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Abstract Fragmentomic features of circulating cell free mitochondrial DNA (ccf-mtDNA) including fragmentation profile, 5’ end base preference and motif diversity are poorly understood. Here, we generated ccf-mtDNA sequencing data of 1607 plasma samples using capture-based next generation sequencing. We firstly found that fragmentomic features of ccf-mtDNA were remarkably different from those of circulating cell free nuclear DNA. Furthermore, region-specific fragmentomic features of ccf-mtDNA were observed, which was associated with protein binding, base composition and special structure of mitochondrial DNA. When comparing to non-cancer controls, six types of cancer patients exhibited aberrant fragmentomic features. Then, cancer detection models were built based on the fragmentomic features. Both internal and external validation cohorts demonstrated the excellent capacity of our model in distinguishing cancer patients from non-cancer control, with all area under curve higher than 0.9322. The overall accuracy of tissue-of-origin was 89.24% and 87.92% for six cancer types in two validation cohort, respectively. Altogether, our study comprehensively describes cancer-specific fragmentomic features of ccf-mtDNA and provides a proof-of-principle for the ccf-mtDNA fragmentomics-based multi-cancer detection and tissue-of-origin classification.

The amount of As(III) adsorbed and the interfacial process are closely associated with the phase transformation of Schwertmannite (SCH). At present, studies on the adsorption characteristics of As(III) on SCH and the accompanying phase transformation process, especially the related mechanisms under the mediation of iron-reducing bacteria (FeRB) and sulfate-reducing bacteria (SRB), are limited in existing literature. With the help of continuous characterization, the adsorption behavior of As(III) on SCH was explored, as well as the transformation processes of SCH during these processes. The findings revealed that the SCH, synthesized by the KMnO4 oxidation and ethanol modification methods, exhibited excellent physical adsorption capacity for As(III) due to their increasing specific surface area and porosity. At room temperature (20°C), the saturation adsorption capacities of As(III) by M-SCH and Y-SCH reached 62.69 and 58.62 mg/g, respectively. Moreover, the generation and phase transformation of As(III)-bearing ferrihydrite were observed within a 60-min timeframe. It is the first time this phenomenon has been observed in such a short time, which is presumed to be an intermediate stage in the transformation of SCH into goethite. Furthermore, both FeRB and SRB could enhance the adsorption capacity of SCH for As(III). Comparatively, SRB has a more substantial impact on SCH’s phase transformation. These insights are valuable for the practical application of SCH in treating As(III) pollution.

A designed Mg88.7Ni6.3Y5 hydrogen storage alloy containing 14H type LPSO (long-period stacking ordered) and ternary eutectic structure was prepared by regulating the alloy composition and casting. The hydrogen storage performance of the alloy was improved by adding nano-flower-like TiO2@C catalyst. The decomposition of the LPSO structure during hydrogenation led to the formation of plenty of nanocrystals which provided abundant interphase boundaries and activation sites. The nanoscale TiO2@C catalyst was uniformly dispersed on the surface of alloy particles, and the ''hydrogen overflow'' effect of TiO2@C accelerated the dissociation and diffusion of hydrogen on the surface of the alloy particles. As a result, the in-situ endogenous nanocrystals of the LPSO structure decomposition and the externally added flower-like TiO2@C catalyst uniformly dispersed on the surface of the nanoparticles played a synergistic catalytic role in improving the hydrogen storage performance of the Mg-based alloy. With the addition of the TiO2@C catalyst, the beginning hydrogen desorption temperature was reduced to 200 °C. Furthermore, the saturated hydrogen absorption capacity of the sample was 5.32 wt.%, and it reached 4.25 wt.% H2 in 1 min at 200 °C and 30 bar.

Abstract Population mobility is a key component in promoting the re-agglomeration and dissemination of social and economic factors. Based on Spring Festival data from 2019 to 2023 on Baidu Migration Big Data, this paper analyses the spatiotemporal patterns and structural characteristics of population mobility in cities across China through spatiotemporal statistics and social network analysis and investigates the evolution patterns of Chinese population migration behavior under the influence of COVID-19 epidemic during Spring Festival. The results of the study show that: (1) There are significant temporal and spatial differences in the impact of COVID-19 on population migration, with much stronger shocks on the cities of middle migration scale; (2) Population migration in Chinese cities is robust, and the impact of COVID-19 on population movement and community evolution is mainly manifested in short-term effects, with essentially no residual effects; (3) Between 2020 and 2023, a total of 119 cities experience a transfer of communities (32.25%), of which 69 cities transfer once, 20 cities transfer twice, and 30 cities transfer three times. In addition, it is found that the closeness of urban links based on population movements remains subject to geospatial effects, and the boundaries of “communities” coincide very closely with provincial borders. The results of this study have important theoretical and practical implications for a deeper understanding of the long-term impact of major public health events on changes in the geographical characteristics of population distribution and the structure of population mobility networks.

Abstract Magnetization in a ferromagnetic layer could be manipulated by the spin-orbit torque whose generation commonly relies on the spin-orbit coupling from the adjacent heavy-metal layer within the bilayer. The fact that the magnetic topological insulator possesses both the ferromagnetic order with perpendicular anisotropy and inherent spin-orbit coupling inspires to realize such a torque-induced magnetization switching without forming any heterostructure with other materials. Here, only using a single layer of magnetically-doped topological insulator Cr:(Bi,Sb)2Te3, we realize a magnetization switching only by applying a large dc current. Assisted by the magnetic history, such a switching behaves nonvolatile under zero field but becomes volatile otherwise, as consistently shown by magnetoelectric transports and magneto-optical Kerr effect measurements. Static and quasistatic current are found to be equivalent for the switching. We propose that this switching may associate with the torque resulted from the spin-orbit coupling and the compositional asymmetry in the Cr-profile of the single layer.

Abstract The enhanced geothermal system (EGS) is the key to improving the heat production efficiency of hot dry rock (HDR). Due to the existence of EGS, the reservoir produces significant heterogeneity, so the optimal design of well location and injection rate has an important influence on the heat recovery effect of an EGS. To solve this problem, a calculation model for the heat output of an EGS under multifield coupling is established in this paper, and the influence of well location and injection rate on the heat recovery effect under different scales of EGS is deeply analyzed. The results show that the production well location and injection well displacement have a great influence on the heat recovery effect under different fracture‐network scales. The larger the size of the fracture network, the larger the effective utilization area of reservoir heat recovery and the better the effect of heat recovery. The closer the production well is to the fracture network and in the direction of the fracture network, the larger the effective utilization area of reservoir heat recovery is, and the better the effect of heat recovery is. The higher the injection well displacement is, the larger the effective utilization area of reservoir heat recovery is, and the better the heat recovery effect is. The research results have important guiding significance for the optimization of the scale, well placement, and water injection displacement of the EGS in the HDR reservoir.

Abstract Purpose There are few studies on the risk factors of postoperative complications after surgical treatment of hepatic hemangioma (HH). This study aims to provide a more scientific reference for clinical treatment. Methods The clinical characteristics and operation data of HH patients undergoing surgical treatment in the First Affiliated Hospital of Air Force Medical University from January 2011 to December 2020 were retrospectively collected. All enrolled patients were divided into two groups based on the modified Clavien-Dindo classification: Major group (Grade II/III/IV/V) and Minor group (Grade I and no complications). Univariate and multivariate regression analysis was used to explore the risk factors for massive intraoperative blood loss (IBL) and postoperative Grade II and above complications. Results A total of 596 patients were enrolled, with a median age of 46.0 years (range, 22–75 years). Patients with Grade II/III/IV/V complications were included in the Major group (n = 119, 20%), and patients with Grade I and no complications were included in the Minor group (n = 477, 80%). The results of multivariate analysis of Grade II/III/IV/V complications showed that operative duration, IBL, and tumor size increased the risk of Grade II/III/IV/V complications. Conversely, serum creatinine (sCRE) decreased the risk. The results of multivariate analysis of IBL showed that tumor size, surgical method, and operative duration increased the risk of IBL. Conclusions Operative duration, IBL, tumor size, and surgical method are independent risk factors that should be paid attention to in HH surgery. In addition, as an independent protective factor for HH surgery, sCRE should attract more attention from scholars.

