The dual role of FSP1 in programmed cell death: resisting ferroptosis in the cell membrane and promoting necroptosis in the nucleus of THP-1 cells.

BACKGROUND: Acute monocytic leukemia-M5 (AML-M5) remains a challenging disease due to its high morbidity and poor prognosis. In addition to the evidence mentioned earlier, several studies have shown that programmed cell death (PCD) serves a critical function in treatment of AML-M5. However, the role and relationship between ferroptosis and necroptosis in AML-M5 remains unclear. METHODS: THP-1 cells were mainly treated with Erastin and IMP-366. The changes of ferroptosis and necroptosis levels were detected by CCK-8, western blot, quantitative real-time PCR, and electron microscopy. Flow cytometry was applied to detect the ROS and lipid ROS levels. MDA, 4-HNE, GSH and GSSG were assessed by ELISA kits. Intracellular distribution of FSP1 was studied by immunofluorescent staining and western blot. RESULTS: The addition of the myristoylation inhibitor IMP-366 to erastin-treated acute monocytic leukemia cell line THP-1 cell not only resulted in greater susceptibility to ferroptosis characterized by lipid peroxidation, glutathione (GSH) depletion and mitochondrial shrinkage, as the FSP1 position on membrane was inhibited, but also increased p-RIPK1 and p-MLKL protein expression, as well as a decrease in caspase-8 expression, and triggered the characteristic necroptosis phenomena, including cytoplasmic translucency, mitochondrial swelling, membranous fractures by FSP1 migration into the nucleus via binding importin α2. It is interesting to note that ferroptosis inhibitor fer-1 reversed necroptosis. CONCLUSION: We demonstrated that inhibition of myristoylation by IMP-366 is capable of switching ferroptosis and ferroptosis-dependent necroptosis in THP-1 cells. In these findings, FSP1-mediated ferroptosis and necroptosis are described as alternative mechanisms of PCD of THP-1 cells, providing potential therapeutic strategies and targets for AML-M5.

Effect of robbing intensity on reproductive success of Symphytum officinale (Boraginaceae).

The intervention of nectar robbers in plant pollination systems will cause some pollinators to modify their foraging behavior to act as secondary robbers, consequently adopting a mixed foraging strategy. The influence of nectar robbing on pollinator behavior may be affected by spatio-temporal difference of robbing intensity, and consequently, may have different effects on the pollination of host plants. However, whether and how the nectar robbing might influence pollinators under different robbing intensity still needs further investigation. In this study, Symphytum officinale was used to detect the effect of nectar robbers on pollinators under different robbing intensity as well as their effects on plant reproductive success. Six robbing levels and three bumblebees with mixed foraging behaviors were used to evaluate the effect of different robbing intensity on pollinator behavior, visitation rate, flower longevity and pollen deposition. Our results indicated that the robbing rate increased gradually with the proportion of robbed flowers, but which did not affect the frequency of legitimate visits. The increase of robbing rate promoted the corolla abscission, and then enhanced the self-pollen deposition, but which had no significant effect on cross-pollen deposition. These results indicate that the overall fitness of S. officinale was improved by combined self and cross-pollination modes when visited by both pollinators and nectar robbers simultaneously. Although nectar robbing is not uncommon, its consequences for pollination in the interaction web have not been well studied. Our results emphasize the significance of indirect impacts in mediating the adaptive outcomes of species interactions.

Transcriptomic and physiological analyses of Symphytum officinale L. in response to multiple heavy metal stress.

Soil heavy metal contamination has become a global environmental issue, which threaten soil quality, food security and human health. Symphytum officinale L. have exhibited high tolerance and restoration capacity to heavy metals (HMs) stress. However, little is known about the mechanisms of HMs in S. officinale. In this study, transcriptomic and physiological changes of S. officinale response to different HMs (Pb, Cd and Zn) were analyzed and investigated the key genes and pathways involved in HMs uptake patterns. The results showed that phenotypic effects are not significant, and antioxidant enzyme activities were all upregulated. Transcriptome analysis indicated that 1247 differential genes were up-regulated, and 1963 differential genes were down-regulated under Cd stress, while 3752 differential genes were up-regulated, and 7197 differential genes were down-regulated under Pb stress; and 527 differential genes were up-regulated; and 722 differential genes were down-regulated under Zn stress. Based on their expression, we preliminarily speculate that different HMs resistance of S. officinale may be regulated by the differential expression of key genes. These results provide a theoretical basis for determining the exact expression of genes in plants under different heavy metal stress, the processes involved molecular pathways, and how they can be efficiently utilized to improve plant tolerance to toxic metals and improve phytoremediation efficiency.

