Insulin icodec of Novo Nordisk is a novel long-acting insulin analogue that exhibits an extended duration of action, providing a promising treatment option for individuals with diabetes. It has been reported that the incorporation of fatty acid moieties into insulin icodec plays a crucial role in its prolonged action, as these fatty acid chains facilitate the formation of stable hexameric structures, thereby delaying insulin absorption and promoting sustained release. Yet, the underlying biophysics still is elusive of the roles of the three site-specific mutations (Y14A\_E, Y37B\_H, F46B\_H) of insulin icodec in its prolonged activity. Thus, through a comprehensive structural and biophysical analysis of the insulin (both native and icodec) structures bound to its receptor, this article delves deep into the biophysics underlying the molecular design of insulin icodec, and identified a delicate biophysical mechanism through which two missense mutations of insulin icodec (Y37B\_H and F46B\_H) contribute to its prolonged duration of action. Overall, this structural and biophysical investigation provides valuable insights into the mechanisms underlying the relationship between three site-specific mutations and prolonged duration of action of insulin icodec, while understanding these modifications at a structural and biophysical level can aid in the rational design of future long-acting insulin analogues, offering further enhanced therapeutic options for diabetic patients.

Intermolecular interactions are the fabrics underlying almost all processes in living organisms, where two cornerstone concepts, intermolecular binding affinity (K d ) and binding energy (ΔG), have long been established to physically describe the strengths of biomolecular interactions, e.g., drug-target K d and ΔG to describe the strength of drug-target interaction. The past two-three years saw a big step forward in the use of artificial intelligence (AI) in structural biology (e.g., AlphaFold for protein structure prediction) and drug discovery & design. In light of the roles of K d and ΔG in drug discovery & design, the speed of this AI progress raises a question of what’s next for its practical application in the pharmaceutical industry, in addition to a system-wide account of biomolecular structures and motions. Last August, the concept of a general intermolecular binding affinity calculator (GIBAC) was for the first time coined and proposed in an MDPI-published preprint. Here, this article puts forward an updated conceptual and practical framework of GIBAC, including its inception, definition, construction, practical applications, technical challenges and limitations, and future directions. Moreover, this article argues that the time is now ripe for the construction of such an accurate, precise and efficient GIBAC to be on the agenda of the entire drug discovery & design community, to ensure its applicability & reliability, and to enhance its value in drug R&D in future.

Since the launch of Protein Data Bank (PDB) in 1971, Cartesian coordinate system (CCS) has been the default approach to specify atomic positions in biomolecular experimental structures with X, Y and Z. In 2020, a local spherical coordinate system (LSCS) approach was proposed as an alternative to CCS, i.e., ρ, θ and φ. Recently, the continued application of deep learning technology in protein structure prediction (PSP) saw a leap forward in the accuracy of PSP, as evidenced by AlphaFold of Google’s DeepMind. However, there still is room for the improvement of the performances of PSP algorithms to date. Given that geometrically, CCS and LSCS are like the two sides of a coin, this short article puts forward a hypothesis that the time is now ripe to end the half-a-century burial of ρ, θ and φ in PDB, and use them as LSCS features for the design of novel PSP algorithms in future.

Semaglutide is a glucagon-like peptide 1 analog used for the treatment of patients with type 2 diabetes mellitus. With 94% sequence similarity to human GLP-1, semaglutide is a glucagon-like peptide-1 receptor (GLP-1R) agonist, which binds directly to GLP-1R, causing various beneficial downstream effects that reduce blood glucose. Practically, it is favourable for semaglutide to bind not just directly, but also tighter, to its receptor GLP-1R. Therefore, incorporating currently available experimental structural data of semaglutide-GLP-1R, this short article reports for the first time that biophysically, semaglutide is able to bind tighter to GLP-1R with just a simple Val27-Arg28 exchange in its peptide backbone.

Insulin lispro was the first fast acting insulin analogue to obtain regulatory approval for therapeutic use. This article puts forward a novel biophysical mechanism where the net impact of the simple B28Pro-B29Lys exchange from regular insulin to insulin lispro is the establishment of a novel set of interfacial electrostatic interactions between Lys28 of insulin lispro and Asp12 of insulin receptor (IR). In addition, a set of structural analysis was presented in this article to further strengthen the binding of insulin lispro to IR, where two polar amino acid residues (Gln51 and Asn74 of insulin lispro) were put forward as two potential targets for site-directed mutagenesis of insulin lispro at its binding interface with IR.

One notable features of the SARS-CoV-2 genome is that the spike protein of SARS-CoV-2 has a functional polybasic (furin) cleavage site (RRAR) at the S1–S2 boundary through the insertion of 12 nucleotides encoding PRRA. To date, the furin cleavage site (FCS) remains an experimentally uncharted territory both structurally and functionally. For instance, whether or not FCS is actually cleaved, before or after viral cell entry or exit, still remains to be experimentally investigated. With currently available structural data, this article presents a computational structural characterization of the FCS inserted into SARS-CoV-2 spike glycoprotein, and puts forward a set of structural hypothesis against the hypothesis of SARS-CoV-2 from purposeful manipulation: (1), the inserted FCS does not alter, neither stabilize nor de-stabilize, the overall structure of SARS-CoV-2 spike glycoprotein; (2), the net structural consequence of FCS is the insertion of a furin cleavage site into SARS-CoV-2 spike glycoprotein, whose S1 and S2 subunits will still be bonded together even if the FCS is actually cleaved by furin protease.

Protein is the proteios building block of life. Evolutionarily, its sequence is not as conserved as its structure, making it more reasonable for protein structure, instead of protein sequence, to be the descriptor of protein function. Yet, in the National Center for Biotechnology Information (NCBI) database, the number of experimentally identified protein sequences is in great excess of that of experimentally determined protein structures inside the almost-half-a-century old Protein Data Bank (PDB). For instance, GPR151 is an proton-sensing G-protein coupled receptor (GPCR) originally identified as homologous to galanin receptors. As of March 19, 2020, GPR151’s structure has not been experimentally determined and deposited in PDB yet. Thus, an ab initio modelling approach was employed here to build a three-dimensional structure of GPR151. Overall, the ab initio GPR151 model presented herein constitutes the first structural hypothesis of GPR151 to be experimentally tested in future with previously published, currently ongoing and future GPR151 studies.

Ebolavirus has a membrane envelope decorated by trimers of a glycoprotein (GP), which is responsible for host cell attachment and membrane fusion. Therefore, GP is a primary target for antiviral drugs development. Here, this article reports the first, to my knowledge, set of structural analysis of all Ebolavirus GP structures as of March 10, 2020, and also a brief update of the structurally identified electrostatic features of the Ebolavirus GP structures in both apo (unliganded) state and also in bound states with a series of small compounds, including a variety of approved drugs. With this comprehensive set of structural analysis, this article puts forward a hypothesis of two Achilles' heels of Ebolavirus GP structure, where the formation of two interfacial salt bridges, instead of destabilizing the prefusion conformation of Ebolavirus GP, constitutes a positive contribution towards the structural rigidification of the prefusion conformation of the Ebolavirus GP structure, thereby acting against GP-mediated Ebolavirus cell entry and/or preventing fusion between the viral and endosome membranes.

