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BackgroundPrevention of graft-versus-host disease (GvHD) without malignant relapse is the overall goal of allogeneic haemopoietic cell transplantation (HCT). We aimed to evaluate regimens using either maraviroc, bortezomib, or post-transplantation cyclophosphamide for GvHD prophylaxis compared with controls receiving the combination of tacrolimus and methotrexate using a novel composite primary endpoint to identify the most promising intervention to be further tested in a phase 3 trial.MethodsIn this prospective multicentre phase 2 trial, adult patients aged 18-75 years who received reduced-intensity conditioning HCT were randomly assigned (1:1:1) by random block sizes to tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide (cyclophosphamide 50 mg/kg on days 3 and 4, followed by tacrolimus starting on day 5 and mycophenolate mofetil starting on day 5 at 15 mg/kg three times daily not to exceed 1 g from day 5 to day 35); tacrolimus, methotrexate, and bortezomib (bortezomib 1·3 mg/m2 intravenously on days 1, 4, and 7 after HCT); or tacrolimus, methotrexate, and maraviroc (maraviroc 300 mg orally twice daily from day -3 to day 30 after HCT). Methotrexate was administered as a 15 mg/m2 intravenous bolus on day 1 and 10 mg/m2 intravenous bolus on days 3, 6, and 11 after HCT; tacrolimus was given intravenously at a dose of 0·05 mg/kg twice daily (or oral equivalent) starting on day -3 (except the post-transplantation cyclophosphamide, as indicated), with a target level of 5-15 ng/mL. Tacrolimus was continued at least until day 90 and was tapered off by day 180. Each study group was compared separately to a contemporary non-randomised prospective cohort of patients (control group) who fulfilled the same eligibility criteria as the trial, but who were treated with tacrolimus and methotrexate at centres not participating in the trial. The primary endpoint (GvHD-free, relapse-free survival [GRFS]) was defined as the time from HCT to onset of grade 3-4 acute GvHD, chronic GvHD requiring systemic immunosuppression, disease relapse, or death. The study was analysed by modified intention to treat. The study is closed to accrual and this is the planned analysis. This trial is registered with ClinicalTrials.gov, number NCT02208037.FindingsBetween Nov 17, 2014, and May 18, 2016, 273 patients from 31 US centres were randomly assigned to the three study arms: 89 to tacrolimus, methotrexate, and bortezomib; 92 to tacrolimus, methotrexate, and maraviroc; 92 to tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide; and six were excluded. Between Aug 1, 2014, and Sept 14, 2016, 224 controls received tacrolimus and methotrexate. Controls were generally well matched except for more frequent comorbidities than the intervention groups and a different distribution of types of conditioning regimens used. Compared with controls, the hazard ratio for GRFS was 0·72 (90% CI 0·54-0·94; p=0·044) for tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide, 0·98 (0·76-1·27; p=0·92) for tacrolimus, methotrexate, and bortezomib, and 1·10 (0·86-1·41; p=0·49) for tacrolimus, methotrexate, and maraviroc. 238 patients experienced grade 3 or 4 toxicities: 12 (13%) had grade 3 and 67 (73%) grade 4 events with tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide; ten (11%) had grade 3 and 68 (76%) had grade 4 events with tacrolimus, methotrexate, and bortezomib; and 18 (20%) had grade 3 and 63 (68%) had grade 4 events with tacrolimus, methotrexate, and maraviroc. The most common toxicities were haematological (77 [84%] for tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide; 73 [82%] for tacrolimus, methotrexate, and bortezomib; and 78 [85%] for tacrolimus, methotrexate, and maraviroc) and cardiac (43 [47%], 44 [49%], and 43 [47%], respectively).InterpretationTacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide was the most promising intervention, yielding the best GRFS; this regimen is thus being prospectively compared with tacrolimus and methotrexate in a phase 3 randomised trial.FundingUS National Health, Lung, and Blood Institute; National Cancer Institute; National Institute of Allergy and Infectious Disease; and Millennium Pharmaceuticals.

