Phenotypic and transcriptome profiling of spikes reveals the regulation of light regimens on spike growth and fertile floret number in wheat.

The spike growth phase is critical for the establishment of fertile floret (grain) numbers in wheat (Triticum aestivum L.). Then, how to shorten the spike growth phase and increase grain number synergistically? Here, we showed high-resolution analyses of floret primordia (FP) number, morphology and spike transcriptomes during the spike growth phase under three light regimens. The development of all FP in a spike could be divided into four distinct stages: differentiation (Stage I), differentiation and morphology development concurrently (Stage II), morphology development (Stage III), and polarization (Stage IV). Compared to the short photoperiod, the long photoperiod shortened spike growth and stimulated early flowering by shortening Stage III; however, this reduced assimilate accumulation, resulting in fertile floret loss. Interestingly, long photoperiod supplemented with red light shortened the time required to complete Stages I-II, then raised assimilates supply in the spike and promoted anther development before polarization initiation, thereby increasing fertile FP number during Stage III, and finally maintained fertile FP development during Stage IV until they became fertile florets via a predicted dynamic gene network. Our findings proposed a light regimen, critical stages and candidate regulators that achieved a shorter spike growth phase and a higher fertile floret number in wheat.

Low sucrose availability reduces basal spikelet fertility by inducing abscisic acid and jasmonic acid synthesis in wheat.

Within a spike of wheat, the central spikelets usually generate three to four fertile florets, while the basal spikelets generate zero to one fertile floret. The physiological and transcriptional mechanism behind the difference in fertility between the basal and central spikelets is unclear. This study reports a high temporal resolution investigation of transcriptomes, number and morphology of floret primordia, and physiological traits. The W6.5-W7.5 stage was regarded as the boundary to distinguish between fertile and abortive floret primordia; those floret primordia reaching the W6.5-W7.5 stage during the differentiation phase (3-9 d after terminal spikelet stage) usually developed into fertile florets in the next dimorphism phase (12-27 d after terminal spikelet stage), whereas the others aborted. The central spikelets had a greater number of fertile florets than the basal spikelets, which was associated with more floret primordia reaching the W6.5-W7.5 stage. Physiological and transcriptional results demonstrated that the central spikelets had a higher sucrose content and lower abscisic acid (ABA) and jasmonic acid (JA) accumulation than the basal spikelets due to down-regulation of genes involved in ABA and JA synthesis. Collectively, we propose a model in which ABA and JA accumulation is induced under limiting sucrose availability (basal spikelet) through the up-regulation of genes involved in ABA and JA synthesis; this leads to floret primordia in the basal spikelets failing to reach their fertile potential (W6.5-W7.5 stage) during the differentiation phase and then aborting. This fertility repression model may also regulate spikelet fertility in other cereal crops and potentially provides genetic resources to improve spikelet fertility.

Predicting lung cancer survival prognosis based on the conditional survival bayesian network.

Lung cancer is a leading cause of cancer deaths and imposes an enormous economic burden on patients. It is important to develop an accurate risk assessment model to determine the appropriate treatment for patients after an initial lung cancer diagnosis. The Cox proportional hazards model is mainly employed in survival analysis. However, real-world medical data are usually incomplete, posing a great challenge to the application of this model. Commonly used imputation methods cannot achieve sufficient accuracy when data are missing, so we investigated novel methods for the development of clinical prediction models. In this article, we present a novel model for survival prediction in missing scenarios. We collected data from 5,240 patients diagnosed with lung cancer at the Weihai Municipal Hospital, China. Then, we applied a joint model that combined a BN and a Cox model to predict mortality risk in individual patients with lung cancer. The established prognostic model achieved good predictive performance in discrimination and calibration. We showed that combining the BN with the Cox proportional hazards model is highly beneficial and provides a more efficient tool for risk prediction.

Greenness mitigate cause-specific mortality associated with air pollutants in ischemic and hemorrhagic stroke patients: An ecological health cohort study.

