Zingerone attenuates concanavalin A-induced acute liver injury by restricting inflammatory responses.

Autoimmune hepatitis (AIH), an immune-mediated liver injury, plays an important role in the development and pathogenesis of several liver diseases. However, therapeutic alternatives for the treatment of AIH remain limited. Zingerone (ZIN) is a natural non-toxic phenolic compound extracted from ginger that possesses various pharmacological activities. Thus, this study aimed to investigate the effect of ZIN on AIH using a mouse model of acute liver injury induced by concanavalin A (Con A). To establish liver injury, C57BL/6J mice were intraperitoneally administered ZIN, followed by 20 mg/kg Con A after 3 h. Thereafter, the liver and serum were collected for analysis. The results revealed that ZIN pretreatment significantly suppressed the elevation of liver injury markers induced by Con A exposure and improved the survival of mice. Additionally, ZIN significantly ameliorated liver histopathological injury, hepatocyte apoptosis, and oxidative stress. Notably, ZIN inhibited hepatic M1 macrophage polarization and decreased the expression of M1 macrophage-associated pro-inflammatory genes and cytokines, including interleukin-1ß (IL-1ß), IL-12, IL-6, and tumor necrosis factor-α (TNF-α). Western blotting analysis indicated that ZIN inhibited the phosphorylation of extracellular receptor kin, c-Jun N-terminal kinase, and p65 in vitro. Taken together, these results suggest that ZIN exerts a protective effect in the Con A-induced acute liver injury model by inhibiting M1 macrophage polarization and suppressing NF-κB, mitogen-activated protein kinase, and interferon regulatory factor signaling pathways. This highlights the possibility of using ZIN as a safe drug for the treatment of liver injury and provides a novel therapeutic direction for clinical studies on liver diseases.

Sex disparities of clinical manifestations in acute pulmonary embolism and predictive value for in-hospital mortality: Insights from CURES.

BACKGROUND: Pulmonary embolism (PE) is a common and potentially fatal disease, with differences in mortality rates among PE patients of different sexes. This study aims to investigate the disparities in clinical manifestations and in-hospital mortality rates between sexes in PE patients, as well as the association of clinical symptoms with in-hospital mortality. METHODS: We analyzed data from the China pUlmonary thromboembolism REgistry Study (CURES), a nationwide, multicenter, prospective registry focusing on patients with acute PE. Using propensity score matching (PSM) to pair male and female patients with PE, we explored the correlation between clinical symptoms and in-hospital mortality through multivariable regression analysis. RESULTS: A total of 15,203 patients with acute PE were enrolled, and 380 died during hospitalization. The incidence of chest pain, hemoptysis, and palpitations was significantly higher in males compared to females. The incidence of dyspnea, fever, and syncope was higher in females. Hemoptysis and dyspnea were associated with increased in-hospital mortality in males, whereas dyspnea, fever, and palpitations were linked to higher mortality in females. Overall, males exhibited a higher in-hospital mortality than females (2.9 % vs. 2.1 %, p = 0.002). After matching 13,130 patients using the PSM method, the mortality rate of males remained higher than that of females (2.7 % vs. 2.1 %, p = 0.020). CONCLUSIONS: Our study demonstrates that male patients with PE have a higher risk of in-hospital mortality than females. Significant differences in clinical symptoms between sexes are associated with increased mortality risk, emphasizing the need for clinical awareness.

Correlation of Th17/Treg associated transcription factors with clinicopathological features of colorectal cancer and their prognostic significance.

