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Background: Distal embolization as the first manifestation of an abdominal aortic aneurysm (AAA) is relatively rare. AAAs presenting with multiple organs embolization are rarer and serious systemic conditions. There are no reports of life-saving outcomes in patients with AAAs presenting with multiple organs embolization prior to surgery. Case presentation: A 78-year-old man presented with right acute lower limb ischemia (ALLI) and ischemic enteritis coexisting with an 83-mm AAA with a large mural thrombus. Although the patient underwent successful revascularization with endovascular treatment for right ALLI, the manifestation of ischemia of the calf muscles and infection forced right above-knee amputation. The patient also presented with ischemic colitis that resolved with conservative treatment. After receiving appropriate medical therapy and rehabilitation, the patient was successfully treated with open aortic repair for the AAA. Conclusion: We successfully performed open aortic surgery for a rare case of AAA presenting with multiple organs embolization. [ABSTRACT FROM AUTHOR]

Different varieties of the same fruit tree can be classified as a fine granularity. Most them, only a single organ of fruit cannot fully extract the overall feature of the plant. It is also difficult to further improve the accuracy of recognition. Multiorgan features can be expected to recognize the fruit tree in current research. However, the inter-organ features can be interfered with each other in the multi-organ feature recognition. It is still challenging to accurately locate and distinguish different organ features. In this study, an organ segmentation (RSA-YOLOv8s) was proposed for the fruit and leaf using YOLOv8s target detection. The three parts of the model were improved, namely Backbone, Neck, and Head. A cross-stage local residual (Residual CSPLayer 2Conv, RC2) module was also designed in the Backbone part. The sensory field of each network layer was used to construct the hierarchical class residual links in each network layer. The dense and small target features were fully extracted after that. The Scale Spatial Pyramid Pooling (SSPP) module was designed in the Neck part. The spatial and scale information of the network were integrated to introduce 3D convolution. The higher-order and multi-scale features were extracted to detect the multi-scale targets. Furthermore, the Asymmetric decoupling detection head (ADDH) module was designed in the Head part. The regression of the model was realized to classify the features using an asymmetric structure. As such, the classification was focused on the center content, while the regression was the edge information. A total of 950 images of 17 fruit tree varieties were selected from the PlantCLEF2022 public dataset. The experimental results show that the precision rate, recall rate, F1 value and average precision of the RSA-YOLOv8s model were 83.2%, 87.9%, 85.5%, and 90.2%, respectively, in the recognition of fruit and leaf organ, which were 5.6, 6.6, 6.1 and 6.7 percentage points higher than those of the original, respectively; By contrast, the precision rate, recall rate, F1 value and mean precision were 88.2%, 91.7%, 89.9% and 94.3%, respectively, in the recognition of single organ, which were 6.4, 6.6, 6.5 and 7.2 percentage points higher than those of the original, respectively; The precision rate, recall rate, F1 value and the mean precision were 78.2%, 84.1%, 81.0% and 86.1%, respectively, in the recognition of leaf single organ, which were 4.8, 6.6, 5.6 and 6.2 percentage points higher than those of the original, respectively. In addition, the improved model was also applied into the 20 date varieties with a total of 3881 images. A recognition accuracy of 99.1% was achieved, which was 6.6% higher than that of the original model. The finding can provide a strong reference for the organ segmentation and variety recognition using multi-organ features, particularly for common fruit trees. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion (I/R) injury refers to a new injury caused by reperfusion after the restoration of ischemic tissue or organ blood supply. Salvianic acid A (danshensu) is a primary active ingredient extracted from Salvia miltiorrhiza. It has a protective function against I/R injury in the cardiovascular system, brain, liver, kidney, gastrointestinal tract, and other organs. This article reviews evidence of the protective effects of Salvianic acid A and its potential mechanisms of action in organ I/R injury protection. The aim of this review is to investigate the role of Salvianic acid A in the treatment of I/R injury, providing a reference resource that could facilitate subsequent studies.

Background: Positron emission tomography (PET) scanning is an important diagnostic imaging technique used in disease diagnosis, therapy planning, treatment monitoring, and medical research. The standardized uptake value (SUV) obtained at a single time frame has been widely employed in clinical practice. Well beyond this simple static measure, more detailed metabolic information can be recovered from dynamic PET scans, followed by the recovery of arterial input function and application of appropriate tracer kinetic models. Many efforts have been devoted to the development of quantitative techniques over the last couple of decades. Challenges: The advent of new-generation total-body PET scanners characterized by ultra-high sensitivity and long axial field of view, i.e., uEXPLORER (United Imaging Healthcare), PennPET Explorer (University of Pennsylvania), and Biograph Vision Quadra (Siemens Healthineers), further stimulates valuable inspiration to derive kinetics for multiple organs simultaneously. But some emerging issues also need to be addressed, e.g., the large-scale data size and organ-specific physiology. The direct implementation of classical methods for total-body PET imaging without proper validation may lead to less accurate results. Conclusions: In this contribution, the published dynamic total-body PET datasets are outlined, and several challenges/opportunities for quantitation of such types of studies are presented. An overview of the basic equation, calculation of input function (based on blood sampling, image, population or mathematical model), and kinetic analysis encompassing parametric (compartmental model, graphical plot and spectral analysis) and non-parametric (B-spline and piece-wise basis elements) approaches is provided. The discussion mainly focuses on the feasibilities, recent developments, and future perspectives of these methodologies for a diverse-tissue environment. [ABSTRACT FROM AUTHOR]

Medication during pregnancy is widespread, but there are few reports on its fetal safety. Recent studies suggest that medication during pregnancy can affect fetal morphological and functional development through multiple pathways, multiple organs, and multiple targets. Its mechanisms involve direct ways such as oxidative stress, epigenetic modification, and metabolic activation, and it may also be indirectly caused by placental dysfunction. Further studies have found that medication during pregnancy may also indirectly lead to multi-organ developmental programming, functional homeostasis changes, and susceptibility to related diseases in offspring by inducing fetal intrauterine exposure to too high or too low levels of maternal-derived glucocorticoids. The organ developmental toxicity and programming alterations caused by medication during pregnancy may also have gender differences and multi-generational genetic effects mediated by abnormal epigenetic modification. Combined with the latest research results of our laboratory, this paper reviews the latest research progress on the developmental toxicity and functional programming alterations of multiple organs in offspring induced by medication during pregnancy, which can provide a theoretical and experimental basis for rational medication during pregnancy and effective prevention and treatment of drug-related multiple fetal-originated diseases.