The suppression of hyperlipid diet-induced ferroptosis of vascular smooth muscle cells protests against atherosclerosis independent of p53/SCL7A11/GPX4 axis.

Ferroptosis as a novel programmed cell death that involves metabolic dysfunction due to iron-dependent excessive lipid peroxidation has been implicated in atherosclerosis (AS) development characterized by disrupted lipid metabolism, but the atherogenic role of ferroptosis in vascular smooth muscle cells (VSMCs), which are principal components of atherosclerotic plaque fibrous cap, remains unclear. The aim of this study was to determine the effects of ferroptosis on AS induced by lipid overload, and the effects of that on VSMCs ferroptosis. We found intraperitoneal injection of Fer-1, a ferroptosis inhibitor, ameliorated obviously high-fat diet-induced high plasma levels of triglycerides, total cholesterol, low-density lipoprotein, glucose and atherosclerotic lesions in ApoE-/- mice. Moreover, in vivo and in vitro, Fer-1 reduced the iron accumulation of atherosclerotic lesions through affecting the expression of TFR1, FTH, and FTL in VSMCs. Interestingly, Fer-1 did augment nuclear factor E2-related factor 2/ferroptosis suppressor protein 1 to enhance endogenous resistance to lipid peroxidation, but not classic p53/SCL7A11/GPX4. Those observations indicated inhibition of VSMCs ferroptosis can improve AS lesions independent of p53/SLC7A11/GPX4, which preliminarily revealed the potential mechanism of ferroptosis in aortic VSMCs on AS and provided new therapeutic strategies and targets for AS.

TYRO3 protects podocyte via JNK/c-jun-P53 pathway.

Podocyte injury plays a critical role in diabetic kidney disease (DKD). Our previous work demonstrated a protective role of tyrosine-protein kinase receptor TYRO3 in glomerular disease; However, the downstream signaling of TYRO3 remains unclear. Our data showed that genetic ablation of tyro3 in zebrafish recapitulated a nephrotic syndrome phenotype. TYRO3 expression was suppressed by high glucose and TGF-ß, which may contribute to the decreased TYRO3 expression in progressive DKD. Moreover, knockdown of TYRO3 expression with siRNA induced podocytes apoptosis and cytoskeleton rearrangement. Further study revealed that TYRO3 conferred antiapoptotic effects through the activation of JNK/c-jun-P53 in podocytes. Our results revealed a novel signaling module of TYRO3 in podocyte homeostasis, which provides a new molecular insight of TYRO3 effect in podocyte protection.

Complications and related risk factors of transradial access cannulation for hemodynamic monitoring in general surgery: a prospective observational study.

PURPOSE: To examine the short-term complications of arterial cannulation for intraoperative monitoring and their related risk factors. METHODS: We included adult inpatients (≥ 18 years old) who underwent an initial transradial access (TRA) cannulation and were scheduled for general surgery between April 8 and November 30, 2020. We used 20G arterial puncture needles for puncturing and manual compression for hemostasis. Demographic, clinical, surgical, anesthetic, and laboratory data were extracted from electronic medical records. Vascular, neurologic, and infectious complications of TRA cannulation were recorded and analyzed. Logistic regression analyses were used to identify risk factors related to TRA cannulation for intraoperative monitoring. RESULTS: Among 509 included patients, 174 developed TRA cannulation-related complications. Puncture site bleeding/hematoma and median nerve injury were observed in 158 (31.0%) and 16 (3.1%) patients, respectively. No patient developed cannula-related infections. Logistic regression analysis revealed increased odds of puncture site bleeding/hematoma in women (odds ratio 4.49, 95% CI 2.73-7.36; P < 0.001) and patients who received intraoperative red blood cell (RBC) suspension transfusion ≥ 4U (odds ratio 5.26, 95% CI 1.41-19.57; P = 0.01). No risk factors for nerve injury were identified. CONCLUSION: Bleeding/hematoma were a common complication of TRA cannulation for intraoperative hemodynamic monitoring during general surgery. Median nerve injury may be an under recognized complication. Female sex and extensive intraoperative RBC transfusion are associated with an increased risk of bleeding/hematoma; however, the risk factors for nerve injury remain unclear. TRIAL REGISTRATION: The study protocol was registered at https://www.chictr.org.cn (ChiCTR1900025140).

