Ambient temperature and the risk of childhood epilepsy hospitalizations: Potentially neglected risk of temperature extremes and modifying effects of air pollution.

PURPOSE: Extreme temperatures and air pollution are increasingly important risk factors for human health in the background of climate change, with limited evidence available for neurological disorders. This study intended to investigate the short-term effects of extreme temperatures on childhood epilepsy and explore the potential modifying effect of air pollution. METHODS: Daily childhood epilepsy hospitalization, meteorological and air pollution data were collected from 10 cities in Anhui Province of China during 2016-2018. We firstly employed a space-time-stratified case-crossover design and conditional logistic regression model to fit the short-term relationship between temperature and epilepsy. Then, we conducted stratified analyses by the level of air pollution and individual characteristics. RESULTS: Both extreme heat and extreme cold increased the risk of hospitalization for childhood epilepsy. The effect of extreme heat [97.5th vs. minimum hospitalization temperature (MHT)] on hospitalization was acute and emerged at lag0 [OR: 1.229 (95 %CI: 1.035 to 1.459)], while the effect of extreme cold (2.5th vs. MHT) was delayed and appeared at lag5 [OR: 1.098 (95 %CI: 1.043 to 1.156)]. We also found children aged 6-18 years were more susceptible to extreme cold than children aged 0-5 years. Besides, extreme heat and cold effects differed by the level of air pollutants. CONCLUSION: This study suggests that extreme temperatures might be the novel but currently neglected risk factor for childhood epilepsy, and air pollution could further amplify the adverse effect of temperature.

Medium-term exposure to size-fractioned particulate matter and asthma exacerbations in China: A longitudinal study of asthmatics with poor medication adherence.

BACKGROUND: Studies have shown that short- and long-term exposure to particulate matter (PM) can increase the risk of asthma morbidity and mortality. However, the effect of medium-term exposure remains unknown. We aim to examine the effect of medium-term exposure to size-fractioned PM on asthma exacerbations among asthmatics with poor medication adherence. METHODS: We conducted a longitudinal study in China based on the National Mobile Asthma Management System Project that specifically and routinely followed asthma exacerbations in asthmatics with poor medication adherence from April 2017 to May 2019. High-resolution satellite remote-sensing data were used to estimate each participant's medium-term exposure (on average 90 days) to size-fractioned PM (PM1, PM2.5, and PM10) based on the residential address and the date of the follow-up when asthma exacerbations (e.g., hospitalizations and emergency room visits) occurred or the end of the follow-up. The Cox proportional hazards model was employed to examine the hazard ratio of asthma exacerbations associated with each PM after controlling for sex, age, BMI, education level, geographic region, and temperature. RESULTS: Modelling results revealed nonlinear exposure-response associations of asthma exacerbations with medium-term exposure to PM1, PM2.5, and PM10. Specifically, for emergency room visits, we found an increased hazard ratio for PM1 above 22.8 µg/m3 (1.060, 95 % CI: 1.025-1.096, per 1 µg/m3 increase), PM2.5 above 38.2 µg/m3 (1.032, 95 % CI: 1.010-1.054), and PM10 above 78.6 µg/m3 (1.019, 95 % CI: 1.006-1.032). For hospitalizations, we also found an increased hazard ratio for PM1 above 20.3 µg/m3 (1.055, 95 % CI: 1.001-1.111) and PM2.5 above 39.2 µg/m3 (1.038, 95 % CI: 1.003-1.074). Furthermore, the effects of PM were greater for a longer exposure window (90-180 days) and among participants with a high BMI. CONCLUSION: This study suggests that medium-term exposure to PM is associated with an increased risk of asthma exacerbations in asthmatics with poor medication adherence, with a higher risk from smaller PM.

Volumetric analysis of effectiveness of embolization for preventing type II endoleaks following endovascular aortic aneurysm repair.

