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As a little girl, Li Zhang was brisk and outgoing, and always spoke cheerfully which made her families believe she was especially congenial to be a doctor. Followed the advices of the elders who were doctors as well, the innocent Li Zhang chose the road of Medicine.

The ancient Greek aphorism “know thyself” engraved on the forecourt of the Temple of Apollo epitomizes the human desire for the exploration into the unknown. In fact, never has mankind dragged their feet in understanding themselves, as in the achievements scientists have made all these years in the studies of disease and pathology.

The relatively recent emergence of Chinese NGOs has drawn the attention of many scholars for good reason. For those interested in state–society relations, Chinese NGOs are at the nexus of a far-rea...

Battery-powered mobile devices are typically featured with fast varying workloads and constrained power supply, demanding more efficient run-time power management. In this paper, we propose a DVFS design and simulation framework to explore the design space for DVFS. The framework leverages the existing tool chains and uses several machine learning models to support the architectural simulation and run-time profiling. When using the proposed framework to evaluate different management methods, the proposed deep-reinforcement-learning approach can achieve 5.8-7.3% performance improvement compared with the other alternatives.

Growing evidence from animal and human studies show that opioids have a major impact on the composition and function of gut microbiota. This leads to disruption in gut permeability and altered microbial metabolites, driving both systemic and neuroinflammation, which in turn impacts central nervous system (CNS) homeostasis. Tolerance and dependence are the major comorbidities associated with prolonged opioid use. Inflammatory mediators and signaling pathways have been implicated in both opioid tolerance and dependence. We provide evidence that targeting the gut microbiome during opioid use through prebiotics, probiotics, antibiotics, and fecal microbial transplantation holds the greatest promise for novel treatments for opioid abuse. Basic research and clinical trials are required to examine what is more efficacious to yield new insights into the role of the gut-brain axis in opioid abuse.

We propose a strategy for magnetic navigation of collective stem cell microrobots in blood environments under ultrasound Doppler imaging. The cell microrobots are fabricated through a coculture process of stem cells and iron microparticles, they have spheroidal structures and are actuated under external magnetic fields. The collective cell microrobots can be reversibly gathered and spread by adjusting the magnetic interaction, and these microrobots are able to exhibit collective motion in whole blood under rotating magnetic fields. Simulation results indicate that the induced blood flow around the collective pattern affects the motion of red blood cells, and experimental results show that Doppler signals are observed when emitting ultrasound waves to the microrobots. Due to the induced three-dimensional blood flow, Doppler signals can also be observed when the imaging plane is above the collective microrobots, which enables indirect localization when performing navigation on uneven surfaces. Moreover, collective patterns of different numbers of microrobots are formed in flowing conditions, and these collective biohybrid agents are actively navigated against flowing blood with a flow rate up to 4.5 mL/min (mean velocity: 5.97 mm/s). Our study investigates a strategy for pattern formation and navigation of collective microrobots under ultrasound Doppler imaging, demonstrating the integration of collective control approach and medical imaging holds great potential for real-time active delivery tasks.

Central nervous system (CNS) injuries, including traumatic brain injury (TBI), spinal cord injury (SCI) and subarachnoid hemorrhage (SAH), are the most common cause of death and disability around the world. As a key subset of extracellular vesicles (EVs), exosomes have recently attracted great attentions due to their functions in remodeling extracellular matrix, and transmitting signals and molecules. A large number of studies have suggested that exosomes played an important role in brain development and involved in many neurological disorders, particularly in CNS injuries. It has been proposed that exosomes could improve cognition function, inhibit apoptosis, suppress inflammation, regulate autophagy and protect blood brain barrier (BBB) in CNS injuries via different molecules and pathways including microRNA (miRNA), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), ph1osphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT), Notch1 and extracellular regulated protein kinases (ERK). Therefore, exosomes showed great promise as potential targets in CNS injuries. In this article, we present a review highlighting the applications of exosomes in CNS injuries. Hence, on the basis of these properties and effects, exosomes may be developed as therapeutic agents for CNS injury patients.

In pull-based development process, contributors submit their code to open-source projects by pull requests, which are accepted or rejected by reviewers. Contributors may modify their code, which causes several iterations of code review process, and makes code reviews time-consuming for both contributors and reviewers. In this article, we set out to study pull request modifications in a code review process. We collect nine projects on GitHub with 104 307 pull requests, and investigate pull request modifications through analyzing added commits after pull requests’ submission. By studying four research questions, we conclude our major findings as follow. First, 34.56% of collected pull requests have modifications. Pull requests with modifications have longer lifetime but higher pass rates. Second, we conclude eight modification types indicating why pull requests are modified. Third, we propose a novel method called MClassify to automatically classify pull request modifications, which achieves the accuracy of 0.807. Fourth, various modification types affect code review differently from the perspective of lifetime and pass rate. Pull requests with source control system management modifications have the longest lifetime. These findings enable developers and researchers to understand a pull-based code review process better and make improvements.

Continuous-flow microfluidic biochips have attracted high research interest over the past years. Inside such a chip, fluid samples of milliliter volumes are efficiently transported between devices (e.g., mixers, heaters, etc.) to automatically perform various laboratory procedures in biology and biochemistry. Each transportation task, however, requires an exclusive flow path composed of multiple contiguous microchannels during its execution period. Excess/waste fluids, in the meantime, should be discarded by independent flow paths connected to waste ports. All these paths are etched in a very tiny chip area using multilayer soft lithography and driven by flow ports connecting with external pressure sources, forming a highly integrated chip architecture that determines the final performance of biochips. In this paper, we propose a new and practical design flow called PathDriver+ for the architecture design of microfluidic biochips, integrating the actual fluid manipulations into both high-level synthesis and physical design, which has never been considered in prior work. With this design flow, highly efficient chip architectures with a flow-path network that enables the actual fluid transportation and removal can be constructed automatically. Meanwhile, fluid volume management between devices and flowpath minimization are realized for the first time, thus ensuring the correctness of assay outcomes while reducing the complexity of chip architectures. Additionally, diagonal channel routing is implemented to fundamentally improve the chip performance. The tradeoff between the numbers of channel intersections and fluidic ports is evaluated to further reduce the fabrication cost of biochips. Experimental results on multiple benchmarks confirm that the proposed design flow leads to high assay execution efficiency and low overall chip cost.

