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Cardiovascular disease is one of the leading causes of mortality in diabetes. High fructose consumption has been linked with the development of diabetes and cardiovascular disease. Serum and cardiac tissue fructose levels are elevated in diabetic patients, and cardiac production of fructose via the intracellular polyol pathway is upregulated. The question of whether direct myocardial fructose exposure and upregulated fructose metabolism have potential to induce cardiac fructose toxicity in metabolic stress settings arises. Unlike tightly-regulated glucose metabolism, fructose bypasses the rate-limiting glycolytic enzyme, phosphofructokinase, and proceeds through glycolysis in an unregulated manner. In vivo rodent studies have shown that high dietary fructose induces cardiac metabolic stress and functional disturbance. In vitro, studies have demonstrated that cardiomyocytes cultured in high fructose exhibit lipid accumulation, inflammation, hypertrophy and low viability. Intracellular fructose mediates post-translational modification of proteins, and this activity provides an important mechanistic pathway for fructose-related cardiomyocyte signaling and functional effect. Additionally, fructose has been shown to provide a fuel source for the stressed myocardium. Elucidating the mechanisms of fructose toxicity in the heart may have important implications for understanding cardiac pathology in metabolic stress settings.

This review describes a brief history of the discovery and studies in Russia and associated countries of the main stress protein (Hsp70) that plays important roles both in the normal function of the cell and body as well as under various stressful stimuli. Research on this protein at the Institute of Molecular Biology (Moscow) began with the elucidation of its adaptive functions at the cellular level and at the level of the whole organism. These studies examined the function of Hsp70 under normal and extreme conditions using a wide range of model and non-model animal species, from Leishmania and Drosophila to camels and humans. These analyses made it possible to elucidate the primary regulations in the evolution and function of heat shock (HS) genes in the studied organisms. Next, we studied the structure and characteristic features of heat shock genes and proteins in species with contrasting habitat temperatures. The systems of Hsp70 expression and isolation we developed using various research objects allowed us to proceed to study the protective properties of human recombinant Hsp70 in normal-aging animal models as well as animal models experiencing sepsis, Alzheimer's disease, and stroke. The results obtained open the prospects of using recombinant Hsp70 for the treatment of various neuropathologies in humans. This review describes the logic and history of investigation of Hsp70 performed by one group of scientists from Engelhardt Institute of Molecular Biology, Russian Academy of Sciences. It was not the goal of this paper to give a comprehensive general picture of other similar studies carried out in Russia during this period.

Burkholderia are intracellular pathogenic bacteria which can produce biofilm. This biofilm protects the intracellular pathogenic bacteria from antibiotic treatment and the immunological system of the host. Therefore, this review aims to describe the capacity of Burkholderia to form a biofilm, the regulation of its biofilm formation, the efficacy of antibiotics to eradicate biofilm, and the novel therapy which targets its biofilm. Burkholderia's biofilm is characterized by its lipopolysaccharides, exopolysaccharides (EPSs), biofilm-associated proteins, and eDNA. Its regulation is made by quorum sensing, c-di-AMP, sRNA, and two component systems. Many antibiotics have been used as sole or mixture agents; however, they are not always effective in eradicating the biofilm-forming Burkholderia. Inhibitors of quorum sensing and other non-conventional antibiotic approaches are promising to discover effective treatment of Burkholderia infections.

Over the past decades, low‐dose computed tomography (LD‐CT) screening has been widely used for the early detection of lung cancer. Increasing numbers of indeterminate pulmonary nodules are now being discovered. However, it remains challenging to distinguish malignant from benign pulmonary nodules, especially those considered to be small or ground‐glass (GGN) nodules. Liquid biopsies have been successfully applied in the diagnosis of advanced lung cancer, and the potential value for early detection of lung cancer has made great progress. Recent studies have demonstrated the value of various blood‐based tumor biomarkers in determining the nature of pulmonary nodules, including cell‐free DNA (cfDNA), microRNAs (miRNAs), circulating tumor cells (CTCs) and tumor‐associated autoantibodies (AAbs). In this review, we summarize the latest progress of liquid biopsies, and their potential applications and challenges in the diagnosis of malignant pulmonary nodules., Schematic representation of liquid biopsies for aiding in the diagnosis of pulmonary nodules detected by LD‐CT. The biomarkers for liquid biopsies include cell‐free DNA (cfDNA), microRNAs (miRNAs), circulating tumor cells (CTCs) and autoantibodies (AAbs).

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) as a new human coronavirus has begun spreading over Wuhan City/China in December 2019, and then spread rapidly worldwide, causing pneumonia called COVID-19. Up to now, the scientists have extensively attempted to find effective vaccines and drugs for treatment of coronavirus infections. To this end, various pharmaceutical agents are undergoing the clinical studies to assess their potency and efficacy against COVID-19. Based on the new findings, the U.S. food and drug administration (FDA) has issued an emergency use authorization for remdesivir as an effective anti-viral for remedying the hospitalized COVID-19 patients. Recently, the European medicines agency has authorized the use of remdesivir for the treatment of COVID-19. Remdesivir as a nucleotide prodrug exhibits broad-spectrum antiviral activities against RNA viruses. In this short review, we have rendered a brief overview of discovery and synthesis for remdesivir.

Genomics is both a data- and compute-intensive discipline. The success of genomics depends on an adequate informatics infrastructure that can address growing data demands and enable a diverse range of resource-intensive computational activities. Designing a suitable infrastructure is a challenging task, and its success largely depends on its adoption by users. In this article, we take a user-centric view of the genomics, where users are bioinformaticians, computational biologists, and data scientists. We try to take their point of view on how traditional computational activities for genomics are expanding due to data growth, as well as the introduction of big data and cloud technologies. The changing landscape of computational activities and new user requirements will influence the design of future genomics infrastructures.

Foodomics is a valuable tool to understand the biochemistry and relevant compounds associated with meat quality traits. This approach is composed of four main strategies (transcriptomics, metabolomics, proteomics and lipidomics) that allow comprehensive and high-throughput characterization of the genetic expression, metabolites, proteins and lipids of meat and meats products to improve the knowledge about the underlying mechanisms and molecules involved in the meat quality traits to produce high-quality cuts. Therefore, this mini review highlights and presents potential biomarkers (RNA, metabolites, proteins and lipids) and the biological processes associated with the main meat quality attributes (such as color, IMF, tenderness and drip loss).