Since the Coronavirus disease (COVID-19) outbreak at the end of 2019, the past two month has seen an acceleration both in and outside China in the R&D of the diagnostics, vaccines and therapeutics for this novel coronavirus. As one of the molecular forces that determine protein structure, electrostatic effects dominate many aspects of protein behaviour and biological function. Thus, incorporating currently available experimental structures related to COVID-19, this article reports a simple python-based analysis tool and a LaTeX-based editing tool to extract and summarize the electrostatic features from experimentally determined structures, to strengthen our understanding of COVID-19's structure and function and to facilitate machine-learning and structure-based computational design of its neutralizing antibodies and/or small molecule(s) as potential therapeutic candidates. Finally, this article puts forward a brief update of the structurally observed electrostatic features of the COVID-19 coronavirus.

The importance of antibodies in health care and the biotechnology research and development demands not only knowledge of their experimental structures at high resolution, but also practical implementation of this knowledge for both effective and efficient design and production of antibody for its use in both medical and research applications. While the experimental wet-lab approach is usually costly, laborious and time-consuming, computational (dry-lab) approaches, in spite of their intrinsic limitations in comparison with its experimental (wet-lab) counterpart, provide a cheaper and faster alternative option. For the first time, this article reports a comprehensive set of structural electrostatic features extracted from experimentally determined antigen-antibody-related structures, including especially those structural electrostatic features at the interfaces of all experimentally determined antigen-antibody complex structures as of February 29, 2020, to facilitate effective and efficient machine learning-based computational antibody design using currently available experimental structures inside Protein Data Bank.

The spike protein of SARS coronavirus (SARS-CoV) attaches the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2), which is mediated by the receptor binding domain (RBD) of the spike protein. Recently, an analysis based on decade-long structural studies of SARS was reported to illustrate with atomic-level details receptor recognition by the novel coronavirus from Wuhan, i.e., 2019-nCoV. Here, this article reports a comprehensive set of structural electrostatic analysis of all SARS-CoV spike protein RBD-related structures as of February 13, 2020, aiming at identifying the electrostatic hot spots for SARS-CoV spike protein to be complexed with ACE2 and its neutralizing antibodies. First, this article identified a structural action mechanism of the F26G19 antibody (of SARS-CoV spike protein), where its Asp56 residue binds to the Arg426 of the SARS-CoV spike protein RBD against the formation of the interfacial Arg426-Glu329 salt bridges between ACE2 and the SARS-CoV spike protein RBD. Second, a hypothesis is reported that a pair of electrostatic clips exist at the interface between ACE2 and the SARS-CoV spike protein RBD, including both Arg426-Glu329 and His445-Glu23-Lys447 salt bridges. Last, this article reports a structurally identified interfacial Glu35-Arg479 salt bridge which helps stabilize the complex structure of ACE2 and the SARS-CoV spike protein RBD. Overall, the structurally identified electrostatic hot spots reported here may be useful for the design of SARS-CoV-neutralizing antibodies in future.

For voltage-gated Ca2+ channel (VGCC), its α2δ subunits are traditionally considered to be auxiliary subunits that regulates VGCC trafficking to the plasma membrane. The antiepileptic, antinociceptive and anxiolytic gabapentin (GBP) has previously been shown to bind the VGCC α2δ subunits with high affinity to disrupt VGCC trafficking. Yet, the interaction between GBP and α2δ still remains poorly understood from a structural point of view. For instance, it is not clear yet what the structural implication is of α2δ-1-bound GBP against VGCC trafficking. With a set of experimental data-driven structural analysis of the VGCC α2δ-1 and its ligand GBP, this article postulates for the first time that: 1), α2δ-1 bound GBP stabilizes the α2δ-1-GBP complex structure; 2), α2δ-1 bound GBP restrains the conformational flexibility of α2δ-1; 3), α2δ-1-bound GBP establishes an electrostatic axis consisting of Q535 (Gln535)-R241 (Arg241)-GBP (gabapentin)-D452 (Asp452), which constitutes an energetically favourable contribution towards the structural stability of the α2δ-1-GBP complex and helps restrains the conformational flexibility and local structural rigidification of α2δ-1; and 4), GBP-induced local conformational inflexibility and structural rigidification of α2δ-1 is one key step in the pharmacological disruption of VGCC trafficking by GBP.

As of today, there is not any direct report yet of the degree to which missing residues exist for experimentally determined membrane protein (MP) structures, which constitute more than half of current drug targets. With a chain- and position-specific visualisation and a statistical analysis of all MP structures inside PDB (as of September 25, 2019), this article argues that the experimentally uncharted territories (EUTs, i.e., consisting of missing residues) within PDB are pluggable and should be plugged with an experimental data-driven hybrid approach, and calls for continued development of MP structural determination with less and less EUTs, in light of MPs' crucial role in biological and biomedical research, both fundamental and pharmaceutical.

To date, Cartesian (x, y, z) coordinate system (CCS) has been the default approach to geometrically specify atomic spatial positions in protein structures since the launch of Protein Data Bank (PDB) in 1971. To this end, this paper proposes a local spherical coordinate system (SCS) approach as an alternative to the default approach and a previously reported global SCS approach. The local SCS approach here requires only two parameters (θ and φ), instead of x, y and z as required by the default CCS approach. Essentially, CCS and SCS are like the two sides of one coin, i.e., geometric coordinate system for three-dimensional position specification. Therefore, this paper furthermore argues that it is time to flip the coin over, and have a look at the other side of the coin, e.g., the local SCS approach, which possesses an intrinsically lower degree of descriptional complexity than that of the default CCS approach, and constitutes a potentially useful alternative perspective for all protein structural research field.

PD-1/PD-L1 axis is one key therapeutic target against tumor cell immune escape. Structurally essential to the PD-1/PD-L1-linked immune escape is the binding interface of the PD-1/PD-L1 complex structure. Incorporating currently available PD-1/PD-L1-related experimental structures, this article unveils two sets of experimentally observed inter-molecular electrostatic interactions which stabilize the binding interface of the PD-1/PD-L1 complex structure. For the first time, this article proposes an evolutionary structural hypothesis that, as a result of natural selection, PD-1 is able to genetically mutate itself to structurally disrupt the PD-1/PD-L1 axis towards the restoration of T cell-mediated anti-tumor immunity.