OBJECTIVE: To analyze the correlation of Th17/Treg associated transcription factors (TFs) with clinicopathological features of colorectal cancer (CRC) and their prognostic significance. METHODS: This research enrolled 56 CRC patients (experimental group, EG) and 50 healthy controls (control group, CG), who presented to Deqing People's Hospital between June 2017 and January 2019. The levels of Th17, Treg and their TFs [forkhead box protein P3 (Foxp3), retinoid acid receptor-related orphan receptor gamma t (RORγt)] and secreted inflammatory factors (IFs) [interleukin-17 (IL-17), interleukin-22 (IL-22)] were detected in the peripheral blood (PB) of both groups, and the TFs' phosphorylated protein expression was observed by Western blot. Further, the correlation of TFs with patients' pathological features was analyzed. Finally, a 3-year prognostic follow-up was performed on CRC patients. Receiver operating characteristic (ROC) determined the predictive value of Th17/Treg on the prognostic mortality of patients. RESULTS: Peripheral blood Th17 and Treg showed higher levels in the EG than in the CG, demonstrating excellent diagnostic effects on CRC (P<0.05). The EG also exhibited reduced Foxp3 and p-Foxp3 protein expression, and elevated RORγt and p-RORγt levels compared with the CG (all P<0.0001). In addition, the EG exhibited statistically higher IL-17 and IL-22 levels than the CG (all P<0.05). Further, the analysis of pathological features revealed close correlations of Th17/Treg, RORγt and Foxp3 with tumor size, TNM staging, degree of differentiation, and lymph node metastasis (LNM) of CRC patients (all P<0.001). Finally, the prognostic follow-up results identified that TNM staging, degree of differentiation, LNM, RORγt, Th17 and Treg were independent risk factors for prognostic mortality of CRC patients, while Foxp3 was an independent protective factor (all P<0.001). CONCLUSION: Th17/Treg associated TFs are of great significance for the prognosis evaluation of CRC, the imbalance of which can cause aggravation of the inflammatory reaction and promote malignancy of CRC.

Relationship between right-to-left shunt and white matter lesions in patients with migraine: a single-center study.

Background: Migraine patients have an increased long-term risk of cardio and cerebrovascular events. However, whether these patients are more susceptible to white matter lesions (WMLs) remains debated. To explore this question, our study assessed the proportion of RLS in migraine patients and explored the association between right-to-left shunt (RLS) and WMLs. Methods: In this study, we included 998 migraine patients. Contrast transcranial doppler (c-TCD) was used to diagnose RLS and assess the extent of the shunt in RLS patients. Of the 998 patients, 505 underwent cranial magnetic resonance imaging (MRI) assessments. WMLs were classified into periventricular white matter lesions (pvWMLs) and deep white matter lesions (dWMLs). Results: Among the 998 migraine patients, 946 had migraine without aura (MO; mean age 36.68 ± 10.46 years; 80.5% female), and 52 had migraine with aura (MA; mean age 29.85 ± 8.59 years; 71.2% female). Compared with MO patients, MA patients had an earlier onset age (23.1 ± 7.97 vs. 28.44 ± 10.38 years, p < 0. 001) and a shorter disease duration (6.76 vs. 8.34 years, p = 0.024). The overall proportion of RLS patients was 41.9%, with a greater proportion of RLS patients in the MA group than in the MO group (55.8% vs. 41. 1%, p = 0.037). The percentage of RLS-positive patients with no/small shunt was greater in the MO group than in the MA group (81.5% vs. 65.4%, p = 0.004), whereas the percentage of RLS-positive patients with moderate/large shunt was greater in the MA group (34.6% vs. 18.5%, p = 0.024). The proportion of RLS patients was lower in the WML-positive group (n = 173) than in the WML-negative group (n = 332), but the difference was not significant (40.5% vs. 45.8%, p = 0.253). Conclusion: This study revealed that 41.9% of migraine patients had RLS, and the proportion of RLS patients was 41. 1% in the MO group and 55.8% in the MA group. The rate of RLS positivity in migraine patients may not be related to the incidence of WMLs.

Neoadjuvant everolimus in renal angiomyolipoma with or without tuberous sclerosis complex: Results from a multicenter, retrospective study.