The gut–brain axis (GBA) is a biochemical link that connects the central nervous system (CNS) and enteric nervous system (ENS). Clinical and experimental evidence suggests gut microbiota as a key regulator of the GBA. Microbes living in the gut not only interact locally with intestinal cells and the ENS but have also been found to modulate the CNS through neuroendocrine and metabolic pathways. Studies have also explored the involvement of gut microbiota dysbiosis in depression, anxiety, autism, stroke, and pathophysiology of other neurodegenerative diseases. Recent reports suggest that microbe-derived metabolites can influence host metabolism by acting as epigenetic regulators. Butyrate, an intestinal bacterial metabolite, is a known histone deacetylase inhibitor that has shown to improve learning and memory in animal models. Due to high disease variability amongst the population, a multi-omics approach that utilizes artificial intelligence and machine learning to analyze and integrate omics data is necessary to better understand the role of the GBA in pathogenesis of neurological disorders, to generate predictive models, and to develop precise and personalized therapeutics. This review examines our current understanding of epigenetic regulation of the GBA and proposes a framework to integrate multi-omics data for prediction, prevention, and development of precision health approaches to treat brain disorders.

This guidance provides clear, concise strategies for identifying coronaviruses by transmission electron microscopy of ultrathin sections of tissues or infected tissue cultures. These include a description of virus morphology as well as cell organelles that can resemble viruses. Biochemical testing and caveats are discussed. Numerous references provide information for documentation and further study., To summarize, intracellular coronaviruses are 60 to 140-nm round-to-ovoid particles, with dark 6 to 12-nm dots inside and will be contained inside a vacuole; spikes (if visible) will touch the vacuolar contents, not the cell cytosol, and will not be as prominent as those on clathrin-coated vesicles. Extracellular virus particles, released through the plasma membrane by exocytosis, will cling to the cell surface, and may be more likely to show surface projections, and the spikes will face the extracellular space. Thus, the ultrastructural findings in tissue described in many of the published articles does not confirm the presence of coronavirus directly in tissue, and, when in doubt, investigators should consult an ultrastructural virologist or one of the virology authors listed.6,29, 30, 31, 32, 33, 34, 35, 36, 37,39, 40, 41, 42, 43, 44, 45,47, 48, 49

Skin is a rather complex, yet useful organ of our body. Besides, skin aging is a complicated process that gains a growing interest as mediates many molecular processes in our body. Thus, an efficient skin model is important to understand skin aging function as well as to develop an effective innovative product for skin aging treatment. In this mini review, we present in vitro methods for assessments of skin aging in an attempt to pinpoint basic molecular mechanisms behind this process achieving both a better understanding of aging function and an effective evaluation of potential products or ingredients that counteract aging. Specifically, this study presents in vitro assays such as 2D or 3D skin models, to evaluate skin aging-related processes such as skin moisturization, photoaging, wound healing, menopause, and skin microbiome as novel efforts in the designing of efficacy assessments in the development of skincare products.

Saliva has been proposed as an alternative to upper airway swabs when testing for severe acute respiratory syndrome coronavirus 2. Although some studies have suggested higher viral loads and clinical sensitivity when testing saliva, studies have been relatively small and have given rise to contradictory results. To better understand the relative performance characteristics of saliva and upper airway samples, I performed a rapid systematic review (registered on PROSPERO as CRD42020205035), focusing on studies that included at least 20 subjects who provided diagnostic saliva and upper airway samples on the same day, which were tested by nucleic acid amplification methods and for which a confusion matrix could be constructed for based on a composite reference standard. Nineteen studies comprising 21 cohorts that met predetermined acceptance criteria were identified following a search of PubMed, medRxiv, and bioRxiv. Seven of these cohorts were incorporated into a meta-analysis using a random effects model, which suggests that nasopharyngeal swabs are somewhat more sensitive than saliva samples for the diagnosis of early disease in ambulatory patients, such as in drive-through centers or community health centers. Nevertheless, the difference is modest, and the reduced need for personal protective equipment for saliva sampling may justify the difference. Conclusions are limited by the significant heterogeneity of disease prevalence in the study populations and variation in the approaches to saliva sample collection.

Thoracoscopic lobectomy has become the preferred approach for surgical management of early stage lung cancer, but the potential higher operative costs limit its widespread use. Theoretically, higher direct costs may be significantly counterbalanced by lower indirect costs, resulting in lower overall costs for thoracoscopic than for open lobectomy. To support this hypothesis, we reviewed the literature until May 2020, analyzing all papers comparing the cost of thoracoscopic versus open lobectomy.A total of 20 studies provided the most applicable evidence to evaluate this issue. In all the studies apart from one, thoracoscopic lobectomy was associated with higher operative costs due to the increased use of disposable instruments, and prolonged operative time. By contrast, in 17 studies the increased operative costs were significantly offset by indirect costs which were lower in thoracoscopic than in open lobectomy due to fewer postoperative complications, faster recovery, and lower readmission rates. It translated into lower overall costs for thoracoscopic than for open lobectomy in 10 studies, similar costs in seven, and higher in three, despite the lower hospitalization costs. The low bed fees and high prices of disposable instruments in these three studies may explain the discordance. The careful use of disposable instruments, and the minimizing hospitalization costs can reduce the total costs of thoracoscopic lobectomy to levels similar or to below those of open lobectomy. The worry that video‐assisted thoracoscopic surgery lobectomy (VATSL) might be associated with an increased overal cost is thus not warranted, and should not be used as an excuse against the use of VATS in surgery for early stage lung cancers., Is video‐assisted thoracoscopic lobectomy associated with higher overall costs compared with open surgery? A review of the literature until May 2020 was performed, and 20 studies provided the most applicable evidence to evaluate this issue.Thoracoscopic lobectomy was associated with higher operative costs than open lobectomy, but lower indirect costs. It translated into lower overall costs for thoracoscopic than for open lobectomy in 10 studies, similar in seven, and higher in three studies.The worry that thoracoscopic lobectomy might be associated with increased total cost is thus not warranted, and should not be used as an excuse against the use of thoracoscopy in surgery for early stage lung cancers.

