Molecular basis of signal transduction mediated by the human GIPR splice variants.

Glucose-dependent insulinotropic polypeptide receptor (GIPR) is a potential drug target for metabolic disorders. It works with glucagon-like peptide-1 receptor and glucagon receptor in humans to maintain glucose homeostasis. Unlike the other two receptors, GIPR has at least 13 reported splice variants (SVs), more than half of which have sequence variations at either C or N terminus. To explore their roles in endogenous peptide-mediated GIPR signaling, we determined the cryoelectron microscopy (cryo-EM) structures of the two N terminus-altered SVs (referred as GIPR-202 and GIPR-209 in the Ensembl database, SV1 and SV2 here, respectively) and investigated the outcome of coexpressing each of them in question with GIPR in HEK293T cells with respect to ligand binding, receptor expression, cAMP (adenosine 3,5-cyclic monophosphate) accumulation, ß-arrestin recruitment, and cell surface localization. It was found that while both N terminus-altered SVs of GIPR neither bound to the hormone nor elicited signal transduction per se, they suppressed ligand binding and cAMP accumulation of GIPR. Meanwhile, SV1 reduced GIPR-mediated ß-arrestin 2 responses. The cryo-EM structures of SV1 and SV2 showed that they reorganized the extracellular halves of transmembrane helices 1, 6, and 7 and extracellular loops 2 and 3 to adopt a ligand-binding pocket-occupied conformation, thereby losing binding ability to the peptide. The results suggest a form of signal bias that is constitutive and ligand-independent, thus expanding our knowledge of biased signaling beyond pharmacological manipulation (i.e., ligand specific) as well as constitutive and ligand-independent (e.g., SV1 of the growth hormone-releasing hormone receptor).

Photocatalytic water splitting for hydrogen production with high efficiency monolayer In2Te5: a theoretical study.

Employing density functional theory (DFT) calculations, we explore the excellent performance of two-dimensional (2D) semiconductor In2Te5 in photocatalytic water splitting at the theoretical level. The calculated results illustrate that 2D In2Te5 is a direct band gap semiconductor with a moderate band gap value and an ultrahigh optical absorption coefficient in the visible light region. It was found that its conduction band edge is higher than the reduction potential of water (-4.44 eV), which proves that it can split water to produce hydrogen. Furthermore, its excellent hydrogen evolution activity can be tuned under an appropriate biaxial strain. In addition, 2D In2Te5 shows a remarkable photo-generated current, suggesting that electrons and holes can be separated efficiently. Our results offer a superior candidate material for realizing photocatalytic water splitting for hydrogen evolution.

Systematic Identification of Proteins Binding with Cisplatin in Blood by Affinity Chromatography and a Four-Dimensional Proteomic Method.

Cisplatin is widely used for the treatment of various solid tumors. It is mainly administered by intravenous injection, and a substantial amount of the drug will bind to plasma proteins, a feature that is closely related to its pharmacokinetics, activity, toxicity, and side effects. However, due to the unique properties of platinum complexes and the complexity of the blood proteome, existing methods cannot systematically identify the binding proteome of cisplatin in blood. In this study, high-abundance protein separation and an ion mobility mass spectrometry-based 4D proteomic method were combined to systematically and comprehensively identify the binding proteins of cisplatin in blood. The characteristic isotope patterns of platinated peptides and a similarity algorithm were utilized to eliminate false-positive identification. Finally, 39 proteins were found to be platinated. Bioinformatics analysis showed that the identified proteins were mainly involved in the complement and coagulation cascade pathways. The binding ratio of some peptides with cisplatin was measured based on the area ratio of the free peptide using the parallel reaction monitoring method. This study provides a new method for systematically identifying binding proteins of metal drugs in blood, and the identified proteins might be helpful for understanding the toxicity of platinum anticancer drugs.

Funding of health professional education: China's 20-year process and a global comparison.

