Synthesis, Cytotoxic Activity, and DNA Binding Properties of Copper (II) Complexes with Hesperetin, Naringenin, and Apigenin

Complexes of copper (II) with hesperetin, naringenin, and apigenin of general composition [CuL(2)(H(2)O)(2)] ⋅ nH(2)O (1–3) have been synthesized and characterized by elemental analysis, UV-Vis, FT-IR, ESI-MS, and TG-DTG thermal analysis. The free ligands and the metal complexes have been tested in vitro against human cancer cell lines hepatocellular carcinoma (HepG-2), gastric carcinomas (SGC-7901), and cervical carcinoma (HeLa). Complexes 1 and 3 were found to exhibit growth inhibition of SGC-7901 and HepG2 cell lines with respect to the free ligands; the inhibitory rate of complex 1 is 43.2% and 43.8%, while complex 3 is 46% and 36%, respectively. The interactions of complex 1 and its ligand Hsp with calf thymus DNA were investigated by UV-Vis, fluorescence, and CD spectra. Both complex 1 and Hsp were found to bind DNA in intercalation modes, and the binding affinity of complex 1 was stronger than that of free ligand

High-resolution cryo-electron microscopy structure of photosystem II from the mesophilic cyanobacterium, Synechocystis sp. PCC 6803

Photosystem II (PSII) enables global-scale, light-driven water oxidation. Genetic manipulation of PSII from the mesophilic cyanobacterium Synechocystis sp. PCC 6803 has provided insights into the mechanism of water oxidation; however, the lack of a highresolution structure of oxygen-evolving PSII from this organism has limited the interpretation of biophysical data to models based on structures of thermophilic cyanobacterial PSII. Here, we report the cryo-electron microscopy structure of PSII from Synechocystis sp. PCC 6803 at 1.93-Å resolution. A number of differences are observed relative to thermophilic PSII structures, including the following: the extrinsic subunit PsbQ is maintained, the C terminus of the D1 subunit is flexible, some waters near the active site are partially occupied, and differences in the PsbV subunit block the Large (O1) water channel. These features strongly influence the structural picture of PSII, especially as it pertains to the mechanism of water oxidation

Identification and mechanistic basis of non-ACE2 blocking neutralizing antibodies from COVID-19 patients with deep RNA sequencing and molecular dynamics simulations

Variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continue to cause disease and impair the effectiveness of treatments. The therapeutic potential of convergent neutralizing antibodies (NAbs) from fully recovered patients has been explored in several early stages of novel drugs. Here, we identified initially elicited NAbs (Ig Heavy, Ig lambda, Ig kappa) in response to COVID-19 infection in patients admitted to the intensive care unit at a single center with deep RNA sequencing (>100 million reads) of peripheral blood as a diagnostic tool for predicting the severity of the disease and as a means to pinpoint specific compensatory NAb treatments. Clinical data were prospectively collected at multiple time points during ICU admission, and amino acid sequences for the NAb CDR3 segments were identified. Patients who survived severe COVID-19 had significantly more of a Class 3 antibody (C135) to SARS-CoV-2 compared to non-survivors (15059.4 vs. 1412.7, p = 0.016). In addition to highlighting the utility of RNA sequencing in revealing unique NAb profiles in COVID-19 patients with different outcomes, we provided a physical basis for our findings via atomistic modeling combined with molecular dynamics simulations. We established the interactions of the Class 3 NAb C135 with the SARS-CoV-2 spike protein, proposing a mechanistic basis for inhibition via multiple conformations that can effectively prevent ACE2 from binding to the spike protein, despite C135 not directly blocking the ACE2 binding motif. Overall, we demonstrate that deep RNA sequencing combined with structural modeling offers the new potential to identify and understand novel therapeutic(s) NAbs in individuals lacking certain immune responses due to their poor endogenous production. Our results suggest a possible window of opportunity for administration of such NAbs when their full sequence becomes available. A method involving rapid deep RNA sequencing of patients infected with SARS-CoV-2 or its variants at the earliest infection time could help to develop personalized treatments using the identified specific NAbs