Abstract Driving in interactive dynamic traffic is a huge challenge for autonomous vehicles, especially for motion planning. The autonomous vehicle not only needs to predict the future states of the social vehicles to avoid a collision but also realizes the comfort and continuous plan. To deal with the problem, a spatio‐temporal decision‐making and motion planning framework with flexible constraints based on previous work is proposed. Improvements can be highlighted in three aspects. First, a neural network for trajectory prediction is trained and it is integrated into the framework, which can learn the social vehicles' reactions in the negotiation better and give more accurate predictions. Second, instead of setting the fixed local targets, the flexible‐constraint mechanism is introduced to increase the success rate of continuous planning, specifically, the local planning target is determined conditioned on the situation with an elastic factor. Third, two popular simulators with randomly disposed traffic participants are exploited, where vehicles are mutually influenced, more similar to real‐world traffic. The closed‐loop tests with zero crashes and the comparative experiments with traditional models demonstrate the superior performance and practical significance of the proposed framework.

Abstract Reasonable volumetric fracturing effect evaluation is the key to effective stimulation of fractured reservoir. Traditional fracturing effect evaluation is mainly conducted by the SRV (stimulated reservoir volume), fracture length, fracture width and other indicators, ignoring the influence of failure mode on fracturing performance. In this paper, the different fracture modes including main fractures, branch fractures and self-supporting fractures contained in the fracture network and their contributions to fracturing effect were studied in depth by numerical simulation. The results show that the main fracture formed by tensile failure has the largest width but simple shape and relatively small distribution range, while the branch fracture has a slightly smaller width but effectively expands the main fracture. Although the self-supporting fracture by shear failure is not connected, it can still improve the overall flow conductivity. The angle and number of natural fractures in fractured reservoir have a significant effect on fracture network scale and fracturing effect. When the number of natural fractures is larger, both of the number and proportion of branching fractures and self-supported fractures are larger, although the isolated self-supported fractures account for a larger proportion, the overall flow conductivity of the final fracture network is stronger. When the angle of natural fractures is larger, the natural fractures in uniform stress field are easier to be connected by hydraulic fractures and the final fracturing effect is better. The research methods and results have a certain guiding significance for the evaluation of volumetric fracturing effect in fractured reservoirs and are conducive to the reasonable selection of favorable fracturing areas and engineering parameters.

Abstract Background The positive prediction of prognosis and immunotherapy within tertiary lymphoid structure (TLS) in cancerous tissue has been well demonstrated, including liver cancer. However, the relationship between TLS and prognosis in the peritumoral region of hepatocellular carcinoma (HCC) has received less attention. Few studies on whether TLS, as a typical representative of acquired immune cell groups, is associated with innate immune cells. The aim of this paper was to identify the prognostic role of peritumor TLS in HCC and to simply explore the relationship with neutrophils infiltration. Methods This study included cancerous and paracancerous tissue from 170 patients after surgical resection of HCC. TLS was examined and identified by pathological H&E examination, and the impact on prognosis was further classified by determination of total TLS area. Immunohistochemical staining of CD15+ neutrophils was also performed on half of the cases. The obtained results were validated by external public database, as TLS has been widely shown to be tagged with 12 chemokines. Results In peritumoral tissue, the TLS− group had better overall survival (OS) and disease‐free survival (DFS) outcomes compared with the TLS+ group. On the contrary, the intratumor TLS+ group showed better DFS outcomes. When further investigating the relationship between TLS area distribution and DFS, progressively worse prognosis was only found in the peritumor region with increasing TLS density (TLS− vs. TLSL vs. TLSH). In addition, neutrophil infiltration increased in parallel with TLS density in the peritumoral region, which was not observed in the intratumoral region. Conclusions TLS might have a dual prognostic role in different regions of HCC. The abundance of peritumoral TLS is an independent influence of DFS. The inconsistent correlation between neutrophils and corresponding TLS in different regions may indicate different pathways of immune aggregation and may serve as an explanation for the different prognosis of TLS, which needs to be specifically explored.

Summary: Background: The use of artificial intelligence (AI) in detecting colorectal neoplasia during colonoscopy holds the potential to enhance adenoma detection rates (ADRs) and reduce adenoma miss rates (AMRs). However, varied outcomes have been observed across studies. Thus, this study aimed to evaluate the potential advantages and disadvantages of employing AI-aided systems during colonoscopy. Methods: Using Medical Subject Headings (MeSH) terms and keywords, a comprehensive electronic literature search was performed of the Embase, Medline, and the Cochrane Library databases from the inception of each database until October 04, 2023, in order to identify randomized controlled trials (RCTs) comparing AI-assisted with standard colonoscopy for detecting colorectal neoplasia. Primary outcomes included AMR, ADR, and adenomas detected per colonoscopy (APC). Secondary outcomes comprised the poly missed detection rate (PMR), poly detection rate (PDR), and poly detected per colonoscopy (PPC). We utilized random-effects meta-analyses with Hartung-Knapp adjustment to consolidate results. The prediction interval (PI) and I2 statistics were utilized to quantify between-study heterogeneity. Moreover, meta-regression and subgroup analyses were performed to investigate the potential sources of heterogeneity. This systematic review and meta-analysis is registered with PROSPERO (CRD42023428658). Findings: This study encompassed 33 trials involving 27,404 patients. Those undergoing AI-aided colonoscopy experienced a significant decrease in PMR (RR, 0.475; 95% CI, 0.294–0.768; I2 = 87.49%) and AMR (RR, 0.495; 95% CI, 0.390–0.627; I2 = 48.76%). Additionally, a significant increase in PDR (RR, 1.238; 95% CI, 1.158–1.323; I2 = 81.67%) and ADR (RR, 1.242; 95% CI, 1.159–1.332; I2 = 78.87%), along with a significant increase in the rates of PPC (IRR, 1.388; 95% CI, 1.270–1.517; I2 = 91.99%) and APC (IRR, 1.390; 95% CI, 1.277–1.513; I2 = 86.24%), was observed. This resulted in 0.271 more PPCs (95% CI, 0.144–0.259; I2 = 65.61%) and 0.202 more APCs (95% CI, 0.144–0.259; I2 = 68.15%). Interpretation: AI-aided colonoscopy significantly enhanced the detection of colorectal neoplasia detection, likely by reducing the miss rate. However, future studies should focus on evaluating the cost-effectiveness and long-term benefits of AI-aided colonoscopy in reducing cancer incidence. Funding: This work was supported by the Heilongjiang Provincial Natural Science Foundation of China (LH2023H096), the Postdoctoral research project in Heilongjiang Province (LBH-Z22210), the National Natural Science Foundation of China’s General Program (82072640) and the Outstanding Youth Project of Heilongjiang Natural Science Foundation (YQ2021H023).

ABSTRACTTo understand the influence of corrosion and fracturing of prestressed steel on structural deformation, accelerated corrosion testing was carried out using a self-made test beam and applying DC power. Distributed optical fibre sensing technology based on pulse prepumped Brillouin optical time-domain analysis (PPP-BOTDA) was used to monitor the deformation of the prestressed concrete beam in the process of corrosion and fracture in real time. The finite-element model of local corrosion fracture of prestressed steel is established, and the monitoring results are verified based on various corrosion fracture simulation methods. The results show that when the sensing optical fibre pasted on the beam is less than 150 mm from the prestressed steel, the significant change of concrete strain when the steel breaks can be monitored and the fracture location can be determined at the same time. However, when the distance is greater than 150 mm, the change in monitoring data with the strain is not obvious. The distributed optical fibre sensing technology has high monitoring efficiency and abundant measurement data, and the underwater environment does not affect the transmission of monitoring data. This technology is applicable to the deformation monitoring of large prestressed concrete structures and could be widely used in practical engineering.