The biomimetic design of engineering structures is based on biological structures with excellent mechanical properties, which are the result of billions of years of evolution. However, current biomimetic structures, such as ordered lattice materials, are still inferior to many biological materials in terms of structural complexity and mechanical properties. For example, the structure of \textit{Euplectella aspergillum}, a type of deep-sea glass sponge, is an eye-catching source of inspiration for biomimetic design; however, guided by scientific theory, how to engineer structures surpassing the mechanical properties of \textit{E. aspergillum} remains an unsolved problem. The lattice structure of the skeleton of \textit{E. aspergillum} consists of vertically, horizontally, and diagonally oriented struts, which provide superior strength and flexural resistance compared with the conventional square lattice structure. Herein, the structure of \textit{E. aspergillum} was investigated in detail, and by using the theory of elasticity, a lattice structure inspired by the bionic structure was proposed. The mechanical properties of the sponge-inspired lattice structure surpassed the sponge structure under a variety of loading conditions, and the excellent performance of this configuration was verified experimentally. The proposed lattice structure can greatly improve the mechanical properties of engineering structures, and it improves strength without much redundancy of material. This study achieved the first surpassing of the mechanical properties of an existing sponge-mimicking design. This design can be applied to lattice structures, truss systems, and metamaterial cells.

Nature-based solutions (NbS) rapidly develop globally to address societal challenges and provide human well-being and biodiversity. Watershed restoration plays an essential role in enhancing the ecological and socio-economic benefits of the region. The design and implementation of watershed restoration projects play a crucial role in their effectiveness, and NbS has been applied as a concept in ecosystem-related projects. This paper provides an idea to evaluate the design or implementation of watershed restoration projects based on the eight criteria proposed by the IUCN Global Standard for Nature-Based Solutions and to adjust the projects based on the evaluation results. The aim is to standardize the implementation process of watershed restoration projects to achieve more significant benefits and practically apply the concept of NbS in watershed restoration. implementation scheme of the Shan-Shui Initiative in the Jiulong River Watershed and concludes that the method is feasible in evaluating and improving the design and implementation scheme of ecological restoration projects in the actual basin. According to the assessment results, the degree of matching based on NbS for the implementation scheme of the Jiulong River Watershed Shan-Shui Initiative is 73%, which meets the criteria of NbS but needs to be improved in terms of monitoring and assessment, synergistic management, and benefit trade-offs.

In this study, three new demountable joints consisting of reinforced concrete columns and steel beams were proposed and their seismic performance was investigated using cyclic loading tests. The test results demonstrated that the three demountable RCS joints had good seismic performance. Using the finite element software ABAQUS, the influence of parameters such as beam flange thickness, bolt strength, and connector steel strength on the seismic performance of each joint was analyzed, and the influence of different parameters on the seismic behavior of the joint was determined. The results also showed that the three demountable RCS joints were sensitive to changes in the thickness of the steel beam flange, while the connector steel strength and bolt type had little impact on the joint's capacity. Additionally, shear capacity calculation formulas for the joint core area provided by different codes and researchers were compared with test and finite element results. The results showed that the calculation results of the ASCE guidance method, the Nishiyama method, and the CECS 347-2013 method were higher than the test values, while the calculation results of the Para method were lower because it did not consider the contribution of the cylindrical steel plate to the shear capacity of the joint core area.

In the world city theory, most researchers focus on the service sector in the urban economy and less discuss the role of manufacturing. However, the path of only emphasizing financial and corporate service could not fit the sustainability concept. Compared to Anglo-American world city, Global South’s world cities have distinct pathway to be industrialization, tertiarization and globalization. This paper adopted dynamic historic perspective with first-hand materials including in-depth interviews with managers and government officers and second-hand data including yearbook statics and economic census to closely examine the emerging world city-- ‘World Factory’ in Global South, Guangzhou in China, from 1949 to 2015, to emphasize how manufacturing affects the urban globalization through three dimensions, economic, social and spatial dimensions. To make the confirmation of the role of manufacturing in Guangzhou as sustainable world city, we find manufacturing in Guangzhou builds up the basic foundation of export-oriented economy and makes positive effects on urban economic transformation. In addition, manufacturing remains important source of employment and foreign immigration. Along with urbanization and industrialization, urban spatial expansion and aggregation changes with different urban development concept. We provide new insights on multiple globalization on manufacturing for sustainable world city.

This paper applied the space-time generalized finite difference scheme for solving the nonlinear dispersive shallow water waves as the modified Camassa−Holm equation, modified Degasperis-Procesi equation, Fornberg-Whitham equation, and its modified form. The proposed meshless numerical scheme was composed of the space-time generalized finite difference method, the two-step Newton-Raphson method, and the time-marching method. The space-time approach can treat the temporal derivative as one of the spatial derivatives. This numerical technique enables all the partial derivatives in the governing equation can be discretized by a spatial discretization method, and the mixed derivative can efficiently deal with using the proposed meshless numerical scheme. The space-time generalized finite difference method is advanced from the Taylor series expansion and the moving-least square method. The numerical discretization process is only related to functional data and weighting coefficients on the central node and its nearby nodes. Thus, the matrix system composed of nonlinear algebraic equations will be a sparse matrix and can be efficiently solved by the two-step Newton-Raphson method. Furthermore, the time-marching method was utilized to proceed with the space-time domain along the time axis. In this paper, several numerical examples were tested to verify the capability of the proposed space-time generalized finite difference scheme.

To deal with the uncertainties in modeling offshore wind turbines, we proposed a parameter inversion method for the pile-soil interaction model based on structural health monitoring results and the numerical model. The proposed parameter inversion method has a numerical model, an objective function selected using both the numerical and identified results, and an inverse optimization using a random search algorithm in the assumed parameter space. The parameter results in the minimum optimization objective function are identified as the in-situ parameter. The proposed method is confirmed to converge after some iterations, whatever the initial parameter values are. However, different initial parameter cases may converge to slightly different optimal parameters, implying the pile results are sensitive to geological parameters. Moreover, a comparison with the original design results shows design redundancy or risks. Though the proposed method has several flaws, it can shed some light on the influence of uncertainties in offshore wind turbines, such as soil parameters in geological surveys.

A novel simplifying Volterra structure algorithm is proposed for intensity modulation direct detection (IM-DD) optical fiber short distance communication system by using the decision feedback equalization algorithm (DFE). Based on this algorithm, the signal damage for four-level pulse amplitude modulation signal (PAM-4) is compensated, which is caused by device bandwidth limitation and dispersion during transmission. Experiments have been carried out using a 25GHz Electro-absorption Modulated Laser (EML), showing that PAM-4 signals can transmit over 10km in standard single-mode fiber (SSMF). The 112Gbps and 128Gbps signals can reach the error rate threshold of KP4-FEC (BER=2*10-4) and HD-FEC (BER=3.8*10-3), respectively. The simplified principle and process of proposed Volterra-based equalization algorithm are presented. Experimental results show that the algorithm complexity is greatly reduced by 75%, which provides an effective theoretical support for the commercial application of this algorithm.