Medication during pregnancy is widespread, but there are few reports on its fetal safety. Recent studies suggest that medication during pregnancy can affect fetal morphological and functional development through multiple pathways, multiple organs, and multiple targets. Its mechanisms involve direct ways such as oxidative stress, epigenetic modification, and metabolic activation, and it may also be indirectly caused by placental dysfunction. Further studies have found that medication during pregnancy may also indirectly lead to multi-organ developmental programming, functional homeostasis changes, and susceptibility to related diseases in offspring by inducing fetal intrauterine exposure to too high or too low levels of maternal-derived glucocorticoids. The organ developmental toxicity and programming alterations caused by medication during pregnancy may also have gender differences and multi-generational genetic effects mediated by abnormal epigenetic modification. Combined with the latest research results of our laboratory, this paper reviews the latest research progress on the developmental toxicity and functional programming alterations of multiple organs in offspring induced by medication during pregnancy, which can provide a theoretical and experimental basis for rational medication during pregnancy and effective prevention and treatment of drug-related multiple fetal-originated diseases. This review summarizes the intrauterine mechanisms, gender differences, and multi-generational genetic effects of offspring's multi-organ developmental toxicity, programming alterations and susceptibility to multiple diseases induced by medication during pregnancy. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary: Background: Neurological damage caused by coronavirus disease 2019 (COVID-19) has attracted increasing attention. Recently, through autopsies of patients with COVID-19, the direct identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in their central nervous system (CNS) has been reported, indicating that SARS-CoV-2 might directly attack the CNS. The need to prevent COVID-19-induced severe injuries and potential sequelae is urgent, requiring the elucidation of large-scale molecular mechanisms in vivo. Methods: In this study, we performed liquid chromatography-mass spectrometry-based proteomic and phosphoproteomic analyses of the cortex, hippocampus, thalamus, lungs, and kidneys of SARS-CoV-2-infected K18-hACE2 female mice. We then performed comprehensive bioinformatic analyses, including differential analyses, functional enrichment, and kinase prediction, to identify key molecules involved in COVID-19. Findings: We found that the cortex had higher viral loads than did the lungs, and the kidneys did not have SARS-COV-2. After SARS-CoV-2 infection, RIG-I-associated virus recognition, antigen processing and presentation, and complement and coagulation cascades were activated to different degrees in all five organs, especially the lungs. The infected cortex exhibited disorders of multiple organelles and biological processes, including dysregulated spliceosome, ribosome, peroxisome, proteasome, endosome, and mitochondrial oxidative respiratory chain. The hippocampus and thalamus had fewer disorders than did the cortex; however, hyperphosphorylation of Mapt/Tau, which may contribute to neurodegenerative diseases, such as Alzheimer's disease, was found in all three brain regions. Moreover, SARS-CoV-2-induced elevation of human angiotensin-converting enzyme 2 (hACE2) was observed in the lungs and kidneys, but not in the three brain regions. Although the virus was not detected, the kidneys expressed high levels of hACE2 and exhibited obvious functional dysregulation after infection. This indicates that SARS-CoV-2 can cause tissue infections or damage via complicated routes. Thus, the treatment of COVID-19 requires a multipronged approach. Interpretation: This study provides observations and in vivo datasets for COVID-19-associated proteomic and phosphoproteomic alterations in multiple organs, especially cerebral tissues, of K18-hACE2 mice. In mature drug databases, the differentially expressed proteins and predicted kinases in this study can be used as baits to identify candidate therapeutic drugs for COVID-19. This study can serve as a solid resource for the scientific community. The data in this manuscript will serve as a starting point for future research on COVID-19-associated encephalopathy. Funding: This study was supported by grants from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, and the Natural Science Foundation of Beijing.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs. However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000 single-nucleus transcriptomes of the lung, liver, kidney, and cerebral cortex in rhesus macaques ( Macaca mulatta) infected with SARS-CoV-2 and healthy controls. Integrated analysis of the multi-organ dataset suggested that the liver harbored the strongest global transcriptional alterations. We observed prominent impairment in lung epithelial cells, especially in AT2 and ciliated cells, and evident signs of fibrosis in fibroblasts. These lung injury characteristics are similar to those reported in patients with coronavirus disease 2019 (COVID-19). Furthermore, we found suppressed MHC class I/II molecular activity in the lung, inflammatory response in the liver, and activation of the kynurenine pathway, which induced the development of an immunosuppressive microenvironment. Analysis of the kidney dataset highlighted tropism of tubule cells to SARS-CoV-2, and we found membranous nephropathy (an autoimmune disease) caused by podocyte dysregulation. In addition, we identified the pathological states of astrocytes and oligodendrocytes in the cerebral cortex, providing molecular insights into COVID-19-related neurological implications. Overall, our multi-organ single-nucleus transcriptomic survey of SARS-CoV-2-infected rhesus macaques broadens our understanding of disease features and antiviral immune defects caused by SARS-CoV-2 infection, which may facilitate the development of therapeutic interventions for COVID-19. [ABSTRACT FROM AUTHOR]

Introduction It is commonly considered that COPD or at least emphysema represents accelerated lung aging induced in part by oxidative damage from cigarette smoke components. However, the issue if there are any aging signs in other organs in patients with COPD or emphysema remains unclear. The aim of this study is to explore whether there is multiple organ aging in the animal model of emphysema induced by cigarette smoke extract (CSE), and to ascertain the possible mechanisms, if any. Methods The animal model of emphysema was induced by CSE. Histomorphological changes in lung, heart, liver, kidney and spleen tissues were measured after staining with hematoxylin and eosin (H&E). The concentrations of stem cell factor (SCF), CyclinD1 and superoxide dismutase (SOD) in serum were determined by ELISA kit. The expressions of p16 (INK4a), Sca-1, eNOS proteins and mRNA in lung, heart, liver, kidney and spleen tissues were detected by Western blotting and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), respectively. Decitabine (Dec) was applied to examine whether it could alter the changes caused by CSE. Results The histomorphology of lung tissue was significantly changed, while other organs exhibited normal structure and histomorphology. The concentrations of SCF, CyclinD1 and SOD in serum were lower in the CSE group than in the control group. The expression levels of p16(INK4a) protein and mRNA in lung, heart, liver, kidney and spleen tissues were higher in the CSE group than in the control group, while the expression levels of Sca-1 and eNOS proteins and mRNA were lower in the CSE group than in the control group, in the tissues described above. Dec could partly alleviate the damages caused by CSE and the degree of alleviation resulted by Dec varied from organ to organ. Conclusions In addition to the aging of the lung tissue in the emphysema animal model induced by CSE, the tissues of the heart, liver, kidney and spleen were also in the progress of aging, but the sensibility and affinity of lung to CSE were higher than those of the other organs. Multiple organ aging may also exist in the animal model of emphysema induced by CSE. DEC can partly alleviate the multiple organ aging caused by CSE.

Ischemia/reperfusion (I/R) injury is a common clinical problem after coronary angioplasty, cardiopulmonary resuscitation, and organ transplantation, which can lead to cell damage and death. Mitsugumin 53 (MG53), also known as Trim72, is a conservative member of the TRIM family and is highly expressed in mouse skeletal and cardiac muscle, with minimal amounts in humans. MG53 has been proven to be involved in repairing cell membrane damage. It has a protective effect on I/R injury in multiple oxygen-dependent organs, such as the heart, brain, lung, kidney, and liver. Recombinant human MG53 also plays a unique role in I/R, sepsis, and other aspects, which is expected to provide new ideas for related treatment. This article briefly reviews the pathophysiology of I/R injury and how MG53 mitigates multi-organ I/R injury.

Atherosclerosis is a chronic inflammatory disease of the vascular system that is characterized by the deposition of modified lipoproteins, accumulation of immune cells, and formation of fibrous tissue within the vessel wall. The disease occurs in vessels throughout the body and affects the functions of almost all organs including the lymphoid system, bone marrow, heart, brain, pancreas, adipose tissue, liver, kidneys, and gastrointestinal tract. Atherosclerosis and associated factors influence these tissues via the modulation of local vascular functions, induction of cholesterol-associated pathologies, and regulation of local immune responses. In this review, we discuss how atherosclerosis interferers with functions of different organs via several common pathways and how the disturbance of immunity in atherosclerosis can result in disease-provoking dysfunctions in multiple tissues. Our growing appreciation of the implication of atherosclerosis and associated microenvironmental conditions in the multi-organ pathology promises to influence our understanding of CVD-associated disease pathologies and to provide new therapeutic opportunities. [ABSTRACT FROM AUTHOR]