The anterior gradient protein 2 (AGR2) plays a crucial role in facilitating the formation of protein disulfide bonds within the endoplasmic reticulum (ER). Research suggests that AGR2 can function as an oncogene, with its heightened expression linked to the advancement of hepatobiliary and pancreatic cancers through invasion and metastasis. Notably, AGR2 not only serves as a pro-oncogenic agent but also as a downstream targeting protein, indirectly fostering cancer progression. This comprehensive review delves into the established functions and expression patterns of AGR2, emphasizing its pivotal role in cancer progression, particularly in hepatobiliary and pancreatic malignancies. Furthermore, AGR2 emerges as a potential cancer prognostic marker and a promising target for immunotherapy, offering novel avenues for the treatment of hepatobiliary and pancreatic cancers and enhancing patient outcomes.

Niangpi (cold skin noodles) with northwestern characteristics is one of the traditional foods in China. To promote the development of traditional food, the current study was designed to improve the formulation and production process of Niangpi. A single factor, Box-Behnken design of response surface methodology (RSM) was employed to investigate the appropriate amount of polysaccharides (including potato starch, konjac flour, and sodium alginate) and their influence on instrumental texture profile analysis (TPA) and sensory evaluation of Niangpi. The effect of different wobbling times (0s, 70s, 140s, 220s) on sensory evaluation, microstructure, face rate, and TPA of Niangpi was explored. The optimum level of potato starch, konjac flour, and sodium alginate determined by the single factor test and RSM was 1.0, 0.15, and 0.03% and 1.24, 0.16, and 0.03%, respectively. The quality of Niangpi was the best at 220 s wobbling time. The wobbling time increased the pore structure and hierarchy of Niangpi, and presented a strongly positive correlation with the hardness, gumminess, and a strongly negative correlation with adhesiveness, chewiness, and cohesiveness. The obtained results revealed that both the optimized formulation and production process not only simplified the preparation but also improved the quality and sensory characteristics of Niangpi.

Some studies have shown that sorafenib could significantly prolong the overall survival of patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoembolization (TACE). However, other studies revealed that patients had no access to sorafenib-related survival benefits after TACE. To identify the predictive biomarkers of therapeutic efficacy of sorafenib, we explored the potential predictive value of vascular endothelial growth factor (VEGF) and other clinical variables for survival benefits from sorafenib in patients treated with TACE previously. The results demonstrated that patients with tumor size > 7 cm or total bilirubin ≤ 17.3 μmol/L showed significant survival benefits from sorafenib after TACE treatment compared with those with tumor size ≤ 7 cm or total bilirubin > 17.3 μmol/L. Meanwhile, patients with VEGF > 131.09 pg/mL may obtain sorafenib-associated survival benefits after TACE when compared to those with VEGF ≤ 131.09 pg/mL, which needs further confirmation. The abovementioned results are helpful to confirm the specific population who are sensitive to targeted therapy. (1) Background: VEGF plays a crucial role in modulating proliferation and metastasis in HCC. We aimed to explore the relationship between VEGF and the prognosis, as well as the mortality risk of HCC patients who received TACE, and whether it and other variables could be considered as potential biomarkers for predicting the benefits from sorafenib. (2) Method: A total of 230 consecutive newly diagnosed patients with unresectable HCC treated with either TACE or TACE–sorafenib were collected retrospectively. Cox regression analyses were performed to evaluate the prognostic value of VEGF. Furthermore, restricted cubic splines were fitted to assess the nonlinear associations between VEGF and OS, and the threshold effect analysis was subsequently performed. Lastly, the potential factors for predicting the survival benefits from sorafenib after the TACE procedure were identified using the Cox proportional hazard model with an interaction term. (3) Results: VEGF was recognized as an independent prognostic factor for OS in the TACE alone cohort (HR = 3.237, p = 0.013). A nonlinear relationship was observed between VEGF and OS in HCC patients with TACE administration after adjustment for confounders (p for nonlinearity = 0.030); the mortality risk increased with increasing the baseline VEGF before the inflection point, and the HR for death was 1.008. There was no significant interaction between the VEGF levels and treatment modality (p for interaction = 0.233), and further studies are needed to identify its predictive value on the efficacy of sorafenib. Patients with tumor size > 7 cm or total bilirubin ≤ 17.3 μmol/L derived significant sorafenib-related benefits in OS when compared to those with tumor size ≤ 7 cm or total bilirubin > 17.3 μmol/L (p for interaction = 0.004 and 0.031, respectively). (4) Conclusions: Within a certain concentration range, elevated baseline VEGF meant an increased risk of death in HCC patients treated with TACE. Significant improvements in OS associated with sorafenib were observed in patients with higher tumor size and lower total bilirubin after TACE treatment.

Abstract Background Femoral neck fractures are a common traumatic injury. The removal of the internal fixation remains controversial, especially in terms of mechanical stability. Moreover, collapsed necrosis of the femoral head continues to occur after fracture healing. We believe that sclerotic cancellous bone (SCB) formation around the screw is associated with femoral head necrosis. We aimed to compare mechanical features before and after implant removal and determine the effect of SCB formation on stress distribution. Methods Cylindrical cancellous bone sections were collected from a relatively normal region and an SCB region of a necrotic femoral head, and their elastic moduli were measured. Four femoral finite element models were developed: a) femoral neck fracture healing with implants, b) fracture healing without implants, c) sclerosis around the screw with implants, and d) sclerosis around the screw without implants. Results The maximum von Mises peak stresses of models a and b were 66.643 MPa and 63.76 MPa, respectively, and were concentrated in the upper lateral femur. The main stress was scattered at the lowest screw tail, femoral calcar region, and lateral femur shaft. Moreover, coronal plane strain throughout the screw paths near the femoral head in models a and b was mostly in the range of 1000–3000 με. The maximum stress concentrations in models c and d were located at the lower femoral head and reached 91.199 MPa and 78.019 MPa, respectively. Conclusions The stresses in the sclerotic model around the cannulated screws are more concentrated on the femoral head than in the healing model without sclerotic bone. The overall stresses in the healing femoral neck fracture model were essentially unchanged before and after removal of the internal fixation.

How to improve the heat extraction performance of HDR (hot dry rock) is one of the most concerned problems in HDR extraction. The key is to take a reasonable method to evaluate the heat extraction performance of hot dry rock and find out the main factors influencing the heat extraction performance of hot dry rock. The permeability of HDR reservoir, well type, well spacing, well pattern and injection flow rate of cold water have important influence on heat extraction performance of HDR reservoir. Based on this, a multi-field coupling mathematical model for injection and production of HDR is established and solved by finite element method to analyze the evolutions of seepage field, temperature field and stress field in HDR reservoir. Then, high temperature production time and heat extraction rate were introduced to quantitatively evaluate the heat extraction performance of HDR reservoir under different reservoir permeability, different well type, different well spacing, different well pattern and different injection flow rate. The research results show that different reservoir permeability has little influence on the heat extraction performance of HDR reservoir. Comparing the vertical well production system with the horizontal well production system, horizontal well production system has longer high temperature production time, and vertical well production system has higher heat extraction rate. The greater the well spacing and injection flow rate, the better the heat extraction performance of HDR reservoir. The heat extraction performance of the well pattern is not necessarily better than that of the one-injection and one-production well pattern, the heat extraction performance of the one-injection two-production well pattern and the two-injection one-production well pattern is worse than that of the one-injection one-production well pattern, and the heat extraction performance of the four-injection one-production well pattern and the one-injection four-production well pattern is better than that of the one-injection one-production well pattern. The research results can provide a theoretical basis for the formulation of economic and reasonable HDR development program and working system, and realize efficient utilization of HDR reservoir.