Abstract Background Chemoattractant is critical to recruitment of osteoclast precursors and stimulates tumor bone metastasis. However, the role of chemoattractant in bone metastasis of colorectal cancer (CRC) is still unclear. Methods Histochemistry analysis and TRAP staining were utilized to detect the bone resorption and activation of osteoclasts (OCs) after administration of CCL7 neutralizing antibody or CCR1 siRNA. qRT-PCR analysis and ELISA assay were performed to detect the mRNA level and protein level of chemoattractant. BrdU assay and Tunel assay were used to detect the proliferation and apoptosis of osteoclast precursors (OCPs). The migration of OCPs was detected by Transwell assay. Western blots assay was performed to examine the protein levels of pathways regulating the expression of CCL7 or CCR1. Results OCPs-derived CCL7 was significantly upregulated in bone marrow after bone metastasis of CRC. Blockage of CCL7 efficiently prevented bone resorption. Administration of CCL7 promoted the migration of OCPs. Lactate promoted the expression of CCL7 through JNK pathway. In addition, CCR1 was the most important receptor of CCL7. Conclusion Our study indicates the essential role of CCL7-CCR1 signaling for recruitment of OCPs in early bone metastasis of CRC. Targeting CCL7 or CCR1 could restore the bone volume, which could be a potential therapeutical target. Video Abstract

Functional porous materials are of increasing importance in energy conversion and catalysis. Improved analysis is needed to guide optimization. Four-dimensional (4D) imaging [chemical mapping in three-dimensional (3D) by spectro-tomography] of an Al2O3 aerogel coated with ZnO by atomic layer deposition was performed using soft X-ray ptychography at the Zn L-edge. A two-dimensional spatial resolution of 14(2) nm was achieved. Visualizations of the 3D chemical structure are provided. The degree of ZnO coverage of the surface of the Al2O3 aerogel framework in two different samples was estimated and found to be both thicker and less homogeneous than expected. Other analyses of the 4D results, including the degree of contact between Al2O3 and ZnO, were extracted from the reconstructed 3D data. This pioneering soft X-ray spectro-ptycho-tomography study will anchor further studies of functional porous materials.

● Crop pests are a major factor restricting agricultural production in China. ● The National Monitoring and Early Warning System (NMEWS) was established > 40 years ago. ● Application of NMEWS has increased national capability to tackle pests. The importance of food security, especially in combating the problem of acute hunger, has been underscored as a key component of sustainable development. Considering the major challenge of rapidly increasing demands for both food security and safety, the management and control of major pests is urged to secure supplies of major agricultural products. However, owing to global climate change, biological invasion (e.g., fall armyworm), decreasing agricultural biodiversity, and other factors, a wide range of crop pest outbreaks are becoming more frequent and serious, making China, one of the world’s largest country in terms of agricultural production, one of the primary victims of crop yield loss and the largest pesticide consumer in the world. Nevertheless, the use of science and technology in monitoring and early warning of major crop pests provides better pest management and acts as a fundamental part of an integrated plant protection strategy to achieve the goal of sustainable development of agriculture. This review summarizes the most fundamental information on pest monitoring and early warning in China by documenting the developmental history of research and application, Chinese laws and regulations related to plant protection, and the National Monitoring and Early Warning System, with the purpose of presenting the Chinese model as an example of how to promote regional management of crop pests, especially of cross border pests such as fall armyworm and locust, by international cooperation across pest-related countries.

