L-Theanine Prolongs the Lifespan by Activating Multiple Molecular Pathways in Ultraviolet C-Exposed Caenorhabditis elegans.

L-theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effects, regulation of the immune response, relaxing neural tension, and reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also upregulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provides a theoretical basis for the possibility that tea drinking may prevent mitochondrial-related diseases.

ROS-Induced Gingival Fibroblast Senescence: Implications in Exacerbating Inflammatory Responses in Periodontal Disease.

Periodontal disease is the pathological outcome of the overwhelming inflammation in periodontal tissue. Cellular senescence has been associated with chronic inflammation in several diseases. However, the role of cellular senescence in the pathogenesis of periodontal disease remained unclear. This study aimed to investigate the role and the mechanism of cellular senescence in periodontal disease. Using single-cell RNA sequencing, we first found the upregulated level of cellular senescence in fibroblasts and endothelial cells from inflamed gingival tissue. Subsequently, human gingival fibroblasts isolated from healthy and inflamed gingival tissues were labeled as H-GFs and I-GFs, respectively. Compared to H-GFs, I-GFs exhibited a distinct cellular senescence phenotype, including an increased proportion of senescence-associated ß-galactosidase (SA-ß-gal) positive cells, enlarged cell morphology, and significant upregulation of p16INK4A expression. We further observed increased cellular reactive oxygen species (ROS) activity, mitochondrial ROS, and DNA damage of I-GFs. These phenotypes could be reversed by ROS scavenger NAC, which suggested the cause of cellular senescence in I-GFs. The migration and proliferation assay showed the decreased activity of I-GFs while the gene expression of senescence-associated secretory phenotype (SASP) factors such as IL-1ß, IL-6, TGF-ß, and IL-8 was all significantly increased. Finally, we found that supernatants of I-GF culture induced more neutrophil extracellular trap (NET) formation and drove macrophage polarization toward the CD86-positive M1 pro-inflammatory phenotype. Altogether, our findings implicate that, in the inflamed gingiva, human gingival fibroblasts acquire a senescent phenotype due to oxidative stress-induced DNA and mitochondrial damage, which in turn activate neutrophils and macrophages through the secretion of SASP factors.

Comparison of the osteogenic potential of fibroblasts from different sources.

OBJECTIVE: With the growing interest in the role of fibroblasts in osteogenesis, this study presents a comparative evaluation of the osteogenic potential of fibroblasts derived from three distinct sources: human gingival fibroblasts (HGFs), mouse embryonic fibroblasts (NIH3T3 cells), and mouse subcutaneous fibroblasts (L929 cells). MC3T3-E1 pre-osteoblast cells were employed as a positive control for osteogenic behavior. DESIGN: Our assessment involved multiple approaches, including vimentin staining for cell origin verification, as well as ALP and ARS staining in conjunction with RT-PCR for osteogenic characterization. RESULTS: Our findings revealed the superior osteogenic differentiation capacity of HGFs compared to MC3T3-E1 and NIH3T3 cells. Analysis of ALP staining confirmed that early osteogenic differentiation was most prominent in MC3T3-E1 cells at 7 days, followed by NIH3T3 and HGFs. However, ARS staining at 21 days demonstrated that HGFs produced the highest number of calcified nodules, indicating their robust potential for late-stage mineralization. This late-stage osteogenic potential of HGFs was further validated through RT-PCR analysis. In contrast, L929 cells displayed no significant osteogenic differentiation potential. CONCLUSIONS: In light of these findings, HGFs emerge as the preferred choice for seed cells in bone tissue engineering applications. This study provides valuable insights into the potential utility of HGFs in the fields of bone tissue engineering and regenerative medicine.

The Critical Role of Pyroptosis in Peri-Implantitis.

