Arabidopsis TIC236 contributes to proplastid development and chloroplast biogenesis during embryogenesis.

Plastids are essential, semi-autonomous organelles in plants that carry out a multitude of functions during development. Plastids existing in different subtypes are derived from proplastids progenitors and interconvert in response to environmental and growth cues. Most efforts focus on the differentiation from proplastid to other forms. However, the studies of proplastid development are insufficient and whether proplastid biogenesis affects plant growth is yet to be determined. Arabidopsis TIC236, a translocon component at the inner membrane of the chloroplast envelope, is critical for importing chloroplast-targeted preproteins and chloroplast division. In this study, we uncovered the fundamental influence of proplastid biogenesis on embryo development by exploring the function of TIC236 during embryogenesis. Widespread and strong expression of TIC236 was observed in leaves and embryos. The null mutant tic236 had an embryo-lethal phenotype, with cell division in the mutant embryos delayed starting at the octant stage and arrested at the globular stage. Transmission electron microscopy revealed enlarged proplastids with an aberrant inner structure at the dermatogen and globular stages that ultimately did not differentiate into chloroplasts. Additionally, the fluorescence signal distribution patterns of tic236 embryos carrying the pDR5rev::3xVENUS-N7, pPIN1::PIN1-GFP, pWOX5::GFP, and pSCR::H2B-YFP reporter systems were altered. Together, we provide genetic evidence supporting proplastid biogenesis plays a vital role in embryo development and TIC236 is identified as an indispensable player, ensuring normal proplastid development.

The relationships between blood lead levels and nocturia prevalence in adults: A retrospective study.

PURPOSE: The purpose of this study was to examine the association between blood lead levels and the prevalence of nocturia in American adults. METHODS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2020, focusing on individuals aged 20 years or older (n = 11,919). Blood lead levels were categorized into two groups (<2 µg/dL and ≥2 µg/dL), and the presence of nocturia was assessed based on questionnaire responses. We used multivariable logistic regression models to explore the association between blood lead levels and nocturia while adjusting for various covariates, including sex, ratio of family income to poverty (RIP), lipid profile, age, body mass index (BMI), race, citizenship, sleep trouble, diabetes, and hypertension. To verify whether certain covariates influence blood lead levels and the risk of nocturia, we conducted subgroup analyses. RESULTS: Of the study participants, 31.70% reported experiencing nocturia. Individuals with higher blood lead levels (≥2 µg/dL) exhibited a higher likelihood of experiencing nocturia compared to those with lower levels (<2 µg/dL) in all three models (Model 1: OR 1.46, 95% CI 1.29-1.66, p < 0.0001; Model 2: OR 1.25, 95% CI 1.09-1.44, p = 0.002; Model 3: OR 1.22, 95%CI 1.06-1.41, p = 0.01). Subgroup analyses revealed that factors such as age, sex, sleep trouble, diabetes, hypertension, BMI, RIP, and race did not affect the association between blood lead levels and the risk of nocturia (P for interaction >0.05). CONCLUSIONS: This study reported the correlation between blood lead levels and nocturia. We found that compared to blood lead levels below 2 µg/dL, when lead levels reached or exceeded 2 µg/dL, the risk of nocturia occurrence increased by 22%. CLINICAL TRIAL REGISTRATION: This study is based on existing data from a public database and not from a specific clinical trial; hence, clinical registration information is not provided.

Association of diarrhea or constipation with urinary incontinence in adults: A cross-sectional analysis of the National Health and Nutrition Examination Survey.

