The application of multi-criteria decision analysis in evaluating the value of drug-oriented intervention: a literature review.

Objectives: Multi-Criteria Decision Analysis (MCDA) has gained increasing attention in supporting drug risk-benefit assessment, pricing and reimbursement, as well as optimization of clinical interventions. The objective of this study was to systematically collect and categorize evaluation criteria and techniques of weighting and scoring of MCDA for drug value assessment. Methods: A systematic review of the literature was conducted across seven databases to identify articles utilizing the MCDA frameworks for the evaluation of drug value. Evaluation criteria mentioned in the included studies were extracted and assigned to 5 dimensions including clinical, economic, innovative, societal and humanistic value. A descriptive statistical analysis was performed on the identified drug value evaluation criteria, as well as the weighting and scoring techniques employed. The more a criterion or technique were mentioned in articles, the more important we consider it. Results: Out of the 82 articles included, 111 unique criteria were identified to evaluate the value of drug. Among the 56 unique criteria (448 times) used to measure clinical value, the most frequently mentioned were "comparative safety/tolerability" (58 times), "comparative effectiveness/efficacy" (56 times), "comparative patient-perceived health/patient reported outcomes" (37 times), "disease severity" (34 times), and "unmet needs" (25 times). Regarding economic value measurement, out of the 20 unique criteria (124 times), the most frequently utilized criteria were "cost of intervention" (17 times), "comparative other medical costs" (16 times), and "comparative non-medical costs" (18 times). Out of the 10 criteria (18 times) for assessing innovative value, "a novel pharmacological mechanism" was the most frequently mentioned criterion (5 times). Among the 22 criteria (73 times) used to measure societal value, "system capacity and appropriate use of intervention" was the most frequently cited criterion (14 times). Out of the 3 criteria (15 times) utilized to measure humanistic value, "political/historical/cultural context" was the most frequently mentioned criterion (9 times). Furthermore, 11 scoring and 11 weighting techniques were found from various MCDA frameworks. "Swing weighting" and "a direct rating scale" were the most frequently used techniques in included articles. Conclusion: This study comprehensively presented the current evaluation dimensions, criteria, and techniques for scoring and weighting in drug-oriented MCDA articles. By highlighting the frequently cited evaluation criteria and techniques for scoring and weighting, this analysis will provide a foundation to reasonably select appropriate evaluation criteria and technique in constructing the MCDA framework that aligns with research objectives.

A study on the application of radiomics based on cardiac MR non-enhanced cine sequence in the early diagnosis of hypertensive heart disease.

BACKGROUND: The prevalence of hypertensive heart disease (HHD) is high and there is currently no easy way to detect early HHD. Explore the application of radiomics using cardiac magnetic resonance (CMR) non-enhanced cine sequences in diagnosing HHD and latent cardiac changes caused by hypertension. METHODS: 132 patients who underwent CMR scanning were divided into groups: HHD (42), hypertension with normal cardiac structure and function (HWN) group (46), and normal control (NOR) group (44). Myocardial regions of the end-diastolic (ED) and end-systolic (ES) phases of the CMR short-axis cine sequence images were segmented into regions of interest (ROI). Three feature subsets (ED, ES, and ED combined with ES) were established after radiomic least absolute shrinkage and selection operator feature selection. Nine radiomic models were built using random forest (RF), support vector machine (SVM), and naive Bayes. Model performance was analyzed using receiver operating characteristic curves, and metrics like accuracy, area under the curve (AUC), precision, recall, and specificity. RESULTS: The feature subsets included first-order, shape, and texture features. SVM of ED combined with ES achieved the highest accuracy (0.833), with a macro-average AUC of 0.941. AUCs for HHD, HWN, and NOR identification were 0.967, 0.876, and 0.963, respectively. Precisions were 0.972, 0.740, and 0.826; recalls were 0.833, 0.804, and 0.863, respectively; and specificities were 0.989, 0.863, and 0.909, respectively. CONCLUSIONS: Radiomics technology using CMR non-enhanced cine sequences can detect early cardiac changes due to hypertension. It holds promise for future use in screening for latent cardiac damage in early HHD.