Summary: Women with absolute uterine factor infertility cannot get pregnant. The current experience in uterine transplantation is limited and the use of a deceased donor uterus in this area is incipient after some initial unsuccessful attempts. The birth of healthy babies through this modality in four different centers has given a new impetus to the use of this transplantation technique. We aimed to develop a technique for uterus procurement and preparation for transplantation from a brain dead donor. Fifteen uteri were retrieved from multi‐organ donor patients, 10 of these were used in bench surgeries with the proposed technique. All procedures were performed after obtaining family's consent. This study allowed the clinical use of two of the 15 organs that were procured for transplantation. One of these organs resulted in the first live birth worldwide using a uterus transplanted from a deceased donor, a landmark in reproductive medicine. Another outcome was the optimization of the surgical technique involving less manipulation of the uterine vascular pedicles. The success of this novel technique suggests that the proposed model can be replicated and optimized further to facilitate the transplantation of uterus from deceased donors. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) may cause a hypercoagulability state and thrombotic complications. Multiorgan infarctions in young patients are very rare. Here we report a 35-year-old male patient with COVID-19 complicated by multiorgan infarctions. The patient had a past medical history of uncontrolled insulin-dependent diabetes mellitus and was admitted to the intensive care unit with progressive hypoxia in the setting of SARSCoV- 2 infection. The patient received prophylactic anticoagulant during the entire hospital course. During the hospitalization, the patient developed hypoxic respiratory arrest, diffuse anoxic brain injury and brain herniation. Postmortem examination demonstrated multiple infarctions and thromboses involving the heart, bilateral lungs, kidneys, and spleen. In conclusion, multiple organ infarctions may occur in young patients with COVID-19 despite prophylactic anticoagulation therapy. [ABSTRACT FROM AUTHOR]

Acidic mammalian chitinase (CHIA) belongs to the 18-glycosidase family and is expressed in epithelial cells and certain immune cells (such as neutrophils and macrophages) in various organs. Under physiological conditions, as a hydrolase, CHIA can degrade chitin-containing pathogens, participate in Type 2 helper T (Th2)-mediated inflammation, and enhance innate and adaptive immunity to pathogen invasion. Under pathological conditions, such as rhinitis, ocular conjunctivitis, asthma, chronic atrophic gastritis, type 2 diabetes, and pulmonary interstitial fibrosis, CHIA expression is significantly changed. In addition, studies have shown that CHIA has an anti-apoptotic effect, promotes epithelial cell proliferation and maintains organ integrity, and these effects are not related to chitinase degradation. CHIA can also be used as a biomolecular marker in diseases such as chronic atrophic gastritis, dry eye, and acute kidney damage caused by sepsis. Analysis of the authoritative TCGA database shows that CHIA expression in gastric adenocarcinoma, liver cancer, renal clear cell carcinoma and other tumors is significantly downregulated compared with that in normal tissues, but the specific mechanism is unclear. This review is based on all surveys conducted to date and summarizes the expression patterns and functional diversity of CHIA in various organs. Understanding the physiological and pathophysiological relevance of CHIA in multiple organs opens new possibilities for disease treatment.

OBJECTIVE: To investigate the protective mechanism of thymosin α1 on liver injury in a rat model of multiple organ failure, based on adiponectin (ADPN)/ protein kinase B (Akt)/nuclear factor κB (NF-κB) signaling pathway. METHODS: Male SPF Sprague-Dawley rats were randomly divided into four groups: normal group, model group, experimental group, and control group. Rats in the model group, experimental group, and control group were given intraperitoneal injection of 500 mg/kg zymosan (50 g/L) to construct the rat multiple organ failure model. Normal rats were injected intraperitoneally with equal doses of normal saline. Thirty minutes after the injection, the rats in the experimental group and the control group were injected intraperitoneally with 2 mL of thymosin α1 and ganlixin with the dose of 0.5 mg/kg daily, respectively. The normal group and the model group were injected intraperitoneally with the same dose of normal saline. After 7 days of continuous administration, liver function parameters were tested; histopathological changes of rat liver tissues and cell apoptosis were detected using hematoxylin-eosin staining and TUNEL staining; immunohistochemistry and western blot were used to detect the expression of interleukin-10, tumor necrosis factor α (TNF-α), adiponectin (ADPN), adiponectin recepror 2, AdipoR2, p-AKT and NF-κB. RESULTS AND CONCLUSION: Compared with the normal group, the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin in the serum, the pathological scores of liver injury, the cell apoptotic rate, and the expression levek of TNF-α and NF-κB were significantly increased in the model group, while the serum levels of total protein, interleukin-10, ADPN, AdipoR2 and p-AKT were significantly reduced in the model group (all P < 0.05). Compared with the model group, the serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, the pathological scores of liver injury, and cell apoptotic rate in the experimental group and control group were significantly reduced, and the serum levels of total protein, interleukin-10, ADPN, AdipoR2 and p-AKT were significantly increased (all P < 0.05). To conclude, thymosin α1 has a protective effect on the liver of rats with multiple organ failure induced by zymosan. The mechanism is related to the ADPN/Akt/NF-κB signaling pathway. ADPN/Akt is activated and the activation of NF-κB is inhibited, then reducing the inflammatory response. [ABSTRACT FROM AUTHOR]

Background Carbon (C), nitrogen (N) and phosphorus (P) stoichiometric ratios are important indicators of ecosystem function and productivity. However, few studies have assessed the nutrient relationship between plant, litter and soil, and the nutrient stock in different secondary mixed forest types. Methods We investigated the C, N and P concentrations and stoichiometric ratios in trees, understory plants, litter and soil layers in three different secondary mixed forest types (broadleaf mixed forests (BM), broadleaf-conifer mixed forests (BCM) and coniferous mixed forests (CM)) in the Qinling Mountains. Results The results showed that significant differences in C:N:P stoichiometry were detected in multiple organs in the vegetation layers in the different forest types. Trees, shrubs and herbs all allocated more N and P in leaves and had a higher N:P ratio in leaves than in other organs. The C concentrations, C:N ratios and C:P ratios of all tree organs showed a decreasing order: BM < BCM < CM, while the N and P concentrations showed an increasing order: BM > BCM > CM. For litter and soil, BM had generally higher N and P concentrations than those of BCM and CM. The highest N and P stock was in tree branches-not in the stem, which had the highest biomass (except for P in CM). Compared with other forest types, CM stored more nutrients in the labile litter layer, while BM stored more nutrients in the stable soil layer. The net ecosystem nutrient element stock in BM was generally higher than that in BCM and CM. The C, N and P concentrations and stoichiometry in the plant organs, litter and soil were significantly correlated. Conclusion Our findings demonstrate that nutrient concentrations in plant organs, litter and soil are tightly linked in secondary mixed forests.