OBJECTIVES: To assess the efficacy and safety of preoperative neoadjuvant everolimus in renal angiomyolipomas (AML) patients with or without Tuberous Sclerosis Complex (TSC). MATERIALS AND METHODS: This multi-institutional retrospective study enrolled renal AML patients who underwent partial nephrectomy (PN) or total nephrectomy after receiving at least 1 month of pre-operative everolimus. Imaging evaluations were collected before and after treatment, along with demographic, surgical, and follow-up information. The primary outcome was tumor volume reduction of ≥25%, with additional outcomes including recurrence, perioperative outcomes, renal function, and safety. RESULTS: From January 2015 to July 2022, 68 renal AML patients were studied-41 with TSC and 27 without. During everolimus treatment, 61.0% (25/41) of TSC patients and 44.4% (12/27) of non-TSC patients achieved tumor reduction of ≥25%. Additionally, 41.5% (17/41) of TSC patients and 18.5% (5/27) of non-TSC patients achieved a ≥ 50% reduction. Three TSC patients and 1 non-TSC patient discontinued treatment due to side-effects. Most patients (92.7% TSC, 85.2% non-TSC) underwent PN. After everolimus treatment, the necessary total nephrectomy decreased to 41.2% (7/17) from baseline. Postoperatively, 1 grade 3 and 3 grade 2 complications occurred, with no grade 4 or 5 complications. After a median follow-up of 24 months, only 1 TSC patient recurred with a diameter >3 cm. Retrospective nature is the major limitation of this study. CONCLUSION: Everolimus was effective and well-tolerated in neoadjuvant treatment for renal AML, especially in TSC patients. This neoadjuvant combination strategy of everolimus and PN could effectively controls recurrence and preserves renal function.

Intramolecular CH⋯π attraction mediated conformational polymorphism of constrained helical peptides.

In nature, biochemical processes depend on polymorphism, a phenomenon by which discrete biomolecules can adopt specific conformations based on their environment. However, it is often difficult to explore the generation mechanism and achieve polymorphic control in artificial supramolecular assembly systems. In this work, we propose a feasible thought for exploring the transformation mechanism of polymorphism in peptide assembly from the perspective of thermodynamic regulation, which enables polymorphic composition to be limited by switchable intramolecular CH⋯π attraction within a certain temperature range. Combined with the density functional theory calculations, we obtained thermodynamic theoretical data supporting the conformation transition and the underlying polymorphism formation principle. Afterward, we properly designed the peptide to alter the probability of CH⋯π attraction occurring. Then, we selectively obtained a homogeneous morphological form with corresponding molecular conformation, which further demonstrated the important role of molecular conformational manipulation in polymorphism selection. This unique template-based strategy developed in this study may provide scientists with an additional line of thought to guide assembly paths in other polymorphic systems.

Myocyte enhancer factor 2 upregulates expression of myostatin promoter in Yesso scallop, Patinopecten yessoensis.

Myostatin (MSTN) plays an important role in muscle development in animals, especially for mammals and fishes. However, little information has been reported on the regulation of MSTN in marine invertebrates, such as bivalves. In the present study, we cloned the MSTN promoter sequence of Yesso scallop Patinopecten yessoensis, identifying 4 transcription start sites, eleven TATA boxes and one E-box. Additionally, transcription factor binding sites, including myocyte enhancer factor 2 (MEF2) and POU homeodomain protein, were identified. The interaction between the MSTN promoter and MEF2 was analyzed to reveal the transcriptional activity of different fragment sizes of promoters through the dual-luciferase reporter assays. The highest transcriptional activity was found in recombinant plasmids with the most MEF2 binding sites, indicating that this transcription factor upregulates MSTN in Yesso scallop. This study provides new insight into the regulation of muscle growth and development in this species.

Tracing nitrogen sources and transformation characteristics in a large basin with spatially heterogeneous pollution distribution.

