Natural product libraries contain specialized metabolites derived from plants, animals, and microorganisms that play a pivotal role in drug discovery due to their immense structural diversity and ...wide variety of biological activities. The strategies to greatly extend natural product scaffolds through available biological and chemical approaches offer unique opportunities to access a new series of natural product analogues, enabling the construction of diverse natural product‐like libraries. The affordability of these structurally diverse molecules has been a crucial step in accelerating drug discovery. This review provides an overview of various approaches to exploit the diversity of compounds for natural product‐based drug development, drawing upon a series of examples to illustrate each strategy.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The immunology of pregnancy is complex and poorly defined. During the complex process of pregnancy, macrophages secrete many cytokines/chemokines and play pivotal roles in the maintenance of ...maternal-fetal tolerance. Here, we summarized the current knowledge of macrophage polarization and the mechanisms involved in physiological or pathological pregnancy processes, including miscarriage, preeclampsia, and preterm birth. Although current evidence provides a compelling argument that macrophages are important in pregnancy, our understanding of the roles and mechanisms of macrophages in pregnancy is still rudimentary. Since macrophages exhibit functional plasticity, they may be ideal targets for therapeutic manipulation during pathological pregnancy. Additional studies are needed to better define the functions and mechanisms of various macrophage subsets in both normal and pathological pregnancy.
The efficacy and synthetic versatility of asymmetric organocatalysis have contributed enormously to the field of organic synthesis since the early 2000s. As asymmetric organocatalytic methods mature, ...they have extended beyond the academia and undergone scale-up for the production of chiral drugs, natural products, and enantiomerically enriched bioactive molecules. This review provides a comprehensive overview of the applications of asymmetric organocatalysis in medicinal chemistry. A general picture of asymmetric organocatalytic strategies in medicinal chemistry is firstly presented, and the specific applications of these strategies in pharmaceutical synthesis are systematically described, with a focus on the preparation of antiviral, anticancer, neuroprotective, cardiovascular, antibacterial, and antiparasitic agents, as well as several miscellaneous bioactive agents. The review concludes with a discussion of the challenges, limitations and future prospects for organocatalytic asymmetric synthesis of medicinally valuable compounds.
This review provides a comprehensive overview of the recent applications of organocatalytic strategies in pharmaceutical synthesis, with a focus on the preparation of antiviral, anticancer, neuroprotective, cardiovascular, antibacterial and antiparasitic agents.
Severe acute respiratory infection (SARI), a significant global health concern, imposes a substantial disease burden. In China, there is inadequate data concerning the monitoring of respiratory ...pathogens, particularly bacteria, among patients with SARI. Therefore, this study aims to delineate the demographic, epidemiological, and aetiological characteristics of hospitalised SARI patients in Central China between 2018 and 2020.
Eligible patients with SARI admitted to the First Affiliated Hospital of Zhengzhou University between 1 January 2018 and 31 December 2020 were included in this retrospective study. Within the first 24 h of admission, respiratory (including sputum, nasal/throat swabs, bronchoalveolar lavage fluid, thoracocentesis fluid, etc.), urine, and peripheral blood specimens were collected for viral and bacterial testing. A multiplex real-time polymerase chain reaction (PCR) diagnostic approach was used to identify human influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, human bocavirus, human coronavirus, human metapneumovirus, and rhinovirus. Bacterial cultures of respiratory specimens were performed with a particular focus on pathogenic microorganisms, including S. pneumoniae, S. aureus, K. pneumoniae, P. aeruginosa, Strep A, H. influenzae, A. baumannii, and E. coli. In cases where bacterial culture results were negative, nucleic acid extraction was performed for PCR to assay for the above-mentioned eight bacteria, as well as L. pneumophila and M. pneumoniae. Additionally, urine specimens were exclusively used to detect Legionella antigens. Furthermore, epidemiological, demographic, and clinical data were obtained from electronic medical records.