OBJECTIVE: The presence of endoleak was associated with the failure of endovascular aortic aneurysm repair (EVAR) treatment. The key to eliminating type II endoleak has shifted from reintervention to prevention. This study aimed to evaluate the effectiveness and safety of applying fibrin sealant to prevent type II endoleak in conjunction with EVAR. METHODS: All patients with abdominal aortic aneurysm who underwent EVAR from June 2019 to July 2021 were reviewed. Patients were grouped as Group A: standard EVAR with preemptive embolization and Group B: standard EVAR alone. The primary endpoint was the incidence of type II endoleak. The secondary endpoints were aneurysm sac regression, the inferior mesenteric artery patency, the numbers of patent lumbar arteries, and all-cause mortality. RESULTS: A total of 104 patients were included in Group A, and 116 were included in Group B. Technical success rate was 100%. The overall incidence of type II endoleak in Group A was significantly lower than that in Group B (4.8% vs 19.0%). The mean time of freedom from type II endoleak was 22.71 months for Group A (95% confidence interval, 21.59-23.83 months) and 19.89 months for Group B (95% confidence interval, 18.08-21.70 months). The Kaplan-Meier estimate of freedom from type II endoleak showed a significantly longer duration of freedom from type II endoleak in Group A (81.0% vs 95.2%). Group A showed a continuous sac regression tendency. In Group B, the sac volume decreased within 12 months but increased by 3.07 cm3 at 24 months. No complications were noted in both groups. CONCLUSIONS: Nonselective preemptive embolization with porcine fibrin sealant during EVAR was safe and effective in preventing type II endoleak in the short and mid-term. Preemptive embolization can lead to a significantly higher sac regression rate. Larger patient populations and longer follow-ups with randomized control designed trials are expected to verify the long-term effectiveness and safety of preemptive embolization in preventing type II endoleak.

[Clinical report and genetic analysis of a child with Aicardi-Goutières syndrome type 3 due to compound heterozygous variants of RNASEH2C gene].

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Aicardi-Goutières syndrome 3 (AGS3). METHODS: Trio whole exome sequencing was carried out for the child and his parents, and candidate variants were verified by Sanger sequencing. To further clarify their pathogenicity, the crystal structure of the variants was simulated and analyzed, and the plasmid of variants was expressed in vitro. A literature search was also carried out to summarize the phenotypic and genetic characteristics of AGS3. RESULTS: The child was found to harbor novel compound heterozygous variants of the RNASEH2C gene, namely c.434G>T (p.Arg145Leu) and c.494G>C (p.Ter165Ser), which were inherited from his mother and father, respectively. Analysis of protein crystal structure suggested that the c.434G>T (p.Arg145Leu) variant may affect the stability of local structure, and in vitro experiments showed that this variant can lead to protein degradation. The c.494G>C (p.Ter165Ser) variant has destroyed the stop codon, resulting in prolonged variant. CONCLUSION: The novel compound heterozygous variants of the RNASEH2C gene probably underlay the AGS3 in this child, which has enriched the phenotypic and mutational spectrum of this disorder.

Effects of long-term exposure to PM2.5 and chemical constituents on blood lipids in an essential hypertensive population: A multi-city study in China.

Previous studies on the effects of fine particulate matter (PM2.5) and chemical constituents on lipid disorder among hypertension populations, particularly in China, are very limited. We aimed to examine the effects of long-term exposure to PM2.5 and chemical constituents on dyslipidemias in China. Finally, we included 34,841 participants with essential hypertension from 19 regions in China during 2010-2011. Data were modeled using the generalized additive mixed model. We found that PM2.5 and chemical constituents exposure were positively associated with the increased risk of dyslipidemias and increased levels of total cholesterol (TC) and triglyceride (TG). The odds ratio for hypercholesterolemia was 1.356 [95% confidence interval (CI): 1.246, 1.477] for PM2.5, and the strongest association with PM2.5 constituents was found for nitrate. Each 10 µg/m3 increase in PM2.5 showed a significant increase of TC by 2.60% (95% CI: 2.03, 3.17) and TG by 2.91% (95% CI: 1.60, 4.24), respectively. Meanwhile, an interquartile range increase in nitrate, ammonium and organic matter had stronger associations with TC and TG parameters than black carbon, sulfate, and mineral dust. Our findings may contribute to a better understanding of the chronic effects of PM2.5 and chemical constituents on lipid disorder in an essential hypertensive population.