BACKGROUND: Air pollution is one of the most serious environmental risks to mortality of stroke. However, there exists a noteworthy knowledge gap concerning the different stroke subtypes, causes of death, the susceptibility of stroke patient, and the role of greenness in this context. METHODS: We analyzed data from an ecological health cohort, which included 334,261 patients aged ≥40 years with stroke (comprising 288,490 ischemic stroke and 45,771 hemorrhagic stroke) during the period 2013-2019. We used Cox proportional hazards models with time-varying exposure to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the associations of annual average fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) with both all-cause and cause-specific mortality. Additionally, we conducted analyses to examine the effect modification by greenness and identify potential susceptibility factors through subgroup analyses. RESULT: In multivariable-adjusted models, long-term exposure to PM2.5 and NO2 was associated with increased risk of all-cause mortality (HR: 1.038, 95% CI: 1.029-1.047 for PM2.5; HR: 1.055, 95% CI: 1.026-1.085 for NO2, per 10 µg/m3, for ischemic stroke patients; similar for hemorrhagic stroke patients). Gradually increasing effect sizes were shown for CVD mortality and stroke mortality. The HRs of mortality were slightly weaker with high versus low vegetation exposure. Cumulative exposures increased the HRs of pollutant-related mortality, and greater greenness decreased this risk. Two subtypes of stroke patients exhibited diverse patterns of benefit. CONCLUSION: Increasing residential greenness attenuates the increased risk of mortality with different patterns due to chronic air pollutants for ischemic and hemorrhagic stroke, offering valuable insights for precise tertiary stroke prevention strategies.

The combined effect of air pollution and non-optimal temperature on mortality in Shandong Province, China: establishment of air health index.

PURPOSE: The air health index (AHI) captures the combined effects of air pollution and non-optimal temperatures and helps assess the atmospheric environment's overall health risk. Shandong Province is a crucial industrial base in China, and the health effects of air pollution and non-optimal temperature cannot be ignored. To construct an AHI for Shandong Province and assess the district-level mortality burden due to AHI in the study area. METHODS: Daily district-specific mortality, meteorological, and air pollution data over 2013-2018 were collected in Shandong Province, China. The AHI construction eventually incorporated PM2.5 and NO2, O3, and non-optimal temperatures. Attributable fraction (AF) and attributable number (AN) were used to estimate the district-specific mortality burden attributable to AHI. RESULTS: The average AHI value observed in Shandong Province was 6. Our research revealed a positive association between the total AHI and total mortality, with an overall trend of a slow increase followed by a rapid increase. The exposure-response curves, when stratified by gender, age, and cause of death, were approximately consistent with the overall trend. The provincial attributable fraction (AF) was 5.31% (95% CI 4.58%, 5.91%), and the attributable number (AN) was 188,246 (95% CI 162,396, 209,533). Overall, higher ANs mainly appeared in the southwestern area, while higher values of AF were observed in the central-eastern and central-northern areas. CONCLUSIONS: The air health index performs well in predicting death burden and can convey health risks related to exposure to the ambient environment to the public.

Association Between Peritoneal Glucose Absorption, Lipid Metabolism, and Cardiovascular Disease Risk in Nondiabetic Patients on Peritoneal Dialysis.

BACKGROUND: Excessive sugar intake increases the energy metabolic burden and the risk of cardiovascular disease (CVD). Patients on peritoneal dialysis absorb much more glucose than the World Health Organization recommends, but the link to CVD is unclear. OBJECTIVE: To identify the association between peritoneal glucose absorption, lipid metabolism, and CVD. METHODS: We applied generalized additive mixed effects and mixed effects Cox proportional hazard models to evaluate the impact of peritoneal glucose absorption on lipid profiles and CVD risk. We performed subgroup analyses by using protein intake (normalized protein nitrogen appearance [nPNA] and normalized protein catabolic rate [nPCR] were used to assess protein intake) and high-sensitivity C-reactive protein (hs-CRP). RESULTS: After multivariable adjustment, peritoneal glucose absorption per 10 g/d increase was associated with an increase in cholesterol of 0.145 (95% confidence interval [CI]: 0.086-0.204) mmol/L. No link with the total risk of CVD was observed; however, protein intake and hs-CRP levels affected the relationship between glucose absorption and CVD risk. Patients with values for nPNA and nPCR <1.0 g/(kg·d) were associated with a lower risk of CVD (hazard ratio [HR] 95% CI: 0.68 (0.46-0.98)) with glucose absorption per 10 g/d increase. While patients with hs-CRP levels ≥3 mg/d or values for nPNA or nPCR ≥1.0 g/(kg·d) were associated with a higher risk of CVD (HR 95% CI: 1.32 (1.07-1.63); 1.31 (1.02-1.68)) for glucose absorption per 10 g/d increase. CONCLUSIONS: Our study found a positive correlation between peritoneal glucose absorption and lipid profiles. Increased glucose absorption was associated with a lower risk of CVD in lower protein intake patients and a higher risk of CVD in higher hs-CRP or protein intake levels in patients on peritoneal dialysis.