Percutaneous thermal ablation is an important treatment for lung cancer and is widely used in hospitals. Puncture biopsy is generally required for pathological diagnosis before or after thermal ablation. Pathological diagnosis provides both evidence of benign and malignant lesions for ablation therapy and is of important significance for the next step in disease management. Furthermore, the sequence of ablation and biopsy affects the accuracy of pathological diagnosis, the complete ablation rate of thermal ablation, and incidence of surgery‐related complications. Ultimately, it may affect the patient's benefit from local treatment. This article reviews the research progress of traditional asynchronous biopsy followed by ablation, the emerging methods of synchronous biopsy followed by ablation, and synchronous ablation followed by biopsy in the last decade. Key points The sequence of ablation and biopsy affects the accuracy of pathological diagnosis, the complete ablation rate of thermal ablation, and the incidence of surgical‐related complications. This article reviewed the recent 10 years' literature on the surgical sequence of biopsy and ablation for lung tumors, the advantages, disadvantages and indications of different orders were analyzed., This article reviews the research progress of traditional asynchronous biopsy followed by ablation, the emerging methods of synchronous biopsy followed by ablation, and synchronous ablation followed by biopsy in the last decade.

It has long been acknowledged that changes in the regulation of gene expression may account for major organismal differences. However, we still do not fully understand how changes in gene expression evolve and how do such changes influence organisms’ differences. We are even less aware of the impact such changes might have in restricting gene flow between species. Here, we focus on studies of gene expression and speciation in the Drosophila model. We review studies that have identified gene interactions in post-mating reproductive isolation and speciation, particularly those that modulate male gene expression. We also address studies that have experimentally manipulated changes in gene expression to test their effect in post-mating reproductive isolation. We highlight the need for a more in-depth analysis of the role of selection causing disrupted gene expression of such candidate genes in sterile/inviable hybrids. Moreover, we discuss the relevance to incorporate more routinely assays that simultaneously evaluate the potential effects of environmental factors and genetic background in modulating plastic responses in male genes and their potential role in speciation.

The renin–angiotensin system and its key hormone angiotensin II (AngII) are known to play an important role in the physiology and pathophysiology of the kidney. AngII exerts its vasoconstrictor and vasodilator responses controlling the major renal functions via AngII type 1 receptor (AT1R) and AngII type 2 receptor , respectively, belonging to the family of G protein–coupled receptors. However, the implication of other receptors communicating or functionally interacting with AngII receptors via cross talk at their downstream signaling or heterodimerization has been well documented. In this mini review, the different AT1R heterodimers identified in vitro and in vivo are described with an emphasis on their potential implication in the renal functions and disorders. This shows the importance of AT1R as a hub receptor in the renal system but also illustrates the complexity of such a system with new perspectives in the pharmacological targeting of the renin–angiotensin system, AngII–AT1R axis, and its related heterodimers.

Background The decision of whether frozen embryo transfer (FET) should be performed in the cycle immediately after OPU or at least one cycle later is controversial. FET could improve pregnancy rates in IVF; however, how much time is needed for the endometrium to return to optimal receptivity after ovarian stimulation is not known. Methods Electronic search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify studies providing data on the influence of the interval between embryo freezing (or OPU) and FET in FET cycles published between January 1, 2007, and February 1, 2020. Main findings Data analyzed indicated that in the immediate FET cycles, there was a trend to an increased biochemical pregnancy rate (RR = 1.08; CI = 1.00‐1.18), whereas the clinical pregnancy rate was somewhat higher, but without reaching statistical significance (RR = 1.07; CI = 0.99‐1.15). The live birth rate was similar in the two groups (RR = 1.05; CI = 0.95‐1.15), as was the implantation rate (RR = 0.98; CI = 0.83‐1.16). Stratifying by embryo stage or FET type (freeze‐all or FET after failed fresh transfer) showed no differences. Conclusion Systematically delaying FET does not offer benefits to IVF outcomes. In addition, immediate transfer is associated with a nonsignificant trend to better clinical pregnancy rate and it also avoids the psychological effects of prolonging the stress on prospective parents., These meta‐analysis showed that systematically delaying FET does not offer benefits to IVF outcomes. In addition, immediate transfer is associated with a non‐significant trend to better clinical PR and it also avoids the psychological effects of prolonging the stress on prospective parents.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a pandemic infection in 2020 has presented many therapeutic challenges. Not least among these is the importance of abnormal host response to infection that is one of the main drivers of more severe disease. Despite significant research endeavours, very few effective therapies have been identified, in part related to the different pathogenic mechanisms underlying different stages of clinical COVID-19. This mini review summarises data related to current and potential future therapies for COVID-19 and highlights the many challenges inherent in developing effective therapeutic options for new pandemic infection.

Background Endometriosis is a common gynecological condition in which stromal or glandular epithelium is implanted in extrauterine locations. Endometriosis causes detrimental effects on the granulosa cells, and phthalate interferes with the biological and reproductive function of endometrial cells at a molecular level. Methods This article retrospectively reviewed the studies on phthalate exposure and its relationship with endometriosis. A literature search was performed for scientific articles using the keywords “phthalate and endometriosis,” “endometriosis and granulosa cells,” “phthalate and granulosa cells,” and “phthalates and endometrial cells.” Results Endometriosis can affect cytokine production, steroidogenesis, cell cycle progression, expression of estrogen receptor‐α (ER‐α)/progesterone receptor (PR), and cause endoplasmic reticulum stress, senescence, apoptosis, autophagy, and oxidative stress in the granulosa cells. Mono‐n‐butyl phthalate (MnBP) alters the expression of cytokines, cell cycle‐associated genes, ovarian stimulation, steroidogenesis, and progesterone production. Several in vitro studies have demonstrated that phthalate caused inflammation, invasion, change in cytokines, increased oxidative stress, viability, resistance to hydrogen peroxide, and proliferation of endometrial cells. Conclusion This might provide new insights about the impact of phthalate on the pathogenesis of endometriosis and its consequences on the ovarian function.

