Study on energy evolution and fractal characteristics of sandstone with different fracture dip angles under uniaxial compression.

In order to investigate the failure modes and instability mechanism of fractured rock. Uniaxial compression tests were conducted on sandstone specimens with different dip angles. Based on rock energy dissipation theory and fractal theory, the energy evolution characteristics and fragmentation fractal characteristics in the process of deformation and failure of specimens were analyzed. The results show that the peak strength and elastic modulus of fractured rock mass are lower than those of intact samples, and both show an exponential increase with the increase of fracture dip angle. The energy evolution laws of different fracture specimens are roughly similar and can be classified into four stages based on the stress-strain curve: pressure-tight, elastic, plastic, and post-destructive. The total strain energy, elastic strain energy, and dissipated strain energy of the specimen at the peak stress point increased exponentially with crack inclination, and the dissipated strain energy and compressive strength conformed to a power function growth relationship. The distribution of the fragments after the failure of the fracture sample has fractal characteristics, and the fractal dimension increases with the increase of the fracture dip angle. In addition, the higher the compressive strength of the specimen, the greater the energy dissipation, the more serious the degree of fragmentation, and the greater the fractal dimension. The data fitting further shows that there is a power function relationship between the dissipated strain energy and the fractal dimension. The research results can provide a theoretical basis for the stability of rock mass engineering and structural deformation control.

Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

Facile Fabrication of Highly Efficient Chitosan-Based Multifunctional Coating for Cotton Fabrics with Excellent Flame-Retardant and Antibacterial Properties.

Interest in the development of eco-friendly, sustainable, and convenient bio-based coatings to enhance flame retardancy and antibacterial properties in cotton fabrics is growing. In this work, chitosan was protonated at its amino groups using a method with a high atom economy using an equimolar amount of amino trimethylene phosphonic acid (ATMP), resulting in the fabrication of a single-component chitosan-based multifunctional coating (ATMP-CS), thereby avoiding any additional neutralization or purification steps. Cotton fabrics coated with various loads of ATMP-CS were prepared through a padding-drying-curing process. The morphology, thermal stability, mechanical properties, antibacterial properties, flame-retardant behavior, and flame-retardant mechanism of these fabrics were investigated. The coating exhibited excellent film-forming properties, and it imparted a uniform protective layer onto the surfaces of the cotton fabrics. When the load capacity reached 11.5%, the coated fabrics achieved a limiting oxygen index of 29.7% and successfully passed the VFT test. Moreover, the ATMP-CS coating demonstrated antibacterial rates against Escherichia coli and Staphylococcus aureus reaching 95.1% and 99.9%, respectively. This work presents a straightforward and gentle approach to fabricating colorless, environmentally friendly, and highly efficient fabric coatings that have potential applications in promoting the use of bio-based materials.

Deubiquitinase Ubiquitin-Specific Protease 10 Deficiency Regulates Sirt6 signaling and Exacerbates Cardiac Hypertrophy.

Background Cardiac hypertrophy (CH) is a physiological response that compensates for blood pressure overload. Under pathological conditions, hypertrophy can progress to heart failure as a consequence of the disorganized growth of cardiomyocytes and cardiac tissue. USP10 (ubiquitin-specific protease 10) is a member of the ubiquitin-specific protease family of cysteine proteases, which are involved in viral infection, oxidative stress, lipid drop formation, and heat shock. However, the role of USP10 in CH remains largely unclear. Here, we investigated the roles of USP10 in CH. Methods and Results Cardiac-specific USP10 knockout (USP10-CKO) mice and USP10-transgenic (USP10-TG) mice were used to examined the role of USP10 in CH following aortic banding. The specific functions of USP10 were further examined in isolated cardiomyocytes. USP10 expression was increased in murine hypertrophic hearts following aortic banding and in isolated cardiomyocytes in response to hypertrophic agonist. Mice deficient in USP10 in the heart exhibited exaggerated cardiac hypertrophy and fibrosis following pressure overload stress, which resulted in worsening of cardiac contractile function. In contrast, cardiac overexpression of USP10 protected against pressure overload-induced maladaptive CH. Mechanistically, we demonstrated that USP10 activation and interaction with Sirt6 in response to angiotensin II led to a marked increase in the ubiquitination of Sirt6 and resulted in Akt signaling downregulation and attenuation of cardiomyocyte hypertrophy. Accordingly, inactivation of USP10 reduced Sirt6 abundance and stability and diminished Sirt6-induced downstream signaling in cardiomyocytes. Conclusions USP10 functions as a Sirt6 deubiquitinase that induces cardiac myocyte hypertrophy and triggers maladaptive CH.

The solvothermal synthesis and characterization of quaternary arsenic chalcogenides CsTMAsQ3 (TM = Hg, Cd; Q = S, Se) using Cs+ as a structure directing agent: from 1D anionic chains to 2D anionic layers.