Chronic subclinical systemic inflammation has a key role in stimulating several chronic conditions associated with cardiovascular diseases, cancer, rheumatoid arthritis, diabetes, and neurodegenerative diseases. Hence, developing in vivo models of chronic subclinical systemic inflammation are essential to the study of the pathophysiology and to measure the immunomodulatory agents involved. Male Sprague–Dawley rats were subjected to intraperitoneal, intermittent injection with saline, or lipopolysaccharide (LPS) (0.5, 1, 2 mg/kg) thrice a week for 30 days. Hematological, biochemical, and inflammatory mediators were measured at different timepoints and at the end of the study. The hearts, lungs, kidneys, and livers were harvested for histological evaluation. Significant elevation in peripheral blood leukocyte includes neutrophils, monocytes, and lymphocytes, as well as the neutrophils-to-lymphocyte ratio. The pro-inflammatory mediator levels [C-reactive protein, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-8] along with the biochemical profile (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatine kinase, creatinine, and urea) were increased significantly (P < 0.05) and increased the expression of monocyte chemoattractant protein-1 and TNF-β. The histopathological changes of heart, lung, kidney, and liver tissues revealed degeneration, cellular infiltration of leukocyte in the inflammatory foci and interstitial space, edema, early signs of fibrosis, apoptosis, and necrosis. In conclusion, these results indicate that intermittent exposure to LPS produces chronic subclinical systemic inflammation in multiple organs leading to chronic conditions and supports this model to be a useful preclinical tool for developing immunotherapeutic agents that could prevent, or reduce, chronic inflammatory diseases associated with, or without, bacterial translocation. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion (I/R) injury refers to a new injury caused by reperfusion after the restoration of ischemic tissue or organ blood supply. Salvianic acid A (danshensu) is a primary active ingredient extracted from Salvia miltiorrhiza . It has a protective function against I/R injury in the cardiovascular system, brain, liver, kidney, gastrointestinal tract, and other organs. This article reviews evidence of the protective effects of Salvianic acid A and its potential mechanisms of action in organ I/R injury protection. The aim of this review is to investigate the role of Salvianic acid A in the treatment of I/R injury, providing a reference resource that could facilitate subsequent studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Yang, Chen, Su, Luo, Liao, Wang, Xiong, Zhang, Li, Chen and Wang.)

Pseudotaxus chienii, a rare tertiary relict species with economic and ecological value, is a representative of the monotypic genus Pseudotaxus that is endemic to China. P. chienii can adapt well to habitat isolation and ecological heterogeneity under a variety of climate and soil conditions, and is able to survive in harsh environments. However, little is known about the molecular and genetic resources of this long-lived conifer. Herein, we sequenced the transcriptomes of four organs of P. chienii using the PacBio Isoform Sequencing and Illumina RNA Sequencing platforms. Based on the PacBio Iso-Seq data, we obtained 44,896, 58,082, 50,485, and 67,638 full-length unigenes from the root, stem, leaf, and strobilus, respectively, with a mean length of 2692 bp, and a mean N50 length of 3010.75 bp. We then comprehensively annotated these unigenes. The number of organ-specific expressed unigenes ranged from 4393 in leaf to 9124 in strobilus, suggesting their special roles in physiological processes, organ development, and adaptability in the different four organs. A total of 16,562 differentially expressed genes (DEGs) were identified among the four organs and clustered into six subclusters. The gene families related to biotic/abiotic factors, including the TPS, CYP450, and HSP families, were characterized. The expression levels of most DEGs in the phenylpropanoid biosynthesis pathway and plant–pathogen interactions were higher in the root than in the three other organs, suggesting that root constitutes the main organ of defensive compound synthesis and accumulation and has a stronger ability to respond to stress. The sequences were analyzed to predict transcription factors, long non-coding RNAs, and alternative splicing events. The expression levels of most DEGs of C2H2, C3H, bHLH, and bZIP families in the root and stem were higher than those in the leaf and strobilus, indicating that these TFs may play a crucial role in the survival of the root and stem. These results comprise the first comprehensive gene expression profiles obtained for different organs of P. chienii. Our findings will facilitate further studies on the functional genomics, adaptive evolution, and phylogeny of P. chienii, and lay the foundation for the development of conservation strategies for this endangered conifer.

Transepithelial Cl- and HCO3- transport is crucial for the function of all epithelia, and HCO3- is a biological buffer that maintains acid-base homeostasis. In most epithelia, a series of Cl-/HCO3- exchangers and Cl- channels that mediate Cl- absorption and HCO3- secretion have been detected in the luminal and basolateral membranes. Slc26a9 belongs to the solute carrier 26 (Slc26) family of anion transporters expressed in the epithelia of multiple organs. This review summarizes the expression pattern and functional diversity of Slc26a9 in different systems based on all investigations performed thus far. Furthermore, the physical and functional interactions between Slc26a9 and cystic fibrosis transmembrane conductance regulator (CFTR) are discussed due to their overlapping expression pattern in multiple organs. Finally, we focus on the relationship between slc26a9 mutations and disease onset. An understanding of the physiological and pathophysiological relevance of Slc26a9 in multiple organs offers new possibilities for disease therapy.

Transepithelial Cl- and HCO3- transport is crucial for the function of all epithelia, and HCO3- is a biological buffer that maintains acid-base homeostasis. In most epithelia, a series of Cl-/HCO3- exchangers and Cl- channels that mediate Cl- absorption and HCO3- secretion have been detected in the luminal and basolateral membranes. Slc26a9 belongs to the solute carrier 26 (Slc26) family of anion transporters expressed in the epithelia of multiple organs. This review summarizes the expression pattern and functional diversity of Slc26a9 in different systems based on all investigations performed thus far. Furthermore, the physical and functional interactions between Slc26a9 and cystic fibrosis transmembrane conductance regulator (CFTR) are discussed due to their overlapping expression pattern in multiple organs. Finally, we focus on the relationship between slc26a9 mutations and disease onset. An understanding of the physiological and pathophysiological relevance of Slc26a9 in multiple organs offers new possibilities for disease therapy. [ABSTRACT FROM AUTHOR]

C-C chemoattractant cytokine (chemokine) receptor 6 (CCR6) and its exclusive binding molecule CCL20 is an extremely important chemokine receptor-ligand pair which controls cell migration and immune induction during inflammatory disease. Not many scientific studies have been undertaken to study its immune mechanisms in detail, but its unique contribution to steady state cell chemotaxis in upholding immune tolerance and regulating immune homeostasis during inflammation is evident in multiple systems in the human body, including skin, liver, lung, kidney, brain, eye, joints, gonads and the gut. The role of CCR6 is constitutively expressed as a series of much debilitating severe inflammatory and autoimmune diseases, Human Immunodeficiency Virus (HIV) and cancer metastasis. CD4+ T cells, the central organizers of adaptive immunity, are stringently mobilized by the CCR6/CCL20 axis also induced by cytokines and a host of other factors in a carefully executed immune modulation scenario, to bring about a delicate balance between inflammation inducing TH17 cells and regulatory Treg cells. Although the exact immune regulatory role is not elucidated as yet, the CCR6/CCL20 axis is implicated as a front runner which determines the polarization of TH17 and regulatory Treg cells, upon which depends the resolution or progression of many debilitating disorders. This review therefore aims at emphasizing the pleiotropic significance of the chemokines CCR6 and CCL20 in immunologic function in multiple organ systems, thereby hoping to accentuate its value in future therapeutic modalities.