Background Reproductive medicine deals with fertility and is closely related to heredity. In reproductive medicine, it is necessary to provide genetic information for the patients prior to assisted reproductive technology (ART). Japan Society for Reproductive Medicine (JSRM) requires doctors involved in reproductive medicine to have standard knowledge of reproductive genetics and knowledge of reproductive medicine, which is covered in their publication, “required knowledge of reproductive medicine.” Methods With the aim of providing straightforward explanations to patients in the clinical situation at pre‐ART counseling, we provide the following five topics, such as (a) risk of birth defects in children born with ART, (b) chromosomal abnormalities, (c) Y chromosome microdeletions (YCMs), (d) possible chromosomal abnormal pregnancy in oligospermatozoa requiring ICSI (intracytoplasmic sperm injection), and (e) epigenetic alterations. Main findings The frequency of chromosome abnormalities in infertile patients is 0.595%‐0.64%. YCMs are observed in 2%‐10% of severe oligospermic men. High incidence of spermatozoa with chromosomal abnormalities has been reported in advanced oligospermia and asthenozoospermia that require ICSI. Some epigenetic alterations were reported in the children born with ART. Conclusion Certain genetic knowledge is important for professionals involved in reproductive medicine, even if they are not genetic experts.

Bone is a hard connective tissue that undergoes a systematic renewal. This highly dynamic organ is made up of four different types of cells, however, bone formation is commonly attributed to osteoblasts and bone resorption to osteoclasts. Bone tissue formation occurs during embryonic development and in certain post-birth pathological conditions. The immune system could influence the functions of bone cells, and the crosstalk between hematopoietic, immune, and bone cells is known as osteoimmunology. Indeed, cytokines produced by immune cells, including TNF-α and IL-6, are critically implicated in bone pathogenesis. It is well established that diet plays an important role in bone health and function. Indeed, an antioxidant nutraceuticals-rich diet, of which pearl millet is one, can be effective in treating osteoporosis. Pearl millet (PM) is an African native cereal that constitutes the staple food for African Sahel region inhabitants as well as for many peoples in rural regions in India. Pearl millet grains’ content in amino acids, minerals, and phytochemicals may contribute to promoting bone health and metabolism. Accordingly, in the current review, we discuss the putative effects of PM nutrients, with a focus on polyphenols, bone metabolism and osteoimmunology. In the light of our previous studies and others from the literature, we suggest that PM whole grains can be effective in the prevention and management of bone pathogenesis. Keywords: PM whole grains, nutrients, polyphenols, osteoblasts, osteoclasts, osteoimmunology, TNF-α.

Microbial biofilms are a natural adaptation of microorganisms, typically composed of multiple microbial species, exhibiting complex community organization and cooperation. Biofilm dynamics and thei...

Highlights • Clinical picture generally manifests as “overlap syndrome” and leads to vicious circle. • Early identification of rising cytokine storm and multilevel course of treatment is imperative. • Adjunctive treatment improves the success in fight with consequences of CRS. • Recognition of epigenetic factors might lead to personalized approach., Cytokine storm is a form of uncontrolled systemic inflammatory reaction activated by a variety of factors and leading to a harmful homeostatic process, even to patient´s death. Triggers that start the reaction are infection, systemic diseases and rarely anaphylaxis. Cytokine storm is frequently mentioned in connection to medical interventions such as transplantation or administration of drugs. Presented mini-review would like to show current possibilities how to fight or even stop such a life-threatening, immune-mediated process in order to save lives, not only in COVID-19 patients. Early identification of rising state and multilevel course of treatment is imperative. The most widely used molecule for systemic treatment remains tocilizumab. Except for anti-IL-6 treatment, contemporary research opens the possibilities for combination of pharmaceutical, non-pharmaceutical and adjunctive treatment in a successful fight with consequences of cytokine storm. Further work is needed to discover the exact signaling pathways that lead to cytokine storm and to determine how these effector molecules and/or combination of processes can help to resolve this frequently fatal episode of inflammation. It is a huge need for all scientists and clinicians to establish a physiological rational for new therapeutic targets that might lead to more personalized medicine approaches.

Coronavirus disease 2019 (COVID-19) pandemic has uprooted our lives like never before since its onset in the late December 2019. The world has seen mounting infections and deaths over the past few months despite the unprecedented measures countries are implementing, such as lockdowns, social distancing, mask-wearing, and banning gatherings in large groups. Interestingly, young individuals seem less likely to be impacted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19. While the rate of transmission, symptom presentation, and fatality is lower in children than people from other age groups, they have been disproportionately affected by strict lockdown measures needed to curb viral spread. In this review, we describe the association between patient age and COVID-19, epidemiology of SARS-CoV-2 infection in children, psychological effects associated with lockdowns and school closures, and possible mechanisms underlying lower transmission rate of COVID-19 in children.

O-GlcNAcylation is an atypical, reversible, and dynamic glycosylation that plays a critical role in maintaining the normal physiological functions of cells by regulating various biological processes such as signal transduction, proteasome activity, apoptosis, autophagy, transcription, and translation. It can also respond to environmental changes and physiological signals to play the role of "stress receptor" and "nutrition sensor" in a variety of stress responses and biological processes. Even, a homeostatic disorder of O-GlcNAcylation may cause many diseases. Therefore, O-GlcNAcylation and its regulatory role in stress response are reviewed in this paper.

Background Pathogenic mitochondrial (mt)DNA mutations, which often cause life‐threatening disorders, are maternally inherited via the cytoplasm of oocytes. Mitochondrial replacement therapy (MRT) is expected to prevent second‐generation transmission of mtDNA mutations. However, MRT may affect the function of respiratory chain complexes comprised of both nuclear and mitochondrial proteins. Methods Based on the literature and current regulatory guidelines (especially in Japan), we analyzed and reviewed the recent developments in human models of MRT. Main findings MRT does not compromise pre‐implantation development or stem cell isolation. Mitochondrial function in stem cells after MRT is also normal. Although mtDNA carryover is usually less than 0.5%, even low levels of heteroplasmy can affect the stability of the mtDNA genotype, and directional or stochastic mtDNA drift occurs in a subset of stem cell lines (mtDNA genetic drift). MRT could prevent serious genetic disorders from being passed on to the offspring. However, it should be noted that this technique currently poses significant risks for use in embryos designed for implantation. Conclusion The maternal genome is fundamentally compatible with different mitochondrial genotypes, and vertical inheritance is not required for normal mitochondrial function. Unresolved questions regarding mtDNA genetic drift can be addressed by basic research using MRT., This review discusses current approaches and legality regarding mitochondrial replacement for preventing the inheritance of mitochondrial diseases such as encephalomyopathy, cardiomyopathy, hearing loss, diabetes, and renal impairment, caused by pathogenic mutations in mtDNA. Although relevant advances have been achieved in the field of treatments for preventing mutant mtDNA transmission, some concerns and challenges remain such as mtDNA carryover, mtDNA genetic drift, and donor‐recipient compatibility.

