Climate-driven changes of global marine mercury cycles in 2100.

Human exposure to monomethylmercury (CH3Hg), a potent neurotoxin, is principally through the consumption of seafood. The formation of CH3Hg and its bioaccumulation in marine food webs experience ongoing impacts of global climate warming and ocean biogeochemistry alterations. Employing a series of sensitivity experiments, here we explicitly consider the effects of climate change on marine mercury (Hg) cycling within a global ocean model in the hypothesized twenty-first century under the business-as-usual scenario. Even though the overall prediction is subjected to significant uncertainty, we identify several important climate change impact pathways. Elevated seawater temperature exacerbates elemental Hg (Hg0) evasion, while decreased surface wind speed reduces air-sea exchange rates. The reduced export of particulate organic carbon shrinks the pool of potentially bioavailable divalent Hg (HgII) that can be methylated in the subsurface ocean, where shallower remineralization depth associated with lower productivity causes impairment of methylation activity. We also simulate an increase in CH3Hg photodemethylation potential caused by increased incident shortwave radiation and less attenuation by decreased sea ice and chlorophyll. The model suggests that these impacts can also be propagated to the CH3Hg concentration in the base of the marine food web. Our results offer insight into synergisms/antagonisms in the marine Hg cycling among different climate change stressors.

Bradyrhizobium japonicum HmuP is an RNA-binding protein that positively controls hmuR operon expression by suppression of a negative regulatory RNA element in the 5' untranslated region.

The hmuR operon encodes proteins for the uptake and utilization of heme as a nutritional iron source in Bradyrhizobium japonicum. The hmuR operon is transcriptionally activated by the Irr protein and is also positively controlled by HmuP by an unknown mechanism. An hmuP mutant does not express the hmuR operon genes nor does it grow on heme. Here, we show that hmuR expression from a heterologous promoter still requires hmuP, suggesting that HmuP does not regulate at the transcriptional level. Replacement of the 5' untranslated region (5'UTR) of an HmuP-independent gene with the hmuR 5'UTR conferred HmuP-dependent expression on that gene. Recombinant HmuP bound an HmuP-responsive RNA element (HPRE) within the hmuR 5'UTR. A 2 nt substitution predicted to destabilize the secondary structure of the HPRE abolished both HmuP binding activity in vitro and hmuR expression in cells. However, deletion of the HPRE partially restored hmuR expression in an hmuP mutant, and it rescued growth of the hmuP mutant on heme. These findings suggest that the HPRE is a negative regulatory RNA element that is suppressed when bound by HmuP to express the hmuR operon.

Topical ophthalmic instillation of engineered hMSCs-derived exosomes: A novel non-invasive therapeutic strategy for ocular posterior-segment disorder.

Due to the presence of protective mechanisms and blood-ocular barriers in the eye, drugs aimed at treating posterior segment ophthalmic disorder have to be administrated mostly through periocular or intravitreal injection. In the current study, we sought to investigate whether topical ophthalmic instillation of human mesenchymal stem cells (hMSCs)-derived exosomes can prevent and treat experimental autoimmune uveitis (EAU), a posterior segment ophthalmic disease induced in animals and considered a model of human autoimmune diseases of the eye. Our studies reveal that topical ophthalmic instillation of hMSCs-derived exosomes can effectively ameliorate EAU. More importantly, we demonstrate that exosomes modified by trans-activator of transcription peptide (TAT) were more effective than naive exosomes in penetrating ocular barrier and preventing/treating EAU. Taken together, these results indicate that topical ophthalmic instillation of TAT-peptide modified exosomes represents a novel non-invasive therapeutic strategy for posterior-segment ophthalmic disorders.

Contemporaneous Symptom Networks of Breast Cancer-Related Upper Limb Lymphedema: A Network Analysis.

