Refined Prediction Method for Production Performance of Deep-Water Turbidite Sandstone Oilfield: A Case Study of AKPO in Niger Delta Basin, West Africa.

Deep-water oilfields frequently employ large or superlarge well spacing, leading to significant production dynamics influenced by reservoir factors. Traditional methodologies often disregard these influences, resulting in poor accuracy. Therefore, an enhanced prediction methodology rooted in reservoir characteristics is proposed. This approach introduces the dynamic relative permeability law as a bridge, capturing macroscopic oil/water movement within the reservoir. For the first time, it integrates production dynamics with key controlling reservoir factors, encompassing reservoir architecture, injection-production connectivity, and reservoir heterogeneity. The results indicate that (1) In deep-water turbidite sandstone fields with ultralarge injector-producer well spacings, the distribution of oil-water movement is primarily influenced by reservoir connectivity and heterogeneity. The injection water sweeping ability coefficient can quantitatively describe the water flooding capacity, with a strong negative correlation between the injection water sweeping ability coefficient and interwell nonconnectivity coefficient and reservoir homogeneity coefficient. This suggests that better reservoir connectivity or weaker heterogeneity results in stronger water flooding capacity, leading to a wider range of water flooding under the same injection volume. (2) For regions with strong water flooding capacity (injection water sweeping ability coefficient 0.30-0.80), the water-free production period is the main production stage, with a focus on improving the planar flooding conditions. For regions with poor water flooding capacity (injection water sweeping ability coefficient 0.00-0.10), the middle and late water-cut periods are the main production stages, with a focus on improving interlayer dynamic differences in the later stages. For regions with moderate water flooding capacity (injection water sweeping ability coefficient 0.10-0.30), the initial focus should be on expanding planar flooding, followed by a focus on improving interlayer dynamic differences in the later stages. (3) The dynamic relative permeability law, capable of comprehensively portraying the reservoir's influence on macroscopic oil/water movement, emerges as a rational choice for production performance prediction in such contexts. Our method can improve the accuracy, compared with traditional method without geographical factors, from 45% to 90% during water-cut rising stage and 31% to 81% during production declining stage. The high prediction accuracy (90%) observed in the AKPO oilfields underscores the method's efficacy in directing on-site optimization and adjustments for the development of deep-water turbidite sandstone oilfields.

Neural Network Based Aliasing Spectral Decoupling Algorithm for Precise Mid-Infrared Multicomponent Gases Sensing.

Owing to the overlapping and cross-interference of absorption lines in multicomponent gases, the simultaneous measurement of such gases via laser absorption spectroscopy frequently necessitates the use of supplementary pressure sensors to distinguish the spectral lines. Alternatively, it requires multiple lasers combined with time-division multiplexing to independently scan the absorption peaks of each gas, thereby preventing interference from other gases. This inevitably escalates both the cost of the system and the complexity of the gas pathway. In response to these challenges, a mid-infrared sensor employing a neural network-based decoupling algorithm for aliasing spectral is developed, enabling the simultaneous detection of methane(CH4), water vapor(H2O), and ethane(C2H6). The sensor system underwent evaluation in a controlled laboratory environment. Allan deviation analysis revealed that the minimum detection limits for CH4,H2O, and C2H6 were 6.04, 118.44, and 1 ppb, respectively, with an averaging time of 3 s. The performance of the proposed sensor demonstrates that the aliasing spectral decoupling algorithm based on neural network combined with wavelength-modulated spectroscopy technology has the advantages of high sensitivity, low cost and low complexity, showing its potential for simultaneous detection of multicomponent trace gases in various fields.

Safety, Tolerability, and Pharmacokinetics of Single Doses of Exidavnemab (BAN0805), an Anti-α-Synuclein Antibody, in Healthy Western, Caucasian, Japanese, and Han Chinese Adults.