The Ocean Color - Simultaneous Marine and Aerosol Retrieval Tool (OC-SMART) is a robust data processing platform that supports a large array of multi-spectral and hyper-spectral sensors. It provides accurate aerosol optical depths and remote sensing reflectances (Rrs estimates) that can be used to generate products such as absorption coefficients due to phytoplankton and detritus/Gelbstoff as well as backscattering coefficients due to particulate matter. The OC-SMART platform yields improved performance in complex environments by utilizing scientific machine learning (SciML) in conjunction with comprehensive radiative transfer computations. This paper expands the capability of OC-SMART by quantifying uncertainties in ocean color retrievals. Bayesian inversion is used to relate measured top of atmosphere radiances and a priori data to estimate posterior probability density functions and associated uncertainties. A framework of the methodology and implementation strategy is presented and uncertainty estimates for Rrs retrievals are provided to demonstrate the approach by applying it to MODIS, OLCI Sentinel-3, and VIIRS sensor data.

Considering that consumers are more willing to buy products online, companies are increasingly selling remanufactured products online through e-commerce platforms. Notwithstanding the high attention it elicits from researchers and companies, the study about the remanufacturing trading platform is in its infancy. Thus, we investigate 20 remanufacturing trading platforms related nowadays and make a gap analysis among them in terms of: (i) business model, (ii) product display, (iii) delivery products, (iv) quality assurance and after-sales service, (v) product review and star rate and (vi) transaction and payment. On this basis, we analyze features and trends for the development of remanufacturing trading platforms and propose six key applications aimed at filling the identified gaps. The consortium blockchain has the characteristics of security and transparency, high credibility, traceability and unfalsifiability, low cost, and strong scalability, which can provide effective support for the six key applications. Then, we construct the technical framework and the model of a consortium blockchain-supported remanufacturing trading platform. Further, we analyze the coupling mechanism between consortium blockchain and remanufacturing trading platform to explain how the remanufacturing trading platform supported by consortium blockchain achieves development characteristics. This study provides important guidance for the development, construction, and operation management of remanufacturing trading platforms.

Sodium substitution Li1-xNaxMn2O4 cathodes were synthesized by a solid-state reaction method. The morphologies and crystal structures of Li1-xNaxMn2O4 were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD), respectively. All Li1-xNaxMn2O4 samples exhibited a single phase LiMn2O4 spinel structure with good crystallinity. The effect of Na+ ions on the electrochemical performance of Li1-xNaxMn2O4 was investigated by galvanostatic charge-discharge test. The results showed that lithium substituted by sodium deteriorated its capacity retention but enhance its discharge capacity when it worked at large current densities. The initial discharge capacity was 114.2 mAh/g for Li0.94Na0.06Mn2O4, and 93.1 mAh/g remained after 300 cycles at a current density of 2220 mA/g in the voltage range 3.0–4.3 V at room temperature.

The pre-chamber technologies can improve the ignition performance of IC engines by more than two orders in magnitude and thereby substantial economic benefits. Compared with the common pre-chamber, a plug-and-play passive scheme is suitable for quick retrofit, which is getting more attention from the automobile industry. Good scavenging is the precondition for improving turbulent jet ignition performance for a passive pre-chamber. Therefore, detailed evaluations of the scavenging process and turbulent jet ignition deserve investigations for new pre-chamber schemes. In this paper, the effects of design parameters on ignition processes of plug-and-play passive pre-chamber were numerically studied, allowing for the lateral angle, orifice diameter, and vertical angle design. Seven pre-chamber schemes were evaluated, and four optimal ones were selected for bench tests. The characteristics of the scavenging process, turbulent jet ignition, and main-chamber combustion were investigated and analyzed. The results show that allowing for the trade-off between ignition energy and scavenging efficiency, the volume ratio of the pre-chamber to clearance is recommended to be 0.2~0.7%, and the corresponding area-volume ratio is 0.003~0.006 mm-1. Compared with the original natural gas engine, the pre-chamber retrofit can save up to 13.2% fuel consumption, which presents a significant improvement in fuel economy.

A new longitudinal flow heat dissipation theory for cylindrical batteries is proposed in order to increase the energy density and uniform temperature performance of cylindrical lithium-ion battery packs while also shrinking their size by roughly 10%. First, a genetic algorithm is used to identify the single cell's thermal properties. Based on this, modeling and simulation are used to examine the thermal properties of the longitudinal flow-cooled battery pack. It is found that the best coolant flow scheme has one inlet and one outlet from the end face, taking into account the cooling effect of the battery pack and engineering viability. Lastly, Thermal Dummy Cells (TDC) is used to conduct a validation test of the liquid cooling strategy. Additionally, the simulation and test results demonstrated that the liquid cooling solution can keep the battery pack's maximum temperature rise under the static conditions of a continuous, high-current discharge at a rate of 3C to 20 °C and under the dynamic conditions of the New European Driving Cycle (NEDC) to 2 °C. In applications where the space requirements for the battery pack are quite severe, the longitudinal flow cooling method has some advantages.

Snow parameters have traditionally been retrieved using discontinuous, multi-band sensors; however, continuous hyperspectral sensor are now being developed as an alternative. In this paper we investigate the performance of various sensor configurations using machine learning neural networks trained on a simulated dataset. Our results show improvements in accuracy of retrievals of snow grain size and impurity concentration for continuous hyperspectral channel configurations. Retrieval accuracy of snow albedo was found to be similar for all channel configurations.

A 'little brother' of pain, itch is an unpleasant sensation that creates a specific urge to scratch. To date, various machine-learning based image classifiers (MBICs) have been proposed for quantitative analysis of itch-induced scratch behaviour of laboratory animals in an automated, non-invasive, inexpensive and real-time manner. In spite of MBICs' advantages, the overall performances (accuracy, sensitivity and specificity) of current MBIC approaches remains inconsistent, with their values varying from ~50% to ~99%, for which the reasons underlying have yet to be investigated further, both computationally and experimentally. To look into the variation of the performance of MBICs in automated detection of itch-induced scratch, this article focuses on the experimental data recording step, and reports here for the first time that MBICs' overall performance is inextricably linked to the sharpness of experimentally recorded video of laboratory animal scratch behaviour. This article furthermore demonstrates for the first time that a linearly correlated relationship exists between video sharpness and overall performance (accuracy and specificity, but not sensitivity) of MBICs, and highlight the primary role of experimental data recording in rapid, accurate and consistent quantitative assessment of laboratory animal itch.

Therapeutics antibodies have increasingly shifted the paradigm of disease treatments, from small molecules to biologics, especially in cancer therapy. Despite the increasing number of antibody candidates, much remains unknown about the antibody and how its various regions interact. In fact, the constant region can govern effects that might be useful in reducing the unwanted consequences resulted from systemic circulation. For this reason, apart from the commonly used IgG isotypes, IgA antibodies are promising therapeutics drugs, given its localized mucosal effects. While the antibody Fc effector cell activity has been well explored, recent research has shown evidences that the constant region of the antibody can also influence antigen binding, challenging the conventional idea of region-specific antibody functions. To further investigate this, we analyzed the IgA antibody constant and its allosteric effects onto the antigen binding regions, using recombinant Pertuzumab IgA1 and IgA2 variants. We found mutations in the C-region to reduce Her2 binding, and our computational structural analysis showed that such allosteric communications were highly dependent on the antibody hinge, providing the evidence to consider antibodies as a whole protein rather than a sum of functional regions.