CONTEXT: Funding is an essential requirement for ensuring the quality of health professional education worldwide. Adequate funding is of immense significance in training health professionals. Due to the difficulty of accessing relevant data, quantitative research of the kind is scarce. OBJECTIVES: This study aims at analysing the trends of funding levels and funding sources for health professional institutions in China spanning the past 20 years and making a global comparison. METHODS: We used data from Ministry of Education (MOE) of the People's Republic of China to analyse its funding level and structure of funding sources of health professional education in China during 1998-2017. When analysing funding level, we used two indicators: total funding and funding per student. We chose the United States, and analysed its funding level and structure to allow easy comparison to the situation in China. The data from a Lancet report (Lancet, 376, 2010, 1923) were also used to analyse global funding status to make an international comparison. RESULTS: Funding levels of health professional institutions in China has increased significantly in the past 20 years, while the average annual growth rate of funding per student (4.5%) is lower than that of total funding (19.9%). In terms of the structure of funding sources, fiscal appropriation accounts for 51.1% on average, and tuition, fees and scientific research income explains 37.0%. CONCLUSION: From 1998 to 2017, the total funding and funding per student of HPE in China increased continuously, and the total funding increased at a faster rate. The increase in funding of HPE in China is closely related to the efforts of the Chinese government and the implementation of relevant policies. Even so, funding of HPE in China is likely to remain relatively low compared to other countries.

Ego-Lane Index Estimation Based on Lane-Level Map and LiDAR Road Boundary Detection.

Correct ego-lane index estimation is essential for lane change and decision making for intelligent vehicles, especially in global navigation satellite system (GNSS)-challenged environments. To achieve this, we propose an ego-lane index estimation approach in an urban scenario based on particle filter (PF). The particles are initialized and propagated by dead reckoning with inertial measurement unit (IMU) and odometry. A lane-level map is used to navigate the particles taking advantage of topologic and geometric information of lanes. GNSS single-point positioning (SPP) can provide position estimation with meter-level accuracy in urban environments, which can limit drift introduced by dead reckoning for updating the weight of each particle. Light detection and ranging (LiDAR) is a common sensor in an intelligent vehicle. A LiDAR-based road boundary detection method provides distance measurements from the vehicle to the left/right road boundaries, which provides a measurement for importance weighting. However, the high precision of the LiDAR measurements may put a tight constraint on the distribution of particles, which can lead to particle degeneration with sparse particle sets. To deal with this problem, we propose a novel step that shifts particles laterally based on LiDAR measurements instead of importance weighting in the traditional PF scheme. We tested our methods on an urban expressway at a low traffic volume period to ensure road boundaries can be detected by LiDAR measurements at most time steps. Experimental results prove that our improved PF scheme can correctly estimate ego-lane index at all time steps, while the traditional PF scheme produces wrong estimations at some time steps.

Information technology solutions, challenges, and suggestions for tackling the COVID-19 pandemic.

Various technology innovations and applications have been developed to fight the coronavirus pandemic. The pandemic also has implications for the design, development, and use of technologies. There is an urgent need for a greater understanding of what roles information systems and technology researchers can play in this global pandemic. This paper examines emerging technologies used to mitigate the threats of COVID-19 and relevant challenges related to technology design, development, and use. It also provides insights and suggestions into how information systems and technology scholars can help fight the COVID-19 pandemic. This paper helps promote future research and technology development to produce better solutions for tackling the COVID-19 pandemic and future pandemics.

Butterfly Wing Hears Sound: Acoustic Detection Using Biophotonic Nanostructure.

The biophotonic nanostructures of Morpho butterfly wing display iridescent colors through the combined effect of light diffraction and interference. These nanostructures have attracted wide attention due to their high optical sensitivity and deformable material properties and have been applied to various infrared (IR), volatile organic compound (VOC), and pH sensors. This work explores the application of such biophotonic nanostructures of butterfly wing for acoustic detection and voice recognition. The pressure variation of the acoustic waves induces the vibration of butterfly wing diaphragm, resulting in the periodic change of reflectance. The integrated butterfly wing-based acoustic sensor shows high fidelity in replicating the original acoustic signals. The sensor also demonstrates promise in distinguishing human voices, which provides an alternative approach for voice recognition.