Background A novel procedure called shark mouth pancreaticojejunostomy (SMP) was developed, for the reconstruction of the pancreatic stump which has a theoretical advantage for anastomosis healing and wide applicability. Methods A comparative study of the patients who underwent SMP (SMP cohort) and those who underwent end-to-end dunking pancreaticojejunostomy (historic cohort) at Peking University Third Hospital was conducted. Each group was analyzed for the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) and morbidities. Results The clinicopathological data of 151 patients from the SMP cohort and 82 patients from the historic cohort were analyzed. In the SMP group, the rate of CR-POPF was 7.3% (11/151), which was significantly lower than the rate of CR-POPF in the historic group as 19.5% (16/82) (P = 0.005). The primary results were unaffected by sensitivity analyses based on several risk factors for CR-POPF. The rates of morbidities besides CR-POPF were 15.9% (24/151) in the SMP group and 17.1% (14/82) in the historic cohort (P = 0.194). The principal results were not changed by the propensity score matched (PSM) analysis. Conclusion SMP is a safe and simple surgical procedure for the reconstruction of the pancreatic stump compared with end-to-end dunking pancreticojejunostomy.

Intentional electromagnetic interference is a serious threat to the safety of electronic devices. Multiple electromagnetic pulses will be coupled and transmitted to electronic devices through the cables. Accumulative effects are generated, which make it easier for damage to occur in the electronic devices. In this article, the working principle of micro-silicon acceleration sensors is introduced. The accumulative effects of multiple pulses on acceleration sensors is studied by a large number of injection experiments. The accumulation trends of multiple pulses with different pulse numbers and intervals are analyzed. The damaged structures inside abnormal sensor amplifiers were observed via optical microscopy and scanning electron microscopy. The experimental results show that the accumulative effect is strengthened with increased pulse number or decreased pulse interval, and the threshold voltage for multiple pulses on the acceleration sensor decreases. The threshold voltage for a single pulse is 321.57 V. When the pulse interval is 1 μs and the pulse number is 5, the threshold voltage for multiple pulses is 163.42 V, which is reduced by 49.12% compared with a single pulse. These results provide a reference for the damage design of electromagnetic pulse weapons.

Di Chen, Mengmeng Wang, Yushuang Xu, Xin Jiang, Lina Xiong, Li Zhang, Honglu Yu, Zhifan Xiong Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Zhifan XiongDepartment of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430061, People’s Republic of ChinaTel +86 13517281937Email xiongzhifan@126.comPurpose: Autophagy plays a crucial role in the initiation and progression of gastric cancer (GC). However, the role of autophagy-related lncRNAs in GC remains unknown. This study aimed to investigate the prognostic value of the autophagy-related lncRNA signature and its role in the tumor immune microenvironment (TIME) of GC.Methods: RNA-sequencing (RNA-seq) and clinical data of GC patients were extracted from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analyses were performed to identify the autophagy-related lncRNA prognostic signature which was validated in the test set and entire set. The survival and predictive performance were analyzed based on the Kaplan–Meier and ROC curves. Furthermore, the CIBERSORT algorithm was applied to explore the relationship between this signature and the immune cell infiltration. To elucidate the potential functions of autophagy-related lncRNAs in GC, we constructed the lncRNA-mRNA co-expression network and performed enrichment analysis. Principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA) were further performed to compare the different statuses between the high-risk and low-risk groups.Results: We identified 5 autophagy-related lncRNAs (AL355574.1, AC010768.2, AP000695.2, AC087286.2, and HAGLR) to construct a prognostic signature. This signature could be an independent prognostic indicator for GC patients and had a higher prediction efficiency than other clinicopathological parameters. Furthermore, patients in the high-risk score group had a stronger immunosuppressive microenvironment than the low-risk group. The enrichment analysis for mRNAs co-expressed with these lncRNAs indicated that autophagy-related signaling pathways were remarkably enriched. PCA and GSEA further revealed different autophagy and immune statuses in the high- and low-risk groups.Conclusion: The 5 autophagy-related lncRNA signature has significant clinical implications in prognosis prediction of GC. Meanwhile, our study elucidates the critical role of the autophagy-related lncRNA signature in the TIME of GC.Keywords: gastric cancer, long non-coding RNAs, autophagy, prognostic signature, tumor immune microenvironment

Purpose To identify risk factors for surgical failure after gonioscopy-assisted transluminal trabeculotomy (GATT) in juvenile open angle glaucoma (JOAG). Design Prospective, interventional case series. Methods Seventy eyes of 70 patients with JOAG underwent GATT as the initial surgery. Surgical success was defined as a post-operative intraocular pressure (IOP) of ≤21 mmHg with at least a 20% reduction from pre-operative IOP with or without the use of anti-glaucoma medication (qualified and complete success, respectively) at each post-operative visit. IOP spike was defined as IOP >30 mmHg and an increase of at least 10 mmHg from IOP prior to the spike, and then reduced to ≤21 mmHg. Results The median age at the time of surgery was 19.3 (range: 4.9-37.5) years with a visual field mean deviation (MD) -17.4±10.6 dB. Mean IOP decreased from 31.3±9.5 mmHg pre-operatively to 15.8±2.7 at 12 months post-operatively. The complete and qualified success rates were 74.3% and 91.4%, respectively. Fifty-two (74%) eyes had an IOP spike with a median spike duration of 3.5 days (range 1-21). Longer duration of IOP spike (P=0.009) and older age at the time of surgery (P=0.025) were both associated with worse surgical outcomes. Advanced disease was associated with prolonged IOP spike (P=0.007). Conclusions GATT provided excellent outcomes in patients with severe JOAG. Older age and longer duration of post-operative IOP spike are risk factors for failure. Severe cases are more likely to have longer durations of IOP spike. Frequent IOP monitoring during the early post-operative period is needed to detect IOP spikes in these patients.

The three-phase three-leg four-wire (3P3L4W) three-level (3L) inverter demands large split dc-bus capacitors for limiting the voltage ripple resulting from the neutral current, which mainly pulsates at the fundamental output frequency, and the midpoint current, which mainly pulsates at triple the output frequency. This paper embeds a power decoupling network (PDN) in the basic 3P3L4W 3L inverter for reducing the split dc-bus capacitance. To curb excessive power losses, partial power processing is proposed to make the PDN partially bypass the neutral current and the midpoint current, such that the split dc-bus capacitance could be reduced at the expense of affordable power losses. Finally, a 10 kVA PDN embedded 3P3L4W 3L T-type inverter is built and tested in the lab, and experimental results are presented to verify the feasibility of the proposed work.

A dynamic self-assembly is a promising approach for inducing the collective behavior of agents to perform coordinated tasks at small scales. However, efficient pattern formation and navigation in environments with complex conditions remain a challenge. In this article, we propose a strategy for micromanipulation using dynamically self-assembled magnetic droplets with needle guidance. An iron needle was controlled by a three-degree-of-freedom (3-DoF) manipulator and magnetized by precessing magnetic fields. The process of self-assembly was optimized based on real-time vision feedback and a genetic algorithm. Affected by the locally induced field gradient near the needle, reconfigurable assembled magnetic droplets were formed beneath the air-liquid interface with high time efficiency, and the geometric center of the pattern was determined. Following the magnetized needle, assembled patterns were navigated along preplanned paths and exhibited reversible pattern expansion and shrinkage. Moreover, cargo can be trapped and caged by exploiting the induced fluid flow around the assembled droplets. To perform cargo transportation tasks in a multiple-obstacle environment, an optimal path planner with obstacle-avoidance capability was designed based on the particle swarm optimization (PSO) algorithm. Experiments demonstrated effective pattern formation, navigation, cargo trapping, and obstacle-avoidance transportation. The proposed method opens new prospects of using a dynamically self-assembled pattern as an untethered end-effector for micromanipulation.