Exidavnemab is a monoclonal antibody (mAb) with a high affinity and selectivity for pathological aggregated forms of α-synuclein and a low affinity for physiological monomers, which is in clinical development as a disease-modifying treatment for patients with synucleinopathies such as Parkinson's disease. Safety, tolerability, pharmacokinetics, immunogenicity, and exploratory biomarkers were assessed in two separate Phase 1 single ascending dose studies, including single intravenous (IV) (100 to 6000 mg) or subcutaneous (SC) (300 mg) administration of exidavnemab in healthy volunteers (HVs). Across the two studies, a total of 98 Western, Caucasian, Japanese, and Han Chinese HVs were enrolled, of which 95 completed the study. Exidavnemab was generally well tolerated. There were no serious adverse events or safety issues identified in laboratory analyses. Headache, asymptomatic COVID-19, back pain, and post lumbar puncture syndrome were the most frequently reported treatment-emergent adverse events. Following IV infusion, the pharmacokinetics of exidavnemab was approximately dose linear in the range 100-6000 mg. The terminal half-life was approximately 30 days, and the exposure was comparable across Western, Caucasian, Japanese, and Han Chinese volunteers. The absolute SC bioavailability was ∼71%. Cerebrospinal fluid exposure relative to serum after single dose was within the range expected for mAbs (approximately 0.2%). The anti-drug antibody rates were low and there was no effect of immunogenicity on the pharmacokinetics or safety. Dose-dependent reduction of free α-synuclein in plasma was observed. In summary, exidavnemab was found to have an excellent pharmacokinetic profile and was well tolerated in HVs, supporting the continued clinical development.

[Application scenario design and prospect of generative artificial intelligence (AI) in intelligent manufacturing and supply chain of traditional Chinese medicine].

Intelligent manufacturing technologies, including databases, mathematical modeling, and information systems have played a significant role in process control, production management, and supply chain management in traditional Chinese medicine(TCM) industry. However, their ability to process and utilize unstructured data, such as research and development reports, batch production records, quality inspection records, and supplier documents, is relatively weak. For text, images, language, and other unstructured data, generative artificial intelligence(AI) technology has shown strong potential for development in extracting information, extracting knowledge, semantic retrieval, and content generation. Generative AI is expected to provide a feasible set of tools for the utilization of unstructured data resources in the TCM industry. Based on years of research and industrial application experience in TCM intelligent manufacturing technology, this study reviewed the current situation of intelligent manufacturing in TCM and the utilization of unstructured data, analyzed the application value of generative AI in the TCM manufacturing process and supply chain, summarized four typical application scenarios, including intelligent pharmaceutical knowledge base/knowledge graph, intelligent on-the-job trai-ning, intelligent production quality control, and intelligent supply chain. Furthermore, this study also explained the data collection and processing, business process design, application potential, and value of each scenario based on industry demands. Finally, based on the integration of generative AI and TCM industrial models, the study proposed a preliminary concept of a smart industrial brain for TCM, aiming to provide a reference for the application of AI technology in the field of TCM manufacturing.

DARS expression in BCR/ABL1-negative myeloproliferative neoplasms and its association with the immune microenvironment.

DARS, encoding for aspartyl-tRNA synthetase, is implicated in the pathogenesis of various cancers, including renal cell carcinoma, glioblastoma, colon cancer, and gastric cancer. Its role in BCR/ABL1-negative myeloproliferative neoplasms (MPNs), however, remains unexplored. This study aimed to elucidate the expression of DARS in patients with MPNs (PV 23, ET 19, PMF 16) through immunohistochemical analysis and to examine the profiles of circulating immune cells and cytokines using flow cytometry. Our findings indicate a significant overexpression of DARS in all MPNs subtypes at the protein level compared to controls (P < 0.05). Notably, elevated DARS expression was linked to splenomegaly in MPNs patients. The expression of DARS showed a negative correlation with CD4+ T cells (R = - 0.451, P = 0.0004) and CD4+ T/CD8+ T cell ratio (R = - 0.3758, P = 0.0040), as well as with CD68+ tumor-associated macrophages (R = 0.4037, P = 0.0017). Conversely, it was positively correlated with IL-2 (R = 0.5419, P < 0.001), IL-5 (R = 0.3161, P = 0.0166), IL-6 (R = 0.2992, P = 0.0238), and IFN-γ (R = 0.3873, P = 0.0029). These findings underscore a significant association between DARS expression in MPNs patients and specific clinical characteristics, as well as immune cell composition. Further investigation into the interplay between DARS and the immune microenvironment in MPNs could shed light on the underlying mechanisms of MPNs pathogenesis and immune dysregulation.