AIMS: This study aimed to investigate the association between diarrhea or constipation and urinary incontinence (UI) in adults. METHODS: Data from the National Health and Nutrition Examination Survey for 2009-2010 was used to include 4686 adults aged 20 and over in the analysis. Stress urinary incontinence (SUI) and urgency urinary incontinence (UUI) were used as outcome variables, with diarrhea and constipation as exposure factors. We first compared the baseline characteristics of those with and without SUI, as well as those with and without UUI. The impact of diarrhea or constipation on SUI and UUI was assessed using multivariate logistic regression models. To ensure the stability of the results, subgroup and stratified analyses were conducted. RESULTS: The prevalence rates of UUI and SUI were 22.49% and 23.39%, respectively. Adjusted multivariate logistic regression analysis revealed that the risk of UUI was increased by either diarrhea (OR 1.66, 95% CI 1.36-2.04) or constipation (OR 1.42, 95% CI 1.11-1.83). The risk of SUI was also elevated by either diarrhea (OR 1.36, 95% CI 1.11-1.67) or constipation (OR 1.32, 95% CI 1.06-1.63). Subgroup analysis revealed no significant differences in the interaction tests between constipation or diarrhea and UI. CONCLUSIONS: This study found that both constipation and diarrhea increase the risk of UUI and SUI.

Associations between waist circumference and nocturia in adults: National health and nutrition examination survey 2005-2020.

BACKGROUND: The relationship between waist circumference and nocturia has not been previously studied. This study investigated the association between waist circumference and the occurrence of nocturia in adults. METHODS: We analyzed data from the National Health and Nutrition Examination Survey covering 2005-2020, encompassing 6287 adults aged ≥20. Nocturia was defined as the need to urinate two or more times during the night. First, we compared baseline characteristics between the nocturia and non-nocturia groups. Subsequently, we used multivariate logistic regression analysis to investigate the relationship between waist circumference and nocturia prevalence. We also employed restricted cubic spline analysis to study the potential nonlinear correlation between waist circumference and the prevalence of nocturia. Recognizing the baseline data's heterogeneity based on nocturia prevalence, we conducted subgroup analyses according to age, sex, body mass index (BMI), and ethnicity. RESULTS: Our findings indicated that females, individuals aged ≥50, citizens, Non-Hispanic Black, those with lower education levels (high school or less), higher BMIs, lower family income-to-poverty ratios, higher waist circumference, hypertension, and diabetes were more likely to experience nocturia. Compared with individuals in the lowest waist circumference quartile (Q1), those in the higher quartiles (Q4) exhibited an increased risk of nocturia in Model 1 (Q4, OR:2.00, 95% CI:1.64, 2.45, p < 0.0001). These results remained consistent after adjusting for covariates in models 2 and 3. A restricted cubic spline analysis suggested a linear association between waist circumference and nocturia (P for nonlinearity = 0.066). Subgroup analyses based on age, sex, BMI, and ethnicity revealed no significant differences in the interaction tests between waist circumference and nocturia (P for interaction = 0.437, 0.331, 0.121, and 0.889, respectively), indicating that these baseline characteristics did not influence the association. CONCLUSIONS: Our findings indicated an association between increased waist circumference and a higher prevalence of nocturia. Knowledge of this association reinforces the importance of lifestyle modifications in maintaining a healthy waist circumference and informs public health strategies to address other potential risk factors for nocturia.

Examining the safety of mirabegron: an analysis of real-world pharmacovigilance data from the US FDA adverse event reporting system (FAERS) database.

Background: Mirabegron, the first ß-3 adrenergic receptor agonist, received approval from the Food and Drug Administration (FDA) in 2012 for the treatment of overactive bladder (OAB). This pharmacovigilance study investigated the safety profile of mirabegron treatment using the US FDA Adverse Event Reporting System (FAERS) database. Methods: This study employed disproportionality analyses, including the reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) algorithm, to quantify signals of adverse events associated with mirabegron. Results: From the first quarter of 2012 to the third quarter of 2023, a comprehensive total of 14,356,234 adverse event (AE) reports were submitted to the FDA Adverse Event Reporting System database. Within this dataset, encompassing 18,763 reports specifically associated with mirabegron, healthcare professionals notably contributed 2,902 of these reports. A total of 80 preferred terms (PTs) of interest were identified using both the ROR and information component algorithms. The most common AEs included blood pressure increased, urinary retention, atrial fibrillation, dry mouth, and tachycardia, which were consistent with the product instructions. Unexpected significant AEs, such as arrhythmia, palpitations, dementia, transient ischemic attack, Parkinson's disease, anti-neutrophil cytoplasmic antibody positive vasculitis, lip swelling, and swollen tongue, were also identified. The study findings indicated that the majority of onset time occurred within 30 days (n = 358, 55.68%). However, AEs were still possible after 1 year of mirabegron treatment. Conclusion: This study provided valuable evidence for the real-world safety of mirabegron, helping clinical professionals enhance their understanding of mirabegron's safety in clinical practice. It also contributed valuable evidence for further safety studies on mirabegron.

