Key genes and metabolites that regulate wool fibre diameter identified by combined transcriptome and metabolome analysis.

BACKGROUND: Fibre diameter is an important economic trait of wool fibre. As the fibre diameter decreases, the economic value of wool increases. Therefore, understanding the mechanism of wool fibre diameter regulation is important in improving the value of wool. RESULTS: In this study, we used non-targeted metabolome and reference transcriptome data to detect differences in metabolites and genes in groups of Alpine Merino sheep with different wool fibre diameter gradients, and integrated metabolome and transcriptome data to identify key genes and metabolites that regulate wool fibre diameter. We found 464 differentially abundant metabolites (DAMs) and 901 differentially expressed genes (DEGs) in four comparisons of groups with different wool fibre diameters. Approximately 25% of the differentially abundant metabolites were lipid and lipid-like molecules. These molecules were predicted to be associated with skin development and keratin filament by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. Key genes, including COL5A2, COL5A3, CREB3L4, COL1A1, and SFRP4, were identified by gene set enrichment analysis. CONCLUSIONS: Key genes regulating wool fibre diameter were identified, the effects of lipid molecules on wool performance were investigated, and potential synergies between genes and metabolites were postulated, providing a theoretical framework for fine wool sheep breeding.

Molecular Regulation of Shoot Architecture in Soybean.

Soybean (Glycine max [L.] Merr.) serves as a major source of protein and oil for humans and animals. Shoot architecture, the spatial arrangement of a plant's above-ground organs, strongly affects crop yield and is therefore a critical agronomic trait. Unlike wheat and rice crops that have greatly benefitted from the Green Revolution, soybean yield has not changed significantly in the past six decades owing to its unique shoot architecture. Soybean is a pod-bearing crop with pods adhered to the nodes, and variation in shoot architecture traits, such as plant height, node number, branch number and number of seeds per pod, directly affects the number of pods and seeds per plant, thereby determining yield. In this review, we summarize the relationship between soybean yield and these major components of shoot architecture. We also describe the latest advances in identifying the genes and molecular mechanisms underlying soybean shoot architecture and discuss possible directions and approaches for breeding new soybean varieties with ideal shoot architecture and improved yield.

Synthesis of Efficient S-Scheme Heterostructures Composed of BiPO4 and KNbO3 for Photocatalytic N2 Fixation and Water Purification.

The preparation of catalysts with heterojunction structures is a strategy to achieve efficient charge separation and high photocatalytic activity of photocatalysts. In this work, BiPO4/KNbO3 heterostructure photocatalysts were fabricated by a combination of hydrothermal and precipitation methods and subsequently employed in catalyzing N2-to-NH3 conversion and RhB degradation under light illumination. Morphological analysis revealed the effective dispersion of BiPO4 on KNbO3 nanocubes. Band structure analysis suggests that KNbO3 and BiPO4 exhibit suitable band potentials to form an S-scheme heterojunction. Under the joint action of the built-in electric field at the interface, energy band bending, and Coulomb attraction force, photogenerated electrons and holes with low redox performance are consumed, while those with high redox performance are effectively spatially separated. Consequently, the BiPO4/KNbO3 shows enhanced photocatalytic activity. The NH3 production rate of the optimal sample is 2.6 and 5.8 times higher than that of KNbO3 and BiPO4, respectively. The enhanced photoactivity of BiPO4/KNbO3 is also observed in the photocatalytic degradation of RhB. This study offers valuable insights for the design and preparation of S-scheme heterojunction photocatalysts.

LGBTQ Utilization of a Statewide Tobacco Quitline: Engagement and Quitting Behavior, 2010-2022.