Almost a decade ago, the sudden rise of breast muscle defects in fast-growing commercial broiler breeds challenged the broiler production industry and meat scientists to address the issue of these novel muscle abnormalities. After that, a widespread hypothesis showing a correlation between high muscle yield and incidence of these muscle myopathies received much acceptance from the research community. Increased muscle hypertrophy and unbalanced growth of connective tissues lead to an inadequate blood supply that ultimately causes hypoxia in muscle fibers. Reduced blood vascular density in muscle fibers induces oxidative stress and mitochondrial dysfunction, leading to muscle fibrosis, lipidosis and myodegeneration. Along with physical changes, the myopathic muscles exhibit poor sensory properties, abnormal texture properties and a low nutritional profile. As these myopathies alter meat’s physical appearance, they have a negative impact on customer’s behavior and preference. A better production environment with proper dietary supplementation with balanced breeding strategies can minimize the incidence of muscle myopathies in broiler chicken. This review aims to address the underlying mechanism behind these myopathies and their impact on poultry meat quality, including nutritional value and consumer behavior. It describes the link between genetic and non-genetic elements influencing myopathies, along with the strategies to minimize the occurrence of breast muscle myopathies.

Purpose: To establish recommended phase II dose (RP2D) in phase I and evaluate safety and efficacy of abivertinib in patients with EGFR Thr790Met point mutation (T790M)-positive(+) non–small cell lung cancer (NSCLC) with disease progression from prior EGFR inhibitors in phase II. Patients and Methods: This multicenter, open-label study included 367 adult Chinese patients. Abivertinib at doses of 50 mg twice a day to 350 mg twice a day was evaluated in phase I in continual 28-day cycles, and the RP2D of 300 mg twice a day was used in phase II in continual 21-day cycles. Primary endpoints include RP2D in phase I and objective response rate (ORR) at RP2D in phase II. Results: The RP2D of 300 mg twice a day for abivertinib was established based on pharmacokinetics, efficacy, and safety profiles across doses in phase I. In phase II, 227 patients received RP2D for a median treatment duration of 24.6 weeks (0.43–129). Among 209 response–evaluable patients, confirmed ORR was 52.2% [109/209; 95% confidence interval (CI): 45.2–59.1]. Disease control rate (DCR) was 88.0% (184/209; 95% CI: 82.9–92.1). The median duration of response (DoR) and progression-free survival (PFS) was 8.5 months (95% CI: 6.1–9.2) and 7.5 months (95% CI: 6.0–8.8), respectively. The median overall survival (OS) was 24.9 months [95% CI: 22.4–not reachable (NR)]. All (227/227) patients reported at least 1 adverse event (AE), with 96.9% (220/227) of treatment-related AEs. Treatment-related serious AEs were reported in 13.7% (31/227) of patients. Death was reported in 4.4% (10/227) of patients, and none was deemed as treatment-related. Conclusions: Abivertinib of 300 mg twice a day demonstrated favorable clinical efficacy with manageable side effects in patients with EGFR T790M+ NSCLC.

Objectives The aim of this study was to establish a time-resolved fluorescent immunoassay (TRFIA) for the detection of serum galactose agglutinin 3 (Gal-3) and apply this method to evaluate the clinical significance of serum Gal-3 in predicting Idiopathic Membranous Nephropathy (IMN) progression. Methods The Gal-3-TRFIA was established using the double antibody sandwich method, with the capture antibodies coated on a 96-well microplate and the detection antibodies chelated to Europium (III) (Eu3+). Serum Gal-3 was detected in 81 patients with IMN and 123 healthy controls to further evaluate the value of the Gal-3 in staging of IMN. Results The sensitivity of the Gal-3-TRFIA assay was 0.85 ng/mL, and the detection range was 0.85–1000 ng/mL. The Gal-3 intra-batch and inter-batch coefficients of variation were 3.45% and 5.12%, respectively. The correlation coefficient (R) between the Gal-3-TRFIA assay and commercially available enzyme-linked immunosorbent assay kits was 0.83. The serum Gal-3 concentration was higher in patients with IMN (65.57 ± 55.90 ng/mL) compared to healthy controls (16.29 ± 9.91 ng/mL, P 3+) chelates for the detection of Gal-3 concentrations in serum. The Gal-3-TRFIA also detected the severity of the IMN course.

Traditional personalized tag recommendation methods cannot guarantee that the collaborative signal hidden in the interactions among entities is effectively encoded in the process of learning the representations of entities, resulting in insufficient expressive capacity for characterizing the preferences or attributes of entities. In this paper, we firstly propose a graph neural networks boosted personalized tag recommendation model, namely NGTR, which integrates the graph neural networks into the pairwise interaction tensor factorization model. Specifically, we exploit the graph neural networks to capture the collaborative signal, and integrate the collaborative signal into the learning of representations of entities by transmitting and assembling the representations of neighbors along the interaction graphs. In addition, we also propose a light graph neural networks boosted personalized tag recommendation model, namely LNGTR. Different from NGTR, our proposed LNGTR model removes feature transformation and nonlinear activation components as well as adopts the weighted sum of the embeddings learned at all layers as the final embedding. Experimental results on real world datasets show that our proposed personalized tag recommendation models outperform the traditional tag recommendation methods.

With the rapid development of the influencer marketing industry in recent years, the cooperation between brands and micro-influencers on marketing has achieved much attention. As a key sub-task of influencer marketing, micro-influencer recommendation is gaining momentum. However, in influencer marketing campaigns, it is not enough to only consider marketing effectiveness. Towards this end, we propose a concept-based micro-influencer ranking framework, to address the problems of marketing effectiveness and self-development needs for the task of micro-influencer recommendation. Marketing effectiveness is improved by concept-based social media account representation and a micro-influencer ranking function. We conduct social media account representation from the perspective of historical activities and marketing direction. And two adaptive learned metrics, endorsement effect score and micro-influencer influence score, are defined to learn the micro-influencer ranking function. To meet self-development needs, we design a bi-directional concept attention mechanism to focus on brands and micro-influencers marketing direction over social media concepts. Interpretable concept-based parameters are utilized to help brands and micro-influencers make marketing decisions. Extensive experiments conducted on a real-world dataset demonstrate the advantage of our proposed method compared with the state-of-the-art methods.