The complete genomic sequence of a Cassava common mosaic virus Linggao isolate (CsCMV-LG) was determined from cassava (Manihot esculenta Crantz) with mild leafy mosaic symptom to no symptom in China. Excluding the poly(A) tail, the CsCMV-LG genome (GenBank accession No. MT038420) is 6374 nucleotides (nts) in length, with five major open reading frames encoding a 1450-amino acids (aa) RNA-dependent RNA polymerase (RdRp), three triple gene block (TGB) proteins (231-aa, 110-aa and 95-aa), and a 229-aa coat protein (CP). Phylogenetic analysis indicated that the complete genome of the CsCMV-LG is closely related to that of CsCMV-Brazilian which has been assigned to the genus Potexvirus, but the sequence identity shared only 88.0%. Notable, the mild CsCMV-LG isolate can also infect Nicotiana benthamiana in laboratory through rub inoculation causing mild vein yellowing at 15-day post inoculation. This is the first full-length genome sequence of a distinct isolate of Cassava common mosaic virus (CsCMV) infecting cassava in Hainan, China.

Curcumin is a promising anti-cancer drug but its applications in cancer therapy are limited due to its poor solubility, short half-life and low bioavailability. In this study, curcumin loaded magnetic alginate / chitosan nanoparticles were fabricated to improve the bioavailability, uptake efficiency and cytotoxicity of curcumin to MDA-MB-231 breast cancer cells. Alginate and chitosan were deposited on Fe3O4 magnetic nanoparticles based on their electrostatic properties. The sizes of the nanoparticles (120-200 nm) were within the optimum range for drug delivery. Sustained curcumin release was obtained use the nanoparticles with the ability to control the curcumin release rate by altering the number of chitosan and alginate layers. Confocal fluorescence microscopy results showed that targeted delivery of curcumin with the aid of magnetic field were achieved. The FACS assay indicated that MDA-MB-231 cells treated with curcumin loaded nanoparticles had a 3-6 folds uptake efficiency to those treated with free curcumin. MTT assay indicated that the curcumin loaded nanoparticles exhibited significantly higher cytotoxicity toward MDA-MB-231 cells than toward HDF cells. The sustained release profiles, enhanced uptake efficiency and cytotoxicity to cancer cells as well as the targeting potential make MACPs a promising candidate for cancer therapy.

Land surface temperature (LST) is a crucial parameter in climate and ecology, exerting significant influence on meteorological conditions, ecosystems, and human life. LST data sources are diverse, with remote sensing being the prevailing means of acquisition. FY-4A/AGRI offers high-quality LST products for East Asia. In this study, we evaluated the performance of the product in Hunan Province and conducted refined analysis of surface heat resources based on the 4km/1h resolution product over a two-year period. The results demonstrate that the FY-4A LST product effectively captures surface temperature (R=0.893), albeit with a relatively high error level (Bias=-6.295℃; RMSE=8.58℃), particularly in capturing high LST values. The performance of this product is superior in the eastern flat terrain area of Hunan Province compared to its performance in the western mountainous region due to environmental conditions causing systematic errors that contribute to instability in detection deviation for this product. Surface heat resources are more abundant in eastern Hunan Province than in mountainous areas located west and southwardly, and the detailed distribution of them at finer scales is mainly influenced by the terrain and climate conditions. There is no obvious seasonal difference in the distribution of heat resources except in winter, and rapid urbanization within Chang-Zhu-Tan urban agglomeration during two years has significantly altered the spatial distribution pattern of surface heat resources across Hunan Province. These findings provide a quantitative baseline for assessing FY-4A satellite's detection capability while serving as a reference for further application of its LST products and establishing foundations for divisional classification and utilization strategies pertaining to surface heat resources within Hunan Province.

Understanding the thermal cracks of rock caused by high temperature is of great help to the development of underground engineering, such as geothermal mining, underground coal gasification. Although there has been many study on thermal cracking, it is not systematic and in-depth enough. In order to deeply study the thermal crack mechanism of rock, this paper conducted thermal cracking experiments on granite at different temperatures and heating/cooling paths, and qualitative and quantitative analysis was conducted on the crack initiation characteristics, propagation paths, and crack network morphology of rock thermal crack under different test conditions. The thermal crack mechanism was also analyzed from the perspectives of mineral petrology, fracture mechanics, thermodynamics, and other aspects. The research results show that there are two obvious mutation points in the study temperature range for samples with fast cooling paths (SF path: slow heating and fast cooling; FF path: fast heating and fast cooling), around 200-300 ℃ and 600 ℃, respectively, while for samples with slow cooling paths (SS path: slow heating and slow cooling; FS path: fast heating and slow cooling), there is only one mutation point around 600 ℃. The initiation positions of thermal cracking under all temperature paths are relatively similar, with intergranular crack located between particles at the edge of the sample or intercrystalline crack in the middle of feldspar or quartz aggregates. The initiation temperature of SF and FF path specimens is relatively low compared to SS and FS path specimens, and the number and size of cracks is small. The crack network structure formed by the SF path is the most complex, with the largest crack ratio and cumulative crack length; The crack network structure formed by the FF path is relatively complex, with a larger main crack size but relatively fewer secondary cracks; The FS and SS paths do not form a complex network with good connectivity. The process of thermal crack development can be divided into three stages: the development of small cracks, the joint development of main cracks and small cracks, and the connection of cracks into a network structure. The mechanism of thermal crack propagation is that the expansion and thermal conductivity between different crystals are different. The thermal stress caused by temperature gradient and the tension or shear stress caused by the inconsistent deformation of crystals form stress concentration in weak areas such as particles boundary, cleavage, and original cracks. Firstly, it causes some crystals with smaller strength or less rounded shape to crack, and when the combined stress is large, the cracks will gradually expand along the existing fine cracks. This also explains that the most main cracks of the SF and FF path specimens mainly surround some large mineral aggregates or between particles.