This study used dual stable isotopes to examine nitrate sources and geographical distribution in the Liao River Basin (LRB), one of China's seven major river basins. During a normal hydrological season in April 2021, water samples were taken from the main streams of the Liao River (MLR), Shuangtaizi River (STR), Hun River (HR), Taizi River (TZR), and Daliao River (DLR). Monitoring results indicated that 93% of the water samples had a total nitrogen level exceeding the Class IV limit (1.5 mg/L) of the 'Environmental Quality Standards (EQS) for surface water', indicating a serious nitrogen pollution status. 71.3% of the total nitrogen on average was in the form of nitrate. The scatterplots of δD-H2O and δ18O-H2O showed that water in TZR and DLR were mainly affected by precipitation, while MLR, STR and HR were additionally impacted by evaporation and groundwater. The overall δ15N and δ18O of NO3- varied from 7.7‰ to 17.9‰ and 0.6‰-11.2‰, respectively. The correlations between δ15N-NO3- and δ18O-NO3-, along with attribution results from the Bayesian isotopic mixing model, indicated a predominant role of manure/sewage (MS) pollution in affecting river nitrate, accounting for 78% of total nitrate in MLR and 72% in DLR. A positive correlation between δ15N-NO3- and δ18O-NO3- in MLR indicated the occurrence of denitrification process. Overall, attribution results showed that the primary nitrate sources varied in different river systems within such a large basin, mainly due to spatially varied land use and human activities. Tailored nitrogen management strategies should be implemented to address the main anthropogenic pressures.

Estrogen receptor is involved in the osteoarthritis mediated by Atg16L1-NLRP3 activation.

OBJECTIVES: This study aims to explore the mechanisms of dual regulation of osteoarthritis (OA) progression by the involvement of estrogen receptor (ER) in autophagy and inflammation. MATERIALS AND METHODS: Bioinformatics methods were used to explore the relationship among associated genes. Western blot assays were used to detect related protein expression of OA in C28I2 and induced OA cellular model. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis were used to detect OA related gene expression in C28I2 and induced OA cellular model. Co-immunoprecipitation (CO-IP) analysis were used to verify the direct interaction between ER and NOD-like receptor thermal protein domain associated protein 3 (NLRP3). RESULTS: The C28I2 cellular model of OA was induced by interleukin-1ß (IL-1ß). The small interfering ribonucleic acid (SiRNA)-mediated knockdown of autophagy-related 16 like 1 (ATG16L1) in C28I2 decreased the expression of MAP1LC3B (LC3B) and NLRP3. Besides, ER-beta (ERß) agonist changed the gene expression of NLRP3 and ATG16L1. Moreover, CO-IP analysis indicated the direct interaction between ER and NLRP3. CONCLUSION: Our study results revealed that ATG16L1, NLRP3, and IL-1ß interacted closely and ERß was involved in OA process by affecting autophagy and inflammatory activation.

Exploring the promoting behavior of weak electric mediation on indole and pyridine biodegradation under anaerobic condition.

Indole and pyridine, which are highly produced refractory compounds in the industrial wastewater, exhibit poor degradation capabilities in natural environments. In this study, we developed an anaerobic digestion system coupled with weak electric mediation (ED), and investigated the promoting effect of weak electricity on indole and pyridine biodegradation. The degradation characteristics were systematically explored, and the results showed that the degradation rate and mineralization of indole and pyridine were significantly enhanced, the production of CH4 was increased 1.4-fold, and the optimal voltages were 1.0 V and 0.8 V in the ED, respectively. Moreover, simultaneous removal of carbon and nitrogen was achieved. Gas chromatography-mass spectrometry analysis verified the transformation products, and possible pathways were proposed. Several byproducts of indole and pyridine were identified, with oxindole and glutaric dialdehyde being the main metabolites, respectively. Additionally, density functional theory (DFT) analysis was performed to investigated the radical indices and stabilities of the molecules to further confirm the degradation pathway. Microbial structure analysis demonstrated that the electrically mediated enhanced metabolism and activity of functional microbes, led to the promotion of indole and pyridine mineralization. Moreover, such species as degrading bacteria (Alicycliphilus, Shinella) and electroactive bacteria (Achromobacter), anaerobic ammonia-oxidizing bacteria (SM1A02), and denitrifying bacteria (Thiobacillus) coexisted. This study demonstrates that weak electric mediation is a promising methodology for enhancing the removal of indole and pyridine from wastewater under anaerobic conditions.

Application of the updated International IgA Nephropathy Prediction Tool in children one or two years post-biopsy.

