Sustained depression of B cell counts in lupus nephritis after treatment with rituximab and/or belimumab is associated with fewer disease flares.

OBJECTIVE: To study the risk of lupus nephritis flare (LNF) or severe lupus flare (SLF) as a function of B cell count kinetics in lupus nephritis (LN) patients after they achieve at least a partial renal response (PRR) with induction treatment that includes rituximab (RTX) and/or belimumab (BLM). METHODS: We performed a retrospective analysis of a cohort of 19 patients with severe LN that received a B cell agent (BCA), RTX and/or BLM, as part of an initial treatment regimen for an LN flare and had subsequent CD19+ B cell measurements in peripheral blood. We then characterized the follow-up periods, after B cell depressions occurred and PRR were achieved, by the corresponding trajectories of B cell counts (BCC). Time periods with sustained low BCC were type 1 (T1) episodes, while those with repletion of BCC>100 cells/µL were called type 2 (T2) episodes. Time periods with rapid BCC repletion, defined as >50 cells/µL in ≤6 months, were called T2b episodes. Corresponding C3, C4, and anti-dsDNA levels were recorded for each episode. The time from PRR until an event, either a LNF or SLF, or to censoring, either at the end of the study period or the end of available patient follow-up, was assessed for each episode type. Kaplan-Meier survival analysis was used to compare time to flare between T1 and T2 episodes. RESULTS: There were 26 episodes of B cell depression. Seventeen (65%) were T1 and 9 (35%) were T2. Compared to T1 episodes, T2 episodes were 9.0 times more likely to result in flare over the follow-up period (hazard ratio (HR) = 9.0, 95% CI for HR = 2.2-36.7); this risk was even larger for T2b vs T1 episodes. Median BCC was 14 cells/µL in T1 and 160 cells/µL in T2 episodes. Both C3 and C4 levels significantly increased over the duration of the episode in T1 episodes only. CONCLUSION: Sustained low BCC was associated with prolonged serologic and clinical response, whereas repletion, and particularly rapid repletion, of B cells after treatment with BCA was associated with subsequent disease flare.

[Transition metal accumulation and cellular senescence].

Aging refers to a progressive decline in biological functions, leading to age-related diseases and mortality. The transition metals, including iron, copper, and manganese, play important roles in human physiological and pathological processes. Substantial research has demonstrated that senescent cells accumulate higher levels of transition metals, which in turn accelerates the process of cellular senescence and related diseases through mechanisms such as production of excessive reactive oxygen species (ROS), induction of oxidative stress, DNA damage, and mitochondrial dysfunction. This review article provides a comprehensive overview of the causes of transition metal accumulation in senescent cells, as well as the mechanisms by which it further promotes cellular senescence and related diseases. The aim is to provide insights into anti-aging and treatment of aging-related diseases caused by transition metal accumulation.

Targeting NR1D1 in organ injury: challenges and prospects.

Nuclear receptor subfamily 1, group D, member 1 (NR1D1, also known as REV-ERBα) belongs to the nuclear receptor (NR) family, and is a heme-binding component of the circadian clock that consolidates circadian oscillators. In addition to repressing the transcription of multiple clock genes associated with circadian rhythms, NR1D1 has a wide range of downstream target genes that are intimately involved in many physiopathological processes, including autophagy, immunity, inflammation, metabolism and aging in multiple organs. This review focuses on the pivotal role of NR1D1 as a key transcription factor in the gene regulatory network, with particular emphasis on the milestones of the latest discoveries of NR1D1 ligands. NR1D1 is considered as a promising drug target for treating diverse diseases and may contribute to research on innovative biomarkers and therapeutic targets for organ injury-related diseases. Further research on NR1D1 ligands in prospective human trials may pave the way for their clinical application in many organ injury-related disorders.

Quantitative evaluation of colorectal tumour vasculature using contrast-enhanced ultrasound: Correlation with angiogenesis and prognostic significance.