Production of silkworm silk is the most economically important traits in the silk industry. Silk protein synthesis is regulated by juvenile hormone (JH) and 20-Hydroxyecdysone (20E). Therefore, it is important to understand the genetic regulation of silk production is thus a priority. JH binding protein (JHBP) transports JH from the hemolymph to target organs and cells and protects JH. In a previous study, we identified 41 genes containing a JHBP domain in the Bombyx mori genome. Only one JHBP gene, that is, BmJHBPd2, is highly expressed in the posterior silk gland (PSG) and its function remains unknown. In the present study, we investigated the expression levels of BmJHBPd2 and the major silk protein genes in the high silk-producing practical strain 872 (S872) and the low silk-producing local strain Dazao. Our results have shown that BmJHBPd2 was more highly expressed in S872, than in the Dazao strain, which is consistent with the expression pattern of fibroin genes. A subcellular localization assay indicated that BmJHBPd2 is located in the cytoplasm. In vitro hormone induction experiments showed that BmJHBPd2 was upregulated by treatment with juvenile hormone analogue (JHA). BmKr-h1 upregulation was significantly inhibited by overexpression of BmJHBPd2 at the cell level when induced by JHA. However, overexpression of BmJHBPd2 in the posterior silk gland by transgenic methods led to the inhibition of the expression of the silk fibroin gene, resulting in a reduction in silk yield. Further investigation has shown that in the BmJHBPd2OE individual, the key transcription factor Krüppel homolog 1 (Kr-h1) of the JH signaling pathway was inhibited, and 20E signaling pathway genes, such as broad complex (Brc), E74A, and ultraspiracle protein(USP), were upregulated. Our results have indicated that BmJHBPd2 plays an important role in the JH signaling pathway and was important for silk protein synthesis. Furthermore, our findings have helped to elucidate the mechanisms by which JH regulates silk protein synthesis.

Modeling and assessing the sustainability of machining systems has been considered to be a crucial approach to improving the environmental performance of the machining processes. As the most common machining system, the computer numerical control (CNC) milling system is a typical man-machine cooperative system where the activities of the machine tool and operator generate material and energy consumption. However, the energy consumption of the operator in the CNC milling system has often been ignored in most existing research. Therefore, existing methods fail to provide a comprehensive understanding of the sustainability of the CNC milling system. To fill this gap, an exergy loss assessment method is proposed to investigate the sustainability of the CNC milling system, where the energy consumption of the operator, the energy consumption of the machine tool, and material consumption are taken into consideration. The key performance indexes of the energy consumption of the operator, the energy consumption of the machine tool, the exergy loss, and the specific exergy loss (SEL) are analyzed and modeled. To demonstrate the feasibility of the proposed method, a case study was carried out on a three-axis machining center (XH714D), in which SEL was found to be 88.04J/mm3. The proposed method is effective to assess the sustainability of the CNC milling system, and the established exergy loss models build a good basis for exergy efficiency optimization.

Transcription factors (TFs) in the homeodomain-leucine zipper (HD-ZIP) family serve as essential regulators of plant development and control responses to environmental stimuli. To date, however, the HD-ZIP gene family in Prunus nana remains to be fully characterized. Accordingly, a genome-wide analysis of P. nana HD-ZIP family genes was performed using the most recent genomic data available, leading to the classification of 30 HD-ZIP TFs. These genes were annotated and subjected to systematic analyses of phylogenetic relationships, protein physicochemical properties, sequence-based structural characteristics, chromosomal distributions, and associated cis-acting regulatory elements. High levels of diversity were observed with respect to the gene structures for these PnaHD-Zip genes and the cis-regulatory elements found in the promoter regions upstream of these genes, suggesting that they play diverse roles in a range of biological contexts. These 30 PnaHD-Zip genes were further classified into four subgroups based on the results of phylogenetic, gene structure, and conserved motif analyses. Subsequent qPCR analyses indicated that PnaHD-Zip1 and PnaHD-Zip7 expression levels tended to increase was continuously inhibited in response to cold stress, suggesting that proteins in this HD-ZIP gene family may exhibit distinct responses to low-temperature stress exposure. Overall, these results offer a robust foundation for future studies seeking to explore the functional roles that HD-ZIP TFs play as regulators of cold stress tolerance in P. nana, in addition to offering more general insight regarding the regulatory functions and characteristics of these different HD-ZIP genes in P. nana.

We propose a new approach of extending the laser filament plasma channel. By adding a circular aperture quartz plate before the focusing lens, the extension of the plasma channel is doubled. The effects of different diameters, thicknesses of the circular aperture quartz plate and different pulse energies on the length of the plasma channel were investigated. The experimental results show that the thickness of the quartz plate and the depth of the hole have little effects on the plasma channel of the filament, and the diameter of the hole in the center of the quartz plate has a significant effect on the length of the optical filament. The moving-focus model is used to explain the extension of the optical filament.

Particulate matter is a severe source of atmospheric pollution in urban cities, and it has adverse effects on human health. This study was conducted during the whole year of 2016 to monitor the concentrations of PM₁₀ and PM_2.5 on the Beijing Hanshiqiao wetland and bare land in Beijing to analyze their correlations with meteorological factors and compare the removal efficiency between two land surface types. The results indicated that (1) the PM₁₀ and PM_2.5 concentrations on the bare land were higher than those on wetland as a whole, reaching the highest value both at night and dusk and the lowest value near noon. The average concentration of PM₁₀ was higher in winter (wetland: 137.48 μg·m^-3; bare land: 164.75 μg·m^-3) and spring (wetland: 205.18 μg·m^-3; bare land: 244.85 μg·m^-3) and the concentration of PM_2.5 on the wetland also reached the higher value in winter and spring with the average of 84.52 μg·m^-3 and 98.98 μg·m^-3, whereas, it was higher in spring and summer on the bare land; (2) concentrations of PM₁₀ and PM_2.5 were significantly positively affected by the relative humidity (P < 0.01) and negatively influenced by wind speed (P < 0.05). The relationship between PM₁₀ and PM_2.5 concentrations and temperature was found complicated: it showed a significantly negative correlation (P < 0.01) in winter and spring and was insignificant in autumn, but in summer, only the correlation between the PM₁₀ concentration and temperature on wetland was significant (P < 0.01); (3) the removal efficiencies of PM₁₀ and PM_2.5 followed the order of spring > winter > autumn > summer on the wetland, and the removal efficiency of PM₁₀ was greater than that of PM_2.5. This study is aim to provide practical measures to improve the air quality and facilitate sustainable development in Beijing.

Saline water irrigation contributes significantly to forage yield. However, the salinity threshold for safe saline water irrigation of tall wheatgrass in coastal saline-alkaline land remains unclear. In this study, 2 g L‒1, 3 g L‒1, 4 g L‒1, 5 g L‒1, and 8 g L‒1 saline waters were used for irrigation. Two irrigations with 2+3 g L‒1 saline waters produced the highest yield, followed by one irrigation with 4 g L‒1 or 5 g L‒1 saline water. After rainfall’s leaching, the soil electrical conductivity (EC1:5) reduced by 41.7%‒79.3% for the saline water irrigation treatments. In combination with saline water irrigation, plastic film mulching can be used for sward establishment of seed propagated tall wheatgrass. However, irrigation with high salinity of drainage water enhanced the risk of plant death. Further, a pot experiment demonstrated that irrigation with 5 g L‒1 saline water led to the least reduction of forage yield and the highest crude protein content in leaves. However, the plants irrigated with ≥7 g L‒1 saline water enhanced soil salinity and reduced plant height, leaf size, and gas exchange rate. Conclusively, one irrigation with ≤5 g L‒1 saline water at the end of April or early May could be acceptable to maximize the forage yield of tall wheatgrass and minimize soil salinization risk in the coastal saline-alkaline land around the Bohai Sea.