Graphical abstract, Highlights • Synovial fibrosis was positively correlated with pain sensitivity in KOA rats. • Synovial fibrosis was most prominent in DMM group 14 days after modeling. • ACLT replaced DMM to be the most typical at 28 days after modeling. • Increased synovial sensory innervation followed the same trend as fibrosis. • ACLT is more applicable for KOA pain research., Introduction Knee osteoarthritis (KOA) showed synovial fibrosis and hyperalgesia, although the correlation between the two is unclear. Besides, the specific changes of sensory innervation in animal models are still controversial, which makes it difficult to choose the modeling methods for KOA pain research. Objectives Study the characteristics of sensory innervation within three commonly used KOA rat models and the correlation between synovial fibrosis and hyperalgesia. Methods KOA models were induced by destabilization of medial meniscus (DMM), anterior cruciate ligament transection (ACLT), and monoiodoacetate (MIA), respectively. Mechanical, cold and thermal withdrawal threshold (MWT, CWT and TWT) were measured. The harvested tissues were used for pathological sections, immunofluorescence and quantitative analysis. Results KOA synovium showed more type I collagen deposition, increased expression of CD31, VEGF and TGF-β. These changes were most pronounced in surgical models, with DMM presenting the most prominent at Day 14 and ACLT at Day 28. Day 14, changes in mechanical hyperalgesia and cold hyperalgesia were most typical in DMM model and statistically different from MIA. There was a negative correlation between the percentage of type I collagen and MWT value (r = −0.88), as well as CWT value (r = −0.95). DMM synovium showed more axonal staining, upregulated CGRP, TRPV1, NGF and Netrin1 compared with MIA. Above changes were also observed at Day 28, but ACLT replaced DMM as the most typical. In DRG, only the levels of CGRP and NGF were different among KOA models at Day 14, and the highest in DMM, which was statistically different compared with MIA. Conclusions This study described the details of sensory innervation in different KOA model of rats, and the degree of synovial fibrosis was positively correlated with the pain sensitivity of KOA model rats. Additionally, surgical modeling especially ACLT method is more recommended for KOA pain research.

Two-dimensional halide perovskite composites exhibit enhanced performances not observed in their individual components for versatile optoelectronic applications and beyond, manifesting the positive “1 + 1 > 2” effect.

Li Zhang, Xiaoping Li, Jiang Lu, Yi Qian, Tao Qian, Xing Wu, Qinghua Xu Department of Hepatobiliary and Pancreatic Surgery, LiYang People’s Hospital, LiYang, 213300, Jiangsu, People’s Republic of ChinaCorrespondence: Qinghua Xu; Xing WuDepartment of Hepatobiliary and Pancreatic Surgery, LiYang People’s Hospital, 70# JianShe West Road, LiYang, 213300, Jiangsu, People’s Republic of ChinaTel/Fax +86-519-68091108Email xqh7888882@163.com; sxj6628@126.comBackground: Previous studies have shown that epidermal growth factor receptor (EGFR) promotes cell proliferation through the PI3K-Akt-mTOR signaling pathway and participates in the occurrence and development of hepatocellular carcinoma (HCC). Here, we focused on the functional polymorphism of EGFR in the 3ʹ-untranslated region (UTR), aiming to reveal the potential mechanisms by which functional polymorphism is associated with the risk and development of HCC in the Han Chinese population.Methods: This study was a hospital-based case-control study. A total of 600 patients were enrolled, and another 600 healthy volunteers served as controls. The miR-associated SNPs in EGFR were screened, and genotyping was performed by TaqMan allele differential analysis. In this study, genotyping, real-time PCR, cell transfection and double luciferase reporter gene were used for subsequent analysis.Results: HBV/HCV infection instead of alcohol exposure, smoking exposure, hypertension or diabetes mellitus was associated with an increased risk of HCC. Compared with TT genotypes, TG and GG genotypes of EGFR rs884225 were significantly associated with reduced HCC risk. The stratified analysis of association between rs884225 and HCC subgroup feature reveal a highly correlation with tumor size. Furthermore, qRT-PCR confirmed that EGFR rs884225, TG and GG genotypes were more likely to bind to miR-3196 and down-regulate EGFR level in cells, thereby inhibiting cell proliferation.Conclusion: This study suggested that EGFR rs884225 is associated with a reduced risk of liver cancer and may be a developing biomarker.Keywords: miR-3196, polymorphism, proliferation, hepatocellular carcinoma, HCC, epidermal growth factor receptor, EGFR

Xiaomin Xie,* Guirong Bai,* Huili Liu, Li Zhang, YanTing He, Dan Qiang, Xiaoyan Zou Department of Endocrinology, The First People’s Hospital of Yinchuan, Yinchuan, 750001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaomin XieDepartment of Endocrinology, The First People’s Hospital of Yinchuan, 2 Liqun Street, Xingqing District, Yinchuan, 750001, Ningxia, People’s Republic of ChinaTel +86 13895189599Email xxm2324@126.comPurpose: This study investigates the possible roles and potential prediction ability of metabolic parameters in the early development of T2D by detecting their serum levels at different fasting blood glucose (FBG) levels.Methods: The subjects were included and divided into normal glucose tolerance (NGT), prediabetes (PD), and T2Dsubgroups. Apart from detecting the levels of routine biochemical parameters, fasting serum insulin (FINS), 25(OH)D, thioredoxin-interacting protein (TXNIP), thioredoxin (TRX), and NOD-like receptor family, pyrin domain-containing 3 (NLRP3) were detected. β-cell dysfunction (HOMA-β) and insulin resistance (HOMA-IR) were assessed by homeostasis model assessment. Both univariate and multivariate logistic regression analyses were used to estimate the risk of metabolic parameters, and their optimal cut-off values were obtained in the receiver operating characteristic (ROC) curve analysis and the Youden index.Results: Among the 207 subjects, aged from 20 to 60 years (44.62+12.92) contain 118 males and 89 females. There was a significantly lower trend of TRX, HOMA-β, and 25(OH)D following the higher FBG level among these three subgroups, while a significantly higher trend of all the other metabolic parameters. The multivariate analysis showed that subjects with higher values of TRX, HOMA-β, and 25(OH)D had a significantly lower risk for patients to be diagnosed as PD (aOR: 0.945, 0.961, and 0.543) and T2D (aOR: 0.912, 0.947, 0.434). Under the reliable 95% CI, TXNIP with a cut-off value of 119.27 showed the highest AUC value, sensitivity, and specificity (AUC: 0.981, 95% CI: 0.8524– 0.9839, 91.49%, and 83.33%) to diagnose PD. FINS with a cut-off value of 28.1 also showed the highest ones (AUC=0.9872, 95% CI: 0.9753– 0.9992, 100%, and 92.91%) to diagnose T2D.Conclusion: Early prediction of T2D is vital for timely intervention. Based on the FBG ≥ 100.8 mg/dl, the results provide evidence that 25(OH)D might be the protective factor in the early development of T2D. Besides, TXNIP and FINS might be the predictor for PD and T2D, respectively.Keywords: prediabetes, PD, type 2 diabetes, T2D, 25-hydroxyvitamin D, 25(OH)D, thioredoxin-interacting protein, TXNIP, β-cell dysfunction, insulin resistance