BACKGROUND: Ultrasound is a vital tool for the diagnosis and management of colorectal cancer (CRC). Contrast-enhanced ultrasound (CEUS) is a non-invasive, safe, and cost-effective method for evaluating tumour blood vessels, that play a crucial role in tumour growth and progression. AIM: To explore CEUS's role in the quantitative evaluation of CRC blood vessels and their correlation with angiogenesis markers and prognosis. METHODS: This study prospectively enrolled 100 patients with CRC confirmed by histopathology. All patients received preoperative CEUS examinations. Quantitative parameters, such as peak intensity (PI), time to peak (TTP), and area under the curve (AUC), were derived from time-intensity curve (TIC) analysis. Tumour tissue samples were obtained during surgery and examined immunohistochemically to assess the expression of angiogenesis markers, including vascular endothelial growth factor (VEGF) and microvessel density (MVD). The correlation between CEUS parameters, angiogenesis markers, and clinicopathological features was evaluated using appropriate statistical tests. RESULTS: Quantitative CEUS parameters (PI, TTP, and AUC) showed significant correlations with VEGF expression (P < 0.001) and MVD (P < 0.001), indicating a strong link between tumour blood vessels and angiogenesis. Increased PI, reduced TTP, and expanded AUC values were significantly related to higher tumour stage (P < 0.001), lymph node metastasis (P < 0.001), and distant metastasis (P < 0.001). Furthermore, these parameters were recognized as independent predictors of overall survival and disease-free survival in multivariate analysis (P < 0.001). CONCLUSION: CEUS has a high potential in guiding treatment planning and predicting patient outcomes. However, more comprehensive, multicentre studies are required to validate the clinical utility of CEUS in CRC management.

Joint effects of prenatal exposure to air pollution and pregnancy-related anxiety on birth weight: A prospective birth cohort study in Ma'anshan, China.

BACKGROUND: A growing number of studies have shown that prenatal exposure to chemical and non-chemical stressors has effects on fetal growth. The co-exposure of both better reflects real-life exposure patterns. However, no studies have included air pollutants and pregnancy-related anxiety (PrA) as mixtures in the analysis. METHOD: Using the birth cohort study method, 576 mother-child pairs were included in the Ma'anshan Maternal and Child Health Hospital. Evaluate the exposure levels of six air pollutants during pregnancy using inverse distance weighting (IDW) based on the pregnant woman's residential address and air pollution data from monitoring stations. Prenatal anxiety levels were assessed using the PrA Questionnaire. Generalized linear regression (GLR), quantile g-computation (QgC) and bayesian kernel machine regression (BKMR) were used to assess the independent or combined effects of air pollutants and PrA on birth weight for gestational age z-score (BWz). RESULT: The results of GLR indicate that the correlation between the six air pollutants and PrA with BWz varies depending on the different stages of pregnancy and pollutants. The QgC shows that during trimester 1, when air pollutants and PrA are considered as a whole exposure, an increase of one quartile is significantly negatively correlated with BWz. The BKMR similarly indicates that during trimester 1, the combined exposure of air pollutants and PrA is moderately correlated with a decrease in BWz. CONCLUSION: Using the method of analyzing mixed exposures, we found that during pregnancy, the combined exposure of air pollutants and PrA, particularly during trimester 1, is associated with BWz decrease. This supports the view that prenatal exposure to chemical and non-chemical stressors has an impact on fetal growth.

Association of urinary heavy metal combined exposure with periodontitis among US adults from NHANES 2011-2014.

Some heavy metals are associated with periodontitis; whereas most of these associations have focused on individual metal, there are no specific studies on the effects of combined heavy metal exposure on periodontitis. We conducted an analysis on the association between urinary heavy metal exposure and periodontitis in participants aged 30 years and older using multiple logistic regression and Bayesian kernel machine regression (BKMR). This analysis was performed on data from the National Health and Nutrition Examination Survey from 2011 to 2014. The study found that using logistic regression, the 4th quartile of urinary lead and molybdenum and the 3rd quartile of urinary strontium were positively associated with periodontitis compared to the reference quartile after adjusting for covariates. Odds ratio (OR) with 95% confidence interval (CI) was 1.738 (1.069-2.826), 1.515 (1.025-2.239), and 1.498 (1.010-2.222), respectively. The 3rd and 4th quartiles of urinary cobalt were negatively associated with periodontitis, and their ORs and 95% CIs were 0.639 (0.438-0.934) and 0.571 (0.377-0.964), respectively. The BKMR model showed that urinary barium, lead, and molybdenum were positively associated with periodontitis in a range of concentrations and urinary cobalt, manganese, tin, and strontium were negatively correlated with periodontitis. Furthermore, the overall association between urinary heavy metals and periodontitis was positive. Our study provides evidence for an association between exposure to multiple urinary heavy metals and periodontitis. However, further longitudinal studies are needed to explore the specific mechanisms involved.

