HPA1-29w Genotyping and the Foundation for the Platelet Apheresis Registry in Jiangsu Province of China by MassARRAY Spectrometry.

Introduction: This study aimed to investigate the allele frequencies of the human platelet antigens (HPA) HPA-1-29w system in Jiangsu (China) and establish the platelet apheresis registry in blood donors. Methods: HPA genotyping was performed using the MassARRAY iPLEX® platform. Allele and genotype frequencies were estimated by direct counting and tested for Hardy-Weinberg equilibrium. The transfusion mismatch probability was calculated for every HPA specificity. Results: The HPA allele frequencies in the Jiangsu Han population of HPA-1b, -2b, -3b, -4b, -5b, -6b, -11b, -15b, and -21b were 0.0055, 0.0530, 0.4116, 0.0015, 0.0155, 0.0162, 0.0003, 0.4683, and 0.0070, respectively, in which a heterozygote of HPA-11a/b was first detected in China. Only allele a was detected for HPA-7-10w,-12-14w,-16-20w, and -22-29w quasi-systems. The highest mismatch rate of HPA genes in 1,640 platelet donors was the HPA-15 system, followed by the HPA-3 system with a rate of 37.4% and 36.71%, respectively. Conclusion: China's largest-scale platelet registry of HPA-1-29w has been explored. The MassARRAY platform may help found the platelet apheresis registry which would be useful to provide matching platelets and lead to a more accurate, effective, and safe transfusion for patients with platelet therapy.

Lung cancer survival by immigrant status: a population-based retrospective cohort study in Ontario, Canada.

BACKGROUND: Lung cancer is one of the most common cancers and causes of cancer death in Canada. Some previous literature suggests that socioeconomic inequalities in lung cancer screening, treatment and survival may exist. The objective of this study was to compare overall survival for immigrants versus long-term residents of Ontario, Canada among patients diagnosed with lung cancer. METHODS: This population-based retrospective cohort study utilized linked health administrative databases and identified all individuals (immigrants and long-term residents) aged 40 + years diagnosed with incident lung cancer between April 1, 2012 and March 31, 2017. The primary outcome was 5-year overall survival with December 31, 2019 as the end of the follow-up period. We implemented adjusted Cox proportional hazards models stratified by age at diagnosis, sex, and cancer stage at diagnosis to examine survival. RESULTS: Thirty-eight thousand seven hundred eighty-eight individuals diagnosed with lung cancer were included in our cohort including 7% who were immigrants. Immigrants were younger at diagnosis and were more likely to reside in the lowest neighbourhood income quintile (30.6% versus 24.5%) than long-term residents. After adjusting for age at diagnosis, neighbourhood income quintile, comorbidities, visits to primary care in the 6 to 30 months before diagnosis, continuity of care, cancer type and cancer stage at diagnosis, immigrant status was associated with a lower hazard of dying 5-years post-diagnosis for both females (0.7; 95% CI 0.6-0.8) and males (0.7; 95% CI 0.6-0.7) in comparison to long-term residents. This trend held in adjusted models stratified by cancer stage at diagnosis. For example, female immigrants diagnosed with early stage lung cancer had a hazard ratio of 0.5 (95% CI 0.4-0.7) in comparison to long-term residents. CONCLUSION: Overall survival post diagnosis with lung cancer was better among Ontario immigrants versus long-term residents. Additional research, potentially on the protective effects of immigrant enclave and the intersection of immigrant status with racial/ethnic identity, is needed to further explore why better overall survival for immigrants remained.

Eight-year total, cognitive-affective, and somatic depressive symptoms trajectories and risks of cardiac events.