Background: AZD9833 is an oral selective estrogen receptor (ER) antagonist and degrader (SERD) in Phase 2 clinical development for the treatment of ER+ HER2− breast cancer. Here we report data from Parts C and D of the ongoing Phase 1 study (SERENA-1) examining AZD9833 in combination with palbociclib, together with updated data from Parts A and B examining AZD9833 monotherapy. Methods: SERENA-1 (NCT03616587) is an ongoing open-label Phase 1 study of AZD9833 in pre- and post-menopausal women with ER+, HER2− advanced breast cancer who have previously received ≥1 endocrine therapy and ≤2 prior chemotherapies. Prior treatment with fulvestrant and/or CDK4/6 inhibitors was permitted. The primary objective is to determine the safety and tolerability of once daily (QD) AZD9833, with dose-limiting toxicities (DLTs) in the first 28 days defining the maximum tolerated dose. Secondary objectives include anti-tumor response (including circulating tumor [ct] DNA response) and pharmacokinetics. Parts A (escalation) and B (expansion) assess AZD9833 as a monotherapy, and Parts C (escalation) and D (expansion) assess AZD9833 in combination with palbociclib. Results: At a data cut-off of March 24 2020, 17 patients had received either 150 mg or 300 mg AZD9833 in combination with palbociclib, given according to its product labeling. Eighty patients had received AZD9833 monotherapy at doses of 25, 75, 150, 300, and 450 mg QD. In patients treated with AZD9833 and palbociclib, treatment-related adverse events (AEs; experienced by ≥10% of patients) included visual disturbances*, bradycardia*, asthenia, anemia, QTcF prolongation, nausea, neutropenia, decreased white blood cell count, and vomiting (*combined terms). All instances of AZD9833-related bradycardia were Grade 1. One DLT was observed in the 150 mg cohort: CTCAE Grade 2 visual disturbances, which began on Cycle 1 Day 8 and resolved by Cycle 1 Day 9 following dose interruption. The patient restarted treatment on Cycle 1 Day 15 at 75 mg and continued this dose until data cut-off. No causally related AEs led to discontinuation of AZD9833. The tolerability of AZD9833 with palbociclib was consistent with the observed tolerability profile of AZD9833 monotherapy, and the known tolerability profile of palbociclib. Pharmacokinetic analysis showed similar AZD9833 exposure for monotherapy and palbociclib combination therapy. Similarly, palbociclib exposure was comparable with simulations using a published population pharmacokinetic model. In Part A, ESR1 hotspot mutations were detected in ctDNA at baseline in 26/56 (46%) patients; 13/26 (50%) of these patients achieved a partial response or stable disease at 24 weeks, including 5/10 (50%) with a Y537S ESR1 mutation. Further, in patients with ESR1 mutations and samples available for longitudinal ctDNA analysis, 17/20 (85%) exhibited a reduction or loss of mutant ESR1 on treatment with AZD9833. Efficacy data to be presented include objective response rate and clinical benefit rate at 24 weeks. Of note, unconfirmed partial responses have been observed in Part C after the data cut-off for this abstract. Conclusions: AZD9833 continues to show an encouraging efficacy and dose-dependent safety profile as a monotherapy or in combination with palbociclib. A Phase 2 study comparing the efficacy and safety of three doses of AZD9833 versus fulvestrant (NCT04214288), and a Phase 2 pre-surgical ‘window of opportunity’ study (EUDRA-CT; 2019-003706-2) are ongoing. Citation Format: Richard Baird, Mafalda Oliveira, Eva Maria Ciruelos Gil, Manish R Patel, Begoña Bermejo de las Heras, Manuel Ruiz-Borrego, Javier García-Corbacho, Anne Armstrong, Udai Banerji, Chris Twelves, Valentina Boni, Jason Incorvati, Peter Kabos, Adam L Cohen, Bruno de Paula, Marta Capelán Rodríguez, Judy S Wang, Christina Hernando, Alejandro Falcón Gonzalez, Ivan Victoria Ruiz, Julia Lai-Kwon, Anosheh Afghani, Christos Vaklavas, Tim Brier, Steven Fox, Bistra Kirova, Teresa Klinowska, Chris Leach, Justin PO Lindemann, Richard Mather, Rhiannon Maudsley, Christopher J Morrow, Nitharsan Sathiyayogan, Andy Sykes, Li Zhang, Erika Hamilton. Updated data from SERENA-1: A Phase 1 dose escalation and expansion study of the next generation oral SERD AZD9833 as a monotherapy and in combination with palbociclib, in women with ER-positive, HER2-negative advanced breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-05.

Background & aims Ischemia reperfusion (I/R) injury is an inevitable complication of liver transplantation and compromises its prognosis. Glycosyltransferases have been recognized as promising targets for disease therapy, but their roles remain largely unknown in hepatic I/R injury. Here, we aim to demonstrate the exact function and molecular mechanism of a glycosyltransferase, N-Acetylgalactosaminyltransferase-4 (GALNT4), in hepatic I/R injury. Approach & results Via an RNA-seq data-based correlation analysis, we found a close correlation between GALNT4 expression and hepatic I/R-related molecular events in murine model. The mRNA and protein expression of GALNT4 were markedly upregulated upon reperfusion surgery in both clinical samples from subjects underwent liver transplantation and mouse model. We found that GALNT4 deficiency significantly exacerbated I/R-induced liver damage, inflammation and cell death, whereas GALNT4 overexpression led to the opposite phenotypes. Our in-depth mechanistic exploration clarified that GALNT4 directly binds to the apoptosis signal-regulating kinase1 (ASK1) to inhibit its N-terminal dimerization and subsequent phosphorylation, leading to a robust inactivation of the downstream c-Jun N-terminal kinase (JNK) / p38 and nuclear factor kappa B (NF-κB) signalling. Intriguingly, the inhibitory capacity of GALNT4 on ASK1 activation is independent of its glycosyltransferase activity. Conclusions GALNT4 represents a promising therapeutic target for liver I/R injury and improve liver surgery prognosis by inactivating ASK1-JNK/p38 signalling pathway.