Effect of gaseous pollutant and greenness exposure on mortality during treatment of newly treated tuberculosis patients: a provincial population-based cohort study.

BACKGROUND: Previous studies addressing the impact of environmental factors on TB prognosis are scarce, with only some studies examining the effect of particulate pollutants on TB mortality. Moreover, few studies have evaluated the effects of multiple gaseous pollutants and greenness exposures on newly treated TB patients on a large population scale. METHODS: Through the Centers for Disease Control and Prevention, data were collected from January 1, 2015 to December 31, 2020 for newly treated TB patients in Anhui Province, China. Data on gaseous pollutants sulfur dioxide, nitrogen dioxide, carbon monoxide, and ozone were collected through the National Earth System Science Data Center of China. Normalized vegetation index data were obtained through NASA. The Cox proportional risk model was also applied to calculate the hazard ratios of SO2, NO2, CO, O3, and NDVI with 95% confidence intervals for mortality among newly treated TB patients. RESULTS: Multifactorial Cox regression analysis showed that for every 0.10 µg/m3 increase in SO2, the risk of death among newly treated TB patients increased by 13.2% (HR = 1.132, 95% CI: 1.045-1.1.225), for every 10 µg/m3 increase in NO2, the risk of death among newly treated TB patients increased by 11.4%, and for each 0.1 mg/m3 increase in CO, the risk of death among newly treated TB patients increased by 5.8%. For each 0.1 increase in NDVI 250m-buffer and 500m-buffer, the risk of death among newly treated TB patients decreased by 8.5% and 6.4%, respectively. The effect of gaseous pollutants on mortality decreased progressively with elevated greenness exposure when greenness exposure was grouped from low to high. CONCLUSION: Gaseous pollutants are a risk factor during the treatment of newly treated TB patients and greenness exposure is a protective factor. Higher greenness exposure reduces the risk of death due to exposure to gaseous pollutants.

The impact of household fuel usage on adverse pregnancy outcomes in rural Ma'anshan City, Anhui Province: a birth cohort study.

The combustion of cooking fuels generates detrimental gases significantly impacting human health, particularly for vulnerable populations like expectant mothers. Prenatal exposure of such hazardous emissions raises the probability of adverse pregnancy outcomes, including preterm birth (PTB) and low birth weight (LBW). Our research aims to explore the association between cooking fuel utilization and adverse birth outcomes in rural Ma'anshan, Anhui Province. A prospective cohort study was executed, employing the Maternal and Infant Health Assessment questionnaire to classify fuels into clean (natural gas, electricity) and polluting energy sources (coal, coal gas, firewood). Multivariate logistic regression models were conducted to evaluate the association between fuel consumption and postpartum maternal and infant outcomes. Among the 442 surveyed pregnant women, 38.2% (N=169) utilized polluting fuels. After adjusting for covariates such as age and BMI, the relative risks of preterm birth, low birth weight, and postpartum hemorrhage in the polluting fuel group compared to the clean fuel group were OR: 3.27, 95% CI: 1.34, 8.00; OR: 3.50, 95% CI: 1.12, 10.90; and OR: 3.18, 95% CI: 1.06, 9.46, respectively. These results indicate that the usage of polluting fuels during pregnancy may heighten the risk of adverse birth outcomes. Consequently, additional research is advised to mitigate the harmful emissions generated by cooking fuels and advocate for clean energy adoption, enhancing maternal and infant well-being.

Evaluation and development strategy of urban-rural integration under ecological protection in the Yellow River Basin, China.

The problem of imbalanced urban-rural development in China is becoming increasingly serious. Urban-rural integration (URI) is an inevitable way to narrow the urban-rural gap and promote rural development. The Yellow River Basin (YRB) is an important barrier to China's ecological security and plays a crucial role in promoting ecological protection and in high-quality development strategies. Therefore, this article constructs an evaluation index system for URI from five dimensions: economic integration, social integration, ecological integration, element integration, and spatial integration. The simulated annealing-projection pursuit model and time degree are used to analyze the dynamic urban-rural integration level (URIL) of 373 counties from 2000 to 2019. Building upon this foundation, this study classifies four types of URI zones and proposes development strategies tailored to each zone. The results indicate (1) that the URIL in the YRB continues to increase, and that there has been a significant increase in high-level integration areas since 2010. (2) The URIL exhibits a distinct spatial clustering pattern, characterized by lower levels in the upper reaches, and higher levels in the middle and lower reaches. (3) There exists a spatial disparity between economic development and the ecological environment, and it is particularly noticeable in the lower reaches regions. These results contribute to a better understanding of URI in the YRB and provide a reference for the sustainable development of URI in various regions.