BACKGROUND: Upper limb lymphedema (ULL) is a common and deliberating complication for breast cancer survivors (BCSs). Breast cancer survivors with ULL reported a wide range of symptoms. However, little is known about symptom patterns and interrelationships among them. This study was designed to explore symptom clusters and construct symptom networks of ULL-related symptoms among BCSs and to identify the core symptoms. METHODS: This study is a secondary data analysis using datasets from three cross-sectional studies of BCSs in China. A total of 341 participants with maximum interlimb circumference ≥2 cm and complete responses in Part I of the Breast Cancer and Lymphedema Symptom Experience Index were included. Symptom clusters were identified through principal component analysis, and multiple linear regression analysis was employed to explore factors associated with severity of overall ULL-related symptoms. A contemporaneous network with 20 frequently reported symptoms were constructed after controlling for covariates. RESULTS: Three symptom clusters, including lymph stasis symptom cluster, nerve symptom cluster, and movement limitation symptom cluster, were identified. Postsurgery time, axillary lymph node dissection, and radiotherapy were associated with the severity of ULL-related symptoms. Tightness (rs = 1.379; rscov = 1.097), tingling (rs = 1.264; rscov = 0.925), and firmness (rs = 1.170; rscov = 0.923) were the most central symptoms in both networks with and without covariates. CONCLUSIONS: Breast cancer survivors with ULL experienced severe symptom burden. Tightness, tingling, and firmness were core symptoms of ULL among BCSs. Our findings demonstrated that the assessment and targeted intervention of specific core symptoms might help to relive effectively the burden of ULL-related symptom among BCSs.

Advances in the application of extracellular vesicles derived from three-dimensional culture of stem cells.

Stem cells (SCs) have been used therapeutically for decades, yet their applications are limited by factors such as the risk of immune rejection and potential tumorigenicity. Extracellular vesicles (EVs), a key paracrine component of stem cell potency, overcome the drawbacks of stem cell applications as a cell-free therapeutic agent and play an important role in treating various diseases. However, EVs derived from two-dimensional (2D) planar culture of SCs have low yield and face challenges in large-scale production, which hinders the clinical translation of EVs. Three-dimensional (3D) culture, given its ability to more realistically simulate the in vivo environment, can not only expand SCs in large quantities, but also improve the yield and activity of EVs, changing the content of EVs and improving their therapeutic effects. In this review, we briefly describe the advantages of EVs and EV-related clinical applications, provide an overview of 3D cell culture, and finally focus on specific applications and future perspectives of EVs derived from 3D culture of different SCs.

Prognostic nomogram for patients with tongue squamous cell carcinoma: A SEER-based study.

OBJECTIVES: In order to predict the patients' prognosis with tongue squamous cell carcinoma (SCC), this study set out to develop a clinically useful and trustworthy prognostic nomogram. SUBJECTS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) Program was used to compile clinical information on patients with tongue SCC between 2010 and 2015. The likelihood of Cancer-Specific Survival (CSS) and Overall Survival (OS) for specific patients was predicted using a prognostic nomogram created with the help of the RStudio software. The nomogram's predictive ability was evaluated using the consistency index (C-index) and decision curve analysis, and the nomogram was calibrated for 1-, 2-, 3-, 5-, and 10-year CSS and OS. RESULTS: Patients numbering 6453were enrolled in this study. The primary cohort (3895) and validation cohort (2558) were each randomly assigned. Sex, age, tumor-node-metastasis (TNM) stage, surgery, chemotherapy, and radiation were significant risk factors for OS, whereas age, TNM stage, surgery, chemotherapy, and radiotherapy were significant risk factors for CSS. Additionally, C-index and calibration curves indicated that the prognostic nomogram prediction and the actual observation in both cohorts would be very coherent. CONCLUSIONS: The predictive nomogram created in this study can offer patients with tongue SCC customized treatment and survival risk assessment.

Plastic waste release caused by COVID-19 and its fate in the global ocean.

The COVID-19 pandemic has led to an increased demand for single-use plastics that intensifies pressure on an already out-of-control global plastic waste problem. While it is suspected to be large, the magnitude and fate of this pandemic-associated mismanaged plastic waste are unknown. Here, we use our MITgcm ocean plastic model to quantify the impact of the pandemic on plastic discharge. We show that 8.4 ± 1.4 million tons of pandemic-associated plastic waste have been generated from 193 countries as of August 23, 2021, with 25.9 ± 3.8 thousand tons released into the global ocean representing 1.5 ± 0.2% of the global total riverine plastic discharge. The model projects that the spatial distribution of the discharge changes rapidly in the global ocean within 3 y, with a significant portion of plastic debris landing on the beach and seabed later and a circumpolar plastic accumulation zone will be formed in the Arctic. We find hospital waste represents the bulk of the global discharge (73%), and most of the global discharge is from Asia (72%), which calls for better management of medical waste in developing countries.