The Effects of Six Weeks of Fasted Aerobic Exercise on Body Shape and Blood Biochemical Index in Overweight and Obese Young Adult Males.

Background/Objective: The effects of fasted aerobic exercise on body composition and whether it causes adverse effects remain controversial. This study was to compare the effects of fasted and non-fasted aerobic exercise on body shape and blood biochemical indexes in overweight and obese young adult males, and observe whether FAE triggers adverse reactions. Methods: Thirty overweight and obese young adult males were randomly divided into fasted aerobic exercise (FAE) group, non-fasted aerobic exercise (NFAE) group, and control group. They were subjected to indoor treadmill intervention five days a week combined with diet control for six weeks. The FAE group had breakfast 0.5 h after exercise, and the NFAE group exercised 1 h after breakfast. Both groups filled out adverse reaction questionnaires during exercise, and the control group did not have any intervention. Height, weight, body mass index (BMI), and body fat percentage of the three groups of subjects before and after the experiment were measured by the GAIA KIKO bio-resistance antibody composition analyzer in Korea; waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were measured by the tape measure method; fasting plasma glucose (FPG), fasting insulin (FINs), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein (VLDL), and HDL-C/LDL-C were measured by Roche C8000 automatic biochemical analysis instrument. Results: Weight, BMI, body fat percentage, WC, HC, WHR, WHtR, TG, TC, LDL-C and VLDL decreased very significantly (P < 0.01) in the FAE and NFAE groups after the 6-week experiment. The decrease in FINS was significant in the FAE group (P < 0.05) and the decrease in HDL-C was very significant in the NFAE group (P < 0.01). There was no significant difference in the frequency of adverse reactions between two groups (P > 0.05). Conclusion: Six-week FAE and NFAE significantly improved body shape in overweight and obese young adult males, while FAE significantly reduced fasting insulin levels and increased tissue cell sensitivity to insulin. And compared to NFAE, 30 min of FAE in the morning did not increase adverse effects.

Analysis of endophyte diversity of two Gentiana plants species and the association with secondary metabolite.

BACKGROUND: The influence of external environmental factors on secondary metabolites of medicinal plants has always been studied. However, little is known about the relationships between endophytes and host metabolites, especially the relationship differences between different plant species. Thus, we used high-throughput sequencing methods to compare endophyte diversity from roots of two closely related species, Gentiana officinalis and G. siphonantha, from the same production area, and analyze the association with four secondary metabolites (Gentiopicroside, Loganic acid, Swertiamarine and Sweroside). RESULTS: The fungal and bacteria communities' richness and diversity of G. siphonantha was higher than G. officinalis. Ascomycota and Proteobacteria were dominant fungal and bacterial phylum of the two closely related species. At the genus level, Tetracladium and Cadophora were dominant fungal genus in G. officinalis and G. siphonantha samples, respectively. While Pseudomonas was dominant bacterial genus in two closely related species, with relative abundances were 8.29 and 8.05%, respectively. Spearman analysis showed that the content of loganic acid was significantly positively correlated with endophytic fungi, the content of gentiopicroside, swertiamarine and sweroside were significantly positively correlated with endophytic bacteria in the two related species. PICRUSt and FUNGuild predictive analysis indicated that metabolism and saprotroph was primary function of endophytic bacteria and fungi in the two related species. CONCLUSION: Our results will expand the knowledge on relationships of plant-microbe interactions and offer pivotal information to reveal the role of endophytes in the production of Gentiana plant and its important secondary metabolite.

Metal-Free, Adjustable, and Recyclable Catalytic Systems for the Construction of C-C Bonds by Activating Propargylic Alcohols.