Low Peripheral B-Cell Counts in Patients With Systemic Rheumatic Diseases Due to Treatment With Belimumab and/or Rituximab Are Associated With Low Antibody Responses to Primary COVID-19 Vaccination.

Background: Immunosuppressive agents inhibit COVID-19 vaccine antibody (Ab) responses in patients with systemic rheumatic diseases. Rituximab may fully block Ab responses when B cells become undetected. The effect of detected but low number of B cells due to treatment with a B-cell agent (belimumab and/or rituximab) has not been established. Purpose: We sought to examine whether there is an association between a low number of B cells due to treatment with belimumab and/or rituximab and impaired primary COVID-19 vaccination spike Ab responses in patients with systemic rheumatic diseases. Methods: We retrospectively examined Ab responses to COVID-19 vaccinations, especially in relation to B-cell counts after treatment with belimumab and/or rituximab, in 58 patients with systemic rheumatic diseases: 22 on and 36 not on B-cell agents. We used Kruskal-Wallis and Mann-Whitney U tests for comparison of Ab values between the groups and Fisher exact test for relative risk calculations. Results: Median (interquartile range) postvaccination Ab responses were lower in patients on versus those not on B-cell agents: 3.91 (0.77-20.00) versus 20.00 (14.32-20.00), respectively. Among patients on belimumab and/or rituximab, Ab responses of less than 25% of the assay's upper limit were exclusively observed in those with B-cell counts lower than 40/µL. Patients with B-cell counts lower than 40/µL exhibit a relative risk of 6.092 (95% CI: 2.75-14.24) for Ab responses of less than 25% of the upper limit compared with patients not on B-cell agents. This relative risk remained significant, even after excluding patients with undetected B cells. Conclusion: This retrospective study found an association between low B-cell counts (less than 40/µL) and decreased Ab responses to primary COVID-19 vaccination in patients with systemic rheumatic diseases treated with belimumab and/or rituximab. Despite the small number of patients studied, these findings add to the accumulating evidence on the importance of B-cell count in predicting spike Ab responses to COVID-19 vaccination.

Establishment and Application Evaluation of an Improved Obstructive Sleep Apnea Screening Questionnaire for Chinese Community: The CNCQ-OSA.

Objective: Obstructive sleep apnea (OSA) is a common sleep-disordered breathing disease. We aimed to establish an improved screening questionnaire without physical examinations for OSA named the CNCQ-OSA (Chinese community questionnaire for OSA). Methods: A total of 2585 participants who visited sleep medicine center and underwent overnight polysomnography were grouped into two independent cohorts: derivation (n = 2180) and validation (n = 405). The CNCQ-OSA was designed according to the baseline of patients in derivation cohort. We comprehensively analyzed the data to evaluate the predictive value of the CNCQ-OSA, compared to the GOAL questionnaire, STOP-Bang questionnaire (SBQ) and NoSAS questionnaire. Results: The CNCQ-OSA included seven variables: loud snoring, BMI ≥ 25 kg/m2, male gender, apnea, sleepiness, hypertension and age ≥30, with a total score ranging from 7 to 16.7 points (≥13.5 points indicating high risk of OSA, ≥14.5 points indicating extremely high risk). In the derivation and validation cohorts, the areas under the curve of the CNCQ-OSA were 0.761 and 0.767, respectively. In the validation cohort, the sensitivity and specificity of a CNCQ-OSA score ≥13.5 points for the apnea-hypopnea index (AHI) ≥5/h were 0.821 and 0.559, respectively (Youden index, 0.380), and the score ≥14.5 points were 0.494 and 0.887, respectively (Youden index, 0.375). The CNCQ-OSA had a better predictive value for AHI ≥ 5/h, AHI > 15/h and AHI > 30/h, with the highest Youden index, compared to the other questionnaires. Conclusion: The CNCQ-OSA can effectively identify the risk of OSA, which is appropriate for self-screening at home without physical examinations.