Clinical characteristics and outcomes of overt gastrointestinal bleeding in children undergoing haploidentical hematopoietic stem cell transplantation: a single-center retrospective analysis.

BACKGROUND: Overt gastrointestinal bleeding (GIB) is a potentially serious and life-threatening condition in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, relatively little information is available regarding overt GIB in children. OBJECTIVES: To assess the prevalence, clinical patterns, and outcomes of overt GIB in children undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). METHODS: A total of 123 consecutive patients with malignant or non-malignant blood disorders who received haplo-HSCT were reviewed in our hospital between October 2017 and October 2022. Overt GIB was determined as hematemesis, melena or hematochezia. Continuous variables were compared by Mann Whitney U test. Categorical parameters were compared by the χ2 test or Fisher's exact test. Kaplan-Meier curves and log-rank tests were used to assess overall survival (OS), non-relapse mortality (NRM) and relapse. Univariate and multivariate analyses were performed to identify potential risk factors of overt GIB development. RESULTS: The median follow-up was 26.3 (range,1.7-74.8) months. Overt GIB occurred in 31 patients (25.2% incidence), with a median time elapsed after haplo-HSCT of 376 days (range, 58-1275 days). Compared with the non-GIB group, patients with overt GIB had reduced OS and increased NRM. In multivariate analysis, grade III-IV gut acute graft versus-host disease (aGvHD), thrombotic microangiopathy (TMA) and cytomegalovirus (CMV) viremia were significant risk factors for the occurrence of overt GIB after haplo-HSCT. CONCLUSIONS: Overt GIB is a frequent complication after haplo-HSCT in pediatric patients, and associated with worse survival. Grade III-IV gut aGvHD, TMA and CMV viremia were associated with its development.

Comparing the Saccule-to-Utricle Ratio in Early- Versus Late-Stage Meniere's Disease Patients.

OBJECTIVE: To compare the saccule-to-utricle ratio in early- versus late-stage Meniere's disease (MD) patients based on magnetic resonance imaging (MRI) images. METHODS: In this retrospective study, we performed 3-dimensional real inversion recovery (3D-real IR) MRI 24 h after intratympanic gadolinium administration in unilateral MD patients at early-stage (n = 56) and late-stage (n = 70). Two radiologists independently graded endolymphatic hydrops (EH) and the saccule-to-utricle ratio inversion (SURI) was compared between the two groups. Furthermore, early-stage MD patients were further divided into two subgroups based on disease duration: ≤6 months (n = 20) and >6 months (n = 36) and the SURI was compared. RESULTS: Among the 56 patients in the early-stage group, 26 cases (46.43%) exhibited an enlarged saccule that is larger than the utricle, showing SURI. In contrast, among the late-stage MD, only four cases (5.71%) showed SURI (p < 0.001). In the early-stage MD subgroup with a disease duration of ≤6 months, the proportion of SURI was 70% (14/20), which was higher than that in the subgroup with a disease duration of >6 months (33.33%, 12/36, p = 0.02). CONCLUSION: SURI may serve as an effective imaging marker for diagnosis of early-stage MD. Our finding suggests that endolymphatic hydrops in MD may primarily originate from the saccule. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 2024.

Bibliometric and Visual Analysis of Studies on Ceramic Membranes: A Review.

As a high-performance separation material, the ceramic membrane has played a crucial role in addressing resource, energy, and environmental challenges. Here, we carried out literature retrieval and collection for the research of ceramic membranes based on the Web of Science. The retrieval strategy was quantitatively evaluated from two dimensions: recall and precision. The distributions of publication time, journal, and related subjects were systematically analyzed. With the help of CiteSpace and VOSviewer, the literature was visually analyzed through the co-occurrence map of authors and the cluster network of keywords. The findings indicate a strong correlation between ceramic membrane research and the field of Chemical Engineering. A core group of authors has emerged as prominent contributors in this area of study. Additionally, there is a notable long-tail effect observed in the application of ceramic membranes. Despite their current low-frequency usage and high-volume potential, these applications hold substantial promise for future scientific research and industrial development.

EMA-YOLO: A Novel Target-Detection Algorithm for Immature Yellow Peach Based on YOLOv8.