Hyperthyroidism is a common disease mainly manifested by hyperexcitability of multiple systems and hypermetabolism. Currently, antithyroid drugs (ATDs), radioiodine therapy (RIT), and surgery are mainly used in the clinical treatment for primary hyperthyroidism. We reported a case of a 28-year-old female who received a novel treatment for primary hyperthyroidism. This patient had poor control of thyroid function while taking ATD, and her oral Methimazole (MMI) dose varied repeatedly between 20 mg qd and 15 mg qd, failing to maintain a stable status. To minimize the possible complication and to achieve drug reduction or withdrawal, she refused RIT and surgery and showed up in our department. The patient, diagnosed with Graves’ disease (GD) and met the surgical indication after systematic clinical evaluation, was subject to ultrasound-guided percutaneous microwave ablation (MWA) of the partial thyroid gland with continuous oral administration of 20 mg qd MMI. The post-ablation condition was stable and the patient was discharged 2 days after the operation. Thyroid ultrasound and serum thyroid function test were examined regularly after ablation and the MMI dosage was gradually reduced according to the results of the biochemical examination. Five weeks after the operation, the patient completely discontinued the medication. Ultrasound-guided percutaneous microwave ablation is minimally invasive, safe, and effective, and has potential to be an alternative treatment besides the 3 classical treatments of hyperthyroidism.

The Baha® Attract system can provide effective and stable hearing amplification for patients with microtia. Concurrent surgeries of auricle reconstruction and Baha® Attract implantation do not result in more soft tissue complications. The number of adverse events increased with the duration of implantation, even one year postoperatively. Benign skin evolutions, including skin thinning and erythema at the implant side, are commonly seen in Baha® Attract users. Implants are not necessarily removed when skin necrosis occurs in Baha® Attract users.

BACKGROUND In the context of aortic dissection, increasing pressure within the newly formed false lumen can result in the progressive compression of the true aortic channel. However, true lumen collapse in chronic type B aortic dissection (cTBAD) patients is rare, with few clinical or experimental studies to date having explored the causes of such collapse. CASE SUMMARY In the present report, we describe a rare case of true-lumen collapse in an 83-year-old patient diagnosed with cTBAD, and we discuss potential therapeutic interventions for such cases. Following thoracic endovascular aortic repair (TEVAR), computed tomography angiography revealed satisfactory stent-graft positioning, no endoleakage, true lumen enlargement, thrombus formation in the false lumen, and slight enlargement of the true lumen distal to the stent-graft. Computational hemodynamic analyses indicated that the wall shear stress and pressure within the false lumen were significantly reduced following TEVAR. CONCLUSION TEVAR treatment of cTBAD patients suffering from proximal true lumen collapse can facilitate some degree of effective remodeling.

Superfluous low-frequency microwave radiation becomes a serious problem gradually at current age, herein, the Sn-Fe-O multiphase compounds were combined with novel biochar by using Salvia miltiorrhiza Bunge's leaves as carbon source, which can realize the recycling of this useless Chinese medicinal waste for economy. Also, the influence of preparation process on the final components, structures and properties in composites have been evaluated, the P2 composite possesses the optimal electromagnetic absorbing property i.e. the maximum reflection loss achieves −45.09 dB at 0.48 GHz with efficient absorbing bandwidth of 0.14–1.16 GHz at the matching thickness of 2 mm, moreover, a broad efficient absorbing bandwidth of 0.86–3 GHz can obtained for only 0.71 mm as well. The outstanding absorption of this sample can be ascribed to the synergistic effect of multiple low-frequency absorption mechanisms such as nature resonance, eddy current, conduction and electron hopping, multi-ply interfacial polarization etc., suggesting its superiority for being applied as a new-type low frequency electromagnetic wave absorber for practical use.

Purpose Sleep disturbance is one of the common symptoms in Parkinson’s disease (PD). The study of sleep disturbance used to concentrate on treated PD. This study aimed to investigate the factors that are associated with the sleep quality of drug-naïve patients with PD. Patients and Methods All participants were interviewed using a standard questionnaire to collect basic information. PD severity, depression symptoms, anxiety symptoms, sleep quality, cognitive status, life quality, and the presence of rapid eye movement (REM) sleep behavior disorder (RBD) and minor hallucination were assessed using corresponding rating scales. The patients with a Pittsburgh Sleep Quality Index score ≤6 fell into the poor sleep group, and those with REM Sleep Behavior Disorder Screening Questionnaire score ≥5 were considered to have probable RBD. Results Seventy drug-naive patients with PD and 30 healthy controls matched for age, sex, and education were recruited. Up to 41.4% of the patients suffered from sleep disturbance, and 24.3% of the patients had RBD. Poor sleepers were more likely to have left-side predominant motor symptoms. Compared with good sleepers, poor sleepers, particularly female patients, had more burden in the aspect of anxiety and depression. RBD was associated with more nonmotor symptoms, poor sleep quality, bad performance in cognition orientation domain, anxiety, depression, presence of minor hallucination, and poor life quality. Conclusion Sleep disturbances are common in drug-naïve PD and require wide attention. Motor symptom laterality and gender difference in mood are associated with sleep quality. Depression, anxiety, and RBD are highly related to sleep disturbance. RBD has many comorbidities, which can influence the cognitive function and life quality of the patients.

In the recent decade, temporary frequency support derived from variable speed wind turbine generator has been drawing increasing attention in the electronic‐growing power system. Frequency nadir and rate of change of frequency are two key indicators temporary frequency support strives to improve. This paper proposes a novel insight on frequency regulation of wind power. Note that considerable part of load is shared by synchronous generators and wind turbine generator and the system frequency still will be dominated by the former for a period of time. Simultaneously taking the frequency regulation characteristic of synchronous and power balance into account, a novel frequency regulation scheme aiming at improving system's frequency regulation performance is proposed and tested in a 7‐machine power system with an aggregated wind farm on MATLAB/Simulink to investigate what inherently determines the performance of frequency regulation. Results show that with differential cooperation of synchronous generator and doubly fed induction generator, frequency nadir and rate of change of frequency can be partially improved. Particularly, regarding to handling the issue of control delay, an appropriately slower action upon detecting a frequency event may not screw up it but contribute to a higher frequency nadir, which benefits from the spontaneous cooperation of synchronous generator and wind power with constraint of power balance.

Background: Group B streptococcus (GBS) is a leading cause of serious infection in infants. Understanding its regional molecular epidemiology is helpful for regulating efficient prevention practice. Methods: A retrospective study was conducted to collected data from infants and pregnant women with culture-proven GBS disease in the largest women and children's medical center in Shanxi between January 2017 and September 2019. All GBS isolates were analyzed by multi-locus sequence typing (MLST) as well as distribution of pilus island (PI) genes. Results: A total of 54 GBS isolates were obtained from 36 (66.7%) pregnant women and 18 (33.3%) infants with invasive disease. Among invasive GBS strains, the most common sequence type was ST10 (72.2%, P

In this article, a triple-coil-based coil positioning approach is proposed for the wireless electric vehicle charger to realize the accurate coil positioning with low electromagnetic field. Based on the working principle of the proposed triple-coil architecture and the discussion of the sensing-coil configuration, the received signal strength (RSS) equations are derived, revealing the way of enhancing the positioning signals by taking advantage of the quality factor ( QM ). Thereafter, an RSS fingerprint positioning algorithm is proposed for obtaining coordinates in x -, y -, and z -direction. Specific considerations are also given for designing the exciting frequency and the coil parameters. Finally, the proposed positioning system is tested on a 3.3-kW wireless charger. The RSS of the proposed positioning system has been proved to be 3.2 times as that of the state-of-the-art one, whereas the excitation current is reduced by more than half. A number of positioning cases, with the targeted coil placed in an area of 32 cm × 32 cm, are tested in the lab. The experimental results show that more than 95% of these test cases have been well positioned with test errors less than 1.5 cm.