NmrA-like proteins are NAD(P) (H) interacting molecules whose structures are similar to that of short-chain dehydrogenases. In this review, we focus on an NADP(H) sensor, HSCARG (also named NMRAL1), which is a NmrA-like protein that is widely present in mammals, and provide a comprehensive overview of the current knowledge of its structure and physiological functions. HSCARG selectively binds to the reduced form of type II coenzyme NADPH via its Rossmann fold domain. In response to reduction of intracellular NADPH concentration, HSCARG transforms from homodimer to monomer and exhibits enhanced interactions with its binding partners. In the cytoplasm, HSCARG negatively regulates innate immunity through impairing the activities of NF-κB and RLR pathways. Besides, HSCARG regulates redox homeostasis via suppression of ROS and NO generation. Intensive and persistent oxidative stress leads to translocation of HSCARG from the cytoplasm to the nucleus, where it regulates the DNA damage response. Taken together, HSCARG functions as a linkage between cellular redox status and other signaling pathways and fine-tunes cellular response to redox changes., Graphical abstract Image 1, Highlights • HSCARG is a NmrA-like protein that selectively binds to reduced form of type II coenzyme NADPH. • Oxidative stress disrupts NADPH-promoted homodimerization and activates nuclear translocation of HSCARG. • HSCARG suppresses innate immunity pathways and impairs production of nitric oxide in the cytoplasm. • HSCARG downregulates DNA damage response and promotes cancer development in the nucleus.

Pseudohypoparathyroidism (PHP), the first known post-receptorial hormone resistance, derives from a partial deficiency of the α subunit of the stimulatory G protein (Gsα), a key component of the PTH/PTHrP signaling pathway. Since its first description, different studies unveiled, beside the molecular basis for PHP, the existence of different subtypes and of diseases in differential diagnosis associated with genetic alterations in other genes of the PTH/PTHrP pathway. The clinical and molecular overlap among PHP subtypes and with different but related disorders make both differential diagnosis and genetic counseling challenging. Recently, a proposal to group all these conditions under the novel term “inactivating PTH/PTHrP signaling disorders (iPPSD)” was promoted and, soon afterwards, the first international consensus statement on the diagnosis and management of these disorders has been published. This review will focus on the major and minor features characterizing PHP/iPPSDs as a group and on the specificities as well as the overlap associated with the most frequent subtypes.

The recent advancements in artificial intelligence (AI) and machine learning have wide applications in plant pathology with sensors, drones, robots and intelligent monitoring systems. Computer vision based phenotyping of plant stress, diagnostics and severity assessment of plant diseases has gained momentum in horticultural and field crops. Internet of things based on networking sensors for biomarkers of disease like volatile organic compounds are being used for early detection and prediction of plant diseases and host-pathogen interaction studies. Unmanned arial vehicles are employed for phenotyping orchards for precise application of plant protection chemicals. Smartphone based field diagnostics are gaining popularity across the world especially in the remote locations where the laboratory diagnostics of diseases is difficult. AI in plant pathology is still at its infancy. Integration of AI and augmented reality will enhance the accuracy and automation for remote diagnostics of plant diseases and precision plant protection. The “self sufficient, disease free, perfect plant” concept will soon become reality with the help of plant-robot bio-hybrids. This mini review explores the present status of AI technologies in plant pathology and tries to find answers for the questions like what are the common platforms used, which are the diseases where technology is applied, what are the challenges and the future prospects.

AlphaB-crystallin (HSPB5) is one of the most prominent and well-studied members of the small heat shock protein (sHsp) family. To date, it is known that this protein modulates significant cellular processes and therefore, it is not surprising that its deregulation is involved in various human pathologies, including cancer diseases. Despite the pathogenic significance of HSPB5 in cancer and its regulatory mechanism related to aggressiveness is poorly understood, several reports describe the association of breast carcinoma progression with HSPB5, whose expression is also considered an independent predictor of breast cancer metastasis to the brain. Indeed, numerous authors indicate HSPB5 as a new valuable biomarker for clinicopathological parameters and poor prognosis in breast cancer. Considering the cytoprotective, anti-apoptotic, pro-angiogenic, and pro-metastatic properties of the sHsps, it is not surprising that they are considered as promising targets for anticancer treatment, even though, at present, a deeper understanding of their mode of action is needed to allow the development of precise therapeutic interventions. Data on the direct inhibition of different sHsps demonstrate promising results in cancer pathologies; however, specific strategies against HSPB5 have not been considered. This review highlights the most relevant findings on HSPB5 and its role in breast cancer, as well as the possible strategies in using HSPB5 inhibition for therapeutic purposes.

Background Between 30% and 80% of patients with male infertility produce excessive reactive oxygen species (ROS) in their ejaculate even though the cause of male infertility is unexplained in approximately half of cases. The strong connection between oxidative stress (OS) and male infertility has led recent investigators to propose the term “Male Oxidative Stress Infertility (MOSI)” to describe OS‐associated male infertility. Methods We searched the PubMed database for original and review articles to survey the effects of OS on male infertility, and then verified the effects and treatments. Main findings Seminal plasma contains many antioxidants that protect sperm from ROS, because low amounts of ROS are required in the physiological fertilization process. The production of excessive ROS causes OS which can lower fertility through lipid peroxidation, sperm DNA damage, and apoptosis. Several assays are available for evaluating OS, including the MiOXSYS® analyzer to measure oxidation‐reduction potential. Several measures should be considered for minimizing OS and improving clinical outcomes. Conclusion Accurately diagnosing patients with MOSI and identifying highly sensitive biomarkers through proteomics technology is vital for better clinical outcomes., Excessive ROS levels lead to OS which can reduce fertile capacity through lipid peroxidation of the membrane, sperm deoxyribonucleic acid fragmentation, and apoptosis

Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most common mutant oncogenes in non‐small cell lung cancer (NSCLC). The survival of patients with KRAS mutations may be much lower than patients without KRAS mutations. However, due to the complex structure and diverse biological properties, it is difficult to achieve specific inhibitors for the direct elimination of KRAS activity, making KRAS a challenging therapeutic target. At present, with the tireless efforts of medical research, including KRAS G12C inhibitors, immunotherapy and other combination strategies, this dilemma is expected to an end. In addition, inhibition of the downstream signaling pathways of KRAS may be a promising combination strategy. Given the rapid development of treatments, understanding the details will be important to determine the individualized treatment options, including combination therapy and potential resistance mechanisms., The survival of patients with KRAS mutations may be much lower than patients without KRAS mutations. At present, with the tireless efforts of medical research, including KRAS G12C inhibitors, immunotherapy and other combination strategy, this dilemma of KRAS mutated NSCLC is expected to an end.