Piezoelectric Transducer-Based Structural Health Monitoring for Aircraft Applications.

Structural health monitoring (SHM) is being widely evaluated by the aerospace industry as a method to improve the safety and reliability of aircraft structures and also reduce operational cost. Built-in sensor networks on an aircraft structure can provide crucial information regarding the condition, damage state and/or service environment of the structure. Among the various types of transducers used for SHM, piezoelectric materials are widely used because they can be employed as either actuators or sensors due to their piezoelectric effect and vice versa. This paper provides a brief overview of piezoelectric transducer-based SHM system technology developed for aircraft applications in the past two decades. The requirements for practical implementation and use of structural health monitoring systems in aircraft application are then introduced. State-of-the-art techniques for solving some practical issues, such as sensor network integration, scalability to large structures, reliability and effect of environmental conditions, robust damage detection and quantification are discussed. Development trend of SHM technology is also discussed.

[Study on the Application and Classifcation of the Laparoscopy Pouch].

With the development of minimally invasive surgery, many open surgery has been replaced by intracavity surgery. In laparoscopic surgery, an electric fibroid morcellator must be used to remove large tissue specimens from a small abdominal incision. Of course, there are some complications in the use, in order to follow the principle of no tumor, the doctor used the laparoscopic pouch in clinical operation to reduce the risk of spreading potential tumor tissue. There are various kinds of pouches, which are classified according to their existing state before use, it can be classified into two categories:overlapping and non-overlapping. The advantages and disadvantages of different bags and pockets are also analyzed. It provides a theoretical basis for technological innovation and equipment improvement.

Improved Seam-Line Searching Algorithm for UAV Image Mosaic with Optical Flow.

Ghosting and seams are two major challenges in creating unmanned aerial vehicle (UAV) image mosaic. In response to these problems, this paper proposes an improved method for UAV image seam-line searching. First, an image matching algorithm is used to extract and match the features of adjacent images, so that they can be transformed into the same coordinate system. Then, the gray scale difference, the gradient minimum, and the optical flow value of pixels in adjacent image overlapped area in a neighborhood are calculated, which can be applied to creating an energy function for seam-line searching. Based on that, an improved dynamic programming algorithm is proposed to search the optimal seam-lines to complete the UAV image mosaic. This algorithm adopts a more adaptive energy aggregation and traversal strategy, which can find a more ideal splicing path for adjacent UAV images and avoid the ground objects better. The experimental results show that the proposed method can effectively solve the problems of ghosting and seams in the panoramic UAV images.

Population pharmacokinetic analysis of tacrolimus early after Chinese pediatric liver transplantation.

OBJECTIVE: The purpose of this study was to describe the population pharmacokinetics (PK) of tacrolimus (TAC) in 52 Chinese pediatric patients early after liver transplantation. METHODS: Details of drug dose, sampling times and concentrations were collected retrospectively from routine therapeutic drug monitoring data from the first day after surgery. A total of 488 concentration data were obtained and analyzed by a nonlinear mixed-effect modeling (NONMEM) method. A number of demographic and clinical variables were tested for their influence on TAC PK parameters. RESULTS: The PK of TAC were best described by a one-compartment model with first-order absorption and elimination. Apparent clearance (CL/F) and apparent volumes of distribution (V/F) in final population model were 5.72 L/h and 131 L, respectively. The absorption rate constant (Ka) was fixed in 4.48 h-1. The inter-individual variabilities in CL/F and V/F were 13.5% and 78.1%. In the final analysis performed in all 52 patients, the post-operation day (POD) and alanine aminotransferase (ALT) influenced TAC CL/F and V/F, and total protein (TP) was the only covariate retained on V/F. CONCLUSION: A population PK model of TAC was developed in Chinese pediatric patients early after liver transplantation. It identified significant relationships between the PK of TAC and the characteristics of the patients. POD, ALT, and TP were identified as the main factors influencing the PK of TAC. The developed model could be useful to optimize individual pediatric TAC dosing regimen in routine clinical practice.

