Moderate alternate wetting and drying irrigation enhances drought-resistance abilities by improving structural mesophyll conductance of water-saving and drought-resistant rice under severe drought.

Water-saving and drought-resistant rice (WDR) coupled with alternate wetting and drying irrigation (AWDI) possesses a high photosynthetic potential due to higher mesophyll conductance (gm) under drought conditions. However, the physiological and structural contributions to the gm of leaves and their mechanisms in WDR under AWDI are still unclear. In this study, WDR (Hanyou 73) and drought-sensitive rice (Huiliangyou 898) were selected as materials. Three irrigation patterns were established from transplanting to the heading stage, including conventional flooding irrigation (W1), moderate AWDI (W2), and severe AWDI (W3). A severe drought with a soil water potential of -50 kPa was applied for a week at the heading stage across all treatments and cultivars. The results revealed that severe drought reduced gas exchange parameters and gm but enhanced antioxidant enzyme activities and malondialdehyde content in the three treatments and both cultivars. The maximal photosynthetic rate (Amax) of HY73 in the W2 treatment was greater than that in the other combinations of cultivars and irrigation patterns. The contribution of leaf structure (54%) to gm (gm-S, structural gm) was higher than that of leaf physiology (46%) to gm (gm-P, physiological gm) in the W2 treatment of Hanyou 73. Additionally, gm-S was significantly and linearly positively correlated with gm under severe drought. Moreover, both the initial and apparent quantum efficiencies were significantly and positively with gm in rice plants (p < 0.05). These results suggest that the improvements in photosynthesis and yield in the WDR combined with moderate AWDI can mainly be attributed to the enhancement of gm-S under severe drought conditions. Quantum efficiency may be a potential factor in regulating photosynthesis by cooperating with the gm of rice plants under severe drought conditions.

Chemical Isotope Labeling and Dual-Filtering Strategy for Comprehensive Profiling of Urinary Glucuronide Conjugates.

Glucuronidation, a crucial process in phase II metabolism, plays a vital role in the detoxification and elimination of endogenous substances and xenobiotics. A comprehensive and confident profiling of glucuronate-conjugated metabolites is imperative to understanding their roles in physiological and pathological processes. In this study, a chemical isotope labeling and dual-filtering strategy was developed for global profiling of glucuronide metabolites in biological samples. N,N-Dimethyl ethylenediamine (DMED-d0) and its deuterated counterpart DMED-d6 were used to label carboxylic acids through an amidation reaction. First, carboxyl-containing compounds were extracted based on a characteristic mass difference (Δm/z, 6.037 Da) observed in MS between light- and heavy-labeled metabolites (filter I). Subsequently, within the pool of carboxyl-containing compounds, glucuronides were identified using two pairs of diagnostic ions (m/z 247.1294/253.1665 and 229.1188/235.1559 for DMED-d0/DMED-d6-labeled glucuronides) originating from the fragmentation of the derivatized glucuronic acid group in MS/MS (filter II). Compared with non-derivatization, DEMD labeling significantly enhanced the detection sensitivity of glucuronides, as evidenced by a 3- to 55-fold decrease in limits of detection for representative standards. The strategy was applied to profiling glucuronide metabolites in urine samples from colorectal cancer (CRC) patients. A total of 685 features were screened as potential glucuronides, among which 181 were annotated, mainly including glucuronides derived from lipids, organic oxygen, and phenylpropanoids. Enzymatic biosynthesis was employed to accurately identify unknown glucuronides without standards, demonstrating the reliability of the dual-filtering strategy. Our strategy exhibits great potential for profiling the glucuronide metabolome with high coverage and confidence to reveal changes in CRC and other diseases.

Native and Gd-EOB-DTPA-Enhanced T1 mapping for Assessment of Liver Fibrosis in NAFLD: Comparative Analysis of Modified Look-Locker Inversion Recovery and Water-specific T1 mapping.