Magnesium–lithium alloys are arguably the lightest metal structural materials but have low strength. In order to increase strength, friction stir processing (FSP) is applied to a hot-rolled Mg-10Li-3Al-3Zn (LA103Z) sheet to study the effects on the microstructure and mechanical properties. In this study, the strengthening mechanisms of various FSP regions of an Mg-Li alloy were clarified by a combination of numerical simulation and experimental method. Based on ANSYS APDL, a finite element model with a moving heat source is established. Rotational speeds of 800, 1000, and 1200 rpm and traverse speeds of 100, 110, and 120 mm/min were used in this research. The simulation results confirm that the influence of the rotation speed on the alloy temperature field is greater than that of the travel speed. The temperature of the processing area increases with an increase in rotation speed and decreases with an increase in travel speed. Then, hot-rolled LA103Z alloy plates are processed by FSP. The correspondence between the numerical simulation and experiment was verified by infrared thermography. The results indicate that FSP decreases the grain size significantly for the dynamic recrystallization and dramatic mechanical crushing of the stirring pin. The α-Mg and AlLi are solid soluted in the β-Li matrix. The tensile strength of the processing zone is 260.67 MPa (1000 rpm, 110 mm/min) versus the 170.47 MPa of the base metal. The SZ has the highest microhardness of 77.8 HV (800 rpm, 120 mm/min) and decreases gradually to the BM. The severe deformation, recrystallization, and solid solution of the α-Mg are important factors contributing to the improved mechanical properties.

Objective To analyze necrotic femoral head after long‐term internal fixation for femoral neck fractures using micro‐computed tomography (CT) for bone histomorphometry. Methods The experimental group included six patients (two men and four women; mean age 62.00 ± 9.36 years) who underwent hip arthroplasty at 47.67 ± 14.22 months after internal fixation. Surgery was performed because of femoral head necrosis after femoral neck fracture between October 2018 and October 2020. The control group included three patients (two men and one woman; mean age 69.33 ± 4.62 years) who underwent hip arthroplasty for femoral neck fracture. In the experimental group, micro‐CT quantitative analysis of the whole femur, sclerotic region around screws, screw paths, sclerotic region and screw paths, and relatively normal region was performed. The bone volume fraction (BV/TV), number of bone trabeculae (Tb.N), connection density (Conn.D), thickness of bone trabeculae (Tb.Th), separation of bone trabeculae (Tb.SP), structural model index (SMI), and bone mineral density (BMD) of each part were quantitatively analyzed. Results The BV/TV (0.3180 ± 0.0617), Conn.D (6.9261 ± 2.4715/mm3), Tb.Th (0.3262 ± 0.0136 μm), and BMD (298.9241 ± 54.2029 g/cm3) of the sclerotic region around the screws were significantly higher in the experimental group than the BV/TV (0.1248 ± 0.0390), Conn.D (2.5708 ± 0.5187/mm3), Tb.Th (0.1713 ± 0.0333 μm), and BMD (66.5181 ± 43.0380 g/cm3) in the control group (P

Medicago truncatula has been selected as one of the model legume species for gene functional studies. To elucidate the functions of the very large number of genes present in plant genomes, genetic mutant resources are very useful and necessary tools. Fast Neutron (FN) mutagenesis is effective in inducing deletion mutations in genomes of diverse species. Through this method, we have generated a large mutant resource in M. truncatula. This mutant resources have been used to screen for different mutant using a forward genetics methods. We have isolated and identified a large amount of symbiotic nitrogen fixation (SNF) deficiency mutants. Here, we describe the detail procedures that are being used to characterize symbiotic mutants in M. truncatula. In recent years, whole genome sequencing has been used to speed up and scale up the deletion identification in the mutant. Using this method, we have successfully isolated a SNF defective mutant FN007 and identified that it has a large segment deletion on chromosome 3. The causal deletion in the mutant was confirmed by tail PCR amplication and sequencing. Our results illustrate the utility of whole genome sequencing analysis in the characterization of FN induced deletion mutants for gene discovery and functional studies in the M. truncatula. It is expected to improve our understanding of molecular mechanisms underlying symbiotic nitrogen fixation in legume plants to a great extent.

Objectives: The meta-analysis was conducted to systematically assess the efficacy and safety of generic stent-graft/bare-stent combination compared with Fluency stent alone in transjugular intrahepatic portosystemic shunt procedure for refractory variceal bleeding. Methods: PubMed, EMBASE, Scopus, Web of Science and the Cochrane Database were searched for relevant studies from January 1990 to September 2020; outcome measures studied were primary patency, hepatic encephalopathy, survival, re-bleeding and portal venous pressure. Results: Four studies (1 randomised controlled trial and 3 retrospective studies) with 449 subjects (157 patients in the combined stent group and 292 patients in the covered stent group) were included. No significant difference was observed in the incidence of mortality (hazard ratio [HR] = 1.069, 95% confidence interval [CI] [0.524, 2.178]), hepatic encephalopathy (odds ratio [OR] = 0.860, 95% CI [0.341, 2.169], P = 0.750) and re-bleeding (OR = 1.049, 95% CI [0.226, 4.881], P = 0.951). Compared with Fluency stent alone, combination therapy was associated with moderate decrease in outcomes on the post-operative portal venous pressure (standard mean difference [SMD] −0.210, 95% CI [−0.418, −0.001], P = 0.049) and was not associated with significant decrease in outcomes on the pre-operative portal venous pressure (SMD − 0.129, 95% CI [−0.336, 0.078], P = 0.223). The primary patency was significantly lower in the Fluency/bare-stent combination group (HR = 0.473, 95% CI [0.288, 0.776]). Conclusions: Generic stent-graft/bare-stent combination therapy was associated with significantly lower primary patency compared to Fluency stent alone.

The inner roller exerts a supportive and thinning effect on the inner side of the tube during counter-roller spinning. In this paper, the Finite Element Analysis (FEA) model of counter-roller spinning for a 6061 aluminum alloy tube was established based on the ABAQUS/Explicit module. The deformation characteristics and the influence of inner roller geometrical parameters on the tube spinning were analyzed. The results showed that the stress–strain on the outer of the tube was greater than that of the inner, and flaring was more prone to occur in the initial stage of counter-roller spinning compared to traditional mandrel spinning. The order of the effects of geometrical parameters of the inner roller on the roundness error and wall thickness deviation was as follows: nose radius > diameter > front angle. The order of factors influencing the inner and outer spinning force was as follows: diameter > nose radius > front angle. Increasing the diameter of the inner roller can improve the spinning stability and forming accuracy of counter-roller spinning. It was beneficial to improve the forming accuracy when the nose radius of the inner roller was slightly larger than that of the outer roller. The front angle of the inner roller has little influence on the spinning forming accuracy.