Association of ambient ozone exposure and greenness exposure with hemorrhagic stroke mortality at different times: A cohort study in Shandong Province, China.

Evidence on the association between long-term ozone exposure and greenness exposure and hemorrhagic stroke (HS) is limited, with mixed results. One potential source of this inconsistency is the difference in exposure time metrics. This study aimed to investigate the association between long-term exposure to ambient ozone, greenness, and mortality from HS using exposure metrics at different times. We also examined whether greenness exposure modified the relationship between ozone exposure and mortality due to HS. The study population consisted of 45771 participants aged ≥40 y residing in 20 counties in Shandong Province who were followed up from 2013 to 2019. Ozone exposure metrics (annual mean and warm season) and the normalized difference a measure of greenness exposure, were calculated. The relationship between environmental exposures (ozone and greenness exposures) and mortality from HS was assessed using time-dependent Cox proportional hazards models, and the modification of greenness exposure was examined using stratified analysis with interaction terms. The person-years at the end of follow-up were 90,663. With full adjustments, the risk of death from hemorrhagic stroke increased by 5% per interquartile range increase in warm season ozone [hazard ratio =1.05; 95 % confidence interval: 1.01-1.08]. No clear association was observed between annual ozone and mortality HS. Both the annual and summer NDVI were found to reduce the risk of HS mortality. The relationships were influenced by age, sex, and residence (urban or rural). Furthermore, greenness exposure was shown to have a modifying effect on the relationship between ozone exposure and the occurrence of HS mortality (P for interaction = 0.001). Long-term exposure to warm season O3 was positively associated with HS mortality, while greenness exposure was inversely associated with HS mortality. Greenness exposure may mitigate the negative effects of warm season ozone exposure on HS mortality.

Impacts of heatwaves on type 2 diabetes mortality in China: a comparative analysis between coastal and inland cities.

The impacts of extreme temperatures on diabetes have been explored in previous studies. However, it is unknown whether the impacts of heatwaves appear variations between inland and coastal regions. This study aims to quantify the associations between heat exposure and type 2 diabetes mellitus (T2DM) deaths in two cities with different climate features in Shandong Province, China. We used a case-crossover design by quasi-Poisson generalized additive regression with a distributed lag model with lag 2 weeks, controlling for relative humidity, the concentration of air pollution particles with a diameter of 2.5 µm or less (PM2.5), and seasonality. The wet- bulb temperature (Tw) was used to measure the heat stress of the heatwaves. A significant association between heatwaves and T2DM deaths was only found in the coastal city (Qingdao) at the lag of 2 weeks at the lowest Tw = 14℃ (relative risk (RR) = 1.49, 95% confidence interval (CI): 1.11-2.02; women: RR = 1.51, 95% CI: 1.02-2.24; elderly: RR = 1.50, 95% CI: 1.08-2.09). The lag-specific effects were significant associated with Tw at lag of 1 week at the lowest Tw = 14℃ (RR = 1.14, 95% CI: 1.03-1.26; women: RR = 1.15, 95% CI: 1.01-1.31; elderly: RR = 1.15, 95% CI: 1.03-1.28). However, no significant association was found in Jian city. The research suggested that Tw was significantly associated with T2DM mortality in the coastal city during heatwaves on T2DM mortality. Future strategies should be implemented with considering socio-environmental contexts in regions.