Destabilization of ultra-instantaneous UHT sterilization milk stored at different temperatures.

Ultra-instantaneous UHT (UI-UHT, > 155°C, < 0.1 s) treated milk exhibits higher retention of active protein than regular UHT milk. However, UI-UHT products demonstrate increased susceptibility to destabilization during storage. This study aimed at monitoring the destabilizing process of UI-UHT milk across different storage temperatures and uncovering its potential mechanisms. Compared with regular UHT treatment, ultra-instantaneous treatment markedly accelerated the milk's destabilization process. Aged gel formation occurred after 45 d of storage at 25°C, while creaming and sedimentation were observed after 15 d at 37°C. To elucidate the instability mechanism, measurements of plasmin activity, protein hydrolysis levels, and proteomics of the aged gel were conducted. In UI-UHT milk, plasmin activity, and protein hydrolysis levels significantly increased during storage. Excessive protein hydrolysis at 37°C resulted in sedimentation, while moderate hydrolysis and an increase in protein particle size at 25°C resulted in aged gel formation. Proteomics analysis results indicated that the aged gel from UI-UHT milk contained intact caseins, major whey proteins, and their derived peptides. Furthermore, specific whey proteins including albumin, lactotransferrin, enterotoxin-binding glycoprotein PP20K, and MFGM proteins were identified in the gel. Additionally, MFGM proteins in UI-UHT milk experienced considerable hydrolysis during storage, contributing to fat instability. This study lays a theoretical foundation for optimizing UI-UHT milk storage conditions to enhance the quality of liquid milk products.

Transcriptomic analysis provides insight into the genetic regulation of shade avoidance in Aegilops tauschii.

BACKGROUND: Weeds are not only economically important but also fascinating models for studying the adaptation of species in human-mediated environments. Aegilops tauschii is the D-genome donor species of common wheat but is also a weed that influences wheat production. How shading stress caused by adjacent wheat plants affects Ae. tauschii growth is a fundamental scientific question but is also important in agriculture, such as for weed control and wheat breeding. RESULT: The present study indicated that shade avoidance is a strategy of Ae. tauschii in response to shading stress. Ae. tauschii plants exhibited growth increases in specific organs, such as stem and leaf elongation, to avoid shading. However, these changes were accompanied by sacrificing the growth of other parts of the plants, such as a reduction in tiller number. The two reverse phenotype responses seem to be formed by systemically regulating the expression of different genes. Fifty-six genes involved in the regulation of cell division and cell expansion were found to be downregulated, and one key upstream negative regulator (RPK2) of cell division was upregulated under shading stress. On the other hand, the upregulated genes under shading stress were mainly enriched in protein serine/threonine kinase activity and carbon metabolism, which are associated with cell enlargement, signal transduction and energy supply. The transcription factor WRKY72 may be important in regulating genes in response to shading stress, which can be used as a prior candidate gene for further study on the genetic regulation of shade avoidance. CONCLUSIONS: This study sheds new light on the gene expression changes and molecular processes involved in the response and avoidance of Ae. tauschii to shading stress, which may aid more effective development of shading stress avoidance or cultivars in wheat and other crops in the future.

Characterization of histone chaperone MCM2 as a key regulator in arsenic-induced depletion of H3.3 at genomic loci.

Arsenic exposure is associated with an increased risk of many cancers, and epigenetic mechanisms play a crucial role in arsenic-mediated carcinogenesis. Our previous studies have shown that arsenic exposure induces polyadenylation of H3.1 mRNA and inhibits the deposition of H3.3 at critical gene regulatory elements. However, the precise underling mechanisms are not yet understood. To characterize the factors governing arsenic-induced inhibition of H3.3 assembly through H3.1 mRNA polyadenylation, we utilized mass spectrometry to identify the proteins, especially histone chaperones, with reduced binding affinity to H3.3 under conditions of arsenic exposure and polyadenylated H3.1 mRNA overexpression. Our findings reveal that the interaction between H3.3 and the histone chaperon protein MCM2 is diminished by both polyadenylated H3.1 mRNA overexpression and arsenic treatment in human lung epithelial BEAS-2B cells. The increased binding of MCM2 to H3.1, resulting from elevated H3.1 protein levels, appears to contribute to the reduced availability of MCM2 for H3.3. To further investigate the role of MCM2 in H3.3 deposition during arsenic exposure and H3.1 mRNA polyadenylation, we overexpressed MCM2 in BEAS-2B cells overexpressing polyadenylated H3.1 or exposed to arsenic. Our results demonstrate that MCM2 overexpression attenuates H3.3 depletion at several genomic loci, suggesting its involvement in the arsenic-induced displacement of H3.3 mediated by H3.1 mRNA polyadenylation. These findings suggest that changes in the association between histone chaperone MCM2 and H3.3 due to polyadenylation of H3.1 mRNA may play a pivotal role in arsenic-induced carcinogenesis.

