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Targeted Auger Therapy represents great potential for the therapy of diseases which require a high degree of selectivity on the cellular level (e.g. for therapy of metastatic cancers). Due to their high Linear Energy Transfer (LET), Auger emitters, combined with selective biological systems which enable delivery of radionuclides close to the DNA of the targeting cell, can be extremely selective and powerful treatment tools. There are two main aspects associated with the development of efficient radiopharmaceuticals based on Auger Emitters: a) the availability of suitable Auger-emitting radionuclides for therapy and b) the design of targeting vectors which can deliver Auger emitters into/close to the nucleus. In the present review, we address the first aspect by defining important parameters for the selection of radionuclides for application to Targeted Auger Therapy and form a categorized list of the most promising radionuclides, their possible production routes, and their use in the synthesis of radiopharmaceuticals.

Flow cytometry (FCM) is a sophisticated technique that works on the principle of light scattering and fluorescence emission by the specific fluorescent probe-labeled cells as they pass through a laser beam. It offers several unique advantages as it allows fast, relatively quantitative, multiparametric analysis of cell populations at the single cell level. In addition, it also enables physical sorting of the cells to separate the subpopulations based on different parameters. In this constantly evolving field, innovative technologies such as imaging FCM, mass cytometry and Raman FCM are being developed in order to address limitations of traditional FCM. This review explains the general principles, main applications and recent advances in the field of FCM.

Genetically identical cells in a tissue can respond differently to perturbations in their environment or “stress.” Such stresses can be physicochemical, mechanical, or infectious or may come from competition with other cells in the tissue. Here, I discuss how the varying responses to stress influence the decision of a cell to repair or die, and how one cell's response can have effects on surrounding cells. Such responses control the health and fitness of single cells and how they compete with other genetically identical cells. See related article on p. 129

The article presents the current state of knowledge on the differences between the sexes in the contraction features of motor units, motor and sensory innervation of skeletal muscles, features of motor neurons, proportions of contractile proteins and muscle fibers of various types, and morphometric features of muscles and muscle fibers. These studies, conducted at the cellular level, on animals, allow to explain the foundations of significant differences in the motor conditions of women and men.

Rozważania pierwszej części pracy dotyczą składu ciała człowieka, rozpatrywanego na pięciu różnych poziomach: A) poziom pojedynczych atomów, poprzez B) poziom związków chemicznych, C) skład ciała uwzględniający istnienie błony komórkowej (poziom komórkowy) i D) skład tkankowo-narządowy (poziom tkankowy), aż po E) ocenę ustroju jako całości. Szczególnie dużo uwagi w rozważaniach tych poświęcono mięśniom szkieletowym, w tym czynnikom warunkującym ich siłę i moc. W dalszych częściach pracy przedstawiono proces starzenia się organizmu człowieka, w tym starzenie się mięśni szkieletowych, z uwzględnieniem zjawiska otyłości sarkopenicznej oraz jej negatywnych skutków dla zdrowia człowieka. Omówiono również zjawisko starzenia się mięśni szkieletowych sportowców w przebiegu ich kariery sportowej jak i po jej zakończeniu. W końcowej części pracy przedstawiono dowody na korzystne oddziaływanie aktywności fizycznej / treningu na organizm osób w starszym wieku, nawet po przekroczeniu 100 roku życia.

Understanding the metabolic interactions between bacteria in natural habitat at the single-cell level and the contribution of individual cell to their functions is essential for exploring the dark matter of uncultured bacteria. The combination of Raman-activated cell sorting (RACS) and single-cell Raman spectra (SCRS) with unique fingerprint characteristics makes it possible for research in the field of microbiology to enter the single cell era. This review presents an overview of current knowledge about the research progress of recognition and assessment of single bacterium cell based on RACS and further research perspectives. We first systematically summarize the label-free and non-destructive RACS strategies based on microfluidics, microdroplets, optical tweezers, and specially made substrates. The importance of RACS platforms in linking target cell genotype and phenotype is highlighted and the approaches mentioned in this paper for distinguishing single-cell phenotype include surface-enhanced Raman scattering (SERS), biomarkers, stable isotope probing (SIP), and machine learning. Finally, the prospects and challenges of RACS in exploring the world of unknown microorganisms are discussed. KEY POINTS: • Analysis of single bacteria is essential for further understanding of the microbiological world. • Raman-activated cell sorting (RACS) systems are significant protocol for characterizing phenotypes and genotypes of individual bacteria.

Background: Allometric scaling is a well-known research tool used for the metabolic rates of organisms. It measures the living systems with fractal physiology. The metabolic rate versus the mass of the living species has a definite scaling and behaves like a four-dimensional phenomenon. The extended investigations focus on the mass-dependence of the various physiological parameters. Objective: Proving the length of vascularization is the scaling parameter instead of mass in allometric relation. Method: The description of the energy balance of the ontogenic growth of the tumor is an extended cell-death parameter for studying the mass balance at the cellular level. Results: It is shown that when a malignant cellular cluster tries to maximize its metabolic rate, it changes its allometric scaling exponent. A growth description could follow the heterogenic development of the tumor. The mass in the allometric scaling could be replaced by the average length of the circulatory system in each case. Conclusion: According to this concept, the dependence of the mass in allometric scaling is replaced with a more fundamental parameter, the length character of the circulatory system. The introduced scaling parameter has primary importance in cancer development, where the elongation of the circulatory length by angiogenesis is in significant demand.