Dynamic gene regulatory networks improving spike fertility through regulation of floret primordia fate in wheat.

The developmental process of spike is critical for spike fertility through affecting floret primordia fate in wheat; however, the genetic regulation of this dynamic and complex developmental process remains unclear. Here, we conducted a high temporal-resolution analysis of spike transcriptomes and monitored the number and morphology of floret primordia within spike. The development of all floret primordia in a spike was clearly separated into three distinct phases: differentiation, pre-dimorphism and dimorphism. Notably, we identified that floret primordia with meiosis ability at the pre-dimorphism phase usually develop into fertile floret primordia in the next dimorphism phase. Compared to control, increasing plant space treatment achieved the maximum increasement range (i.e., 50%) in number of fertile florets by accelerating spike development. The process of spike fertility improvement was directed by a continuous and dynamic regulatory network involved in transcription factor and genes interaction. This was based on the coordination of genes related to heat shock protein and jasmonic acid biosynthesis during differentiation phase, and genes related to lignin, anthocyanin and chlorophyll biosynthesis during dimorphism phase. The multi-dimensional association with high temporal-resolution approach reported here allows rapid identification of genetic resource for future breeding studies to realise the maximum spike fertility potential in more cereal crops.

Recent Advances in Corrosion Science Applicable To Disposal of High-Level Nuclear Waste.

High-level radioactive waste is accumulating at temporary storage locations around the world and will eventually be placed in deep geological repositories. The waste forms and containers will be constructed from glass, crystalline ceramic, and metallic materials, which will eventually come into contact with water, considering that the period of performance required to allow sufficient decay of dangerous radionuclides is on the order of 105-106 years. Corrosion of the containers and waste forms in the aqueous repository environment is therefore a concern. This Review describes the recent advances of the field of materials corrosion that are relevant to fundamental materials science issues associated with the long-term performance assessment and the design of materials with improved performance, where performance is defined as resistance to aqueous corrosion. Glass, crystalline ceramics, and metals are discussed separately, and the near-field interactions of these different material classes are also briefly addressed. Finally, recommendations for future directions of study are provided.

Estimating future PM2.5-attributed acute myocardial infarction incident cases under climate mitigation and population change scenarios in Shandong Province, China.

BACKGROUND: The effects of fine particulate matter (PM2.5) on acute myocardial infarction (AMI) have been widely recognized. However, no studies have comprehensively evaluated future PM2.5-attributed AMI burdens under different climate mitigation and population change scenarios. We aimed to quantify the PM2.5-AMI association and estimate the future change in PM2.5-attributed AMI incident cases under six integrated scenarios in 2030 and 2060 in Shandong Province, China. METHODS: Daily AMI incident cases and air pollutant data were collected from 136 districts/counties in Shandong Province from 2017 - 2019. A two-stage analysis with a distributed lag nonlinear model was conducted to quantify the baseline PM2.5-AMI association. The future change in PM2.5-attributed AMI incident cases was estimated by combining the fitted PM2.5-AMI association with the projected daily PM2.5 concentrations under six integrated scenarios. We further analyzed the factors driving changes in PM2.5-related AMI incidence using a decomposition method. RESULTS: Each 10 µg/m3 increase in PM2.5 exposure at lag05 was related to an excess risk of 1.3 % (95 % confidence intervals: 0.9 %, 1.7 %) for AMI incidence from 2017 - 2019 in Shandong Province. The estimated total PM2.5-attributed AMI incident cases would increase by 10.9-125.9 % and 6.4-244.6 % under Scenarios 1 - 3 in 2030 and 2060, whereas they would decrease by 0.9-5.2 % and 33.0-46.2 % under Scenarios 5 - 6 in 2030 and 2060, respectively. Furthermore, the percentage increases in PM2.5-attributed female cases (2030: -0.3 % to 135.1 %; 2060: -33.2 % to 321.5 %) and aging cases (2030: 15.2-171.8 %; 2060: -21.5 % to 394.2 %) would wholly exceed those in male cases (2030: -1.8 % to 133.2 %; 2060: -41.1 % to 264.3 %) and non-aging cases (2030: -41.0 % to 45.7 %; 2060: -89.5 % to -17.0 %) under six scenarios in 2030 and 2060. Population aging is the main driver of increased PM2.5-related AMI incidence under Scenarios 1 - 3 in 2030 and 2060, while improved air quality can offset these negative effects of population aging under the implementation of the carbon neutrality and 1.5 °C targets. CONCLUSION: The combination of ambitious climate policies (i.e., 1.5 °C warming limits and carbon neutrality targets) with stringent clean air policies is necessary to reduce the health impacts of air pollution in Shandong Province, China, regardless of population aging.