In this study, we analyzed pooled data from two prospective population-based cohorts-the Health Retirement Study (HRS) and the English Longitudinal Study of Ageing (ELSA)-to explore the association between trajectories of depressive symptoms and the risk of cardiac events. Depressive symptoms were assessed using the 8-item CES-D scale and categorized into somatic and cognitive-affective subtypes. Trajectories were tracked for four surveys from baseline. Heart disease was identified based on self-reported physician-diagnosed conditions. Hazard ratios and 95% confidence intervals were calculated with Cox proportional risk models that adjusted for potential confounders. In total, 17,787 subjects (59.7% female, median age 63 years) were enrolled at baseline. During a 10-year follow-up, 2409 cases of heart disease were identified. Participants with fluctuating (HR = 1.13, 95% CI: 1.06-1.20), increasing (HR = 1.43, 95% CI: 1.25-1.64), and consistently high (HR = 1.64, 95% CI: 1.45-1.84) depressive symptom trajectories exhibited an increased risk of heart disease compared to those with consistently low depressive symptoms, while a decreasing (HR = 1.07, 95% CI: 0.96-1.19) depressive symptom trajectory did not significantly affect the risk of heart disease. Moreover, the association between heart disease and somatic depressive symptoms was found to be stronger than with cognitive-affective symptoms. These findings suggest a significant link between depressive symptom trajectories and heart disease, with particular emphasis on stronger associations with somatic symptoms. It is recommended that the identification and management of depressive symptoms be incorporated into heart disease prevention strategies.

Developmental responses of roots to limited phosphate availability: research progress and application in cereals.

Phosphorus (P), an essential macronutrient, is crucial for plant growth and development. However, available inorganic phosphate (Pi) is often scarce in soil, and its limited mobility exacerbates P deficiency in plants. Plants have developed complex mechanisms to adapt to Pi-limited soils. The root, the primary interface of the plant with soil, plays an essential role in plant adaptation to Pi-limited soil environments. Root system architecture significantly influences Pi acquisition via the dynamic modulation of primary root and/or crown root length, lateral root proliferation and length, root hair development, and root growth angle in response to Pi availability. This review focuses on the physiological, anatomical, and molecular mechanisms underpinning changes in root development in response to Pi starvation in cereals, mainly focusing on the model monocot plant rice (Oryza sativa). We also review recent efforts to modify root architecture to enhance P uptake efficiency in crops and propose future research directions aimed at the genetic improvement of Pi uptake and use efficiency in crops based on root system architecture.

Serum folate levels and risk of metabolic dysfunction-associated steatotic liver disease: results from a cross-sectional study and Mendelian randomization analysis.

Background: Evidence from observational studies on the association between folate and metabolic dysfunction-associated steatotic liver disease (MASLD) is conflicting. Aims: This study aimed to investigate the association between serum folate concentration and MASLD and further assess the causal relationship using Mendelian randomization (MR) analysis. Methods: To investigate the causal relationship between serum folate and MASLD, we conducted a cross-sectional study that selected 1,117 participants from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). The association between serum folate level and the risk of MASLD was evaluated under a multivariate logistic regression model. In addition, we conducted a two-sample MR study using genetic data from a large genome-wide association study (GWAS) to compare serum folate level (37,465 individuals) and MASLD (primary analysis: 8,434 cases/770,180 controls; Secondary analysis:1,483 cases/17,781 controls) were performed to infer causal relationships between them. Inverse variance weighted (IVW) was used as the primary method of MR Analysis. Results: The results from the NHANES database showed that Tertile 3 group (Tertile 3: ≥ 48.6 nmol/L) had a significantly lower risk (OR = 0.58, 95% CI: 0.38-0.88, p = 0.010) of MASLD than Tertile 1 group (Tertile 1: < 22.3 nmol/L) after complete adjustments. However, in the IVW of MR analysis, there was no causal relationship between serum folate level and MASLD risk in the primary analysis (OR = 0.75, 95% CI: 0.55-1.02, p = 0.065) and secondary analysis (OR = 0.83, 95% CI: 0.39-1.74, p = 0.618). Conclusion: In observational analyses, we observed an inverse association between higher serum folate concentrations and a reduced risk of MASLD. Our MR study generated similar results, but the association failed to reach the significance threshold of p < 0.05, suggesting that our MR study does not support a causal relationship between serum folate levels and MASLD risk. Additional research involving a larger number of cases would contribute to enhancing the confirmation of our preliminary findings.