INTRODUCTION: Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) individuals use tobacco at disproportionately high rates but are as likely as straight tobacco users to want to quit and to use quitlines. Little is known about the demographics and geographic distribution of LGBTQ quitline participants, their engagement with services, or their long-term outcomes. AIMS AND METHODS: Californians (N = 333 429) who enrolled in a statewide quitline 2010-2022 were asked about their sexual and gender minority (SGM) status and other baseline characteristics. All were offered telephone counseling. A subset (n = 19 431) was followed up at seven months. Data were analyzed in 2023 by SGM status (LGBTQ vs. straight) and county type (rural vs. urban). RESULTS: Overall, 7.0% of participants were LGBTQ, including 7.4% and 5.4% of urban and rural participants, respectively. LGBTQ participants were younger than straight participants but had similar cigarette consumption. Fewer LGBTQ participants reported a physical health condition (42.1% vs. 48.4%) but more reported a behavioral health condition (71.1% vs. 54.5%; both p's < .001). Among both LGBTQ and straight participants, nearly 9 in 10 chose counseling and both groups completed nearly three sessions on average. The groups had equivalent 30-day abstinence rates (24.5% vs. 23.2%; p = .263). Similar patterns were seen in urban and rural subgroups. CONCLUSIONS: LGBTQ tobacco users engaged with and appeared to benefit from a statewide quitline even though it was not LGBTQ community-based. A quitline with staff trained in LGBTQ cultural competence can help address the high prevalence of tobacco use in the LGBTQ community and reach members wherever they live. IMPLICATIONS: This study describes how participants of a statewide tobacco quitline broke down by sexual orientation and gender. It compares participants both by SGM status and by type of county to provide a more complete picture of quitline participation both in urban areas where LGBTQ community-based cessation programs may exist and in rural areas where they generally do not. To our knowledge, it is the first study to compare LGBTQ and straight participants on their use of quitline services and quitting aids, satisfaction with services received, and rates of attempting quitting and achieving prolonged abstinence from smoking.

Both arthroscopic one-step Broström-Gould and Lasso-loop stitch techniques achieved favourable clinical outcomes for chronic lateral ankle instability.

PURPOSE: Both the arthroscopic Broström-Gould and Lasso-loop stitch techniques are commonly used to treat chronic lateral ankle instability (CLAI). The purpose of this study is to introduce an arthroscopic one-step outside-in Broström-Gould (AOBG) technique and compare the mid-term outcomes of the AOBG technique and Lasso-loop stitch technique. METHODS: All CLAI patients who underwent arthroscopic lateral ankle stabilization surgery in our department from 2018 to 2019 were retrospectively enrolled. The patients were divided into two groups according to the surgical methods employed: the AOBG technique (Group A) and the Lasso-loop technique (Group B). The visual analogue scale pain score, American Orthopaedic Foot and Ankle Society ankle hindfoot score, Tegner activity score and Karlsson-Peterson score were evaluated preoperatively and during the follow-up from June to December 2022. The surgical duration, return to sports, sprain recurrence and surgical complications were also recorded and compared. RESULTS: A total of 74 patients (Group A, n = 42; Group B, n = 32) were included in this study with a mean follow-up of 39 months. No statistically significant differences were observed in demographic parameters or follow-up time between the two groups. Postoperative clinical scores indicated a significant improvement (all with p < 0.001) with no significant difference between the two groups (not significant [n.s.]). There was no significant difference in the surgical duration (46.1 vs. 49.7 min, n.s.), return to sports (92.9% vs. 93.8%, n.s.), or sprain recurrence (4.8% vs. 6.3%, n.s.). Only two cases in Group A reported knot irritation (4.8% vs. 0, n.s.), and one case in Group A experienced local skin numbness (0 vs. 3.1%, n.s.), with no significant difference. CONCLUSION: Both the AOBG and Lasso-loop stitch techniques yielded comparable favourable mid-term outcomes and return to sports with a low rate of surgical complications. Both procedures could be feasible strategies for CLAI patients. LEVEL OF EVIDENCE: Level III.

Two new cassane diterpenoids from the seed kernels of Caesalpinia sinensis.

Two new cassane diterpenoids, sucupiranin MN (1) and sucupiranin ML (2), together with two known compounds sucutinirane C (3) and deacetylsucutinirane C (4) were isolated from the seed kernels of Caesalpinia sinensis. Their structures were elucidated by means of analysis of comprehensive spectroscopic data, especially HRESIMS and 1D/2D NMR spectroscopy. Compounds 1-4 are typical furan-type cassane derivatives with an aromatized C ring. Biological evaluation revealed that compounds 1-4 at the concentration of 10 µM could inhibit the overproduction of NO in LPS-stimulated RAW 264.7 macrophages.

A new cassane diterpenoid from the seed of Caesalpinia sappan.