Pyrano[3,2-c]coumarin derivatives and C3-substituted 4-hydroxycoumarins as important skeletal structures of active natural products and pharmaceutically relevant molecules have received increasing attention. However, developing an adjustable system for selectively synthesizing them is still a challenging task. Herein, sulfonic acid-functionalized ionic liquid was successfully used as the catalyst for the alkylation of 4-hydroxycoumarin derivatives with secondary aromatic propargylic alcohols using dimethyl carbonate as the green solvent, giving up to 98% yield. On the other hand, protonated imidazole-based ionic liquid-catalyzed cyclization was also selectively achieved with a nearly quantitative yield. Developed metal-free catalytic systems exhibited well adjustable and recyclable properties, avoiding the contamination of metal and halogen, reducing the neutralization after the reaction, and benefiting the separation between the catalyst and the product. New strategies were applied for performing the gram-scale reaction smoothly. The adjustable systems might occur through two different mechanisms involving propargylic or allenic carbocation and hydrogen bonding effects between the catalysts and the substrates.

[Whole Genome Sequence Determination and Analysis of Bacillus Subtilis Strain CGMCC 12426].

Objective To describe the microbiological characteristics of Bacillus subtilis(B. subtilis)CGMCC 12426 and determine and analyze its complete genome sequences.Methods B. subtilis strain CGMCC 12426 genomic DNA sequencing was performed on a single molecule real-time sequencing(SMRT)platform and the annotation was completed in the NCBI Prokaryotic Genomic Annotation Pipeline(pGAP).Results The complete genomic sequences of the released B. subtilis CGMCC 12426 consisted of a 4 138 265-bp circular chromosome and a 74 165-bp plasmid,which resulted in the prediction of 4581 genes including 4222 coding sequences,87 tRNAs,and 30 rRNAs(which included 5S rRNA,16S rRNA,and 23S rRNA).Conclusion The genome sequencing provided a basis for further investigations on the genetic background of B. subtilis and on the metabolic and regulatory mechanisms.

Fabrication of TiO2 Nanostructures on Ti3SiC2 Substrate by Anodic Oxidation.

A TiO2 nanostructure was prepared on a Ti3SiC2 substrate with different water and NH4F concentrations in a fluoride-containing ethylene glycol electrolyte via an anodization process using the same constant-anodization potentials, anodization duration and temperature. The as-prepared samples were characterized by a field-emission scanning electron microscope equipped with an energy dispersive X-ray spectroscope, as well as by X-ray diffraction and X-ray photoelectron spectroscopy. The influence of the anodizing parameters and annealing temperature on the morphology of the nanostructure and the phase structure was studied. The results showed that the scattered TiO2 nanotubes and TiO2 nanoporous films were successfully fabricated in the glycol electrolyte containing (3.0 wt%) NH4F +(5.0 vol%) H2O. The as-prepared samples before calcination were amorphous and could transform to the anatase phase at temperatures higher than 500 °C. As the annealing temperature increased, the crystallization of the anatase phase was enhanced, and the rutile phase appeared at 600 °C. The as-prepared samples mainly consisted of oxides. Ti2O3 and SiO2 oxides were present in addition to TiO2.

The responses of photosystem II and intracellular ATP production of Arabidopsis leaves to salt stress are affected by extracellular ATP.

Hypertonic salt stress with different concentrations of NaCl increased the levels of extracellular ATP of Arabidopsis leaves. And, hypertonic salt stress decreased the levels of F v /F m (the maximal efficiency of photosystem II), Φ PSII (the photosystem II operating efficiency), qP (photochemical quenching), and intracellular ATP (iATP) production. The treatment with ß,γ-methyleneadenosine 5'-triphosphate (AMP-PCP), which can exclude extracellular ATP from its binding sites of extracellular ATP receptors, caused a further decrease in the levels of F v /F m , Φ PSII, qP, and iATP production of the salt-stressed Arabidopsis leaves, while the addition of exogenous ATP rescued the inhibitory effects of AMP-PCP on Φ PSII , qP, and iATP production under hypertonic salt stress. Under hypertonic salt stress, the values of F v /F m , Φ PSII , qP, and iATP production were lower in the dorn 1-3 mutant than in the wild-type plants. These results indicate that the responses of photosystem II and intracellular ATP production to salt stress could be affected by extracellular ATP.

Insights into water-mediated ion clustering in aqueous CaSO4 solutions: pre-nucleation cluster characteristics studied by ab initio calculations and molecular dynamics simulations.