LcDel: deletion variation detection based on clustering and long reads.

Motivation: Genomic structural variation refers to chromosomal level variations such as genome rearrangement or insertion/deletion, which typically involve larger DNA fragments compared to single nucleotide variations. Deletion is a common type of structural variants in the genome, which may lead to mangy diseases, so the detection of deletions can help to gain insights into the pathogenesis of diseases and provide accurate information for disease diagnosis, treatment, and prevention. Many tools exist for deletion variant detection, but they are still inadequate in some aspects, and most of them ignore the presence of chimeric variants in clustering, resulting in less precise clustering results. Results: In this paper, we present LcDel, which can detect deletion variation based on clustering and long reads. LcDel first finds the candidate deletion sites and then performs the first clustering step using two clustering methods (sliding window-based and coverage-based, respectively) based on the length of the deletion. After that, LcDel immediately uses the second clustering by hierarchical clustering to determine the location and length of the deletion. LcDel is benchmarked against some other structural variation detection tools on multiple datasets, and the results show that LcDel has better detection performance for deletion. The source code is available in https://github.com/cyq1314woaini/LcDel.

Enhanced Hydrogen Evolution Catalysis of Pentlandite due to the Increases in Coordination Number and Sulfur Vacancy during Cubic-Hexagonal Phase Transition.

The search for new phases is an important direction in materials science. The phase transition of sulfides results in significant changes in catalytic performance, such as MoS2 and WS2 . Cubic pentlandite [cPn, (Fe, Ni)9 S8 ] can be a functional material in batteries, solar cells, and catalytic fields. However, no report about the material properties of other phases of pentlandite exists. In this study, the unit-cell parameters of a new phase of pentlandite, sulfur-vacancy enriched hexagonal pentlandite (hPn), and the phase boundary between cPn and hPn are determined for the first time. Compared to cPn, the hPn shows a high coordination number, more sulfur vacancies, and high conductivity, which result in significantly higher hydrogen evolution performance of hPn than that of cPn and make the non-nano rock catalyst hPn superior to other most known nanosulfide catalysts. The increase of sulfur vacancies during phase transition provides a new approach to designing functional materials.

Predicting Risk Stratification in Early-Stage Endometrial Carcinoma: Significance of Multiparametric MRI Radiomics Model.

Endometrial carcinoma (EC) risk stratification prior to surgery is crucial for clinical treatment. In this study, we intend to evaluate the predictive value of radiomics models based on magnetic resonance imaging (MRI) for risk stratification and staging of early-stage EC. The study included 155 patients who underwent MRI examinations prior to surgery and were pathologically diagnosed with early-stage EC between January, 2020, and September, 2022. Three-dimensional radiomics features were extracted from segmented tumor images captured by MRI scans (including T2WI, CE-T1WI delayed phase, and ADC), with 1521 features extracted from each of the three modalities. Then, using five-fold cross-validation and a multilayer perceptron algorithm, these features were filtered using Pearson's correlation coefficient to develop a prediction model for risk stratification and staging of EC. The performance of each model was assessed by analyzing ROC curves and calculating the AUC, accuracy, sensitivity, and specificity. In terms of risk stratification, the CE-T1 sequence demonstrated the highest predictive accuracy of 0.858 ± 0.025 and an AUC of 0.878 ± 0.042 among the three sequences. However, combining all three sequences resulted in enhanced predictive accuracy, reaching 0.881 ± 0.040, with a corresponding increase in the AUC to 0.862 ± 0.069. In the context of staging, the utilization of a combination involving T2WI with CE-T1WI led to a notably elevated predictive accuracy of 0.956 ± 0.020, surpassing the accuracy achieved when employing any singular feature. Correspondingly, the AUC was 0.979 ± 0.022. When incorporating all three sequences concurrently, the predictive accuracy reached 0.956 ± 0.000, accompanied by an AUC of 0.986 ± 0.007. It is noteworthy that this level of accuracy surpassed that of the radiologist, which stood at 0.832. The MRI radiomics model has the potential to accurately predict the risk stratification and early staging of EC.