RATIONALE AND OBJECTIVES: To investigate the diagnostic performance of water-specific T1 mapping for staging liver fibrosis in a non-alcoholic fatty liver disease (NAFLD) rabbit model, in comparison to Modified Look-Locker Inversion recovery (MOLLI) T1 mapping. MATERIALS AND METHODS: 60 rabbits were randomly divided into the control group (12 rabbits) and NAFLD model groups (eight rabbits per subgroup) corresponding to different durations of high-fat high cholesterol diet feeding. All rabbits underwent MRI examination including MOLLI T1 mapping and 3D multi-echo variable flip angle (VFAME- GRE) sequences were acquired before and 20 min after the administration of Gd- EOB-DTPA. Histological assessments were performed to evaluate steatosis, inflammation, ballooning, and fibrosis. Statistical analysis included the intraclass correlation coefficient, analysis of variance, spearman correlation, multiple linear regression, and receiver operating characteristic curve. RESULTS: A moderate correlation was observed between conventional native T1 and MRI-PDFF (r = -0.513, P < 0.001), as well as between conventional native T1 and liver steatosis grades (r = -0.319, P = 0.016). However, no significant correlation was found between the native wT1 and PDFF (r = 0.137, P = 0.314), or between the native wT1 and steatosis grades (r = 0.106, P = 0.435). In the multiple regression analysis, liver fibrosis, and hepatocellular ballooning were identified as independent factors influencing native wT1 in this study (R2 =0.545, P < 0.05), while steatosis was independently associated with conventional native T1 (R2 =0.321, P < 0.05). The AUC values for native T1, native wT1, HBP T1, and HBP wT1 were 0.549(0.410-0.682), 0.811(0.684-0.903), 0.775(0.644-0.876), and 0.752(0.619-0.858) for F1 or higher, 0.581(0.441-0.711), 0.828(0.704-0.916), 0.832(0.708-0.919), and 0.854(0.734-0.934) for F2 or higher, respectively. CONCLUSION: The native wT1 may provide a more reliable assessment of early liver fibrosis in the context of NAFLD compared to conventional native T1.

Factors associated with blood donation among college and university students in Wuhan, China: structural equation model.

BACKGROUND: College and university students were an important population group of blood donors, especially in the current situation of tight blood supply. This study aimed to investigate the current status and determinants of blood donation among this population group in Wuhan using a structural equation model. METHODS: We conducted a cross-sectional study involving 12 colleges and universities in Wuhan, China, including 5168 students. Sociodemographic characteristics, health status, knowledge about blood donation, and attitude toward blood donation were treated as latent variables, with blood donation as the observed variable. Confirmatory factor analysis was conducted using the Mplus 8.0 statistical software application, followed by the establishment of a structural equation model to assess the relationships that exist between these variables. RESULTS: The overall blood donation rate among college and university students was 24.71%. The established model indicated that sociodemographic characteristics, health status, knowledge about blood donation, and attitude toward blood donation showed significant positive effects (0.135, 0.056, 0.321, and 0.389, respectively) on blood donation, among them, the direct effects were 0.076, -0.110, 0.143, and 0.389, respectively (P < 0.01). Additionally, sociodemographic characteristics, health status, and knowledge about blood donation had indirectly affected blood donation through the mediating effect of attitude towards blood donation. Their effects on attitude towards blood donation were 0.099, 0.243, and 0.468, respectively. (P < 0.01). The model could explain explained 22.22% of the variance in blood donation behavior among college and university students in Wuhan. CONCLUSION: Blood donation among college and university students in Wuhan was associated with sociodemographic characteristics, health status, knowledge about blood donation, and attitude towards blood donation, with attitude being the primary influencing factor. Tailored recruitment strategies for blood donation among students should prioritize initiatives aimed at enhancing knowledge about blood donation and fostering positive attitudes toward it.

Bud shapes dictate tiller-rhizome transition in African perennial rice (Oryza longistaminata).