Accurate determination of the number and location of immature small yellow peaches is crucial for bagging, thinning, and estimating yield in modern orchards. However, traditional methods have faced challenges in accurately distinguishing immature yellow peaches due to their resemblance to leaves and susceptibility to variations in shooting angles and distance. To address these issues, we proposed an improved target-detection model (EMA-YOLO) based on YOLOv8. Firstly, the sample space was enhanced algorithmically to improve the diversity of samples. Secondly, an EMA attention-mechanism module was introduced to encode global information; this module could further aggregate pixel-level features through dimensional interaction and strengthen small-target-detection capability by incorporating a 160 × 160 detection head. Finally, EIoU was utilized as a loss function to reduce the incidence of missed detections and false detections of the target small yellow peaches under the condition of high density of yellow peaches. Experimental results show that compared with the original YOLOv8n model, the EMA-YOLO model improves mAP by 4.2%, Furthermore, compared with SDD, Objectbox, YOLOv5n, and YOLOv7n, this model's mAP was improved by 30.1%, 14.2%,15.6%, and 7.2%, respectively. In addition, the EMA-YOLO model achieved good results under different conditions of illumination and shooting distance and significantly reduced the number of missed detections. Therefore, this method can provide technical support for smart management of yellow-peach orchards.

A novel mitochondrial-related lncRNA signature mediated prediction of overall survival, immune landscape, and the chemotherapeutic outcomes for bladder cancer patients.

OBJECTIVE: To develop a prognostic risk model for Bladder Cancer (BLCA) based on mitochondrial-related long non-coding RNAs (lncRNAs). METHODS: Transcriptome and clinical data of BLCA patients were retrieved from the TCGA database. Mitochondrial-related lncRNAs with independent prognostic significance were screened to develop a prognostic risk model. Patients were categorized into high- and low-risk groups using the model. Various methods including Kaplan-Meier (KM) analysis, ROC curve analysis, Gene Set Enrichment Analysis (GSEA), immune analysis, and chemotherapy drug analysis were used to verify and evaluate the model. RESULTS: A mitochondrial-associated lncRNA prognostic risk model with independent prognostic significance was developed. High-risk group (HRG) patients exhibited significantly shorter survival periods compared to low-risk group (LRG) patients (P < 0.01). The risk score from the model was an independent predictor of BLCA prognosis, correlating with tumor grade, pathological stage, and lymph node metastasis (P < 0.05). The HRG showed significant positive correlations with high expressions of immune checkpoints (CTLA4, LAG3, PD-1, TIGIT, PD-L1, PD-L2, and TIM-3) and lower IC50 for chemotherapy drugs (cisplatin, docetaxel, paclitaxel, methotrexate, and vinblastine) (P < 0.001). CONCLUSIONS: The mitochondrial-related lncRNA-based prognostic risk model effectively predicts BLCA prognosis and can guide individualized treatment for BLCA patients.

Lipids and Statin Medication With Sensorineural Hearing Loss: A Mendelian Randomization Study.

BACKGROUND: Recent insights suggest that lipids and statin medication play a role in the development of sensorineural hearing loss (SNHL), yet the exact role remains controversial. This research applied Mendelian randomization (MR) to assess whether lipids and statin medication are associated with an increased risk of SNHL. METHODS: A two-sample MR was used in this study. Genetic instruments were constructed from variants associated with risk factors. Data for lipids and statin medication were obtained from the IEU OpenGWAS project, and for SNHL from the Finngen research project, which comprises 32,487 individuals with SNHL and 331,736 control individuals. RESULTS: Genetically predicted higher levels of triglycerides were associated with an increased risk of SNHL. The use of genetically predicted atorvastatin was associated with a lower risk of SNHL. Rosuvastatin has demonstrated potential in treating SNHL, yet further investigations are warranted to elucidate its relationship with SNHL. Insufficient evidence was available to suggest that the genetically predicted level of high-density lipoprotein cholesterol or low-density lipoprotein cholesterol or the use of simvastatin were associated with SNHL. CONCLUSIONS: The study provides genetic evidence suggesting that increased levels of triglycerides in the blood could be a risk factor for SNHL and that the use of certain statin medications, including atorvastatin and rosuvastatin, could reduce the risk of SNHL. These results align with findings from previous observational studies that have linked hyperlipidemia with the risk of SNHL. LEVEL OF EVIDENCE: According to the Oxford Centre for Evidence-Based Medicine 2011 levels of Evidence, the study has a third level of Evidence Laryngoscope, 2024.