Conservation and Divergence of the Trihelix Genes in Brassica and Expression Profiles of BnaTH Genes in Brassica napus under Abiotic Stresses.

Trihelix (TH) proteins are a family of plant-specific transcription factors that play a role in light response and are extensively involved in plant growth and development, as well as in various stress responses. However, the function of TH genes in Brassica napus (B. napus) remains unclear, as does the evolution and differentiation pattern of TH genes in Brassica plants. Here, we identified a total of 455 TH genes in seven species, including six Brassica species and Arabidopsis, which were grouped into five clades, GT-1, GT-2, GTγ, SH4, and SIP1, each with 69, 142, 44, 55, and 145 members, respectively. The types and distributions of motifs of the TH proteins and the structures of the TH genes are conserved in the same subgroup, and some variations in certain amino acid residues occur in B. napus when inheriting motifs from Brassica rapa (B. rapa) and Brassica oleracea (B. oleracea). Collinearity analysis revealed that the massive expansion of TH genes in tetraploid species was attributed to the hetero-tetraploidization of diploid ancestors and gene duplication events within the tetraploid species. Comparative analysis of the membership numbers of five subgroups in different species revealed that the GT-2 and SIP1 genes underwent significant expansion during evolution, possibly to support the better adaptation of plants to their environments. The differential expression of the BnaTH genes under five stresses indicates that the BnaTH genes are involved in plant responses to stresses such as drought, cold, and heat. The presence of different stress-responsive cis-elements in the upstream promoter region of the genes indicated that BnaTH genes have the potential to cope with variable environments. Meanwhile, qRT-PCR analyses also confirmed that five TH genes respond to different abiotic stresses. Our results provide information and candidates for further studies on the role of TH genes in stress resistance of B. napus.

Clinicopathological and prognostic significance of PD-L1 expression in colorectal cancer: a meta-analysis.

PURPOSE: To systematically evaluate the correlation between PD-L1 expression and clinicopathological features and prognosis of colorectal cancer (CRC). METHODS: Seven databases (PubMed, Cochrane Library, EMBASE, Web of Science, CBM, Wanfang, and CNKI) were searched through May 2020. Risk of bias and quality of evidence were assessed by using the Newcastle-Ottawa scale (NOS), and meta-analysis was carried out by using the Review Manager 5.3 software on the studies with the quality evaluation scores ≥ 6. Meta-regression analysis was used to determine the independent role of PD-L1 expression on CRC prognosis after adjusting clinicopathological features and treatment methods. RESULTS: A total of 8823 CRC patients in 32 eligible studies. PD-L1 expression was correlated with lymphatic metastasis (yes/no; OR = 1.24, 95% CI (1.11, 1.38)), diameter of tumor (≥ 5 cm/< 5 cm; OR = 1.34, 95% CI (1.06, 1.70)), differentiation (high-middle/low; OR = 0.68, 95% CI (0.53, 0.87)), and vascular invasion (yes/no; OR = 0.80, 95% CI (0.69, 0.92)). PD-L1 expression shortened the overall survival (hazard ratio (HR) = 1.93, 95% CI (1.66, 2.25)), disease-free survival (HR = 1.76, 95% CI (1.50, 2.07)), and progression-free survival (HR = 1.93, 95% CI (1.55, 2.41)). Meta-regression showed that PD-L1 expression played a significant role on poor CRC OS (HR = 1.95, 95% CI (1.92, 3.98)) and disease-free survival (HR = 2.14, 95% CI (0.73, 4.52)). CONCLUSION: PD-L1 expression independently predicted a poor prognosis of CRC.