KEY MESSAGE: Rhizome formation of Oryza longistaminata was dependent on the bud shape. The loci qBS3.1, qBS3.2 and qBS3.3 for controlling rhizome formation were functional redundant under Oryza longistaminata background. The rhizome, a root-like underground stem, is the key organ for grasses to achieve perennial growth. Oryza longistaminata, the only rhizomatous wild Oryza species with the same AA genome as cultivated rice, is an important germplasm for developing perennial rice. Our study found that the rhizome formation of O. longistaminata was dependent on the bud shape: the dome-like axillary bud (dome bud) usually penetrated through the leaf sheaths, developing into rhizome (extravaginal branching), but the flat axillary bud (flat bud) wrapped by the leaf sheaths only developed into tiller (intravaginal branching). The genetic loci (QTL) controlling the bud shape (BS) were mapped by entire population genotyping method (F2 population from crossing O. longistaminata with Balilla (Oryza sativa) and selective genotyping mapping method (BC1F2 population from backcrossing F1 with Balilla). A total of twelve loci were identified, including four major-effect QTL: qBS2, qBS3.1, qBS3.2 and qBS3.3, and the genetic network of these twelve loci was established. The dome bud lost the potential to develop into rhizome with the increase in backcross generations under Balilla background. Considering the rapid loss of rhizome under Balilla background, the near-isogenic lines under O. longistaminata background were used to identify the effect of major-effect loci. According to the BC3F2, BC4F2 and BC5F2 under O. longistaminata background, there was some functional redundancy among qBS3.1, qBS3.2 and qBS3.3. Our results provided a new perspective for analyzing the genetic basis of perenniality and laid the foundation for fine mapping and verification of related genes.

The application of dynamic contrast-enhanced ultrasonography in immediate distinguishing residual tumour from benign periablational enhancement after hepatocellular carcinoma radiofrequency ablation.

AIM: This study set out to access the performance of quantitative analysis of contrast-enhanced ultrasound (CEUS) in distinguishing between benign periablational enhancement (BPE) and residual tumor (RT) following radiofrequency ablation (RFA). MATERIALS AND METHODS: 165 tumors from 124 patients with hepatocellular carcinoma between 2021 and 2023 underwent RFA, contrast-enhanced computed tomography (CECT), and CEUS in less than 24 hours. Analysis was done on the quantitative parameters from RT and BPE found by CEUS. RESULTS: Complete ablation was obtained in 89.1% of lesions. When compared to BPE, RT had significantly greater peak intensity (PI), time to peak (TTP), area under the curve (AUC), ratio of PI and base intensity (PI/BI), and enhanced intensity (EI) values (all p<0.05). PI, TTP, AUC, PI/BI, and EI had large areas under the receiver operating (ROC) curves. A binary logistic regression analysis, respectively, demonstrated that PI and PI/BI were independent favorable prognostic variables. CONCLUSIONS: Multiple parameters of quantitative analysis of CEUS can aid in distinguishing immediately between RT and BPE lesions. PI and PI/BI may be a more promising parameter. Immediate CEUS evaluation following RFA may allow immediate retreatment of RT during the same operation time, which reduces patients' hospital stays and financial costs.

[Effects of Biochar-loaded Ammonia Nitrogen on Soil Carbon Emissions, Enzyme Activity, and Microbial Communities].

The form of soil nitrogen input significantly affects soil CO2 emission. As a new form of nitrogen input, biochar-loaded ammonia nitrogen not only reduces the input of chemical nitrogen fertilizer in farmland but also reduces the cost of environmental treatment. It is of great significance to promote the zero growth of national chemical fertilizer, the prevention and control of farmland non-point source pollution, and the realization of the national goal of "carbon peak" and "carbon neutralization." Through an indoor culture experiment, the effects of different nitrogen input forms on soil carbon emission, enzyme activity, and microbial community were studied through four treatments:no fertilization (CK), single application of chemical nitrogen fertilizer (CF), biochar combined application of chemical nitrogen fertilizer (BF), and biochar-loaded ammonia nitrogen (BN). The results showed that compared with that in CF, BF significantly increased cumulative carbon emissions (66.24 %), whereas BN had no significant difference. It is worth noting that the cumulative carbon emissions were significantly reduced by 35.28 % compared with that in BF and BN. Compared with those in CF and BF, the activities of ß-glucosidase, peroxidase, and polyphenol oxidase treated with BN significantly increased by 20.25 % and 5.20 %, respectively. Compared with that in CF, the BF treatment increased microbial community richness and community diversity, whereas the BN treatment decreased microbial community richness. Compared with that in BF, the relative abundance of Proteobacteria decreased by 11.16 %, and the relative abundance of Actinobacteria and Bacteroidota increased by 8.12 % and 5.83 %, respectively, in which xylosidase activity was the most important soil factor affecting microbial community structure. The relative abundance of Chloroflexi was significantly correlated with cellobiose hydrolase activity, and the relative abundance of Gemmatimonadetes was significantly correlated with ß-glucosidase activity. There was a very significant correlation between the relative abundance of Proteobacteria and cumulative carbon emissions. To summarize, compared with those under biochar combined with chemical nitrogen fertilizer, biochar loaded with ammonia nitrogen significantly reduced cumulative carbon emissions, and its emission reduction effect was better. The results of this study will be beneficial to the landing of the national "double carbon strategy," the healthy development of the biological natural gas industry, the construction of the national green cultivation circular agriculture system, and the realization of the national zero growth strategy of chemical fertilizer.

