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Abstract Solution coating of organic semiconductors offers great potential for achieving low‐cost and high‐throughput manufacturing of large‐area and flexible electronics. However, the solution processability of semiconducting small molecules for fabricating uniform and reliable thin‐film devices poses challenges due to the low viscosities of small‐molecule solutions. Here, we report a universal approach employing a primer template (PT) to enhance the spreadability of small‐molecule solutions on silicon wafers, enabling the spin‐coating fabrication of uniform thin films composed of millimeter‐scale grains with complete large‐area coverage and well‐ordered molecular packing. Using PT, we fabricated organic thin‐film transistors (OTFTs) using solutions containing various small molecules such as rubrene and 2‐decyl‐7‐phenyl‐[1]benzothieno[3,2‐b][1]benzothiophene. The device yield of all fabricated OTFTs is consistently 100% while achieving a high average mobility of 1.62 cm2 V−1 s−1 with a device‐to‐device variation of 7.7% measured in ambient air condition. In addition, the utilization of PT resulted in a batch‐to‐batch variation of 12.5% in device performance over dozens of OTFT devices. The key industrial manufacturing metrics, such as device yield, reproducibility, and performance uniformity of the PT OTFTs, are among the best for devices fabricated using solution spin‐coating techniques.

Abstract Background Peritoneal dialysis (PD) and conventional in‐center hemodialysis (HD) are treatment options for patients with end‐stage kidney disease (ESKD). However, their impact on all‐cause mortality is unclear. Methods We conducted a multicenter, open‐label, randomized, non‐inferiority trial to determine the effect of dialysis modality on mortality in patients with ESKD. Eligible patients were recruited from 30 sites across China and assigned to receive either PD or HD in a ratio of 1:1. The primary outcome was all‐cause mortality. Non‐inferiority was defined as the upper bound of the one‐sided 95% confidence interval (CI) for the hazard ratio (HR) being ≤1.25. Results A total of 414 patients with incident ESKD were randomly assigned to PD (n = 213) or HD (n = 201). During a median follow‐up of 1.7 years, 37 patients in the PD group and 31 in the HD group died, giving respective event rates per patient‐year of 0.061 and 0.071. The HR for mortality on PD in comparison with HD was 0.76 (95% CI 0.47–1.24) after adjustment for age, sex, and diabetes status, achieving the limit for non‐inferiority. There were more adverse events (p = 0.003), serious adverse events (p = 0.009), and adverse events leading to hospitalization (p = 0.003) in the PD group than in the HD group; however, there was no significant between‐group difference in adverse events leading to death or discontinuation of treatment. Conclusions PD was non‐inferior to conventional in‐center HD in terms of survival in patients with ESKD. Our findings underscore the need for shared decision‐making between physicians and patients regarding the selection of dialysis modality. Trial registration Registered at ClinicalTrials.gov (NCT01413074).

Abstract Hyperuricemia (HUA) is a common metabolic disease and kidney injury is one of its main complications. As a typical natural flavonoid, puerarin (PEA) has a range of pharmacological activity but the antihyperuricemic mechanism of PEA has not been reported. Herein, the inhibitory activity of PEA against xanthine oxidase (XOD) was evaluated by in vitro enzymatic reaction, and kinetic analysis, the antihyperuricemic activity, and nephroprotective effect of PEA were studied in HUA mice. The enzymatic reaction showed that the inhibitory effect of PEA (half maximal inhibitory concentration [IC50] = 4.39 µmol/L) on XOD was at the same level as allopurinol (IC50 = 4.05 µmol/L), and kinetic analysis indicated that PEA was a mixed competitive inhibitor. In vivo studies demonstrated that PEA exhibited excellent antihyperuricemic activity by inhibiting XOD and urate transporter 1 (URAT1), to reduce uric acid level. At the same time, PEA reduced the level of inflammatory cytokines and exerted significant nephroprotective effect through anti‐inflammatory activity. Molecular docking indicated that PEA closely bind to both XOD and URAT1, which had the potential to become an inhibitor of XOD and URAT1. In summary, PEA has important application value in developing novel functional food and medicine for the treatment of HUA and its complications.