In this study, a previously undescribed cassane diterpenoid, named caesalpinin JF (1), along with two known cassane diterpenoids caesanine C (2) and tomocinol B (3), was isolated from 95% EtOH extract of the seeds of Caesalpinia sappan Linn. Additionally, three known compounds including pulcherrin R (4), syringaresinol-4'-O-ß-D-glucopyranoside (5) and kaempferol (6) were also identified. The structures of the isolated compounds were elucidated by comprehensive 1D and 2D NMR spectroscopic analyses. Additionally, electronic circular dichroism (ECD) calculation was used to identify the absolute structure of compound 1. Among the isolated compounds, compound 1 displayed a potent anti-neuroinflammation with an IC50 value of 9.87 ± 1.71 µM.

The mechanism of action and chemical synthesis of FDA newly approved drug molecules.

In 2023, the U.S. Food and Drug Administration has approved 29 small molecule drugs. These newly approved small molecule drugs possess the distinct scaffolds, thereby exhibiting diverse mechanisms of action and binding modalities. Moreover, the marketed drugs have always been an important source of new drug development and creative inspiration, thereby fostering analogous endeavors in drug discovery that potentially extend to the diverse clinical indications. Therefore, conducting a comprehensive evaluation of drug approval experience and associated information will facilitate the expedited identification of highly potent drug molecules. In this review, we comprehensively summarized the relevant information regarding the clinical applications, mechanisms of action and chemical synthesis of 29 small molecule drugs, with the aim of providing a promising structural basis and design inspiration for pharmaceutical chemists.

[Metabolite identification of isochlorogenic acid A in rats by HPLC-Q-Exactive Orbitrap-MS].

Isochlorogenic acid A(ICA) is the main active component of several TCMs, such as Artemisiae Scopariae Herba. This study aims to identify the metabolites of orally administered ICA in rat plasma, urine, and feces, and to speculate on its potential metabolic pathways. Rats were administered ICA orally, and samples of plasma, urine, and feces were collected at different time points. High-performance liquid chromatography-quadrupole Exactive Orbitrap-mass spectrometry(HPLC-Q-Exactive Orbitrap-MS) was used in combination with reference standards, retention time comparison, fragmentation pattern analysis, and literature data to identify the metabolites in the biological samples. A total of 39 metabolites(M1-M39) of ICA were preliminarily identified from rat samples, including 31 from plasma(M1-M10, M12-M24, M26-M28, M30, M34-M35, M38-M39), 34 from urine(M1-M11, M13-M15, M19-M25, M27-M39), and 11 from feces(M2-M3, M6, M15, M21-M23, M32, M34, M36-M37). The main metabolic pathways included hydrolysis, glucuronidation, methylation, and sulfonation reactions. This study revealed the metabolic profile of ICA in rat plasma, urine, and feces, providing references for the in-depth elucidation of its pharmacologically active components.

[Correlation of nutritional status with clinical characteristics and lung function in children with cystic fibrosis]. / å›Šæ€§çº¤ç»´åŒ–å„¿ç«¥è¥å »çŠ¶å†µä¸Žä¸´åºŠç‰¹å¾å’Œè‚ºåŠŸèƒ½çš„ç›¸å ³æ€§åˆ†æž.

OBJECTIVES: To investigate the nutritional status of children with cystic fibrosis (CF) and understand the correlation between malnutrition and clinical characteristics as well as lung function. METHODS: A retrospective analysis was performed on clinical data of CF children admitted from January 2016 to June 2023. Clinical characteristics of CF children with different nutritional statuses were compared, and the correlation between malnutrition and lung function was analyzed. RESULTS: A total of 52 CF children were included, comprising 25 boys (48%) and 27 girls (52%), aged between 7 months and 17 years. Respiratory symptoms were the predominant clinical manifestations (96%, 50/52). The prevalence of malnutrition was 65% (34/52), with moderate/severe malnutrition being the most common (65%, 22/34). The malnutrition group had a longer duration of illness, higher proportion of digestive system symptoms, and lower levels of serum albumin (P<0.05). Pulmonary function parameters, including forced expiratory volume in one second as a percentage of the predicted value, ratio of forced expiratory volume in one second to forced vital capacity, forced expiratory flow at 25% of forced vital capacity exhaled, forced expiratory flow at 50% of forced vital capacity exhaled, forced expiratory flow at 75% of forced vital capacity exhaled, and maximum mid-expiratory flow as a percentage of the predicted value, were lower in the malnutrition group compared to the normal nutrition group (P<0.05). Correlation analysis showed body mass index Z-score was positively correlated with the above six pulmonary function parameters (P<0.05). CONCLUSIONS: The prevalence of malnutrition is high in CF children and is associated with decreased lung function. CF children with higher body mass index have better lung function. Therefore, screening and evaluation of nutritional status as well as appropriate nutritional intervention should be emphasized in CF children.