The pediatric International IgA Nephropathy (IgAN) Prediction Tool comprises two models with and without ethnicity and is the first method to predict the risk of a 30% decline in estimated glomerular filtration rate (eGFR) or kidney failure in children at the time of biopsy using clinical risk factors and Oxford MEST histology scores. However, it is unknown if the Prediction Tool can be applied after a period of observation post-biopsy. Using an international multi-ethnic cohort of 947 children with IgAN, 38% of whom were followed into adulthood, the Prediction Tool was updated for use one year after biopsy. Compared to the original pediatric Prediction Tool, the updated post-biopsy Prediction Tool had a better model fit with higher R2D (51%/50% vs 20%), significant increase in 4-year C-statistics (0.83 vs 0.73/0.69, ΔC 0.09 [95% confidence interval 0.07-0.10] and ΔC 0.14 [0.12-0.15]) and better 4-year calibration with lower integrated calibration indices (0.74/0.54 vs 2.45/1.01). Results were similar after internal validation and when the models were applied two years after biopsy. Trajectories of eGFR after a baseline one year post-biopsy were non-linear and those at higher predicted risk started with a lower eGFR and experienced a more rapid decline over time. In children, eGFR had a variable rate of increase until 15-18 years old and then decreased linearly with a more rapid decline in higher risk groups that was similar to young adults of comparable risk. Thus, the original pediatric Prediction Tool should be used in children at the time of biopsy, and the updated pediatric Prediction Tool should be used to re-evaluate risk one or two years after biopsy.

Chemometrics of the composition and antioxidant capacity of essential oils obtained from six Cupressaceae taxa.

Essential oils (EOs) are complex and susceptible to environmental conditions, they have a wide range of biological activities and are often used to differentiate between similar species. In this study, gas chromatography-mass spectrometry (GC-MS) coupled with chemometric analysis was applied to systematically analyse and evaluate EOs constituents and antioxidant activity of six Chinese Cupressaceae taxa (Platycladus orientalis Franco, P. orientalis Franco 'Sieboldii', P. orientalis Franco 'Aurea', Juniperus chinensis Roxb., J. chinensis Roxb. 'Kaizuca', and J. sabina L.) under identical conditions. The antioxidant activity of the EOs was evaluated using 2,2 -diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and ferric reducing power (FRAP), and the total phenolic content (TPC) of the EOs was determined by Folin-Ciocalteau reagent. In total, seventy individual constituents were identified with the main components being α-pinene, sabinene, D-limonene, bornyl acetate, δ-3-carene and ß-myrcene. Principal component analysis (PCA) and hierarchal cluster analysis (HCA) successfully discriminated the six taxa into three chemotypes and the unique chemotype revealed that J. chinensis 'Kaizuca' may be a species rather than a cultivar of J. chinensis. The results of OPLS-DA analysis showed that the three compounds screened, namely, α-pinene, sabinene, and δ-3-carene, can completely distinguish Platycladus spp. from Juniperus spp. The DPPH assay results ranged from 576.14 (J. chinensis 'Kaizuca') to 1146.12 (J. sabina) µmol eq Trolox/mL EO, while the ABTS values ranged from 1579.62 (P. orientalis 'Aurea') to 5071.82 (J. sabina) µmol eq Trolox/mL. In the FRAP assay, the values ranged from 1086.50 (J. chinensis 'Kaizuca') to 1191.18 (J. sabina) µmol eq Trolox/ml and the TPC of the EOs studied ranged from 15.17 (J. chinensis 'Kaizuca') to 39.37 (J. sabina) mg GAE/mL EO. The results consistently showed that J. sabina possessed the strongest antioxidant activity and can be preferentially used as a rich source of potentially natural antioxidants.

Pupillary response to cognitive control in depression-prone individuals.