Objectives: To develop an instrument to facilitate the risk assessment of falls in older outpatients. Design: A quantitative methodological study using the cross‐sectional data. Methods: This study enrolled 1988 older participants who underwent comprehensive geriatric assessment (CGA) in an outpatient clinic from May 2020 to November 2022. The history of any falls (≥1 falls in a year) and recurrent falls (≥2 falls in a year) were investigated. Potential risk factors of falls were selected by stepwise logistic regression, and a screening tool was constructed based on nomogram. The tool performance was compared with two reference tools (Fried Frailty Phenotype; CGA with 10 items, CGA‐10) by using receiver operating curves, sensitivity (Sen), specificity (Spe), and area under the curve (AUC). Results: Age, unintentional weight loss, depression measured by the Patient Health Questionnaire‐2, muscle strength measured by the five times sit‐to‐stand test, and stand balance measured by semi‐ and full‐tandem standing were the most important risk factors for falls. A fall risk screening tool was constructed with the six measurements (FRST‐6). FRST‐6 showed the best AUC (Sen, Spe) of 0.75 (Sen = 0.72, Spe = 0.69) for recurrent falls and 0.65 (Sen = 0.74, Spe = 0.48) for any falls. FRST‐6 was comparable to CGA‐10 and outperformed FFP in performance. Conclusions: Age, depression, weight loss, gait, and balance were important risk factors of falls. The FRST‐6 tool based on these factors showed acceptable performance in risk stratification. Impact: Performing a multifactorial assessment in primary care clinics is urgent for falls prevention. The FRST‐6 provides a simple and practical way for falls risk screening. With this tool, healthcare professionals can efficiently identify patients at risk of falling and make appropriate recommendations in resource‐limited settings. Patient or Public Contribution: No patient or public contribution was received, due to our study design. [ABSTRACT FROM AUTHOR]

After conventional oil recovery operations, more than half of the crude oil still remains in a form, which is difficult to extract. Therefore, exploring and developing new enhanced oil recovery (EOR) technologies have always been priority research in oilfield development. Microbial enhanced oil recovery (MEOR) is a promising tertiary oil recovery technology that has received widespread attention from the global oil industry in recent years due to its environmental friendliness, simplicity of operation, and cost-effectiveness. This review presents the: principle, characteristics, classification, recent development, and applications of MEOR technology. Based on hundreds of field trials conducted worldwide, the microbial strains, nutrient systems, and actual effects used in these technologies are summarized, with an emphasis on the achievements made in the development and application of MEOR in China in recent years. These technical classifications involve: microbial huff and puff recovery (MHPR), microbial flooding recovery (MFR), microbial selective plugging recovery (MSPR), and microbial wax removal and control (MWRC). Most of them have achieved good results, with a success rate of approximately 80%. These successful cases have accumulated into rich experiential indications for the popularization and application of MEOR technology, but there are still important yet uncertain factors that hinder the industrialization of this technology. Finally, based on the extensive research and development of MEOR by the authors, especially in both laboratory and industrial large scales, the main challenges and future perspectives of the industrial application for MEOR are presented. [ABSTRACT FROM AUTHOR]

The development of the open-pit mining industry has set higher performance standards for mining electric shovels. Addressing issues such as low efficiency, high energy consumption, and high failure rates in working mining electric shovel devices, this paper comprehensively considers bulk mechanics, structural mechanics, and dynamics to conduct a multidisciplinary, collaborative design optimization for electric shovels by introducing the BLISCO method, which is based on an approximated model, into the structural-optimization design process of working electric shovel devices, aiming to enhance the overall performance of electric shovels. Firstly, a dynamic model of an electric shovel is established to analyze the hoist force and crowd force during the excavation process, and an accurate load input for the dynamic analysis is provided through the bulk material mechanics model. Additionally, to ensure that the stiffness of the boom meets the requirements, the maximum stress at the most critical position of the optimized boom is considered. Subsequently, the design variables are screened through experimental design, and an approximate model is established. Focusing on the hoist force, crowd force, maximum stress at the critical position of the boom, and the angle between the dipper arm and the wire rope, a mathematical model is constructed and optimized using a two-level integrated system co-optimization framework based on an approximate model (BLISCO-AM), followed by a simulation. Finally, a test bench for the electric shovel working device is constructed to compare pre- and post-optimization performance. Experimental results show that through the optimized design, the hoist force and crowd force required in a single excavation process are reduced by 6% and 8.48%, respectively, and the maximum angle between the wire rope and the dipper arm is increased by 4%, significantly improving excavation efficiency while ensuring the safety and reliability of the equipment. [ABSTRACT FROM AUTHOR]