Quantifying substantial carcinogenesis of genetic and environmental factors from measurement error in the number of stem cell divisions.

BACKGROUND: The relative contributions of genetic and environmental factors versus unavoidable stochastic risk factors to the variation in cancer risk among tissues have become a widely-discussed topic. Some claim that the stochastic effects of DNA replication are mainly responsible, others believe that cancer risk is heavily affected by environmental and hereditary factors. Some of these studies made evidence from the correlation analysis between the lifetime number of stem cell divisions within each tissue and tissue-specific lifetime cancer risk. However, they did not consider the measurement error in the estimated number of stem cell divisions, which is caused by the exposure to different levels of genetic and environmental factors. This will obscure the authentic contribution of environmental or inherited factors. METHODS: In this study, we proposed two distinct modeling strategies, which integrate the measurement error model with the prevailing model of carcinogenesis to quantitatively evaluate the contribution of hereditary and environmental factors to cancer development. Then, we applied the proposed strategies to cancer data from 423 registries in 68 different countries (global-wide), 125 registries across China (national-wide of China), and 139 counties in Shandong province (Shandong provincial, China), respectively. RESULTS: The results suggest that the contribution of genetic and environmental factors is at least 92% to the variation in cancer risk among 17 tissues. Moreover, mutations occurring in progenitor cells and differentiated cells are less likely to be accumulated enough for cancer to occur, and the carcinogenesis is more likely to originate from stem cells. Except for medulloblastoma, the contribution of genetic and environmental factors to the risk of other 16 organ-specific cancers are all more than 60%. CONCLUSIONS: This work provides additional evidence that genetic and environmental factors play leading roles in cancer development. Therefore, the identification of modifiable environmental and hereditary risk factors for each cancer is highly recommended, and primary prevention in early life-course should be the major focus of cancer prevention.

Inulin-type prebiotics reduce serum uric acid levels via gut microbiota modulation: a randomized, controlled crossover trial in peritoneal dialysis patients.

PURPOSE: Increased levels of uric acid (UA), which is mainly excreted through the kidneys, are independently associated with higher mortality in end-stage renal disease (ESRD) patients. The uricolysis of gut microbiota plays an important role in extrarenal excretion of UA. This study aimed to examine the effect of inulin-type prebiotics (a type of fermentable dietary fiber) on intestinal microbiota modulation and serum UA levels in ESRD patients. METHODS: Continuous ambulatory peritoneal dialysis (CAPD) patients were recruited to a randomized, double-blind, placebo-controlled crossover trial of 12-week inulin-type prebiotics. Participants were visited before and after treatment with prebiotics or placebo. Serum UA levels, dietary purine intake, serum xanthine oxidase (XO) activity, daily "renal excretion" of UA, and fecal UA degradation capability were measured at each visit. Fecal metagenomic analysis was conducted to assess microbial composition and function. RESULTS: Sixteen participants (mean age = 37 y; 10 men and 6 women) completed the trial, and 64 specimens were analyzed. The average concentration of serum UA decreased by approximately 10% in the prebiotic intervention group in comparison to the placebo group (p = 0.047) without an increase in daily "renal excretion" of UA via urine and dialysate. There were no significant changes in purine intake or activity of XO. Notably, enhanced fecal UA degradation was observed after prebiotic intervention (p = 0.041), and the ratio of Firmicutes/Bacteroidetes, which was positively associated with fecal UA degradation, increased in the prebiotic period (p = 0.032). Furthermore, prebiotics enriched purine-degrading species in the gut microbiota, including unclassified_o_Clostridiales, Clostridium sp. CAG:7, Clostridium sp. FS41, Clostridium citroniae, Anaerostipes caccae, and Clostridium botulinum. CONCLUSIONS: Inulin-type prebiotics is a promising therapeutic candidate to reduce serum UA levels in renal failure patients, and this urate-lowering effect could possibly be attributed to intestinal microbial degradation of UA. TRIAL REGISTRY: This study was registered at the Chinese Clinical Trials Registry ( http://www.chictr.org.cn/ ), registration ID: ChiCTR-INR-17013739, registration date: 6th Dec 2017.