Predictors of pathological complete response to neoadjuvant treatment in invasive breast cancer with different human epidermal growth factor receptor 2 (HER2) subcategories.

Background: Among human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients who receive anti-HER2 treatment, a noteworthy correlation between pathological complete response (pCR) and longer survival has been observed. The rate of pCR varies with the tumor's degree of HER2 protein expression. The aim of this study was to assess the correlations between clinicopathological characteristics, magnetic resonance imaging (MRI) parameters, and pCR in breast cancer with different HER2 subcategories. Methods: A total of 281 invasive breast cancer patients diagnosed with HER2-positivity were included. HER2-positive translated to immunohistochemistry (IHC) 3+ or IHC 2+/fluorescence in situ hybridization (FISH)(+). All enrolled patients underwent baseline MRI examination and received neoadjuvant chemotherapy, dual anti-HER2 therapy, and subsequent therapeutic surgery from January 2021 to May 2022. A logistic regression model was used to evaluate the effects of covariates on pCR. Results: Compared to the IHC 2+/FISH(+) group, patients with IHC 3+ tumors had a higher pCR rate (58.1% vs. 26.7%, P<0.001), clinical stage (58.6% vs. 40%, P=0.038), apparent diffusion coefficient (ADC) value (0.96 vs. 0.88 mm2/s, P=0.004), and were more likely to be estrogen receptor (ER) negative (55.9% vs. 31.1%, P=0.002) and progesterone receptor (PR) negative (72.5% vs. 46.7%, P=0.001). In both groups, univariate analysis showed that the pCR group more often had ER-negative and PR-negative status than the non-pCR group (P<0.001). The final multivariable analysis showed that ER-negativity was associated with pCR in the IHC 2+/FISH(+) group (P=0.004). ER-negativity and the longest diameter were two independent predictors of pCR in the IHC 3+ group (P<0.001 for ER, P=0.026 for longest diameter). Conclusions: The IHC 3+ group had a higher pCR rate than the IHC 2+/FISH(+) group. Along with clinicopathological characteristics, MRI parameters were supplemental predictors of pCR, particularly in IHC 3+ patients.

Optimization of Minocycline-Containing Bismuth Quadruple Therapy for Helicobacter pylori Rescue Treatment: A Real-World Evidence Study.

BACKGROUND: The optimal dosage of minocycline remains unclear for Helicobacter pylori (H. pylori) eradication. We aimed to evaluate the efficacy and safety of four different regimens with minocycline and metronidazole compared to classical bismuth quadruple therapy for H. pylori rescue treatment. MATERIALS AND METHODS: From March 2021 to March 2024, refractory H. pylori-infected patients with at least two previous treatment failures who received 14-day therapy with b.i.d. proton pump inhibitor 20 mg and bismuth 220 mg, plus tetracycline 400 mg q.i.d and metronidazole 400 mg q.i.d (BQT), or minocycline 50 mg q.i.d and metronidazole 400 mg q.i.d (PBMn4M4), or minocycline 50 mg t.i.d and metronidazole 400 mg t.i.d (PBMn3M3), or minocycline 50 mg b.i.d and metronidazole 400 mg q.i.d (PBMn2M4), or minocycline 50 mg b.i.d and metronidazole 400 mg t.i.d (PBMn2M3) were included in this retrospective study. H. pylori eradication was assessed by 13C-urea breath test at least 6 weeks after treatment. All adverse effects during treatment were recorded. RESULTS: Totally, 823 patients were enrolled: 251 with BQT, 97 with PBMn4M4, 191 with PBMn3M3, 108 with PBMn2M4, and 176 with PBMn2M3. The eradication rates of BQT, PBMn4M4, PBMn3M3, PBMn2M4, and PBMn2M3 were 89.2%, 87.6%, 91.6%, 88.0%, and 91.5%, respectively, by intention-to-treat analysis; 96.1%, 97.7%, 97.8%, 96.9%, and 97.6%, respectively, by modified intention-to-treat analysis; 97.1%, 97.5%, 97.7%, 96.8%, and 97.6%, respectively, by per-protocol analysis. Metronidazole resistance did not affect the efficacy of all groups. PBMn2M3 group achieved the greatest compliance and the fewest moderate and severe adverse events. CONCLUSIONS: The novel bismuth-containing quadruple therapy with a low dose of minocycline and metronidazole is an alternative to classical bismuth quadruple therapy for H. pylori rescue treatment with superior safety and compliance. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06332599.