The relationship between obstructive sleep apnea and asthma severity and vice versa: a systematic review and meta-analysis.

BACKGROUND: There is a great association between the prevalence of obstructive sleep apnea (OSA) and asthma. Nonetheless, whether OSA impacts lung function, symptoms, and control in asthma and whether asthma increases the respiratory events in OSA are unknown. This meta-analysis aimed to examine the relationship between obstructive sleep apnea and asthma severity and vice versa. METHODS: We carried out a systematic search of PubMed, EMBASE, and Scopus from inception to September 2022. Primary outcomes were lung function, parameters of polysomnography, the risk of OSA in more severe or difficult-to-control asthmatic patients, and the risk of asthma in patients with more severe OSA. Heterogeneity was examined with the Q test and I2 statistics. We also performed subgroup analysis, Meta-regression, and Egger's test for bias analysis. RESULTS: 34 studies with 27,912 subjects were totally included. The results showed that the comorbidity of OSA aggravated lung function in asthmatic patients with a consequent decreased forced expiratory volume in one second %predicted (%FEV1) and the effect was particularly evident in children. %FEV1 tended to decrease in adult asthma patients complicated with OSA, but did not reach statistical significance. Interestingly, the risk of asthma seemed to be slightly lower in patients with more severe OSA (OR = 0.87, 95%CI 0.763-0.998). Asthma had no significant effect on polysomnography, but increased daytime sleepiness assessed by the Epworth Sleepiness Scale in OSA patients (WMD = 0.60, 95%CI 0.16-1.04). More severe asthma or difficult-to-control asthma was independently associated with OSA (odds ratio (OR) = 4.36, 95%CI 2.49-7.64). CONCLUSION: OSA was associated with more severe or difficult-to-control asthma with decreased %FEV1 in children. The effect of OSA on lung function in adult patients should be further confirmed. Asthma increased daytime sleepiness in OSA patients. More studies are warranted to investigate the effect of asthma on OSA severity and the impact of different OSA severity on the prevalence of asthma. It is strongly recommended that people with moderate-to-severe or difficult-to-control asthma screen for OSA and get the appropriate treatment.

[Effects of Green, Blue, and Blue-green Roofs on Runoff Quality].

Roofs occupy a great proportion of urban impervious surfaces, and the implementation of eco-roof construction in urban areas is beneficial to alleviate the ecological and environmental problems caused by rapid urbanization. In this study, different eco-roofs (i.e., 68.6%-90.7%, and 39.8%-54.5%, respectively. However, all the eco-roofs were sources of NO-3-N, DCr, DFe, and DNi. The blue roof was a sink of DCu (with a pollutant load reduction rate of 21.9%) and did not affect the cumulative load of PO3-4-P in runoff. However, the green roof and blue-green roof were the sources of PO3-4-P and DCu. The RQI value of the blue roof was the highest, followed by that of the blue-green roof and green roof. The RQI value of the green roof was significantly lower than that of the blue and blue-green roofs (P<0.05). These results indicated that the runoff quality of the blue roof was the best, whereas that of the green roof was the worst. Adding a storage layer to the green roofs could significantly improve the runoff quality. The results of this study provide scientific references for the selection and design of eco-roof facilities.

CTRP family in diseases associated with inflammation and metabolism: molecular mechanisms and clinical implication.

C1q/tumor necrosis factor (TNF) related proteins (CTRPs) is a newly discovered adipokine family with conservative structure and ubiquitous distribution and is secreted by adipose tissues. Recently, CTRPs have attracted increasing attention due to the its wide-ranging effects upon inflammation and metabolism. To-date, 15 members of CTRPs (CTRP1-15) with the characteristic C1q domain have been characterized. Earlier in-depth phenotypic analyses of mouse models of CTRPs deficiency have also unveiled ample function of CTRPs in inflammation and metabolism. This review focuses on the rise of CTRPs, with a special emphasis on the latest discoveries with regards to the effects of the CTRP family on inflammation and metabolism as well as related diseases. We first introduced the structure of characteristic domain and polymerization of CTRPs to reveal its pleiotropic biological functions. Next, intimate association of CTRP family with inflammation and metabolism, as well as the involvement of CTRPs as nodes in complex molecular networks, were elaborated. With expanding membership of CTRP family, the information presented here provides new perspectives for therapeutic strategies to improve inflammatory and metabolic abnormalities.

Association Between Smoking Behavior and Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis.