In this study, we have successfully prepared surface modified zinc oxide quantum dots (M-ZnO QDs) with ultra-stable fluorescence and excellent hydrophilicity through introducing (3-aminopropyl)triethoxysilane (APTES). The as-prepared M-ZnO QDs under the optimum condition presented strong yellow fluorescence emission under 355 nm excitation and showed satisfied reproducibility. Physical and chemical properties of the synthesized ZnO QDs were further studied by various characterization techniques. Transmission electron microscopy showed homogeneous distribution of spherical M-ZnO QDs with the average particle size of 4.03 nm. According to the characteristic that metal ions can quench fluorescence, M-ZnO QDs-based fluorescence sensor for the detection of Cu2+ in aqueous solution is developed in this work, which has the advantages of excellent selectivity, good sensitivity and a wide linear range. The limit of detection was 0.51 μM and the linear detection range was 1–200 μM for Cu2+ determination. The practicability of the fluorescent probe is further validated in the lake water and the satisfactory spiked recoveries of Cu2+ ranges from 99.1 % to 108.8 %. Besides, M-ZnO QDs displayed concentration inhibition effect and strain effect on the growth of fungi. Thus, the as-prepared M-ZnO QDs are demonstrated to be promising for Cu2+ determination and anti-fungal applications.

A controllable magnetoelectric phase based on symmetry engineering is challenge in natural bulk crystals. Here, via engineering of interfacial Dzyaloshinskii-Moriya interaction, the authors design a magnetoelectric phase transition in oxide superlattices of correlated electron systems.

Abstract This study investigates the protective effect of Erigeron breviscapus injection, a classic traditional Chinese medicine most typically used by Chinese minority to treat stroke, on cerebral ischemia–reperfusion injury and the related signaling pathways. Use network pharmacology methods to study the relationship between E. breviscapus (Vant.) Hand-Mazz. and ischemic stroke, predict the mechanism and active ingredients of E. breviscapus (Vant.) Hand-Mazz. in improving ischemic stroke disease. We study the protective effect of E. breviscapus injection on blood–brain barrier (BBB) injuries induced by cerebral ischemia in rats by regulating the ROS/RNS-MMPs-TJs signaling pathway. The rat model of focal cerebral ischemia–reperfusion injury has been prepared using the wire-suppository method. Firstly, the efficacy of E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid in protecting BBB injury caused by cerebral ischemia has been evaluated. Secondly, the following two methods have been used to study the mechanism of E. breviscapus injection in regulating the ROS/RNS-MMPS-TJS signaling pathway: real-time PCR and western blot for the determination of iNOS, MMP-9, claudin-5, occludin, ZO-1 mRNA and protein expression in brain tissue. We find that PI3K-Akt signaling pathway predicted by network pharmaology affects the blood–brain barrier function, so we chose the blood–brain barrier-related MMP-9, claudin-5, iNOS, occludin and ZO-1 proteins are used for research. The results of our research show that 3 drugs can reduce the rate of cerebral infarction in rats, relieve the abnormal neuroethology of rats, reduce the degree of brain tissue lesion, increase the number of the Nissl corpuscle cells and repair the neuron ultrastructure in injured rats. At the same time, it can obviously reduce the ultrastructure damage of the BBB in rats. All three drugs significantly reduced the content of Evans blue in the ischemic brain tissue caused by cerebral ischemia in rats with BBB injury. In addition, E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid can decrease the protein expression of iNOS and MMP-9 in rat ischemic brain tissue. In addition, 3,5-dicaffeoylquinic acid can increase the protein expression of claudin-5. We conclude that E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid have obvious therapeutic effects on BBB and neuron injury induced by cerebral ischemia in rats. Our results from studying the mechanism of action show that E. breviscapus injection and Scutellarin inhibited the activation of MMP-9 by inhibiting the synthesis of iNOS, 3,5-dicaffeoylquinic acid inhibits the expression and activation of MMP-9 by inhibiting the activation of iNOS and reducing the generation of free radicals, thus reducing the degradation of important cytoskeleton connexin claudin-5 in the tight junction (TJ) structure by inhibiting the expression and activation of MMP-9. Finally BBB structure integrity was protected.

Background: Chondrons are composed of chondrocytes and the surrounding pericellular matrix (PCM) and function to enhance chondrocyte-mediated cartilage tissue engineering. This study aimed at investigating the potential effect of combined chondrocytes with chondrons on the production of proteoglycan and collagen-II (Col-2) and the repair of defective knee cartilage in rabbits. Methods: Chondrocytes and chondrons were isolated from the knee cartilage of rabbits, and cultured alone or co-cultured for varying periods in vitro. Their morphology was characterized by histology. The levels of aggrecan (AGG), Col-2 and glycosaminoglycan (GAG) expression were quantified by qRT-PCR, Alcian blue-based precipitation and ELISA. The effect of combined chondrocytes with chondrons in alginate spheres on the repair of defective knee cartilage was examined in rabbits. Results: The isolated chondrocytes and chondrons displayed unique morphology and began to proliferate on day 3 and 6 post culture, respectively, accompanied by completely degenerated PCM on day 6 post culture. Evidently, chondrocytes had stronger proliferation capacity than chondrons. Longitudinal analyses indicated that culture of chondrons, but not chondrocytes, increased AGG mRNA transcripts and GAG levels with time and Col-2 mRNA transcripts only on day 3 post culture. Compared with chondrocytes or chondrons alone, co-culture of chondrocytes and chondrons significantly up-regulated AGG and Col-2 expression and GAG production, particularly at a ratio of 1:1. Implantation with chondrocytes and chondrons at 1:1 significantly promoted the repair of defective knee cartilage in rabbits, accompanied by reduced the Wakiteni scores with time. Conclusion: Combined chondrons with chondrocytes promoted the production of extracellular matrix and the repair of defective knee cartilage in rabbits. The translational potential of this article: This study explores that the combination of chondrons and chondrocytes may be new therapeutic strategy for cartilage tissue engineering and repair of defective cartilage.

BackgroundTertiary lymphoid structures (TLS) have an effect on hepatocellular carcinoma (HCC), but the underlying mechanism remains to be elucidated.MethodsIntratumoral TLS (iTLS) was classified in the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort using pathological sections from the Cancer Digital Slide Archive. Univariate and multivariate Cox regression analyses were performed to validate the effect of iTLS on overall survival (OS), relapse-free survival (RFS), and disease-free survival (DFS). The genes differentially expressed between the iTLS-negative and iTLS-positive groups were analyzed in combination with sequencing data. Gene set enrichment analysis (GSEA) was used to explore the signaling pathways affected by these differentially expressed genes. The random forest algorithm was used to identify genes with the highest correlation with the iTLS in the training set. Multivariate logistic regression was used to build a model to predict iTLS in tissue samples. Spearman’s correlation was used to analyze the relationship between TLS-associated chemokines and signature genes, and CIBERSORT was used to calculate immune infiltration scores. Copy number variation and its relationship with immune cell infiltration and signature genes were assessed using the gene set cancer analysis (GSCA). The Correlation R package was used for gene ontology (GO), disease ontology (DO), and gene mutation analyses. The GSCA was used for drug sensitivity analysis. LASSO regression was used to build prognostic models, and external data were used to validate the models.ResultsThere were 218 positive and 146 negative samples for iTLS. iTLS was significantly associated with better RFS and DFS according to Cox regression analysis. Twenty signature genes that were highly associated with iTLS positivity were identified. GO and mutation analyses revealed that the signature genes were associated with immunity. Most signature genes were sensitive to immune checkpoint inhibitors. Risk scores calculated using a characteristic gene-based prognostic model were found to be an independent prognostic factor for OS.ConclusionsThe improvement of RFS in HCC by iTLS was not limited to the early period as previously reported. iTLS improved DFS in patients. Characteristic genes are closely related to the formation of iTLS and TLS chemokines in HCC. These genes are closely related to immunity in terms of cellular infiltration, biological functions, and signaling pathways. Most are sensitive to immune checkpoint inhibitors, and their expression levels can affect prognosis.

