LNCHC directly binds and regulates YBX1 stability to ameliorate metabolic dysfunction-associated steatotic liver disease progression.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the foremost cause of chronic liver disease, yet its underlying mechanisms remain elusive. Our group previously discovered a novel long non-coding RNA (lncRNA) in rats, termed lncHC and its human counterpart, LNCHC. This study aimed to explore the role of LNCHC in the progression of MASLD. METHODS: RNA-binding proteins bound to LNCHC were searched by mass spectrometry. The target genes of LNCHC and Y-Box binding protein 1 (YBX1) were identified by RNA-seq. MASLD animal models were utilised to examine the roles of LNCHC, YBX1 and patatin-like phospholipase domain containing 3 (PNPLA3) in MASLD progression. RESULTS: Here, we identified LNCHC as a native restrainer during MASLD development. Notably, LNCHC directly binds YBX1 and prevents protein ubiquitination. Up-regulation of YBX1 then stabilises PNPLA3 mRNA to alleviate lipid accumulation in hepatocytes. Furthermore, both cell and animal studies demonstrate that LNCHC, YBX1 and PNPLA3 function to improve hepatocyte lipid accumulation and exacerbate metabolic dysfunction-associated steatohepatitis development. CONCLUSIONS: In summary, our findings unveil a novel LNCHC functionality in regulating YBX1 and PNPLA3 mRNA stability during MASLD development, providing new avenues in MASLD treatment.

Influence of flaxseed-derived diglyceride-based high internal phase Pickering emulsions on the rheological and physicochemical properties of myofibrillar protein gels.

The study aimed to investigate the influence of flaxseed-derived diglyceride-based high internal phase Pickering emulsions (HIPPE) at different levels (0%, 10%, 20%, 30%, 40%, and 50%) on the rheological and physicochemical properties of myofibrillar protein (MPs) gels. The study indicated that with increasing HIPPE levels, there was a significant increase in whiteness while a decrease in water-holding capacity. The gels with 10% HIPPE levels had higher ionic bonds, while those with 40% and 50% HIPPE levels showed higher hydrogen bonds. By increasing HIPPE levels in the formation of MP gels, the T2 relaxation time was found to decrease. Additionally, in all MP gels, G' values were significantly higher than G" values over time. Adding lower contents of HIPPE levels resulted in a more compact microstructure. These findings indicate that flaxseed-derived diglyceride-based HIPPEs could be utilized as fat substitutes in meat products to enhance their nutritional quality.

Chromosome-level genome assembly of Solanum pimpinellifolium.

Solanum pimpinellifolium, the closest wild relative of the domesticated tomato, has high potential for use in breeding programs aimed at developing multi-pathogen resistance and quality improvement. We generated a chromosome-level genome assembly of S. pimpinellifolium LA1589, with a size of 833 Mb and a contig N50 of 31 Mb. We anchored 98.80% of the contigs into 12 pseudo-chromosomes, and identified 74.47% of the sequences as repetitive sequences. The genome evaluation revealed BUSCO and LAI score of 98.3% and 14.49, respectively, indicating high quality of this assembly. A total of 41,449 protein-coding genes were predicted in the genome, of which 89.17% were functionally annotated. This high-quality genome assembly serves as a valuable resource for accelerating the biological discovery and molecular breeding of this important horticultural crop.

Reprogramming the future: Capitalizing on in vitro embryo culture by advancing stem cell technologies in the fight against rare genetic disorders.

Capitalizing on breakthroughs in reproductive genetics, the utilization of in vitro embryo culture and stem cell technologies heralds a transformative era in addressing global challenges posed by rare genetic diseases. These cutting-edge practices illuminate the intricacies of early human development, elucidate the mechanisms behind rare diseases, and guide the development of potential therapies. Balancing this remarkable innovation with necessary ethical considerations, these technologies have the potential to revolutionize the trajectory of rare genetic disorders, transforming the landscape of diagnosis, treatment, and genetic counseling while offering renewed hope for affected individuals and families worldwide.

Efficacy and Safety of Anti-Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Antibodies Plus Chemotherapy as First-Line Treatment for NSCLC in the People's Republic of China: a Systematic Review and Meta-Analysis.