Background: Neurological damage caused by coronavirus disease 2019 (COVID-19) has attracted increasing attention. Recently, through autopsies of patients with COVID-19, the direct identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in their central nervous system (CNS) has been reported, indicating that SARS-CoV-2 might directly attack the CNS. The need to prevent COVID-19-induced severe injuries and potential sequelae is urgent, requiring the elucidation of large-scale molecular mechanisms in vivo., Methods: In this study, we performed liquid chromatography-mass spectrometry-based proteomic and phosphoproteomic analyses of the cortex, hippocampus, thalamus, lungs, and kidneys of SARS-CoV-2-infected K18-hACE2 female mice. We then performed comprehensive bioinformatic analyses, including differential analyses, functional enrichment, and kinase prediction, to identify key molecules involved in COVID-19., Findings: We found that the cortex had higher viral loads than did the lungs, and the kidneys did not have SARS-COV-2. After SARS-CoV-2 infection, RIG-I-associated virus recognition, antigen processing and presentation, and complement and coagulation cascades were activated to different degrees in all five organs, especially the lungs. The infected cortex exhibited disorders of multiple organelles and biological processes, including dysregulated spliceosome, ribosome, peroxisome, proteasome, endosome, and mitochondrial oxidative respiratory chain. The hippocampus and thalamus had fewer disorders than did the cortex; however, hyperphosphorylation of Mapt/Tau, which may contribute to neurodegenerative diseases, such as Alzheimer's disease, was found in all three brain regions. Moreover, SARS-CoV-2-induced elevation of human angiotensin-converting enzyme 2 (hACE2) was observed in the lungs and kidneys, but not in the three brain regions. Although the virus was not detected, the kidneys expressed high levels of hACE2 and exhibited obvious functional dysregulation after infection. This indicates that SARS-CoV-2 can cause tissue infections or damage via complicated routes. Thus, the treatment of COVID-19 requires a multipronged approach., Interpretation: This study provides observations and in vivo datasets for COVID-19-associated proteomic and phosphoproteomic alterations in multiple organs, especially cerebral tissues, of K18-hACE2 mice. In mature drug databases, the differentially expressed proteins and predicted kinases in this study can be used as baits to identify candidate therapeutic drugs for COVID-19. This study can serve as a solid resource for the scientific community. The data in this manuscript will serve as a starting point for future research on COVID-19-associated encephalopathy., Funding: This study was supported by grants from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, and the Natural Science Foundation of Beijing., Competing Interests: Declaration of interests The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Arsenic trioxide (ATO)-based therapy has demonstrated high potency in treating leukemia but limited efficacy in solid tumors. Here we report a potent multiple organ-specific anti-metastatic mechanism of nanodiamonds (NDs) in ATO-based therapy for liver cancer, which is characterized by its high metastatic potential that underlies the cause for cancer-related death. In a liver tumor mouse model, NDs co-treatment effectively inhibited the ATO-associated metastasis of liver cancer in the liver, spleen, and intestines, with inhibition potencies closely correlated with the biodistribution of NDs among different organs. Consequently, NDs co-treatment improved the survival rate of ATO-treated mice from 0% to 100% during 135–174 days from the initiation of therapy, with ∼ 20% survival of mice for over 10 months. Mechanistically, NDs co-treatment inhibited autophagy by upregulating LC3-II and p62, thereby inhibiting metastasis dissemination by inactivating the TGF-β/Smad3 pathway. Our study unravels a potentially generalizable strategy for inhibiting multiple-organ cancer metastasis via nanoparticle-mediated modulation of autophagy. [Display omitted] • Nanodiamonds (NDs) inhibited the arsenic trioxide (ATO) -associated metastasis in multiple organs. • Inhibition potencies were closely correlated with the biodistribution of NDs. • Co-treatment improved the survival rate of mice from 0% to 100% during 135–174 days. • Co-treatment led to ∼ 20% survival of mice for over 10 months. • Multiple-organ metastasis inhibition was regulated by NDs-mediated autophagy modulation. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction has recently received considerable attention as it plays an important role in adult human pathology caused by various drugs, endogenous agents and environmental agents. Benzo(a)pyrene (BaP), is a ubiquitous environmental contaminant mainly derived from anthropogenic activity during incomplete combustion of organic materials from various sources. The present study aimed to evaluate the effects of benzo(a)pyrene (BaP) on mitochondrial enzymes in the multiple organs including liver, lung, brain, stomach and kidney. ICR mice were exposed to different doses of BaP (2.5, 5 and 10 mg/kg body weight) through oral gavage and intraperitoneal injection treatment for 13 weeks consecutively. The induced mitochondrial damage in the examined organs was assayed in terms of significant increase in lipid peroxidation (LPO) and prominent decrease in antioxidant enzymes. Non enzymatic antioxidants and Krebs cycle’s enzymes were also significantly decreased in mitochondria. Additionally, BaP induced the body growth retardation and decrease in relative liver weight, increase in relative lung, stomach, kidney and brain weights, and this was further certified through histopathological lesions. Liver and lungs were more prominently damaged by BaP. The mitochondrial depletion increased in BaP dose-dependent manner. [ABSTRACT FROM AUTHOR]

Previous study have demonstrated that not only the anorectal development but also the general conditions of anorectal malformations (ARMs) male rats are severely affected by di- n -butyl phthalate (DBP) maternal exposure. However, the mechanisms underlying DBP-induced congenital defects remain elusive. Reportedly, Fgf10/Fgfr2 and androgen receptor (AR) are pivotal for the development of multiple organs. In this study, we therefore investigated the expression of Fgf10/Fgfr2 together with AR in the terminal rectum and multiple organs of ARM male rats induced by in utero exposure to DBP. DBP was administered to pregnant rats to establish the model and the incidence of ARMs in male offspring was 39.5%. On postnatal day(PND)1, the gross photograph and histopathological staining confirmed the abnormal manifestations in these organs of newborn ARMs. Decreased anogenital distance, body weight and serum testosterone level were observed in ARM male offspring. The reduced expression of Fgf10/Fgfr2 mRNA and protein was seen in terminal rectum and kidney, spleen, liver, heart in ARM male rats, whereas the reduced expression of AR was only observed in the kidney and terminal rectum. Our findings suggest the potential involvement of altered Fgf10/Fgfr2 signaling and AR in pathogenesis of local and systemic development defects in ARMs male rats induce by DBP. [ABSTRACT FROM AUTHOR]

Abstract The NOD2 gene has been associated with susceptibility to Crohn's disease and individuals with Crohn's disease are at increased risk for cancer at a number of organ sites. We studied the association between the 3020insC allele of the NOD2 gene and cancer among 2604 cancer patients and 1910 controls from Poland. Patients were diagnosed with one of twelve types of cancer in the Szczecin region between 1994 and 2004. Significant associations were found for colon cancer (OR = 1.8; 95% CI 1.2 to 2.6), for lung cancer (OR = 1.7; 95% CI = 1.1 to 2.5) and for ovarian cancer (OR = 1.6; 95% CI 1.1 to 2.3). In addition, a significant association was found for early-onset laryngeal cancer (OR = 2.9; 95% CI 1.4 to 6.2) and for breast cancer in the presence of DCIS (OR = 2.1 95% CI = 1.2 to 3.6). The NOD2 3020insC allele is relatively common (in Poland 7.3% of individuals) and may be responsible for an important fraction of cancer cases. We estimate that the lifetime cancer risk among carriers of this allele is 30% higher than that of individuals with two wild-type alleles.

Ischemia/reperfusion (I/R) injury is a common clinical problem after coronary angioplasty, cardiopulmonary resuscitation, and organ transplantation, which can lead to cell damage and death. Mitsugumin 53 (MG53), also known as Trim72, is a conservative member of the TRIM family and is highly expressed in mouse skeletal and cardiac muscle, with minimal amounts in humans. MG53 has been proven to be involved in repairing cell membrane damage. It has a protective effect on I/R injury in multiple oxygen-dependent organs, such as the heart, brain, lung, kidney, and liver. Recombinant human MG53 also plays a unique role in I/R, sepsis, and other aspects, which is expected to provide new ideas for related treatment. This article briefly reviews the pathophysiology of I/R injury and how MG53 mitigates multi-organ I/R injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Wang, Chen, Zhang, Gong, Zhong and Yang.)

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs. However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000 single-nucleus transcriptomes of the lung, liver, kidney, and cerebral cortex in rhesus macaques ( Macaca mulatta ) infected with SARS-CoV-2 and healthy controls. Integrated analysis of the multi-organ dataset suggested that the liver harbored the strongest global transcriptional alterations. We observed prominent impairment in lung epithelial cells, especially in AT2 and ciliated cells, and evident signs of fibrosis in fibroblasts. These lung injury characteristics are similar to those reported in patients with coronavirus disease 2019 (COVID-19). Furthermore, we found suppressed MHC class I/II molecular activity in the lung, inflammatory response in the liver, and activation of the kynurenine pathway, which induced the development of an immunosuppressive microenvironment. Analysis of the kidney dataset highlighted tropism of tubule cells to SARS-CoV-2, and we found membranous nephropathy (an autoimmune disease) caused by podocyte dysregulation. In addition, we identified the pathological states of astrocytes and oligodendrocytes in the cerebral cortex, providing molecular insights into COVID-19-related neurological implications. Overall, our multi-organ single-nucleus transcriptomic survey of SARS-CoV-2-infected rhesus macaques broadens our understanding of disease features and antiviral immune defects caused by SARS-CoV-2 infection, which may facilitate the development of therapeutic interventions for COVID-19.

