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Purpose: The retrospective study was to explore the effectiveness and safety of GemOx (gemcitabine, oxaliplatin) plus sintilimab (belongs to the class of drugs known as immune checkpoint inhibitors, particularly targeting the PD-1 receptor) in relapse or refractory nodal PTCLs. Methods: Patients with nodal PTCL who initiated salvage therapy with sintilimab and GemOx between January 2020 to September 2021 were identified from the database of the hematology department of the Second Affiliated Hospital of Zhejiang University School of Medicine. All patients received 2–4 cycles (3 weeks/cycle) of treatment of sintilimab (200 mg, I.V, D1) in combination with GemOx. Treatment response was assessed every six weeks during the salvage treatment phase. Eligible patients received maintenance therapy according to the investigator’s decision. Follow-ups were routinely conducted every three months. Results: 31 patients with r/r nodal PTCLs were enrolled, including 23 PTCL-NOS, 4 AITL, and 4 ALCL. 21 (67.7%) patients received at least two lines of therapy. 71.0% (95% CI, 53.4%-83.9%) of patients documented objective response of 2–4 cycles of sintilimab plus GemOx therapy, including 9 complete response and 13 partial response. 21 (67.7%) patients received consolidation therapy, including 5 autologous stem-cell transplantation and 12 histone deacetylase inhibitors. After a median 25.6 months follow-up, the median PFS was 22.0 (95% CI,11.8–24.7) months, and the median OS was 26.2 (95% CI, 24.4 –NA) months. 29 (93.5%) patients experienced at least one adverse event, and 26 (83.9% patients only had mild (grade 1–2) AEs.Univariable Cox regression showed the progression risk of AITL is 22.7 (3.9- 131.0, p < 0.01) times of PTCL-NOS, while the HR of ALCL was 1.14 (0.33–3.96,p = 0.833). Conclusion: Sintilimab plus GemOx showed encouraging activity and manageable toxicity for patients with r/r PTCL. [ABSTRACT FROM AUTHOR]