Comparison of upfront haploidentical hematopoietic stem cell transplantation and salvage haploidentical hematopoietic stem cell transplantation after immunosuppressive therapy in children with acquired severe aplastic anemia - a multicenter study.

Background: For children with severe aplastic anemia, if the first immunosuppressive therapy (IST) fails, it is not recommended to choose a second IST. Therefore, for patients without matched sibling donor (MSD) and matched unrelated donor (MUD), haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) can be chosen as a salvage treatment. This article aims to explore the comparison between upfront Haplo-HSCT and salvage Haplo-HSCT after IST. Methods: 29 patients received salvage Haplo-HSCT, and 50 patients received upfront Haplo-HSCT. The two groups received Bu (Busulfan, 3.2mg/kg/d*2d on days -9 to-8), CY (Cyclophosphamide, 60mg/kg/d*2d on days -4 to-3), Flu (fludarabine, 40mg/m2/d*5d on days -9 to -5) and rabbit ATG (Anti-thymocyte globulin, total dose 10mg/kg divided into days -4 to -2). Results: The OS of the salvage Haplo-HSCT group showed no difference to the upfront Haplo-HSCT group (80.2 ± 8.0% vs. 88.7 ± 4.8%, p=0.37). The FFS of the salvage Haplo-HSCT group also showed no difference to the frontline Haplo-HSCT group (75 ± 8.2% vs. 84.9 ± 5.3%, p=0.27). There was no significant difference in the incidence of other complications after transplantation between the two groups, except for thrombotic microangiopathy (TMA). In the grouping analysis by graft source, the incidence of II-IV aGVHD in patients using PBSC ± BM+UCB was lower than that in the PBSC ± BM group (p=0.010). Conclusion: Upfront Haplo-HSCT and salvage Haplo-HSCT after IST in children with acquired severe aplastic anemia have similar survival outcomes. However, the risk of TMA increases after salvage Haplo-HSCT. This article provides some reference value for the treatment selection of patients. In addition, co-transplantation of umbilical cord blood may reduce the incidence of GVHD.

Transient cavity-cavity strong coupling at terahertz frequency on LiNbO3 chips.

Terahertz (THz) microcavities have garnered considerable attention for their ability to localize and confine THz waves, allowing for strong coupling to remarkably enhance the light-matter interaction. These properties hold great promise for advancing THz science and technology, particularly for high-speed integrated THz chips where transient interaction between THz waves and matter is critical. However, experimental study of these transient time-domain processes requires high temporal and spatial resolution since these processes, such as THz strong coupling, occur in several picoseconds and microns. Thus, most literature studies rarely cover temporal and spatial processes at the same time. In this work, we thoroughly investigate the transient cavity-cavity strong-coupling phenomena at THz frequency and find a Rabi-like oscillation in the microcavities, manifested by direct observation of a periodic energy exchange process via a phase-contrast time-resolved imaging system. Our explanation, based on the Jaynes-Cummings model, provides theoretical insight into this transient strong-coupling process. This work provides an opportunity to deeply understand the transient strong-coupling process between THz microcavities, which sheds light on the potential of THz microcavities for high-speed THz sensor and THz chip design.

Upgrading CO2 to sustainable aromatics via perovskite-mediated tandem catalysis.

The directional transformation of carbon dioxide (CO2) with renewable hydrogen into specific carbon-heavy products (C6+) of high value presents a sustainable route for net-zero chemical manufacture. However, it is still challenging to simultaneously achieve high activity and selectivity due to the unbalanced CO2 hydrogenation and C-C coupling rates on complementary active sites in a bifunctional catalyst, thus causing unexpected secondary reaction. Here we report LaFeO3 perovskite-mediated directional tandem conversion of CO2 towards heavy aromatics with high CO2 conversion (> 60%), exceptional aromatics selectivity among hydrocarbons (> 85%), and no obvious deactivation for 1000 hours. This is enabled by disentangling the CO2 hydrogenation domain from the C-C coupling domain in the tandem system for Iron-based catalyst. Unlike other active Fe oxides showing wide hydrocarbon product distribution due to carbide formation, LaFeO3 by design is endowed with superior resistance to carburization, therefore inhibiting uncontrolled C-C coupling on oxide and isolating aromatics formation in the zeolite. In-situ spectroscopic evidence and theoretical calculations reveal an oxygenate-rich surface chemistry of LaFeO3, that easily escape from the oxide surface for further precise C-C coupling inside zeolites, thus steering CO2-HCOOH/H2CO-Aromatics reaction pathway to enable a high yield of aromatics.