Association between TV and/or video time and nocturia in adults: An analysis of the National Health and Nutrition Examination Survey.

AIMS: This study aimed to examine the correlation between television (TV) and/or video viewing time and the occurrence of nocturia in adults. METHODS: An analysis of data from the National Health and Nutrition Examination Survey for 2011-2016 was conducted, involving 13 294 adults aged 20 and older. The main outcome was specified as nocturia, which refers to the requirement of urinating two or more times during the night. Initially, baseline characteristics were contrasted between individuals with and without nocturia. The effects of TV and/or video viewing time on nocturia were further explored using multivariable logistic regression models. To acknowledge the variation in baseline data regarding the prevalence of nocturia, subgroup analyses were performed. RESULTS: Adjusted multivariate analysis revealed that individuals in the group with the longest TV and/or video viewing time had a significantly 48% higher risk of experiencing nocturia compared to those with the shortest TV and/or video viewing time. The results of subgroup analyses revealed no significant differences in the interaction tests between TV and/or video viewing time and nocturia. CONCLUSIONS: Our research showed that individuals who spent 5 or more hours a day watching TV and/or videos were significantly more likely to develop nocturia.

The efficacy and safety of an improved percutaneous peritoneal dialysis catheter placement technique in urgent-start peritoneal dialysis patients: a retrospective cohort study.

BACKGROUND: Urgent-start peritoneal dialysis has high catheterization skill requirements and that early complications. The optimal catheter placement method remains debatable in urgent-start peritoneal dialysis patients. Safe and effective peritoneal dialysis catheterization is needed in clinical work. METHODS: We retrospectively analyzed the data of 34 patients diagnosed with end-stage renal disease who opt for peritoneal dialysis, 19 males and 15 females, with an average age of 62.3±14.7 years, peritoneal dialysis catheter implantation was completed by the improved percutaneous catheterization technique. They were followed for 6 months, early and late complications were observed and the survival rate of the catheter technique was calculated. RESULTS: All 34 patients diagnosed with end-stage renal disease successfully underwent catheter placement using the improved percutaneous technique; the catheterization success rate was 100%. No severe organ injuries, such as intestinal perforation and bladder perforation, occurred intraoperatively. Peritoneal dialysis was started immediately after surgery. The early complications included one case of leakage, one case of omental wrapping, and six cases of rectus abdominis hemorrhage. The late complications included one case of pleuro-abdominal fistula and two cases of peritonitis. The 6-month technical survival rate for the catheter was 94.1% (32/34). Compared to previously reported studies, this technique may reduce leakage and early catheter dysfunction, and improve the technical survival of catheters. CONCLUSIONS: The improved percutaneous peritoneal dialysis catheter placement technique might be an effective and safe method for urgent­start peritoneal dialysis patients.

The safety and urate-lowering efficacy of febuxostat in patients undergoing peritoneal dialysis: a retrospective single-arm cohort study of 84 patients.