Microbubble contrast agent SonoVue combined with oxytocin improves the efficiency of high-intensity focused ultrasound ablation for adenomyosis.

BACKGROUND: To investigate the combined enhancing effects of microbubble-contrast SonoVue and oxytocin on high-intensity focused ultrasound (HIFU) ablation of adenomyosis. METHODS: 330 patients with adenomyosis were randomly assigned to SonoVue and oxytocin group (group A, n = 82), oxytocin (group B, n = 85), SonoVue (group C, n = 81), or the control (group D, n = 82) for HIFU ablation. In group A, oxytocin was dripped 0.32 IU/min, and HIFU ablation was started one minute after SonoVue injection. In group B, oxytocin was dripped 0.32 IU/min during ablation. In group C, HIFU ablation was started one minute after SonoVue injection. In group D, neither oxytocin nor SonoVue was applied. The clinical data, treatment results, and complications were analyzed. RESULTS: All participants underwent HIFU treatment safely, and the mean energy efficiency factor (EEF) in the four groups was 4.7 ± 0.9J/mm3, 8.5 ± 0.6J/mm3, 8.9 ± 0.7J/mm3, and 12.6 ± 1.8J/mm3, respectively, with the mean ablation time (AT) of 633.7 ± 55.1 s, 874.2 ± 65.6 s, 936.3 ± 85.2 s, and 1103.2 ± 96.2 s, respectively. The non-perfused volume ratios (NPVR) were 90.4 ± 8.8%, 88.7 ± 9.1%, 89.4 ± 7.2%, 80.5 ± 7.9%, respectively. In addition, EEF and AT were the shortest in group A (p < 0.05). NPVR was significantly higher in group A than in the control group D (p < 0.05). The incidence rates of adverse events were not significantly different in the four groups (p > 0.05). CONCLUSIONS: Compared to the control group, oxytocin combined with SonoVue in HIFU for adenomyosis can significantly decrease the energy and time needed for the ablation and safely enhance the treatment efficiency by improving the cavitation and heating of HIFU ablation and increasing the non-perfused volume ratio.

The influence of hepatitis B virus infection in pregnant women.

We carried out the investigation to evaluate hepatitis B virus (HBV) infection status and the influence of HBV infection in pregnant women in Tianjin of China. We founded that the prevalence of HBsAg was 3.77% (69/1829). 88.57% (1620/1829) pregnant women conducted HBsAg screening in last pregnancy. Spontaneous abortion and premature delivery did not show significant differences between HBV infected and uninfected pregnant women. But ALT and AST levels were significantly higher in infected women. And 56.65% of participants (997/1760) were anti-HBs positive. In conclusion, HBsAg prevalence was moderate in pregnant women in this region, which was consistent with the total population in western Pacific regions. And HBV infection did not influence spontaneous abortion and premature delivery. But the HBsAg screening was conducted mostly in the last pregnancy. Early screening and intervention were suggested in pregnant women within countries of moderately endemic regions.

Genome-wide association study (GWAS) reveals genetic loci of lead (Pb) tolerance during seedling establishment in rapeseed (Brassica napus L.).

BACKGROUND: Lead (Pb) pollution in soil has become one of the major environmental threats to plant growth and human health. Safe utilization of Pb contaminated soil by phytoremediation require Pb-tolerant rapeseed (Brassica napus L.) accessions. However, breeding of new B. napus cultivars tolerance to Pb stress has been restricted by limited knowledge on molecular mechanisms involved in Pb tolerance. This work was carried out to identify genetic loci related to Pb tolerance during seedling establishment in rapeseed. RESULTS: Pb tolerance, which was assessed by quantifying radicle length (RL) under 0 or 100 mg/L Pb stress condition, shown an extensive variation in 472 worldwide-collected rapeseed accessions. Based on the criterion of relative RL > 80%, six Pb-tolerant genotypes were selected. Four quantitative trait loci (QTLs) associated with Pb tolerance were identified by Genome-wide association study. The expression level of nine promising candidate genes, including GSTUs, BCATs, UBP13, TBR and HIPP01, located in these four QTL regions, were significantly higher or induced by Pb in Pb-tolerant accessions in comparison to Pb-sensitive accessions. CONCLUSION: To our knowledge, this is the first study on Pb-tolerant germplasms and genomic loci in B. napus. The findings can provide valuable genetic resources for the breeding of Pb-tolerant B. napus cultivars and understanding of Pb tolerance mechanism in Brassica species.