Surgical resection and neoadjuvant therapy in patients with gastric cancer and ovarian metastasis: A real-world study.

BACKGROUND: Regarding when to treat gastric cancer and ovarian metastasis (GCOM) and whether to have metastatic resection surgery, there is presently debate on a global scale. The purpose of this research is to examine, in real-world patients with GCOM, the survival rates and efficacy of metastatic vs non-metastasized resection. AIM: To investigate the survival time and efficacy of metastatic surgery and neoadjuvant therapy in patients with GCOM. METHODS: This study retrospectively analyzed the data of 41 GCOM patients admitted to Zhejiang Provincial People's Hospital from June 2009 to July 2023. The diagnosis of all patients was confirmed by pathology. The primary study endpoints included overall survival (OS), ovarian survival, OS after surgery (OSAS), disease-free survival (DFS), differences in efficacy. RESULTS: This study had 41 patients in total. The surgical group (n = 27) exhibited significantly longer median OS (mOS) and median overall months (mOM) compared to the nonoperative group (n = 14) (mOS: 23.0 vs 6.9 months, P = 0.015; mOM: 18.3 vs 3.8 months, P = 0.001). However, there were no significant differences observed in mOS, mOM, median OSAS (mOSAS), and median DFS (mDFS) between patients in the surgical resection plus neoadjuvant therapy group (n = 11) and those who surgical resection without neoadjuvant therapy group (n = 16) (mOS: 26.1 months vs 21.8 months, P = 0.189; mOM: 19.8 vs 15.2 months, P = 0.424; mOSAS: 13.9 vs 8.7 months, P = 0.661, mDFS: 5.1 vs 8.2 months, P = 0.589). CONCLUSION: Compared to the non-surgical group, the surgical group's survival duration and efficacy are noticeably longer. The efficacy and survival time of the direct surgery group and the neoadjuvant therapy group did not differ significantly.

AI-based strategies in breast mass ≤ 2 cm classification with mammography and tomosynthesis.

PURPOSE: To evaluate the diagnosis performance of digital mammography (DM) and digital breast tomosynthesis (DBT), DM combined DBT with AI-based strategies for breast mass ≤ 2 cm. MATERIALS AND METHODS: DM and DBT images in 483 patients including 512 breast masses were acquired from November 2018 to November 2019. Malignant and benign tumours were determined by biopsies using histological analysis and follow-up within 24 months. The radiomics and deep learning methods were employed to extract the breast mass features in images and finally for benign and malignant classification. The DM, DBT and DM combined DBT (DM + DBT) images were fed into radiomics and deep learning models to construct corresponding models, respectively. The area under the receiver operating characteristic curve (AUC) was employed to estimate model performance. An external dataset of 146 patients from March 2021 to December 2022 from another center was enrolled for external validation. RESULTS: In the internal testing dataset, compared with the DM model and the DBT model, the DM + DBT models based on radiomics and deep learning both showed statistically significant higher AUCs [0.810 (RA-DM), 0.823 (RA-DBT) and 0.869 (RA-DM + DBT), P ≤ 0.001; 0.867 (DL-DM), 0.871 (DL-DBT) and 0.908 (DL-DM + DBT), P = 0.001]. The deep learning models present superior to the radiomics models in the experiments with only DM (0.867 vs 0.810, P = 0.001), only DBT (0.871 vs 0.823, P = 0.001) and DM + DBT (0.908 vs 0.869, P = 0.003). CONCLUSIONS: DBT has a clear additional value for diagnosing breast mass less than 2 cm compared with only DM. AI-based methods, especially deep learning, can help achieve excellent performance.