Pulmonary alveolar microlithiasis combined with gastric mucosal calcification: a case report.

Background: Pulmonary alveolar microlithiasis (PAM) is a rare disease whose clinical and imaging manifestations are non-specific, characterized by the deposition of microliths, which primarily consist of calcium and phosphorus, within the alveoli. In the cases of PAM, patients combined with calcification of other organs such as gastric mucosal calcification are less common. Case presentation: A 59-year-old woman was admitted to our hospital due to cough producing white, foamy sputum, accompanied by dyspnea and fever for 20 days. The CT scan showed diffuse ground-glass opacities and calcification of the gastric mucosa. Lung tissue biopsy revealed the presence of calcification and granulomatous foreign bodies in the interstitium and alveolar cavity. In the later stages, she developed painful skin petechiae. For this patient, the diagnosis of PAM, gastric mucosal calcification, and purpura fulminans was made. However, the genetic test results hinted that the patient and her son had a heterozygous mutation in the FBN1 gene, but her daughter's genetic test results were normal. Although the patient received anti-infection treatment, steroids, and oxygen therapy, her condition did not improve. Conclusion: We reported a rare case of PAM combined with calcification of other organs and purpura fulminans. Treatment of steroids did not show any benefit. The causative mechanism and effective treatment of this disease remain unclear. More treatments need to be explored.

Visible-light-driven photoelectrochemical sensor based on conjugated microporous polymer-grafted graphene for o-aminophenol detection.

The pollutant o-aminophenol (o-AP) presents considerable risk to environmental safety, and its detection is therefore critical. Although various optical and electrochemical methods have been proposed for the detection of o-AP, there are a limited number of detection methods based on photoelectrochemical (PEC) sensors. In this study, a sensitive visible-light-driven PEC sensor was developed for o-AP detection in water. A conjugated microporous polymer (CMP)-coated graphene heterostructure (CMP-rGO) was synthesized and used to develop a PEC sensor. Under optimal conditions, the proposed sensor exhibited a high sensitivity of 0.03 µM with a wide linear range of 0.0034-37.6 µM. The PEC sensor also displayed acceptable repeatability and reproducibility, good long-term stability, and excellent recovery (98-102%). In addition, the binding patterns of CMP to o-AP and o-AP analog molecules were analyzed by molecular docking. Therefore, this study provides a new and feasible PEC sensor-based detection scheme for o-AP detection.

Iodine-doped carbon nanotubes boosting the adsorption effect and conversion kinetics of lithium-sulfur batteries.

Compared with lithium-ion batteries (LIBs), lithium-sulfur batteries (LSBs), based on electrochemical reactions involving multi-step 16-electron transformations provide higher specific capacity (1672 mAh g-1) and specific energy (2600 Wh kg-1), exhibiting great potential in the field of energy storage. However, the inherent insulation of sulfur, slow electrochemical reaction kinetics and detrimental shuttle-effect of lithium polysulfides (LiPSs) restrict the development of LSBs in practical applications. Herein, the iodine-doped carbon nanotubes (I-CNTs) is firstly reported as sulfur host material to the enhance the adsorption-conversion kinetics of LSBs. Iodine doping can significantly improve the polarity of I-CNTs. Iodine atoms with lone pair electrons (Lewis base) in iodine-doped CNTs can interact with lithium cations (Lewis acidic) in LiPSs, thereby anchoring polysulfides and suppressing subsequent shuttling behavior. Moreover, the charge transfer between iodine species (electron acceptor) and CNTs (electron donor) decreases the gap band and subsequently improves the conductivity of I-CNTs. The enhanced adsorption effect and conductivity are beneficial for accelerating reaction kinetics and enhancing electrocatalytic activity. The in-situ Raman spectroscopy, quasi in-situ electrochemical impedance spectroscopy (EIS) and Li2S potentiostatic deposition current-time (i-t) curves were conducted to verify mechanism of complex sulfur reduction reaction (SRR). Owing to above advantages, the I-CNTs@S composite cathode exhibits an ultrahigh initial capacity of 1326 mAh g-1 as well as outstanding cyclicability and rate performance. Our research results provide inspirations for the design of multifunctional host material for sulfur/carbon composite cathodes in LSBs.