Fluorescence-guided surgery provides surgeons with improved visualization of tumor tissue in the operating room to allow for maximal safe resection of brain tumors. Multiple fluorescent agents have been studied for fluorescence-guided surgery. Both nontargeted and targeted fluorescent agents are currently being used for glioblastoma multiforme visualization and resection. Fluorescence detection in the visible light or near infrared spectrum is possible. Visualization device advancements have permitted greater detection of fluorescence down to the cellular level, which may provide even greater ability for the neurosurgeon to resect tumors.

Molecular imaging is a non-invasive process that enables the visualization, characterization, and quantitation of biological processes at the molecular and cellular level. With the emergence of theragnostic agents to diagnose and treat disease for personalized medicine there is a growing need for matched pairs of isotopes. Matched pairs offer the unique opportunity to obtain patient specific information from SPECT or PET diagnostic studies to quantitate in vivo function or receptor density to inform and tailor therapeutic treatment. There are several isotopes of arsenic that have emissions suitable for either or both diagnostic imaging and radiotherapy. Their half-lives are long enough to pair them with peptides and antibodies which take longer to reach maximum uptake to facilitate improved patient pharmacokinetics and dosimetry then can be obtained with shorter lived radionuclides. Arsenic-72 even offers availability from a generator that can be shipped to remote sites and thus enhances availability. Arsenic has a long history as a diagnostic agent, but until recently has suffered from limited availability, lack of suitable chelators, and concerns about toxicity have inhibited its use in nuclear medicine. However, new production methods and novel chelators are coming online and the use of radioarsenic in the pico and nanomolar scale is well below the limits associated with toxicity. This manuscript will review the production routes, separation chemistry, radiolabeling techniques and in vitro/in vivo studies of three medically relevant isotopes of arsenic (arsenic-74, arsenic-72, and arsenic-77).

Interdisciplinary researches have been well appraised in recent times and has to a greater extent helped the CAM community to develop scientific validation for the safety and efficacy of traditional and indigenous formulations. Bhasmas or incinerated organometallic preparations are highly acclaimed with regard to therapeutic efficacy among the Ayurvedic practitioners and has thus, created an arena for various unvalidated and unscientific claims. Bringing order in chaos is a basic purpose that interdisciplinary researches serves to. Addressing the various concerns on the lack of scientific validation on chemical characterization and preclinical studies at cellular level, an attempt is being made to develop a biological safety profile protocol for bhasmas using advanced instrumentation techniques and in vitro methods.

Cancer stem cells (CSCs) are a subpopulation of cancer cells with functions similar to those of normal stem cells. Although few in number, they are capable of self-renewal, unlimited proliferation, and multi-directional differentiation potential. In addition, CSCs have the ability to escape immune surveillance. Thus, they play an important role in the occurrence and development of tumors, and they are closely related to tumor invasion, metastasis, drug resistance, and recurrence after treatment. Therefore, specific targeting of CSCs may improve the efficiency of cancer therapy. A series of corresponding promising therapeutic strategies based on CSC targeting, such as the targeting of CSC niche, CSC signaling pathways, and CSC mitochondria, are currently under development. Given the rapid progression in this field and nanotechnology, drug delivery systems (DDSs) for CSC targeting are increasingly being developed. In this review, we summarize the advances in CSC-targeted DDSs. Furthermore, we highlight the latest developmental trends through the main line of CSC occurrence and development process; some considerations about the rationale, advantages, and limitations of different DDSs for CSC-targeted therapies were discussed., Graphical abstract Emerging CSCs-targeted drug delivery systems for efficient cancer therapy following the main line of CSCs occurrence and development process from the whole to the part and from the outside to the inside.Image 1

Lanthanides as a separate group of metals geochemically belong to rare earth elements (REEs). For a long time, they have not received proper attention of researchers, whose interest was focused on other harmful environmental pollutants. However, the importance of REEs for modern technologies along with significant gaps in the knowledge about their effects on living organisms has changed the situation. Thanks to the active interest of researchers, a fairly large body of data on REEs in various areas has been accumulated, including their chemical and physical properties, their potential in engineering and instrumentation, their content in various natural objects, effects on human health, and interaction with other living organisms at the cellular level. This review analyzes and generalizes the new information about REEs as a relevant ecological factor with a special focus on the sources of REEs, specific features in their behavior in the soil, the effects of their interaction with plants, their manifestation, and putative mechanisms at the cellular level. The economic importance of plants to humans as well as their role for the entire biosphere as primary producers and their ability to be among the first ecosystem components that respond to negative changes requires focusing on these issues. The purpose of this review is to emphasize the research aspects that need a deeper insight, in particular, the soil–plant interaction and the effect of REEs on plant cell division.