In order to improve the crushing efficiency of drilling machinery, laser-assisted mechanical rock-breaking technology has gained wide attention in the field of engineering construction. In this method, the weakening effect of the laser on the compressive strength of the rock is a key factor of the technology. To reveal the weakening effect of the laser on the compressive strength of rocks, standard uniaxial compression tests were carried out on irradiated rocks using a uniaxial compression testing machine. The weakening effect of laser power and irradiation time on rock strength and rock failure mode was investigated. The experimental results show that the laser power and irradiation time have similar effects on the mechanical properties of the rocks. With the increase of laser power and irradiation time, the peak stress of the specimens shows a tendency to decrease rapidly and then slowly. At the same time, the rock elastic modulus decreases and peak strain increases, and the behavior eventually transform from brittle damage to plastic damage. Melting pit holes and crack networks are the root cause of the weakness of the compressive strength. On one hand, the vertical melting pit hole provides a conical free surface, which reduces the rock deformation constraint and generates stress concentration at the bottom of the hole, so that it facilitates the splitting-tension damage of the specimen. On the other hand, the axial load induces symmetric tensile cracks in the thermal cracks, and adjacent tensile cracks interpenetrate to create a surface of tensile damage, leading to fragmentation of the specimen in the form of rock blocks, ultimately undermining the rock. This work provides an improved understanding of the effect of lasers on the compressive strength of rocks in engineering applications. Highlights: The effect of laser irradiation on the compressive strength weakening of rock was investigated. Failure modes and strength weakening mechanisms of irradiated rocks were revealed. The advantage parameters of laser-assisted rock breaking were clarified. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the optimal threshold for measuring thyroid volume in patients with Grave's hyperthyroidism (GH) by SPECT/CT. Materials and methods: A 53 mL butterfly-shaped hollow container made of two 45-degree transparent elbows was put into a NEMA IEC phantom tank. The butterfly-shaped container and the tank were then filled with Na99mTcO4 of different radioactive concentrations, respectively, which could simulate thyroid gland with GH by different target-to-background ratios (T/B) (200:1, 600:1, 1000:1). The different T/B of planar imaging and SPECT/CT were acquired by a Discovery NM/CT 670 Pro SPECT/CT. With Thyroid software (Version 4.0) of GE-Xeleris workstation, the region of the thyroid gland in planar imaging was delineated. The thyroid area and average long diameter of both lobes were substituted into the Allen formula to calculate the thyroid volume. The calculation error was compared with the actual volume. Q-Metrix software was used to perform CT-based attenuation correction, scatter correction, resolution recovery. Ordered-subsets expectation maximization was used to reconstruct SPECT data. 20%, 25%, 30%, 40%, 50%, 60% thresholds were selected to automatically delineate the volume of interest and compared with the real volume, which determinated the optimal threshold. We measured the thyroid volume of 40 GH patients using the threshold and compared the volumes obtained by planar imaging and ultrasound three-dimensional. The differences of the volumes with different T/B and thresholds were compared by the ANOVA and least significant difference t test. The volumes delineated by SPECT/CT were evaluated using ANOVA, least significant difference t test, correlation analysis and, linear regression and Bland–Altman concordance test plot. The differences and consistency of thyroid volume were compared among the above three methods. Results: There was no significant difference in the results between different T/B models (P > 0.05). The thyroid volume calculated by the planar imaging formula method was higher than the real volume, with an average overestimation of 22.81%. The volumes delineated by SPECT/CT threshold automatically decreased while the threshold increased. There were significant differences between groups with different thresholds (P < 0.001). With an average error of 3.73%, the thyroid volume analyzed by the threshold of 25% was close to the results of ultrasound measurement (P > 0.05). Thyroid volume measured by planar imaging method was significantly higher than ultrasound and SPECT/CT threshold automatic delineation method (P < 0.05). The agreement between the SPECT/CT 25% threshold and ultrasound (r = 0.956, b = 0.961) was better than that between the planar imaging and ultrasound (r = 0.590, b = 0.574). The Bland–Altman plot also showed that the thyroid volume measured by the 25% threshold automatic delineation method was in good agreement with the ultrasound measurement. Conclusions: The T/B has no effect on the measurement of thyroid volume in GH patients; planar imaging method can significantly overestimate thyroid volume in GH patients, and 25% threshold automatic delineation method can obtain more accurate thyroid volume in GH patients. [ABSTRACT FROM AUTHOR]

This paper is concerned with the following Schrödinger–Newton equation - ε 2 Δ u + V (x) u = 1 ε 2 ∫ R 3 u 2 y x - y d y u , x ∈ R 3 , where ε is a positive parameter and V(x) is the potential function. We demonstrate an interesting phenomenon, which we call dichotomy, for concentrating solutions of the above Schrödinger–Newton equation. More specifically, we show the existence of infinitely many concentrating solutions which concentrate both in a bounded domain and near infinity. In addition, the non-degeneracy of the ground state is established for the above Schrödinger–Newton equation with non-constant potentials. [ABSTRACT FROM AUTHOR]

Experiences worldwide indicate that the relationship between energy consumption and economic development is complex. Guangdong Province has experienced a more than threefold increase in GDP since 2005, but it is not clear whether rapid economic growth is at the cost of a large amount of energy consumption. In this study, we employ spatial autocorrelation and hotspot analysis to discover the spatial agglomeration of GDP per capita and energy intensity in Guangdong, China, from 2005 to 2018. Furthermore, panel vector autoregression coupled with a system generalized method of moments is performed to examine the dynamic causal relationship between energy consumption and economic growth under the framework of the Cobb–Douglas production function. We used a multivariate model and grouped studies based on the differences in regional economic development and the results with similar research. The results show that the GDP per capita of the Pearl River Delta (PRD) is significantly higher than that of the peripheral municipalities. However, energy intensity shows an entirely different spatial distribution. The development of the regional economy depends on its own "assembling effect". In regions with significant differences in economic development, it is necessary to conduct grouping studies; otherwise, the overall results will not represent partial results. GDP explains approximately 68.3% of the total variation in energy consumption in the PRD but only approximately 34.5% of that in the peripheral municipalities. We do not confirm Granger causality between energy consumption and economic development. Guangdong can decrease its energy consumption growth without substantially sacrificing its economic growth. The contribution of this study is to propose an analytical framework of the relationship between energy consumption and economic development that integrates time and space perspectives to account for spatial effects in panel analysis. [ABSTRACT FROM AUTHOR]