BACKGROUND: Studies have shown that hyperuricemia (HUA) is an independent risk factor for all-cause death and residual kidney function loss in peritoneal dialysis (PD) patients. The control of blood uric acid (UA) is an important link to improve the prognosis of end-stage renal disease (ESRD). As a therapeutic drug for HUA, febuxostat is rarely studied in PD patients. The purpose of our study is to investigate the safety, efficacy, and effect on residual renal function (RRF) of febuxostat in patients undergoing PD. METHODS: This is a retrospective single-arm cohort study. During the study period which from September 2016 to November 2020, 191 patients underwent PD at this hospital. Among these patients, 84 were administrated for over a period of 3 months and were eventually included. These 84 patients (51 males and 33 females; average age: 55.18 years) were undergoing PD complicated with HUA or gout who received febuxostat during a regular follow-up from January 2018 to November 2020. Serum UA (sUA) levels, blood routine, liver function, and RRF were compared before and after febuxostat administration. Adverse events (AEs) resulting from febuxostat treatment were collected from medical records. RESULTS: All 84 patients were administered febuxostat for over 3 months, including 39 for over 6 months and 26 for over 12 months. Some 60 patients were treated with febuxostat dose of 20 mg/day and the remaining 24 patients received 40 mg/day. Compared with pretreatment level, the mean sUA level was observed to be markedly reduced at 1 month after febuxostat administration (320.2±87.27 vs. 498.8±81.47 µmol/L, P<0.0001) and at 3 months (291.6±82.66 vs. 498.8±81.47 µmol/L, P<0.0001) and subsequently remained at a significantly low level for 12 months. Only 5 patients stopped febuxostat because of its associated AEs. An initial dose of 40 mg/day was associated with a higher rate of AEs compared with dose of 20 mg/day (25% vs. 18.33%, respectively). After febuxostat treatment, no significant differences were observed between RRF in the two groups. CONCLUSIONS: Febuxostat may be safe and efficient in patients undergoing PD and may not impair RRF. Febuxostat administration at dose of 20 mg/day may be an appropriate dose for patients undergoing PD.

Long-term efficacy, safety, and medication compliance of roxadustat on peritoneal dialysis patients with renal anemia affected by the COVID-19 pandemic: a retrospective study.

BACKGROUND: Current studies have limited data on long-term treatment safety and medication compliance of roxadustat for renal anemia in peritoneal dialysis (PD) patients. We aimed to analyze the long-term efficacy, safety, and medication compliance of roxadustat in the treatment of renal anemia in patients with PD who discontinued recombinant human erythropoietin (rhEPO) treatment due to the corona virus disease 2019 (COVID-19) outbreak. METHODS: We retrospectively collected patients who were switched from rhEPO to roxadustat in our hospital due to the pandemic. The criteria for subject inclusion: aged >18 years with a dialysis vintage >3 months, without malignant tumor, no severe cardiovascular and cerebrovascular diseases, and not combined hemodialysis. Patients were followed up until the end of December 2021. Hemoglobin (Hb), red blood cell (RBC) and hematocrit (Hct) were recorded at baseline, month 1-12 and month 20, and iron parameters at baseline, 3, 6, 9, 12, and 20 months were collected. The Morisky Medication Adherence Scale-8 (MMAS-8) was used to score medication compliance during rhEPO treatment and roxadustat treatment, and adverse reactions occurred during treatment were collected. The efficacy and medication compliance of roxadustat were analyzed using Wilcoxon rank sum test or t-test. RESULTS: The median follow-up time was 21.1 (20.6, 21.7) months. After 1 month of treatment, the Hb level was significantly increased by 9.4 g/L (95% CI: 6.0-12.8 g/L) compared with the baseline, follow up at 20 months showed the Hb level had remained stable, increased by 20.7 g/L (95% CI: 15.9-25.4 g/L) compared with before treatment. At the beginning of treatment, total iron binding capacity increased, transferrin saturation and serum ferritin decreased, serum iron remained stable during treatment. During roxadustat treatment, no patient discontinued treatment due to the pandemic, and the Morisky score was improved compared with that during rhEPO treatment [5.75 (4.25, 6.00) vs. 6.75 (5.75, 7.00), P=0.000]. There were no serious adverse events associated with roxadustat were observed. CONCLUSIONS: Roxadustat can effectively improve anemia and had good tolerance in patients undergoing PD who have difficult using rhEPO, and the medication compliance was better than rhEPO during the COVID-19.

COPII genes SEC31A/B are essential for gametogenesis and interchangeable in pollen development in Arabidopsis.