Roles of extracellular vesicles in ageing-related chronic kidney disease: Demon or angel.

Ageing is a universal and unavoidable phenomenon that significantly increases the risk of developing chronic kidney disease (CKD). It has been reported that ageing is associated with functional disruption and structural damage to the kidneys. Extracellular vesicles (EVs), which are nanoscale membranous vesicles containing lipids, proteins, and nucleic acids, are secreted by cells into the extracellular spaces. They have diverse functions such as repairing and regenerating different forms of ageing-related CKD and playing a crucial role in intercellular communication. This paper reviews the etiology of ageing in CKD, with particular attention paid to the roles of EVs as carriers of ageing signals and anti-ageing therapeutic strategies in CKD. In this regard, the double-edged role of EVs in ageing-related CKD is examined, along with the potential for their application in clinical settings.

Toward a Global Model of Methylmercury Biomagnification in Marine Food Webs: Trophic Dynamics and Implications for Human Exposure.

Marine fish is an excellent source of nutrition but also contributes the most to human exposure to methylmercury (MMHg), a neurotoxicant that poses significant risks to human health on a global scale and is regulated by the Minamata Convention. To better predict human exposure to MMHg, it is important to understand the trophic transfer of MMHg in the global marine food webs, which remains largely unknown, especially in the upper trophic level (TL) biota that is more directly relevant to human exposure. In this study, we couple a fish ecological model and an ocean methylmercury model to explore the influencing factors and mechanisms of MMHg transfer in marine fish food webs. Our results show that available MMHg in the zooplankton strongly determines the MMHg in fish. Medium-sized fish are critical intermediaries that transfer more than 70% of the MMHg circulating in food webs. Grazing is the main factor to control MMHg concentrations in different size categories of fish. Feeding interactions affected by ecosystem structures determine the degree of MMHg biomagnification. We estimate a total of 6.1 metric tons of MMHg potentially digested by the global population per year through marine fish consumption. The model provides a useful tool to quantify human exposure to MMHg through marine fish consumption and thus fills a critical gap in the effectiveness evaluation of the convention.

Modeling the Mercury Cycle in the Sea Ice Environment: A Buffer between the Polar Atmosphere and Ocean.

Sea ice (including overlying snow) is a dynamic interface between the atmosphere and the ocean, influencing the mercury (Hg) cycling in polar oceans. However, a large-scale and process-based model for the Hg cycle in the sea ice environment is lacking, hampering our understanding of regional Hg budget and critical processes. Here, we develop a comprehensive model for the Hg cycle at the ocean-sea ice-atmosphere interface with constraints from observational polar cryospheric data. We find that seasonal patterns of average total Hg (THg) in snow are governed by snow thermodynamics and deposition, peaking in springtime (Arctic: 5.9 ng/L; Antarctic: 5.3 ng/L) and minimizing during ice formation (Arctic: 1.0 ng/L, Antarctic: 0.5 ng/L). Arctic and Antarctic sea ice exhibited THg concentration peaks in summer (0.25 ng/L) and spring (0.28 ng/L), respectively, governed by different snow Hg transmission pathways. Antarctic snow-ice formation facilitates Hg transfer to sea ice during spring, while in the Arctic, snow Hg is primarily moved through snowmelt. Overall, first-year sea ice acts as a buffer, receiving atmospheric Hg during ice growth and releasing it to the ocean in summer, influencing polar atmospheric and seawater Hg concentrations. Our model can assess climate change effects on polar Hg cycles and evaluate the Minamata Convention's effectiveness for Arctic populations.