Short-term effects of exposure to ambient PM1, PM2.5, and PM10 on ischemic and hemorrhagic stroke incidence in Shandong Province, China.

BACKGROUND: Short-term exposure to ambient PM2.5 and PM10 is associated with increased risk of mortality and hospital admissions for stroke. However, there is less evidence regarding the effect of exposure to PM1 on stroke incidence. We estimated the incidence risk of stroke and the attributable fractions related to short-term exposure to ambient PM1, PM2.5 and PM10 in China. METHODS: County-specific incidence of stroke was obtained from health statistics in years 2014-2019. We linked county-level mean daily concentrations of PM1, PM2.5 and PM10 with stroke incidence. We used the time stratified case-crossover design to estimate the associations between stroke incidence and exposure to PM1, PM2.5 and PM10. We also estimated the disease burden fractions attributable to PM1, PM2.5, and PM10. RESULTS: The study included a total of 2,193,954 stroke, from which 1,861,331 were ischemic and 332,623 were hemorrhagic stroke. PM1, PM2.5, and PM10 levels were associated with increased risks of total stroke and ischemic stroke at when assessing the associations in exposure at lag0-4 days. The increase of 10 µg/m3 in PM1, PM2.5, and PM10 was associated with total stroke, and the relative risks were 1.012 (95% confidence interval: 1.008, 1.015), 1.006 (1.004, 1.007) and 1.003 (1.002, 1.004), while the associations with ischemic stroke were 1.013 (1.010, 1.017), 1.006 (1.005, 1.008) and 1.003 (1.002, 1.004), respectively. There was no significant association between PM and risk of hemorrhagic stroke. The attributable fractions of total stroke were 6.9% (5.1%, 8.5%), 5.6% (4.2%, 6.8%) and 5.6% (3.9%, 7.1%) for PM1, PM2.5, and PM10, respectively. CONCLUSIONS: PM1 showed a stronger association with stroke, with a larger attributable fraction of outcomes, than PM2.5 and PM10. Clean air policies should target the whole scope of PM, including PM1.

Perioperative stroke in patients undergoing spinal surgery: a retrospective cohort study.

BACKGROUND: The incidence of perioperative stroke following spinal surgery, including ischemic and hemorrhagic stroke, has not been fully investigated in the Chinese population. Whether specific spinal or emergency/elective procedures are associated with perioperative stroke remains controversial. This study aimed to investigate the incidence of perioperative stroke, health economic burden, clinical outcomes, and associated risk factors. METHOD: A retrospective cohort study using an electronic hospital information system database was conducted from Jan 1, 2015, to Jan 1, 2021, in a tertiary hospital in China. Patients aged ≥18 years who had undergone spinal surgery were included in the study. We recorded patient demographics, comorbidities, and health economics data. Clinical outcomes included perioperative stroke during hospitalization and associated risk factors. The patients' operative data, anesthetic data, and clinical manifestations were recorded. RESULT: A total of 17,408 patients who had undergone spinal surgery were included in this study. Twelve patients had perioperative stroke, including seven ischemic stroke (58.3%) and five hemorrhagic stroke (41.7%). The incidence of perioperative stroke was 0.07% (12/17,408). In total, 12 stroke patients underwent spinal fusion. Patients with perioperative stroke were associated with longer hospital stay (38.33 days vs. 9.78 days, p < 0.001) and higher hospital expenses (RMB 175,642 vs. RMB 81,114, p < 0.001). On discharge, 50% of perioperative patients had severe outcomes. The average onset time of perioperative stroke was 1.3 days after surgery. Stroke history (OR 146.046, 95% CI: 28.102-759.006, p < 0.001) and hyperlipidemia (OR 4.490, 95% CI: 1.182-17.060, p = 0.027) were associated with perioperative stroke. CONCLUSION: The incidence of perioperative stroke of spinal surgery in a tertiary hospital in China was 0.07%, with a high proportion of hemorrhagic stroke. Perioperative stroke patients experienced a heavy financial burden and severe outcomes. A previous stroke history and hyperlipidemia were associated with perioperative stroke.