Focusing on the analysis of specific energy SE and crack development characteristics, this research aims to clarify the rock breaking effect of worn TBM cutters. Based on the geometric characteristics of rock face under the action of the worn cutters, the rock breaking method affected by the ridge was proposed, and the discrete element method was used to establish a double-cutter indentation model for simulation. The blade height difference h and blade width T caused by cutter wear were used as variables, and the influence of cutting spacing and cutting sequence was considered. Study showed that the specific energy SE of rock-breaking decreased slowly with the increasing h, and then rose sharply when h exceeded the critical blade height difference hc. When the cutting distance s = 60, 70, 80 mm,the corresponding hc values were 10, 15, 15 mm, respectively. From the perspective of rock breaking process, worn cutters formed ridges on the rock surface, which affected the direction of crack development. When h < hc, the lateral cracks produced by the cutter extrusion developed in the direction of adjacent cutter inside the ridge, forming a large through rock fragment. When h > hc, the cracks emerged from the slope of the ridge, no large rock fragments were formed, resulting in a sudden increase in SE. Experimental verification showed that the simulation results were effective and can provided reference for worn TBM cutter changing. [ABSTRACT FROM AUTHOR]

For a tunnel boring machine (TBM), the cutter rock-breaking effect and mechanism are key components of the machine design and construction. Each cutter on the TBM cutterhead is affected by adjacent cutters and exhibits different rock-breaking effects under different rock-breaking sequences. Considering the influence of two adjacent cutters, the target cutter has three rock-breaking sequences, A–C, for which the target cutter cuts as the second, first, or last tool, respectively. Most previous studies considered the sequential rock-breaking method, i.e., sequence A, and ignored jumping rock-breaking, i.e., sequences B and C. To quantify the obvious differences in rock-breaking effects between jumping and sequential rock-breaking, and to analyze the jumping rock-breaking mechanism itself, a series of special experiments was performed in this work. The experiment results show that, in terms of the rock-breaking force and boreability index values, the order is sequence B > A > C. For the specific energy, when the penetration is greater than the optimal penetration of the sequence C, the order is sequence B < A < C. These differences in rock-breaking effects can be reasonably explained from the perspective of pre-damage using the crack development method. As jumping rock-breaking constitutes a considerable proportion of the TBM cutter operation, consideration of this mechanism with its unique rock-breaking characteristics provides new directions for fine-tuning the design of TBM cutterheads and selection of TBM construction parameters. [ABSTRACT FROM AUTHOR]

To improve the efficiency of tunnel boring machines (TBMs) in hard rock environment, the technology of pre-grooving-assisted disc cutters for rock breaking was studied. Firstly, considering the relative position of the pre-grooving and the disc cutter, the same trajectory (SM) and different trajectory (DM) pre-grooving-assisted rock-breaking modes were proposed. Secondly, the discrete element method was used to simulate the crushing process of the pre-grooved rock by the cutter, and the rock-breaking mechanism and laws of different pre-grooving-assisted modes were revealed. Thirdly, a full-scale linear cutting experiment was conducted, which proved the correctness of the research results. Finally, suggestions for the use of the assisted rock-breaking mode were provided. Results show that the DM and SM modes achieve the effect of assisted the disc cutter in breaking the rock by promoting the tensile failure of the rock. Groove has the effect of inducing crack propagation. The groove in DM induces the crack to develop to both sides, and that in SM induces the crack to develop vertically. Compared with the complete cutting mode (CM), the SM and DM modes exhibit improved rock-breaking performance. Specifically, DM and SM are more helpful in reducing specific energy and cutting force, respectively. For the DM mode, with an increase in groove spacing, rock-breaking specific energy decreases and cutting force increases. This study provides ideas and guidance for the application of water jet pre-grooving-assisted TBM rock-breaking technology. [ABSTRACT FROM AUTHOR]