Abstract Background Gastric cancer patients with peritoneal metastasis (GCPM) experience a rapidly deteriorating clinical trajectory characterized by therapeutic resistance and dismal survival, particularly following the development of malignant ascites. However, the intricate dynamics within the peritoneal microenvironment (PME) during the treatment process remain largely unknown. Methods Matched samples from primary tumours (PT), peritoneal metastases (PM), and paired pre‐treatment and post‐chemo/immunotherapy (anti‐PD‐1/PD‐L1) progression malignant ascites samples, were collected from 48 patients. These samples were subjected to single‐cell RNA sequencing (n = 30), multiplex immunofluorescence (n = 30), and spatial transcriptomics (n = 3). Furthermore, post hoc analyses of a phase 1 clinical trial (n = 20, NCT03710265) and an in‐house immunotherapy cohort (n = 499) were conducted to validate the findings. Results Tracing the evolutionary trajectory of epithelial cells unveiled the terminally differentially MUC1+ cancer cells with a high epithelial‐to‐mesenchymal transition potential, and they demonstrated spatial proximity with fibroblasts and endothelial cells, correlating with poor prognosis. A significant expansion of macrophage infiltrates, which exhibited the highest proangiogenic activity, was observed in the ascites compared with PT and PM. Besides, higher C1Q+ macrophage infiltrates correlated with significantly lower GZMA+ T‐lymphocyte infiltrates in therapeutic failure cases, potentially mediated by the LGALS9‐CD45 and SPP1‐CD44 ligand–receptor interactions. In the chemoresistant group, intimate interactions between C1Q+ macrophages and fibroblasts through the complement activation pathway were found. In the group demonstrating immunoresistance, heightened TGF‐β production activity was detected in MUC1+ cancer cells, and they were skewed to interplay with C1Q+ macrophages through the GDF15‐TGF‐βR2 axis. Ultimately, post hoc analyses indicated that co‐targeting TGF‐β and PDL1 pathways may confer superior clinical benefits than sole anti‐PD‐1/PD‐L1 therapy for patients presenting with GCPM at the time of diagnosis. Conclusions Our findings elucidated the cellular differentiation trajectories and crucial drug resistance features within PME, facilitating the exploration of effective targets for GCPM treatment. Highlights MUC1+ cancer cells with a high epithelial‐to‐mesenchymal transition potential and exhibiting spatial proximity to fibroblasts and endothelial cells constitute the driving force of gastric cancer peritoneal metastasis (GCPM). Higher C1Q+ macrophage infiltrates correlated with significantly lower GZMA+ T‐lymphocyte infiltrates within the peritoneal microenvironment in therapeutic failure cases. Co‐targeting TGF‐β and PDL1 pathways may confer superior clinical benefits than sole anti‐PD‐1/PD‐L1 therapy for patients presenting with GCPM at diagnosis.

Abstract Previous studies have shown a bidirectional communication between human gut microbiota and the brain, known as the microbiota–gut–brain axis (MGBA). The MGBA influences the host's nervous system development, emotional regulation, and cognitive function through neurotransmitters, immune modulation, and metabolic pathways. Factors like diet, lifestyle, genetics, and environment shape the gut microbiota composition together. Most research have explored how gut microbiota regulates host physiology and its potential in preventing and treating neurological disorders. However, the individual heterogeneity of gut microbiota, strains playing a dominant role in neurological diseases, and the interactions of these microbial metabolites with the central/peripheral nervous systems still need exploration. This review summarizes the potential role of gut microbiota in driving neurodevelopmental disorders (autism spectrum disorder and attention deficit/hyperactivity disorder), neurodegenerative diseases (Alzheimer's and Parkinson's disease), and mood disorders (anxiety and depression) in recent years and discusses the current clinical and preclinical gut microbe‐based interventions, including dietary intervention, probiotics, prebiotics, and fecal microbiota transplantation. It also puts forward the current insufficient research on gut microbiota in neurological disorders and provides a framework for further research on neurological disorders.

Abstract Background The vast majority of patients with ROS1 positive non‐small cell lung cancer (NSCLC) derive clinical benefit from currently approved ROS1 therapies, including crizotinib and entrectinib. However, a small proportion of patients treated with ROS1 inhibitors fail to derive any clinical benefit and demonstrate rapid disease progression. The biological mechanisms underpinning intrinsic resistance remain poorly understood for oncogene‐driven cancers. Methods We generated a patient‐derived cell line, CUTO33, from a ROS1 therapy naive patient with CD74‐ROS1+ NSCLC, who ultimately did not respond to a ROS1 inhibitor. We evaluated a panel of ROS1+ patient‐derived NSCLC cell lines and used cell‐based assays to determine the mechanism of intrinsic resistance to ROS1 therapy. Results The CUTO33 cell line expressed the CD74‐ROS1 gene fusion at the RNA and protein level. The ROS1 fusion protein was phosphorylated at baseline consistent with the known intrinsic activity of this oncogene. ROS1 phosphorylation could be inhibited using a wide array of ROS1 inhibitors, however these inhibitors did not block cell proliferation, confirming intrinsic resistance in this model and consistent with the patient's lack of response to a ROS1 inhibitor. CUTO33 expressed high levels of AXL, which has been associated with drug resistance. Combination of an AXL inhibitor or AXL knockdown with a ROS1 inhibitor partially reversed resistance. Conclusions In summary, we demonstrate that AXL overexpression is a mechanism of intrinsic resistance to ROS1 inhibitors.