Tripterygium wilfordii Hook.f induced kidney injury through mediating inflammation via PI3K-Akt/HIF-1/TNF signaling pathway: A study of network toxicology and molecular docking.

We intend to explore potential mechanisms of Tripterygium wilfordii Hook.f (TwHF) induced kidney injury (KI) using the methods of network toxicology and molecular docking. We determined TwHF potential compounds with its targets and KI targets, obtained the TwHF induced KI targets after intersecting targets of TwHF and KI. Then we conducted protein-protein interaction (PPI) network, gene expression analysis, gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis to explore the mechanism of TwHF-induced KI. Finally we conducted molecular docking to verify the core toxic compounds and the targets. We obtained 12 TwHF toxic compounds and 62 TwHF-induced KI targets. PPI network, gene expression analysis and GO function enrichment analysis unveiled the key biological process and suggested the mechanism of TwHF-induced KI might be associated with inflammation, immune response, hypoxia as well as oxidative stress. KEGG pathway enrichment analysis indicated PI3K-Akt signaling pathway, HIF-1 signaling pathway and TNF signaling pathway were key signaling pathways of TwHF induced KI. Molecular docking showed that the binding energy of core targets and toxic compounds was all less than -6.5 kcal/mol that verified the screening ability of network pharmacology and provided evidence for modifying TwHF toxic compounds structure. Through the study, we unveiled the mechanism of TwHF induce KI that TwHF might activate PI3K-Akt signaling pathway as well as TNF signaling pathway to progress renal inflammation, mediate hypoxia via HIF-1 signaling pathway to accelerate inflammatory processes, and also provided a theoretical basis for modifying TwHF toxic compounds structure as well as supported the follow-up research.

Study on Synergistic Effects of Nanohydroxyapatite/High-Viscosity Carboxymethyl Cellulose Scaffolds Stimulated by LIPUS for Bone Defect Repair of Rats.

Despite the self-healing capacity of bone, the regeneration of critical-size bone defects remains a major clinical challenge. In this study, nanohydroxyapatite (nHAP)/high-viscosity carboxymethyl cellulose (hvCMC, 6500 mPa·s) scaffolds and low-intensity pulsed ultrasound (HA-LIPUS) were employed to repair bone defects. First, hvCMC was prepared from ramie fiber, and the degree of substitution (DS), purity, and content of NaCl of hvCMC samples were 0.91, 99.93, and 0.017%, respectively. Besides, toxic metal contents were below the permissible limits for pharmaceutically used materials. Our results demonstrated that the hvCMC is suitable for pharmaceutical use. Second, nHAP and hvCMC were employed to prepare scaffolds by freeze-drying. The results indicated that the scaffolds were porous, and the porosity was 35.63 ± 3.52%. Subsequently, the rats were divided into four groups (n = 8) randomly: normal control (NC), bone defect (BD), bone defect treated with nHAP/hvCMC scaffolds (HA), and bone defect treated with nHAP/hvCMC scaffolds and stimulated by LIPUS (HA-LIPUS). After drilling surgery, nHAP/hvCMC scaffolds were implanted in the defect region of HA and HA-LIPUS rats. Meanwhile, HA-LIPUS rats were treated by LIPUS (1.5 MHz, 80 mW cm-2) irradiation for 2 weeks. Compared with BD rats, the maximum load and bone mineral density of HA-LIPUS rats were increased by 20.85 and 51.97%, respectively. The gene and protein results indicated that nHAP/hvCMC scaffolds and LIPUS promoted the bone defect repair and regeneration of rats significantly by activating Wnt/ß-catenin and inhibiting OPG/RANKL signaling pathways. Overall, compared with BD rats, nHAP/hvCMC scaffolds and LIPUS promoted bone defect repair significantly. Furthermore, the research results also indicated that there are synergistic effects for bone defect repair between the nHAP/hvCMC scaffolds and LIPUS.

Enrichment efficiency of lutein in eggs and its function in improving fatty liver hemorrhagic syndrome in aged laying hens.