Revealing the pupillary correlates of depression-prone individuals is conducive to the early intervention and treatment of depression. This study recruited 31 depression-prone and 31 healthy individuals. They completed an emotional task-switching task combined with a go/no-go task, and task-evoked pupillary responses (TEPR) were recorded. Behavioral results showed no significant differences in behavioral performance in terms of cognitive flexibility and inhibition between the depression-prone group and the healthy control group. The pupillary results revealed that (1) the depression-prone group showed slightly lower TEPRs to positive stimuli than the healthy controls during cue presentation; (2) during target presentation, the depression-prone group did not show an effect of emotional valence on the pupillary response in the task-repeat trials; and (3) compared to the healthy controls, the depression-prone group showed significantly smaller TEPRs to negative no-go stimuli and had a longer latency of the second peak of pupil dilation in no-go trials. These results imply that depression-prone individuals may have slower neural responses in cognitive control tasks and emotion-specific weakened cognitive control than healthy individuals.

Multi-omic characterization of allele-specific regulatory variation in hybrid pigs.

Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.

Machine Vision Analysis of Ujumqin Sheep's Walking Posture and Body Size.

The ability to recognize the body sizes of sheep is significantly influenced by posture, especially without artificial fixation, leading to more noticeable changes. This study presents a recognition model using the Mask R-CNN convolutional neural network to identify the sides and backs of sheep. The proposed approach includes an algorithm for extracting key frames through mask calculation and specific algorithms for head-down, head-up, and jumping postures of Ujumqin sheep. The study reported an accuracy of 94.70% in posture classification. We measured the body size parameters of Ujumqin sheep of different sexes and in different walking states, including observations of head-down and head-up. The errors for the head-down position of rams, in terms of body slanting length, withers height, hip height, and chest depth, were recorded as 0.08 ± 0.06, 0.09 ± 0.07, 0.07 ± 0.05, and 0.12 ± 0.09, respectively. For rams in the head-up position, the corresponding errors were 0.06 ± 0.05, 0.06 ± 0.05, 0.07 ± 0.05, and 0.13 ± 0.07, respectively. The errors for the head-down position of ewes, in terms of body slanting length, withers height, hip height, and chest depth, were recorded as 0.06 ± 0.05, 0.09 ± 0.08, 0.07 ± 0.06, and 0.13 ± 0.10, respectively. For ewes in the head-up position, the corresponding errors were 0.06 ± 0.05, 0.08 ± 0.06, 0.06 ± 0.04, and 0.16 ± 0.12, respectively. The study observed that sheep walking through a passage exhibited a more curved knee posture compared to normal measurements, often with a lowered head. This research presents a cost-effective data collection scheme for studying multiple postures in animal husbandry.

Inflammatory Reprogramming Mediates Changes in Three-Dimensional Strain Capacity and Cardiac Function in Beagle Dogs with Doxorubicin-Related Cardiomyopathy.

Background: The cardiotoxicity of doxorubicin (DOX) limits its use in cancer treatment. To address this limitation, we developed a novel animal model that uses beagle dogs to investigate DOX-induced cardiac disorders. Unfortunately, the lack of effective cardioprotection strategies against DOX-induced cardiotoxicity poses a significant challenge. To establish a canine model for low-mortality DOX-induced cardiac dysfunction and explore the relationship between inflammatory reprogramming and DOX-related cardiotoxicity. Methods: Twenty male beagle dogs aged two years were randomly assigned into the DOX (N = 10) and control (CON) (N = 10) groups. DOX was infused (1.5 mg/kg) every two weeks until doses cumulatively reached 12 mg/kg. Serum biomarkers and myocardial pathology were evaluated, while real-time fluorescence-based quantitative polymerase chain reaction (RTFQ-PCR), two- and three-dimensional echocardiography (2DE and RT3DE), functional enrichment, and matrix correlation were also performed. Results: In the DOX group, high-sensitive cardiac troponin T (hs cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were significantly increased. Myocardial pathology indicated early to medium myocardial degeneration via a decreased cardiomyocyte cross-sectional area (CSA). Increased levels of inflammatory gene transcripts (interleukin 6 (IL6), tumor necrosis factor (TNF), transforming growth factor ß (TGF ß ), intercellular adhesion molecule 1 (ICAM1), interleukin 1 (IL1), interleukin 1 ß (IL1 ß ), and interleukin 8 (IL8)), of collagen metabolism and deposition regulatory genes (matrix metalloproteinase (MMP) family and tissue inhibitor of matrix metalloproteinase (TIMP) family), and the natriuretic peptide family (NPS) (natriuretic peptide A, B and C (NPPA, NPPB, and NPPC)) were observed. Strain abnormalities in the right ventricular longitudinal septal strain (RVLSS), right ventricular longitudinal free-wall strain (RVLFS), left ventricular global longitudinal strain (LVGLS), and left ventricular global circumferential strain (LVGCS) were detected at week 28 (vs. week 0 or CON group, p < 0.05, respectively). A significant decline in RVLSS and RVLFS occurred at week 16, which was earlier than in the corresponding left ventricular areas. A significant right ventricular ejection fraction (RVEF) decline was noted at week 16 (vs. week 0, 33.92 ± 3.59% vs. 38.58 ± 3.58%, p < 0.05), which was 12 weeks earlier than for the left ventricular ejection fraction (LVEF), which occurred at week 28 (vs. week 0, 49.02 ± 2.07% vs. 54.26 ± 4.38%, p < 0.01). The right ventricular strain and functional damages correlated stronger with inflammatory reprogramming (most R from 0.60 to 0.90) than the left ones (most R from 0.30 to 0.65), thereby indicating a more pronounced correlation. Conclusions: Inflammatory reprogramming mediated disorders of strain capacity and cardiac function predominantly in the right side of the heart in the newly established DOX-related cardiomyopathy beagle dog model.