Genome-wide analysis of the rice PPR gene family and their expression profiles under different stress treatments.

BACKGROUND: Pentatricopeptide-repeat proteins (PPRs) are characterized by tandem arrays of a degenerate 35-amino-acid (PPR motifs), which can bind RNA strands and participate in post-transcription. PPR proteins family is one of the largest families in land plants and play important roles in organelle RNA metabolism and plant development. However, the functions of PPR genes involved in biotic and abiotic stresses of rice (Oryza sativa L.) remain largely unknown. RESULTS: In the present study, a comprehensive genome-wide analysis of PPR genes was performed. A total of 491 PPR genes were found in the rice genome, of which 246 PPR genes belong to the P subfamily, and 245 genes belong to the PLS subfamily. Gene structure analysis showed that most PPR genes lack intron. Chromosomal location analysis indicated that PPR genes were widely distributed in all 12 rice chromosomes. Phylogenetic relationship analysis revealed the distinct difference between the P and PLS subfamilies. Many PPR proteins are predicted to target chloroplasts or mitochondria, and a PPR protein (LOC_Os10g34310) was verified to localize in mitochondria. Furthermore, three PPR genes (LOC_Os03g17634,LOC_Os07g40820,LOC_Os04g51350) were verified as corresponding miRNA targets. The expression pattern analysis showed that many PPR genes could be induced under biotic and abiotic stresses. Finally, seven PPR genes were confirmed with their expression patterns under salinity or drought stress. CONCLUSIONS: We found 491 PPR genes in the rice genome, and our genes structure analysis and syntenic analysis indicated that PPR genes might be derived from amplification by retro-transposition. The expression pattern present here suggested that PPR proteins have crucial roles in response to different abiotic stresses in rice. Taken together, our study provides a comprehensive analysis of the PPR gene family and will facilitate further studies on their roles in rice growth and development.

Palliative pain relief and safety of percutaneous radiofrequency ablation combined with cement injection for bone metastasis.

PURPOSE: To investigate the pain relief effect and safety of percutaneous radiofrequency ablation (RFA) with a multitined electrode combined with cement injection in patients with painful metastatic bone tumors. MATERIALS AND METHODS: Sixteen patients with 34 osteolytic metastatic lesions were treated with RFA including 4 males and 12 females (age range 54-84). Thirteen patients with spinal metastases received additional cement injection. Medical imaging, a visual analog scale (VAS) and the EORTC QLQ-C30 were performed to evaluate the metastatic lesion, pain and quality of life, respectively, before and after RFA and at follow-ups. RESULTS: The RFA and/or vertebroplasty with cement injection were successful in all patients (100%). Except for one patient who had cement leakage, no intraprocedural complications occurred. After RFA, severe refractory pain was greatly relieved in all patients, with pretreatment VAS score of 8.1 ± 1.4 significantly reduced to 5.5 ± 1.1 at 24 h, 2.8 ± 0.6 at 1 week and 1.4 ± 0.8 at 6 months (P < 0.01). The EORTC QLQ-C30 scale at 1 month demonstrated significant improvement (P < 0.05) in the physical (P = 0.03) and emotion function (P = 0.003), global health status (P = 0.002), pain (P = 0.001) and insomnia (P = 0.002). The analgesics were reduced after the procedure and stopped 2 months later in all patients, with greatly improved quality of life and no apparent pain. Followed up for 6-12 months, all patients remained alive with no recurrence of pain. Palliative pain relief and safety of percutaneous radiofrequency ablation combined with cement injection for bone metastasis. CONCLUSION: RFA with or without bone cement is safe and effective in the palliative treatment of pain caused by metastatic bone tumors.