Background It is still unclear whether endometrial injury (EI) has a beneficial effect on reproductive outcomes, and if so, the optimal procedure characteristics are not clear. All previous papers concluded that more research is needed, and as additional studies were recently published, the insights on EI have changed significantly. Methods Searches were conducted in MEDLINE, Embase, Web of Science, and Cochrane Library, to identify randomized controlled trials examining the EI effect on IVF outcomes in women at least one previous failed cycle. Results 2015 references were identified through database searching. Ultimately, 17 studies were included, involving 3016 patients. Clinical pregnancy rate (CPR) (RR = 1.19, [95% CI 1.06–1.32], P = .003) and live birth rate (LBR) (RR = 1.18, [95%CI 1.04–1.34], P = .009) were significantly improved after EI. Number of previous failed cycles, maternal age, and hysteroscopy were found to be relevant confounders. Higher CPR and LBR were found when EI was performed twice, while performing EI once did not significantly improve reproductive rates. Conclusion According to the present meta‐analysis, EI may be offered to younger patients with few previous failed cycles and should be additionally studied in an RCT comparing different timing and more than one EI before treatment., According to the present meta‐analysis, EI may be offered to younger patients with few previous failed cycles. As higher CPR and LBR were found when EI was performed twice, it should be additionally studied in an RCT comparing different timing and more than one EI before treatment.

For many years tissue biopsy has been the primary procedure to establish cancer diagnosis and determine further treatment and prognosis. However, this method has multiple drawbacks, including, to mention some, being an invasive procedure carrying significant risk for fragile patients and allowing only for a “snapshot” of the tumor biology in time. The process of liquid biopsy allows for a minimally invasive procedure that provides molecular information about underlying cancer by analyzing circulating tumor DNA (ctDNA) via next-generation sequencing technology and circulating tumor cells. This paper focuses on describing the basis of ctDNA and its current utilities.

Non‐small cell lung cancer (NSCLC) is the leading cause of cancer death and in most cases it is often diagnosed at an advanced stage. Many genetic and microenvironmental factors are able to modify the cell cycle inducing carcinogenesis and tumor growth. Among the metabolic and genetic factors that come into play in carcinogenesis and tumor cell differentiation and growth there are two different proteins that should be considered which are glucose transporters (GLUTs) and p16INK4 The first are glucose transporters which are strongly involved in tumor metabolism, notably accelerating cancer cell metabolism both in aerobic and anaerobic conditions. There are different subtypes of GLUT family factors of which GLUT 1 is the most important and widely expressed. By contrast, p16 is mainly a tumor‐suppressor protein that acts on cyclin‐dependent kinase favoring cell cycle arrest in the G1 phase. Our search focused on the action of the aforementioned factors., This review highlights the role of p16 and GLUT‐1 and GLUTs proteins in malignancies especially in lung cancer, focusing on the pathways activated leading to cell cycle dysregulation, cancer growth and migration. Since they have a clinical prognostic value, they may become targets for novel therapies.

Retinitis pigmentosa (RP) is a common retinal dystrophy that affects millions of individuals, of both sexes, worldwide. The age of onset and the phenotypic characteristics vary between patients of different ethnicities. It may be syndromic when it coexists with several syndromes, like Usher syndrome, or nonsyndromic. It follows autosomal dominant, autosomal recessive or X-linked inheritance. RP is genetically heterogeneous with, approximately, one hundred genes identified to date. The present mini review includes articles about the pathogenesis of syndromic and non-syndromic RP. Eighty-seven papers written in English and published in the last decade, about the pathogenesis of RP were reviewed and analyzed in order to summarize and highlight the major genes implicated in RP. We identified more than 80 genes associated with syndromic and 30 genes with non-syndromic RP. Among them RHO and RPGR, followed by PRPH2, PRPF31 and RP2 are the major genes involved in RP. Keywords: Autosomal dominant, Autosomal recessive, Genes, Retinitis pigmentosa (RP) Xlinked RP.

In the current world, development and spread of antimicrobial resistance among bacteria have been raised and antimicrobial-resistant bacteria are one of the most important health challenges. The antimicrobial resistance genes can easily move and transfer among diverse bacterial species and strains. The human gut microbiota consists of a dense microbial population including trillions of microorganisms. Recently, studies have shown that the bacteria which make the major part of gut microbiota, harbor a variety of antimicrobial resistance genes which are called gut resistome. The transfer of resistance genes from commensal bacteria to gut-resident opportunistic bacteria may involve in the emergence of multi-drug resistant (MDR) bacteria. Thus, the main aim of the current mini-review was to study the mechanisms of exchange of antimicrobial resistance genes by commensal and opportunistic pathogenic bacteria in the human gut.

A phytotherapeutic approach for the development of modern drug agents can provide various vital drugs from the conventional medicinal plants. Exploration of pure phytocompounds as drug agent is expensive and time taken. Various plants and their herbal formulations are found to be useful for the cure of liver diseases. However, in some cases, the results of treatment are not up to the mark but experimental studies are carried out on a number of valuable plants and their formulations. The therapeutic efficacy is tested against some chemically induced liver damages in liver cancer cell lines and animal models. Antioxidants from the medicinal plants and common dietary sources can provide protection against the liver damages caused by the chemicals and oxidative stress mechanism.