The molecular structure of growth units building crystals is a fundamental issue in the crystallization processes from aqueous solutions. In this work, a systematic investigation of pre-nucleation clusters and their hydration characteristics in aqueous CaSO4 solutions was performed using ab initio calculations and molecular dynamics (MD) simulations. The results of ab initio calculations and MD simulations indicate that the dominant species in aqueous CaSO4 solutions are monodentate ion-associated structures. Compared with charged ion clusters, neutral clusters are more likely to be present in an aqueous CaSO4 solution. Neutral (CaSO4)m clusters are probably the growth units involved in the pre-nucleation or crystallization processes. Meanwhile, hydration behavior around ion associated species in aqueous CaSO4 solutions plays an important role in related phase/polymorphism selections. Upon ion clustering, the residence of some water molecules around Ca2+ in ion-associated species is weakened while that of some bridging waters is enhanced due to dual interaction by Ca2+ and SO42-. Some phase/polymorphism selections can be achieved in aqueous CaSO4 solutions by controlling the hydration around pre-nucleation clusters. Moreover, the association trend between calcium and sulfate is found to be relatively strong, which hints at the low solubility of calcium sulfate in water.

Associations between endothelial nitric oxide synthase polymorphisms and risk of diabetic nephropathy: an updated meta-analysis.

BACKGROUND: Genetic polymorphism of endothelial nitric oxide synthase (eNOS) has been implicated in the risk of diabetic nephropathy (DN), but the published findings were inconsistent. We performed a comprehensive meta-analysis to derive a more precise estimation of the association between genetic polymorphisms of eNOS and the risk of DN. METHODS: Six online database were researched on the associations between polymorphisms of eNOS (T786C, G894T, 4b/4a) and DN risk. PRISMA statement and Hardy-Weinberg equilibrium assessment were used in this report. Odds ratio and 95% confidence interval were estimated based on the following genetic contrast/models: allelic model, dominant model, recessive model and co-dominant model. The publication bias and sensitivity analysis were also performed to guarantee the statistical power. RESULTS: A total of 49 case-control studies with 11,990/9754/5131 participants for DN/DM/HC group were eligible for meta-analysis (7/25/31 studies for T786C/G984T/4b/a). For the eNOS-T786C, C allele showed a weak association between C allele and DN risk in DN/T2DM group. For eNOS-G894T, there was an association between T allele and DN risk in the global, Asian and African population in DN/T2DM group. For the eNOS-4b/4a, 4a allele was found contributing significantly to increased DN risk in the global population. CONCLUSION: Our comprehensive meta-analysis suggests that three polymorphisms of eNOS may be the increased risk factors of DN development, especially in Asian population and T2DM group.

Commercial Nafion Membranes for Harvesting Osmotic Energy from Proton Gradients that Exceed the Commercial Goal of 5.0 W/m2.

Osmotic energy from proton gradients in industrial acidic wastewater can be harvested and converted to electricity through membranes, making it a renewable and sustainable power source. However, the currently designed membranes for harvesting proton gradient energy in acidic wastewater cannot simultaneously achieve excellent chemical/mechanical stability and high power density under a large-scale area and require high cost and complex operations. Here, we demonstrate that commercial Nafion membranes with high chemical/mechanical stability and proton transport selectivity can generate a power density of 5.1 W/m2 for harvesting osmotic energy from proton gradients under a test area of 0.2 mm2, which exceeds the commercial goal of 5.0 W/m2. Even under a test area of 12.5 mm2, a power density of 2.1 W/m2 can be achieved under a strong acid condition. In addition, the heat can greatly promote proton transport, and the power density is increased, i.e., 8.1 W/m2 at 333 K (5.1 W/m2 at 293 K) under a test area of 0.2 mm2. By matching membranes with ion selectivity, our work demonstrates the potential of Nafion membranes for harvesting proton gradient energy in acidic wastewater and provides an approach for large-scale conversion of osmotic energy.

Exploring the Effects of S-Nitrosylation on Caspase-3 Modification and Myofibril Degradation of Beef In Vitro.