Bioluminescence is a powerful imaging modality for monitoring biological phenomena both in vitro and in vivo. Bioluminescence imagin (BLI) is becoming a seamless imaging technology covering the range from cells to organs of small animals. Long-term imaging at the single cell level would lead to a true understanding of the dynamics of life phenomena. This work presents a long-term single cell bioluminescence imaging technology accomplished with C-3 position protected furimazines (FMZs), a CTZ analogues, which generate intense blue emission when paired with a highly stable engineered luciferase, Nanoluc. Four types of FMZs protected at the C-3 position have been synthesized. The type and steric bulkiness of the protection group strongly contributed to storage stability and the kinetics of the bioluminescence reactions of the analogues in human living cells. In particular, two developed FMZ analogues resulted in significantly longer bioluminescence emission with higher S/N ratio than FMZ at single cell level. Long-term bioluminescence single cell imaging technology with the developed FMZ analogues will lead to seamless imaging in the range from cells to organs of small animals.

A microfluidics-based three-dimensional skin-on-chip (SoC) model is developed in this study to enable quantitative studies of transendothelial and transepithelial migration of human T lymphocytes in mimicked skin inflammatory microenvironments and to test new drug candidates. The keys results include 1) CCL20-dependent T cell transmigration is significantly inhibited by an engineered CCL20 locked dimer (CCL20LD), supporting the potential immunotherapeutic use of CCL20LD for treating skin diseases such as psoriasis; 2) transepithelial migration of T cells in response to a CXCL12 gradient mimicking T cell egress from the skin is significantly reduced by a sphingosine-1-phosphate (S1P) background, suggesting the role of S1P for T cell retention in inflamed skin tissues; and 3) T cell transmigration is induced by inflammatory cytokine stimulated epithelial cells in the SoC model. Collectively, the developed SoC model recreates a dynamic multi-cellular micro-environment that enables quantitative studies of T cell transmigration at a single cell level in response to physiological cutaneous inflammatory mediators and potential drugs.

The ability to kill infecting microbes is an essential facet of our immune response to an infection. However, phagocytic ability is often overlooked as a part of immunological profile in infected patients' diagnosis, as the understanding of phagocytic capabilities in disease states is incomplete. In this work, we have evaluated for the first time the relationship between blood lactate level and the neutrophil phagocytic activity at a single-cell level. Blood samples (N = 19) were grouped on the basis of their blood lactate levels i.e., below (control) or above 2 mmol L−1 (high-risk) (i.e., 2 mmol L−1 is a common clinical lactate threshold used for patients' triage). Neutrophils were isolated from whole blood and then incubated with fluorescent IgG coated beads for 40 minutes, and the ability of each neutrophil to internalize beads was quantified. Single-cell phagocytic activity analysis has shown interesting findings such as: (i) a single neutrophil was able to internalize up to 7 beads, (ii) for a control group, 39.76% cells didn't internalize any beads, while for a high-risk group, 30.65% cells didn't show any phagocytic activity, (iii) similarly, 30.46% cells internalize only 1 bead in a control group, while for a high-risk group the activity is slightly higher with only 31.73% cells showing single bead internalization, and (iv) 7 bead internalization activity was much higher for samples in a high-risk group (0.6% cells) compared to a control group (0.17% cells). We used multiple statistical tests to compare these differences. For a two-tailed T-test, we used the mean phagocytic activity of the cells (i.e., the average number of beads internalized by cells) isolated from the blood samples in the two groups (1.14 vs. 1.35) and found the p-value to be 0.08. We also used principal component analysis (PCA) on this high dimensional phagocytic activity distribution data and performed dimension reduction. However, the first 3 principal components didn't show a clear distinction between groups. Next, we developed machine learning models using artificial neural networks (ANNs) to differentiate between the distribution of phagocytic activity in neutrophil populations of the two groups. Our models yielded area under curve (AUC) values below 0.7 for receiver operator characteristic curves. Although our study highlighted interesting phagocytic activity findings at a single cell level, it further highlights the need for integration of an individual patient's medical record to get more personalized insights into individual phagocytic activity in the future.

A cocktail [1 + 2] dual-fluorescent probe system was developed to realize the real-time visualization of dynamic iron state changes between Fe2+ and Fe3+ at the cellular level and in multicellular organisms, providing insights into the effect of DMT1 and ferroportin on iron regulation.

Low-intensity pulsed ultrasound (LIPUS), as physical therapy, is widely used in both research and clinical settings. It induces multiple bioeffects, such as alleviating pain, promoting tissue repair, and shortening disease duration. LIPUS can also mediate inflammation. This paper reviews the application of LIPUS in inflammation and discusses the underlying mechanism. In basic experiments, LIPUS can regulate inflammatory responses at the cellular level by affecting some signaling pathways. In a clinical trial, LIPUS has been shown to alleviate inflammatory responses efficiently. As a cheap, safe, and convenient physical method, LIPUS is promising as anti-inflammatory therapy.