Abstract Background Limited data have been used to evaluate the efficacy of immunotherapy in metastatic colorectal cancer (mCRC). Furthermore, potential markers that can be used to identify responding patients and to further improve efficacy have not been fully explored. Methods and Results In our study, we included a total of 97 patients with mCRC, who each received programmed death‐1 (PD‐1) inhibitor‐based combination therapy at our center. All 12 hypermutated patients benefited from immunotherapy, with median progression‐free survival (mPFS) reaching 28.3 months, regardless of liver metastasis. The objective response rate (ORR) of non‐hypermutated patients was 16.5% (14/85), with an mPFS of 4.0 months. For non‐hypermutated patients, multivariate analysis revealed that the combination of liver metastasis and baseline lesion number significantly stratified response and survival. The lesion‐based analysis indicated that the lymph node was the most responsive, followed by the peritoneum and lung, with liver metastasis being the least responsive. None of the patients (0/7) with negative programmed ligand‐1 (PD‐L1) expression responded, and positive PD‐L1 expression may serve as a biomarker (mPFS 5.7 vs. 2.2 months, p = 0.002) that can be used to further guide treatment in non‐hypermutated mCRC with liver metastasis (CRLMs). Conclusion Patients with hypermutated mCRC benefited significantly from immunotherapy, whereas the non‐hypermutated cohort with liver metastasis and numerous lesions showed less benefit. The lesion sites reflected varying levels of efficacy, among which PD‐L1 potentially cooperated to guide the immunotherapy of CRLMs.

Abstract Background Pediatric interventional oncology (PIO) is a growing field intended to provide additional or alternative treatment options for pediatric patients with benign or malignant tumors. Large series of patients treated uniformly and subjected to rigorous endpoints for efficacy are not available. Methods We designed a collaborative initiative to capture data from pediatric patients with benign and malignant tumors who underwent a therapeutic interventional radiology procedure. Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was utilized as a measure of radiologic response and data were collected regarding improvement in pain and functional endpoints. Cumulative incidence of progressive disease was calculated using both the treated site and the patient as the analytic unit. Findings Forty patients, 16 with malignant tumors and 24 with benign tumors, underwent a total of 88 procedures. Cryo‐ and radiofrequency ablation were the most frequently utilized techniques for both cohorts of patients. A complete or partial response, or prolonged disease stability, were achieved in approximately 40% of patients with malignant tumors and 60% of patients with benign tumors. No patients had progressive disease as their best response. Resolution of pain and improved mobility with return‐to‐baseline activity were demonstrated across patients from both cohorts. Only minor complications were experienced. Interpretation Interventional radiology‐guided interventions can serve as an alternative or complementary approach to the treatment of benign and malignant tumors in pediatric patients. Prospective, multi‐institutional trials are required to adequately study utility, treatment endpoints, and durability of response.

Due to the particularity of the construction technology of the CRTS I slab track bagging method, there is a certain roughness between the track slab and the mortar layer in the actual project. In this work, the W–M fractal function was used to simulate the cement asphalt mortar layer in unit slab track with roughness rough surface morphology. To investigate the effects of interlayer rough contact surfaces, an interactive modeling approach using Python–Abaqus was developed, namely, the track structure performance, interlayer contact behavior, and vertical dynamic responses. The fastener pivot point reaction of the vehicle–track coupled model interacts with the track structure to examine the impact of different fractal dimensions and scale coefficients under the dynamic train load. The numerical results demonstrate that as the fractal dimension D and characteristic scale factor G increase, the dynamic response of the track slab gradually increases, and the contact area between layers decreases. The stress of rough contact surface is pointing distribution. Among the components of the track structure, the displacement of the track slab is most affected by the roughness. The rough surface affects the fatigue life of the mortar and consequently affects the service performance of the track structure. This study explores the effect of rough surfaces on the performance of CRTS I slab track structures under dynamic train load and provides a reference for improving the design of track structures and enhancing its life.

Abstract Mononuclear phagocytes (MPs) are vital components of host immune defenses against cancer. However, tumor‐infiltrating MPs often present tolerogenic and pro‐tumorigenic phenotypes via metabolic switching triggered by excessive lipid accumulation in solid tumors. Inspired by viral infection‐mediated MP modulation, here enveloped immunometabolic nanoparticles (immeNPs) are designed to co‐deliver a viral RNA analog and a fatty acid oxidation regulator for synergistic reshaping of intratumoral MPs. These immeNPs are camouflaged with cancer cell membranes for tumor homing and opsonized with anti‐CD163 antibodies for specific MP recognition and uptake. It is found that internalized immeNPs coordinate lipid metabolic reprogramming with innate immune stimulation, inducing M2‐to‐M1 macrophage repolarization and tolerogenic‐to‐immunogenic dendritic cell differentiation for cytotoxic T cell infiltration. The authors further demonstrate that the use of immeNPs confers susceptibility to anti‐PD‐1 therapy in immune checkpoint blockade‐resistant breast and ovarian tumors, and thereby provide a promising strategy to expand the potential of conventional immunotherapy.

Abstract In this paper, a vehicle‐to‐vehicle (V2V) trajectory planning algorithm for two vehicles driving in an arc‐shaped road is represented, in which the characteristics of human drivers are taken into consideration. Safety constraints including vehicle stability, road boundaries, and vehicles collision avoidance are considered. The boundary constraint of the arc‐shaped road is realized with a potential field method. The potential field method is also employed to realize the vehicles collision avoidance constraint and vehicle distance margin. The concept of partial cooperative control is presented, which can depict the collaboration of the vehicles more accurately. The algorithm is designed with a partial cooperative control pattern, employing model predictive control (MPC). The effectiveness of the algorithm is verified by software simulation in a scenario of overtaking in arc‐shaped roads. The algorithm can accomplish the V2V collaboration trajectory planning task successfully. The performance of the algorithm representing different collaboration degrees and phases grouping in complex scenarios is also studied.