[Clinical Analysis of Mitoxantrone Liposome in the Treatment of Children with High-Risk Acute Myeloid Leukemia].

OBJECTIVE: To investigate the safety and efficacy of mitoxantrone liposome in the treatment of children with high-risk acute myeloid leukemia (AML). METHODS: The children with high-risk AML who received the mitoxantrone liposome regimen at Wuhan Children's Hospital from January 2022 to February 2023 were collected as the observation group, and the children with high-risk AML who received idarubicin regimen were enrolled as controls, and their clinical data were analyzed. Time to bone marrow recovery, the complete remission rate of bone marrow cytology, the clearance rate of minimal residual disease, and treatment-related adverse reactions were compared between the two groups. RESULTS: The patients treated with mitoxantrone liposome showed shorter time to recovery of leukocytes(17 vs 21 day), granulocytes(18 vs 24 day), platelets(17 vs 24 day), and hemoglobin(20 vs 26 day) compared with those treated with idarubicin, there were statistical differences (P <0.05). The effective rate and MRD turning negative rate in the observation group were 90.9% and 72.7%, respectively, while those in the control group were 94.1% and 76.4%, with no statistical difference (P >0.05). The overall response rate of the two groups of patients was similar. CONCLUSION: The efficacy of mitoxantrone liposome is not inferior to that of idarubicin in children with high-risk AML, but mitoxantrone liposome allows a significantly shorter duration of bone marrow suppression and the safety is better.

Associations of the circulating levels of cytokines with the risk of myeloproliferative neoplasms: a bidirectional mendelian-randomization study.

OBJECTIVE: In the pathogenesis of myeloproliferative neoplasms (MPN), inflammation plays an important role. However, it is unclear whether there is a causal link between inflammation and MPNs. We used a bidirectional, two-sample Mendelian randomization (MR) approach to investigate the causal relationship between systemic inflammatory cytokines and myeloproliferative neoplasms. METHODS: A genome-wide association study (GWAS) of 8293 European participants identified genetic instrumental variables for circulating cytokines and growth factors. Summary statistics of MPN were obtained from a GWAS including 1086 cases and 407,155 controls of European ancestry. The inverse-variance-weighted method was mainly used to compute odds ratios (OR) and 95% confidence intervals (Cl). RESULTS: Our results showed that higher Interleukin-2 receptor, alpha subunit (IL-2rα) levels, and higher Interferon gamma-induced protein 10 (IP-10) levels were associated with an increased risk of MPN (OR = 1.36,95%CI = 1.03-1.81, P = 0.032; OR = 1.55,95%CI = 1.09-2.22, P = 0.015; respectively).In addition, Genetically predicted MPN promotes expression of the inflammatory cytokines interleukin-10 (IL-10) (BETA = 0.033, 95% CI = 0.003 ~ 0.064, P = 0.032) and monokine induced by interferon-gamma (MIG) (BETA = 0.052, 95% CI = 0.002-0.102, P = 0.043) and, on activation, normal T cells express and secrete RANTES (BETA = 0.055, 95% CI = 0.0090.1, P = 0.018). CONCLUSION: Our findings suggest that cytokines are essential to the pathophysiology of MPN. More research is required if these biomarkers can be used to prevent and treat MPN.

Boswellianols A-I, Structurally Diverse Diterpenoids from the Oleo-Gum Resin of Boswellia carterii and Their TGF-ß Inhibition Activity.