Biochemical systems have numerous practical applications, in particular to the study of critical intracellular processes. Frequently, biochemical kinetic models depict cellular processes as systems of chemical reactions. Many biological processes in a cell are inherently stochastic, due to the existence of some low molecular amounts. These stochastic fluctuations may have a great effect on the biochemical system’s behaviour. In such cases, stochastic models are necessary to accurately describe the system’s dynamics. Biochemical systems at the cellular level may entail many species or reactions and their mathematical models may be non-linear and with multiple scales in time. In this work, we provide a numerical technique for simplifying stochastic discrete models of well-stirred biochemical systems, which ensures that the main properties of the original system are preserved. The proposed technique employs sensitivity analysis and requires solving an optimization problem. The numerical tests on several models of practical interest show that our model reduction strategy performs very well.

The field of single-cell technologies, in particular single-cell genomics with transcriptomics and epigenomics, and most recently single-cell proteomics, is rapidly growing and holds promise to advance our understanding of organ homoeostasis and disease, and facilitate the identification of novel therapeutic targets and biomarkers. This review offers an introduction to these technologies. In addition, as the size and complexity of the data require sophisticated computational methods for analysis and interpretation, we will also provide an overview of these methods and summarize the single-cell literature specifically pertaining to the kidney.

The physiological processes of cells and organisms are regulated by various biological macromolecules, including long-noncoding RNAs (lncRNAs), which cannot be translated into protein and are different from small-noncoding RNAs on their length. In animals, lncRNAs are involved in development, metabolism, reproduction, aging and other life events by cis or trans effects. For many functional lncRNAs, there is growing evidence that they play different roles on cellular level and organismal level. On the other hand, many annotated lncRNAs are not essential and could be transcription noises. In this minireview, we investigate the physiological function of lncRNAs in cells and focus on their functions and functional mechanisms on the organismal level. The studies on lncRNAs using different classic animal models such as worms and flies are summarized and discussed in this article.

Measurement of gene expression at the single-cell level has led to important advances in the study of transcriptional regulation programs in healthy and disease states. In particular, single-cell gene expression approaches have shed light on the high level of transcriptional heterogeneity of individual cells, both at baseline and in response to experimental or environmental perturbations. We have developed a method for High-Content Imaging (HCI)-based quantification of transcript abundance at the single-cell level in primary human immune cells and have validated its performance under multiple experimental conditions to demonstrate its general applicability. This method, which we abbreviate as hcHCR, combines the high sensitivity of the hybridization chain reaction (HCR) for the visualization of mRNA molecules in single cells, with the speed, scalability, and technical reproducibility of HCI. We first tested eight microscopy-compatible attachment substrates for short-term culture of primary human B cells, T cells, monocytes, or neutrophils. We then miniaturized HCR in a 384-well format and documented the ability of the method to detect increased or decreased transcript abundance at the single-cell level in thousands of cells for each experimental condition by HCI. Furthermore, we demonstrated the feasibility of multiplexing gene expression measurements by simultaneously assaying the abundance of two transcripts per cell, both at baseline and in response to an experimental stimulus. Finally, we tested the robustness of the assay to technical and biological variation. We anticipate that hcHCR will be a suitable and cost-effective assay for low- to medium-throughput chemical, genetic or functional genomic screens in primary human cells, with the possibility of performing personalized screens or screens on cells obtained from patients with a specific disease.

Objective To generate a comprehensive transcriptomic profile of cellular signifures and transcriptomes of human placenta in GDM by single-cell RNA-sequencing (scRNA-seq), and built a comprehensive cell atlas. We hope to reveal the molecular mechanism of pregnancy risk for GDM women. Design Scientific study. Setting University Hospital and laboratories. Population or Sample Pregnant women Methods 20 GDM women and 20 normal pregnant women were recruited in present study. ScRNA-seq were loaded on the Chromium Single Cell Controller Instrument (10×Genomics) to generate single cell gel beads in emulsions (GEMs). Results A total of 27,220 cells from placenta samples were obtained. First, with the cell-type-specific marker genes, we annotated 15 cell clusters into more than 9 different cell types. Second, beside the classcial markers, we also found some novel markers for distinguishing three kinds of trophoblast and subtypes, which cloud be confirmed by immunohistochemistry imaging. Third, we demonstrated the specific placental function in GDM by the bioinformatics analysis of differentially expressed genes, such as estrogen signaling pathway, natural killer cell mediated cytotoxicity down- regulated. Fourth, there are abundant ligand-receptor interactions between trophoblast and immune cells in the maternal fetal interface microenvironment, such as VEGFB-FLT1, MIF-EGFR, RPS19-C5AR1, SPP1-CD44These dysfunctional ligand-receptor interactions may play the important roles in the development of GDM. Conclusion This study provided the first cell-type-specific transcriptomic alterations GDM placenta from single cell level, exploded the cell identities and cell-type-specific marker genes in the human placenta. In addition, it demonstrated the features of placental function and cell interactions for GDM.

Vedic astrology which is one of the most important study in India. Since ancient times, in India rituals were suggested as per the planets and other cosmic influences. Planets have the influence at cell level, eukaryotic, prokaryotic as well as viruses. Beside the concept of nakshatra tree, in this paper emphasis is given on the role of microorganisms in astrology. As a part of ritual, we are using the microbial products or processes. Microorganisms are also mentioned in Vedas. Biomineralization derived crystals has been suggested for healing practices. Meteroite-microbial interaction has also been reported which suggests extra-terrestrial existence of microorganisms.