Abstract Background ROS1 tyrosine kinase inhibitors (TKIs) have demonstrated significant clinical benefit for ROS1+ NSCLC patients. However, TKI resistance inevitably develops through ROS1 kinase domain (KD) modification or another kinase driving bypass signaling. While multiple TKIs have been designed to target ROS1 KD mutations, less is known about bypass signaling in TKI‐resistant ROS1+ lung cancers. Methods Utilizing a primary, patient‐derived TPM3‐ROS1 cell line (CUTO28), we derived an entrectinib‐resistant line (CUTO28‐ER). We evaluated proliferation and signaling responses to TKIs, and utilized RNA sequencing, whole exome sequencing, and fluorescence in situ hybridization to detect transcriptional, mutational, and copy number alterations, respectively. We substantiated in vitro findings using a CD74‐ROS1 NSCLC patient's tumor samples. Last, we analyzed circulating tumor DNA (ctDNA) from ROS1+ NSCLC patients in the STARTRK‐2 entrectinib trial to determine the prevalence of MET amplification. Results CUTO28‐ER cells did not exhibit ROS1 KD mutations. MET TKIs inhibited proliferation and downstream signaling and MET transcription was elevated in CUTO28‐ER cells. CUTO28‐ER cells displayed extrachromosomal (ecDNA) MET amplification without MET activating mutations, exon 14 skipping, or fusions. The CD74‐ROS1 patient samples illustrated MET amplification while receiving ROS1 TKI. Finally, two of 105 (1.9%) entrectinib‐resistant ROS1+ NSCLC STARTRK‐2 patients with ctDNA analysis at enrollment and disease progression displayed MET amplification. Conclusions Treatment with ROS1‐selective inhibitors may lead to MET‐mediated resistance. The discovery of ecDNA MET amplification is noteworthy, as ecDNA is associated with more aggressive cancers. Following progression on ROS1‐selective inhibitors, MET gene testing and treatments targeting MET should be explored to overcome MET‐driven resistance.

Abstract Objectives Executive function in people with depression is linked to the integrity of white matter fibers in the brain. We hypothesized that the maze tests in neuropsychological tests assessed reasoning and problem‐solving abilities dependent on the integrity of brain white matter fibers, and assessed this relationship using diffusion tensor imaging (DTI) in depressed patients and healthy controls. Methods Participants aged from 18 to 50 years were recruited from Zhumadian Second People's Hospital from July 2018 to August 2019. The sample included 33 clinically diagnosed individuals with major depressive disorder (MDD) and 24 healthy volunteers (HVs). All subjects underwent Neuropsychological assessment battery (NAB) maze tests and DTI. Tract‐based spatial statistics technology in FSL software was used to process DTI data, and threshold‐free cluster enhancement (TFCE) was used to perform multiple comparison corrections. The fractional anisotropy (FA) of white matter fibers in the MDD group and HVs group were compared and extracted. Pearson correlation was used to analyze the relationship between FA and NAB scores and HAMD scores. Results The mean NAB maze test score for the MDD group was lower than the HVs group, and the difference was statistically significant (F = 11.265, p = .037). The FA value of the body of corpus callosum and cerebral peduncle right in the depression group was lower than that in the healthy control group, and the difference was statistically significant (p

Herein, point light detection and ranging inertial odometry (LIO) is presented: a robust and high‐bandwidth light detection and ranging (LiDAR) inertial odometry with the capability to estimate extremely aggressive robotic motions. Point‐LIO has two key novelties. The first one is a point‐by‐point LIO framework that updates the state at each LiDAR point measurement. This framework allows an extremely high‐frequency odometry output, significantly increases the odometry bandwidth, and fundamentally removes the artificial in‐frame motion distortion. The second one is a stochastic process‐augmented kinematic model which models the IMU measurement as an output. This new modeling method enables accurate localization and reliable mapping for aggressive motions even with inertial measurement unit (IMU) measurements saturated in the middle of the motion. Various real‐world experiments are conducted for performance evaluation. Overall, Point‐LIO is capable to provide accurate, high‐frequency odometry (4–8 kHz) and reliable mapping under severe vibrations and aggressive motions with high angular velocity (75 rad s−1) beyond the IMU measuring ranges. Furthermore, an exhaustive benchmark comparison is conducted. Point‐LIO achieves consistently comparable accuracy and time consumption. Finally, two example applications of Point‐LIO are demonstrated, one is a racing drone and the other is a self‐rotating unmanned aerial vehicle, both have aggressive motions.