AQP4-A25Q Point Mutation in Mice Depolymerizes Orthogonal Arrays of Particles and Decreases Polarized Expression of AQP4 Protein in Astrocytic Endfeet at the Blood-Brain Barrier.

Aquaporin-4 (AQP4) is characterized by the formation of orthogonal arrays of particles (OAPs) comprising its M1 and M23 isoforms in the plasma membrane. However, the biological importance of OAP formation is obscure. Here, we developed an OAP depolymerization male mouse model by transgenic knock-in of an AQP4-A25Q mutation. Analyses of the mutant brain tissue using blue native polyacrylamide gel electrophoresis, super-resolution imaging, and immunogold electron microscopy revealed remarkably reduced OAP structures and glial endfeet localization of the AQP4-A25Q mutant protein without effects on its overall mRNA and protein expression. AQP4A25Q/A25Q mice showed better survival and neurologic deficit scores when cerebral edema was induced by water intoxication or middle cerebral artery occlusion/reperfusion. The brain water content and swelling of pericapillary astrocytic endfeet processes in AQP4A25Q/A25Q mice were significantly reduced, functionally supporting decreased AQP4 protein expression at the blood-brain barrier. The infarct volume and neuronal damage were also reduced in AQP4A25Q/A25Q mice in the middle cerebral artery occlusion/reperfusion model. Astrocyte activation in the brain was alleviated in AQP4A25Q/A25Q mice, which may be associated with decreased cell swelling. We conclude that the OAP structure of AQP4 plays a key role in its polarized expression in astrocytic endfeet processes at the blood-brain barrier. Therefore, our study provided new insights into intervention of cerebral cellular edema caused by stroke and traumatic brain injury through regulating AQP4 OAP formation.SIGNIFICANCE STATEMENT Aquaporin-4 (AQP4) is characterized by orthogonal arrays of particles (OAPs) comprising the M1 and M23 isoforms in the membrane. Here, an OAP depolymerization male mouse model induced by AQP4-A25Q mutation was first established, and the functions of OAP depolymerization in cerebral edema have been studied. The results revealed that AQP4 lost its OAP structure without affecting AQP4 mRNA and protein levels in AQP4-A25Q mice. AQP4-A25Q mutation mice has neuroprotective effects on cerebral edema induced by water intoxication and middle cerebral artery occlusion/reperfusion through relieving the activation of astrocytes and suppressed microglia-mediated neuroinflammation. We concluded that the OAP structure of AQP4 plays a key role in its polarized expression in astrocytic endfeet processes at the blood-brain barrier. Therefore, our study provided new insights into intervention of cerebral cellular edema caused by stroke and traumatic brain injury through regulating AQP4 OAP formation.

SARS-CoV-2 hijacks macropinocytosis to facilitate its entry and promote viral spike-mediated cell-to-cell fusion.

Revealing the mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and cell-to-cell spread might provide insights for understanding the underlying mechanisms of viral pathogenesis, tropism, and virulence. The signaling pathways involved in SARS-CoV-2 entry and viral spike-mediated cell-to-cell fusion remain elusive. In the current study, we found that macropinocytosis inhibitors significantly suppressed SARS-CoV-2 infection at both the entry and viral spike-mediated cell-to-cell fusion steps. We demonstrated that SARS-CoV-2 entry required the small GTPase Rac1 and its effector kinase p21-activated kinase 1 by dominant-negative and RNAi assays in human embryonic kidney 293T-angiotensin-converting enzyme 2 cells and that the serine protease transmembrane serine protease 2 reversed the decrease in SARS-CoV-2 entry caused by the macropinocytosis inhibitors. Moreover, in the cell-to-cell fusion assay, we confirmed that macropinocytosis inhibitors significantly decreased viral spike-mediated cell-to-cell fusion. Overall, we provided evidence that SARS-CoV-2 utilizes a macropinocytosis pathway to enter target cells and to efficiently promote viral spike-mediated cell-to-cell fusion.

Cascade DNA Circuits Mediated CRISPR-Cas12a Fluorescent Aptasensor based on Multifunctional Fe3 O4 @hollow-TiO2 @MoS2 Nanochains for Tetracycline Determination.