Background/Aim: Mandibular condylar fractures in pediatric patients may exhibit distinct epidemiological characteristics attributed to their unique growth and development phase, as well as various anatomical, physiological, biomechanical, and behavioral factors that differentiate them from adults. This study aimed to investigate the demographics, injurious factors, classifications, clinical manifestations, and treatments of pediatric mandibular condylar fractures, as well as the concomitant injuries in maxillofacial and other body parts. Materials and Methods: This retrospective study analyzed the clinical data of 189 pediatric patients with mandibular condylar fractures between 2011 and 2022. Variables investigated included age, gender, timing of onset, causes, classification of condylar fracture, concomitant injuries, clinical manifestations, and treatment modalities. Results: A total of 189 patients, a higher proportion of boys compared to girls was observed, with the highest incidence rate in children aged 1–3 years. They occurred primarily in July, June, and September as well as on Saturdays and Sundays. The most prevalent cause of mandibular condylar fractures was falls from heights in 73 patients (38.62%). Pediatric patients exhibited a higher susceptibility to condylar head fractures. A significant majority (81.48%) of these fractures were accompanied by soft tissue injuries in the maxillofacial region, with the chin being particularly vulnerable to injury. In addition, 61.90% of pediatric patients experienced fractures in other areas of the maxillofacial region, with the mandibular symphysis being the most commonly affected site. Dental trauma predominantly occurred in the anterior region (44.97%). Notably, a substantial proportion (28.04%) of cases also presented with multiple systemic injuries. Conclusions: The characteristics of pediatric mandibular condylar fractures exhibit distinct features in terms of age, gender, timing of onset, etiology, location and type, the presence of concomitant maxillofacial soft/hard tissue injuries and multiple systemic injuries, as well as clinical manifestations and treatment modalities. Therefore, clinicians should pay special attention to the diagnosis and treatment of pediatric condylar fractures. [ABSTRACT FROM AUTHOR]

In order to solve the problem of unstable fluid supply pressure and serious impact caused by the complicated and changeable working condition of a fully mechanized mining face in coal mines and the sluggish response of the fluid supply system to the fluid demand for the hydraulic support, a control method based on online updating generalized regression neural network (GRNN) was proposed. Firstly, the simulated hydraulic support test platform and co-simulation model were built. Secondly, The optimal flow dataset of steady-pressure fluid supply under different working conditions is calculated by simulation. Furthermore, the GRNN prediction model was established by using dataset and online updating learning technology to predict the optimal fluid supply flow according to environmental parameters. Finally, the optimal flow control method of online updating GRNN was established, and numerical research and experimental verification were also carried out in different working conditions. The results indicated that the proposed control method could track the working conditions of the working face in real time and adjusted the fluid supply flow of the emulsion pump station adaptively, which effectively alleviated the pressure fluctuation and pressure shock, and the system pressure was more stable, meeting the demand of steady-pressure fluid supply on the working face. [ABSTRACT FROM AUTHOR]