Abstract Background This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis. Method This study was a multicenter, randomized, open‐label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8‐week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: −1.0 g/dl) was tested between the two treatments. The time‐dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron‐binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results Four hundred and sixty‐six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per‐protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were −0.07 and −0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: −0.22 to 0.39), and the lower limit of the 95% CI was −0.22 > −1.0 g/dl. The average Hb concentrations of the two groups were 10.88–11.43 g/dl (darbepoetin alfa) and 10.91–11.38 g/dl (epoetin alfa) during the study period of Weeks 0–28, with the maintenance rates of the target Hb concentration ranging within 71%–87% and 78%–95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis. Conclusion The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

Abstract Background Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0–12.0 g/dL) for the treatment of renal anemia. Methods Ninety‐five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients (n = 95) aged 18–70 years were randomized into a once per week intravenous darbepoetin alfa group (n = 56) and a twice or three times per week intravenous epoetin alfa group (n = 39) for 28 weeks, who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease (CKD) and were undergoing hemodialysis or hemofiltration with ESA‐naive (erythropoiesis stimulating agent‐naive). The primary efficacy profile was the mean Hb level (the non‐inferiority margin was −1.0 g/dL, week 21–28); the secondary efficacy profiles were the Hb increase rate (week 0–4), the target Hb achievement cumulative rate and time, the change trends of the Hb levels, and the target Hb maintenance ratio. Adverse events (AEs) were observed and compared, and the efficacy and safety were analyzed between the two treatment groups. Additionally, the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (>−1.0 g/dL), and non‐inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis. Conclusion Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.

Abstract Layered vanadium‐based oxides are the promising cathode materials for aqueous zinc‐ion batteries (AZIBs). Herein, an in situ electrochemical strategy that can effectively regulate the interlayer distance of layered NH4V4O10 quantitatively is proposed and a close relationship between the optimal performances with interlayer space is revealed. Specifically, via increasing the cutoff voltage from 1.4, 1.6 to 1.8 V, the interlayer space of NH4V4O10 can be well‐controlled and enlarged to 10.21, 11.86, and 12.08 Å, respectively, much larger than the pristine one (9.5 Å). Among them, the cathode being charging to 1.6 V (NH4V4O10‐C1.6), demonstrates the best Zn2+ storage performances including high capacity of 223 mA h g−1 at 10 A g−1 and long‐term stability with capacity retention of 97.5% over 1000 cycles. Such superior performances can be attributed to a good balance among active redox sites, charge transfer kinetics, and crystal structure stability, enabled by careful control of the interlayer space. Moreover, NH4V4O10‐C1.6 delivers NH4+ storage performances whose capacity reaches 296 mA h g−1 at 0.1 A g−1 and lifespan lasts over 3000 cycles at 5 A g−1. This study provides new insights into understand the limitation of interlayer space for ion storage in aqueous media and guides exploration of high‐performance cathode materials.

Abstract Objective Assessment of the hypothesized correlation between the Chinese Velopharyngeal Insufficiency (VPI) Effects on Life Outcomes (VELO) instrument and measured speech parameters. Methods A cross‐sectional study was conducted in the Oral Clefts Center of West China Hospital of Stomatology between January 2019 and December 2019. Speech parameters including speech intelligibility deficit, VPI severity, VP gap, and need for speech therapy were evaluated by speech‐language pathologists. All patients and their parents completed the VELO instrument. The correlation between aforementioned speech parameters and VELO scores was examined utilizing Spearman correlation coefficients. The reliability of VELO test–retest and parent proxy assessment was estimated utilizing intraclass correlation coefficients (ICC). A receiver operating characteristic curve was used to calculate the cutoff VELO score. Results One hundred and forty patients with their parents were enrolled. The mean age was 12.58 ± 3.72 years. Both parent and youth VELO total and domain scores recorded moderate to strong correlations with all speech parameters (r > −.40, P ˂ .001) except the swallowing domain. Most VELO domain items have shown significant correlations with at least one speech parameter. Moreover, the scales of all speech parameters showed different VELO scores (P ˂ .001). The ICC reported test–retest correlation >.73 in all domains, and parent proxy correlation >.63 in most domains except the emotional and perception domains. The cutoff VELO score was 79.04 in parent version and 85.77 in youth version. Conclusions The correlations between VELO scores and measured speech parameters have provided evidence for test–retest and parent proxy reliability and criterion and construct validity of the Chinese version of the VELO instrument. A VELO score ≥79.04 (in parent version) or ≥85.77 (in youth version) mostly reflects proper speech‐related quality of life. Hence, this instrument could serve as a simple tool to help clinicians understand the social, emotional, and physical influences of VPI.

Abstract The abstract section should read: This is the protocol for a Campbell systematic review. The objectives are as follows: (1) Which formal HBC services for people with dementia have been tested in an RCT? (2) How effective are the different formal HBC services in improving the physical and mental health outcomes of people with dementia? (3) What is the cost and patient's health service usage of different formal HBC services?