Herein, for the first time, the CRISPR-Cas12a system is combined with aptamer, cascaded dynamic DNA network circuits, and Fe3 O4 @hollow-TiO2 @MoS2 nanochains (Fe3 O4 @h-TiO2 @MoS2 NCs) to construct an efficient sensing platform for tetracycline (TC) analysis. In this strategy, specific recognition of the target is transduced and amplified into H1-H2 duplexes containing the specific sequence of Cas12a-crRNA through an aptamer recognition module and the dual amplification dynamic DNA network. Subsequently, the obtained activated Cas12a protein non-specifically cleaves the adjacent reporter gene ssDNA-FAM to dissociate the FAM molecule from the quencher Fe3 O4 @h-TiO2 @MoS2 NCs, resulting in the recovery of the fluorescence signal and further signal amplification. Particularly, the synthesized multifunctional Fe3 O4 @h-TiO2 @MoS2 NCs composites also exhibit superb magnetic separability and photocatalytic degradation ability. Under optimal conditions, the aptasensor displays a distinct linear relationship with the logarithm of TC concentration, and the limit of detection is as low as 0.384 pg mL-1 . Furthermore, the results of spiked recovery confirm the viability of the proposed aptasensor for TC quantification in real samples. This study extends the application of the CRISPR-Cas12a system in the field of analytical sensing and contributes new insights into the exploration of reliable tools for monitoring and treating hazards in food and environment.

Protective effect of inhibiting necroptosis on gentamicin-induced nephrotoxicity.

Necroptosis is defined as a novel programmed cell necrosis that is mediated by receptor interacting serine-threonine protein kinase 1 (RIPK1) and other related signals. Necrosis, apoptosis and inflammation are commonly considered as the leading mechanism in acute kidney injury (AKI) induced by gentamicin (GEN), which is a useful antibiotic for treating the infection of Gram-negative bacterial. However, the necroptosis in the pathogenesis of GEN-induced AKI is unknown. In this study, to investigate the process and function of necroptosis in GEN-induced AKI, NRK-52E and HK-2 cells and SD rats were used as the models. The necroptosis-related proteins, including RIPK1, RIPK3, mixed lineage kinase domain-like (MLKL) and phosphorylated MLKL (p-MLKL), were all increasing time-dependently when GEN was continuously given. By using the RIPK1 inhibitor necrostatin-1 (NEC-1) and RIPK3 inhibitor (CPD42), the GEN-induced toxicity of tubular cells was alleviated. Moreover, it was validated that GEN-induced cell apoptosis and inflammation were attenuated after treating with NEC-1 or CPD42, both in vivo and in vitro. When MLKL was knocked down by siRNA, NEC-1 and CPD42 can not further protect the damage of tubular cells by GEN. Although the using of pan-caspase inhibitor Z-VAD significantly decreased GEN-induced apoptosis, it enhanced necroptosis and slightly promoted the decreased cell viability in GEN-treated cells, with the protective effects weaker than NEC-1 or CPD42. Finally, in vitro minimum inhibitory concentration (MIC) tests and bacteriostatic ring studies showed that NEC-1 did not interfere with the antibiotic effects of GEN. Thus, suppressing necroptosis can serve as a promising strategy for the prevention of GEN-induced nephrotoxicity.

In Situ Fabrication of an S-Scheme NaNbO3/Bi2O2CO3 Heterojunction for Enhanced Performance in Photocatalytic Nitrogen Fixation.

In this study, NaNbO3 microcubes were introduced during the preparation of Bi2O2CO3 nanosheets to construct a series of NaNbO3/Bi2O2CO3 heterojunctions with varying NaNbO3 content. Their photoactivities for N2 fixation were examined and compared. Results demonstrated that 7.5% NaNbO3/Bi2O2CO3 had the highest photoactivity. The NH3 production rate under simulated solar light is 453.1 µmol L-1 g-1 h-1, representing 2.0 and 3.8-fold increases compared to those of Bi2O2CO3 and NaNbO3, respectively. A comprehensive investigation encompassing the physical and chemical properties of the NaNbO3/Bi2O2CO3 photocatalyst was conducted. Bi2O2CO3 nanosheets were discovered to be distributed on the NaNbO3 microcubes surface. The addition of NaNbO3 exhibited nearly no effect on the photoabsorption performance and specific surface area of the Bi2O2CO3. However, the tight contact between NaNbO3 and Bi2O2CO3 and their appropriate band positions led to the formation of a heterojunction structure between them. The electron drift occurring in the interface region induces the creation of an internal electric field and energy band bending. This facilitates the transfer of photogenerated electrons and holes through an S-scheme mechanism, achieving efficient separation without compromising the redox performance. As a result, the NaNbO3/Bi2O2CO3 composite exhibits exceptional performance in the photocatalytic nitrogen fixation reaction. This study expands the application of S-scheme photocatalysts in the field of N2 reduction and provides insights into the preparation of efficient S-scheme photocatalysts.