The study encompassed 1266 patients, with a mean age of 54 years, among whom 61.6% (780/1266) were males, 61.4% (778/1266) were farmers, and 88.8% (1124/1266) sought medical treatment in 2020. Moreover, 80.3% (1017/1266) were housed in general wards. The most common respiratory symptoms included fever (86.8%, 1122/1266) and cough (77.8%, 986/1266). Chest imaging anomalies were detected in 62.6% (792/1266) of cases, and 58.1% (736/1266) exhibited at least one respiratory pathogen, with 28.5% (361/1266) having multiple infections. Additionally, 95.7% (1212/1266) of the patients were from Henan Province, with the highest proportion (38.3%, 486/1266) falling in the 61-80 years age bracket, predominantly (79.8%, 1010/1266) seeking medical aid in summer and autumn. Bacterial detection rate (39.0%, 495/1266) was higher than viral detection rate (36.9%, 468/1266), with the primary pathogens being influenza virus (13.8%, 175/1266), K. pneumoniae (10.0%, 127/1266), S. pneumoniae (10.0%, 127/1266), adenovirus (8.2%, 105/1266), P. aeruginosa (8.2%, 105/1266), M. pneumoniae (7.8%, 100/1266), and respiratory syncytial virus (7.7%, 98/1266). During spring and winter, there was a significant prevalence of influenza virus and human coronavirus, contrasting with the dominance of parainfluenza viruses in summer and autumn. Respiratory syncytial virus and rhinovirus exhibited higher prevalence across spring, summer, and winter. P. aeruginosa, K. pneumoniae, and M. pneumoniae were identified at similar rates throughout all seasons without distinct spikes in prevalence. However, S. pneumoniae showed a distinctive pattern with a prevalence that doubled during summer and winter. Moreover, the positive detection rates of various other viruses and bacteria were lower, displaying a comparatively erratic prevalence trend. Among patients admitted to the intensive care unit, the predominant nosocomial bacteria were K. pneumoniae (17.2%, 43/249), A. baumannii (13.6%, 34/249), and P. aeruginosa (12.4%, 31/249). Conversely, in patients from general wards, predominant pathogens included influenza virus (14.8%, 151/1017), S. pneumoniae (10.4%, 106/1017), and adenovirus (9.3%, 95/1017). Additionally, paediatric patients exhibited significantly higher positive detection rates for influenza virus (23.9%, 11/46) and M. pneumoniae (32.6%, 15/46) compared to adults and the elderly. Furthermore, adenovirus (10.0%, 67/669) and rhinovirus (6.4%, 43/669) were the primary pathogens in adults, while K. pneumoniae (11.8%, 65/551) and A. baumannii (7.1%, 39/551) prevailed among the elderly, indicating significant differences among the three age groups.
In Central China, among patients with SARI, the prevailing viruses included influenza virus, adenovirus, and respiratory syncytial virus. Among bacteria, K. pneumoniae, S. pneumoniae, P. aeruginosa, and M. pneumoniae were frequently identified, with multiple infections being very common. Additionally, there were substantial variations in the pathogen spectrum compositions concerning wards and age groups among patients. Consequently, this study holds promise in offering insights to the government for developing strategies aimed at preventing and managing respiratory infectious diseases effectively.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Artificial Intelligence of Things (AIoT) connects everything with intelligence, while the increase in energy consumption generated by numerous electronic devices puts forward an impending demand ...on the power supply. Energy harvesting technology has emerged as a compelling innovation technology for the net zero emissions of the power supply for the AIoT. Although significant advances have been witnessed in energy harvesting, some issues such as poor electrical output, weak environmental adaptability, and low reliability are difficult to satisfactorily resolve. Mechanical intelligent energy harvesting can be defined as the system identifying the external excitation or its own state and reacting to it, rather than relying on electrical sensing elements or a central controller for certain adaptive or programmed functions. The adaptive and programmed functions exhibit great potential in solving the above‐mentioned issues that seriously restrict the development of the energy harvesting technology. Here, a generalized definition of mechanical intelligent energy harvesting is given critically and the design methodology is elaborated. The typical reported energy harvesting systems with the characteristics of mechanical intelligence are reviewed. The key research directions in mechanical intelligent energy harvesting are discussed. The mechanical intelligence is expected to revolutionize the development of the energy‐harvesting technology and pave the way for applications.
Mechanical intelligent energy harvesting (MIEH) can be defined as the system identifying excitation or its own state and reacting to it, rather than relying on electrical sensing elements or central controllers for certain adaptive or programmed functions. This review proposes a generalized definition and methodology of MIEH for the first time, reviewing state‐of‐the‐art research, and discussing directions for future developments.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The neuroanatomical basis behind acupuncture practice is still poorly understood. Here, we used intersectional genetic strategy to ablate NPY+ noradrenergic neurons and/or adrenal chromaffin cells. ...Using endotoxin-induced systemic inflammation as a model, we found that electroacupuncture stimulation (ES) drives sympathetic pathways in somatotopy- and intensity-dependent manners. Low-intensity ES at hindlimb regions drives the vagal-adrenal axis, producing anti-inflammatory effects that depend on NPY+ adrenal chromaffin cells. High-intensity ES at the abdomen activates NPY+ splenic noradrenergic neurons via the spinal-sympathetic axis; these neurons engage incoherent feedforward regulatory loops via activation of distinct adrenergic receptors (ARs), and their ES-evoked activation produces either anti- or pro-inflammatory effects due to disease-state-dependent changes in AR profiles. The revelation of somatotopic organization and intensity dependency in driving distinct autonomic pathways could form a road map for optimizing stimulation parameters to improve both efficacy and safety in using acupuncture as a therapeutic modality.