Abstract Background Absolute monocyte count (AMC) is often used to be assessed in cancer follow‐up, which has regained interest as a potential prognostic indicator in many solid tumors, though not consistently or comprehensively. In the present study, we set out to perform a comprehensive meta‐analysis of all available data regarding the prognostic significance of AMC in solid tumors. We also evaluated the association between AMC and clinical features in solid tumors. Methods A hazard ratio (HR) and corresponding 95% confidence interval (CI) or a p value (p) from eligible studies were extracted and subsequently pooled analyzed. Subgroup analyses and meta‐regression analyses were conducted according to the confounders of included studies. In addition, the relationships between AMC and clinical characteristics were also explored in the meta‐analysis. Results Overall, ninety‐three articles comprising 104 studies with 32229 patients were finally included. The results showed that elevated AMC was associated with worse overall survival (OS) (HR = 1.615; 95% CI: 1.475‐1.768; p

Osteoporosis and osteoarthritis are orthopedic disorders that affect millions of elderly people worldwide; stimulation of bone formation is a potential therapeutic strategy for the treatment of these conditions. As the only bone‐forming cells, osteoblasts play a key role in bone reconstruction. The microRNA miR‐17‐3p is downregulated during osteogenic differentiation of human bone marrow mesenchymal stem cells, but its precise role in this process is unknown. Here, we investigated the role of miR‐17‐3p in osteoblast differentiation. An in vitro model of osteogenesis was established by treating MC3T3‐E1 murine preosteoblast cells with bone morphogenetic protein 2 (BMP2). The expression of miR‐17‐3p in BMP2‐induced MC3T3‐E1 cells was detected by reverse transcription‐quantitative PCR, and its effects on cells transfected with miR‐17‐3p mimic or inhibitor were evaluated by Alizarin Red staining, alkaline phosphatase (ALP) activity assay, and by detection of osteoblast markers including the ALP, collagen type I α1 chain, and osteopontin genes. Bioinformatics analysis was carried out to identify putative target genes of miR‐17‐3p, and the luciferase reporter assay was used for functional validation. Rescue experiments were performed to determine whether SRY‐box transcription factor 6 (Sox6) plays a role in the regulation of osteoblast differentiation by miR‐17‐3p. We report that miR‐17‐3p was downregulated upon BMP2‐induced osteoblast differentiation in MC3T3‐E1 cells, and this was accompanied by decreased differentiation and mineralization, ALP activity, and expression of osteogenesis‐related genes. Sox6 was confirmed to be a target gene of miR‐17‐3p in osteoblasts, and the inhibitory effect of miR‐17‐3p on osteoblast differentiation was observed to occur via Sox6. These results suggest the existence of a novel mechanism underlying miRNA‐mediated regulation of osteogenesis, which has potential implications for the treatment of orthopedic disorders.

Abstract Graphene, an emerging fabric of carbon atoms, has manifested its versatility in all kinds of fields encompassing electronics, optoelectronics, thermoelectrics, taking advantage of its excellent mechanical strength, exceptional electronic and thermal conductivities, high surface specific area, and so forth. The prosperity of graphene never seen before has led the attention to silicene, siloxene, germanene, stanene, and plumbene due to their promising applications in the quantum spin Hall effect, topological insulator, batteries, capacitors, catalysis, and topological superconductivity. Herein, we review the existing production methods, numerous applications of two‐dimensional group‐IVA materials, and critically discuss the challenges of these materials, providing potential implications to the exploration of uncharted material systems.

Diabetic nephropathy (DN) has become the most common secondary kidney disease causing end-stage renal disease (ESRD). Nevertheless, the underlying mechanisms responsible for DN remain largely unknown. Regulated in development and DNA damage response 1 (REDD1) is a prooxidative molecule known to contribute to diabetes mellitus and its complications. However, it has not been previously examined whether and how REDD1 can further drive renal tubular epithelial cell (RTEC) apoptosis and epithelial-to-mesenchymal transition in DN. The expression of REDD1 was elevated in the kidneys of DN patients and diabetic mice in this study. By generating the DN model in REDD1 knockout mice, we demonstrated that REDD1 deficiency significantly improved apoptosis and EMT in diabetic mice. In vitro experiments showed that REDD1 generation was induced by high glucose (HG) in HK-2 cells. Similarly, the transfection of REDD1 siRNA plasmid also suppressed HG-induced apoptosis and EMT. Furthermore, we discovered that the inhibition of REDD1 suppressed the expression of Nox4-induced HG and reactive oxygen species (ROS) synthesis in HK-2 cells. In addition, HG could induce endogenous REDD1 and TXNIP to form a powerful complex. In summary, our findings demonstrate that blocking the REDD1/TXNIP complex can prevent HG-induced apoptosis and EMT by inhibiting ROS production, highlighting REDD1 as a valuable therapeutic priority site for DN.

Abstract Mechanistic understanding of how living systems sense, transduce, and respond to mechanical cues has important implications in development, physiology, and therapy. Here, the authors use an integrated atomic force microscope (AFM) and brightfield/epifluorescent microscope platform to precisely simulate living single cells or groups of cells under physiological conditions, in real time, concomitantly measuring the single‐cell autophagic response and its transmission to neighboring cells. Dual‐color fluorescence monitoring of the cellular autophagic response reveals the dynamics of autophagosome formation, degradation, and induction in neighboring contacting and noncontacting cells. Autophagosome formation is dependent on both the applied force and contact area of the AFM tip. More importantly, the enhancement of the autophagic responses in neighboring cells via a gap junction‐dependent mechanism is observed. This AFM‐based nanoacupuncture platform can serve as a tool for elucidating the primary mechanism underlying mechanical stimulation of living systems and other biomechanical therapeutics.

