immunotherapy, especially immune checkpoint inhibitors (ICIs), has provided new therapeutic approaches for HCC patients. Nevertheless, most patients with HCC do not benefit from immunotherapy. Exosomes are biologically active lipid bilayer nano-sized vesicles ranging in size from 30 to 150 nm and can be secreted by almost any cell. In the HCC tumor microenvironment (TME), numerous cells are involved in tumor progression, and exosomes—derived from tumor cells and immune cells—exhibit unique composition profiles and act as intercellular communicators by transporting various substances. Showing the dual characteristics of tumor promotion and suppression, exosomes exert multiple functions in shaping tumor immune responses in the crosstalk between tumor cells and surrounding immune cells, mediating immunotherapy resistance by affecting the PD-1/PD-L1 axis or the anti-tumor function of immune cells in the TME. Targeting exosomes or the application of exosomes as therapies is involved in many aspects of HCC immunotherapies (e.g., ICIs, tumor vaccines, and adoptive cell therapy) and may substantially enhance their efficacy. In this review, we discuss the impact of exosomes on the HCC TME and comprehensively summarize the role of exosomes in immunotherapy resistance and therapeutic application. We also discuss the potential of exosomes as biomarkers for predicting the efficacy of immunotherapy to help clinicians in identifying HCC patients who are amenable to immunotherapies. [ABSTRACT FROM AUTHOR]

Mouse embryonic fibroblasts (MEFs) are multi-potent progenitor cells (MPCs), can differentiate into different lineages, such as osteogenic, and adipogenic. PTEN, a tumor suppressor, may be involved in regulating bone development through interacting with COX-2. BMP9, the most potent osteogenic BMPs, can up-regulate COX-2 in MPCs. Whether PTEN is involved in BMP9 induced osteogenic differentiation in MPCs remains unknown. The goal of this investigation is to identify the effect of PTEN on BMP9-induced osteogenic differentiation in MPCs and dissect the possible mechanism underlay this. We found that BMP9 down-regulates PTEN, and PTEN inhibitor (VO) effectively increases different osteogenic markers induced by BMP9 in MEFs. Exogenous expression of PTEN inhibits BMP9 induced ectopic bone formation apparently. Mechanistically, we found that VO can enhance BMP9 induced BMPs/Smads signaling prominently without no substantial effects on cell cycle. Further analysis indicates that VO can promote BMP9-induced expression of COX-2 in MEFs, which can be eliminated by PI3K inhibitor. Additionally, COX-2 knockdown abolishes the effect of VO on BMP9-induced ALP activities in MEFs. Our findings suggest that PTEN plays an important role in regulating BMP9 induced osteogenic differentiation in MPCs, which may be mediated by PTEN/PI3K/Akt signaling to modulate the expression of COX-2. [ABSTRACT FROM AUTHOR]

Based on the engineering background of Jianshan Iron mine in Panzhihua city, the caving mechanism and moving area of wall rock during transformation from open-pit to underground mining using similar material physical models and numerical simulation was researched. Firstly the similar material physical model was monitored with stress database collection box, total station instruments and digital camera shooting equipment to obtain the stress-displacement characteristics and failure process. Systematic analysis was made on stress displacement and crack failure of wall rock to discover the basic caving and moving mechanism of wall rock. Secondly the stress and displacement change, plastic zone distribution and disturbed angle change of model was systematic analyzed using numerical simulation software. The results indicate that the wall rock stress undergoes a course from dramatic change to slow change and finally shows a tendency toward stabilization. The extent of damage and the plastic zone increases with the mining depth increasing. The shear failure of the rock mass mainly appears at the foot of the two sides slopes. [ABSTRACT FROM AUTHOR]

Background and Aim: Salivary characteristics are altered in gastrointestinal diseases and related to oral taste disorder. However, specific salivary biochemical characteristics and their relationships with oral taste disturbances in chronic non‐atrophy gastritis (CNAG) remain uncertain. Methods: Seventy patients with CNAG and 70 subjects in healthy control group (HCG) were enrolled in our study. The levels of salivary flow rate (SFR), pH, salivary α‐amylase (sAA) activity, total protein density (TPD), chloride concentration, and calcium concentration were determined before and after citric acid stimulation and compared between CNAG with and without oral taste disturbances. Results: Average body mass index (BMI) of CNAG (17.75 ± 2.08) was lower than that of HCG (21.96 ± 1.72, P < 0.01). Compared with HCG, CNAG showed increased TPD and calcium concentration but decreased SFR both before and after acid stimulation (P < 0.01), as well as reduced sAA and salivary chloride responses to acid stimulation (P < 0.01). Compared with CNAG with normal BMI (24.29%, 17/70), sAA activity response to acid stimulation was reduced in those with low BMI (75.71%, 53/70, P < 0.05). Under resting condition, CNAG with dry mouth (55.71%, 39/70) showed increased SFR and decreased TPD (P < 0.05), as compared with CNAG without dry mouth (44.29%, 31/70). Compared with CNAG without bitter taste (57.14%, 40/70), pH was decreased in those with bitter taste (42.86%, 30/70) under both resting and stimulated conditions (P < 0.05). Conclusion: Decreased sAA activity may reflect malnutrition state and be one potential marker of poor digestion, decreased salivary pH may contribute to bitter taste perception, and reduced TPD might be a cause of dry mouth in CNAG. [ABSTRACT FROM AUTHOR]

Aberrant expression of microRNAs (miRNAs) plays an important role in gastric cancer (GC) development. miR-93-5p has shown opposing functions in different types of cancers, but the exact expression pattern and molecular mechanism of miR-93-5p in GC development remain to be elucidated. Here, we reported that miR-93-5p expression was increased in GC tissues compared with the adjacent normal tissues and that its overexpression was correlated with distant metastasis and poor survival in GC patients. miR-93-5p knockdown inhibited the migration, invasion and proliferation of GC cells in vitro and in vivo, while its overexpression displayed an opposite result. Using an mRNA microarray, we found that miR-93-5p significantly downregulated IFNAR1 expression in GC cells, which was further identified as a direct target of miR-93-5p. IFNAR1 knockdown promoted GC cell migration and invasion, but its restoration could rescue GC cell migration and invasion induced by miR-93-5p overexpression. Moreover, miR-93-5p-IFNAR1 axis increased MMP9 expression via STAT3 pathway in GC cells. Taken together, we reveal that miR-93-5p overexpression is associated with the poor survival of GC patients and miR-93-5p-IFNAR1 axis promotes GC metastasis through activation of STAT3 pathway. [ABSTRACT FROM AUTHOR]