Nomogram model of serum thymidine kinase 1 combined with ultrasonography for prediction of central lymph node metastasis risk in patients with papillary thyroid carcinoma pre-surgery.

Objective: The aim of this study was to develop a nomogram, using serum thymidine kinase 1 protein (STK1p) combined with ultrasonography parameters, to early predict central lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) pre-surgery. Methods: Patients with PTC pre-surgery in January 2021 to February 2023 were divided into three cohorts: the observation cohort (CLNM, n = 140), the control cohort (NCLNM, n = 128), and the external verification cohort (CLNM, n = 50; NCLNM, n = 50). STK1p was detected by an enzyme immunodot-blot chemiluminescence analyzer and clinical parameters were evaluated by ultrasonography. Results: A suitable risk threshold value for STK1p of 1.7 pmol/L was selected for predicting CLNM risk by receiver operating characteristic (ROC) curve analysis. Multivariate analysis identified the following six independent risk factors for CLNM: maximum tumor size >1 cm [odds ratio (OR) = 2.406, 95% confidence interval (CI) (1.279-4.526), p = 0.006]; capsule invasion [OR = 2.664, 95% CI (1.324-5.360), p = 0.006]; irregular margin [OR = 2.922; 95% CI (1.397-6.111), p = 0.004]; CLN flow signal [OR = 3.618, 95% CI (1.631-8.027), p = 0.002]; tumor-foci number ≥2 [OR = 4.064, 95% CI (2.102-7.859), p < 0.001]; and STK1p ≥1.7 pmol/L [OR = 7.514, 95% CI (3.852-14.660), p < 0.001]. The constructed nomogram showed that the area under the ROC curve for the main dataset was 0.867 and that for the validation dataset was 0.830, exhibiting effectivity, and was recalculated to a total score of approximately 383. Through monitoring the response post-surgery, all patients were assessed as tumor-free at 12 months post-surgery, which was significantly associated with a reduction in STK1p to disease-free levels. Conclusion: We demonstrate for the first time that a novel nomogram including STK1p combined with ultrasonography can assist in the clinical prevention of CLNM, by facilitating timely, individualized prophylactic CLNM dissection, thereby reducing the risk of secondary surgery and the probability of recurrence.

A supramolecular fluorescence sensor array for the differentiation of multiple anions and prediction of iodine in artificial urine using machine learning.

The simultaneous discrimination and detection of multiple anions in an aqueous solution has been a major challenge due to their structural similarity and low charge radii. In this study, we have constructed a supramolecular fluorescence sensor array based on three host-guest complexes to distinguish five anions (F-, Cl-, Br-, I-, and ClO-) in an aqueous solution using anionic-induced fluorescence quenching combined with linear discriminant analysis. Due to the different affinities of the three host-guest complexes for each anion the anion quenching efficiency for each host-guest complex was likewise different, and the five anions were well recognized. The fluorescence sensor array not only distinguished anions at different concentrations (0.5, 10, and 50 µM) with 100% accuracy but also showed good linearity within a certain concentration range. The limit of detection (LOD) was < 0.5 µM. Our interference study showed that the developed sensor array had good anti-interference ability. The practicability of the developed sensor array was also verified by the identification and differentiation of toothpaste brands with different fluoride content and the prediction of the iodine concentration in urine combined with machine learning.

Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism.

Given the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 µmol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride's interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and α-smooth muscle actin (α-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor.