Surface heterojunction based on n-type low-dimensional perovskite film for highly efficient perovskite tandem solar cells.

Enhancing the quality of junctions is crucial for optimizing carrier extraction and suppressing recombination in semiconductor devices. In recent years, metal halide perovskite has emerged as the most promising next-generation material for optoelectronic devices. However, the construction of high-quality perovskite junctions, as well as characterization and understanding of their carrier polarity and density, remains a challenge. In this study, using combined electrical and spectroscopic characterization techniques, we investigate the doping characteristics of perovskite films by remote molecules, which is corroborated by our theoretical simulations indicating Schottky defects consisting of double ions as effective charge dopants. Through a post-treatment process involving a combination of biammonium and monoammonium molecules, we create a surface layer of n-type low-dimensional perovskite. This surface layer forms a heterojunction with the underlying 3D perovskite film, resulting in a favorable doping profile that enhances carrier extraction. The fabricated device exhibits an outstanding open-circuit voltage (VOC) up to 1.34 V and achieves a certified efficiency of 19.31% for single-junction wide-bandgap (1.77 eV) perovskite solar cells, together with significantly enhanced operational stability, thanks to the improved separation of carriers. Furthermore, we demonstrate the potential of this wide-bandgap device by achieving a certified efficiency of 27.04% and a VOC of 2.12 V in a perovskite/perovskite tandem solar cell configuration.

Nonselective Intercalation of G-Quadruplex-Targeting Ligands into Double-Stranded DNA Quantified by Single-Molecule Stretching.

Most G-quadruplex (G4)-targeting ligands reported so far contain planar heteroaromatic groups and can intercalate into adjacent base pairs of double-stranded DNA (dsDNA). However, quantitative data on the binding number γ (ligands/bp) of G4 ligands that intercalate into long dsDNA remain lacking, which are essential for understanding the selectivity of G4 ligands. Here, using a single-molecule stretching assay based on the lengthening of dsDNA, we analyzed the dissociation constants and the binding number of eight most commonly used G4 ligands that intercalate into dsDNA. We showed that five ligands (CX-5461, BRACO-19, RHPS4, TrisQ, and Phen-DC3) intercalate into dsDNA avidly (Kd = 0.5-2.1 µM, saturated γ > 0.2 ligands/bp), which was similar to the typical dsDNA intercalator EB. Two bisquinolines, PDS and 360A, showed moderate intercalation ability (Kd = 22.5 and 48.7 µM) and γ < 0.01 ligands/bp in the presence of 1 µM ligands. Porphyrin NMM showed no intercalative binding even at 200 µM. Molecular docking and molecular dynamics simulations were carried out to further evaluate the intercalative binding of these G4 ligands with dsDNA by calculating the binding energies and π-π stacking probability.

Role of antenatal anxiety in the relationship between maternal exposure to nitrogen dioxide and small for gestational age: A birth cohort study.

BACKGROUND: Both Nitrogen dioxide (NO2) exposure and antenatal anxiety have individually been associated with small for gestational age (SGA). Little is known, however, about whether there is effect modification of antenatal anxiety on NO2-related SGA. METHODS: The prospective birth cohort study included 1823 mother-newborn pairs in Guangzhou, China, from January 2017 to April 2020. Exposure to NO2 during the pre-conceptional and prenatal periods was estimated using an inverse distance weighted method. Antenatal anxiety was assessed by Trait Anxiety Inventory. SGA was determined by the Chinese gestational age- and sex-specific birthweight standards. Cox proportional hazards regression models was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for SGA as per 10 µg/m3 increase in NO2. Modifying effects of trait anxiety on NO2-related SGA were identified by stratified analyses, and three-dimensional response surface plots and two-dimensional heat maps. RESULTS: Each 10 µg/m3 increase in NO2 exposure during the third trimester was significantly associated with SGA risk among overall participants (HR = 1.221, 95 % CI: 1.014-1.471) and primipara (HR = 1.271, 95 % CI: 1.023-1.579). We found significant effect modification of anxiety level for NO2-related SGA in the third trimester (Pinteraction < 0.05). Pregnant women with higher levels of trait anxiety were more likely to deliver SGA newborns, particularly for those with high trait anxiety (HR = 1.781, 95 % CI: 1.007-2.945). Primiparous women were more susceptible. CONCLUSIONS: This study provides evidence that antenatal trait anxiety may modify the effects of maternal NO2 exposure on SGA risk. The third trimester could be a critical window of susceptibility.