In this article, I describe a new curriculum for introductory physics for the life sciences, a 2-semester sequence usually required of all biology majors. Because biology-related applications on the macroscale are complex and require mathematics beyond introductory calculus, the focus is entirely on applications from molecular and cellular biology. Topics that are more relevant for engineering have been removed, and topics relevant to biology have been added. The curriculum is designed around 2 main themes: diffusion and electric dipoles. Diffusion illustrates the concepts of conservation of momentum and energy and provides the framework for introducing entropy from the perspective of statistical mechanics. Electric dipoles illustrate the basic concepts of electromagnetic theory and provide the framework for understanding light waves and light interactions with biomolecules. These themes are supported by small computational activities to help students understand the physics without advanced mathematics. This curriculum has been piloted over the past 4 years at Michigan State University and should be applicable to many colleges and universities.

The protective effect of plant growth regulators epin-extra and zircon under the joint action with herbicides stomp and dianat on the initial stages of onion and barley ontogenesis, as well as on the root meristem of barley (cytogenetic analysis) was studied. The persistent phytotoxicity of herbicides in terms of stem and root length was shown. Cytogenetic studies have shown a strong cytotoxic and mutagenic effect of dianat. Plant growth regulators epin-extra and zircon, by regulating the hormonal status of plants, acting mainly at the cellular level, significantly reduce the negative effect of herbicides on the culture when used together with them.

Osteoarthritis (OA) is a degenerative joint disease in the elderly. Although OA has been considered as primarily a disease of the articular cartilage, the participation of subchondral bone in the pathogenesis of OA has attracted increasing attention. This review summarises the microstructural and histopathological changes in subchondral bone during OA progression that are due, at the cellular level, to changes in the interactions among osteocytes, osteoblasts, osteoclasts (OCs), endothelial cells and sensory neurons. Therefore, we focus on how pathological cellular interactions in the subchondral bone microenvironment promote subchondral bone destruction at different stages of OA progression. In addition, the limited amount of research on the communication between OCs in subchondral bone and chondrocytes (CCs) in articular cartilage during OA progression is reviewed. We propose the concept of ‘OC–CC crosstalk’ and describe the various pathways by which the two cell types might interact. Based on the ‘OC–CC crosstalk’, we elaborate potential therapeutic strategies for the treatment of OA, including restoring abnormal subchondral bone remodelling and blocking the bridge—subchondral type H vessels. Finally, the review summarises the current understanding of how the subchondral bone microenvironment is related to OA pain and describes potential interventions to reduce OA pain by targeting the subchondral bone microenvironment.

Biologics are an innovative class of drugs that can selectively influence immunological responses at a cellular level. Although their use is usually restricted to some specific diseases, such as autoimmune pathologies and tumors, their “off-label” administration has increased widely in the last years. Drug treatment may induce hypersensitivity reactions which currently lack any gold standard therapy but maybe a future field of application for biologics. Agents like anti-IgE (Omalizumab) and Tumor Necrosis Factor-α inhibitors might be used in immediate-type and cell-mediated hypersensitivity caused by medications, respectively, and the first trials in that direction are being reported in the literature. In fact, the refined immunological mechanisms involved in the pathogenesis of drug hypersensitivity might respond successfully to this new class of drugs.

The use of single‐cell RNA sequencing (scRNA‐seq) in microglial research is increasing rapidly. The basic workflow of this approach consists of isolating single cells, followed by sequencing. scRNA‐seq is capable of examining microglial heterogeneity on a cellular level. However, the results gained from applying this technique suffer from discrepancies due to differences between applied methods characteristics such as the number of cells sequenced and the depth of sequencing. This review aims to shed more light on the recent developments that happened in this field and how they are related to the methods used. To do that, we track the progress and limitations of various scRNA‐seq methods currently available. The review then summarizes the current knowledge gained using scRNA‐seq in the field of microglia, including novel subpopulations associated with function and development under homeostasis as well during several pathological conditions such as Alzheimer, lipopolysaccharide response, and HIV in relation to the methods employed. Our review points out that despite major developments found using this technique, current scRNA‐seq methods suffer from high cost, low yields, and nonstandardization of generated data. Additional development of scRNA‐seq methods will raise our awareness of microglia's heterogeneity and plasticity under healthy and pathological conditions., Single‐cell RNA sequencing (scRNA‐seq) reveals that microglia vary by age, brain regions, and by disease. However, scRNA‐seq is still facing challenges the biggest of which is sequencing costs

All-solid-state Li metal batteries (ASLBs) have the potential to surpass the energy density of commercial Li ion batteries and improve safety. However, most reported ASLBs deliver unsatisfactory ce...

Commercial primary zinc–air batteries provide 450 Wh kgcell–1 (at the cell level), but the practical specific energy of secondary zinc–air batteries remains unclear. Using a specific-energy model a...