The interactions of CD4+ T cells and B cells are fundamental for the generation of protective antibody responses, as well as for the development of harmful autoimmune diseases. Recent studies of human tissues and blood samples have established a new subset of CD4+ B helper T cells named peripheral helper T (Tph) cells. Unlike T follicular helper (Tfh) cells, which interact with B cells within lymphoid organs, Tph cells provide help to B cells within inflamed tissues. Tph cells share many B helper-associated functions with Tfh cells and induce B cell differentiation toward antibody-producing cells. The differentiation mechanism is also partly shared between Tph and Tfh cells in humans, and both Tfh and Tph cells can be found within the same tissues, including cancer tissues. However, Tph cells display features distinct from those of Tfh cells, such as the expression of chemokine receptors associated with Tph cell localization within inflamed tissues and a low Bcl-6/Blimp1 ratio. Unlike that of Tfh cells, current evidence shows that the target of Tph cells is limited to memory B cells. In this review, we first summarize recent findings on human Tph cells and discuss how Tph and Tfh cells play shared and distinct roles in human diseases.

Thoracic aortic dissection (TAD) is one of the most lethal aortic diseases due to its acute onset, rapid progress, and high rate of aortic rupture. The pathogenesis of TAD is not completely understood. In this mini-review, we introduce three emerging experimental mouse TAD models using β-aminopropionitrile (BAPN) alone, BAPN for a prolonged duration (four weeks) and then with added infusion of angiotensin II (AngII), or co-administration of BAPN and AngII chronically. We aim to provide insights into appropriate application of these three mouse models, thereby enhancing the understanding of the molecular mechanisms of TAD.

Background Mesenchymal stem cells (MSCs) can be derived from several tissues such as bone marrow, placenta, adipose tissue, or endometrial tissue. MSCs gain a lot of attention for cell‐based therapy due to their characteristics including differentiation ability and immunomodulatory effect. Preclinical and clinical studies demonstrated that MSCs can be applied to treat female infertility by improving of the functions of ovary and uterus. This mini‐ review focuses on the current study of treatment of endometrial infertility by using MSCs. Methods The present study performed a literature review focusing on the effect of MSCs for treatment of women infertility caused by endometrial dysfunction. Results Bone marrow‐, umbilical cord‐, adipose‐, amniotic‐, and menstruation‐derived MSCs enhance endometrial cell proliferation, injury repairs as well as reducing scar formation. The beneficial mechanism probably via immunomodulatory, cell differentiation, stimulates endometrial cell proliferation and down‐regulation of fibrosis genes. The major advantage of using MSCs is to improve endometrial functions resulting in increased implantation and pregnancy. Conclusions MSCs exhibit a potential for endometrial infertility treatment. Adipose‐ and menstruation‐derived stem cells show advantages over other sources because the cells can be derived easily and do not causes graft rejection after autologous transplantation., Mesenchymal stem cells for infertility treatment. A new insight into endometrial factor infertility management.

Eukaryotic cells respond to hypothermic stress through a series of regulatory mechanisms that preserve energy resources and prolong cell survival. These mechanisms include alterations in gene expression, attenuated global protein synthesis and changes in the lipid composition of the phospholipid bilayer. Cellular responses to hyperthermia, hypoxia, nutrient deprivation and oxidative stress have been comprehensively investigated, but studies of the cellular response to cold stress are more limited. Responses to cold stress are however of great importance both in the wild, where exposure to low and fluctuating environmental temperatures is common, and in medical and biotechnology settings where cells and tissues are frequently exposed to hypothermic stress and cryopreservation. This means that it is vitally important to understand how cells are impacted by low temperatures and by the decreases and subsequent increases in temperature associated with cold stress. Here, we review the ways in which eukaryotic cells respond to hypothermic stress and how these compare to the well-described and highly integrated stress response systems that govern the cellular response to other types of stress.

The association of the gut microbiota with many diseased and healthy state is currently of global interest. Gut microbiota is able to alter immune responses and behaviour and it is also involved in the pathophysiology of depression. Depression is a disorder that is etiologically heterogeneous. There is a strong evidence for microbiome links to mental health, which point to a possible future of manipulation of gut microbiota for better health. This review compiled existing literature on the relationship between depression and human gut microbiota.

Background Recently, the Japan Society of Obstetrics and Gynecology initiated a clinical study of preimplantation genetic test for aneuploidy. There will be a great need for a standardized embryo biopsy technique in Japan. However, the gold standard trophectoderm (TE) biopsy procedure has not been established, and this review outlines the clinical use of TE biopsy. Methods Based on literature, the method and associated techniques for TE biopsy, a dissection method of TE cells from blastocysts, were investigated. Main findings Two TE biopsy methods are used, namely assisted hatching (herniating) and non‐assisted hatching (direct suction); however, it is not clear which of these methods is superior. It is critical to understand whether the flicking or pulling method is beneficial. Conclusion Non‐assisted hatching biopsy method may cause blastocyst collapse with a higher probability, and it may extend the biopsy time. The biopsy procedure should be performed within 3 minutes, and thus direct TE suction may have greater disadvantages. It is a fact that pulling method of TE dissection with laser pulse is simple; however, excess laser shots may induce a higher frequency of mosaicism. It is important to understand that each technique of TE biopsy has benefits and disadvantages.

Background Extra‐pelvic endometriosis is a rare type of endometriosis, which occurs in a distant site from gynecological organs. The diagnosis of extra‐pelvic endometriosis can be extremely challenging and may result in a delay in diagnosis. The main objective of this review was to characterize abdominal wall endometriosis (AWE) and thoracic endometriosis (TE). Methods The authors performed a literature search to provide an overview of AWE and TE, which are the major types of extra‐pelvic endometriosis. Main findings Abdominal wall endometriosis includes scar endometriosis secondary to the surgical wound and spontaneous AWE, most of which occur in the umbilicus or groin. Surgical treatment appeared to be effective for AWE. Case reports indicated that the diagnosis and treatment of catamenial pneumothorax or endometriosis‐related pneumothorax (CP/ERP) are challenging, and a combination of surgery and postoperative hormonal therapy is essential. Further, catamenial hemoptysis (CH) can be adequately managed by hormonal treatment, unlike CP/ERP. Conclusion Evidence‐based approaches to diagnosis and treatment of extra‐pelvic endometriosis remain immature given the low prevalence and limited quality of research available in the literature. To gain a better understanding of extra‐pelvic endometriosis, it would be advisable to develop a registry involving a multidisciplinary collaboration with gynecologists, general surgeons, and thoracic surgeons., Abdominal wall endometriosis includes scar endometriosis secondary to the surgical wound and spontaneous AWE, most of which occur in the umbilicus or groin. The diagnosis and treatment of catamenial pneumothorax or endometriosis‐related pneumothorax (CP/ERP) are challenging, and a combination of surgery and postoperative hormonal therapy is essential. Further, catamenial hemoptysis can be adequately managed by hormonal treatment, unlike CP/ERP.