In this study, we evaluated the enrichment efficiency of lutein in eggs and its function in preventing fatty liver hemorrhagic syndrome (FLHS) in aged laying hens. Five groups of laying hens (65 wk old) were fed basal diets supplemented with 0, 30, 60, 90, or 120 mg/kg of lutein. The supplementation period lasted 12 wk followed by 2 wk of lutein depletion in feed. The results revealed that lutein efficiently enriched the egg yolks and improved their color with a significant increase in relative redness (P < 0.001). Lutein accumulation increased in the egg yolk until day 10, then depletion reached a minimum level after 14 d. Overall, zeaxanthin content in all the groups was similar throughout the experimental period. However, triglycerides and total cholesterol were significantly decreased in the liver (P < 0.05) but not significantly different in the serum (P > 0.05). In the serum, the lipid metabolism enzyme acetyl-CoA synthetase was significantly reduced (P < 0.05), whereas dipeptidyl-peptidase 4 was not significantly different (P > 0.05), and there was no statistical difference of either enzyme in the liver (P > 0.05). Regarding oxidation and inflammation-related indexes, malondialdehyde, tumor necrosis factors alpha, interleukin-6, and interleukin-1 beta were decreased, whereas superoxide dismutase and total antioxidant capacity increased in the liver (P < 0.001). The function of lutein for the same indexes in serum was limited. It was concluded that lutein efficiently enriched the egg yolk of old laying hens to improve their color and reached the highest level on day 10 without being subject to a significant conversion into zeaxanthin. At the same time, lutein prevented liver steatosis in aged laying hens by exerting strong antioxidant and anti-inflammatory functions, but also through the modulation of lipid metabolism, which may contribute to reducing the incidence of FLHS in poultry.

Arginine Biosynthesis Pathway Found to Play a Key Role in the Neuroprotective Effect of Liu-Wei-Luo-Bi (LWLB) Granules in Diabetic db/db Mice with Peripheral Neuropathy Using an Untargeted Metabolomics Strategy.

Aim: Liu-Wei-Luo-Bi (LWLB) granules was a Chinese compound prescription for treating diabetic peripheral neuropathy (DPN). The aim of this study was to investigate the effect of LWLB granules on diabetic mice with peripheral neuropathy and to elucidate the potential mechanism based on an untargeted metabolomics approach. Methods: One hundred forty db/db mice were randomly divided into seven groups: the Control group, DPN group, Mudan (MD) granules group, Epalrestat (Epa) group, and the LWLB low, medium, or high dose (LW-l, LW-m, or LW-h) group. After 12 weeks of treatment, body weight, blood glucose, mechanical pain threshold, motor conduction velocity (MCV), sensory conduction velocity (SCV), and Pathological Organization of the Sciatic and Caudal Nerves in mice were measured. Serum samples were collected for untargeted metabolomics analysis using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and multivariate statistics. Disease-related pathways were screened out with function enrichment analyses of candidate biomarkers. Results: LWLB granules can improve the peripheral neuropathy of type 2 diabetic mice with peripheral nerve conduction disorders, mainly through significantly improving the nerve conduction velocity (P < 0.05) and lowering the mechanical pain threshold (P < 0.05). A total of 43 metabolites were identified as potential biomarkers related to the therapeutic effect of LWLB granules. Fifty, 4, and 26; 23, 4, and 22; and 24, 1, and 16 biomarkers were discovered in the LW-l, LW-m, and LW-h groups at the 4th, 6th, and 12th weeks, respectively. Five, three, seven, five, and four metabolic pathways were found in MD, Epa, LW-l, LW-m, and LW-h groups, respectively. The arginine biosynthesis pathway is the overlapping pathway in LW-l, LW-m, and LW-h groups. Conclusion: LWLB granules have an obvious neuroprotective effect on diabetic peripheral neuropathy, and the metabolism mechanism of LWLB is mainly related to the arginine biosynthesis pathway on diabetic db/db mice with peripheral neuropathy.

[Expert consensus on core indicators for lifecycle value assessment of Chinese patent medicine].