Porphyrin-Based Organic Nanoparticles with NIR-IIa Fluorescence for Orthotopic Glioblastoma Theranostics.

The development of efficient theranostic nanoagents for the precise diagnosis and targeted therapy of glioblastoma (GBM) remains a big challenge. Herein, we designed and developed porphyrin-based organic nanoparticles (PNP NPs) with strong emission in the near-infrared IIa window (NIR-IIa) for orthotopic GBM theranostics. PNP NPs possess favorable photoacoustic and photothermal properties, high photostability, and low toxicity. After modification with the RGD peptide, the obtained PNPD NPs exhibited enhanced blood-brain barrier (BBB) penetration capability and GBM targeting ability. NIR-IIa imaging was employed to monitor the in vivo biodistribution and accumulation of the nanoparticles, revealing a significant enhancement in penetration depth and signal-to-noise ratio. Both in vitro and in vivo results demonstrated that PNPD NPs effectively inhibited the proliferation of tumor cells and induced negligible side effects in normal brain tissues. In general, the work presented a kind of brain-targeted porphyrin-based NPs with NIR-IIa fluorescence for orthotopic glioblastoma theranostics, showing promising prospects for clinical translation.

Effects of malnutrition on disease severity and adverse outcomes in idiopathic pulmonary arterial hypertension: a retrospective cohort study.

BACKGROUND: Malnutrition is common in patients with chronic cardiovascular disease and is associated with significantly higher all-cause mortality. Approximately one-third of patients with heart failure are malnourished. However, the relationship between malnutrition and idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study aimed to clarify the prognostic value of malnutrition in patients with IPAH. METHODS: A total of 432 consecutive participants with IPAH were included in this study between March 2013 and August 2021. Three common malnutrition assessment tools, including the geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score, were used to evaluate the nutritional status of patients with IPAH. The relationships between the malnutrition tools and long-term adverse outcomes were determined using restricted cubic splines and multivariate Cox regression models. RESULTS: During a mean follow-up of 3.1 years, 158 participants experienced clinical worsening or all-cause death. Patients were stratified into the low-, intermediate- and high-risk groups based on the European Society of Cardiology (ESC) risk stratification, and the PNI (55.9 ± 5.7 vs. 54.4 ± 7.2 vs. 51.1 ± 7.1, P = 0.005) and CONUT score (2.1 ± 0.9 vs. 2.5 ± 1.2 vs. 3.3 ± 1.1, P < 0.001) identified these patient groups better than the GNRI. All three malnutrition tools were associated with well-validated variables that reflected IPAH severity, such as the World Health Organization functional class, 6-min walk distance, and N-terminal pro-brain natriuretic peptide level. The CONUT score exhibited better predictive ability than both the GNRI (ΔAUC = 0.059, P < 0.001) and PNI (ΔAUC = 0.095, P < 0.001) for adverse outcomes and significantly improved reclassification and discrimination beyond the ESC risk score. Multivariable Cox regression analysis indicated that only the CONUT score (hazard ratio = 1.363, 95% confidence interval 1.147, 1.619 per 1.0-standard deviation increment, P < 0.001) independently predicted adverse outcomes. CONCLUSIONS: The malnutrition status was associated with disease severity in patients with IPAH. The CONUT score provided additional information regarding the risk of clinically worsening events, making it a meaningful risk stratification tool for these patients.