Introduction: The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials. Therefore, a focus on approved anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs in China is needed. This study aims to assess the heterogeneity of anti-PD-1/PD-L1 antibodies manufactured in China (domestic PD-1/PD-L1) and overseas (imported PD-1/PD-L1) when combined with chemotherapy as the first-line treatment of NSCLC. Methods: A systematic search was performed using PubMed, EMBASE, and Cochrane Library of publications up to July 13, 2023. Meta-analysis was applied to compare the efficacy and safety profile between anti-PD-1/PD-L1 antibodies plus chemotherapy (PD-1/PD-L1+Chemo) and chemotherapy alone using STATA software. Pooled hazard ratios for progression-free survival and overall survival, odds ratios for objective response rate, and incidence rate of grade greater than or equal to three treatment-related adverse events with 95% confidence intervals were calculated in the domestic group and imported group by a random-effects model, and the heterogeneity between the two estimates was assessed. Results: There were 14 eligible clinical studies with a total of 3951 patients involved in this analysis, including eight studies of domestic PD-1/PD-L1+Chemo and six studies of imported PD-1/PD-L1+Chemo. The study revealed that there was no significant difference between domestic and imported PD-1/PD-L1+Chemo in overall survival (p = 0.80), progression-free survival (p = 0.53), and incidence rate of grade greater than or equal to three treatment-related adverse events (p = 0.10). Nevertheless, the objective response rate of imported PD-1/PD-L1+Chemo was significantly higher than that of domestic PD-1/PD-L1+Chemo (p = 0.03). Conclusions: Domestic anti-PD-1/PD-L1 antibodies plus chemotherapy were found to have comparable efficacy and safety to those combined with imported anti-PD-1/PD-L1 antibodies based on current evidence.

Dexmedetomidine Attenuates Inflammation in Elderly Patients Following Major Hepatobiliary and Pancreatic Surgery: A Randomized Clinical Trial.

Background: Dexmedetomidine (Dex) may have anti-inflammatory properties and potentially reduce the incidence of postoperative organ injury. Objective: To investigate whether Dex protects pulmonary and renal function via its anti-inflammatory effects in elderly patients undergoing prolonged major hepatobiliary and pancreatic surgery. Design and Setting: Between October 2019 and December 2020, this randomized controlled trial was carried out at a tertiary hospital in Chongqing, China. Patients: 86 patients aged 60-75 who underwent long-duration (> 4 hrs) hepatobiliary and pancreatic surgery without significant comorbidities were enrolled and randomly assigned into two groups at a 1:1 ratio. Interventions: Patients were given either Dex or an equivalent volume of 0.9% saline (Placebo) with a loading dose of 1 µg kg-1 for 10 min, followed by 0.5 µg kg-1 hr-1 for maintenance until the end of surgery. Main Outcome Measures: The changes in serum concentrations of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were primary outcomes. Results: At one hour postoperatively, serum IL-6 displayed a nine-fold increase (P<0.05) in the Placebo group. Administration of Dex decreased IL-6 to 278.09 ± 45.43 pg/mL (95% CI: 187.75 to 368.43) compared to the Placebo group (P=0.019; 432.16 ± 45.43 pg/mL, 95% CI: 341.82 to 522.50). However, no significant differences in TNF-α were observed between the two groups. The incidence of postoperative acute kidney injury was twice as high in the Placebo group (9.30%) compared to the Dex group (4.65%), and the incidence of postoperative acute lung injury was 23.26% in the Dex group, lower than that in the Placebo group (30.23%), although there was no statistical significance between the two groups. Conclusion: Dex administration in elderly patients undergoing major hepatobiliary and pancreatic surgery reduces inflammation and potentially protects kidneys and lungs. Registration: Chinese Clinical Trials Registry, identifier: ChiCTR1900024162, on 28 June 2019.

A Near-Infrared Fluorescent Probe with Large Stokes Shift for Sensitive Detection of Hydrogen Sulfide in Environmental Water, Food Spoilage, and Biological Systems.