Abstract Diabetes mellitus is referred as common metabolic abnormalities characterized as hyperglycemia, mainly caused due to insufficient production of insulin at cellular level or/and defects in insulin action. Such an endocrine disorder is responsible for serious health problems and its worldwide prevalence is rapidly increasing. Common management of diabetes by oral administration of drugs without creating any side effects is still considered a challenging task and increasing cost of conventional medicine in developing countries is another matter of concern. To address these issues, traditional preparations of herbal plant extracts in the form of medicines already gained immense attention. Swertia chirayita is one among such plants which is known for its hypoglycemic potential. Numerous chemical constituents with promising pharmacological properties have been identified from such plant extracts but still, such compounds have not been well characterized, specifically against human application. Hence, more research efforts are necessitated to understand exact mechanism of such compounds and to develop overall safety of such plant formulations. Present review clearly represents antidiabetic properties of Swertia chirayita extract, strategies to be taken to strengthen its safety application on humans and biotechnological interventions that ensure conservation of such endangered species to promote its future application in modern medicine. Graphic Abstract

Current microfluidic methods for studying multicell strains (e.g., m-types) with multienvironments (e.g., n-types) require large numbers of inlets/outlets (m*n), a complicated procedure or expensive machinery. Here, we developed a novel two-layer-integrated method to combine different PDMS microchannel layers with different functions into one chip by a PDMS through-hole array, which improved the design of a PDMS-based microfluidic system. Using this method, we succeeded in converting 2 × m × n inlets/outlets into m + n inlets/outlets and reduced the time cost of loading processing (from m × n to m) of the device for studying multicell strains (e.g., m-types) in varied multitemporal environments (i.e., n-types). Using this device, the dynamic behavior of the cell-stress-response proteins was studied when the glucose concentration decreased from 2% to a series of lower concentrations. Our device could also be widely used in high-throughput studies of various stress responses, and the new concept of a multilayer-integrated fabrication method could greatly improve the design of PDMS-based microfluidic systems.

Pt(II)-based metallacycles, as an important family of supramolecular coordination complexes (SCCs), have exhibited excellent antitumor activity at the cell level. However, the biomedical applications of Pt(II)-based metallacycles for animal studies are still hindered by their poor stability, non-targeted tumour, and lack of detectable feedback for evaluating therapeutic progress. Herein, we propose a strategy that introduces melanin dots as a biomedical platform to load bright-emission Pt(II)-based metallacycles, thereby constructing a theranostic agent that enables photoacoustic imaging (PAI)-guided chemo-photothermal combinational therapy. Melanin dots act as a protective carrier to preserve the integrity of Pt(II)-based metallacycles before uptake by tumour tissues. Meanwhile, the PAI signal from melanin dots furnishes more comprehensive information on the tumour. Moreover, the heat generated after NIR laser irradiation can not only trigger the apoptosis of tumour cells but also promote the deeper penetration of Pt(II)-based SCCs into tumour tissue, thus enhancing the efficiency of chemotherapy.

Microvasculature functions at the tissue and cell level, regulating local mass exchange of oxygen and nutrient-rich blood. While there has been considerable success in the biofabrication of large- and small-vessel replacements, functional microvasculature has been particularly challenging to engineer due to its size and complexity. Recently, three-dimensional bioprinting has expanded the possibilities of fabricating sophisticated microvascular systems by enabling precise spatiotemporal placement of cells and biomaterials based on computer-aided design. However, there are still significant challenges facing the development of printable biomaterials that promote robust formation and controlled 3D organization of microvascular networks. This review provides a thorough examination and critical evaluation of contemporary biomaterials and their specific roles in bioprinting microvasculature. We first provide an overview of bioprinting methods and techniques that enable the fabrication of microvessels. We then offer an in-depth critical analysis on the use of hydrogel bioinks for printing microvascularized constructs within the framework of current bioprinting modalities. We end with a review of recent applications of bioprinted microvasculature for disease modeling, drug testing, and tissue engineering, and conclude with an outlook on the challenges facing the evolution of biomaterials design for bioprinting microvasculature with physiological complexity.

Living cells interpret a variety of signals in different contexts to elucidate functional responses. While the understanding of signalling molecules, their respective receptors and response at the gene transcription level have been relatively well-explored, how exactly does a single cell interpret a plethora of time-varying signals? Furthermore, how their subsequent responses at the single cell level manifest in the larger context of a developing tissue is unknown. At the same time, the biophysics and chemistry of how receptors are trafficked through the complex dynamic transport network between the plasma membrane–endosome–lysosome–Golgi–endoplasmic reticulum are much more well-studied. How the intracellular organisation of the cell and inter-organellar contacts aid in orchestrating trafficking, as well as signal interpretation and modulation by the cells are beginning to be uncovered. In this review, we highlight the significant developments that have strived to integrate endosomal trafficking, signal interpretation in the context of developmental biology and relevant open questions with a few chosen examples. Furthermore, we will discuss the imaging technologies that have been developed in the recent past that have the potential to tremendously accelerate knowledge gain in this direction while shedding light on some of the many challenges.