We have particularly investigated the correlation law of the effect of different carbon black fillings on the hyper-elastic mechanical behavior of natural rubber by conducting uniaxial tensile tests over a wide range of deformations with different volume fractions of carbon black fillings (0%, 4.7%, 8.9%, 12.8%, 16.4%, 19.7%, 22.7%, 25.2%). The results show that the stress-strain curve for carbon black filled rubber increases with the amount of filling, meaning that the rubber gradually becomes "harder". We explore the correlation between the carbon black filling volume and the parameters of the Yeoh constitutive model by examining the Yeoh constitutive model to characterize the hyper-elastic mechanical behavior of rubber with different carbon black fillings. A quantitative relationship between the material parameters and the carbon black filling volume in the Yeoh constitutive model is presented. A method for calculating the material parameters of the Yeoh constitutive model is developed and it predicts the correlation between the hyper-elastic properties of rubber and the volume fraction of carbon black filling.

Abstract: This study observes the characteristics and influencing factors of carbon fluxes of the Momoge salt marsh ecosystem over four years, which behaves as a CO2 sink. The daily, seasonal, and interannual variations of CO2 fluxes in the Momoge salt marshes were observed using the eddy covariance method and compared with various environmental factors. An overall daily “U” shaped distribution was observed, with uptake during the day (negative values) and release at night (positive values). Annually, the carbon fluxes in the study area roughly exhibit a “V” shape. Carbon fluxes during the non-growing season predominantly showed positive values, indicating the release of CO2 into the atmosphere. Photosynthetically active radiation was the primary influencing factor affecting hourly and daytime variations in net ecosystem exchange (NEE) during the growing season, while temperature was the main factor influencing nighttime NEE dynamics. Air temperature, soil temperature, photosynthetically active radiation, precipitation, and water level all had significant impacts on daily net CO2 exchange. At the monthly scale, larger values of soil temperature, air temperature, photosynthetically active radiation, and aboveground biomass correspond to a stronger carbon absorption capacity of the ecosystem. Overall, temperature remains the primary factor for carbon fluxes in the Momoge wetlands.

Three new cembranoids (1–3) and a new casbanoid (4), along with three known analogues (5–7), have been isolated from the soft coral Sinularia nanolobata collected off Ximao Island. The structures including the absolute configurations of new compounds were established by extensive spectro-scopic data analysis, time-dependent density functional theory/electronic circular dichroism (TDDFT-ECD) calculations and the comparison with spectroscopic data of known compounds. In in vitro bioassay, compounds 1 and 5 exhibited moderate cytotoxic activities against human erythroleukemia (HEL) cells line with IC50 values of 37.1 and 42.4 uM, respectively.

Gastrodia elata Bl., one of the well-known edible plants in China, belongs to the family of Orchidaceae. In recent years, the consumption rate of this plant as food supplements or health products is gradually rising in China. However, the traditional industrialization processing procedures (TP) for this plant was found to be too complicated and not friendly to the environment with time and energy consuming. Hence, we investigated whether the processing procedures could be simplified without affecting its overall chemical profile and anti-oxidation activity. In this experiment, a new processing procedure (NP) was designed for processing this plant, and the chemical compositions of the extract for Gastrodia elata produced by two different processing procedures were identified by UPLC-Q-TOF/MS. It was found that phenols and parisins were the most abundant chemical components for this extract. Among all the identified components, the contents of gastrodin and its citric acid derivatives were obviously higher than that of other components. Therefore, the contents of six gastrodin derivatives and ethanol soluble extract rate for Gastrodia elata produced by two different processing procedures, traditional and newly designed processing procedures, were further comparatively investigated for the validation of the applicability. The DPPH radical scavenging activities of the extract from Gastrodia elata produced by two different processing procedures were also investigated. The results demonstrated that the contents of gastrodin and p-hydroxybenzyl alcohol in all samples were slightly decreased in NP samples compared with that of TP samples (except batches of S3 and S6 samples), but no significant difference was observed between these two groups (p = 0.8273 for gastrodin and p= 0.2320 for p-hydroxybenzyl alcohol). Additionally, the total contents of parisins were also in a decreased trend in NP samples but with no significant difference when comparing with that in TP samples (p = 0.1721). The results for ethanol soluble extract rate also had the same situation (p = 0.1094). Taken together, it was suggested that the chemical profiles and contents of gastrodin derivatives and ethanol soluble extract rate for NP samples was not significant different to that of TP samples. The DPPH radical scavenging activity of the extract of Gastrodia elata produced with NP method was not significant different from that of TP samples. As a result, the industrial processing procedures for the preservation of this material plant could be simplified to a more time and energy saving procedure without changing the quality of the products, which is also consistent with the concept of green and sustainable industrial production.

The aim of this study was to develop a novel nanostructured lipid carriers (NLCs) with hepatocytes targeting as carriers for the magnetic resonance imaging (MRI) contrast agent (i.e., magnetic nanostructured lipid carriers, MNLCs), and to evaluate the targeting ability of the MNLCs with T2-weighted MRI both in vitro and in vivo. Here, the galactose-octadecylamine (Gal-ODA) conjugates were synthesized by chemical coupling reaction between lactose acid (LA) and octadecylamine (ODA). Then the superparamagnetic iron oxide (SPIO) loaded nanostructured lipid carrier (conjugated by Gal-ODA, Gal-NLC-SPIO) was prepared by emulsification-ultrasonic method using monoglyceride as lipid materials. The Gal-NLC-SPIO with a diameter of about 50 nm could specifically internalize into LO2 (human hepatic cell line) cells. In vitro MRI results also proved the specific targeting ability of Gal-NLC-SPIO to LO2 cells. The in vivo MR imaging experiments using an orthotopic intrahepatic xenograft tumor model further validated the hepatocytes targeted effect of Gal-NLC-SPIO. The results of this study suggested that Gal-NLC-SPIO can be used as a contrast agent to aid in the diagnosis of hepatic diseases.