The establishment of core indicators for assessment plays an important role in carrying out the lifecycle value assessment of Chinese patent medicine, which are developed based on the concepts such as clinical value oriented, paying attention to the human use experience, and whole process quality control. To this end, the Specialty Committee of Data Monitoring and Decision Making of the World Federation of Chinese Medicine Societies organized experts to draft the Expert Consensus on Core Indicators for Lifecycle Value Assessment of Chinese Patent Medicine based on the research including Chinese Medicine Registration Review Evidence System in Combination of Traditional Chinese Medicine Theory, Human Use Experience, and Clinical Trials(GZY-FJS-2022-206) by National Administration of Traditional Chinese Medicine. This consensus proposed 92 core indicators from four stages, including new drug R&D project approval, pre-clinical research, new drug marketing authorization, and post-marketing, combining the assessment purposes and needs of different stakeholders from different dimensions such as clinical needs, clinical positioning, human use experience, effectiveness, safety, quality control, innovation, accessibility, and suitability. This consensus also interpreted the indicators to clearly elucidate the core elements of the value assessment of Chinese patent medicine in different R&D stages and guided the stakeholders to identify, analyze, and assess the value of Chinese patent medicine in the R&D and use process based on the core indicators in a scientific, objective, and standardized approach. This consensus is expected to play an important role in the high-quality new drug development, drug pricing and compensation of Chinese patent medicine, the development of clinical pathways, and rational clinical application.

Endoscopic characteristics and high-risk background mucosa factors of early gastric cancer after helicobacter pylori eradication: a single-center retrospective study.

Purpose: Gastric cancer still develops after successful Helicobacter pylori(Hp)eradication. In this study, we aimed to explore the characteristics and risks of mucosal factors. Methods: A total of 139 early gastric cancers (EGC) diagnosed in 133 patients after successful eradication from January 2016 to December 2021 were retrospectively included in the Hp-eradication EGC group and 170 EGCs diagnosed in 158 patients were included in the Hp-positive EGC group. We analyzed the clinical, pathological, and endoscopic characteristics between the two groups to identify the features of EGC after Hp eradication. Another 107 patients with no EGC after Hp eradication were enrolled in a Hp-eradication non-EGC group. The background mucosal factors between the Hp-eradication EGC group and the Hp-eradication non-EGC group were compared to analyze the high-risk background mucosal factors of EGC after eradication. In addition, we divided the EGC group after Hp eradication into IIc type and non-IIc type according to endoscopic gross classification to assess the high-risk background factors of IIc-type EGC after Hp eradication. Results: The endoscopic features of EGC after Hp eradication included location in the lower part of the stomach (p=0.001), yellowish color (p= 0.031), and smaller size (p=0.001). The moderate/severe gastric atrophy (GA), intestinal metaplasia (IM) in the corpus, severe diffuse redness, and map-like redness were risk factors for EGC after eradication (p=0.001, p=0.001, p=0.001, and p= 0.005, respectively). The Kyoto classification total score in the EGC group was higher than the non-EGC group (4 vs.3 p<0.001). A multivariate analysis revealed that depressed erosion (OR=3.42, 95% CI 1.35-8.65, p= 0.009) was an independent risk factor for IIc-type EGC after Hp eradication. Conclusion: EGC after eradication are smaller and yellowish lesions located in the lower part of the stomach. The risk background mucosal factors include moderate/severe GA, IM in the corpus, severe diffuse redness, and map-like redness. The Kyoto classification total score of 4 or more after successful eradication treatment might indicate EGC risk. In addition, the IIc-type EGC should be cautioned in the presence of depressed erosion after Hp eradication.

CaWRKY50 Acts as a Negative Regulator in Response to Colletotrichum scovillei Infection in Pepper.