Bis{1-[(1H-benzotriazol-1-yl)meth-yl]-2-methyl-1H-imidazole-κN(3)}dichlorido-cobalt(II).

In the title mononuclear complex, [CoCl(2)(C(11)H(11)N(5))(2)], the Co(II) atom is four-coordinated by two ligand N atoms and two Cl atoms in a distorted tetra-hedral geometry. In the crystal, mol-ecules are stacked through π-π inter-actions [centroid-centroid distances = 3.473 (2), 3.807 (3), 3.883 (2) and 3.676 (2) Å], forming a three-dimensional supra-molecular network.

Configuration of prosocial motivations to enhance employees' innovation behaviors: From the perspective of coupling of basic and applied research.

Prosocial motivation refers to the employees' willingness to invest for the sake of helping others. It improves basic and applied research behaviors of employees and the interaction between them. Employees' innovation behavior depends on prosocial motivation because the motivation to protect the interests of others may promote knowledge sharing and knowledge coupling. However, there is a research gap in solving the optimal solution of prosocial motivations that facilitates different types of innovation behaviors based on the combination of prosocial motivations. We perform a qualitative comparative study on the effect of the motivation configurations on innovation behaviors. We find that highly basic and highly applied research behaviors share in common collectivism-based, principlism-based, contextual, and situational motivations which work in all configurations. But the core conditions between the two are different, which are principlism-based and situational motivations, respectively. In addition, both highly basic-to-applied and highly applied-to-basic transformation behaviors share the same core condition and the same secondary conditions with highly basic and highly applied research behaviors, respectively. Moreover, the behaviors of non-highly basic research and non-highly basic-to-applied transformation share the severe absence of egoism-based motivation as the core condition in common. Non-highly behaviors of applied research and applied-to-basic transformation have a common point of the severe absence of the pressure-based type as the key. Finally, we also analyze active and passive prosocial degrees of all types of high/non-high innovation behaviors. Our study deepens the academics' thinking on multi-dimensional prosocial motivation and the classification management of coupling innovation behavior and provides implications for practice.

Impacts of Corporate Social Responsibility on Employees' Mental Fatigue: Employees' Ethical Perspective.

With the rise of cost of living and coronavirus disease 2019 (COVID-19) global pandemic therewithal, finding reliable measures to reduce employees' mental fatigue has become a great challenge. In this context, scholars have mainly focused on solutions for relieving employees' mental fatigue from the perspective of human resource management but barely from employees' ethical perspectives and that of internal and external corporate social responsibility (CSR) and employees' ethics. This study uses hierarchical regression analysis and attempts to formulate and analyze the relationship between CSR, perceptions of corporate hypocrisy, and employees' mental fatigue along with the mediating role of ethical egoism and altruistic choice. It also conceptualizes models and develops various hypotheses and theoretical logic. A total of 250 questionnaires were distributed, and 176 valid responses were subsequently gathered. The results show that employees' mental fatigue significantly reduces when either internal or external CSR has a positive impact on employees' altruistic choice and significantly increases either internal or external CSR has a negative effect on ethical egoism. Similarly, reducing perceptions of corporate hypocrisy can enhance the positive impact of external CSR on altruistic choice, which consequently reduces employees' mental fatigue.