Abstract Background Family genetic testing of patients newly diagnosed with a rare genetic disease can improve early diagnosis of family members, allowing patients to receive disease‐specific therapies when available. Fabry disease, an X‐linked lysosomal storage disorder caused by pathogenic variants in GLA, can lead to end‐stage renal disease, cardiac arrhythmias, and stroke. Diagnostic delays are common due to the rarity of the disease and non‐specificity of early symptoms. Newborn screening and screening of at‐risk populations, (e.g., patients with hypertrophic cardiomyopathy or undiagnosed nephropathies) can identify individuals with Fabry disease. Subsequent cascade genotyping of family members may disclose a greater number of affected individuals, often at younger age than they would have been diagnosed otherwise. Methods We conducted a literature search to identify all published data on family genetic testing for Fabry disease, and discussed these data, experts’ own experiences with family genetic testing, and the barriers to this type of screening that are present in their respective countries. Results There are potential barriers that make implementation of family genetic testing challenging in some countries. These include associated costs and low awareness of its importance, and cultural and societal issues. Regionally, there are barriers associated with population educational levels, national geography and infrastructures, and a lack of medical geneticists. Conclusion In this review, the worldwide experience of an international group of experts of Fabry disease highlights the issues faced in the family genetic testing of patients affected with rare genetic diseases.

Abstract Background Lipoprotein glomerulopathy (LPG) is a rare kidney disease caused by APOE mutations. The aim of this study was to correlate the genetic and clinical features of LPG. Methods Totally eight LPG patients were recruited in this study and Sanger sequencing of APOE was performed for all available family members. Clinical and histological features were analyzed. A literature review of LPG was also conducted. Results Genetic analysis revealed five patients with APOE‐Kyoto, two with APOE‐Osaka/Kurashiki, and one with APOE‐Chicago mutations. LPG patients with urine protein reduced more than 50% had a slower decrease in renal function than those with less urine protein reduction (estimated glomerular filtration rate reduction rate −5.0 ± 0.8 vs. 1.5 ± 0.7 ml/min per 1.73 m2⋅month−1, p = .03). We then enrolled 95 LPG patients from previous studies and this study. LPG patients had higher blood pressure (mean arterial pressure: 109.4 ± 19.4 vs. 94.4 ± 11.1 mmHg, p

The ranking of influential nodes in networks is of great significance. Influential nodes play an enormous role during the evolution process of information dissemination, viral marketing, and public opinion control. The sorting method of multiple attributes is an effective way to identify the influential nodes. However, these methods offer a limited improvement in algorithm performance because diversity between different attributes is not properly considered. On the basis of the k-shell method, we propose an improved multiattribute k-shell method by using the iterative information in the decomposition process. Our work combines sigmod function and iteration information to obtain the position index. The position attribute is obtained by combining the shell value and the location index. The local information of the node is adopted to obtain the neighbor property. Finally, the position attribute and neighbor attribute are weighted by the method of information entropy weighting. The experimental simulations in six real networks combined with the SIR model and other evaluation measure fully verify the correctness and effectiveness of the proposed method.

The objective of the research is to design a high power energy harvester device through a two-piece trapezoidal geometry approach. The performance of the composite two-piece trapezoidal piezoelectric PZT-PZN polycrystalline ceramic material is simulated using COMSOL Multiphysics. Results are analysed using the series configuration of a two-piece trapezoidal composite bimorph cantilever which vibrates at the first fundamental frequency. The two-piece trapezoidal composite beam designs resulted in a full-width half-maximum electric power bandwidth of 2.5 Hz while providing an electric power density of 16.81 mW/cm3 with a resistive load of 0.08 MΩ. The authors believe that these results could help design a piezoelectric energy harvester to provide local energy source which provides high electric power output.

Abstract Rechargeable high‐energy lithium–sulfur batteries suffer from rapid capacity decay and poor rate capability due to intrinsically intermediate polysulfides' shuttle effect and sluggish redox kinetics. To tackle these problems simultaneously, a layer‐by‐layer electrode structure is designed, each layer of which consists of ultrafine CoS2‐nanoparticle‐embedded porous carbon evenly grown on both sides of reduced graphene oxide (rGO). The CoS2 nanoparticles derived from metal–organic frameworks (MOFs) have an average size of ≈10 nm and can facilitate the conversion between Li2S6 and Li2S2/Li2S in the liquid electrolyte by a catalytic effect, leading to improved polysulfide redox kinetics. In addition, the interconnected conductive frameworks with hierarchical pore structure afford fast ion and electron transport and provide sufficient space to confine polysulfides. As a result, the layer‐by‐layer electrodes exhibit good rate capabilities with 1180.7 and 700 mAh g−1 at 1.0 and 5.0 C, respectively, and maintain an impressive cycling stability with a low capacity decay of 0.033% per cycle within ultralong 1000 cycles at 5.0 C. Even with a high sulfur loading of 3.0 mg cm−2, the electrodes still show high rate performance and stable cycling stability over 300 cycles.