ObjectiveTo evaluate the safety and effectiveness of nimotuzumab in combination with chemoradiotherapy for locally advanced cervical esophageal squamous cell carcinoma.MethodsRetrospective analysis was conducted from September 2012 to February 2017 among 50 locoregional-advanced cervical esophageal carcinoma (CEC) patients who received concurrent chemoradiotherapy (CRT) combined with or without nimotuzumab at Ningbo Medical Center Lihuili Hospital. Intensity-modulated radiotherapy (IMRT) was administrated on all patients. All patients were divided into two groups, of which 26 (Group A) received 200 mg (22 of 50) or 400 mg (4 of 50) of nimotuzumab per week with CRT and 24 (Group B) received definitive CRT.ResultsThe median follow-up time was 23 months. The median overall survival (OS) and progression-free survival (PFS) were 40.6 and 21.1 months for all, respectively. The 1-, 2-, and 3-year OS rates on the whole were 79.6%, 62.1%, and 47.8%. There was no statistical difference in overall response rate and disease control rate between the two groups. Patients treated with nimotuzumab (group A) had better PFS than the definitive CRT group (group B) (P < 0.05). However, the median OS was 41.4 months in group A and 32.4 months in group B, respectively (P = 0.517). Multivariate analysis showed that PFS among those with lower Eastern Cooperative Oncology Group (ECOG) score (HR = 5.11; P < 0.01), stage II (HR = 9.52; P < 0.01) and the application of nimotuzumab combined with CRT (HR = 0.16; P < 0.01) was much longer. Furthermore, ECOG, stage, C-reactive protein (CRP) baseline, and histological grade can also be used as independent predictors of OS. Grade >3 adverse reactions were not observed. The most common adverse event related to nimotuzumab was mild fever and the occurrence rate was 19% (5 of 26). The incidence of anemia was 65.4% in group A and 87.5% in group B (P < 0.05).ConclusionsFor locoregional-advanced CEC, nimotuzumab combined with IMRT and concomitant chemotherapy was tolerated and effective. In addition, patients with a normal pretherapeutic serum CRP level (CRP < 10 mg/L) can achieve better OS.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. Most HCC patients are firstly diagnosed at an advanced stage, and systemic treatments are the mainstay of treatment. Summary: In recent years, immune checkpoint inhibitors have made a breakthrough in the systemic treatment of middle-advanced HCC, breaking the single therapeutic pattern of molecular targeted agents. To better guide the clinical treatment for effective and safe use of immunotherapeutic drugs, the Chinese Association of Liver Cancer and Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the “Chinese Clinical Expert Consensus on Immunotherapy for Hepatocellular Carcinoma (2021)” based on current clinical studies and clinical medication experience for reference in China. Key messages: The consensus contained 17 recommendations, including the preferred regimen for first- and second-line immunotherapy, evaluation and monitoring before/during/after treatment, management of complications, precautions for special patients and potential population for immunotherapy.

Tertiary lymphoid structures (TLSs) are organized aggregates of immune cells found in the tumor microenvironment. TLS can influence primary hepatic carcinoma (PHC) occurrence and have an active role in cancer. TLS can promote or inhibit the growth of PHC depending on their location, and although available findings are controversial, they suggest that TLS have a protective role in PHC tissues and a non-protective role in paracancerous tissues. In addition, the cellular composition of TLS can also influence the outcome of PHC. As an immunity marker, TLS can act as a marker of immunotherapy to predict its effect and help to identify patients who will respond well to immunotherapy. Modulation of TLS formation through the use of chemokines/cytokines, immunotherapy, or induction of high endothelial vein to interfere with tumor growth has been studied extensively in PHC and other cancers. In addition, new tools such as genetic interventions, cellular crosstalk, preoperative radiotherapy, and advances in materials science have been shown to influence the prognosis of malignant tumors by modulating TLS production. These can also be used to develop PHC treatment.

We report GaN high-electron-mobility transistors (HEMTs) with a thick (7.7 µm) GaN buffer on a Czochralski low resistivity Si (LRS) substrate. The GaN HEMTs exhibit high performance for both radio-frequency (RF) amplification and power conversion. The thick GaN buffer was grown by means of vacancy engineering, delivering a low dislocation density of ∼1.6 × 108 cm−2, contributing to suppressed RF signal coupling to the lossy Si substrate and a high vertical voltage blocking capability. For RF performance, GaN HEMTs with a 650 nm gate exhibit an fT/fMAX value of 25.1/32.3 GHz and a maximum output power POUT of 2.2 W/mm at 4 GHz with a drain voltage VDS of 20 V, which is comparable with the performance of RF GaN HEMTs on a high-resistivity silicon substrate without the existence of the field plate. For power performance, the vertical breakdown voltage of the wafer is 1160 V, and the three-terminal lateral breakdown voltage is 885 V in a GaN HEMT with a gate-to-drain distance of 8 µm. The thick GaN layer on the LRS substrate scheme thus provides a compelling platform for monolithic integration of high-performance RF devices and high-voltage power devices.

With the acceleration of human society’s digitization and the application of innovative technologies to emerging media, popular social media platforms are inundated by fresh news and multimedia content from multiple more or less reliable sources. This abundance of circulating and accessible information and content has intensified the difficulty of separating good, real, and true information from bad, false, and fake information. As it has been proven, most unwanted content is created automatically using bots (automated accounts supported by artificial intelligence), and it is difficult for authorities and respective media platforms to combat the proliferation of such malicious, pervasive, and artificially intelligent entities. In this article, we propose using automated account (bots)-originating content to compete with and reduce the speed of propagating a harmful rumor on a given social media platform by modeling the underlying relationship between the circulating contents when they are related to the same topic and present relative interest for respective online communities using differential equations and dynamical systems. We studied the proposed model qualitatively and quantitatively and found that peaceful coexistence could be obtained under certain conditions, and improving the controlled social bot’s content attractiveness and visibility has a significant impact on the long-term behavior of the system depending on the control parameters.

Background: BTBD10 serves as an activator of Akt family members through decreasing the protein phosphatase 2A-mediated dephosphorylation. The present study attempted to investigate the prognostic value of BTBD10 in hepatocellular carcinoma (HCC), specially, its relationship with tumor-infiltrating lymphocytes (TILs).Methods: BTBD10 expression was evaluated in HCC using The Cancer Genome Atlas (TCGA) and Xijing Hospital database, and verified in HCC cell lines. Cox analyses were performed to analyze independent prognostic risk factors for HCC. The optimal cut-off value of BTBD10 was calculated, by which all patients were divided into two groups to compare the overall survival (OS). The signaling pathways were predicted, by which BTBD10 may affect the progression of HCC. To investigate the impact of BTBD10 on HCC immunotherapy, correlations between BTBD10 and TILs, immune checkpoints, m6A methylation-related genes and ferroptosis-related genes were assessed. The distribution of half-maximal inhibitory concentration (IC50) of diverse targeted drugs was observed based on the differential expression of BTBD10.Results: BTBD10 expression was higher in HCC tissues and cell lines than that of normal liver tissues and cells. The patients with high expression of BTBD10 showed a worse OS, as compared to that of BTBD10 low-expressing group. Cox analyses indicated that BTBD10 was an independent prognostic risk factor for HCC. Several molecular pathways of immune responses were activated in HCC patients with high-expressing of BTBD10. Furthermore, BTBD10 expression was demonstrated to be positively correlated with tumor-infiltrating B cells, T cells, macrophages, neutrophils and dendritic cells. Meanwhile, the expression of BTBD10 was synchronized with that of several m6A methylation-related genes, ferroptosis-related genes and immune checkpoints. The IC50 scores of Sorafenib, Navitoclax, Veliparib, Luminespib, and Imatinib were found to be lower in BTBD10 high-expressing HCC group.Conclusion: BTBD10 negatively regulates tumor immunity in HCC and exhibits adverse effect on the prognosis of HCC, which could be a potential target for immunotherapy.