Gambogic acid impairs the maintenance and therapeutic resistance of glioma stem cells by targeting B-cell-specific Moloney leukemia virus insert site 1.

BACKGROUND: Glioblastoma (GBM) is the most common and lethal primary brain tumor with low effectiveness of available treatments. The tumor heterogeneity and therapeutic resistance are largely due to the presence of glioma stem cells (GSCs). Therefore, eliminating GSCs can overcome the progression, relapse, and resistance of GBM. Previous studies have shown that gambogic acid (GA), a natural active ingredient, has anti-glioma properties. Nonetheless, it is still unclear whether it has an inhibitory effect on GSCs and what its target might be. This study aimed to investigate the anti-tumor effects of GA on GSCs. In addition, this study found the target of GA in GSCs and elucidated the potential specific mechanisms by conducting both in vitro and in vivo experiments. B-cell-specific Moloney leukemia virus insert site 1 (BMI1) is a key stem cell factor of the polycomb group (PcG) family with important effects on the development, recurrence, and chemoresistance of several cancers. In both normal and cancer stem cells, BMI1 maintains stem cell self-renewal by regulating the cell cycle, cellular immortalization, and senescence. Its high expression in a variety of cancers correlates with poor clinical prognosis and chemoresistance. These mechanisms of BMI1 make it a potential therapeutic target for cancer therapy, and future studies may further reveal the specific roles of BMI1 mechanism and provide a basis for the development of new cancer therapeutic strategies. PURPOSE: This study investigated the in vitro and in vivo effects of GA in inducing apoptosis in GSCs and inhibiting GSCs self-renewal, as well as its underlying mechanisms. METHODS: This study synthesized biotinylated gambogic acid for the first time and angled for the target of gambogic acid using LC-MS/MS analysis, which has not been reported previously. Human-derived glioma stem cells GSC123 and GSC111 were used for in vitro studies, analyzing functions and mechanisms via microscale thermophoresis (MST), Annexin V/PI staining, Western blotting, immunofluorescence, and co-immunoprecipitation. The orthotopic glioma mouse model was used to assess the anti-tumor effects of GA in vivo. RESULTS: This study demonstrated that GA is a specific inhibitor of BMI1, a key regulator controlling stem cell growth and self-renewal. GA binds to BMI1's RING domain, accelerating K51-dependent degradation and suppressing H2A ubiquitination. Importantly, GA induces apoptosis, and inhibits GSC self-renewal, but minimally impacts neural progenitor cells (NPCs). GA can also be combined effectively with temozolomide and radiotherapy to increase their sensitivities in resistant cells. Furthermore, exogenous induction of BMI1 expression significantly hinders the disruption of GSCs by GA. In vivo, GA inhibits tumorigenicity, enhances the effect of temozolomide, and reduces BMI1 expression. CONCLUSION: These findings suggest that GA is a potential candidate for targeting GSCs and therefore be used to treat GBM.

TREM2, a critical activator of pyroptosis, mediates the anti­tumor effects of piceatannol in uveal melanoma cells via caspase 3/GSDME pathway