Association between renal α-klotho and renal pathology among patients with chronic kidney disease.

INTRODUCTION: This study was designed to investigate whether renal α-klotho levels are associated with renal pathology. This is the first report on patients with chronic kidney disease (CKD). METHODS: We conducted a retrospective observational study. A total of 65 CKD patients were enrolled. Serum and renal biopsy samples were collected. Estimated glomerular filtration rate (eGFR) was examined by biochemical test. And α-klotho expressions were assessed by RT-PCR and immunohistochemistry. In addition, detailed microscopic findings were reviewed. RESULTS: Renal α-klotho levels are associated positively with eGFR, and negatively with renal pathology, including interstitial fibrosis, inflammatory cell infiltration, and tubular atrophy. CONCLUSIONS: The renal α-klotho is related to renal pathology.

The effect of oral motor intervention with different initiation times to improve feeding outcomes in preterm infants: protocol for a single-blind, randomized controlled trial.

BACKGROUND: Premature infants commonly encounter difficulties with oral feeding, a complication that extends hospital stays, affects infants' quality of life, and imposes substantial burdens on families and society. Enhancing preterm infants' oral feeding skills and facilitating their transition from parenteral or nasal feeding to full oral feeding pose challenges for neonatal intensive care unit (NICU) healthcare professionals. Research indicates that oral motor interventions (OMIs) can enhance preterm infants' oral feeding capabilities and expedite the transition from feeding initiation to full oral feeding. Nonetheless, the most suitable timing for commencing these interventions remains uncertain. METHODS: This is a single-blind, randomized controlled trial. Preterm with a gestational age between 29+0 to 34+6 weeks will be eligible for the study. These infants will be randomized and allocated to one of two groups, both of which will receive the OMIs. The intervention commences once the infant begins milk intake during the early OMIs. Additionally, in the late OMIs group, the intervention will initiate 48 h after discontinuing nasal continuous positive airway pressure. DISCUSSION: OMIs encompass non-nutritive sucking and artificial oral stimulation techniques. These techniques target the lips, jaw, muscles, or tongue of premature infants, aiming to facilitate the shift from tube feeding to oral feeding. The primary objective is to determine the ideal intervention timing that fosters the development of oral feeding skills and ensures a seamless transition from parenteral or nasal feeding to full oral feeding among preterm infants. Furthermore, this study might yield insights into the long-term effects of OMIs on the growth and neurodevelopmental outcomes of preterm infants. Such insights could bear substantial significance for the quality of survival among preterm infants and the societal burden imposed by preterm birth. TRIAL REGISTRATION: chictr.org.cn ChiCTR2300076721. Registered on October 17, 2023.

Large skin defect in Type V aplasia cutis congenita treated with conservative treatment: a case report.

Aplasia cutis congenita (ACC) is a congenital disorder that can be classified into nine types, with Type I ACC being the most common. Type V ACC associated with fetus papyraceus is a rare subtype of ACC. We report the case of a Type V ACC in a male newborn with extensive abdominal skin defects. The patient received conservative treatment using hydrogel foam and silicone foam dressings. Approximately five weeks later, the patient was discharged when more than 60% of the skin had completed epithelialization. After discharge from West China Second University Hospital, Chengdu , the patient continued to be followed up regularly at the Burns and Plastic Surgery Clinic at local hospital in Gansu. We followed up the child by telephone. After 4 months of follow-up, scar tissue formation was observed in the trunk area. The infant is 2 years and 5 months old now, physical examination did not reveal any organ problems.

Dissolved oxygen and ammonia affect ammonia production via GDH/AMPK signaling pathway and alter flesh quality in Chinese perch (Siniperca chuatsi).