A 30-year-old woman presented with an acute-onset high-grade fever (103°F), multiple episodes of throbbing abdominal pain in the right quadrant, and pustular red lesions on the left leg. The radiological findings were suggestive of autoimmune cholangitis and pancreatitis. The skin lesions recurred on different portions of the body, and histopathological findings showed lobular and septal lymphohistiocytic infiltrate without vasculitis. The epidermis had focal ulcerations, and the dermis showed the presence of subcutaneous fat and an infiltrate of lymphocytes, histiocytes, and neutrophils (described as lobular and septal panniculitis without vasculitis). Based on the clinical and histopathological features, a diagnosis of migratory panniculitis was made. The patient was managed with analgesics, antibiotics, and a long course of steroids; the patient responded well to these medications. To the best of our knowledge, this is one of the first case reports of migratory panniculitis associated with IgG4-related disease. Patients with migratory panniculitis should be investigated for the presence of IgG4-related autoimmune disease. However, steroids remain the drug of choice when these conditions occur together. [ABSTRACT FROM AUTHOR]

Objective: To investigate the protective effects and mechanisms of action of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis (SAP). Methods: The rats were divided into sham-operated, model control, dexamethasone treated, and Salvia miltiorrhiza treated groups. At 3, 6, and 12 h after operation, the mortality rate of different groups, pathological changes, Bcl-2-associated X protein (Bax) and nuclear factor-κB (NF-κB) protein expression levels in multiple organs (the pancreas, liver, kidneys, and lungs), toll-like receptor 4 (TLR-4) protein levels (only in the liver), intercellular adhesion molecule 1 (ICAM-1) protein levels (only in the lung), and terminal deoxynucleotidy transferase mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) staining expression levels, as well as the serum contents of amylase, glutamate-pyruvate transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), blood urea nitrogen (BUN), and creatinine (CREA) were observed. Results: The mortality rate of the dexamethasone treated group was significantly lower than that of the model control group ( P<0.05). The pathological changes in multiple organs in the two treated groups were relieved to different degrees ( P<0.05 and P<0.01, respectively), the expression levels of Bax and NF-κB proteins, and apoptotic indexes of multiple organs were reduced ( P<0.05 and P<0.01, respectively). The contents of amylase, GPT, GOT, BUN, and CREA in the two treated groups were significantly lower than those in model control groups ( P<0.05 and P<0.01, respectively). The expression level of ICAM-1 protein in the lungs (at 3 and 12 h) in the dexamethasone treated group was significantly lower than that in the Salvia miltiorrhiza treated group ( P<0.05). The serum contents of CREA (at 12 h) and BUN (at 6 h) of the Salvia miltiorrhiza treated group were significantly lower than those in the dexamethasone treated group ( P<0.05). Conclusions: Both dexamethasone and Salvia miltiorrhiza can reduce the inflammatory reaction, regulate apoptosis, and thus protect multiple organs of rats with SAP. [ABSTRACT FROM AUTHOR]

The aim of this study was to observe scutellarin parenteral solution's therapeutic effects and mechanisms in rats with severe acute pancreatitis (SAP). We divided SD rats into four groups randomly: (1) sham-operated group, (2) model control group, (3) scutellarin-treated group, and (4) Salvia miltiorrhiza-treated group. All of those rats in the abovementioned groups are randomly subdivided into 6 and 12 h subgroups, respectively, according to the postoperative time. Rats have been mercifully killed at different time after operation, and then detected their serum amylase, contents of ALT, AST, BUN, and Cr and observed the pathologic changes of multiple organs (pancreas, liver, kidneys, and lungs). We found that the survival rates have no marked differences ( P < 0.05) between model control group and two treated groups at any time points. AST and BUN serum contents have no marked difference ( P > 0.05). ALT serum contents in S. miltiorrhiza-treated group (6 and 12 h) and scutellarin-treated group (12 h) are obviously less than those in model control group ( P < 0.05). The serum contents of Cr and amylase in scutellarin-treated group (6 h) are obviously less than those in model control group ( P < 0.05). There is a different degree of relief on the pathologic changes of multiple organs in the two treated groups compared with those in model control group, of which pancreas and liver's pathologic severity scores in scutellarin-treated group (6 and 12 h) have reduced ( P < 0.01) significantly compared with those in the model control group. However, there are no significant differences between scutellarin-treated group and S. miltiorrhiza-treated group ( P > 0.05). We think the scutellarin parenteral solution has a certain protective effect on SAP rats' multiple organ injuries. [ABSTRACT FROM AUTHOR]

To observe the protective effects of Salvia miltiorrhizae injection on multiple organs of rats with SAP or OJ. Two hundred eighty-eight rats were used for SAP-associated experiments and OJ-associated experiments. The rats were randomly divided into sham-operated, model control and treated group. According to the different time points after operation, the SAP rats in each group were subdivided into 3, 6 and 12 h groups while the OJ rats were divided into 7, 14, 21 and 28 days groups. The mortality rates, pathological changes and ICAM-1 (only in lung), TLR4 (only in liver), Bax and NF-κB proteins expression in multiple organs (liver, kidney, lung, intestinal mucosa, spleen, thymus and lymph nodes) were observed, respectively. The mortality rates of treated groups decreased in both SAP and OJ experiments. Compared to model control group, the pathological changes can be seen in treated groups including; (1) the pathological changes of multiple organs in SAP and OJ experiments were improved, the pathological severity scores of kidney (at 6 h), intestinal mucosa (at 12 h), spleen (at 6 and 12 h), thymus (at 3 and 6 h) and lymph nodes (at 3 and 6 h) in SAP experiment and of liver (on 21 and 28 days), lung (21 days), intestinal mucosa (on 21 and 28 days) and spleen (on 21 and 28 days) in OJ experiment significantly declined ( P < 0.05 or P < 0.01); (2) the positive rate of Bax protein in pancreas (at 3 h) and liver (on 6 and 12 h) in SAP experiment and in liver (on 28 days), kidney (on 21 days), and thymus (on 28 days) in OJ experiment were significantly lower ( P < 0.05 or P < 0.01); (3) the positive rate of NF-κB in liver (at 12 h) and kidney (at 6 h) in SAP experiment and in liver (on 21 days), kidney (on 28 days), intestinal mucosa (on 28 days) and thymus (on 14 days) in OJ experiment significantly decreased ( P < 0.05). (4) the positive rate of ICAM-1 in lungs (at 12 h) in SAP experiment was significantly less ( P < 0.05). Salvia miltiorrhizae injection can protect multiple organs of SAP or OJ rats and inhibit the expression of ICAM-1, TLR4, NF-κB and regulate Bax proteins. Salvia miltiorrhizae may relieve the inflammation response and enhance the immunity function of SAP and OJ rats. [ABSTRACT FROM AUTHOR]