Hydrogen sulfide (H2S) is an important endogenous gas transmitter that plays a critical role in various physiological and pathological processes and can also cause a negative impact on foodstuffs. In this study, we designed and synthesized a simple, easily available, high-yield, and low-cost near-infrared (λem = 710 nm) fluorescent probe, DEM-H2S, with a substantial Stokes shift (205 nm) for the detection of H2S. DEM-H2S features high selectivity and sensitivity (LOD = 80 nM) toward H2S, accompanied by a noticeable color change. Upon interaction with H2S, DEM-H2S exhibits a restored ICT (Intramolecular Charge Transfer) process, thereby manifesting near-infrared fluorescence. DEM-H2S has been successfully utilized to detect H2S in actual water samples and to monitor the spoilage of food items, such as pork, shrimp, and eggs. Furthermore, DEM-H2S enables the imaging of endogenous and exogenous H2S in living MCF-7 cells and zebrafish. Hence, DEM-H2S provides an attractive method for the detection of H2S in environmental, food, and biological systems, holding potential value in physiological and pathological research.

The emerging role of the semaphorin family in cartilage and osteoarthritis.

In the pathogenesis of osteoarthritis, various signaling pathways may influence the bone joint through a common terminal pathway, thereby contributing to the pathological remodeling of the joint. Semaphorins (SEMAs) are cell-surface proteins actively involved in and primarily responsible for regulating chondrocyte function in the pathophysiological process of osteoarthritis (OA). The significance of the SEMA family in OA is increasingly acknowledged as pivotal. This review aims to summarize the mechanisms through which different members of the SEMA family impact various structures within joints. The findings indicate that SEMA3A and SEMA4D are particularly relevant to OA, as they participate in cartilage injury, subchondral bone remodeling, or synovitis. Additionally, other elements such as SEMA4A and SEMA5A may also contribute to the onset and progression of OA by affecting different components of the bone and joint. The mentioned mechanisms demonstrate the indispensable role of SEMA family members in OA, although the detailed mechanisms still require further exploration.

The relationship between the structural changes in the cervical spinal cord and sensorimotor function of children with thoracolumbar spinal cord injury (TLSCI).

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To study the relationship between the structural changes in the cervical spinal cord (C2/3 level) and the sensorimotor function of children with traumatic thoracolumbar spinal cord injury (TLSCI) and to discover objective imaging biomarkers to evaluate its functional status. SETTING: Xuanwu Hospital, Capital Medical University, China; Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, China. METHODS: 30 children (age range 5-13 years) with TLSCI and 11 typically developing (TD) children (age range 6-12 years) were recruited in this study. Based on whether there is preserved motor function below the neurological level of injury (NLI), the children with TLSCI are divided into the AIS A/B group (motor complete) and the AIS C/D group (motor incomplete). A Siemens Verio 3.0 T MR scanner was used to acquire 3D high-resolution anatomic scans covering the head and upper cervical spinal cord. Morphologic parameters of the spinal cord at the C2/3 level, including cross-sectional area (CSA), anterior-posterior width (APW), and left-right width (LRW) were obtained using the spinal cord toolbox (SCT; https://www.nitrc.org/projects/sct ). Correlation analyses were performed to compare the morphologic spinal cord parameters and clinical scores determined by the International Standard for Neurological Classification of Spinal Cord Injuries (ISNCSCI) examination. RESULTS: CSA and LRW in the AIS A/B group were significantly lower than those in the TD group and the AIS C/D group. LRW was the most sensitive imaging biomarker to differentiate the AIS A/B group from the AIS C/D group. Both CSA and APW were positively correlated with ISNCSCI sensory scores. CONCLUSIONS: Quantitative measurement of the morphologic spinal cord parameters of the cervical spinal cord can be used as an objective imaging biomarker to evaluate the neurological function of children with TLSCI. Cervical spinal cord atrophy in children after TLSCI was correlated with clinical grading; CSA and APW can reflect sensory function. Meanwhile, LRW has the potential to be an objective imaging biomarker for evaluating motor function preservation.

The 14-3-3 protein nt GF14e interacts with CIPK2 and increases low potassium stress in tobacco.