Objectives: Due to the government's liberalization of epidemic control, the current 2019 novel coronavirus disease (COVID‐19) has started to spread widely within China. This study aimed to use the fetal heart quantification (fetal HQ) technique to assess the cardiac function and morphology of the fetuses of pregnant women diagnosed with COVID‐19 in the early stages of pregnancy. Methods: Exactly 86 pregnant women diagnosed with COVID‐19 infection in early pregnancy (COVID‐19 group) and 90 healthy pregnant women (control group) who underwent fetal echocardiography were prospectively included in this study. The fetal HQ technique was applied to compare the differences in the global sphericity index (GSI), global strain values (GS), fractional area change (FAC), and 24‐segment fractional shortening (FS) of the left and right ventricles, between the COVID‐19 group and the control group. Results: Compared with the control group, the differences in GS and 24‐segment FS of the left ventricle in the COVID‐19 group were not statistically significant. However, the COVID‐19 group showed lower GSI values compared with the control group (1.24 vs 1.28). FAC (48.12%) of the left ventricle and GS (−23.55%), FAC (41.74%) of the right ventricle in the COVID‐19 group were reduced compared with FAC (50.50%) of the left ventricle and GS (−27.63%), FAC (46.01%) of the right ventricle in the control group. Segmental analysis revealed reduced FS in segments 20–24 in the COVID‐19 group compared with the control group. Right ventricular GS was an independent predictor of adverse pregnancy outcome with an optimal cutoff value of −18.66%. Conclusions: The results suggest that COVID‐19 infection in early pregnancy may have a negative impact on fetal cardiac morphology and function. Fetal HQ may offer a new assessment method for the early identification of fetal cardiac alterations in pregnant women infected with COVID‐19. [ABSTRACT FROM AUTHOR]

Abstract Background Bone metastasis of colorectal cancer (CRC) often indicates a poor prognosis. Osteolysis can be observed in metastatic sites, implying an aberrant activation of osteoclasts. However, how osteoclastogenesis is regulated in metastatic microenvironment caused by colorectal cancer is still unclear. Methods In this study, mice bone metastatic model of CRC was established through injection of MC-38 or CT-26 cells. BrdU assays showed primary CD115 ( +) osteoclast precursors (OCPs) proliferated at the first 2 weeks. Transcriptomic profiling was performed to identify differentially expressing genes and pathways in OCPs indirectly co-cultured with CRC cells Results The expression of IL4Rα was found to be significantly upregulated in OCPs stimulated by tumor conditioned medium (CM). Further investigation indicated that IL-4 signaling regulated proliferation of OPCs through interacting with type I IL4 receptor, and neutrophils were the main source of IL-4 in bone marrow. The proliferation of OCPs can be inhibited in IL4 deficiency mice. In addition, ERK pathway was activated by IL4/IL4R signaling. Ravoxertinib, an ERK antagonists, could significantly prevent bone destruction through inhibiting the proliferation of OCPs. Conclusion Our study indicates the essential role of IL4/IL4R signaling for the proliferation of OCPs in early metastasis of CRC predominantly through activating ERK pathway, which remarkedly impacts the number of osteoclasts in later stage and leads to osteolytic lesions. Moreover, Ravoxertinib could be a new therapeutical target for bone metastasis of CRC.

Additional guide vane (GV) to the Savonius rotor is used to overcome the low rotor efficiency. This study is experimentally carried out to know the influence of guide vane in improving two blades Savonius rotor performance. There were four designs of guide vane which are 4, 5, 6 blades and installed at different tilt angles, which were 0°, 20°, 40°, and 60°. The experiment was done under wind speed of 5.9 m/s, 7.0 m/s, 8.1 m/s, 9.3 m/s and 10.4 m/s. The results show that the 6 blades of GV at a 60° tilt angle attained the best Cp, which was 0.0279 at the tip speed ratio of 0.53. The Cp increased up to 40% with six blades of GV. Wind direction identified significantly affected the rotor performance. The rotor performed best on the wind direction of 0° attained Cp of 0.079, but when the wind direction was modified on 30°, the rotor with 6 GV attained Cp of 0.0153 did not perform better than without GV that produced Cp of 0.0166. The guide vanes improve the Savonius rotor performance compared to the rotor without a guide vane. However, the wind direction also needs to be considered no less important factor affecting the Savonius rotor performance.