Abstract: Using the European common frog, Rana temporaria, as a model, we have studied the organ-specific gene expression patterns of thyroid hormone receptor isoforms after exposure to an organochlorine (OC) compound, p,p′-DDE. Four groups of frogs were subcutaneously injected with p,p′-DDE at 0.01, 0.1, 1 and 10mg/kg body weight, respectively. In addition, one group, serving as the control group, was injected with pure corn oil. TH receptor isoforms (TRα and TRβ) gene expressions were evaluated in the brain, kidney, testis and liver using real-time PCR with gene-specific primers. Our results show that p,p′-DDE doses induced slight elevations of TRα and TRβ mRNA in the brain. In the testis, p,p′-DDE induced an initial significant 3-fold increase of TRα mRNA at 0.01mg/kg and thereafter clear dose-dependent decreases of TRα mRNA levels were observed. For testicular TRβ mRNA levels, p,p′-DDE induced a slight elevation at 0.01mg/kg and thereafter significant decreases in TRβ mRNA levels were observed. p,p′-DDE induced significant 2–4-fold elevations of both TR isoforms in frog kidney. The strongest transcriptional effect of p,p′-DDE on TR isoforms was observed in the kidney. While TRα mRNA was not measurable in the liver, p,p′-DDE induced an initial 1.7-fold increase at 0.01mg/kg of TRβ mRNA and thereafter an apparent dose-dependent decrease was observed. The relative abundance of TRα and TRβ gene expression in different organs are in the order: kidney>testis>brain>liver. While the induction TRα and TRβ might result to hypersensitivity and subsequent gain of biological functions, the inhibition might result to loss of biological function. Given the high persistency in the environment and continued use in developing countries coupled with the tendency for global atmospheric transport, DDT and its metabolites such as p,p′-DDE will remain a focus of concern both for scientific and societal reasons. [Copyright &y& Elsevier]

Mice and/or rats are usually used to detect chemical carcinogenicity and it has been known that there are species differences in carcinogenicity. To know whether there are species difference in genotoxicity, we conducted comparative investigation of multiple organs of mice and rats in the comet assay. Since the sensitivity to xenobiotics is different for different species, we queried species difference in the genotoxic sensitivity at one equitoxic level but not at one equidose. Therefore, groups of four mice or rats were treated once intraperitoneally or orally with a chemical at highest dose without death and distinct toxic manifestation. When the death was not observed at 2000 mg/kg of a chemical, 2000 mg/kg was used for the comet study. The stomach, colon, liver, kidney, bladder, lung, brain, and bone marrow were sampled 3, 8, and 24 h after treatment.Among chemicals tested, benzyl acetate, chlorodibromomethane and p-chloro-o-toluidine are carcinogenic to mice but not rats, and aniline, azobenzene, o-phenylphenol Na, and d-limonene are carcinogenic to rats but not mice. Although the two species differed in genotoxicity target organs and migration values, the judgement of a positive or negative response was the same for all chemicals studied except for 2,4-dimethoxyaniline, 2,5-diaminotoluene, and p,p′-DDT when chemicals with positive responses in at least one organ are judged to be comet assay-positive. 2,4-Dimethoxyaniline and 2,5-diaminotoluene that are Ames test-positive non-carcinogens in both species were positive in one organ (urinary bladder for 2,4-dimethoxyaniline and stomach for 2,5-diaminotoluene) in rats, but negative in all mouse organs. p,p′-DDT, which is an Ames test-negative but in vitro cytogenetic test-positive hepatic carcinogen in mice and rats, was positive in multiple rat organs, but not in any mouse organ. These results suggest that species differences in genotoxicity at one equitoxic level are not consistent with species difference in carcinogenicity and that the use of both species is appropriate to indicate a carcinogenic potential in the comet assay with multiple organs, when chemicals being positive in at least one organ are judged to be comet assay-positive. [Copyright &y& Elsevier]

Introduction: It is commonly considered that COPD or at least emphysema represents accelerated lung aging induced in part by oxidative damage from cigarette smoke components. However, the issue if there are any aging signs in other organs in patients with COPD or emphysema remains unclear. The aim of this study is to explore whether there is multiple organ aging in the animal model of emphysema induced by cigarette smoke extract (CSE), and to ascertain the possible mechanisms, if any., Methods: The animal model of emphysema was induced by CSE. Histomorphological changes in lung, heart, liver, kidney and spleen tissues were measured after staining with hematoxylin and eosin (H&E). The concentrations of stem cell factor (SCF), CyclinD1 and superoxide dismutase (SOD) in serum were determined by ELISA kit. The expressions of p16 (INK4a), Sca-1, eNOS proteins and mRNA in lung, heart, liver, kidney and spleen tissues were detected by Western blotting and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), respectively. Decitabine (Dec) was applied to examine whether it could alter the changes caused by CSE., Results: The histomorphology of lung tissue was significantly changed, while other organs exhibited normal structure and histomorphology. The concentrations of SCF, CyclinD1 and SOD in serum were lower in the CSE group than in the control group. The expression levels of p16(INK4a) protein and mRNA in lung, heart, liver, kidney and spleen tissues were higher in the CSE group than in the control group, while the expression levels of Sca-1 and eNOS proteins and mRNA were lower in the CSE group than in the control group, in the tissues described above. Dec could partly alleviate the damages caused by CSE and the degree of alleviation resulted by Dec varied from organ to organ., Conclusions: In addition to the aging of the lung tissue in the emphysema animal model induced by CSE, the tissues of the heart, liver, kidney and spleen were also in the progress of aging, but the sensibility and affinity of lung to CSE were higher than those of the other organs. Multiple organ aging may also exist in the animal model of emphysema induced by CSE. DEC can partly alleviate the multiple organ aging caused by CSE., Competing Interests: The authors have each completed and submitted an ICMJE form for disclosure of potential conflicts of interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. Z. He reports that since the initial planning of the work, funding was received from Natural Science Foundation of China (81870040) and from Hunan province science and technology project (2015JC3033)., (© 2022 Liang G. et al.)

Acidic mammalian chitinase (CHIA) belongs to the 18-glycosidase family and is expressed in epithelial cells and certain immune cells (such as neutrophils and macrophages) in various organs. Under physiological conditions, as a hydrolase, CHIA can degrade chitin-containing pathogens, participate in Type 2 helper T (Th2)-mediated inflammation, and enhance innate and adaptive immunity to pathogen invasion. Under pathological conditions, such as rhinitis, ocular conjunctivitis, asthma, chronic atrophic gastritis, type 2 diabetes, and pulmonary interstitial fibrosis, CHIA expression is significantly changed. In addition, studies have shown that CHIA has an anti-apoptotic effect, promotes epithelial cell proliferation and maintains organ integrity, and these effects are not related to chitinase degradation. CHIA can also be used as a biomolecular marker in diseases such as chronic atrophic gastritis, dry eye, and acute kidney damage caused by sepsis. Analysis of the authoritative TCGA database shows that CHIA expression in gastric adenocarcinoma, liver cancer, renal clear cell carcinoma and other tumors is significantly downregulated compared with that in normal tissues, but the specific mechanism is unclear. This review is based on all surveys conducted to date and summarizes the expression patterns and functional diversity of CHIA in various organs. Understanding the physiological and pathophysiological relevance of CHIA in multiple organs opens new possibilities for disease treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Pseudotaxus chienii, a rare tertiary relict species with economic and ecological value, is a representative of the monotypic genus Pseudotaxus that is endemic to China. P. chienii can adapt well to habitat isolation and ecological heterogeneity under a variety of climate and soil conditions, and is able to survive in harsh environments. However, little is known about the molecular and genetic resources of this long-lived conifer. Herein, we sequenced the transcriptomes of four organs of P. chienii using the PacBio Isoform Sequencing and Illumina RNA Sequencing platforms. Based on the PacBio Iso-Seq data, we obtained 44,896, 58,082, 50,485, and 67,638 full-length unigenes from the root, stem, leaf, and strobilus, respectively, with a mean length of 2692 bp, and a mean N50 length of 3010.75 bp. We then comprehensively annotated these unigenes. The number of organ-specific expressed unigenes ranged from 4393 in leaf to 9124 in strobilus, suggesting their special roles in physiological processes, organ development, and adaptability in the different four organs. A total of 16,562 differentially expressed genes (DEGs) were identified among the four organs and clustered into six subclusters. The gene families related to biotic/abiotic factors, including the TPS, CYP450, and HSP families, were characterized. The expression levels of most DEGs in the phenylpropanoid biosynthesis pathway and plant–pathogen interactions were higher in the root than in the three other organs, suggesting that root constitutes the main organ of defensive compound synthesis and accumulation and has a stronger ability to respond to stress. The sequences were analyzed to predict transcription factors, long non-coding RNAs, and alternative splicing events. The expression levels of most DEGs of C2H2, C3H, bHLH, and bZIP families in the root and stem were higher than those in the leaf and strobilus, indicating that these TFs may play a crucial role in the survival of the root and stem. These results comprise the first comprehensive gene expression profiles obtained for different organs of P. chienii. Our findings will facilitate further studies on the functional genomics, adaptive evolution, and phylogeny of P. chienii, and lay the foundation for the development of conservation strategies for this endangered conifer. [ABSTRACT FROM AUTHOR]