Background: Peri-implantitis (PI) is a prevalent complication of implant treatment. Pyroptosis, a distinctive inflammatory programmed cell death, is crucial to the pathophysiology of PI. Despite its importance, the pyroptosis-related genes (PRGs) influencing PI's progression remain largely unexplored. Methods: This study conducted histological staining and transcriptome analyze from three datasets. The intersection of differentially expressed genes (DEGs) and PRGs was identified as pyroptosis-related differentially expressed genes (PRDEGs). Functional enrichment analyses were conducted to shed light on potential underlying mechanisms. Weighted Gene Co-expression Network Analysis (WGCNA) and a pyroptotic macrophage model were utilized to identify and validate hub PRDEGs. Immune cell infiltration in PI and its relationship with hub PRDEGs were also examined. Furthermore, consensus clustering was performed to identify new PI subtypes. Protein-protein interaction (PPI) network, competing endogenous RNA (ceRNA) network, mRNA-mRNA binding protein regulatory (RBP) network, and mRNA-drugs regulatory network of hub PRDEGs were also analyzed. Results: Eight hub PRDEGs were identified: PGF, DPEP1, IL36B, IFIH1, TCEA3, RIPK3, NET7, and TLR3, which are instrumental in the PI's progression. Two PI subtypes were distinguished, with Cluster 1 exhibiting higher immune cell activation. The exploration of regulatory networks provided novel mechanisms and therapeutic targets in PI. Conclusion: Our research highlights the critical role of pyroptosis and identifies eight hub PRDEGs in PI's progression, offering insights into novel immunotherapy targets and laying the foundation for advanced diagnostic and treatment strategies. This contributes to our understanding of PI and underscores the potential for personalized clinical management.

Identification of immunological bioprocesses involved in peri-implantitis using weighted gene co-expression network analysis.

BACKGROUND: Peri-implantitis is an irreversible infectious disease that occurs with high incidence. Exploring the immune responses of peri-implantitis is key to developing targeted treatment strategies. However, there is limited research on the immune response of peri-implantitis. METHODS: This study performed a weighted gene co-expression network analysis to identify the peri-implantitis related gene network and conducted a functional enrichment analysis of the gene network. Thereafter, the candidate hub genes were selected by constructing a protein-protein interaction network and drawing an upset plot. The hub genes were identified through their significant associations with disease condition and validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Using the gene set variation analysis, the hub genes were further used to explore infiltrating immunocytes and immune factors in peri-implantitis. Finally, the immunocytes and immune factor related hub genes were intersected to obtain the therapeutic target, which was validated using histological staining. RESULTS: The peri-implantitis related gene network was enriched in innate and adaptive immune response. Subsequently, interleukin (IL)1B, IL10, ITGAM, ITGB1, STAT3, and TLR4 were identified as hub genes. Plasmacytoid dendritic cells, macrophages, myeloid-derived suppressor cells, natural killer T cells, and immature B cells were positively and significantly related to the hub genes IL1B, TLR4, ITGAM, and ITGB1 (correlation coefficient > 0.80). While immune factors CXCL10, IL6, and CXCL12 and hub genes IL10 and IL1B held the highest degree in the immune factors network. IL1B may be a promising therapeutic target. CONCLUSION: This study provides new insights into the hub genes, immunocytes, and immune factors underlying peri-implantitis immunological bioprocess.

Development and validation of a CECT-based radiomics model for predicting IL1B expression and prognosis of head and neck squamous cell carcinoma.

Introduction: It is necessary to explore a noninvasive method to stratify head and neck squamous cell carcinoma (HNSCC)'s prognosis and to seek new indicators for individualized precision treatment. As a vital inflammatory cytokine, IL1B might drive a new tumor subtype that could be reflected in overall survival (OS) and predicted using the radiomics method. Methods: A total of 139 patients with RNA-Seq data from The Cancer Genome Atlas (TCGA) and matched CECT data from The Cancer Image Archive (TCIA) were included in the analysis. The prognostic value of IL1B expression in patients with HNSCC was analyzed using Kaplan-Meier analysis, Cox regression analysis and subgroup analysis. Furthermore, the molecular function of IL1B on HNSCC was explored using function enrichment and immunocytes infiltration analyses. Radiomic features were extracted with PyRadiomics and processed using max-relevance minredundancy, recursive feature elimination, and gradient boosting machine algorithm to construct aradiomics model for predicting IL1B expression. The area under the receiver operating characteristic curve (AUC), calibration curve, precision recall (PR) curve, and decision curve analysis (DCA) curve were used to examine the performance of the model. Results: Increased IL1B expression in patients with HNSCC indicated a poor prognosis (hazard ratio [HR] = 1.56, P = 0.003) and was harmful in patients who underwent radiotherapy (HR = 1.87, P = 0.007) or chemotherapy (HR = 2.514, P < 0.001). Shape_Sphericity, glszm_SmallAreaEmphasis, and firstorder_Kurtosis were included in the radiomics model (AUC: training cohort, 0.861; validation cohort, 0.703). The calibration curves, PR curves and DCA showed good diagnostic effect of the model. The rad-score was close related to IL1B (P = 4.490*10-9), and shared the same corelated trend to EMT-related genes with IL1B. A higher rad-score was associated with worse overall survival (P = 0.041). Discussion: The CECT-based radiomics model provides preoperative IL1B expression predictionand offers non-invasive instructions for the prognosis and individualized treatment of patients withHNSCC.