The Accumulation of Gut Microbiome-derived Indoxyl Sulfate and P-Cresyl Sulfate in Patients With End-stage Renal Disease.

OBJECTIVES: Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are two important gut microbiota-generated protein-bound uremic toxins. The present study aims to explore the alterations of serum IS and pCS concentrations, their production, and daily removal in end-stage renal disease (ESRD). METHODS: A case-controlled study was conducted based on 11 patients with ESRD and 11 healthy volunteers. The metabolic processes for IS and pCS were compared in these two groups, including gut microbiome, fecal indole and p-cresol, indole-producing bacteria and p-cresol-producing bacteria, serum total IS and pCS concentrations, and their daily removal by urine and spent dialyzate. RESULTS: Compared with healthy controls, patients with ESRD exhibited higher relative abundance of the indole-producing bacteria Escherichia coli (P < .001) and Bacteroides fragilis (P = .010) and p-cresol-producing bacteria Bacteroides fragilis (P = .010) and Bacteroides caccae (P = .047). The predicted functional profiles of gut microbiome based on 16S rRNA gene PhyloChip analysis showed that the microbial tryptophan metabolism pathway (map00380, P = .0006) was significantly enriched in patients with ESRD. However, the fecal precursors indole (P = .332) and p-cresol concentrations (P = .699) were comparable between the two groups. The serum IS (P < .001) and pCS (P < .001) concentrations were far higher in patients with ESRD than those in healthy controls, whereas the daily total removal by urine and dialyzate was much lower for the former than that for the latter (P = .019 for IS, P = .016 for pCS). CONCLUSIONS: The present study showed serious IS and pCS accumulation in patients with ESRD, with significant expansion of indole-producing bacteria and p-cresol-producing bacteria, upregulation of the bacterial tryptophan metabolism pathway, and greatly increased serum IS and pCS concentrations, whereas significant decline of daily IS and pCS removal.

Increased risk of modality failure with higher serum uric acid level in continuous ambulatory peritoneal dialysis patients: a prospective cohort study.

BACKGROUND: Peritoneal dialysis (PD) is one of the most important kidney replacement therapies for patients with end-stage kidney disease (ESKD). PD technique failure can lead to an escalated cost and increased infectious and cardiovascular risk, up and including to death. The accumulation of uric acid (UA) was associated with adverse outcomes in ESKD patients. However, the relationship between serum UA and technique failure is little explored. METHODS: Here, a total of 266 continuous ambulatory peritoneal dialysis (CAPD) patients (age, 41.8 ± 12.6 years; 125 males) were enrolled and followed up for 31.7 months. Serum UA levels were examined at baseline and each visit. Subjects were divided into three groups according to their baseline serum UA concentrations. Multivariable Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of PD technique failure. RESULTS: The level of serum UA increased gradually as time prolonged. During the follow-up period, 77 (28.9%) patients occurred PD technique failure, of which 56 (21.1%) transferred to hemodialysis (HD) and 21 (7.9%) died. Compared to the lowest UA tertile, after adjusting for potential confounders, HRs of technique failure in tertile 2 and tertile 3 were 1.82 (95% CI: 0.95-3.49) and 2.03 (95% CI: 1.05-3.92), respectively, and p for trend was 0.043. Adjusted HRs of all-cause technique failure, transferring to HD and mortality with each 1 mg/dL increase in serum UA were 1.20 (95% CI: 1.03-1.40, p = 0.019), 1.22 (95% CI: 1.01-1.48, p = 0.039), and 1.25 (95% CI: 0.94-1.67, p = 0.128), respectively. CONCLUSION: Higher serum UA level predicted higher risk of technique failure in CAPD patients.