Uveal melanoma (UM) is the most prevalent type of primary intraocular malignancy and is prone to metastasize, particularly to the liver. However, due to the poor understanding of the pathogenesis of UM, effective therapeutic approaches are lacking. As a phenolic compound extracted from grapes, piceatannol (PIC) exhibits anti­cancer properties. To the best of our knowledge, however, the effects of PIC on UM have not been well investigated. Therefore, in the present study, considering the impact of pyroptosis on modulating cell viability, the mechanism underlying the effects of PIC on UM cell proliferation was explored. The inhibitory effect of PIC on proliferation of UM cells was detected by cell counting kit­8 assay. Wound healing was used to investigate the effects of PIC on the migration of UM cells. Activity detecting assays were performed to test the apoptosis and oxidant level in UM cells. Western blotting and RT­qPCR were used to detect the inflammatory and pyroptotic levels of UM cell after PIC treatment. PIC­treated UM cells were screened by high­throughput sequencing to detect the differential expression of RNA and differential genes. Si­TREM2 transfection was used to verify the important role of TREM2 in the effects of PIC. Immunohistochemical staining was used to observe the expressions of TREM2 and GSDMR of tumor in nude mice after PIC administration. PIC effectively inhibited proliferation ability of C918 and Mum­2b UM cell lines via enhancing apoptosis, as evidenced by enhanced activities of caspase 3 and caspase 9. In addition, treatment of UM cells with PIC attenuated cell migration in a dose­dependent manner. PIC increased reactive oxygen species levels and suppressed the activity of the antioxidant enzymes superoxide dismutase, glutathione­S­transferase, glutathione peroxidase and catalase. PIC inhibited inflammatory responses in C918 cells. PIC treatment upregulated IL­1ß, IL­18 and Nod­like receptor protein 3 and downregulated gasdermin D (GSDMD). RNA sequencing results revealed the activation of an unconventional pyroptosis­associated signaling pathway, namely caspase 3/GSDME signaling, following PIC treatment, which was mediated by triggering receptor expressed on myeloid cells 2 (TREM2) upregulation. As an agonist of TREM2, COG1410­mediated TREM2 upregulation inhibited proliferation of C918 cells, displaying similar effects to PIC. Furthermore, PIC inhibited tumor growth via regulating the TREM2/caspase 3/GSDME pathway in a mouse model. Collectively, the present study revealed a novel mechanism underlying the inhibitory effects of PIC on UM, providing a potential treatment approach for UM in clinic.

High-Yield Expressed Human Ferritin Heavy-Chain Nanoparticles in K. marxianus for Functional Food Development.

The use of Generally Recognized as Safe (GRAS)-grade microbial cell factories to produce recombinant protein-based nutritional products is a promising trend in developing food and health supplements. In this study, GRAS-grade Kluyveromyces marxianus was employed to express recombinant human heavy-chain ferritin (rhFTH), achieving a yield of 11 g/L in a 5 L fermenter, marking the highest yield reported for ferritin nanoparticle proteins to our knowledge. The rhFTH formed 12 nm spherical nanocages capable of ferroxidase activity, which involves converting Fe2+ to Fe3+ for storage. The rhFTH-containing yeast cell lysates promoted cytokine secretion (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and -1ß (IL-1ß)) and enhanced locomotion, pharyngeal pumping frequency, egg-laying capacity, and lifespan under heat and oxidative stress in the RAW264.7 mouse cell line and the C. elegans model, respectively, whereas yeast cell lysate alone had no such effects. These findings suggest that rhFTH boosts immunity, holding promise for developing ferritin-based food and nutritional products and suggesting its adjuvant potential for clinical applications of ferritin-based nanomedicine. The high-yield production of ferritin nanoparticles in K. marxianus offers a valuable source of ferritin for the development of ferritin-based products.

Recent Advances in Polymeric Delivery Vehicles for Controlled and Sustained Drug Release.

In the realm of modern therapeutics, the development of polymeric delivery vehicles has revolutionized drug administration, offering a sophisticated approach to controlled and sustained drug release [...].

Over-activation of iNKT cells aggravate lung injury in bronchopulmonary dysplasia mice.