Investigation into the communication between unheated and heat-stressed Caenorhabditis elegans via volatile stress signals.

Our research group has recently found that radiation-induced airborne stress signals can be used for communication among Caenorhabditis elegans (C. elegans). This paper addresses the question of whether heat stress can also induce the emission of airborne stress signals to alert neighboring C. elegans and elicit their subsequent stress response. Here, we report that heat-stressed C. elegans produces volatile stress signals that trigger an increase in radiation resistance in neighboring unheated C. elegans. When several loss-of-function mutations affecting thermosensory neuron (AFD), heat shock factor-1, HSP-4, and small heat-shock proteins were used to test heat-stressed C. elegans, we found that the production of volatile stress signals was blocked, demonstrating that the heat shock response and ER pathway are involved in controlling the production of volatile stress signals. Our data further indicated that mutations affecting the DNA damage response (DDR) also inhibited the increase in radiation resistance in neighboring unheated C. elegans that might have received volatile stress signals, indicating that the DDR might contribute to radioadaptive responses induction by volatile stress signals. In addition, the regulatory pattern of signal production and action was preliminarily clarified. Together, the results of this study demonstrated that heat-stressed nematodes communicate with unheated nematodes via volatile stress signals.

Neurotoxicity of bisphenol A exposure on Caenorhabditis elegans induced by disturbance of neurotransmitter and oxidative damage.

Bisphenol A (BPA) is putatively regarded as an environmental neurotoxicant found in everyday plastic products and materials, however, the possible neurobehavioral adverse consequences and molecular mechanisms in animals have not been clearly characterized. The nematode Caenorhabditis elegans has become a promising animal model for neurotoxicological researches. To investigate the dose-effect relationships of BPA-induced neurotoxicity effects, the locomotion behavior and developmental parameters of the nematode were determined after BPA exposure. The present data demonstrated that BPA caused neurobehavioral toxicities, including head thrashes and body bends inhibition. In addition, when C. elegans was exposed to BPA at a concentration higher than 2 µM, growth and survival rate were decreased. The serotonergic, dopaminergic and GABAergic neurons were damaged by BPA. Furthermore, lower levels of mRNA expression related to dopamine, serotonin and GABA were detected in the worms exposed to 50 µM BPA. Increased SOD-3 expression might be adaptive response to BPA exposure. Moreover, oxidative damage triggered by BPA was manifested by changes in GST-4 expression, accompany with abnormity of ATP synthesis, but not nuclear localization of DAF-16/FOXO. Finally, we showed that epigallocatechin-3-gallate partially rescued BPA-induced reactive oxygen species (ROS) production and neurobehavioral toxicity. Altogether, the neurobehavioral and developmental toxicity of BPA may be induced by neurotransmission abnormity and oxidative damage. The present data imply that oxidative stress is linked to neuronal damage and neurobehavioral harm resulting from developmental BPA exposure.

Osteotomy combined with the trephine technique for invisible implant fracture: A case report.