Characterization of winter PM2.5 source contributions and impacts of meteorological conditions and anthropogenic emission changes in the Sichuan Basin, 2002-2020.

In this study, the Weather Research and Forecasting (WRF) model and Community Multiscale Air Quality-Integrated Source Apportionment Method (CMAQ-ISAM) were utilized, which were integrated with the Multiresolution Emission Inventory for China (MEIC) emission inventory, to simulate winter PM2.5 concentrations, regional transport, and changes in emission source contributions in the Sichuan basin (SCB) from 2002 to 2020, considering variations in meteorological conditions and anthropogenic emissions. The results indicated a gradual decrease in the basin's winter average PM2.5 concentration from 300 µg/m3 to 120 µg/m3, with the most significant decrease occurring after 2014, reflecting the actual impact of China's air pollution control measures. Spatially, the main pollution area shifted from Chongqing to Chengdu and the western basin. The sources of PM2.5 at the eastern and western margins of the basin have remained stable and have been dominated by local emissions for many years, while the sources of PM2.5 in the central part of the basin have evolved from a multiregional co-influenced source during the early period to a high proportion of local emissions; except for boundary condition sources, residential sources were the main PM2.5 sources in the basin (approximately 29.70 %), followed by industrial sources (approximately 14.11 %). Industrial sources exhibited higher contributions in Chengdu and Chongqing and gradually stabilized with residential sources over the years, while residential sources dominated in the eastern and western parts of the basin and exhibited a declining trend. Meteorological conditions exacerbated pollution in the whole basin from 2008 to 2014, especially in the west (21-40 µg/m3). The eastern basin and Chongqing exhibited more years with alleviated meteorological pollution, including a 40+ µg/m3 decrease in Chongqing from 2002 to 2005. Reduced anthropogenic emissions alleviated annual pollution levels, with a greater reduction (> -20 µg/m3) after 2011 due to pollution control measures.

Fabricating a high-performance anode by coating a carbon layer on a yolk-shell bimetallic selenide microsphere for enhanced lithium storage.

The rational synthesis of an electrode material with a highly active and stable architecture is very critical to achieving high-performance electrochemical energy storage. Herein, N-doped carbon restricting yolk-shell CoSe2/Ni3Se4 (CoSe2/Ni3Se4@NC) flower-like microspheres were successfully synthesized from solid CoNi-glycerate microspheres using a coating technology as an anode material for lithium-ion batteries (LIBs). The unique yolk-shell CoSe2/Ni3Se4@NC microspheres with hierarchical pores can increase the contact area with the electrolyte and provide enough transfer channels for the diffusion of Li+. The carbon layer on the surface of CoSe2/Ni3Se4@NC can not only improve the conductivity of the electrode but also provide the protective effect of active nanosheets during the process of synthesis, avoiding the overall structure collapse during the charge/discharge process of LIBs. Benefiting from the high conductivity, hollow structure, and elastic NC shell bestowed by the unique architecture, the yolk-shell CoSe2/Ni3Se4@NC anode shows excellent lithium storage performances, such as an excellent reversible specific capacity of 319 mA h g-1 at a current density of 1000 mA g-1 after 500 cycles and excellent cycling stability. This synthesis strategy provides a new way to optimize the lithium storage performance of transition metal compound electrode materials, which is helpful to the design of the next generation of high-performance LIBs.