INTRODUCTION: To systematically review the association between smoking behavior and obstructive sleep apnea (OSA). AIMS AND METHODS: PubMed, Medline, the Cochrane Library, EMBASE, and Scopus databases were used to conduct this review. The two researchers independently screened the literatures, conducted the quality assessment, and data extraction according to the inclusion and exclusion criteria. The RevMan 5.3 was used to analysis the apnea hypopnea index (AHI) index, min saturation of oxyhemoglobin (SaO2), Epworth Sleepiness Scale (ESS) score, and oxygen desaturation index (DOI) and publication bias analysis to assess the effect of smoking on OSA patients. Furthermore, we performed subgroup of the severity of OSA, different countries of sample origin (western countries or eastern countries), and pack-years (PYs < 10 or PYs ≥ 20) to analyze the heterogeneity. RESULTS: Thirteen studies were included in this analysis that conformed to inclusion criteria and exclusion criteria. Totally 3654 smokers and 9796 non-smokers have participated. The meta-analysis of 13 studies demonstrated that AHI levels were significantly higher in smoker group compared with non-smoker, ESS scores were also significantly higher in smoker group compared with non-smoker, min SaO2 levels were obviously lower in smoker group compared with non-smoker, however, DOI levels hadn't significantly different between two groups. The subgroup analysis showed that there was an association between severe OSA, eastern countries, pack-years, and smoking. CONCLUSIONS: Smoking behavior is a significant association with OSA. Heavy smokers with histories of more than 20 PYs were at a higher risk of OSA. Moreover, patient with severe OSA exhibited a significantly association with smoking compared with patients with mild or moderate OSA. IMPLICATIONS: The relationship between smoking and OSA was controversial, especially, whether smoking increase or aggravate the risk of OSA. In our review and meta-analysis, we demonstrated that smoking behavior is a significant association with OSA. Heavy smokers with histories of more than 20 PYs were at a higher risk of OSA. Moreover, patient with severe OSA exhibited a significant association with smoking compared with patients with mild or moderate OSA. More prospective long-term follow-up studies about effect of quit smoking on OSA are recommended to establish the further relationship.

[Integrated Assessment of Runoff Quality from Green Roofs with Different Configurations].

Green roofs are regarded as one of the important measures for the sponge city construction. However, the comprehensive impacts of configuration factors (e.g., vegetation and substrates) on runoff quality from green roofs are not clear, which limits the promotion of green roofs. In this study, 12 green roofs with three vegetation types (i.e., Sedum lineare, Portulaca grandiflora, and non-vegetated substrates), three substrate types (i.e., local planting soil, engineered soil, and light growing medium), and two substrate depths (i.e., 10 cm and 15 cm) were set up in Beijing. During the rainy season of 2019, the rainfall characteristics, runoff volumes, and concentrations of nutrients and heavy metals of runoff from the green roofs were monitored. Based on the measured data, a runoff quality index (RQI) was developed to evaluate the comprehensive influences of configurations on runoff quality of the green roofs. The results showed that vegetation could improve runoff reduction rate and decrease the concentrations of NO3--N in runoff of green roofs. The RQIs of green roofs planted with S. linear and P. grandiflora were similar, and the evaluation results of runoff quality were better than those with non-vegetated substrates. The materials of substrates had significant influences on the runoff reduction rate and pollutant concentrations in runoff from green roofs. The green roofs with light growing medium, which had the lowest runoff reduction rates and the highest concentrations of NH4+-N, DFe, DMn, and DZn in the runoff, showed poorer runoff quality than the green roofs with local planting soil and engineered soil. The green roofs with a substrate depth of 15 cm had higher runoff reduction rates than those with 10 cm deep substrate, and the runoff quality was better than those with a substrate depth of 10 cm. The results of this study provide scientific reference for the design and integrated assessment of green roofs.

Chronic activation of pDCs in autoimmunity is linked to dysregulated ER stress and metabolic responses.