Background At present, one out of six couples is infertile, and in 50% of cases, infertility is attributed to male infertility factors. Genetic abnormalities are found in 10%‐20% of patients showing severe spermatogenesis disorders, including non‐obstructive azoospermia. Methods Literatures covering the relationship between male infertility and genetic disorders or chromosomal abnormalities were studied and summarized. Main findings (Results) Genetic disorders, including Klinefelter syndrome, balanced reciprocal translocation, Robertsonian translocation, structural abnormalities in Y chromosome, XX male, azoospermic factor (AZF) deletions, and congenital bilateral absence of vas deferens were summarized and discussed from a practical point of view. Among them, understanding on AZF deletions significantly changed owing to advanced elucidation of their pathogenesis. Due to its technical progress, AZF deletion test can reveal their delicate variations and predict the condition of spermatogenesis. Thirty‐nine candidate genes possibly responsible for azoospermia have been identified in the last 10 years owing to the advances in genome sequencing technologies. Conclusion Genetic testing for chromosomes and AZF deletions should be examined in cases of severe oligozoospermia and azoospermia. Genetic counseling should be offered before and after genetic testing.

Background Recently, the relationship between nutrition and reproduction is being studied. In particular, when older women receive reproductive treatment, egg aging causes greater problems than organic factors. Methods This study investigated the relationship between nutrition and reproduction with a focus on factors that cause aging, including oxidation, glycation, and chronic inflammation. A large volume of data concerning each nutrient's relationship with reproductive medicine was collected from a number of observational studies. Main findings The results showed that refined carbohydrates should be avoided and care should be taken to achieve proper intake of omega‐3 fatty acids. Folic acid and vitamin D were also effective. For men, antioxidant measures are especially effective. The effects of antioxidants are related to insulin resistance, which causes chronic inflammation. Conclusion Recent research has shown that rather than meal content, meal intervals are more important for improving insulin resistance. Future research should examine lifestyle‐related nutrition factors and their relationships to reproductive treatment., Recent research has shown that rather than meal content, meal intervals are more important for improving insulin resistance and reproduction.

Angiotensin II exerts a cardinal role in the pathogenesis of hypertension and renal injury via action of angiotensin II type 1 (AT(1)) receptors. Local renin-angiotensin system (RAS) activity is essential for the mechanisms mediating pathophysiological functions. Proximal tubular angiotensinogen and tubular AT(1) receptors are augmented by intrarenal angiotensin II. Caveolin 1 plays an important role as a regulatory molecule for the compartmentalization of redox signaling events through angiotensin II–induced NADPH oxidase activation in the kidney. A role for the renin-angiotensin system in the development and/or maintenance of hypertension has been demonstrated in spontaneously hypertensive rats (SHRs). Many effects of angiotensin II are dependent on the AT(1) stimulation of reactive oxygen species (ROS) production by NADPH oxidase. Angiotensin II upregulation stimulates oxidative stress in proximal tubules from SHR. The NADPH oxidase 4 (Nox4) is abundantly expressed in kidney proximal tubule cells. Induction of the stress response includes synthesis of heat shock protein 70, a molecular chaperone that has a critical role in the recovery of cells from stress and in cytoprotection, guarding cells from subsequent insults. HSP70 chaperones function in part by driving the molecular triage decision, which determines whether proteins enter the productive folding pathway or result in client substrate ubiquitination and proteasomal degradation. This review examines regulation of losartan-mediated antioxidative stress responses by the chaperone HSP70 in proximal tubule cells of spontaneously hypertensive rats.

Patients with diabetes who get coronavirus disease 2019 (COVID-19) are at risk of a severe disease course and mortality. Several factors especially the impaired immune response, heightened inflammatory response and hypercoagulable state contribute to the increased disease severity. However, there are many contentious issues about which the evidence is rather limited. There are some theoretical concerns about the effects of different anti-hyperglycaemic drugs. Similarly, despite the recognition of angiotensin converting enzyme 2 (ACE2) as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), and the role of ACE2 in lung injury; there are conflicting results with the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) in these patients. Management of patients with diabetes in times of restrictions on mobility poses some challenges and novel approaches like telemedicine can be useful. There is a need to further study the natural course of COVID-19 in patients with diabetes and to understand the individual, regional and ethnic variations in disease prevalence and course.

Graves’ disease (GD) is an autoimmune condition with the appearance of anti-TSH receptor (TSHR) autoantibodies in the serum. The consequence is the development of hyperthyroidism in most of the patients. In addition, in the most severe cases, patients can develop orbitopathy (GO), achropachy and dermopathy. The central role of the TSHR for the disease pathology has been well accepted. Therefore immunization against the TSHR is pivotal for the creation of in vivo models for the disease. However, TSHR is well preserved among the species and therefore the immune system is highly tolerant. Many differing attempts have been performed to break tolerance and to create a proper animal model in the last decades. The most successful have been achieved by introducing the human TSHR extracellular domain into the body, either by injection of plasmid or adenoviruses. Currently available models develop the whole spectrum of Graves’ disease—autoimmune thyroid disease and orbitopathy and are suitable to study disease pathogenesis and to perform treatment studies. In recent publications new immunomodulatory therapies have been assessed and also diseaseprevention by inducing tolerance using small cyclic peptides from the antigenic region of the extracellular subunit of the TSHR.

Extensive research performed over the past 10 years has resulted in dietary nitrate being considered a nutritional supplement that can improve exercise performance. However, there is still limited insight in the metabolic fate of dietary nitrate following the appearance of nitrate and nitrite in the circulation. Recent observations in humans suggest the storage of nitrate in skeletal muscle tissue. This short review discusses the possibility of nitrate being stored and utilized in human skeletal muscle tissue, and why confirming this may increase our understanding of how the nitrate -nitrite -NO pathway improves exercise performance. Further insight in skeletal muscle nitrate storage and metabolism may provide answers to current gaps in knowledge, such as the ergogenic benefit of acute vs multiday dietary nitrate supplementation, as well as the suggested muscle fiber -type specific effects on exercise performance. In this mini -review, specific questions that need further exploration are also discussed.