Distinct Responses of Thitarodes xiaojinensis ß-1,3-Glucan Recognition Protein-1 and Immulectin-8 to Ophiocordyceps sinensis and Cordyceps militaris Infection.

Melanization and encapsulation are prominent defense responses against microbes detected by pattern recognition receptors of their host insects. In the ghost moth Thitarodes xiaojinensis, an activated immune system can melanize and encapsulate the fungus Cordyceps militaris However, these responses were hardly detected in the host hemolymph postinfection of another fungus Ophiocordyceps sinensis The immune interaction between O. sinensis and the host remains largely unknown, which hinders the artificial cultivation of Chinese cordyceps. We found that T. xiaojinensis ß-1,3-glucan recognition protein-1 (ßGRP1) was needed for prophenoloxidase activation induced by C. militaris Failure of ßGRP1 to recognize O. sinensis is a primary reason for the lack of melanization in the infected host. Lyticase or snailase treatment combined with binding and immunofluorescence detection showed the existence of a protective layer preventing the fungus from ßGRP1 recognition. Coimmunoprecipitation and mass spectrometry analysis indicated that ßGRP1 interacted with immulectin-8 (IML8) via binding to C. militaris IML8 promotes encapsulation. This study suggests the roles of T. xiaojinensis ßGRP1 and IML8 in modulating immune responses against C. militaris Most importantly, the data indicate that O. sinensis may evade melanization by preventing ßGRP1 recognition.

Micro electrical fields induced MSC-sEVs attenuate neuronal cell apoptosis by activating autophagy via lncRNA MALAT1/miR-22-3p/SIRT1/AMPK axis in spinal cord injury.

Spinal cord injury (SCI) is a traumatic condition of the central nervous system that causes paralysis of the limbs. Micro electric fields (EF) have been implicated in a novel therapeutic approach for nerve injury repair and regeneration, but the effects of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles that are induced by micro electric fields (EF-sEVs) stimulation on SCI remain unknown. The aim of the present study was to investigate whether EF-sEVs have therapeutic effects a rat model of SCI. EF-sEVs and normally conditioned human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (CON-sEVs) were collected and injected intralesionally into SCI model rats to evaluate the therapeutic effects. We detect the expression of candidate long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA-MALAT1) in EF-sEVs and CON-sEVs. The targets and downstream effectors of lncRNA-MALAT1 were investigated using luciferase reporter assays. Using both in vivo and in vitro experiments, we demonstrated that EF-sEVs increased autophagy and decreased apoptosis after SCI, which promoted the recovery of motor function. We further confirmed that the neuroprotective effects of EF-sEVs in vitro and in vivo correlated with the presence of encapsulated lncRNA-MALAT1 in sEVs. lncRNA-MALAT1 targeted miR-22-3p via sponging, reducing miR-22-3p's suppressive effects on its target, SIRT1, and this translated into AMPK phosphorylation and increased levels of the antiapoptotic protein Bcl-2. Collectively, the present study identified that the lncRNA-MALAT1 in EF-sEVs plays a neuroprotective role via the miRNA-22-3p/SIRT1/AMPK axis and offers a fresh perspective and a potential therapeutic approach using sEVs to improve SCI.

Predicting lymphedema self-management behaviours in breast cancer patients: A structural equation model with the Integrated Theory of Health Behaviour Change.