Microglia-mediated neuroinflammation in response to injurious self and non-self-stimuli exerts detrimental effects on neurons, which may lead to cognitive impairment. Luteolin, a typical kind of natural flavonoid in honeysuckle, chrysanthemum, and Herba Schizonepetae, is widely recognized to be anti-inflammatory and antioxidant against peripheral inflammation. However, its protective effect against inflammation-induced cognitive impairment is currently unknown. In this paper, we investigated the relief potential of luteolin against lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation and its possible anti-inflammatory mechanisms in lipopolysaccharide-stimulated BV2 microglia cells. In this study, luteolin ameliorated LPS-induced cognitive impairments, indicated by behavioral performance of neuroinflammatory model mice in Morris water maze tests. Protein analyses and histological examination also revealed protective effect of luteolin against neuronal damage, through inhibiting overproduction of inflammatory cytokines in both hippocampus and cortex of mice. We also observed luteolin in vitro significantly suppressed the levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-1 β (IL-1β), and inflammatory mediators like nitric oxide. Taken together, these results demonstrated luteolin was effective in alleviating cognitive impairment and limited neuronal damage via inhibiting the release of inflammatory mediators, suggesting luteolin is potential for further therapeutic research of neuroinflammation-related neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Safe and long lifespan batteries facilitate the development of portable electronics and electric vehicles. Owing to the low-cost, naturally abundance, and trivalent charge carrier of aluminum with the highest theoretical volumetric capacity, rechargeable aqueous aluminum-ion-based batteries are considered as promising next-generation secondary batteries. However, traditional electrolytes and frequent collapse of the host structure of electrode materials greatly jeopardize the cycle stability of the batteries. Here, we develop a novel hydrogel-based electrolyte coupled with stable layered intercalation electrodes for the first time to fabricate a highly safe and flexible rechargeable hybrid Al3+/H+ battery. The as-fabricated hybrid-ion battery (HIB) delivers a high specific capacity of 125 mAh·g−1 at 0.1 A·g−1 and exhibits an unprecedented super long-term cycling stability with no capacity fading over 10,000 cycles at 2 A·g−1. In addition, the hydrogel-based electrolyte possesses smart function of thermoresponsive switching, which can effectively prevent thermal runaway for the batteries. The unprecedented long cycle stability, highly intrinsic safety as well as low-cost indicate that the flexible aqueous HIBs are promising for applications. [ABSTRACT FROM AUTHOR]

This research introduces a support vector regression (SVR) method to predict the cutting forces acting on the constant cross section (CCS) disc cutter, including the normal force (FN) and rolling force (FR), based on linear cutting machine (LCM) test data. To improve the prediction effect, an improved SVR-Outlier Detection (SVR-OD) method and an Additional Input Variable (AIV) method are proposed. After removing the outliers, 148 typical LCM test samples form the training set. Here, 70 samples from the Hangzhou No.2 Water Supply Channel constitute the test set. The prediction results show that the Root-mean-squared Relative Error (RMRE) values of the normal force and rolling force are 19.5% and 24.8%, respectively, and the corresponding determination coefficients are 0.845 and 0.807, respectively. For the prediction of the peak cutting force with an important reference to tunnel boring machine (TBM) design, the proportions of samples with an Absolute Relative Error (ARE) value of less than 20% for FN and FR are 9/10 and 7/7, respectively. The above prediction results are better than those of the common SVR method; thus, the developed method can effectively simulate the cutting force required by a rock mass with good integrity. The cutting force prediction using LCM test data is feasible and practical. In addition, the comparison of the prediction results between the improved SVR and common SVR methods shows that the improved SVR-OD and AIV methods play an active role in improving the prediction accuracy of the SVR method. [ABSTRACT FROM AUTHOR]

The mechanical characteristics and stress state caused by water jet loading are influenced by many factors that have restricted studies on the jet mechanism. Using the basic theory of elasticity and fluid dynamics, the mechanical effects of water jet loading are analyzed. Based on the simplified jet distribution pressure, the elastic analytical solution of the stress distribution in a semi-infinite plane under the jet distribution pressure is derived, and the stress distribution characteristics are discussed. In addition, the Mohr–Coulomb yield criterion served as a fracture criterion, enabling establishment of the relationship between jet pressure and rock strength. The results indicate that the compressive stress is symmetrically distributed around the jet axis with the maximum at the center. Conversely, the shear stress is Anti-symmetrically distributed around the jet axis with the maximum at the point (0.5r, ± 0.65r). The initial fracture of rock under the impact of water jet is mainly shear compression failure. The Mohr–Coulomb yield criterion is useful for estimating the relationships between the rock failure zone diameter with the water jet impact pressure. [ABSTRACT FROM AUTHOR]