Four new quaternary transition metal arsenic chalcogenide Cs-TM-As-Q compounds (TM = Hg, Cd; Q = S, Se) were synthesized using different mixed solvents. A 1,4-diaminobutane(1,4-dab)/water mixed solvent system was used to solvothermally synthesize the selenoarsenates CsTMAsSe3 (TM = Hg (1), Cd (2)). In 1, the eight-membered ring anion chain consists of trigonal-planar [HgSe3] and trigonal-pyramid [AsSe3]. Compound 2 is similar to the eight-membered ring chain anion of compound 1, and [CdAsSe3]- further joins, through µ3-Se and Cd, to form the layer anions [CdAsSe3]-. A 2-diaminopropane (1,2-dap) and water mixed solvent system was used to synthesize two thioarsenates, Cs2TM2As2S6 (TM = Cd (3), Hg (4)). Compounds 3, 4 and 2 are isostructural; the Cd and Hg atoms are four coordinated. Compounds 1-4 utilize Cs+ cations as a structural directing agent. Finally, the structural and optical properties of the novel series of arsenic chalcogenides were characterized.

Dual Specificity Phosphatase 12 Regulates Hepatic Lipid Metabolism Through Inhibition of the Lipogenesis and Apoptosis Signal-Regulating Kinase 1 Pathways.

Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide. Due to the growing economic burden of NAFLD on public health, it has become an emergent target for clinical intervention. DUSP12 is a member of the dual specificity phosphatase (DUSP) family, which plays important roles in brown adipocyte differentiation, microbial infection, and cardiac hypertrophy. However, the role of DUSP12 in NAFLD has yet to be clarified. Here, we reveal that DUSP12 protects against hepatic steatosis and inflammation in L02 cells after palmitic acid/oleic acid treatment. We demonstrate that hepatocyte specific DUSP12-deficient mice exhibit high-fat diet (HFD)-induced and high-fat high-cholesterol diet-induced hyperinsulinemia and liver steatosis and decreased insulin sensitivity. Consistently, DUSP12 overexpression in hepatocyte could reduce HFD-induced hepatic steatosis, insulin resistance, and inflammation. At the molecular level, steatosis in the absence of DUSP12 was characterized by elevated apoptosis signal-regulating kinase 1 (ASK1), which mediates the mitogen-activated protein kinase (MAPK) pathway and hepatic metabolism. DUSP12 physically binds to ASK1, promotes its dephosphorylation, and inhibits its action on ASK1-related proteins, JUN N-terminal kinase, and p38 MAPK in order to inhibit lipogenesis under high-fat conditions. Conclusion: DUSP12 acts as a positive regulator in hepatic steatosis and offers potential therapeutic opportunities for NAFLD.

Spirometric Reference Equations for Elderly Chinese in Jinan Aged 60-84 Years.

BACKGROUND: The interpretation of spirometry varies on different reference values. Older people are usually underrepresented in published predictive values. This study aimed at developing spirometric reference equations for elderly Chinese in Jinan aged 60-84 years and to compare them to previous equations. METHODS: The project covered all of Jinan city, and the recruitment period lasted 9 months from January 1, 2017 to September 30, 2017, 434 healthy people aged 60-84 years who had never smoked (226 females and 208 males) were recruited to undergo spirometry. Vital capacity (VC), forced VC (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, FEV1/VC, FEV6, peak expiratory flow, and forced expiratory flow at 25%, 50%, 75%, and 25-75% of FVC exhaled (FEF25%, FEF50%, FEF75%, and FEF25-75%) were analyzed. Reference equations for mean and the lower limit of normal (LLN) were derived using the lambda-mu-sigma method. Comparisons between new and previous equations were performed by paired t-test. RESULTS: New reference equations were developed from the sample. The LLN of FEV1/FVC, FEF25-75%computed using the 2012-Global Lung Function Initiative (GLI) and 2006-Hong Kong equations were both lower than the new equations. The biggest degree of difference for FEV1/FVC was 19% (70.46% vs. 59.29%, t = 33.954, P < 0.01) and for maximal midexpiratory flow (MMEF, equals to FEF25-75%) was 22% (0.82 vs. 0.67, t = 21.303, P < 0.01). The 1990-North China and 2009-North China equations predicted higher mean values of FEV1/FVC and FEF25-75%than the present model. The biggest degrees of difference were -4% (78.31% vs. 81.27%, t = -85.359, P < 0.01) and -60% (2.11 vs. 4.68, t = -170.287, P < 0.01), respectively. CONCLUSIONS: The newly developed spirometric reference equations are applicable to elderly Chinese in Jinan. The 2012-GLI and 2006-Hong Kong equations may lead to missed diagnoses of obstructive ventilatory defects and the small airway dysfunction, while traditional linear equations for all ages may lead to overdiagnosis.