Bronchopulmonary dysplasia (BPD) is a severe lung disease in preterm infants, the abnormal proliferate and differentiate ability of type II epithelial cells (AEC II) is the key to the pathological basis of BPD. Mechanisms regarding abnormal AEC II in BPD remain unclear. The present work investigated the role and mechanisms of invariant natural killer T (iNKT) cells in lung disorder in BPD using public datasets, clinical samples, a hyperoxia-induced BPD mouse model and AEC II-iNKT cells transwell co-culture system. Firstly, we found that the NKT cells development factor IL-15 increased over time in patients with BPD in public databases, and clinically collected peripheral blood NKT cells in patients with BPD were increased. Subsequently, the percentage of iNKT cells increased in hyperoxia group compared with normoxia group, with the highest at P7, accompanied by increased activation with abnormal lung development. The administration of anti-CD1d neutralizing antibody to inhibit iNKT cells could alleviate the abnormal lung development of hyperoxia group mice, while α-GalCer administration could aggravate lung injury in hyperoxia group mice, and adoptive transfer of iNKT cells could aggravate the abnormal lung development in hyperoxia group mice. In addition, to further verify the role of iNKT cells on AEC II, AEC II-iNKT cells co-culture system was established. The presence of iNKT cells could aggravate the abnormal expression of SP-C and T1α under hyperoxia. Meanwhile, RNA-seq analysis showed that ferroptosis-related genes were highly expressed in AEC II co-cultured with iNKT cells under hyperoxia. We further validated the effect of the presence of iNKT cells under hyperoxia environment on AEC II ferroptosis levels, suggested that iNKT cells promote AEC II ferroptosis under hyperoxia, accompanied by decreased expression of SP-C and T1α. Our study found that the recruitment of iNKT cells in the lung may be an important cause of alveolarization disorder in BPD.

Bifunctional sludge-derived redox carbon dots with photoelectron storage and delivery properties for ammonia production by photosensitized Shewanella oneidensis MR-1.

Combining the light-harvesting capabilities of photosensitizers with microbial catalysis shows great potential in solar-driven biomanufacturing. However, little information is available about the effects of photosensitizers on the photoelectron transport during the dissimilatory nitrate reduction to ammonium (DNRA) process. Herein, redox carbon dots (CDs-500) were prepared from sludge via the pyrolysis-Fenton reaction and then used to construct a photosynthetic system with Shewanella oneidensis MR-1. The MR-1/CDs-500 photosynthetic system showed a 5.9-fold increase in ammonia production (4.9 mmol(NH3)·g-1(protein)·h-1) with a high selectivity of 94.0 %. The photoelectrons were found to be stored in CDs-500 and transferred into the cells. During the inward electron transport, the intracellular CDs-500 could be used as the direct photoelectron transfer stations between outer membrane cytochrome c and DNRA-related enzymes without the involvement of CymA and MtrA. This work provides a new method for converting waste into functional catalysts and increases solar-driven NH3 production to a greater extent.

Quantification of Microsphere Drug Release by Fluorescence Imaging with the FRET System.

Accurately measuring drug and its release kinetics in both in vitro and in vivo environments is crucial for enhancing therapeutic effectiveness while minimizing potential side effects. Nevertheless, the real-time visualization of drug release from microspheres to monitor potential overdoses remains a challenge. The primary objective of this investigation was to employ fluorescence imaging for the real-time monitoring of drug release from microspheres in vitro, thereby simplifying the laborious analysis associated with the detection of drug release. Two distinct varieties of microspheres were fabricated, each encapsulating different drugs within PLGA polymers. Cy5 was selected as the donor, and Cy7 was selected as the acceptor for visualization and quantification of the facilitated microsphere drug release through the application of the fluorescence resonance energy transfer (FRET) principle. The findings from the in vitro experiments indicate a correlation between the FRET fluorescence alterations and the drug release profiles of the microspheres.

Myeloid-Specific Thrombospondin-1 Deficiency Exacerbates Aortic Rupture via Broad Suppression of Extracellular Matrix Proteins.

Rationale: Rupture of abdominal aortic aneurysms (AAA) is associated with high mortality. However, the precise molecular and cellular drivers of AAA rupture remain elusive. Our prior study showed that global and myeloid-specific deletion of matricellular protein thrombospondin-1 (TSP1) protects mice from aneurysm formation primarily by inhibiting vascular inflammation. Objective: To investigate the cellular and molecular mechanisms that drive AAA rupture by testing how TSP1 deficiency in different cell populations affects the rupture event. Methods and Results: We deleted TSP1 in endothelial cells and macrophages --- the major TSP1-expressing cells in aneurysmal tissues ---- by crossbreeding Thbs1 flox/flox mice with VE-cadherin Cre and Lyz2-cre mice, respectively. Aortic aneurysm and rupture were induced by angiotensin II in mice with hypercholesterolemia. Myeloid-specific Thbs1 knockout, but not endothelial-specific knockout, increased the rate of lethal aortic rupture by more than 2 folds. Combined analyses of single-cell RNA sequencing and histology showed a unique cellular and molecular signature of the rupture-prone aorta that was characterized by a broad suppression in inflammation and extracellular matrix production. Visium spatial transcriptomic analysis on human AAA tissues showed a correlation between low TSP1 expression and aortic dissection. Conclusions: TSP1 expression by myeloid cells negatively regulates aneurysm rupture, likely through promoting the matrix repair phenotypes of vascular smooth muscle cells thereby increasing the strength of the vascular wall.