Plasmacytoid dendritic cells (pDCs) chronically produce type I interferon (IFN-I) in autoimmune diseases, including systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). We report that the IRE1α-XBP1 branch of the unfolded protein response (UPR) inhibits IFN-α production by TLR7- or TLR9-activated pDCs. In SSc patients, UPR gene expression was reduced in pDCs, which inversely correlated with IFN-I-stimulated gene expression. CXCL4, a chemokine highly secreted in SSc patients, downregulated IRE1α-XBP1-controlled genes and promoted IFN-α production by pDCs. Mechanistically, IRE1α-XBP1 activation rewired glycolysis to serine biosynthesis by inducing phosphoglycerate dehydrogenase (PHGDH) expression. This process reduced pyruvate access to the tricarboxylic acid (TCA) cycle and blunted mitochondrial ATP generation, which are essential for pDC IFN-I responses. Notably, PHGDH expression was reduced in pDCs from patients with SSc and SLE, and pharmacological blockade of TCA cycle reactions inhibited IFN-I responses in pDCs from these patients. Hence, modulating the IRE1α-XBP1-PHGDH axis may represent a hitherto unexplored strategy for alleviating chronic pDC activation in autoimmune disorders.

Ultrastructural Analysis of Er:YAG Lased Bovine Dentin Contaminated by Cariogenic Bacteria.

Objective: The purpose of this study is to investigate the crystal structure of bacteria-contaminated bovine dentin after Er:YAG laser irradiation at various energy densities from macroscale, microscale, and nanoscale. Background: Er:YAG laser can change the morphology and chemical components of dentin. Few preliminary researchers investigate the laser effect on crystal in dentin tissue. Methods: Twenty dentin specimens from bovine incisors were cocultured with S. mutans (UA 159) and divided into four groups with diverse Er:YAG laser irradiation energy (0, 6.37, 12.73, 19.11 J/cm2). The ultrastructure of dentin before and after laser irradiation was investigated with nanoanalytical electron microscopy. X-ray diffraction provided the information of lattice parameters in dentin. The morphology of dentin was observed by scanning electron microscopy. High-resolution transmission electron microscope images and selected-area electron diffraction patterns were obtained for characterizing crystal domain size, structure, and microenvironment of dentin. Results: The combination of these methods disclosed that there exist mineralized, demineralized, and remineralized dentin in the bacteria-invaded dentin and can be feasibly recognized using morphological features. Laser treatments influence hydroxyapatite (HAp) crystals in dentin tissue in different ways: needle HAp in mineralized dentin tissue keeps intact with laser irradiation of no higher than 19.11 J/cm2; laser irradiation improves the crystallinity of lamella HAp by domain growth and rearranges its growth orientations. Conclusions: We report an unprecedented presence of remineralization zone consisting of lamella HAp crystals with distinct high-index planes. These findings have broad implications on the role of laser operation in driving biomineralization and shed new insights into a possible relationship between laser irradiation and remineralization.

[Inter-annual Changes in Runoff Quality from Green Roofs with Different Vegetation].

As an important measure of the sponge city, green roofs have received extensive attention in recent years. To investigate the inter-annual changes in runoff quality of green roofs with different vegetation types, three green roofs with different vegetation cover (Sedum lineare, Portulaca grandiflora, and a non-vegetated control) were set up in Beijing. The influences of vegetation and monitoring period on runoff quality from the green roofs were evaluated using the plant growth characteristics and the quality of rainwater and runoff from the green roofs during the rainy season of 2017-2019. The results showed that all three green roofs were the sinks of NH4+-N, and the average mass concentration reduction rates were between 50.1% and 79.2%. However, all three green roofs were sources of PO43--P, DCr, DCu, and DNi. The green roofs covered with S. lineare and P. grandiflora were sinks of NO3--N in 2017, and the average mass concentration reduction rates were 71.4% and 99.5%, respectively, but they became sources of NO3--N in both 2018 and 2019. However, the non-vegetated control was the source of NO3--N in all three rainy seasons. Both vegetation type and length of monitoring period had significant effects on the mass concentrations of NO3--N, PO43--P, DNi, and DCu in runoff from the green roofs (P<0.05) but had no significant effects on the mass concentrations of NH4+-N and DCr in runoff from the green roofs (P>0.05). In 2017-2019, the mass concentrations of NO3--N in runoff from the non-vegetated control and the green roofs covered by S. lineare and the mass concentration of PO43--P in runoff from the green roof covered by P. grandiflora increased yearly. The mass concentrations of DNi and DCu in runoff from all three green roofs increased in 2018 but dropped in 2019. Among the green roofs with different vegetation types, the green roof covered by P. grandiflora showed better NO3--N retention capacity than that of the other green roofs but may have increased the concentrations of PO43--P, DNi, and DCu in the runoff.