AIMS: To explore predictors of lymphedema self-management behaviours among Chinese breast cancer survivors based on the Integrated Theory of Health Behaviour Change, and to clarify the interrelationship among these variables. DESIGN: Further analysis of a multicentre cross-sectional and survey-based study. METHODS: A total of 586 participants with breast cancer were recruited from December 2021 to April 2022 in different cities in China. We used self-reported questionnaires to collect data. Descriptive analysis, bivariate analysis and structural equation model were performed. RESULTS: The Integrated Theory of Health Behaviour Change is suitable for predicting lymphedema self-management behaviours. The final structural model showed good model fit. Social support, self-efficacy and lymphedema knowledge positively affected lymphedema self-management behaviours, directly and indirectly. Self-regulation acted as a crucial mediator between these variables and self-management. The direct path between social support and self-regulation was not significant. Lymphedema knowledge and social support also influenced self-management via illness perception, self-efficacy and self-regulation, sequentially. These variables explained 55.9% of the variance in lymphedema self-management behaviours. CONCLUSIONS: The modified model based on the Integrated Theory of Health Behaviour Change fitted well in predicting lymphedema self-management behaviours among breast cancer patients. Lymphedema knowledge, illness perception, self-efficacy, social support and self-regulation directly and indirectly influenced lymphedema self-management behaviours. IMPACT: This study provides a theoretical basis for the assessment and interventions of lymphedema self-management behaviours in breast cancer patients. Lymphedema self-management behaviours should be assessed regularly and comprehensively, taking these predictors into consideration to identify potential barriers. Further research is needed to explore effective interventions integrating these significant predictors. REPORTING METHOD: This study was reported following Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cross-sectional studies. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contributed to the design or conduct of the study, analysis or interpretation of the data, or in the preparation of the manuscript. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: This study focused on identifying and predicting mechanism of self-management based on a theory of behaviour change. The results can be applied among patients with other chronic diseases or high-risk populations, and inspire the assessment and interventions facilitating self-management behaviours. STUDY REGISTRATION: This study was registered as an observational study at Chinese Clinical Trial Registry: http://www.chictr.org.cn (ChiCTR2200057084). IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: For breast cancer patients with poor lymphedema self-management behaviour, attention should be raised among nurses and involved healthcare staffs that lymphedema self-management is multi-faced. Strategies targeted at improving social support, self-regulation, knowledge, self-efficacy and illness perception should be also addressed in lymphedema self-management programs, to facilitate more effective improvement of lymphedema self-management behaviours.

Factors associated with lymphedema self-management behaviours among breast cancer survivors: A cross-sectional study.

AIMS AND OBJECTIVES: The purpose of this empirical study was to explore the current status and associated factors of lymphedema self-management behaviours among Chinese breast cancer survivors. BACKGROUND: Breast cancer-related lymphedema is a lifetime concern for survivors and is currently incurable. Lifetime lymphedema self-management takes a significant role in preventing development and progression of lymphedema. Understanding influencing factors of lymphedema self-management behaviours can help to develop targeted intervention programs. DESIGN: A multicentre cross-sectional study. METHODS: From December 2021 to April 2022, a convenience sample of 586 participants were recruited at four tertiary hospitals in four cities in China. Self-reported questionnaires were used to measure socio-demographic characteristics, disease-and treatment-related characteristics, lymphedema self-management behaviours, lymphedema knowledge, illness perception, self-efficacy, self-regulation and social support. Descriptive analysis, bivariate analysis and hierarchical multiple regression were conducted. This study was registered at Chinese Clinical Trial Registry (ChiCTR2200057084), and was reported followed the STROBE checklist. RESULTS: Breast cancer survivors reported moderate level of lymphedema self-management behaviours. Promotion of lymph reflux management was ranked the least performed self-management behaviours, while the affected limb protection management ranked the most. 36.2% of self-management behaviours was explained by exercise regularly, level of attention on lymphedema prevention, unclear about the tumour stage (vs. stage I), knowledge, self-efficacy, emotional illness representation and social support. CONCLUSIONS: Lymphedema self-management behaviours of breast cancer survivors was insufficient. Performance of lymphedema self-management varied with different socio-demographic characteristics, along with different levels of knowledge, self-efficacy, perception and social support. All these identified predictors should be reckoned in assessment and intervention of lymphedema self-management behaviours. RELEVANCE TO CLINICAL PRACTICE: This study addressed that breast cancer survivors' lymphedema self-management behaviours should be promoted. Focusing on identified predictors, further lymphedema surveillance, knowledge education or social facilitation programs are recommended to enhance their self-management performance and adherence.

Cone beam computed tomography assessment of the prevalence and association of pulp calcification with periodontitis.