BACKGROUND: Implant fracture is one of the most serious mechanical complications of dental implants. Conventional treatment necessitates visibility of the apical portion of the fractured implant, whereas for deep and invisible implant fractures, the traditional trephine method has been ineffective. Surgical removal of the marginal bone to expose the fracture surface would be a time-consuming and extensively damaging procedure. Here, we propose a novel technique to address invisible implant fractures. CASE SUMMARY: A 50-year-old woman was referred to our department with the chief complaint that her right mandibular implant tooth had fallen out 3 mo earlier. Cone-beam computed tomography examination showed an implant fracture with a fracture surface 5.1 mm below the crestal ridge. The patient was treated with osteotomy combined with the trephine technique to expose the surgical field and remove the implant. The invisible fractured implant was successfully removed, with minimal trauma. A modified Wafer technique-supported guided bone regeneration treatment was then administered to restore the buccal bone wall and preserve the bone mass. Six months later, fine regenerative bone and a wide alveolar crest in the edentulous area were observed, and a new implant was placed. Four months later, restoration was completed using a cemented ceramic prosthesis. Clinical and radiographic examinations 12 mo after loading fulfilled the success criteria. The patient reported no complaints and was satisfied. CONCLUSION: Osteotomy combined with the trephine technique can be effectively used to address deep and invisible implant fractures.

Dynamic navigation system-guided trans-inferior alveolar nerve implant placement in the atrophic posterior mandible: A case report.

BACKGROUND: In atrophic posterior mandibular areas, where the bone height superior to the inferior alveolar nerve (IAN) is less than 6 mm, short implants are not applicable. Conventional alternatives such as IAN transposition and various alveolar bone augmentation approaches are technically demanding and prone to complications. CASE SUMMARY: Computer-guided dynamic navigation implantation improves the accuracy, predictability, and safety of implant placement. This case report presents a dynamic navigation system-guided trans-IAN implant placement technique, which can successfully treat a posterior mandibular dentition defect when the bone height is only 4.5 mm. The implant was inserted into the buccal side of the IAN and was 1.7 mm away from the IAN. The implantation deviations were controlled within a satisfying range, and the long-term restoration outcome was stable. CONCLUSION: Dynamic navigation system-guided trans-IAN implant placement might be a recommended technique for patients with extremely insufficient residual bone height and sufficient bone width in the posterior mandibular area.

Thalidomide attenuates oral epithelial cell apoptosis and pro-inflammatory cytokines secretion induced by radiotherapy via the miR-9-3p/NFATC2/NF-κB axis.

Oral mucositis is the most common oral complication of cancer patients receiving radiotherapy or chemotherapy, leading to poor quality of life. Increasing clinical studies demonstrated that thalidomide (THD) can effectively ameliorate radiation-induced oral mucositis (RIOM). Here we established an experimental mouse model, radiation-induced human oral epithelial cells (HOECs), and further investigate the underlying mechanism the THD protective effect against RIOM. Combined with RNA sequencing result, we selected the gene nuclear factor of activated T cells c2 (NFATC2) as the most interesting candidate. THD downregulated NFATC2 expression, attenuated human oral epithelial cells (HOECs) apoptosis and promoted pro-inflammatory factors secretion. Further studies show that overexpression of NFATC2 in HOECs promotes cells apoptosis and pro-inflammatory cytokines level, while inhibition of NFATC2 present an opposite effect. Additionally, the regulatory miRNA of NFATC2 was predicted using StarBase, and the targeting relationship between miR-9-3p and NFATC2 was confirmed using a dual-luciferase reporter gene assay. miR-9-3p mimic reversed the elevated cell apoptosis and pro-inflammatory cytokines level by radiation or NFATC2-overexpression. Furthermore, NFATC2 upregulated the phosphorylation of p65, thus activating the NF-κB pathway in RIOM; while miR-9-3p reduced this effect. In conclusion, THD attenuates oral epithelial cell apoptosis and pro-inflammatory cytokines secretion induced by radiotherapy via the miR-9-3p/NFATC2/NF- NF-κB axis.

Are parents' education levels associated with either their oral health knowledge or their children's oral health behaviors? A survey of 8446 families in Wuhan.