Display omitted
•Intersectional genetic manipulation of NPY+ sympathetic cells•Electroacupuncture stimulation (ES) drives distinct sympathetic pathways•ES operates in somatotopy- and intensity-dependent manners•NPY+ noradrenergic neurons bidirectionally modulate systemic inflammation
Liu et al. reveals a neuroanatomical basis for acupuncture practice, showing that electroacupuncture stimulation can drive distinct autonomic pathways and modulate systemic inflammation in somatotopy-, stimulation-intensity-, and disease-state-dependent manners.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
The recently discovered non-Hermitian skin effect (NHSE) manifests the breakdown of current classification of topological phases in energy-nonconservative systems, and necessitates the ...introduction of non-Hermitian band topology. So far, all NHSE observations are based on one type of non-Hermitian band topology, in which the complex energy spectrum winds along a closed loop. As recently characterized along a synthetic dimension on a photonic platform, non-Hermitian band topology can exhibit almost arbitrary windings in momentum space, but their actual phenomena in real physical systems remain unclear. Here, we report the experimental realization of NHSE in a one-dimensional (1D) non-reciprocal acoustic crystal. With direct acoustic measurement, we demonstrate that a twisted winding, whose topology consists of two oppositely oriented loops in contact rather than a single loop, will dramatically change the NHSE, following previous predictions of unique features such as the bipolar localization and the Bloch point for a Bloch-wave-like extended state. This work reveals previously unnoticed features of NHSE, and provides the observation of physical phenomena originating from complex non-Hermitian winding topology.
Exploration of structurally novel natural products greatly facilitates the discovery of biologically active pharmacophores that are biologically validated starting points for the development of new ...drugs. Endophytes that colonize the internal tissues of plant species, have been proven to produce a large number of structurally diverse secondary metabolites. These molecules exhibit remarkable biological activities, including antimicrobial, anticancer, anti-inflammatory and antiviral properties, to name but a few. This review surveys the structurally diverse natural products with new carbon skeletons, unusual ring systems, or rare structural moieties that have been isolated from endophytes between 1996 and 2016. It covers their structures and bioactivities. Biosynthesis and/or total syntheses of some important compounds are also highlighted. Some novel secondary metabolites with marked biological activities might deserve more attention from chemists and biologists in further studies.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Berry phase associated with energy bands in crystals can lead to quantised observables like quantised dipole polarizations in one-dimensional topological insulators. Recent theories have generalised ...the concept of quantised dipoles to multipoles, resulting in the discovery of multipole topological insulators which exhibit a hierarchy of multipole topology: a quantised octupole moment in a three-dimensional bulk induces quantised quadrupole moments on its two-dimensional surfaces, which in turn induce quantised dipole moments on one-dimensional hinges. Here, we report on the realisation of an octupole topological insulator in a three-dimensional acoustic metamaterial. We observe zero-dimensional topological corner states, one-dimensional gapped hinge states, two-dimensional gapped surface states, and three-dimensional gapped bulk states, representing the hierarchy of octupole, quadrupole and dipole moments. Conditions for forming a nontrivial octupole moment are demonstrated by comparisons with two different lattice configurations having trivial octupole moments. Our work establishes the multipole topology and its full hierarchy in three-dimensional geometries.
Topological acoustics has recently revolutionized fundamental concepts of acoustic propagation, giving rise to strikingly unique acoustic edge modes immune to backscattering. Despite the rapid ...progress in this field, simultaneous realization of reconfigurability, intelligentization, and automatic control over acoustic propagation paths is posing a great challenge. This challenge is overcome by proposing the concept of a programmable acoustic topological insulator based on two digital elements “0” or “1,” which consist of honeycomb‐lattice sonic crystals made of cylindrical rods with different diameters. The acoustic propagation paths in the topological insulators can be controlled automatically by programming different coding sequences, which arises from efficient transformation of pseudospin‐dependent edge modes on both interfaces of the digital elements. More importantly, a unique unit is experimentally fabricated that has either a “0” or “1” response automatically manipulated by an air cylinder, and design topological insulators with programmable functionality, to realize three digital acoustic devices, such as a single‐pole double‐throw switch, a single‐pole single‐throw switch, and a tunable logic gate. The proposed programmable topological insulators may enable future intelligent acoustic devices with exciting reconfigurable and programmable functionalities, which may lead to important advances in various applications, such as integrated acoustics, acoustic security, and information processing.
Programmable acoustic topological insulators (ATIs) enable future intelligent acoustic devices with reconfigurable and programmable functionalities. A unique unit of ATI with either “0” or “1” response automatically manipulated by an air cylinder is fabricated. By programming coding sequences of ATIs, three digital acoustic devices, including a single‐pole double‐throw switch, a single‐pole single‐throw switch, and a tunable logic gate, are demonstrated experimentally.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
PDF