Potassium (K+) plays a role in enzyme activation, membrane transport, and osmotic regulation processes. An increase in potassium content can significantly improve the elasticity and combustibility of tobacco and reduce the content of harmful substances. Here, we report that the expression analysis of Nt GF14e, a 14-3-3 gene, increased markedly after low-potassium treatment (LK). Then, chlorophyll content, POD activity and potassium content, were significantly increased in overexpression of Nt GF14e transgenic tobacco lines compared with those in the wild type plants. The net K+ efflux rates were severely lower in the transgenic plants than in the wild type under LK stress. Furthermore, transcriptome analysis identified 5708 upregulated genes and 2787 downregulated genes between Nt GF14e overexpressing transgenic tobacco plants. The expression levels of some potassium-related genes were increased, such as CBL-interacting protein kinase 2 (CIPK2), Nt CIPK23, Nt CIPK25, H+-ATPase isoform 2 a (AHA2a), Nt AHA4a, Stelar K+ outward rectifier 1(SKOR1), and high affinity K+ transporter 5 (HAK5). The result of yeast two-hybrid and luciferase complementation imaging experiments suggested Nt GF14e could interact with CIPK2. Overall, these findings indicate that NtGF14e plays a vital roles in improving tobacco LK tolerance and enhancing potassium nutrition signaling pathways in tobacco plants.

Heterozygous variants in USP25 cause genetic generalized epilepsy.

USP25 encodes ubiquitin-specific proteases 25, a key member of deubiquitinating enzyme family and is involved in neural fate determination. Although abnormal expression in Down's syndrome was reported previously, the specific role of USP25 in human diseases has not been defined. In this study, we performed trio-based whole exome sequencing in a cohort of 319 cases (families) with generalized epilepsy of unknown etiology. Five heterozygous USP25 variants including two de novo and three co-segregated variants were determined in eight individuals affected by generalized seizures and/or febrile seizures from five unrelated families. The frequency of USP25 variants showed a significantly high aggregation in this cohort compared to the East Asian population and all populations in the gnomAD database. The mean onset ages of febrile and afebrile seizures were 10 months (infancy) and 11.8 years (juvenile), respectively. The patients achieved seizure freedom except one had occasional nocturnal seizures at the last follow-up. Two patients exhibited intellectual disability. Usp25 was ubiquitously expressed in mouse brain with two peaks on embryonic days (E14‒E16) and postnatal day 21, respectively. Similarly, USP25 expressed in fetus/early childhood stage with a second peak at approximately 12‒20 years old in human brain, consistent with the seizure onset age at infancy and juvenile in the patients. To investigate the functional impact of USP25 deficiency in vivo, we established Usp25 knock-out mice, which showed increased seizure susceptibility compared to wild-type mice in pentylenetetrazol-induced seizure test. To explore the impact of USP25 variants, we employed multiple functional detections. In HEK293T cells, the severe phenotype associated variant (p.Gln889Ter) led to a significant reduction of mRNA and protein expressions but formed a stable truncated dimers with increment of deubiquitinating enzyme activities and abnormal cellular aggregations, indicating a gain-of-function effect. The p.Gln889Ter and p.Leu1045del increased neuronal excitability in mice brain, with a higher firing ability in p.Gln889Ter. These functional impairments align with the severity of the observed phenotypes, suggesting a genotype-phenotype correlation. Hence, a moderate association between USP25 and epilepsy was noted, indicating USP25 is potentially a predisposing gene for epilepsy. Our results from Usp25 null mice and the patient-derived variants indicated that USP25 would play epileptogenic role via loss-of-function or gain-of-function effects. The truncated variant p.Gln889Ter would have profoundly different effect on epilepsy. Together, our results underscore the significance of USP25 heterozygous variants in epilepsy, thereby highlighting the critical role of USP25 in the brain.

Scene-based dual domain non-uniformity correction algorithm for stripe and optics-caused fixed pattern noise removal.