Periodontitis has a known association with pathological calcification in the cardiovascular system. Considering the close anatomic and circulatory association between dental pulp and the periodontium, this study aimed to evaluate the prevalence of pulp calcification (PC) under different periodontal conditions, as well as the associations of PC with the degree of periodontal damage, via cone beam computed tomography (CBCT) examination. In this study, 55 patients were categorized into three groups according to periodontal condition: group 1 (healthy controls), group 2 (periodontitis stage I-II), and group 3 (periodontitis stage III-IV). PC and radiographic bone loss (RBL) was assessed by CBCT in sagittal, axial, and coronal views, and statistical analyses were conducted. PC was identified in 378 of 1170 teeth (32.3%). The prevalence significantly differed among the three groups (P < 0.001). Group 2 had a 2.43-fold (P < 0.001, 95% confidence interval [CI] 1.64-3.61) higher risk of PC than group 1; and the risk of PC was 3.04-fold (P < 0.001, 95% CI 2.06-4.48) higher in group 3 than group 1. Teeth with more severe RBL exhibited a higher prevalence of PC (P < 0.001). Molar teeth had a higher risk of PC than incisors and premolars. In conclusion, the occurrence of PC is related to the periodontal state, and the prevalence of PC is higher in teeth with periodontitis; tooth type and periodontitis status are important risk factors for PC.

Conceptual framework for the insect metamorphosis from larvae to pupae by transcriptomic profiling, a case study of Helicoverpa armigera (Lepidoptera: Noctuidae).

BACKGROUND: Insect metamorphosis from larvae to pupae is one of the most important stages of insect life history. Relatively comprehensive information related to gene transcription profiles during lepidopteran metamorphosis is required to understand the molecular mechanism underlying this important stage. We conducted transcriptional profiling of the brain and fat body of the cotton bollworm Helicoverpa armigera (Lepidoptera: Noctuidae) during its transition from last instar larva into pupa to explore the physiological processes associated with different phases of metamorphosis. RESULTS: During metamorphosis, the differences in gene expression patterns and the number of differentially expressed genes in the fat body were found to be greater than those in the brain. Each stage had a specific gene expression pattern, which contributed to different physiological changes. A decrease in juvenile hormone levels at the feeding stage is associated with increased expression levels of two genes (juvenile hormone esterase, juvenile hormone epoxide hydrolase). The expression levels of neuropeptides were highly expressed at the feeding stage and the initiation of the wandering stage and less expressed at the prepupal stage and the initiation of the pupal stage. The transcription levels of many hormone (or neuropeptide) receptors were specifically increased at the initiation of the wandering stage in comparison with other stages. The expression levels of many autophagy-related genes in the fat body were found to be gradually upregulated during metamorphosis. The activation of apoptosis was probably related to enhanced expression of many key genes (Apaf1, IAP-binding motif 1 like, cathepsins, caspases). Active proliferation might be associated with enhanced expression levels in several factors (JNK pathway: jun-D; TGF-ß pathway: decapentaplegic, glass bottom boat; insulin pathway: insulin-like peptides from the fat body; Wnt pathway: wntless, TCF/Pangolin). CONCLUSIONS: This study revealed several vital physiological processes and molecular events of metamorphosis and provided valuable information for illustrating the process of insect metamorphosis from larvae to pupae.

Neutrophil membrane engineered HucMSC sEVs alleviate cisplatin-induced AKI by enhancing cellular uptake and targeting.

Human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (hucMSC-sEVs) have been demonstrated as a therapeutic agent to prevent and treat cisplatin-induced acute kidney injury (AKI). However, hucMSC-sEVs still face many problems and challenges in the repair and treatment of tissue injury, including short circulation time, insufficient targeting, and low therapeutic efficacy. Therefore, we constructed engineered hybrid vesicles fused with nanovesicles derived from human neutrophil membranes and hucMSC-sEVs, named neutrophil membrane engineered hucMSC-sEVs (NEX). NEX significantly enhanced the targeting of hucMSC-sEVs to injured kidney tissues, improved the impaired renal function via reducing pro-inflammatory cytokines expression, promoted the proliferation of renal tissue cells, and inhibited renal cell apoptosis in vivo. In addition, NEX enhanced hucMSC-sEVs uptake by NRK52E cells, but inhibited its uptake by RAW264.7 cells. Moreover, administration of NEX reduced cellular oxidative stress and promoted proliferation of NRK52E cells treated with cisplatin in vitro. In summary, our findings indicate that this design of a universal approach enhances the targeting and therapeutic efficacy of hucMSC-sEVs in kidney tissue regeneration, and provides new evidence promoting its clinical application.