BACKGROUND: Children aged 6-7 years are in the early mixed dentition, which is a period of high prevalence of dental caries and other dental diseases and a critical period for the formation of oral health behaviors. Therefore, good oral hygiene habits of children and oral health knowledge of parents are very important. This study sought to explore the relationship between children's oral health behaviors, parental oral health knowledge, parental choices of pit and fissure sealants, and parents' education levels based on a large-scale sample size for the first time, and to compare the influences of parental education levels between parents. METHODS: Families of the first and second graders of primary schools in Wuhan Hongshan District were included in this study. A total of 8446 questionnaires were collected to obtain comprehensive information on children's oral health behaviors, parents' oral health knowledge and parents' pit and fissure sealants-related choices. The relationship between these outcome variables and parents' education levels were studied using logistic regression analysis and chi-square test. RESULTS: Parents who reported good educational background had more favorable oral health knowledge than those of other parents, and their children had better oral hygiene behaviors. Four indicators of five measures to children's oral health behaviors were significantly associated with mother's education level (P < 0.05), and three of them were related to father's education level (P ≤ 0.01). Moreover, seven indicators of eight measures to parents' oral health knowledge were significantly related to mother's education level (P < 0.05) and four of them were affected by the father's (P < 0.05). In addition, parents with higher educational attainments paid more attention to the completeness of medical facilities, the environment of dental practice, the distance to treatment sites, and took less concern of children's willingness when choosing the pit and fissure sealants sites. CONCLUSIONS: In families with children at the early mixed dentition stage, parents with higher education levels tend to have better oral health knowledge and more oral health care needs, such as pit and fissure sealants. In addition, children of parents who have better educated parents tend to perform better oral hygiene practices.

Enhanced osteogenesis and therapy of osteoporosis using simvastatin loaded hybrid system.

Postmenopausal osteoporosis is a common chronic dynamic bone disorder, caused by estrogen deficiency. To address this issue, we constructed a controlled drug-release system composed of poly (N-isopropylacrylamide) brush modified mesoporous hydroxyapatite (MHA-SIM-P) loaded with simvastatin (SIM) using an ovariectomised (OVX) rat model. Quantitative alkaline phosphatase activity assay, alizarin red staining and RT-PCR were tested to evaluate the osteogenic ability in vitro. The results showed that the MHA-SIM-P nanoparticles significantly improved the osteogenic differentiation of OVX bone marrow stromal cells (BMSCs) in vitro. In osteoporotic animal model, the therapeutic efficiency for bone defect was evaluated by µCT analysis, tartrate-resistant acid phosphatase, haematoxylin and eosin staining, which showed improved bone formation and less osteoclastic response in OVX rats after surgery for 3 and 6 weeks. This polymer brush modified MHA system provided a sustained release system of hydrophobic SIM to inhibit osteoporosis together with MHA nanoparticle promoting the osteogenesis. Thus, this novel strategy exhibited great potential for promoting osteogenic ability and treating local osteoporotic defects.

Proton Pump Inhibitors Augment the Risk of Major Adverse Cardiovascular Events and End-Stage Renal Disease in Patients With Acute Kidney Injury After Temporary Dialysis.

Proton pump inhibitors (PPIs) have been reported to increase the risk of acute and chronic renal disease. However, the data are unclear in patients with acute kidney injury (AKI) requiring dialysis (AKI-D) who are often candidates for PPIs. To investigate this important issue, we identified 26,052 AKI-D patients from Taiwan's National Health Insurance Research Database weaning from dialysis. During a mean follow-up period of 3.52 years, the PPI users had a higher incidence of end-stage renal disease (ESRD) than the PPI nonusers (P < 0.001). After propensity score matching and treating mortality as a competing risk factor, the PPI users had a higher risk of ESRD (subhazard ratio (sHR) 1.40; 95% confidence interval (CI), 1.31-1.50) and major adverse cardiac events (MACE, sHR 1.53; 95% CI, 1.37-1.71) compared with the PPI nonusers with AKI-D survivors. In conclusion, the use of PPIs was associated with a higher risk of ESRD and MACE, compared with the PPI nonusers in AKI-D patients who weaned from dialysis.

Development of an miRNA-Array-Based Diagnostic Signature for Periodontitis.