Non-uniformity is a long-standing problem that significantly degrades infrared images through fixed pattern noise (FPN). Existing scene-based algorithms for non-uniformity correction (NUC) effectively eliminate stripe FPN assuming consistent inter-frame non-uniformity. However, they are ineffective in handling spatially continuous optical FPN. In this paper, a scene-based dual domain correction approach is proposed to address the non-uniformity problem by simultaneously removing stripe and optics-caused FPN. We achieve this through gain correction in the frequency domain and offset correction in the spatial domain. To remove stripes, we approximate the desired image using a guided filter and iteratively update the bias correction parameters frame by frame. For optics-caused noise removal, we separate low frequency noise from the scene using Fourier transform and update the gain correction parameters accordingly. To mitigate ghost artifacts, a combined strategy is introduced to adaptively adjusts learning rates and weights during the updating stage. Comprehensive evaluations demonstrate that our proposed approach outperforms compared methods in both real and simulated non-uniformity infrared videos.

Cross-domain colorization of unpaired infrared images through contrastive learning guided by color feature selection attention.

In challenging lighting conditions, infrared detectors have become vital tools for enhancing visual perception, overcoming the limitations of visible cameras. However, inherent imaging principles and manufacturing constraints confine infrared imaging systems to grayscale, significantly impacting their utility. In comparison to visible imagery, infrared images lack detailed semantic information, color representation, and suffer from reduced contrast. While existing infrared image colorization techniques have made significant progress in improving color quality, challenges such as erroneous semantic color prediction and blurred depiction of fine details persist. Acquiring paired color images corresponding to real-world infrared scenarios poses substantial difficulties, exacerbating challenges in cross-domain colorization of infrared images. To address these critical issues, this paper introduces an innovative approach utilizing contrastive learning for unsupervised cross-domain mapping between unpaired infrared and visible color images. Additionally, we introduce a color feature selection attention module guiding rational infrared image coloring. The proposed method employs the Residual Fusion Attention Network (RFANet) as a generator, enhancing the encoder's ability to represent color and structural features. Furthermore, to ensure structural content consistency and enhance overall color style matching accuracy, we design a comprehensive joint global loss function integrating both detailed content and color style. Experimental evaluations on publicly available datasets demonstrate the superior performance of the proposed unsupervised cross-domain colorization method for infrared images compared to previous approaches.

Broadband wavelength designable achromatic grating based on a cholesteric liquid crystal template.

Liquid crystal (LC) gratings have played important roles in light field control due to the advantages of being lightweight, low cost, having no moving parts, and low power consumption. However, the chromatic aberration limits the bandwidth of the LC device and affects the efficiency of the grating. To solve the chromatic aberration issue, a broadband wavelength designable achromatic grating is proposed. Different grating structures are integrated into a single-layer templated cholesteric liquid crystal (CLC) device, and the achromatic diffraction wavelength of the grating can be freely designed from the visible spectral region to the infrared range within the Bragg reflection band of the CLCs. The diffraction intensity of different orders can be changed with the electric field applied to meet the need for dynamic modulation. This grating shows suitable potential applications in optical communication and displays.

Short-wavelength-infrared upconversion edge enhancement imaging based on a Laguerre-Gaussian composite vortex filter.

Edge-enhanced imaging by spiral phase contrast has proven instrumental in revealing phase or amplitude gradients of an object, with notable applications spanning feature extraction, target recognition, and biomedical fields. However, systems deploying spiral phase plates encounter limitations in phase mask modulation, hindering the characterization of the modulation function during image reconstruction. To address this need, we propose and demonstrate an innovative nonlinear reconstruction method using a Laguerre-Gaussian composite vortex filter, which modulates the spectrum of the target. The involved nonlinear process spectrally transforms the incident short-wavelength-infrared (SWIR) signal from 1550 to 864 nm, subsequently captured by a silicon charge-coupled device. Compared with conventional schemes, our novel filtering method effectively suppresses the diffraction noise, significantly enhancing image contrast and resolution. By loading specific phase holograms on the spatial light modulator, bright-field imaging, isotropic, amplitude-controlled anisotropic, and directional second-order edge-enhanced imaging are realized. Anticipated applications for the proposed SWIR edge-enhanced imaging system encompass domains such as artificial intelligence recognition, deep tissue medical diagnostics, and non-destructive defect inspection. These applications underscore the valuable potential of our cutting-edge methodology in furthering both scientific exploration and practical implementations.