We studied the cytogenetic characteristics of the seed progeny of the walnut (Juglans regia L.) trees introduced to and grown within the territory of the Central Russian Upland. Three seedling groups with polymorphic cytogenetic characteristics were revealed: mutable (with a high level of pathological mitoses), low mutable (with a low level of cytogenetic disturbances), and intermediate groups. Cytogenetic characteristics (mitotic activity, parts of cells at various stages of mitosis, the level and spectrum of pathological mitoses, sizes of nucleoli and the spectrum of their types, the occurrence of cells with a persistent nucleolus in the stages of meta-, ana-, and telophase) in each of the selected groups were described; homeostatic mechanisms at the cellular level were discussed. The sizes of polymorphic groups were established. The small number of seedlings with a high level of cytogenetic disturbances (7.5%) and the predominance of seedlings with medium (70%) and low (22.5%) values of pathological mitoses indicated a high degree of adaptation of the introduced walnut mother trees to the environmental conditions of the Central Russian Upland. Predictors for assigning any seedling to one of the selected model groups (mutable or low mutable) were established using ROC analysis methods. The obtained data on the qualitative and quantitative polymorphism of cytogenetic characteristics can be used for the development of recommendations for improving the system of seed production and the selection of new forms of walnut in the Central Chernozem Region.

Background: Platelet-rich plasma helps in repair because of its growth factor. Platelet-rich plasma has been used in humans for its healing properties. Increased concentration of growth factors and secretory proteins may increase the process of healing on a cellular level. Aim: This study was done to check the effectiveness of PRP injections in patients with chronic lateral epicondylitis. Methodology: This was accomplished in patients visiting the orthopaedic OPD at the Sree Balaji Medical College and Hospital, Chennai, Tamilnadu. There were 40 physicians in this study, among whom 37 were homosexual and 87 were female. The mean age of the patients was 48.1 years (17-82 years). The study period was 3 months. The analytical method used is a visual analog score. Results: Effective therapy was performed with a decline of more than 20% (24 out of 40 patients) in visual analog score after a dual-month period. After 3 months in boys, the mean VAS score dropped from 6.88 to 9.41. Conclusion: Medication of PRP patients with chronic epicondylitis or PRP tennis elbow reduces pain and increases the flexibility of the affected knee joint.

Nanoparticles are ubiquitous and co-occur with microbial life in every environment on Earth. Interactions between microbes and nanoparticles impact the biogeochemical cycles via accelerating various reaction rates and enabling biological processes at the smallest scales. Distinct from microbe-mineral interactions at large, microbe-nanoparticle interactions may involve higher levels of active recognition and utilization of the reactive, changeable, and thereby 'moldable' nano-sized inorganic phases by microbes, which has been given minimal attention in previous reviews. Here we have compiled the various cases of microbe-nanoparticle interactions with clear and potential benefits to the microbial cells and communities. Specifically, we discussed (i) the high bioavailabilities of nanoparticles due to increased specific surface areas and size-dependent solubility, with a focus on environmentally-relevant iron(III) (oxyhydr)oxides and pyrite, (ii) microbial utilization of nanoparticles as 'nano-tools' for electron transfer, chemotaxis, and storage units, and (iii) speculated benefits of precipitating 'moldable' nanoparticles in extracellular biomineralization. We further discussed emergent questions concerning cellular level responses to nanoparticle-associated cues, and the factors that affect nanoparticles' bioavailabilities beyond size-dependent effects. We end the review by proposing a framework towards more quantitative approaches and by highlighting promising techniques to guide future research in this exciting field.

Individual cells and cell populations are at the present time investigated with a myriad of analytical tools. While most of them are commercially available, some of these analytical tools are just emerging from research laboratories and are in the developmental phase. Electrochemical sensors which allow the monitoring of low molecular weight compounds released (and / or uptaken) by cells are among these emerging tools. Such sensors are increasingly built using 2D materials (e.g. graphene-based materials, transition metal dichalcogenides, etc.) with the aim of conferring better analytical performances to these devices. The present work critically reviews studies published during the last 10 years describing electrochemical sensors made with 2D materials and exploited to monitor small compounds (e.g. H2O2, ·NO, glucose, etc.) in living biological systems. It also discusses the very few 2D material-based electrochemical sensors which are wearable or usable in vivo. Finally, the present work includes a specific section about 2D material biocompatibility, a fundamental requirement for 2D material-based sensor applications in vitro and in vivo. As such, the review provides a critical view on the state of the art of electrochemical sensors made with 2D materials and used at cellular level and it evaluates the possibility that such sensors will be used on / in the human body on a wider scale.

Intrinsically disordered proteins/regions (IDPs/IDRs) contribute to a diverse array of molecular functions in eukaryotic systems. There is also growing recognition that membraneless biomolecular condensates, many of which are organized or regulated by IDPs/IDRs, can enable spatial and temporal regulation of complex biochemical reactions in eukaryotes. Motivated by these findings, we assess if (and how) membraneless biomolecular condensates and IDPs/IDRs are functionally involved in key cellular processes and molecular functions in bacteria. We summarize the conceptual underpinnings of condensate assembly and leverage these concepts by connecting them to recent findings that implicate specific types of condensates and IDPs/IDRs in important cellular level processes and molecular functions in bacterial systems.