Semaglutide ameliorates obesity-induced cardiac inflammation and oxidative stress mediated via reduction of neutrophil Cxcl2, S100a8, and S100a9 expression.

Obesity, which is driven by inflammation and oxidative stress, is a risk factor for cardiovascular disease. Semaglutide, a glucagon-like peptide-1 receptor agonist, is an antidiabetic drug with major effects on weight loss. In this study, single-cell transcriptomics was used to examine non-cardiomyocytes to uncover the mechanism of obesity-induced myocardial damage and the cardioprotective impact of semaglutide. We constructed obese mouse models and measured Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), Reactive Oxygen Species (ROS), and Malonic dialdehyde (MDA) levels in serum and heart tissue to determine the levels of inflammation and oxidative stress in obesity and the effect of semaglutide on these levels. Then, utilizing single-cell transcriptomes to screen for key cell populations and differentially expressed genes (DEGs), we assessed the effects of obesity and semaglutide on non-cardiac cells. Finally, a DEG localization analysis was performed to explore DEGs as well as cell types associated with inflammation and oxidative stress. Semaglutide reduced increased TNF-α, IL-6, ROS, and MDA levels in serum and cardiac tissues in obese mouse. Several genes are closely associated with inflammation and oxidative stress. Chemokine (C-X-C motif) ligand 2 (Cxcl2), S100 calcium binding protein A8 (S100a8), and S100 calcium binding protein A9 (S100a9), which were elevated in obesity but decreased following semaglutide treatment, were also expressed particularly in neutrophils. Finally, by decreasing neutrophil Cxcl2, S100a8, and S100a9 expressions, semaglutide may help to reduce cardiac inflammation and oxidative stress. Semaglutide significantly reduced body weight in obese mice as well as exerted anti-inflammatory and antioxidant effects possibly by inhibiting the expression of S100a8, S100a9, and Cxcl2 in neutrophils. These discoveries are expected to reveal new molecular mechanisms underlying obesity-related heart damage and semaglutide's cardioprotective properties.

An oral phenylacrylic acid derivative suppressed hepatic stellate cell activation and ameliorated liver fibrosis by blocking TGF-ß1 signalling.

BACKGROUND AND AIMS: Liver fibrosis is an excessive wound-healing response governed by activated hepatic stellate cells (HSCs). To date, there is no drug available for liver fibrosis. Although ferulic acid (FA) has multiple pharmacological functions, its anti-hepatic fibrosis activity is weak. Based on the activity modification of the FA structure, we synthesized a series of phenylacrylic derivatives and found a superior compound, FA11. In this study, we investigated its antifibrotic effect and mechanism. METHODS: Activated HSC and CCl4 -induced mouse liver fibrosis were established and followed by FA11 treatment. Cell viability was measured by CCK-8 assay. Apoptosis and cell cycle analysis were conducted by flow cytometry. Western blot and Real-time qPCR were used to examine the expression of fibrotic and M1/M2-type macrophages markers. Degree of liver fibrosis was shown by histological staining. RESULTS: In vitro, FA11 inhibited TGF-ß1-induced LX-2 proliferation and led to apoptosis and cycle arrest. Furthermore, elevation of fibrotic markers in TGF-ß1-induced LX-2 and primary activated HSC was reversed by FA11. In vivo, FA11 administration alleviated collagen deposition and blocked HSC activation and epithelial-mesenchymal transition (EMT). Additionally, FA11 reduced macrophage infiltration in fibrotic liver and prevented macrophage polarization to a profibrotic phenotype. Meanwhile, the systemic toxicity of CCl4 was also ameliorated by FA11. Mechanistically, FA11 reversed the phosphorylation of canonical and noncanonical TGF-ß1 signalling, as well as FGFR1 signalling. CONCLUSIONS: We reported an oral phenylacrylic acid derivative, FA11, which showed excellent antifibrotic activity and was expected to be an anti-hepatic fibrosis candidate.