Chili anthracnose is one of the most common and destructive fungal pathogens that affects the yield and quality of pepper. Although WRKY proteins play crucial roles in pepper resistance to a variety of pathogens, the mechanism of their resistance to anthracnose is still unknown. In this study, we found that CaWRKY50 expression was obviously induced by Colletotrichum scovillei infection and salicylic acid (SA) treatments. CaWRKY50-silencing enhanced pepper resistance to C. scovillei, while transient overexpression of CaWRKY50 in pepper increased susceptibility to C. scovillei. We further found that overexpression of CaWRKY50 in tomatoes significantly decreased resistance to C. scovillei by SA and reactive oxygen species (ROS) signaling pathways. Moreover, CaWRKY50 suppressed the expression of two SA-related genes, CaEDS1 (enhanced disease susceptibility 1) and CaSAMT1 (salicylate carboxymethyltransferase 1), by directly binding to the W-box motif in their promoters. Additionally, we demonstrated that CaWRKY50 interacts with CaWRKY42 and CaMIEL1 in the nucleus. Thus, our findings revealed that CaWRKY50 plays a negative role in pepper resistance to C. scovillei through the SA-mediated signaling pathway and the antioxidant defense system. These results provide a theoretical foundation for molecular breeding of pepper varieties resistant to anthracnose.

Low-intensity pulsed ultrasound mitigates cognitive impairment by inhibiting muscle atrophy in hindlimb unloaded mice.

Microgravity leads to muscle loss, usually accompanied by cognitive impairment. Muscle reduction was associated with the decline of cognitive ability. Our previous studies showed that low-intensity pulsed ultrasound (LIPUS) promoted muscle hypertrophy and prevented muscle atrophy. This study aims to verify whether LIPUS can improve cognitive impairment by preventing muscle atrophy in hindlimb unloaded mice. In this study, mice were randomly divided into normal control (NC), hindlimb unloading (HU), hindlimb unloading + LIPUS (HU+LIPUS) groups. The mice in the HU+LIPUS group received a 30 mW/cm2 LIPUS irradiation on gastrocnemius for 20 min/d. After 21 days, LIPUS significantly prevented the decrease in muscle mass and strength caused by tail suspension. The HU+LIPUS mice showed an enhanced desire to explore unfamiliar environments and their spatial learning and memory abilities, enabling them to quickly identify differences between different objects, as well as their social discrimination abilities. MSTN is a negative regulator of muscle growth and also plays a role in regulating cognition. LIPUS significantly inhibited MSTN expression in skeletal muscle and serum and its receptor ActRIIB expression in brain, upregulated AKT and BDNF expression in brain. Taken together, LIPUS may improve the cognitive dysfunction in hindlimb unloaded rats by inhibiting muscle atrophy through MSTN/AKT/BDNF pathway.

Manganese-doped albumin-gelatin composite nanogel loaded with berberine applied to the treatment of gouty arthritis in rats via a SPARC-dependent mechanism.

In this study, manganese-doped albumin-gelatin composite nanogels (MAGN) were prepared and used to load berberine (Ber) for the treatment of gouty arthritis (GA). The nanodrug delivery system (Ber-MAGN) can target inflammatory joints due to the intrinsic high affinity of albumin for SPARC, which is overexpressed at the inflammatory site of GA. Characterization of the pharmaceutical properties in vitro showed that Ber-MAGN had good dispersion, and the particle size was 121 ± 10.7 nm. The sustained release effect significantly improved the bioavailability of berberine. In vitro and in vivo experimental results showed that Ber-MAGN has better therapeutic effects in relieving oxidative stress and suppressing inflammation. Therefore, Ber-MAGN, as a potential pharmaceutical preparation for GA, provides a new reference for the clinical treatment plan of GA.

Encapsulation of Selenium Nanoparticles and Metformin in Macrophage-Derived Cell Membranes for the Treatment of Spinal Cord Injury.