Effects of salt substitute on home blood pressure differs according to age and degree of blood pressure in hypertensive patients and their families.

BACKGROUND: It is known that home blood pressure (HBP) is a more reliable assessment of hypertension treatments than clinical blood pressure (BP). Despite this, HBP response to a salt substitute has only been evaluated by one study which, did not look at the salt substitute's effect on family members and did not analyze by age, gender, or BP degree. The aim of this current study was to assess the effects of a low-sodium and high-potassium salt substitute on HBP among hypertensive patients and their family members. METHODS: A total of 220 households (including 220 hypertensive patients and 380 their families) were randomly assigned to the regular salt or salt substitute groups. HBP was measured at the beginning, 3rd, 6th, and 12th months. Among the patients (n = 220), only home systolic blood pressure (HSBP) was significantly reduced, by an adjusted baseline BP of 4.2 mm Hg (95% CI: 1.3-7.0 mm Hg), in the salt substitute group compared with those in the regular salt group at each visit (all P < 0.05). There were no detectable differences between groups for home diastolic blood pressure (HDBP) at any visit. Among the family members, HSBP and HDBP were not significantly different between the groups. Furthermore, Individuals ≥60 years old, hypertensive patients with stage-2 hypertension, family members with hypertension, and women experienced greater HSBP reduction. CONCLUSIONS: Older subjects, those with higher blood pressure, and women experienced greater home blood pressure reduction from the salt substitute compared to regular salt.

Small RNA and degradome profiling reveals miRNA regulation in the seed germination of ancient eudicot Nelumbo nucifera.

BACKGROUND: MicroRNAs (miRNAs) play important roles in plant growth and development. MiRNAs and their targets have been widely studied in model plants, but limited knowledge is available concerning this small RNA population and their targets in sacred lotus (Nelumbo nucifera Gaertn.). RESULTS: In this study, a total of 145 known miRNAs belonging to 47 families and 78 novel miRNAs were identified during seed germination using high-throughput small RNA sequencing. Furthermore, some miRNA families which have not yet been reported in monocot or eudicot species were detected in N. nucifera, indicating that these miRNAs was divergence from monocots and core eudicots during evolution. Using degradome sequencing, 2580 targets were detected for all the miRNAs. GO (Gene Ontology) and KEGG pathway analyses showed that many target genes enriched in "regulation of transcription" and involved in "carbohydrate", "amino acid and energy metabolism". Nine miRNAs and three corresponding targets of them were further validated by quantitative RT-PCR. CONCLUSIONS: The results present here suggested that many miRNAs were involved in the regulation of seed germination of sacred lotus, providing a foundation for future studies of sacred lotus seed longevity. Comparative analysis of miRNAs from different plants also provided insight into the evolutionary gains and losses of miRNAs in plants.

Comparative transcript profiling of alloplasmic male-sterile lines revealed altered gene expression related to pollen development in rice (Oryza sativa L.).

BACKGROUND: Cytoplasmic male sterility (CMS) is an ideal model for investigating the mitochondrial-nuclear interaction and down-regulated genes in CMS lines which might be the candidate genes for pollen development in rice. In this study, a set of rice alloplasmic sporophytic CMS lines was obtained by successive backcrossing of Meixiang B, with three different cytoplasmic types: D62A (D type), ZS97A (WA type) and XQZ-A (DA type). RESULTS: Using microarray, the anther transcript profiles of the three indica rice CMS lines revealed 622 differentially expressed genes (DEGs) in each of the three CMS lines compared with the maintainer line Meixiang B. GO and MapMan analysis indicated that these DEGs were mainly involved in lipid metabolism and cell wall organization. Compared with the gene expression of sporophytic and gametophytic CMS lines, 303 DEGs were identified and 56 of them were down-regulated in all the CMS lines of rice. These down-regulated DEGs in the CMS lines were found to be involved in tapetum or cell wall formation and their suppressed expression might be related to male sterility. Weighted gene co-expression network analysis (WGCNA) revealed that two modules were significantly associated with male sterility and many hub genes that were differentially expressed in the CMS lines. CONCLUSION: A large set of putative genes involved in anther development was identified in the present study. The results will give some information for the nuclear gene regulation by different cytoplasmic genotypes and provide a rich resource for further functional research on the pollen development in rice.