Research on Mid-term Review System of PPP Project

The mid-term review is a necessary window for the PPP project to move forward objectively, and it is also a tool to adjust the expected goals of all parties to the project. This paper built a mid-term review system for PPP projects based on the whole-of-life cycle, studied the objectives, content and evaluation procedures of the mid-term review of PPP projects, and took the urban and rural water supply and drainage integrated PPP project in Mianzhu city, Sichuan Province as the case for field research and interviews, to verify the feasibility of the review system. The research results have a certain guiding role for the mid-term review of PPP projects

Structural equation model-based performance measurement system for transferring PPP water projects: a China perspective

A series of performance measurement need to be carried out throughout the project life cycle to ensure the successful transfer of public-private partnership (PPP) assets and meet stakeholder needs. More and more water projects are stepping into the transfer phase, but less studies carry out in-depth and systematic discussion on the performance measurement of PPP water projects at the transfer phase. Hence, to fill this gap, this research establishes a new performance measurement system (PMS) for evaluating the performance of the PPP projects stepping into the transfer phase based on the key performance indicators (KPIs). Through case study, expert interview and questionnaire, this paper formulates the logical basis behind PPP water projects at the transfer phase and subsequently constructs the transfer performance measurement system (TPMS) of these projects. Then, it conducts a confirmatory analysis of the impact relationship between the indicators based on structural equation modeling (SEM). Findings of expert interview and questionnaire indicate that there are 7 primary and 26 secondary indicators, and the model has a good fit. The TPMS will provide governments, operators and other stakeholders with a comprehensive and complete understanding as to indicators required of an effective performance measurement of PPP water projects

Urban Expansion Assessment Based on Optimal Granularity in the Huaihe River Basin of China

Determining the optimal granularity, which has often been ignored in the analysis of urban expansion and its landscape pattern, is the core problem in landscape ecology research. Here, we calculate the optimal granularities for differently sized cities in the Huaihe River Basin of China based on scale transformation and area loss evaluation. Accordingly, we construct a landscape index and urban land density function to analyze urban expansion and landscape pattern. The results can be summarized as follows. (1) Within the first scale domain of the landscape indices, the optimal granularities of Zhengzhou, Xuzhou, Yancheng, Xinyang, and Bozhou are 60 m, 50 m, 40 m, 40 m, and 40 m, respectively, which are the optimal units in the study of urban expansion. (2) The urban land density decreases from the urban center to the outskirts, the urban core of each city is more compact than the outskirts, and the land density curve parameter α of Zhengzhou is the largest at 4.693 and its urban core the most compact. (3) There are significant spatial and temporal differences in the urban land densities of differently sized cities. The urban land density functions of different cities are similar before 2000; after that, they are similar to the standard inverse S-shaped function and the land use density curve of large cities is closer to the standard inverse S-shaped function than that of small- and medium-sized cities. (4) Large cities have faster expansion, much larger land density curve parameter c than medium- and small-cities, stronger linkage development with surrounding areas, and a higher degree of urban centralization. Urban expansion compactness was influenced by urban locations and functions except for urban sizes. This study offers a method for identifying the optimal granularities for differently sized cities and also provides information for the decision-making efforts that concern the rapid urbanization in major grain-producing areas of China

Size-differentiated REE characteristics and environmental significance of aeolian sediments in the Ili Basin of Xinjiang, NW China

Aeolian loess in the Ili Basin is an important geological archive for studying the changes in paleoclimate and sources of dust particles. Size-differentiated rare earth elements (REE) may help to distinguish potential dust sources. This study investigates the size-differentiated REE characteristics from three sites including the Zhaosu loess and the Kekdala desert sediments from the Ili Basin, and the Chaona loess from the Chinese Loess Plateau (CLP). Our results show that the patterns of variation of the REE characteristics in different size fractions can act as improved source tracers for aeolian sediments. Moreover, the REE characteristics of the < 2 mu m particles are sensitive indicators for distinguishing dust particles transported over long distances in the semi-arid areas with limited pedogenesis such as the Ili Basin. However, it should be interpreted cautiously in the CLP due to the post-depositional chemical weathering. The REE characteristics of coarse fractions are effective tracers for tracking changes in proximal dust sources and regional boundary level circulations. Our study has implications for identifying the exact source(s) of the Ili loess, which is helpful to understand paleoclimate changes and westerly circulation patterns in Central Asia