Based on the microseismic monitoring data of underground cavern of Shuangjiangkou Hydropower Station, the internal relationship between rockburst and microseismic events is analyzed and the occurrence mechanism of slip-type rockburst in underground cavern of Shuangjiangkou Hydropower Station is analyzed through the change of microseismic monitoring b value to warn the risk level of rockburst. The results show that microseismic events are closely related to excavation activities, and the change of b value reflects the rockburst risk level. The smaller the b value of microseismic events is, the more large magnitude events is and the greater the possibility of rockburst is. The slip-type rockburst was mainly affected by structural plane; it is due to the accumulation of elastic strain energy at the structural plane and the sudden release under the action of unloading or disturbance, driving the block on the structure surface fast slide, mainly manifested as the sliding of large blocks of surrounding rock, and forming a “V” shape pit blasting or cuneate blasting crater, as well as destruction with crackle. Compared with the strained rockburst, the damage is more serious. The research results can provide reference for rockburst prediction and prevention in similar deep rock engineering.

The bottom hole fluctuating pressure has a large influence on the wellbore instability. To address this problem, firstly, according to the principle of seepage mechanics, we established a calculation model of the change in pore pressure around the wellbore radius under fluctuating pressure; then, through laboratory rock mechanics test and rock damage mechanics theory analysis, the change law of formation strength under the action of static hydration and dynamic damage are determined; finally, based on the theory of rock mechanics in porous media, a quantitative evaluation method for the risk of wellbore instability under fluctuating pressure is established and the changing pattern of wellbore instability risk is analyzed. The results show that the pore pressure around the well shows a trend of fluctuation increase under fluctuating pressure, and there is a certain lag in the fluctuation of pore pressure inside the formation; the longer the muddy shale is immersed in drilling fluid, the greater the reduction in strength; the reduction is greater in the early stage of immersion, and the reduction in strength in water-based drilling fluid is greater than that in oil-based drilling fluid. At the beginning of the pressure cycle, the formation damage variable and compressive strength gradually increase and decrease with the increase of the pressure cycle number; after several cycles, the magnitude of change gradually decreases with the increase of the cycle number. When the bottom hole pressure fluctuates at a certain period, the greater the fluctuation, the shorter the period of wellbore stability; when the bottom hole pressure fluctuates at a certain range, the smaller the fluctuation period, the faster the borehole enters the high-risk period, while the shortest period of wellbore stability occurs when the fluctuation period is smallest; and when the wave cycle is in the middle, the wellbore stability period is the longest.

In this paper, the powder metallurgy (P/M) Ni-based superalloy FGH4096 with an incomplete dynamic recrystallization structure was treated by a solution treatment at different temperatures, cooling methods, and holding times. The size, morphology, and distribution of grains and γ′ precipitates were characterized by an optical microscope (OM) and a scanning electron microscope (SEM). Research results showed that with the increase of solution temperature from 1060 °C to 1100 °C, the degree of recrystallization increased continuously, the distribution of grain became uniform, and a large number of annealing twins were found. At the same time, the degree of redissolution of the primary γ′ precipitates at the grain boundary increased, and the size of secondary γ′ phase reprecipitated within the grain decreased. The morphology of the secondary γ′ precipitates is mainly spherical with a single distribution under air cooling (AC), while the morphology is near-spherical, cuboids, octets, petaloid, and dendrites with a bimodal distribution under furnace cooling (FC). The size of the γ′ precipitates decreased and the volume fraction increased with the extension of holding time at a higher solution temperature (1100 °C).

Abstract Mucopolysaccharidosis (MPS) VII is an ultra‐rare, progressively debilitating, life‐threatening lysosomal disease caused by deficiency of the enzyme, β‐glucuronidase. Vestronidase alfa is an approved enzyme replacement therapy for MPS VII. UX003‐CL301 was a phase 3, randomized, placebo‐controlled, blind‐start study examining the efficacy and safety of vestronidase alfa 4 mg/kg intravenously administered every 2 weeks to 12 patients with MPS VII. Due to the rarity of disease, broad eligibility criteria resulted in a highly heterogeneous population with variable symptoms. For an integrated view of the diverse data, the changes from baseline (or randomization for the placebo period) in clinical endpoints were grouped into three functional domains (mobility, fatigue, and fine motor + self‐care) and analyzed post‐hoc as subject‐level heat maps. Mobility assessments included the 6‐minute walk test, 3‐minute stair climb test, Bruininks‐Oseretsky test (BOT‐2) gross motor function subtests, and patient‐reported outcome assessments (PROs) related to movement, pain, and ambulation. Fatigue assessments included the Pediatric Quality of Life Multidimensional Fatigue Scale and other fatigue‐related PROs. Fine motor + self‐care assessments included BOT‐2 fine motor function subtests and PROs for eating, dressing, hygiene, and caregiver assistance. Most subjects showed improvement in at least one domain. Two subjects improved in two or more domains and two subjects did not show clear improvement in any domain. Both severely and mildly affected subjects improved with vestronidase alfa in clinical assessments, PRO results, or both. Heat map analysis demonstrates how subjects responded to treatment across multiple domains, providing a useful visual tool for studying rare diseases with variable symptoms.

BackgroundHepatocellular carcinoma is one of the most common malignant tumors with a very high mortality rate. The emergence of immunotherapy has brought hope for the cure of hepatocellular carcinoma. Only a small number of patients respond to immune checkpoint inhibitors, and ferroptosis and tertiary lymphoid structure contribute to the increased response rate of immune checkpoint inhibitors; thus, we first need to identify those who are sensitive to immunotherapy and then develop different methods to improve sensitivity for different groups.MethodsThe sequencing data of hepatocellular carcinoma from The Cancer Genome Atlas and Gene Expression Omnibus was downloaded to identify the immune-related long non-coding RNAs (lncRNAs). LncRNAs related to survival data were screened out, and a risk signature was established using Cox proportional hazard regression model. R software was used to calculate the riskScore of each patient, and the patients were divided into high- and low-risk groups. The prognostic value of riskScore and its application in clinical chemotherapeutic drugs were confirmed. The relationship between riskScore and immune checkpoint genes, ferroptosis genes, and genes related to tertiary lymphoid structure formation was analyzed by Spearman method. TIMER, CIBERSORT, ssGSEA, and ImmuCellAI were used to evaluate the relative number of lymphocytes in tumor. The Wilcoxon signed-rank test confirmed differences in immunophenoscore between the high- and low-risk groups.ResultsData analysis revealed that our signature could well predict the 1-, 2-, 3-, and 5-year survival rates of hepatocellular carcinoma and to predict susceptible populations with Sorafenib. The risk signature were significantly correlated with immune checkpoint genes, ferroptosis genes, and tertiary lymphoid structure-forming genes, and predicted tumor-infiltrating lymphocyte status. There was a significant difference in IPS scores between the low-risk group and the high-risk group, while the low-risk group had higher scores.ConclusionThe riskScore obtained from an immune-related lncRNA signature could successfully predict the survival time and reflect the efficacy of immune checkpoint inhibitors. More importantly, it is possible to select different treatments for different hepatocellular carcinoma patients that increase the response rate of immune checkpoint inhibitors and will help improve the individualized treatment of hepatocellular carcinoma.