The dissolved oxygen (DO) and ammonia are crucial to the growth of Chinese perch (Siniperca chuatsi). Information on the effects of DO and total ammonia nitrogen (TAN) in regulating ammonia nitrogen excretion and flesh quality in Chinese perch is scanty. This study aimed to evaluate the effects of dissolved DO at oxygen levels of 3 mg/L and 9 mg/L, as well as the TAN concentrations of 0.3 mg/L and 0.9 mg/L on ammonia excretion and flesh quality. Results showed that the ammonia contents in plasma, muscle, and liver of the 9 mg/L DO group were significantly higher than those of the 3 mg/L DO group (P < 0.05). However, the expression of AMPK-related signaling pathway genes (gdh, lkb1, and ampd) and flesh quality indicators (gumminess, chewiness, hardness) in the 9 mg/L DO group were significantly lower than those in the 3 mg/L DO group. Under long-term exposure to 0.9 mg/L TAN, the ammonia contents in plasma and gill filaments, as well as muscle flesh quality (resilience, gumminess, chewiness, cohesiveness), were significantly lower than those in the 0.3 mg/L TAN group (P < 0.05). However, the activities of GDH and AMPD enzymes in the 0.9 mg/L TAN group were significantly higher than those in the 0.3 mg/L TAN group. In summary, when fish are exposed to 3 mg/L DO and 0.9 mg/L TAN in the environment for a long time, their amino acids are used for transamination and deamination, resulting in insufficient energy supply for Chinese perch, whereas 9 mg/L DO and 0.9 mg/L TAN caused deterioration of the flesh quality.

Inspecting mother-to-infant microbiota transmission: disturbance of strain inheritance by cesarian section.

Introduction: The initial acquisition and subsequent development of the microbiota in early life is crucial to future health. Cesarean-section (CS) birth is considered to affect early microbial transmission from mother to infant. Methods: In this study, we collected fecal samples from 34 CS infants and their mothers from West China Second Hospital, Sichuan University to assess the microbiota developmental trajectory of mothers and infants. We explored mother-infant gut microbiome transmission via comparison with corresponding Finnish data. Results: Metagenomic analysis of gut microbiota profiles indicated that the communities of mothers and infants were distinct. The composition of the infant gut microbiome was highly variable but also followed predictable patterns in the early stages of life. Maternal communities were stable and mainly dominated by species from Bacteroidacea spp. We used PStrain to analyze and visualize strain transmission in each mother-infant pair. Excluding missing data, we included 32 mother-infant pairs for analysis of strain transmission. Most CS deliveries (65.6%, 21/32) did not demonstrate transmission of strains from mother to infant. To further explore the mother-infant strain transmission, we analyzed metagenomics data from Finnish mother-infant pairs. A total of 32 mother-infant pairs were included in the analysis, including 28 vaginal delivery (VD) infants and four CS infants. Strain transmission was observed in 30 infants, including 28 VD infants and two CS infants. All VD infants received transmitted stains from their mothers. Finally, a total of 193 strain transmission events were observed, comprising 131 strains and 45 species. Discussion: Taken together, our data suggested that delivery mode was an important factor influencing the mother-infant strain transmission.

Mechanism and treatment of diarrhea associated with tyrosine kinase inhibitors.

Tyrosine kinase inhibitors (TKIs) have become first-line drugs for cancer treatment. However, their clinical use is seriously hindered since many patients experience diarrhea after receiving TKIs. The mechanisms of TKI-associated diarrhea remain unclear. Most existing therapies are symptomatic treatments based on experience and their effects are unsatisfactory. Therefore, clarification of the mechanisms underlying diarrhea is critical to develop effective anti-diarrhea drugs. This article summarizes several potential mechanisms of TKI-associated diarrhea and reviews current treatment progress.

Boosting cartilage repair with silk fibroin-DNA hydrogel-based cartilage organoid precursor.

Osteoarthritis (OA), a common degenerative disease, is characterized by high disability and imposes substantial economic impacts on individuals and society. Current clinical treatments remain inadequate for effectively managing OA. Organoids, miniature 3D tissue structures from directed differentiation of stem or progenitor cells, mimic native organ structures and functions. They are useful for drug testing and serve as active grafts for organ repair. However, organoid construction requires extracellular matrix-like 3D scaffolds for cellular growth. Hydrogel microspheres, with tunable physical and chemical properties, show promise in cartilage tissue engineering by replicating the natural microenvironment. Building on prior work on SF-DNA dual-network hydrogels for cartilage regeneration, we developed a novel RGD-SF-DNA hydrogel microsphere (RSD-MS) via a microfluidic system by integrating photopolymerization with self-assembly techniques and then modified with Pep-RGDfKA. The RSD-MSs exhibited uniform size, porous surface, and optimal swelling and degradation properties. In vitro studies demonstrated that RSD-MSs enhanced bone marrow mesenchymal stem cells (BMSCs) proliferation, adhesion, and chondrogenic differentiation. Transcriptomic analysis showed RSD-MSs induced chondrogenesis mainly through integrin-mediated adhesion pathways and glycosaminoglycan biosynthesis. Moreover, in vivo studies showed that seeding BMSCs onto RSD-MSs to create cartilage organoid precursors (COPs) significantly enhanced cartilage regeneration. In conclusion, RSD-MS was an ideal candidate for the construction and long-term cultivation of cartilage organoids, offering an innovative strategy and material choice for cartilage regeneration and tissue engineering.