Based on the Lagrange equation, a 9-degrees-of-freedom shimmy model with consideration of the coupling effects between the motions of vehicle body and the shimmy of front wheels and a 5-degrees-of-freedom shimmy model ignoring these coupling effects for a vehicle with double-wishbone independent front suspensions are presented here to study the problem of vehicle shimmy. According to the eigenvalue loci of system’s Jacobian matrix plotted on the complex plane, the Hopf bifurcation characteristics of nonlinear shimmy are studied and the conditions for the generation of limit cycle are analyzed. Numerical calculation and simulation are used to study the dynamic behavior of vehicle shimmy. By comparing the dynamic responses of two different shimmy models, the coupling effects of vehicle body on vehicle shimmy are studied. Finally, the relationship between the amplitude of each DoF and vehicle velocity and the influences of vehicle parameters such as the mass of vehicle body, the longitudinal position of the center of gravity of vehicle body, and the inclination angle of front suspension on shimmy are studied.

Objective: Metabolic syndrome (MS) is a combination of medical disorders that increase the risk for cardiovascular disease and diabetes mellitus. It suggests an association between an elevated serum aminotransferase level and MS. Little data show the relationship between the levels of serum aminotransferase and the incidence of MS in Ningxia, China. Methods: A total of 5415 subjects who received medical health checkups from 2007 to 2009 were enrolled in the study. The participants were interviewed by trained health workers under a structured questionnaire. MS was defined according to the modified ATPIII criteria for Asian Americans by the American Heart Association (AHA-ATP III). Results: The prevalence of elevated aspartate aminotransferase (AST) and ALT (>40 U/L) were 7.1% and 22.2% in males, and 2.1% and 4.8% in females respectively. The prevalence of MS was 32.1% in males and 15.4% in females. The components of MS were significantly more in the group with elevated aminotransferase levels than in the group with normal aminotransferase levels. The odds ratios (95% CI) for elevated AST were 1.90 (1.49, 2.42), 2.59 (2.01, 3.39), 1.68 (1.32, 2.15), and 1.81 (1.36, 2.42) in the adults with abdominal obesity, high serum triglycerides levels, high blood pressure, and high plasma glucose levels respectively. After adjustment for age, the odds ratios (95% CI) for elevated ALT were 3.08 (2.63, 3.61), 4.30 (3.64, 5.08), 1.26 (1.08, 1.48), 2.16 (1.93, 2.65) and 2.38 (1.96, 2.87) in adults with abdominal obesity, high serum triglycerides levels, low serum high-density lipoproteincholesterol (HDL-C), high blood pressure, and high plasma glucose levels respectively. The odds ratios (95% CI) for elevated AST were 1.67 (1.06, 2.63), 2.28 (1.46, 3.63), 2.59 (1.59, 4.21) and for elevated ALT 2.02 (1.50, 2.73), 2.68 (1.96, 3.65), 3.94 (2.86, 5.43) for the subjects with 1, 2, and â¥3 risk factors after adjustment for age, gender, and BMI. Conclusion: The serum aminotransferase levels were higher in males compared to females, and serum ALT level was more closely associated with MS than the AST level in adults in Ningxia, China. With an increasing the number of components of MS, the aminotransferase levels and the risks for elevated aminotransferase increase, whereas the AST/ALT ratios decrease. Keywords: Metabolic syndrome, Serum aminotransferase, Odds ratios

Purpose. To investigate changes in eye coats, axial length, and ocular perfusion pressure (OPP) in hemodialysis (HD) patients with chronic renal failure (CRF). Methods. We included HD patients who were diagnosed with CRF in our hospital from January to December 2015. Fifty-two patients met the inclusion criteria; all right eyes were used for observation. Systolic and diastolic blood pressures were recorded to calculate OPP. Approximately 30 minutes before and after HD, we recorded multiple parameters, including lens thickness (LT), axial length of vitreous (VAL), axial length of eye (EAL), ciliary body thickness (CBT), choroidal thickness (CT), and retinal thickness (RT). Results. After HD, OPP significantly decreased (P

It remains unknown whether spinal cord injury (SCI) could indirectly impair or reshape the white matter (WM) of human brain and whether these changes are correlated with injury severity, duration, or clinical performance. We choose tract-based spatial statistics (TBSS) to investigate the possible changes in whole-brain white matter integrity and their associations with clinical variables in fifteen patients with SCI. Compared with the healthy controls, the patients exhibited significant decreases in WM fractional anisotropy (FA) in the left angular gyrus (AG), right cerebellum (CB), left precentral gyrus (PreCG), left lateral occipital region (LOC), left superior longitudinal fasciculus (SLF), left supramarginal gyrus (SMG), and left postcentral gyrus (PostCG) (p