The characteristics of land use/land cover (LULC) types may affect the thermal environment of urban zones. In this study, the urban zones of the Pearl River Delta (PRD) were examined to explore the spatiotemporal variations in land surface temperature (LST) from 2001 to 2017, as well as the relationships between LST and various influencing factors. Landscape pattern analysis was undertaken to explore the correlation between patch metrics and LST with resolutions from 100 m to 1 km. The results showed that (1) the high-temperature zones were mainly distributed on built-up land; the area of LST hot spots increased from 16% (2001) to 23% (2017). (2) The mean LST of each LULC type was calculated, indicating that the temperature of forestland was more than 5 °C lower than that of built-up land. (3) The landscape patterns of different land use types exhibited various effects on LST in terms of magnitude and importance. Considering the significance of the landscape indexes, it is necessary to avoid a large-scale layout of a single built-up land type when planning an urban environment. It is thus recommended that multiple contiguous forestlands be planned to mitigate urban heat island (UHI) effects. Furthermore, the landscape patterns and structure of different LULC types have various effects on LST and need to be explored in fine detail. This study helped reveal the impact of different LULC types on LST and provides urban planners in the PRD with optional schemes for mitigating the impacts of urbanization on the UHI. [ABSTRACT FROM AUTHOR]

The subject of this investigation is the stress evolution characteristics of rock impacted by transverse plain water jet (PWJ), including the application of stress evolution in the interpretation of the laws of breaking rocks (including artificial rock). Based on the semi-infinite plane theory, an analytical solution of the stress evolution of rock subjected to transverse jet loading is obtained, and the evolution of the stress state variable F of the rock microelement based on the Mohr–Coulomb criterion is also obtained. Then, elastic brittle failure and elastic-brittle damage of rock microelements are analyzed. Besides, an expression of the damage variable D based on elastic-brittle failure assumption is proposed. The analysis shows that the peak values of the F evolution curve determines the failure of the rock microelement based on the elastic-brittle failure hypothesis. The area SF surrounded by the evolution curve F and the line (F = F0) is positively correlated with the damage variable D, which can be used to qualitatively explain the time dependence of breaking rock using a transverse PWJ. In addition, the method based on damage variable D presented in this paper shows great potential in quantitative analysis of time dependence of rock failure. [ABSTRACT FROM AUTHOR]

Highlights: A 2.4 V high-voltage flexible aqueous ZIB was fabricated, and superiors performances were achieved: extremely flat charging/discharging voltage plateaus (1.9/1.8 V), the smallest plateau voltage gap of 0.1 V, high energy density of 120 Wh kg−1, high power density of 3700 W kg−1, and excellent rate capability of 25 C. The battery posed application potential in wearable electronics with extreme safety against tough destructions including hammering, sewing, punching, and soaking.Flexible rechargeable aqueous zinc-ion batteries (ZIBs) have attracted extensive attentions in the energy storage field due to their high safety, environmental friendliness, and outstanding electrochemical performance while the exploration of high-voltage aqueous ZIBs with excellent rate capability is still a great challenge for the further application them in flexible and wearable electronics. Herein, we fabricated a 2.4 V high-voltage flexible aqueous ZIB, being among the highest voltage reported in aqueous ZIBs. Moreover, it exhibits extremely flat charging/discharging voltage platforms and the dropout voltage is only 0.1 V, which is the smallest gap in all aqueous batteries to our best knowledge. Furthermore, the prepared ZIB performs high rate capability of 25 C and energy density of 120 Wh kg−1 and exhibits excellent safety under various destructive conditions including hammering, sewing, punching, and soaking. These extraordinary results indicate the great application potential of our high-voltage flexible aqueous ZIB in wearable electronics. [ABSTRACT FROM AUTHOR]