Triglyceride-glucose index and cervical vascular function: outpatient-based cohort study.

OBJECTIVES: The purpose of this study was to investigate the correlation between triglyceride-glucose (TyG) index and cervical vascular function parameters in the general population without cerebrovascular disease. MATERIALS AND METHODS: This was a cross-sectional study that recruited a total of 1996 participants without cerebrovascular disease. TyG index was calculated based on fasting triglycerides and glucose. All patients were divided into two groups based on the median TyG index: the high TyG group and the low TyG group. The differences in basic clinical characteristics and neck vascular function parameters between the two groups of participants were compared, and then the correlation between TyG index and neck vascular function parameters was investigated. RESULTS: Participants with a high TyG index had lower systolic, diastolic, and mean flow velocities in the basilar, vertebral, and internal carotid arteries compared with those with a low TyG index. Participants with a high TyG index had higher pulsatility index in the left vertebral artery and right internal carotid artery, but this difference was not observed in the basilar artery. In addition, TyG index was significantly negatively correlated with systolic, diastolic, and mean flow velocities in the basilar, vertebral, and internal carotid arteries, and the correlation remained after adjusting for confounding factors. CONCLUSION: In the general population, there was a well-defined correlation between TyG index and cervical vascular function parameters, and increased TyG index was independently associated with reduced cervical vascular blood flow velocity.

Gastroprotective 2-(2-phenylethyl)chromone-sesquiterpene hybrids from the resinous wood of Aquilaria sinensis (Lour.) Gilg.

Six previously unprecedented 2-(2-phenylethyl)chromone-sesquiterpene hybrids, aquisinenins A-F (1 - 6), were isolated from the resinous wood of Aquilaria sinensis by a LC-MS-guided fractionation procedure. Their structures were determined by extensive spectroscopic analysis (1D and 2D NMR, UV, IR, and HRMS) and experimental and computed ECD data. Compounds 1 - 6 were rare dimeric 2-(2-phenylethyl)chromone-sesquiterpene derivatives featuring 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone hybridized with different sesquiterpene (eudesmane/guaiane type) moieties via ester bond. Furthermore, all the isolated compounds were evaluated for their protective effects on taurocholic acid (TCA)-induced GES-1 cell injury. The most effective aquisinenin F (6) was used to elucidate the involved mechanism on protection against TCA-induced gastric mucosal damage. Our results indicated that 6 protected against gastric mucosal cell insult by downregulation of the ER stress triggered by TCA.

Paravertebral Muscle Morphology in L4-L5 Disc Herniation: Insights from the Michigan State University Classification.

BACKGROUND Lumbar disc herniation (LDH) at L4-L5 impacts paravertebral muscle morphology. Intervertebral disc degeneration is linked to paravertebral muscle changes, affecting LDH treatment outcomes. This study explored L4-L5 LDH paravertebral muscle alterations, specifically in the erector spinae, multifidus, and psoas major, using Michigan State University's classification to guide LDH treatment. MATERIAL AND METHODS The study enrolled 160 patients, including 39 normal patients and 121 L4-L5 LDH patients. Patients with LDH were grouped according to MSU classification and compared to the normal group according to demographics and imaging changes. RESULTS In patients with L4-L5 herniation in Zone B, the FI of the ES muscle at L3-L4 level, L4-L5 level, and L5-S1 level was higher than that of normal people (P=0.018, P=0.043, P=0.010, respectively), and there was no difference between FI of MF and normal people. The Zone B patients also had a smaller CSA of the ES muscle at L4-L5 level than that in the normal group (P=0.049). Patients in the Zone C group were older than those in the normal group (P=0.014). The CSA of the PM of patients with Grade 3 herniation differed from that of the normal group at the L4-L5 and L5-S1 level. They were higher than in normal people at L4-L5 level (P=0.011) and lower at L5-S1 level (P=0.028). CONCLUSIONS In patients with L4-L5 herniation in Zone B, the FI of ES at L3-S1 level was higher than in normal people, and the CSA at L4-L5 level was smaller than in normal people. In patients with Grade3 herniation, PM CSA was larger at L4-L5 level and smaller at L5-S1 level than in normal people.