Effects of community ecological network construction on physicochemical, microbial, and quality characteristics of inoculated northeast sauerkraut: A new insight in food fermentation processes.

The enhancement of the quality of northeast sauerkraut can be achieved by inoculation with lactic acid bacteria. However, a comprehensive ecological understanding of the intricate dynamic processes involved is currently lacking, which could yield valuable insights for regulating sauerkraut fermentation. This study compares spontaneously sauerkrauts with the sauerkrauts inoculated with autochthonous Lactiplantibacillus plantarum SC-MDJ and commercial L. plantarum, respectively. We examine their physicochemical properties, quality characteristics, bacterial community dynamics, and ecological network interactions. Inoculation with L. plantarum leads to reduced bacterial community richness and niche breadth, but an increase in robustness, interactions, and assembly processes. Notably, there appears to be a potential correlation between bacterial community structure and quality characteristics. Particularly, sauerkraut inoculated with L. plantarum SC-MDJ may produce a sourness more quickly, possibly attributed to the enhanced ecological role of L. plantarum SC-MDJ. This study establishes a foundation for the targeted regulation of sauerkraut fermentation.

Three-year follow-up study reveals improved survival rate in NSCLC patients underwent guideline-concordant diagnosis and treatment.

Background: No studies in China have assessed the guideline-concordance level of the first-course of non-small cell lung cancer (NSCLC) diagnosis and treatment and its relationship with survival. This study comprehensively assesses the current status of guideline-concordant diagnosis (GCD) and guideline-concordant treatment (GCT) of NSCLC in China and explores its impact on survival. Methods: First course diagnosis and treatment data for NSCLC patients in Liaoning, China in 2017 and 2018 (n=1828) were used and classified by whether they underwent GCD and GCT according to Chinese Society of Clinical Oncology (CSCO) guidelines. Pearson's chi-squared test was used to determine unadjusted associations between categorical variables of interest. Logistic models were constructed to identify variables associated with GCD and GCT. Kaplan-Meier analysis and log-rank tests were used to estimate and compare 3-year survival rates. Multivariate Cox proportional risk models were constructed to assess the risk of cancer mortality associated with guideline-concordant diagnosis and treatment. Results: Of the 1828 patients we studied, 48.1% underwent GCD, and 70.1% underwent GCT. The proportions of patients who underwent both GCD and GCT, GCD alone, GCT alone and neither GCD nor GCT were 36.7%, 11.4%, 33.5% and 18.4%, respectively. Patients in advanced stage and non-oncology hospitals were significantly less likely to undergo GCD and GCT. Compared with those who underwent neither GCD nor GCT, patients who underwent both GCD and GCT, GCD alone and GCT alone had 35.2%, 26.7% and 35.7% higher 3-year survival rates; the adjusted lung cancer mortality risk significantly decreased by 29% (adjusted hazard ratio[aHR], 0.71; 95% CI, 0.53-0.95), 29% (aHR, 0.71; 95% CI, 0.50-1.00) and 32% (aHR, 0.68; 95% CI, 0.51-0.90). Conclusion: The 3-year risk of death is expected to be reduced by 29% if patients with NSCLC undergo both GCD and GCT. There is a need to establish an oncology diagnosis and treatment data management platform in China to monitor, evaluate, and promote the use of clinical practice guidelines in healthcare settings.

Shape Self-Adaptive Liquid Embolic Agent for Ultrafast and Durable Vascular Embolization.