Spinal cord injury is an impact-induced disabling condition. A series of pathological changes after spinal cord injury (SCI) are usually associated with oxidative stress, inflammation, and apoptosis. These pathological changes eventually lead to paralysis. The short half-life and low bioavailability of many drugs also limit the use of many drugs in SCI. In this study, we designed nanovesicles derived from macrophages encapsulating selenium nanoparticles (SeNPs) and metformin (SeNPs-Met-MVs) to be used in the treatment of SCI. These nanovesicles can cross the blood-spinal cord barrier (BSCB) and deliver SeNPs and Met to the site of injury to exert anti-inflammatory and reactive oxygen species scavenging effects. Transmission electron microscopy (TEM) images showed that the SeNPs-Met-MVs particle size was approximately 125 ± 5 nm. Drug release assays showed that Met exhibited sustained release after encapsulation by the macrophage cell membrane. The cumulative release was approximately 80% over 36 h. In vitro cellular experiments and in vivo animal experiments demonstrated that SeNPs-Met-MVs decreased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and reduced the expression of inflammatory (TNF-α, IL-1ß, and IL-6) and apoptotic (cleaved caspase-3) cytokines in spinal cord tissue after SCI. In addition, motor function in mice was significantly improved after SeNPs-Met-MVs treatment. Therefore, SeNPs-Met-MVs have a promising future in the treatment of SCI.

Cell type-specific cytonuclear coevolution in three allopolyploid plant species.

Cytonuclear disruption may accompany allopolyploid evolution as a consequence of the merger of different nuclear genomes in a cellular environment having only one set of progenitor organellar genomes. One path to reconcile potential cytonuclear mismatch is biased expression for maternal gene duplicates (homoeologs) encoding proteins that target to plastids and/or mitochondria. Assessment of this transcriptional form of cytonuclear coevolution at the level of individual cells or cell types remains unexplored. Using single-cell (sc-) and single-nucleus (sn-) RNAseq data from eight tissues in three allopolyploid species, we characterized cell type-specific variations of cytonuclear coevolutionary homoeologous expression and demonstrated the temporal dynamics of expression patterns across development stages during cotton fiber development. Our results provide unique insights into transcriptional cytonuclear coevolution in plant allopolyploids at the single-cell level.

ROR1-AS1 might promote in vivo and in vitro proliferation and invasion of cholangiocarcinoma cells.

Long non-coding RNAs (lncRNAs) play important roles in many pathophysiological processes, including cancer progression. Namely, lncRNA Receptor-tyrosine-kinase-like orphan receptor-1 antisense 1 (ROR1-AS1) is crucial for cancer occurrence and progression in organs such as the liver or bladder. However, its expression and role in cholangiocarcinoma (CCA) have not been thoroughly explored.Firstly, we assessed cell viability, proliferation, invasion, and migration using three cell lines (HuCCT-1, QBC399, and RBE) to explore the biological characteristics of ROR1-AS1 in CCA. Secondly, to determine the in vivo effect of ROR1-AS1 on tumor growth, ROR1-AS1 knockdown (KD) HuCCT-1 cells were subcutaneously injected into nude mice to evaluate tumor growth. Finally, we conducted a bioinformatic analysis to confirm the role of ROR1-AS1 in the prognosis and immunity of CCA.In this study, we found that lncRNA ROR1-AS1 was increased in CCA samples and patients with higher ROR1-AS1 expression had a shorter overall survival period. siRNA-mediated KD of ROR1-AS1 significantly reduced cell proliferation and inhibited the migration of CCA cells. In addition, ROR1-AS1 KD HuCCT-1 cells injected into nude mice grew slower than normal CCA cells.In summary, our results show that ROR1-AS1 can promote CCA progression and might serve as a new target for diagnosis and treatment of CCA.

Carotenoid enrichment in eggs: From biochemistry perspective.

The emergence of safe and functional eggs for consumer acceptance has gained focus. The production of carotenoid-enriched eggs has received attention due to its multifunctional biological properties. Nutritional modification of laying hens' diet can be a strategy to produce such eggs. This review presents the chemistry of carotenoids in nature and eggs, the accumulation process of carotenoids into eggs, and the functions of carotenoids in eggs. Our findings showed that carotenoids can be deposited into the egg and contribute to improving its nutritive value. The biosynthesis, chemical structure, and metabolism pathways of carotenoids lead to the deposition of carotenoids into eggs in their original or metabolized forms. Also, some factors modulate the efficiency of carotenoids in fowls before accumulation into eggs. Carotenoid-enriched eggs may be promising, ensuring the availability of highly nutritive eggs. However, further studies are still needed to comprehend the full metabolism process and the extensive functions of carotenoids in eggs.