The pandemic spread of COVID 19 caused by the novel Coronavirus (SARS-CoV- 2) produced a tremendous effect on the life of humanity across the globe. The epidemiological studies revealed the drastic spectrum of SARS-CoV 2 infection ranging from mere flu-like symptoms to severe respiratory suppression within a short period. Initially, cases have been confined in the emerging point, Wuhan, China. But, within a few months, it has spread all over 212 countries around the globe and presently has become a severe threat to human life. Even though it is a severe acute respiratory syndrome virus, recent reports came with multiple organ effects of SARS-CoV 2, suggesting the virulence potential of this novel virus to sweep the planet in the absence of a proper vaccine or therapy. In this review, we discuss the multi-organ pathophysiology of COVID-19 infection, together with the treatment methods adopted and innovative diagnostic methods used., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Carbon (C), nitrogen (N) and phosphorus (P) stoichiometric ratios are important indicators of ecosystem function and productivity. However, few studies have assessed the nutrient relationship between plant, litter and soil, and the nutrient stock in different secondary mixed forest types., Methods: We investigated the C, N and P concentrations and stoichiometric ratios in trees, understory plants, litter and soil layers in three different secondary mixed forest types (broadleaf mixed forests (BM), broadleaf-conifer mixed forests (BCM) and coniferous mixed forests (CM)) in the Qinling Mountains., Results: The results showed that significant differences in C:N:P stoichiometry were detected in multiple organs in the vegetation layers in the different forest types. Trees, shrubs and herbs all allocated more N and P in leaves and had a higher N:P ratio in leaves than in other organs. The C concentrations, C:N ratios and C:P ratios of all tree organs showed a decreasing order: BM < BCM < CM, while the N and P concentrations showed an increasing order: BM > BCM > CM. For litter and soil, BM had generally higher N and P concentrations than those of BCM and CM. The highest N and P stock was in tree branches-not in the stem, which had the highest biomass (except for P in CM). Compared with other forest types, CM stored more nutrients in the labile litter layer, while BM stored more nutrients in the stable soil layer. The net ecosystem nutrient element stock in BM was generally higher than that in BCM and CM. The C, N and P concentrations and stoichiometry in the plant organs, litter and soil were significantly correlated., Conclusion: Our findings demonstrate that nutrient concentrations in plant organs, litter and soil are tightly linked in secondary mixed forests., Competing Interests: The authors declare that they have no competing interests., (© 2020 Pang et al.)

Chronic subclinical systemic inflammation has a key role in stimulating several chronic conditions associated with cardiovascular diseases, cancer, rheumatoid arthritis, diabetes, and neurodegenerative diseases. Hence, developing in vivo models of chronic subclinical systemic inflammation are essential to the study of the pathophysiology and to measure the immunomodulatory agents involved. Male Sprague-Dawley rats were subjected to intraperitoneal, intermittent injection with saline, or lipopolysaccharide (LPS) (0.5, 1, 2 mg/kg) thrice a week for 30 days. Hematological, biochemical, and inflammatory mediators were measured at different timepoints and at the end of the study. The hearts, lungs, kidneys, and livers were harvested for histological evaluation. Significant elevation in peripheral blood leukocyte includes neutrophils, monocytes, and lymphocytes, as well as the neutrophils-to-lymphocyte ratio. The pro-inflammatory mediator levels [C-reactive protein, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-8] along with the biochemical profile (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatine kinase, creatinine, and urea) were increased significantly (P < 0.05) and increased the expression of monocyte chemoattractant protein-1 and TNF-β. The histopathological changes of heart, lung, kidney, and liver tissues revealed degeneration, cellular infiltration of leukocyte in the inflammatory foci and interstitial space, edema, early signs of fibrosis, apoptosis, and necrosis. In conclusion, these results indicate that intermittent exposure to LPS produces chronic subclinical systemic inflammation in multiple organs leading to chronic conditions and supports this model to be a useful preclinical tool for developing immunotherapeutic agents that could prevent, or reduce, chronic inflammatory diseases associated with, or without, bacterial translocation.

C-C chemoattractant cytokine (chemokine) receptor 6 (CCR6) and its exclusive binding molecule CCL20 is an extremely important chemokine receptor-ligand pair which controls cell migration and immune induction during inflammatory disease. Not many scientific studies have been undertaken to study its immune mechanisms in detail, but its unique contribution to steady state cell chemotaxis in upholding immune tolerance and regulating immune homeostasis during inflammation is evident in multiple systems in the human body, including skin, liver, lung, kidney, brain, eye, joints, gonads and the gut. The role of CCR6 is constitutively expressed as a series of much debilitating severe inflammatory and autoimmune diseases, Human Immunodeficiency Virus (HIV) and cancer metastasis. CD4⁺ T cells, the central organizers of adaptive immunity, are stringently mobilized by the CCR6/CCL20 axis also induced by cytokines and a host of other factors in a carefully executed immune modulation scenario, to bring about a delicate balance between inflammation inducing T H 17 cells and regulatory T reg cells. Although the exact immune regulatory role is not elucidated as yet, the CCR6/CCL20 axis is implicated as a front runner which determines the polarization of T H 17 and regulatory T reg cells, upon which depends the resolution or progression of many debilitating disorders. This review therefore aims at emphasizing the pleiotropic significance of the chemokines CCR6 and CCL20 in immunologic function in multiple organ systems, thereby hoping to accentuate its value in future therapeutic modalities., Competing Interests: The authors declare no conflict of interests.

Ischemia-reperfusion (I/R) injury affects o 2 -dependent organs including liver, kidneys, heart, brain, and intestine. I/R injury is described as the cellular injury in an organ caused by ischemia and then further aggravated during the reperfusion due to intracellular alterations. It is a process that happens in clinical settings such as organ transplantation, reperfusion after thrombolytic therapy, and coronary angioplasty. Crocus sativus L. known as saffron used in folk medicine for its beneficial effects. It contains multiple bioactive compounds including the crocin, crocetin, picrocrocin, and safranal. Crocin, a water-soluble carotenoid has antitumor, radical scavenging, anti hyperlipidemia and memory improving effects. Moreover, crocin has antioxidant, and protective effects on I/R models in rats at various organs such as heart, brain, kidney, stomach, liver, and kidney as described in detail in this review., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)