Olibanum, a golden oleo-gum resin from species in the Boswellia genus (Burseraceae family), is a famous traditional herbal medicine widely used around the world. Previous phytochemical studies mainly focused on the non-polar fractions of olibanum. In this study, nine novel diterpenoids, boswellianols A-I (1-9), and three known compounds were isolated from the polar methanolic fraction of the oleo-gum resin of Boswellia carterii. Their structures were determined through comprehensive spectroscopic analysis as well as experimental and calculated electronic circular dichroism (ECD) data comparison. Compound 1 is a novel diterpenoid possessing an undescribed prenylmaaliane-type skeleton with a 6/6/3 tricyclic system. Compounds 2-4 were unusual prenylaromadendrane-type diterpenoids, and compounds 5-9 were new highly oxidized cembrane-type diterpenoids. Compounds 1 and 5 showed significant transforming growth factor ß (TGF-ß) inhibitory activity via inhibiting the TGF-ß-induced phosphorylation of Smad3 and the expression of fibronectin and N-cadherin (the biomarker of the epithelial-mesenchymal transition) in a dose-dependent manner in LX-2 human hepatic stellate cells, indicating that compounds 1 and 5 should be potential anti-fibrosis agents. These findings give a new insight into the chemical constituents of the polar fraction of olibanum and their inhibitory activities on the TGF-ß/Smad signaling pathway.

Characteristics of spatial protein expression in the mouse cochlear sensory epithelia: Implications for age-related hearing loss.

Hair cells in the cochlear sensory epithelia serve as mechanosensory receptors, converting sound into neuronal signals. The basal sensory epithelia are responsible for transducing high-frequency sounds, while the apex handles low-frequency sounds. Age-related hearing loss predominantly affects hearing at high frequencies and is indicative of damage to the basal sensory epithelia. However, the precise mechanism underlying this site-selective injury remains unclear. In this study, we employed a microscale proteomics approach to examine and compare protein expression in different regions of the cochlear sensory epithelia (upper half and lower half) in 1.5-month-old (normal hearing) and 6-month-old (severe high-frequency hearing loss without hair cell loss) C57BL/6J mice. A total of 2,386 proteins were detected, and no significant differences in protein expression were detected in the upper half of the cochlear sensory epithelia between the two age groups. The expression of 20 proteins in the lower half of the cochlear sensory epithelia significantly differed between the two age groups (e.g., MATN1, MATN4, and AQP1). Moreover, there were 311 and 226 differentially expressed proteins between the upper and lower halves of the cochlear sensory epithelia in 1.5-month-old and 6-month-old mice, respectively. The expression levels of selected proteins were validated by Western blotting. These findings suggest that the spatial differences in protein expression within the cochlear sensory epithelia may play a role in determining the susceptibility of cells at different sites of the cochlea to age-related damage.

Delirium and incident dementia in hospital patients in New South Wales, Australia: retrospective cohort study.

OBJECTIVES: To determine the strength and nature of the association between delirium and incident dementia in a population of older adult patients without dementia at baseline. DESIGN: Retrospective cohort study using large scale hospital administrative data. SETTING: Public and private hospitals in New South Wales, Australia between July 2001 and March 2020. PARTICIPANTS: Data were extracted for 650 590 hospital patients aged ≥65 years. Diagnoses of dementia and delirium were identified from ICD-10 (international classification of diseases, 10th revision) codes. Patients with dementia at baseline were excluded. Delirium-no delirium pairs were identified by matching personal and clinical characteristics, and were followed for more than five years. MAIN OUTCOME MEASURES: Cox proportional hazards models and Fine-Gray hazard models were used to estimate the associations of delirium with death and incident dementia, respectively. Delirium-outcome dose-response associations were quantified, all analyses were performed in men and women separately, and sensitivity analyses were conducted. RESULTS: The study included 55 211 matched pairs (48% men, mean age 83.4 years, standard deviation 6.5 years). Collectively, 58% (n=63 929) of patients died and 17% (n=19 117) had a newly reported dementia diagnosis during 5.25 years of follow-up. Patients with delirium had 39% higher risk of death (hazard ratio 1.39, 95% confidence interval 1.37 to 1.41) and three times higher risk of incident dementia (subdistribution hazard ratio 3.00, 95% confidence interval 2.91 to 3.10) than patients without delirium. The association with dementia was stronger in men (P=0.004). Each additional episode of delirium was associated with a 20% increased risk of dementia (subdistribution hazard ratio 1.20, 95% confidence interval 1.18 to 1.23). CONCLUSIONS: The study findings suggest delirium was a strong risk factor for death and incident dementia among older adult patients. The data support a causal interpretation of the association between delirium and dementia. The clinical implications of delirium as a potentially modifiable risk factor for dementia are substantial.