Comparison of the Target Values Established Using a Robust Statistical Method and Roche's Calibration Values.

BACKGROUND: In EQA schemes, results are usually assessed against a target value. METHODS: Outliers in each result were deleted using a robust statistical method. Mean was used as a target value if trimmed results were normally distributed; otherwise, median was used. Differences between target value and Roche's calibration value were calculated. Rates of acceptable performance evaluated by target value and Roche's calibration value were determined. RESULTS: Target values of P, GLU, urea, UA, TP, ALB, TC, TG, ALT, AST, ALP, AMY, LDH, GGT, FE, and HBDH were 1.70 mmol/L, 11.0 mmol/L, 16.8 mmol/L, 307 µmol/L, 54.0 g/L, 38.1 g/L, 4.19 mmol/L, 1.46 mmol/L, 97.7 U/L, 98.2 U/L, 206 U/L, 180 U/L, 242 U/L, 115 U/L, 35.6 µmol/L, and 255 U/L, respectively. Differences between target values and Roche's calibration values were -3.45 to 1.48%. Rates of acceptable performance evaluated by target values and Roche's calibration values were 96.5 - 100.0% and 93.0 - 100.0%, respectively. CONCLUSIONS: Target values established using a robust statistical method and Roche's calibration values were comparable.

Genome-wide analysis of DNA methylation in photoperiod- and thermo-sensitive male sterile rice Peiai 64S.

BACKGROUND: Epigenetic modifications play important roles in the regulation of plant development. DNA methylation is an important epigenetic modification that dynamically regulates gene expression during developmental processes. However, little studies have been reported about the methylation profiles of photoperiod- and thermo-sensitive genic male sterile (PTGMS) rice during the fertility transition. RESULTS: In this study, using methylated DNA immunoprecipitation sequencing (MeDIP-seq), the global DNA methylation patterns were compared in the rice PTGMS line PA64S under two different environments (different temperatures and day lengths). The profiling of the DNA methylation under two different phenotypes (sterility and fertility) revealed that hypermethylation was observed in PA64S (sterility), and 1258 differentially methylated regions (DMRs) were found between PA64S (sterility) and PA64S (fertility). Twenty differentially methylated genes of them were further validated through bisulfite sequencing, and four of these genes were analyzed by qRT-PCR. Especially, a differentially methylated gene (LOC_Os08g38210), which encoded transcription factor BIM2, is a component of brassinosteroid signaling in rice. The hypermethylated BIM2 gene may suppress some downstream genes in brassinosteroid signaling pathway, and thus affect the male fertility in PA64S. CONCLUSIONS: The results presented here indicated that hypermethylation was observed in PA64S (sterility). Gene Ontology (GO) analysis and KEGG analysis revealed that flavone and flavonol biosynthrsis, circadian rhythm, photosynthesis and oxidative phosphorylation pathways were involved in sterility-fertility transition of PA64S.

Effect of CYP2C9 Genetic Polymorphism in a Chinese Population on the Metabolism of Mestranol in vitro.