Abstract Straw return plays an important role in the improvement of farmland ecological environments, increasing soil fertility, crop quality, and yield. However, in the early growth of rice (Oryza sativa L.), straw decomposition and rice growth may be inhibited by suboptimal carbon/nitrogen (C/N) ratios. We, therefore, explored methods that could alleviate the inhibition of straw decomposition using different combinations of ammonium bicarbonate and compound fertilizer. No fertilizer (CK) and compound fertilizer (S0) were used as the control. The ratios of added ammonium bicarbonate were 10% (S1), 20% (S2), 30% (S3), and 40% (S4), respectively. Compared with the S0 treatment, the S2 treatment accelerated straw decomposition, promoted the early growth of tillers and roots, and improved the leaf area index, dry matter accumulation, and N use efficiency (apparent N utilization, agronomic N utilization, and partial factor productivity increased by 4.05‒19.48% in two years). Moreover, panicle number, filled‐grain percentage, and 1000‐grain weight were significantly higher in the S2 treatment than other treatments. The grain yield of S2 treatment was significantly higher than that of S0 treatment by 4.06% (2019) and 5.66% (2020). Regression analysis revealed that the optimal ratios of ammonium bicarbonate for increasing straw decomposition and grain yield were relatively close, 16.27% and 14.60%, respectively. These results suggest that compared with conventional fertilization method (S0), the 20% treatment is a more effective fertilization method that prevents inhibition of straw decomposition, promoting rice growth and yield, and improving nitrogen (N) use efficiency.

Objective: To evaluate the effects of dried ginger rhizome (DGR; Zingiber officinalis (WILLD.) ROSC.), prepared as a membrane, in minor recurrent aphthous stomatitis (miRAS) treatment and explore its mechanism of action by detecting changes in levels of epidermal growth factor (EGF) and tumor necrosis factor (TNF)-α in saliva. Methods: Fifty-nine miRAS patients were enrolled in this study. The number of participants in the dried ginger rhizome membrane (DGRM) group was 30, and 29 were in the placebo membrane (PM) group. Sixty sealed envelopes containing either type of membrane were coded randomly. Investigators and participants were blinded to group assignments. A visual analog scale (VAS) was used for pain, follow-up information for healing time, and enzyme-linked immunosorbent assays to measure the concentrations of EGF and TNF-α. Results: In terms of VAS, there was a significant difference between pre- and post-DGRM treatment (P .05). A significant difference was observed in the healing time between the two groups (6.08 (2.712) vs. 8.04 (2.142) days). The mean healing time in the DGRM group was shorter than that in the PM group (P

Abstract Background Nonalcoholic fatty liver disease (NAFLD) represents one of the most common forms of liver disease worldwide, and it is always regarded as a consequence of a sedentary, food-abundant lifestyle, sitting for an extended time, and a low physical activity level, which often coincide with chronic and long-lasting psychological stress. A Chinese medicine Sinisan (SNS) may be a potential formula for treating this kind of disease. Methods In this study, a long-term chronic restraint stress protocol was used to investigate the mechanism underlying stress-induced NALFD. To investigate the effect of SNS treatment on stress-induced NAFLD, we measured the liver and serum values of total cholesterol (TC), triglyceride (TG), liver free fatty acids (FFA), low-density lipoprotein, superoxide dismutase, tumor necrosis factor-α, malondialdehyde, interleukin (IL)-6, and serum values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase. Results are shown as a mean ± standard deviation. Significant differences between the groups were evaluated using the Student t-test. For multiple comparisons, one-way analysis of variance (ANOVA) was used. If the results of ANOVA indicated significant differences, post hoc analysis was performed with the Tukey test or Dunnett test, and p

Background: The objectives of this phase II study were to determine the clinical activity of the MET tyrosine kinase inhibitor capmatinib (INC280) in patients with MET-dysregulated advanced hepatocellular carcinoma (HCC) and to assess the safety, pharmacokinetics, and correlation of biomarkers with the response. Methods: This phase II, open-label, single-arm study evaluated twice daily (BID) oral capmatinib in a dose-determining stage, utilizing a Bayesian Logistic Regression Model (BLRM) subject to Escalation with Overdose Control criteria, safety, pharmacokinetics, and pharmacodynamic information to determine a recommended dose for expansion (RDE) evaluating efficacy in patients with MET-dysregulated HCC. Results: A total of 38 patients received treatment. In the dose-determining stage, patients received capmatinib 300 mg BID capsules ( n = 8), and in the expansion, patients received 600 mg BID capsules ( n = 28) or 400 mg BID tablets ( n = 2) based on the BLRM and other relevant clinical data. No predefined qualifying adverse events (AEs) were observed during the first 28 days of treatment, and the RDE was 600 mg BID capsules (equivalent pharmacokinetics to 400 mg BID tablets). The most common any causality AEs were nausea (42%), vomiting (37%), and diarrhea (34%). In the expansion stage, in a subgroup of 10 patients with MET-high HCC, the overall response rate was 30%, including 1 durable complete response (>600 days) and 2 partial responses [1 durable (>600 days)]. Conclusions: Single agent capmatinib at the RDE is tolerable with a manageable safety profile. Antitumor activity was seen in a subset of patients with MET-dysregulated (MET-high) HCC. Trial registration: ClinicalTrials.gov: NCT01737827. https://clinicaltrials.gov/ct2/show/NCT01737827

As the climate changed in recent years, an increase in summer indoor temperatures in severe cold and cold regions of China has started to affect thermal comfort. However, the local design standard for energy efficiency does not recognize this phenomenon. This paper reports the potential overheating phenomenon in residential buildings and examines the rationale for the current thermal designs adopted in severe cold and cold regions of China. In this study, the two most commonly used building materials, reinforced concrete (RC) and cross laminated timber (CLT), are used separately in the design of an 18-story residential building envelope located in six different cities in the severe cold and cold regions. The energy consumption and indoor operative temperatures during the operation of these buildings are simulated using Integrated Environmental Solutions Virtual Environment (IES VE). The results demonstrate that both the RC and the CLT buildings experience varying degrees of overheating in any climate subregion. The CLT buildings have longer overheating hours compared to the RC buildings, especially in the cold regions. The results also indicate that for apartments on higher stories, the cooling energy consumption and indoor temperature also increase gradually. The research results suggest that the local design standard for energy efficiency needs to be adjusted by adding thermal design methods for summer to reduce the periods of overheating.

The aim of this research is to investigate the energy sustainability of cross-laminated timber (CLT) and straw residential buildings in the Cold and Severe Cold Regions of China. In the study, three building materials, namely reinforced concrete (RC), CLT, and straw bale, are used separately to design the building envelope in reference residential buildings in different climate zones. The energy consumption during the operation phase of these buildings is then simulated using Integrated Environmental Solutions—Virtual Environment software (IES-VE). The results show that both CLT and straw buildings are more efficient than reinforced concrete with a reduction in energy consumption during the operational phase. Overall, the calculated heating energy-saving ratios for CLT buildings in Hailar, Harbin, Urumchi, Lanzhou, and Beijing are 3.04%, 7.39%, 7.43%, 12.69%, and 13.41%, respectively, when compared with RC. The calculated energy-saving ratios for heating in straw buildings in comparison with RC in these cities are 8.04%, 22.09%, 22.17%, 33.02%, and 34.28%, respectively. The results also reveal that a south orientation of the main building facade results in approximately 5% to 7% energy reduction in comparison with east or west orientations, and as the building height increases, energy consumption decreases gradually. Although RC is the most frequently used building material in Cold and Severe Cold regions in China, as bio-based building materials, there is great potential to promote CLT and straw bale construction in view of the energy sustainability features.

Pancreatic ductal adenocarcinoma (PDAC) remains a common and deadly cancer. Despite numerous efforts, no reliable biomarker is available for daily clinical practice. Circular RNAs (circRNAs) are an abundant, stable and conserved class of RNA molecules that exhibit tissue/developmental-stage-specific expression (Salzman et al., 2012; Jeck et al., 2013; Memczak et al., 2013). CircRNAs play a crucial role in disease, especially in cancer, and provide new potential diagnostic and therapeutic targets for disease (Hansen et al., 2013; Qu et al., 2015).This research was designed to explore the expression profile of circRNAs in PDAC to serve as new diagnosis and treatment strategies for PDAC. Microarray and sample annotation data were deposited in Gene Expression Omnibus (GEO) under accession number GSE69362.