Self-accelerated corrosion of nuclear waste forms at material interfaces.

The US plan for high-level nuclear waste includes the immobilization of long-lived radionuclides in glass or ceramic waste forms in stainless-steel canisters for disposal in deep geological repositories. Here we report that, under simulated repository conditions, corrosion could be significantly accelerated at the interfaces of different barrier materials, which has not been considered in the current safety and performance assessment models. Severe localized corrosion was found at the interfaces between stainless steel and a model nuclear waste glass and between stainless steel and a ceramic waste form. The accelerated corrosion can be attributed to changes of solution chemistry and local acidity/alkalinity within a confined space, which significantly alter the corrosion of both the waste-form materials and the metallic canisters. The corrosion that is accelerated by the interface interaction between dissimilar materials could profoundly impact the service life of the nuclear waste packages, which, therefore, should be carefully considered when evaluating the performance of waste forms and their packages. Moreover, compatible barriers should be selected to further optimize the performance of the geological repository system.

Mitochondria-Immobilized Unimolecular Fluorescent Probe for Multiplexing Imaging of Living Cancer Cells.

Cancer incidence and mortality are fast growing worldwide. Recently, multiplexing imaging methods have been reported to be vital for cancer diagnosis and therapy. Fluorescence imaging, which has intrinsic capabilities for multiplexing imaging, is suitable and ripe for cancer imaging. In biomedical research, using a single probe for multiplexing imaging can avoid larger invasive effects and ensure the same spatiotemporal distributions and metabolisms of the probes, which has advantages over using multiple probes. Therefore, developing unimolecular fluorescent probes for multiplexing imaging of living cancer cells is meaningful. We herein report a unimolecular fluorescent probe (ZED) that simultaneously detects cysteine/homocysteine, hypochlorous acid, mitochondrial membrane potential (Δψm), and opening of the mitochondrial permeability transition (MPT) pore in cells. These four analytes are key indicators predominantly associated with multiple aspects of carcinogenesis and cancer therapy in living cells. Besides, ZED also differentiates MCF-7 cells from HBL-100 cells. The sensing process is fast, selective, and sensitive in living cancer cells. As far as we know, ZED is the first probe that simultaneously detects four analytes in cells and the first probe that simultaneously detects Δψm and opening of the MPT pore in mitochondria.

A bi-enzymatic cascade to yield pyruvate as co-substrate for L-tyrosine production.

L-Tyrosine is a versatile compound used in the fine chemical, pharmaceutical, and functional food industries. Here, we report a bi-enzymatic cascade involving alanine racemase (ALR) and D-amino acid oxidase (DAAO) to produce pyruvate, as co-substrate for L-tyrosine production, from the cheap substrate L-alanine. The BpALR (ALR from Bacillus pseudofirmus) was used as a whole-cell biocatalyst, converting L-alanine to D, L-alanine. The FsDAAO (DAAO from Fusarium solani) was immobilized to oxidize the D-alanine generated in the first step to pyruvate. Both systems were combined as a continuous-flow reactor for maximized L-alanine-to-pyruvate conversion rates. The optimal parameters and appropriate conditions for FsDAAO immobilization were investigated. The pyruvate concentration of 86.6 g/L was achieved within 17 h. Subsequently, a whole-cell biocatalyst system for L-tyrosine production, catalyzed by the tyrosine phenol-lyase (TPL) from Erwinia herbicola (EhTPL), was developed, and a fed-batch approach was applied with phenol and the pyruvate produced with the ALR/DAAO system mentioned above. The concentration of phenol and pyruvate in the reactor should not exceed 7.5 g/L and 10 g/L, respectively. Significantly, the L-tyrosine concentration of 152.5 g/L was achieved within 10 h, demonstrating the great potential for high-efficiency production of L-tyrosine through the approach we established in this paper. Graphical abstract KEY POINTS: • A specific bioreactor system for pyruvate produced from l-alanine was developed • The appropriate condition for immobilization of FsDAAO was investigated • A fed-batch process was established to produce l-tyrosine with recombinant E. coli • The bi-enzymatic cascade was successfully used for l-tyrosine production at low cost.