BACKGROUND: Mestranol is a widely used estrogen, which is converted into its active metabolite ethinyl estradiol by cytochrome P450 (CYP) 2C9. To comprehensively examine the enzymatic activity of reported CYP2C9 variants in Chinese individuals in response to mestranol, wild-type CYP2C9*1 and 35 allelic variants were highly expressed in Sf21 insect cell microsomes and used for the detection of their enzymatic values in vitro. These results showed that the majority of tested variants exhibited decreased clearance values compared to wild type, except for CYP2C9*40 and *36. METHOD: Insect microsomes expressing the 36 CYP2C9 variants were incubated with 0.25-8 µmol/l mestranol for 30 min at 37°C. Then, the production of the metabolite of mestranol, ethinyl estradiol, was analyzed using high-performance liquid chromatography. RESULTS: Most CYP-catalyzed reactions were sufficiently described by classical Michaelis-Menten kinetic parameters (e.g., Km and Vmax), while 9 variants exhibited atypical or non-Michaelis-Menten kinetic values, which were largely due to the self-inhibitory effect in response to mestranol. CONCLUSION: This is the first report of these rare alleles for mestranol metabolism, which provides fundamental data for further clinical studies on CYP2C9 alleles for mestranol metabolism.

Unraveling the gut microbiota's role in salt-sensitive hypertension: current evidences and future directions.

The gut microbiota plays a pivotal role in both maintaining human health and in the pathogenesis of diseases. Recent studies have brought to light the significant correlation between gut microbiota and hypertension, particularly focusing on its role in the development and advancement of SSH, a subtype characterized by elevated blood pressure in response to high salt consumption. The complexity of SSH's etiology is notable, with dysbiosis of the gut microbiome identified as a crucial contributing factor. The gut microbiota participates in the occurrence and development of SSH by affecting the host's immune system, metabolic function, and neuromodulation. Investigations have demonstrated that the gut microbes regulate the development of SSH by regulating the TH17 axis and the activity of immune cells. Moreover, microbial metabolites, such as short-chain fatty acids, are implicated in blood pressure regulation and affect the development of SSH. There is evidence to show that the composition of the gut microbiome can be altered through prebiotic interventions so as to prevent and treat SSH. This review aims to concisely sum up the role of gut microbiota in SSH and to discuss pertinent therapeutic strategies and clinical implications, thereby providing a valuable reference for further research and clinical practice in this area.

The effect of air pollutants on COPD-hospitalized patients in Lanzhou, China (2015-2019).

Background: Lanzhou is the largest heavy industrial city in northwest China and it is a typical geographical valley-like city. However, there are few studies on the relationship between air pollutants and COPD, and their respective sample sizes are small, resulting in inconsistent results. The aim of this study is to analyze the effects of air pollutants on COPD hospitalizations in Lanzhou, China. Methods: An ecological time series study with distributed lag non-linear model (DLNM) was used for analysis. Daily COPD hospitalization data in Lanzhou from 1 January 2015 to 31 December 2019 were collected from 25 hospitals, as well as air pollutant data and meteorological data. Results: A total of 18,275 COPD hospitalizations were enrolled. For 10 µg/m3 increase in PM2.5, PM10, SO2, NO2, and 1 mg/m3 increase in CO at lag 07 day, the RR95%CI of COPD hospitalizations were 1.048 (1.030, 1.067), 1.008 (1.004, 1.013), 1.091 (1.048, 1.135), 1.043 (1.018, 1.068), and 1.160 (1.084, 1.242), respectively. The exposure-response curves between air pollutants (except O3-8h) and COPD hospitalizations were approximately linear with no thresholds. Female, and the harmful effect of PM on aged <65 years, the effect of gaseous pollutant on those aged ≥65 years, were stronger, particularly in the cold season. Exposure to air pollutants (except O3-8h) might increase the risk of COPD hospitalizations. O3-8h has a weak and unstable effect on COPD. Conclusion: Exposure to air pollutants (except O3-8h) increases the risk of COPD hospitalizations. O3-8h has a weak and unstable effect on COPD hospital admissions. The harmful effect of gaseous pollutants (except O3-8h) on COPD-hospitalized patients was stronger than that of PM.