In eukaryotes, coat protein complex II (COPII) vesicles mediate anterograde traffic from the endoplasmic reticulum to the Golgi apparatus. Compared to yeasts, plants have multiple COPII coat proteins; however, the functional diversity among them is less well understood. SEC31A and SEC31B are outer coat proteins found in COPII vesicles in Arabidopsis. In this study, we explored the function of SEC31A and compared it with that of SEC31B from various perspectives. SEC31A was widely expressed, but at a significantly lower level than SEC31B. SEC31A-mCherry and SEC31B-GFP exhibited a high co-localization rate in pollen, but a lower rate in growing pollen tubes. The sec31a single mutant exhibited normal growth. SEC31A expression driven by the SEC31B promoter rescued the pollen abortion and infertility observed in sec31b. A sec31asec31b double mutant was unavailable due to lethality of the sec31asec31b gametophyte. Transmission electron microscopy revealed that one quarter of male gametogenesis was arrested at the uninuclear microspore stage, while confocal laser scanning microscopy showed that 1/4 female gametophyte development was suspended at the functional megaspore stage in sec31a-1/+sec31b-3/+ plants. Our study highlights the essential role of SEC31A/B in gametogenesis and their interchangeable functions in pollen development.

The Cost-Effective Preparation of Green Fluorescent Carbon Dots for Bioimaging and Enhanced Intracellular Drug Delivery.

Doxorubicin entrapped carbon dots (DOX-CDs) were prepared for bioimaging and enhanced intracellular drug delivery. The CDs were synthesized via the hydrothermal method using citrate and urea under 200 °C for 1 h. Then, DOX was successfully conjugated on the CDs via physicochemical interactions. The DOX-CDs exhibited good crystal structure, remarkable aqueous stability, excellent photoluminescence property, and a high quantum yield of 93%. The fluorescent images revealed that the DOX-CDs could be readily taken up by the cancer cells for cell labeling. Furthermore, endo-lysosomal pH-assisted DOX release behavior was observed from DOX-CDs, and the cytotoxicity of DOX-CDs was confirmed by the MTS assay against H0-8910 ovarian cancer cells. In addition, the CDs indicated bright fluorescent signal in the animal imaging test and demonstrated low toxicity after administration for 7 and 21 days. Therefore, the prepared CDs could be a promising imaging probe for biomedical imaging and intracellular drug delivery.

Multifunctional iron oxide-carbon hybrid nanoparticles for targeted fluorescent/MR dual-modal imaging and detection of breast cancer cells.

An efficient method for the highly sensitive and specific detection of cancer cells is crucial for the early diagnosis of cancer. In this work, we propose a one-pot approach to fabricating magnetic-fluorescent iron oxide-carbon hybrid nanomaterials (MCNP) with excellent stable, high quantum yield and excellent magnetic properties for breast cancer cells recognition and detection via magnetic resonance and multicolour fluorescence imaging. MCNPs were efficiently synthesised via one-pot, multi-component reactions of FeCl3, FeCl2•4H2O, citric acid and ethylenediamine in diethylene glycol. The MCNPs showed strong excitation wavelength-dependent fluorescence in the blue-red region with a high quantum yield of 58.4%, and they presented higher stability and T2 relaxivity than pure iron oxide nanoparticles. After conjugating with CD44 monoclonal antibodies, the fabricated targeting nanoprobe, MCNPs-CD44, demonstrated a specific fluorescence/MRI dual imaging contrast effect in 4T1 breast cancer cells. Biological transmission electron microscope imaging showed a significant preferential uptake of the nanoparticle conjugates by the 4T1 cells. By taking advantage of the high binding affinity and specificity of the CD44 antibodies to the overexpressed CD44 on the cancer cell surface, the developed MCNPs-CD44 probe distinguished 4T1 breast cancer cells from normal cells and detected as low as a few hundred cancer cells, thus indicating the potential application of multifunctional nanocomposites in the MR diagnosis and fluorescence positioning of breast cancer at cellular-level resolution.

Synergistic Effects of Gold Nanocages in Hyperthermia and Radiotherapy Treatment.

Gold nanocages (GNCs) are a promising material that not only converts near infrared (NIR) light to heat for the ablation of tumors but also acts as a radiosensitizer. The combination of hyperthermia and radiotherapy has a synergistic effect that can lead to significant tumor cell necrosis. In the current study, we synthesized GNCs that offered the combined effects of hyperthermia and radiotherapy. This combination strategy resulted in increased tumor cell apoptosis and significant tumor tissue necrosis. We propose that GNCs can be used for clinical treatment and to potentially overcome resistance to radiotherapy by clearly increasing the antitumor effect.