PURPOSE OF REVIEW The route of allergen sensing via the skin appears to influence the immune system towards mounting a type 2 response, especially in genetically predisposed individuals. Allergens recognized this way may derive from microbial, animal, food, or other plant sources and trigger atopic dermatitis. Allergens can be grouped into families depending on their structure and function, harboring significant structural and sequence similarities. Cross-reactivity between allergens is believed to arise as a consequence, and to underlie the development of further atopic diseases. RECENT FINDINGS Especially for the plant allergens of the families of PR10-related proteins and profilins, immune cross-reactions have been described. Actual studies support that food and pollen allergens can aggravate skin lesions in patients suffering from atopic dermatitis. Further on, allergens derived from air-borne or skin-borne fungi belong to common allergen families and bear cross-reactivity potential. Cross-reactivity to human homologous proteins, so-called autoallergens, is discussed to contribute to the chronification of atopic dermatitis. SUMMARY Due to high evolutionary conservation, allergic reactions can be triggered by highly homologous members of allergen families on the humoral as well as on the cellular level.

Diffusion Magnetic Resonance Imaging (MRI) plays a very important role in studying biological tissue cellular structure and functioning both in health and disease. Proper interpretation of experimental data requires the development of theoretical models that connect the diffusion MRI signal to salient features of tissue microstructure at the cellular level. In this short review, we present some theoretical approaches to describing diffusion-attenuated magnetic resonance signals. These range from the models based on statistical properties of water molecules diffusing in the tissue- cellular environment, to models allowing exact analytical calculation of the magnetic resonance signal in a specific single-compartment environment. Such theoretical analysis gives important insights into mechanisms contributing to the formation of diffusion magnetic resonance signal and its connection to biological tissue cellular structure.

Richard Feynman's 1959 vision of controlling devices at small scales and swallowing the surgeon has inspired the science-fiction Fantastic Voyage film and has played a crucial role in the rapid development of the microrobotics field. Sixty years later, we are currently witnessing a dramatic progress in this field, with artificial micro- and nanoscale robots moving within confined spaces, down to the cellular level, and performing a wide range of biomedical applications within the cellular interior while addressing the limitations of common passive nanosystems. In this review article, we discuss key recent advances in the field of micro/nanomotors toward important cellular applications. Specifically, we outline the distinct capabilities of nanoscale motors for such cellular applications and illustrate how the active movement of nanomotors leads to distinct advantages of rapid cell penetration, accelerated intracellular sensing, and effective intracellular delivery toward enhanced therapeutic efficiencies. We finalize by discussing the future prospects and key challenges that such micromotor technology face toward implementing practical intracellular applications. By increasing our knowledge of nanomotors' cell entry and of their behavior within the intracellular space, and by successfully addressing key challenges, we expect that next-generation nanomotors will lead to exciting advances toward cell-based diagnostics and therapy.

Cellular heterogeneity in biological systems presents major challenges in the diagnosis and treatment of disease and also complicates the deconvolution of complex cellular phenomena. Single-cell analysis methods provide information that is not masked by the intrinsic heterogeneity of the bulk population and can therefore be applied to gain insights into heterogeneity among different cell subpopulations with fine resolution. Over the last 5 years, an explosion in the number of single-cell measurement methods has occurred. However, most of these methods are applicable to pure populations of cultured cells and are not able to handle high levels of phenotypic heterogeneity or a large background of nontarget cells. Microfluidics is an attractive tool for single cell manipulation as it enables individual encasing of single cells, allowing for high-throughput analysis with precise control of the local environment. Our laboratory has developed a new microfluidics-based analytical strategy to meet this unmet need referred to as magnetic ranking cytometry (MagRC). Cells expressing a biomarker of interest are labeled with receptor-coated magnetic nanoparticles and isolated from nontarget cells using a microfluidic device. The device ranks the cells according to the level of bound magnetic nanoparticles, which corresponds to the expression level of a target biomarker. Over the last several years, two generations of MagRC devices have been developed for different applications. The first-generation MagRC devices are powerful tools for the quantitation and analysis of rare cells present in heterogeneous samples, such as circulating tumor cells, stem cells, and pathogenic bacteria. The second-generation MagRC devices are compatible with the efficient recovery of cells sorted on the basis of protein expression and can be used to analyze large populations of cells and perform phenotypic CRISPR screens. To improve analytical precision, newer iterations of the first-generation and second-generation MagRC devices have been integrated with electrochemical sensors and Hall effect sensors, respectively. Both generations of MagRC devices permit the isolation of viable cells, which sets the stage for a wide range of applications, such as generating cell lines from rare cells and

The drug therapy of elderly and senile patients is characterized by a number of features due to morphological, metabolic and functional disorders that occur in the body during aging at all levels of the body's life activity: the molecular genetic level, cellular level, the organ level, the regulatory level. As a result, the drugs’ pharmacokinetics and pharmacodynamics of drugs change which has a significant impact on the effectiveness and safety of drug therapy in elderly and senile patients.