We report high-performance IGZO TFTs with MoAl/Cu/MoAl and MoMn/Cu/MoMn three-layer electrodes, where MoAl or MoMn alloy is used as the buffer layer. The multilayer electrode has good electrical properties and can effectively prevent the oxidation and diffusion of the middle Cu layer. In addition, the multilayer electrode can be etched in a PAN etchant solution and match the etching rate with Cu. Based on these MoAl/Cu/MoAl and MoMn/Cu/MoMn electrodes, vacuum-processed IGZO TFTs exhibit a turn-on voltage of 0 V, an on-off ratio of 10⁹, and a mobility of 10.7 cm² V⁻¹ s⁻¹ after annealing at 115 °C in N₂. Under the gate bias stress test, devices with MoMn electrodes, which exhibit a small threshold voltage shift, show better performance than those with MoAl electrodes. The presented studies may provide another option for the Cu buffer layer.

This study was to optimize the exercise preconditioning (EP) intensity in protecting from exhaustive exercise-induced cardiac injury (EECI). A total of 98 male Sprague-Dawley rats were divided into 7 groups (n ​= ​14): the control group (C), the exhaustive exercise group (EE) and the EP ​+ ​EE groups, which include the V10 (53.0%̇O2max), V15 (58.4%̇O2max), V20 (67.0%̇O2max), V26 (74.0%̇O2max) and V30 (80.0%̇O2max) groups. Except the C group, the other groups were subjected to treadmill running. The serum contents of N terminal pro B type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTn-I) were detected by the enzyme-linked immunosorbent assay method, ECG was recorded, heart function was detected by pressure volume catheter and the activities of mitochondrial electron transfer pathway (ET pathway) complexes I, Ⅱ and IV were measured by high-resolution respiration instrument. Compared to the EE group, the EP groups have shown decrease of NT-proBNP and cTn-I, improvement of mitochondrial respiratory function and cardiac function. Compared to other EP groups, the V26 group has shown significant decrease of myocardial enzymes and improvement of mitochondrial function. The correlation analysis showed the EP effect was proportional to EP intensity in the range of 53.0%̇O2max-74.0%̇O2max. High intensity and long duration of exhaustive exercise caused cardiac injury and EP could decrease serum level of NT-proBNP and cTn-I, improve electrical derangement and the left ventricular function, and raise the activities of ET pathway complexes I, Ⅱ and IV. The protection of EP on EECI was improved as the EP intensity was increased from 53.0%̇O2max to 74.0%̇O2max and when EP intensity was 74.0%̇O2max, the effect was the most obvious among all the setting EP groups.

Radiotherapy (RT) is a major modality of postoperative treatment in breast cancer. The maximal standardized value (SUVmax) is 18FDG-PET/CT derived parameter that reported to be a valuable prognostic factor in cancer patients. Herein, we aimed to identify a prognostic gene signature associated with glucose uptake for breast cancer patients after RT by leveraging the mRNA expression profiling on public datasets. The glucose uptake signature was constructed using the single sample gene set enrichment analysis (ssGSEA) algorithm and evaluated in GSE21217 where SUVmax value was measured by PET-CT directly. The prognostic value was validated in three post-RT breast cancer cohorts (GSE103744, NKI, and FUSCC databases). The patients were stratified into glucose uptake signature score-high and low groups. Patients with a higher score had worse survival than those with a lower score. Mechanistically, the glucose uptake signature was calculated in each cell type of a single-cell RNA-seq database from five breast cancer patients. Glucose uptake signature score was significantly elevated in the malignant epithelial cells compared with normal ones. The immunosuppression markers including PDCD1, TIGIT, LAG3, and HAVCR2 were significantly upregulated in the T cells bearing a high glucose uptake signature score. Collectively, our results demonstrated the potential prognostic value of a glucose uptake signature in the post-RT breast cancer patients., Graphical abstract, A glucose uptake gene signature was constructed and validated to predict survival in radiotherapy-treated breast cancer patients. The correlation between this gene signature and immunosuppressive markers has been explored.

We aimed to clarify the therapeutic effects of imperatorin (IMP) on knee osteoarthritis (KOA). Thirty 3-month-old SD male rats were randomly divided into Normal, monosodium iodoacetate (MIA) and MIA+IMP groups. Their synovial tissues were subjected to histopathological analysis. Primary synovial fibroblasts obtained from additional normal rats were treated by lipopolysaccharide (LPS) and then IMP. The mRNA and protein expressions of factors related to synovitis and synovial fibrosis were detected by qRT-PCR and Western blotting, respectively. The concentrations of inflammatory factors IL-1β and IL-18 were measured by ELISA. IMP reduced HIF-1α, NLR family pyrin domain-containing 3 inflammasome expression and IL-1β, IL-18 production in synovial fibroblasts induced by LPS. IMP also downregulated synovial fibrosis markers. In vitro study revealed that MIA-induced synovitis and synovial fibrosis were relieved by IMP. IMP relieves the inflammation associated with synovitis and synovial fibrosis. It reduces the production of pro-inflammatory mediators and cytokines and inhibits TGF-β1, TIMP-1 and VEGF expressions that promote synovial fibrosis.

Many studies have focused on the gray matter volume associated with sleep quality, little is known about the relationship between white matter volume and sleep quality. Brain white structure is a crucial component in the structural neuroanatomy. Therefore, in this study, we investigated the association between white matter volume and sleep quality. Data were collected using the Pittsburgh Sleep Quality Index and voxel-based morphometry among 352 college students. Results showed that the global PSQI score was negatively associated with the white matter volume, including in the right middle occipital gyrus, the left superior temporal gyrus, the right the precentral gyrus, the left supramarginal gyrus, the left middle frontal gyrus, the left precunes, and the right superior frontal gyrus. Results also indicated that the white matter volume in specific regions negatively associated with the factor of PSQI. These specific brain regions may be replicated in brain areas related to sleep quality. In summary, we suggested that exploring brain white structure are related to sleep could help to expound the mechanisms by which sleep quality are associated with brain function, behavior and cognition, as well as potentially the networks and systems responsible for variations in sleep themselves.