Periodontitis progression is accompanied by irreversible alveolar bone absorption and leads to tooth loss. Early diagnosis is important for tooth stability and periodontal tissue preservation. However, there is no recognized miRNA diagnostic signature with convincing sensitivity and specificity for periodontitis. In this study, we obtained miRNA array expression profiles of periodontitis from the Gene Expression Omnibus (GEO) database. After screening for differentially expressed miRNAs, the least absolute shrinkage and selection operator (LASSO) method was performed to identify and construct a 17-miRNA-based diagnostic signature (hsa-miR-3917, hsa-mir-4271, hsa-miR-3156, hsa-miR-3141, hsa-miR-1246, hsa-miR-125a-5p, hsa-miR-671-5p, hcmv-mir-UL70, hsa-miR-650, hsa-miR-497-3p, hsa-miR-145-3p, hsa-miR-141-3p, hsa-miR-210-3p, hsa-miR-204-3p, hsa-miR-203a-5p, hsa-miR-99a-3p, and hsa-miR-30a-3p). Periodontal tissue samples with higher risk scores were more likely to show symptoms of periodontitis. Then, the receiver operating characteristic (ROC) curves were used to assess the diagnostic value of the miRNA signature, which indicated that the optimum cutoff value in periodontitis diagnosis was 0.5056 with an area under the ROC curve (AUC) of 0.996, a sensitivity of 97.3%, a specificity of 100.0% in the training cohort; in the testing cohort, the corresponding values were as follows: an AUC of 0.998, a sensitivity of 97.9%, and a specificity of 91.7%. We next evaluated the efficacy of the signature in differentiating disease subtype and affected range. Furthermore, we conducted functional enrichment analysis of the 17 miRNA-targeted mRNAs, including the regulation of mTOR activity and cell autophagy, Th1/Th2 cell balance and immunoregulation, cell apoptosis, and so on. In summary, our study identified and validated a 17-miRNA diagnostic signature with convincing AUC, sensitivity, and specificity for periodontitis.

Enhancement of DNA damage repair potential in germ cells of Caenorhabditis elegans by a volatile signal from their irradiated partners.

Radiation-induced bystander effects have been demonstrated within organisms. Recently, it is found that the organisms can also signal irradiation cues to their co-cultured partners in a waterborne manner. In contrast, there is a limited understanding of radiation-induced airborne signaling between individuals, especially on the aspect of DNA damage responses (DDR). Here, we establish a co-culture experimental system using Caenorhabdis elegans in a top-bottom layout, where communication between "top" and "bottom" worms is airborne. The radiation response of top worms is evaluated using radio-adaptive response (RAR) of embryonic lethality (F1), which reflects an enhancement in repair potential of germ cells to subsequent DNA damage. It is shown that gamma-irradiation of bottom worms alleviates the embryonic lethality of top worms caused by 25 Gy of subsequent gamma-irradiation, i.e. RAR, indicating that a volatile signal might play an essential role in radiation-induced inter-worm communication. The RAR is absent in the top worms impaired in DNA damage checkpoint, nucleotide excision repair, and olfactory sensory neurons, respectively. The induction of RAR is restricted to the mitotic zone of the female germline of hermaphrodites. These results indicate that the top worms sense the volatile signal through cephalic sensory neurons, and the neural stimulation distantly modulates the DDR in germ mitotic cells, leading to the enhancement of DNA damage repair potential. The volatile signal is produced specifically by the L3-stage bottom worms and functionally distinct from the known sex pheromone. Its production and/or release are regulated by water-soluble ascaroside pheromones in a population-dependent manner.

Inclined granular flow in a narrow chute.

In this paper we presents a detailed description of granular flow down a flat, narrow chute using discrete element method simulations, with emphasis on the influence of sidewalls on the flow. The overall phase diagram is provided and it is found that there are four flow regimes (no flow, bulk flow, surface flow, and gas flow). The H̃stop curve is very complicated and quite different from that in the case without sidewalls. The effective friction coefficient [Formula: see text] increases with pile height H̃ and a surface flow occurs when the inclination angle [Formula: see text] exceeds a critical value. The profile of [Formula: see text] shows that the [Formula: see text] rheology is valid in boundary layers. Furthermore, [Formula: see text] increases with the velocity of particles and there is a saturation to a nonzero value in static heap. For small H̃, the static heap vanishes and there is a bulk flow. A similarity between basal particles and sidewall particles indicates a universal role of the boundaries. In this bulk flow, there is a transition of the velocity profile with wall friction [Formula: see text]. When [Formula: see text] is large, the velocity is linear and decreases with increasing height. With small [Formula: see text], the velocity is nonlinear and the flow rate is roughly proportional to H̃3/2.

Long-Term Outcomes in Patients with Incident Chronic Obstructive Pulmonary Disease after Acute Kidney Injury: A Competing-Risk Analysis of a Nationwide Cohort.