Minimally invasive embolization greatly decreases the mortality resulting from vascular injuries while still suffering from a high risk of recanalization and systematic thrombosis due to the intrinsic hydrophobicity and poor adhesion of the clinically used liquid embolic agent of Lipiodol. In this study, a shape self-adaptive liquid embolic agent was developed by mixing biocompatible poly(acrylic acid) (PAA), two-dimensional magnesium-aluminum layered double hydroxide (LDH), and poly(ethylene glycol)200 (PEG200). Upon contact with blood, the injectable PAA-LDH@PEG200 would quickly absorb water to form an adhesive and mechanically strong PAA-LDH thin hydrogel within 5 s, which could firmly adhere to the blood vessel wall for ultrafast and durable embolization. In addition, benefiting from the "positively charged nucleic center effect" of LDH nanosheets, the liquid PAA-LDH@PEG200 could avoid vascular distension by PAA overexpansion and possess high shock-resistant mechanical strength from the blood flow. Furthermore, both in vitro and in vivo embolization experiments demonstrated the complete embolic capacity of liquid PAA-LDH@PEG200 without the occurrence of recanalization for 28 days and also the great potential to act as a platform to couple with chemotherapeutic drugs for the minimized transcatheter arterial chemoembolization (TACE) treatment of VX2 tumors without recurrence for 18 days. Thus, liquid PAA-LDH@PEG200 developed here possesses great potential to act as a shape self-adaptive liquid embolic agent for ultrafast and durable vascular embolization.

Exploring the interplay between angiosperm chlorophyll metabolism and environmental factors.

MAIN CONCLUSION: In this review, we summarize how chlorophyll metabolism in angiosperm is affected by the environmental factors: light, temperature, metal ions, water, oxygen, and altitude. The significance of chlorophyll (Chl) in plant leaf morphogenesis and photosynthesis cannot be overstated. Over time, researchers have made significant advancements in comprehending the biosynthetic pathway of Chl in angiosperms, along with the pivotal enzymes and genes involved in this process, particularly those related to heme synthesis and light-responsive mechanisms. Various environmental factors influence the stability of Chl content in angiosperms by modulating Chl metabolic pathways. Understanding the interplay between plants Chl metabolism and environmental factors has been a prominent research topic. This review mainly focuses on angiosperms, provides an overview of the regulatory mechanisms governing Chl metabolism, and the impact of environmental factors such as light, temperature, metal ions (iron and magnesium), water, oxygen, and altitude on Chl metabolism. Understanding these effects is crucial for comprehending and preserving the homeostasis of Chl metabolism.

Evaluation of Drug-Drug Interaction Between Henagliflozin and Hydrochlorothiazide in Healthy Chinese Volunteers.

Purpose: Henagliflozin is an original, selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. Hydrochlorothiazide (HCTZ) is a common anti-hypertensive drug. This study aimed to evaluate the potential interaction between henagliflozin and HCTZ. Methods: This was a single-arm, open-label, multi-dose, three-period study that was conducted in healthy Chinese volunteers. Twelve subjects were treated in three periods, period 1: 25 mg HCTZ for four days, period 2: 10 mg henagliflozin for four days and period 3: 25 mg HCTZ + 10 mg henagliflozin for four days. Blood samples and urine samples were collected before and up to 24 hours after drug administrations on day 4, day 10 and day 14. The plasma concentrations of henagliflozin and HCTZ were analyzed using LC-MS/MS. The urine samples were collected for pharmacodynamic glucose and electrolyte analyses. Tolerability was also evaluated. Results: The 90% CI of the ratio of geometric means (combination: monotherapy) for AUCτ,ss of henagliflozin and HCTZ was within the bioequivalence interval of 0.80-1.25. For henagliflozin, co-administration increased Css, max by 24.32% and the 90% CI of the GMR was (108.34%, 142.65%), and the 24-hour urine volume and glucose excretion decreased by 0.43% and 19.6%, respectively. For HCTZ, co-administration decreased Css, max by 19.41% and the 90% CI of the GMR was (71.60%, 90.72%), and the 24-hour urine volume and urinary calcium, potassium, phosphorus, chloride, and sodium excretion decreased by 11.7%, 20.8%, 11.8%, 11.9%, 22.0% and 15.5%, respectively. All subjects (12/12) reported adverse events (AEs), but the majority of theses AEs were mild and no serious AEs were reported. Conclusion: Although Css,max was affected by the combination of henagliflozin and HCTZ, there was no clinically meaningful safety interaction between them. Given these results, coadministration of HCTZ should not require any adaptation of henagliflozin dosing. Trial Registration: ClinicalTrials.gov NCT06083116.