With the development of online retailing on third-party e-commerce platforms such as Taobao, the churn of individual shops is becoming increasingly severe. Platform operators are eager to learn the causes of this eroding trust. Based on Hofstede’s cultural dimensions theory, this paper aims to investigate how masculinity, uncertainty avoidance and long-term orientation impact platform trust and the interaction between these three cultural variables. Based on data collected from sellers on the largest Chinese C2C platform, we found that uncertainty avoidance had a negative effect on platform trust, while masculinity and long-term orientation exerted a positive impact on platform trust. A significant association among the cultural factors was also found.

To evaluate the comparative effectiveness and safety of open-door laminoplasty (OLP), French-door laminoplasty (FLP), laminectomy and fusion (LF), and laminectomy alone (LA) in treating multilevel degenerative cervical myelopathy (MDCM). Embase, PubMed, and Cochrane library were searched from their inception date to 7 January 2021. Randomized controlled trials and cohort studies comparing OLP, FLP, LF, and LA were identified to perform a network meta-analysis (NMA). A total of 30 studies with 2671 patients were included. Our NMA results showed no significant difference between LF and OLP, but both are superior to LA and FLP in the comparison of JOA (Japanese Orthopaedic Association) score improvement. LF showed a most unsatisfactory outcome in postoperative range of motion (ROM) compared with LA or OLP or with FLP. For the complication outcome, no significant differences were found. The surface under the cumulative ranking curves (SUCRA) for JOA improvement was as follows: LF, OPL, LA, and FLP. For ROM reduction it was LA, OPL, FPL, and LF. For complications it was LF, LA, OLP, and FLP. Considering all the evaluated criteria, none of the procedures showed the best outcome with least complications and optimal efficacy. However, OLP can be most recommended because of its second-ranking spectra in both of JOA improvement and ROM reduction, also with an acceptable incidence of complications, with the third least.

Under the macro environment of “greening” of the world economy, it is of positive practical significance to effectively identify and reduce the Inter-Organizational relationship risk of green supply chain based on the national green development strategy to build Inter-Organizational relationship based on trust. The paper discusses the connotation of green supply chain knowledge sharing, the influencing factors of green supply chain knowledge sharing, the risk of green supply chain Inter-Organizational relationship, and the operation mechanism of green supply chain Inter-Organizational relationship risk, and provides an outlook on the future research trends. From the current situation, future research should integrate multidisciplinary knowledge system and use a combination of qualitative and quantitative methods to explore the relationship between Inter-Organizational relationship risk and knowledge sharing of green supply chain, to promote the depth and further development of green supply chain research.

Background Early progression of feeding could influence the development of the gut microbiome. Methods We collected fecal samples from extremely preterm infants randomized to receive either early (feeding day 2) or delayed (feeding day 5) feeding progression. After study completion, we compared samples obtained at three different time points (week 1, week 2, and week 3) to determine longitudinal differences in specific taxa between the study groups using unadjusted and adjusted negative binomial and zero-inflated mixed models. Analyses were adjusted for a mode of delivery, breastmilk intake, and exposure to antibiotics. Results We analyzed 137 fecal samples from 51 infants. In unadjusted and adjusted analyses, we did not observe an early transition to higher microbial diversity within samples (i.e., alpha diversity) or significant differences in microbial diversity between samples (i.e., beta diversity) in the early feeding group. Our longitudinal, single-taxon analysis found consistent differences in the genera Lactococcus, Veillonella, and Bilophila between groups. Conclusions Differences in single-taxon analyses independent of the mode of delivery, exposure to antibiotics, and breastmilk feeding suggest potential benefits of early progression of enteral feeding volumes. However, this dietary intervention does not appear to increase the diversity of the gut microbiome in the first 28 days after birth. Trial Registration ClinicalTrials.gov identifier: NCT02915549. Impact Early progression of enteral feeding volumes with human milk reduces the duration of parenteral nutrition and the need for central venous access among extremely preterm infants. Early progression of enteral feeding leads to single-taxon differences in longitudinal analyses of the gut microbiome, but it does not appear to increase the diversity of the gut microbiome in the first 28 days after birth. Randomization in enteral feeding trials creates appealing opportunities to evaluate the effects of human milk diets on the gut microbiome.

Solid-state nanopores of on-demand dimensions and shapes can facilitate desired sensor functions. However, reproducible fabrication of arrayed nanopores of predefined dimensions remains challenging despite numerous techniques explored. Here, bowl-shaped nanopores combining properties of ultrathin membrane and tapering geometry are manufactured using a self-limiting process developed on the basis of standard silicon technology. The upper opening of the bowl-nanopores is 60–120 nm in diameter, and the bottom orifice reaches sub-5 nm. Current-voltage characteristics of the fabricated bowl-nanopores display insignificant rectification indicating weak ionic selectivity, in accordance to numerical simulations showing minor differences in electric field and ionic velocity upon the reversal of bias voltages. Simulations reveal, concomitantly, high-momentum electroosmotic flow downward along the concave nanopore sidewall. Collisions between the left and right tributaries over the bottom orifice drive the electroosmotic flow both up into the nanopore and down out of the nanopore through the orifice. The resultant asymmetry in electrophoretic–electroosmotic force is considered the cause responsible for the experimentally observed strong directionality in λ-DNA translocation with larger amplitude, longer duration, and higher frequencies for the downward movements from the upper opening than the upward ones from the orifice. Thus, the resourceful silicon nanofabrication technology is shown to enable nanopore designs toward enriching sensor applications. Stiftelsen Olle Engkvist

A substantial amount of researches have been done on the understanding and assessment of resilience from multiple perspectives, e.g., ecological, social, economic, and disaster management; however, recent international approach is trending toward more systematic and comprehensive risk assessment processes. Pivotal element of such approach is to emphasizing on promoting resilience in the face of climate change impacts. Conceptualization and identification of parameters to assess climate change resilience is one of the remaining challenges that academia is facing. Reviewing the principles of the climate change resilience highlighted in the literature, the goal of this study is to introduce a theoretical model about the climate change resilience concept to facilitate and enhance future climate change resilience-related researches. The model proposed in this study is named as the climate change resilience of place (C-CROP) model, a geo-based model which is designed to assess climate change resilience for any geographic region with an approach to the incorporation of nature-based solution (NBS). C-CROP model considers vulnerability, exposure, sensitivity to climate change on one side; another side is co-benefit, climate proofing, and disservices of proposed NBS. An operational framework of the C-CROP model is also proposed, that allows spatially explicit assessment of climate change resilience in real world by developing an indicator-based framework and comprehensive mapping using the geospatial approach. Therefore, this model includes vulnerability hotspots identification; better understanding of the pathways of resilience; and solutions (i.e., NBS) to infer the impacts and effectiveness of resilience-building interventions.