Both acute kidney injury (AKI) and chronic obstructive pulmonary disease (COPD) are associated with increased morbidity and mortality. However, the incidence of de novo COPD in patients with AKI, and the impact of concurrent COPD on the outcome during post-AKI care is unclear. Patients who recovered from dialysis-requiring AKI (AKI-D) during index hospitalizations between 1998 and 2010 were identified from nationwide administrative registries. A competing risk analysis was conducted to predict the incidence of adverse cardiovascular events and mortality. Among the 14,871 patients who recovered from temporary dialysis, 1535 (10.7%) were identified as having COPD (COPD group) one year after index discharge and matched with 1473 patients without COPD (non-COPD group) using propensity scores. Patients with acute kidney disease superimposed withs COPD were associated with a higher risk of incident ischemic stroke (subdistribution hazard ratio (sHR), 1.52; 95% confidence interval (95% CI), 1.17 to 1.97; p = 0.002) and congestive heart failure (CHF; sHR, 1.61; (95% CI), 1.39 to 1.86; p < 0.001). The risks of incident hemorrhagic stroke, myocardial infarction, end-stage renal disease, and mortality were not statistically different between the COPD and non-COPD groups. This observation adds another dimension to accumulating evidence regarding pulmo-renal consequences after AKI.

Induction of reproductive cell death in Caenorhabditis elegans across entire linear-energy-transfer range of carbon-ion irradiation.

Heavy-ion radiation has attracted extensive attention as an effective cancer therapy because of the varying energy deposition along its track and its high cell-killing effect. Reproductive cell death (RCD), also known as clonogenic death, is an important mode of death of the cancer cells after radiotherapy. Although RCD induced by heavy-ion irradiation with various linear energy transfers has been demonstrated using clonogenic assay in vitro, little is known about the distribution of RCD across the range of heavy-ion irradiation at the level of whole organisms. In this study, a vulval tissue model of Caenorhabditis elegans was for the first time used to assess RCD in vivo induced by carbon-ion irradiation. A polymethyl methacrylate wedge was designed to provide a gradually varying thickness of shielding, so worms could be exposed to the entire range of carbon-ion irradiation. The carbon-ion irradiation led to a significant induction of RCD over the entire range in a dose-dependent manner. The biological peak did not correspond to the physical Bragg peak and moved forward, rather than spread forward, as radiation dose increased. The degree and shape of the range-distribution of RCD were also affected by the developmental stages of the worms. The gene mutations in DNA-damage checkpoints did not affect the responses of mutant worms positioned in biological peaks, compared to wild-type worms, but decreased radio-sensitivity in the entrance region. An increased induction of RCD was observed in the worms impaired in homologous recombination (HR), but not in non-homologous end jointing pathway, suggesting a crucial role of HR repair in vulval cells of C. elegans in dealing with the carbon-ion-induced DNA damage. These unique manifestations of RCD in vivo in response to carbon-ion irradiation might provide new clues for further investigating the biological effects of heavy-ion irradiation.

Interaction between Radioadaptive Response and Radiation-Induced Bystander Effect in Caenorhabditis elegans : A Unique Role of the DNA Damage Checkpoint.

Although radioadaptive responses (RAR) and radiation-induced bystander effects (RIBE) are two important biological effects of low-dose radiation, there are currently only limited data that directly address their interaction, particularly in the context of whole organisms. In previous studies, we separately demonstrated RAR and RIBE using an in vivo system of C. elegans . In the current study, we further investigated their interaction in C. elegans , with the ratio of protruding vulva as the biological end point for RAR. Fourteen-hour-old worms were first locally targeted with a proton microbeam, and were then challenged with a high dose of whole-body gamma radiation. Microbeam irradiation of the posterior pharynx bulbs and rectal valves of C. elegans could significantly suppress the induction of protruding vulva by subsequent gamma irradiation, suggesting a contribution of RIBE to RAR in the context of the whole organism. Moreover, C. elegans has a unique DNA damage response in which the upstream DNA damage checkpoint is not active in most of somatic cells, including vulval cells. However, its impairment in atm-1 and hus-1 mutants blocked the RIBE-initiated RAR of vulva. Similarly, mutations in the atm-1 and hus-1 genes inhibited the RAR of vulva initiated by microbeam irradiation of the vulva itself. These results further confirm that the DNA damage checkpoint participates in the induction of RAR of vulva in C. elegans in a cell nonautonomous manner.