Addition of α-ketoglutaric acid (AKG) reduces deamination in Chinese perch (Siniperca chuatsi) fed with fermented soybean meal as a substitute for fishmeal.

To alleviate amino acid imbalances in fermented soybean meal as a replacement for fishmeal feeds, this study evaluated the effects of adding lysine (Lys), methionine (Met), and α-ketoglutaric acid (AKG) to fermented soybean meals for Chinese perch. Chinese perch (34 ± 3 g) were fed five diets for 66 days (fishmeal as the protein source of the basal diet [FM]; fermented soybean meal as a substitute for 30% fishmeal in the soybean meal diet [FSM]; addition of crystalline Lys and Met [AA]; addition of α-ketoglutaric acid [AKG]; and simultaneous addition of crystalline Lys, Met, and AKG [BA] to the soybean meal diet). At the end of the feeding trial, the FSM group had the highest feeding rate and the lowest weight gain rate among all the groups. The FM group had the highest protein retention and the lowest feed efficiency among the groups. The mRNA transcription level of genes related to the AMP-activating protein (AMPK) signaling pathway and amino acid response (AAR) signaling pathway (lkb1, atf4, and gcn2) were highest in the AA group (P < 0.05) but lower in the AKG and BA groups. In the AKG group, the mRNA transcription level of the gluconeogenesis pathway-related gene (pepck and g6pase) was significantly higher than that in the other four groups, but the mRNA transcription level of genes related to amino acid catabolism (gdh and ampd) was lower. Among all the groups, the FSM group had the lowest mRNA transcription level of genes associated with the mammalian target of rapamycin (mTOR) signaling pathway (mtor and s6k). These findings imply that the feeding rate of Chinese perch in the fermented soybean meal group was the highest, but the protein retention was the lowest, while the addition of Lys, Met, and AKG improved protein retention. In conclusion, the addition of AKG to fermented soybean meal as a fishmeal substitute reduced amino acid deamination, enhanced gluconeogenesis, and increased protein deposition, which contributed to the growth of Chinese perch, alleviated amino acid imbalances, and improved the feed utilization of Chinese perch.

Reduced functional connectivity of the right dorsolateral prefrontal cortex at rest in obsessive-compulsive disorder.

BACKGROUND: Neuroimaging studies have revealed the role of the right dorsolateral prefrontal cortex (DLPFC) in the neurobiological mechanism of obsessive-compulsive disorder (OCD). However, only a few studies have examined the functional connectivity (FC) pattern of the right DLPFC at rest in OCD. OBJECTIVE: The aim of this research is to examine the FC patterns of the right DLPFC at rest in OCD. METHODS: Twenty-eight medication-free patients with OCD and 20 healthy controls underwent resting-state functional magnetic resonance imaging. Seed-based FC and support vector machine (SVM) were used to analyze the imaging data. RESULTS: The patients with OCD showed reduced FC values in the right middle temporal gyrus (MTG), right superior temporal gyrus, right ventral anterior cingulate cortex (vACC), and left Crus II. No brain regions showed a remarkable difference in FC values in patients with OCD after 8 weeks of medication treatment. The reduced right DLPFC-right MTG and right DLPFC-right vACC connectivities were correlated with the clinical symptoms of OCD. SVM results showed that reduced right DLPFC-right MTG connectivity at rest could predict the therapeutic response to OCD medication. CONCLUSIONS: The findings highlight the important role of the right DLPFC in the pathophysiological mechanism of OCD.