Hypertriglyceridemia as a Key Contributor to Abdominal Aortic Aneurysm Development and Rupture: Insights from Genetic and Experimental Models.

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease without effective medications. This study integrated genetic, proteomic, and metabolomic data to identify causation between increased triglyceride (TG)-rich lipoproteins and AAA risk. Three hypertriglyceridemia mouse models were employed to test the hypothesis that increased plasma TG concentrations accelerate AAA development and rupture. In the angiotensin II-infusion AAA model, most Lpl -deficient mice with severely high plasma TG concentrations died of aortic rupture. Consistently, Apoa5 -deficient mice with moderately increased TG concentrations had accelerated AAA development, while human APOC3 transgenic mice with dramatically increased TG concentrations exhibited aortic dissection and rupture. Increased TG concentrations and palmitate inhibited lysyl oxidase maturation. Administration of antisense oligonucleotide targeting Angptl3 profoundly inhibited AAA progression in human APOC3 transgenic mice and Apoe -deficient mice. These results indicate that hypertriglyceridemia is a key contributor to AAA pathogenesis, highlighting the importance of triglyceride-rich lipoprotein management in treating AAA.

Hepatic Metabolomic Responses to Low-Temperature Stress in the Invasive Turtle, Trachemys scripta elegans.

Investigating the physiological and biochemical changes of ectothermic species before entering hibernation would contribute to the understanding of how they adapt to low-temperature environments. Here, red-eared slider turtle (Trachemys scripta elegans) hatchlings were maintained under different thermal treatments (24 °C, slowly decreasing temperatures from 24 °C to 14 °C, and to 4 °C). Hepatic metabolite alterations were measured to assess the metabolic impacts of low-temperature stress in this species. Of these differentially changed metabolites, some (e.g., raffinose, spermidine, allocholic acid, taurohyocholate, 2-ketobutyric acid, acetylcysteine) were shown to decrease, while others (e.g., stearolic acid, D-mannose) increased in low-temperature treatments. Our results indicated that short-term low-temperature stress might have limited impacts on lipid and energy metabolism in this species. The changes in other metabolites (e.g., allocholic acid, taurohyocholate, spermine, acetylcysteine) might be associated with a low food intake (and thus reduced digestive performance) and weakened immune ability of low-temperature-exposed animals.

Multi-omic analysis of Huntington's disease reveals a compensatory astrocyte state.

The mechanisms underlying the selective regional vulnerability to neurodegeneration in Huntington's disease (HD) have not been fully defined. To explore the role of astrocytes in this phenomenon, we used single-nucleus and bulk RNAseq, lipidomics, HTT gene CAG repeat-length measurements, and multiplexed immunofluorescence on HD and control post-mortem brains. We identified genes that correlated with CAG repeat length, which were enriched in astrocyte genes, and lipidomic signatures that implicated poly-unsaturated fatty acids in sensitizing neurons to cell death. Because astrocytes play essential roles in lipid metabolism, we explored the heterogeneity of astrocytic states in both protoplasmic and fibrous-like (CD44+) astrocytes. Significantly, one protoplasmic astrocyte state showed high levels of metallothioneins and was correlated with the selective vulnerability of distinct striatal neuronal populations. When modeled in vitro, this state improved the viability of HD-patient-derived spiny projection neurons. Our findings uncover key roles of astrocytic states in protecting against neurodegeneration in HD.