The Pingbei area is the main accumulation area of oil and gas in the Xihu Sag. The phase characteristics of oil and gas in this area are complex, and the understanding of their genesis is still unclear. In this paper, based upon discussions of crude oil and natural gas geochemical data, integrated with local geological features, we discuss the sources, migration, and phase state characteristics of oil and gas in the Pingbei area of the Xihu Sag. The study results showed that the crude oil and natural gas in the Pingbei area are coal-derived and the oil and gas produced by the humic organic matter during the maturity stage. The oil and gas source correlation showed that crude oil and natural gas have good affinity with the Eocene Pinghu Formation (PF) coal-bearing source rocks. Crude oil has the characteristics of near-source accumulation and short-distance migration while natural gas is supplied from a dual source: the coal-derived hydrocarbon rocks of PH in the deep part of the study area, supplemented by the coal-derived hydrocarbon rocks of PH on the bottom of the slope, and adjacent hydrocarbon-bearing sub sag. The distribution characteristics and geochemical migration indices of hydrocarbon showed that the oil generated from the hydrocarbon source rocks of PH in the deep Pingbei area mainly migrates vertically along the fault connecting the reservoir and the source rocks to the trap, where it accumulates, while the natural gas exhibits deep and large faults that mainly migrate vertically, supplemented by its lateral migration along the composite transport system composed of faults and sandstone layers in the slope zone. The mechanisms of produced, exhausted, and geochromatographic effects (PGE), as well as evaporative fractionation (EF) and phase-controlled migration fractionation (PMF), result in the obvious discrepancy of hydrocarbon’s properties on the vertical profiles.

Brassica yellows virus (BrYV) is a tentative species of the genus Polerovirus, which occurs widely and mostly damage Brassicaceae plants in East Asia. Since BrYV could not be transmitted mechanically, an insect transmission method is required for further virus research. Here, a reliable and unrestricted method was described, in which non-viruliferous aphids (Myzus persicae) acquired BrYV from transgenic Arabidopsis thaliana plants with virus full length genome germinated from seeds and frozen infected leaves were used to transmit the virus to healthy plants, and there was no significant difference in acquisition rate though transmission rate from frozen infected leaves was somehow lower compared to fresh infected leaves. This novel simple method could be applied to preservation of virus inocula, evaluation of variety resistance to BrYV, biological research on interaction among BrYV, aphid and host, which also provide a new idea on establishing a basic method using virus genomic transgenic plants or frozen infected leaves for other poleroviruses research.

A novel and highly pathogenic coronavirus (2019-nCoV)-induced pneumonia spread worldwide in a short time. However, studies on the effects of 2019-nCoV on the male reproductive system are limited. The aim of this study is to describe the clinical characteristics of the male reproductive system of COVID-19 patients and to explore the presence of 2019-nCoV in semen. Retrospective, single-center case series of 112 male patients with confirmed COVID-19 who were admitted to Renmin Hospital of Wuhan University from January 2 to March 7, 2020. Demographic data, symptoms and signs related to the male reproductive system, throat swabs and semen samples were collected and analyzed. 2019-nCoV RNA measured in throat swab and semen samples. The organ distribution of ACE2 mRNA and protein in human tissue on The Human Protein Atlas portal and investigated immunohistochemistry (IHC) images of the testis. The HPA dataset revealed relatively high levels of ACE2 protein and RNA expression in the testis. A total of 3 severe COVID-19 patients (2.7%) presented with orchidoptosis, while no patients experienced other symptoms or signs related to the male reproductive system. The analysis of 2019-nCoV RNA in semen included 17 patients with fertility needs. Among these patients, 9 (52.9%) remained positive for 2019-nCoV according to throat swab analysis, and 8 (47.1%) became negative. In the semen 2019-nCoV analysis, all 17 patients were negative for the N gene and ORF1ab gene. In view of the potential impairment, long-term follow-up for male COVID-19 patients with fertility needs is of great significance.

Hyperandrogenism and insulin resistance are co-pathologies of polycystic ovary syndrome (PCOS). Recent evidence has suggested that elevated local cortisol levels are associated with ovarian and endometrial insulin resistance in hyperandrogenic PCOS patients, but the molecular mechanisms underlying these clinical findings remain unclear. We and others have used chronic treatment with human chorionic gonadotropin (hCG) and insulin to create an in vivo rodent model for the onset and development of PCOS-like phenotypes. Here, we aimed to determine whether the molecular mechanisms of glucocorticoid receptor (GR) signaling, mitochondrial function, and local inflammation in the ovary and uterus are intrinsically different in PCOS-like rats compared to controls. In both the ovary and the uterus, decreased expression of two GR protein isoforms was concurrent with increased expression of Fkbp51 but not Fkbp52 mRNA in PCOS-like rats compared to controls. However, PCOS-like rats exhibited an opposite regulation of Hsd11b1 or Hsd11b2 mRNAs in the two tissues. Further, the expression of several oxidative phosphorylation-related protein components was decreased in the PCOS-like ovary and uterus, but surprisingly the expression of many genes involved in mitochondrial function and homeostasis was increased in the same tissues and animals. Additionally, PCOS-like rats showed the increased expression of ovarian and uterine NFκB signaling proteins and Tnfaip3 mRNA. In PCOS-like rats, while similar decreased expression of Il1b, Il6, and Mmp2 mRNAs was seen in the ovary and uterus, the opposite regulation of Tnfa, Ccl2, Ccl5, and Mmp3 mRNA expression was observed in the two tissues. Both ovaries and uteri from PCOS-like animals showed increased collagen deposition compared to controls. Collectively, our observations suggest that hyperandrogenism and insulin resistance disrupt ovarian and uterine GR activation and trigger compensatory or adaptive effects for mitochondrial homeostasis, allowing tissue-level maintenance of mitochondrial function in order to limit ovarian and uterine dysfunction. Our study also suggests that hyperandrogenism and insulin resistance-induced activation of NFκB signaling resulting in aberrant regulation of inflammation-related gene expression might be tissue specific in female reproductive tissues.

We monitored the water quality and hydrological conditions of a horizontal subsurface constructed wetland (HSSF-CW) in Beijing, China, for 2 years. We simulated the area rate constant and the temperature coefficient with the first-order kinetic model. We examined the relationships between the nitrogen (N) removal rate, N load, seasonal variations in the N removal rate, and environmental factors, such as the area rate constant, temperature, and dissolved oxygen (DO). The effluent ammonia (NH₄⁺-N) and nitrate (NO₃⁻-N) concentrations were significantly lower than the influent concentrations (p<0.01, n=38). The NO₃⁻-N load was significantly correlated with the removal rate (R²=0.9566, p<0.01), but the NH^₄+-N load was not correlated with the removal rate (R²=0.0187, p>0.01). The area rate constants of NO₃⁻-N and NH₄⁺-N at 20 °C were 27.01±26.49 and 16.63±10.58 m∙yr⁻¹, respectively. The temperature coefficients for NO₃⁻-N and NH₄⁺-N were estimated at 1.0042 and 0.9604, respectively. The area rate constants for NO₃⁻-N and NH₄⁺-N were not correlated with temperature (p>0.01). The NO₃⁻-N area rate constant was correlated with the corresponding load (R²=0.9625, p<0.01). The NH₄⁺-N area rate was correlated with DO (R²=0.6922, p<0.01), suggesting that the factors that influenced the N removal rate in this wetland met Liebig's law of the minimum.