This study aimed to explore the effects of S-nitrosylation on caspase-3 modification and its subsequent effects on beef myofibril degradation in vitro. Recombinant caspase-3 was reacted with different concentrations of S-nitrosoglutathione (GSNO, nitric oxide donor) at 37 °C for 30 min and subsequently incubated with purified myofibrillar protein from bovine semimembranosus muscle. Results indicated that the activity of caspase-3 was significantly reduced after GSNO treatments (P < 0.05) and showed a dose-dependent inhibitory effect, which was attributed to the increased S-nitrosylation extent of caspase-3. LC-MS/MS analysis revealed that caspase-3 was S-nitrosylated at cysteine sites 116, 170, 184, 220, and 264. Moreover, the degradation of desmin and troponin-T was notably suppressed by S-nitrosylated caspase-3 (P < 0.05). To conclude, protein S-nitrosylation could modify the cysteine residues of caspase-3, which accounts for the reduced caspase-3 activity and further represses its proteolytic ability on beef myofibrillar protein.

S-nitrosoproteomics profiling elucidates the regulatory mechanism of S-nitrosylation on beef quality.

This study aimed to quantitively profile the S-nitrosylation in beef semimembranosus (SM) with different treatments (nitric oxide donor or nitric oxide synthase inhibitor) by applying iodoTMT-based nitrosoproteomics. Results showed that 2096 S-nitrosylated cysteine sites in 368 proteins were detected in beef SM. Besides, differential SNO-modified proteins were screened, some of which were involved in crucial biochemical pathways, including calcium-releasing-related proteins, energy metabolic enzymes, myofibrils, and cytoskeletal proteins. GO analysis indicated that differential proteins were localized in a wide range of cellular compartments, such as cytoplasm, organelle, and mitochondrion, providing a prerequisite for S-nitrosylation exerting broad roles in post-mortem muscles. Furthermore, KEGG analysis validated that these proteins participated in the regulation of diverse post-mortem metabolic processes, especially glycolysis. To conclude, changes of S-nitrosylation levels in post-mortem muscles could impact the structure and function of crucial muscle proteins, which lead to different levels of muscle metabolism and ultimately affect beef quality.

N6-methyladenosine-modified circ_0006168 promotes epithelial mesenchymal transition via miR-384/STAT3/Snail axis in esophageal squamous cell carcinoma.

Circular RNAs (circRNAs) are involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). This study aimed to explore the mechanisms of aberrant expression and functions of circ_0006168 in ESCC. In this study, real-time qPCR and fluorescence in situ hybridization (FISH) are adopted to estimate the expression and localization of circ_0006168 in cancer tissues and cells. Methylated RNA immunoprecipitation (MeRIP) was performed to detect the N6-methyladenosine (m6A) modification of circ_0006168. Gain- and loss-of-functions of circ_0006168 were performed to identify its role in ESCC progression. RNA-binding protein immunoprecipitation (RIP) was used to detect the interaction of circ_0006168 with IGF2BP2. Luciferase reporter assay and RIP are used to confirm the circ_0006168/miR-384/STAT3 ceRNA network. Our results showed that the expression of circ_0006168 was upregulated in ESCC tissues and cells. METTL3-mediated m6A modification increased the expression of circ_0006168 via IGF2BP2-dependent way in TE-1 cells. Circ_0006168 promoted cell proliferation, migration, invasion, cell cycle progression and inhibited cell apoptosis, while knockdown of circ_0006168 had the reverse effects. Mechanistically, circ_0006168 acted its functions via miR-384/STAT3/Snail axis in TE-1 cells. In conclusion, circ_0006168 is upregulated in ESCC and m6A methylation increased its expression via IGF2BP2. CircRNA_0006168 promotes cell migration, invasion by regulating EMT via miR-384/STAT3/Snail axis in ESCC.

CXCL13-neutralizing Antibody Alleviate Chronic Skeletal Muscle Degeneration in a Mouse Model.

INTRODUCTION: Skeletal muscle degeneration is a common effect of chronic muscle injuries, including fibrosis and fatty infiltration, which is the replacement of preexisting parenchymal tissue by extracellular matrix proteins and abnormal invasive growth of fibroblasts and adipocytes. METHOD: This remodeling limits muscle function and strength, eventually leading to reduced quality of life for those affected. Chemokines play a major role in the regulation of immunocyte migration, inflammation, and tissue remodeling and are implicated in various fibrotic and degenerative diseases. In this study, we aimed to investigate the role of the B-cell chemokine CXCL13 in the gastrocnemius muscle of the Achilles tendon rupture model mouse. We hypothesize that CXCL13 may promote fibrosis and aggravate skeletal muscle degeneration. We performed RNA sequencing and bioinformatics analysis of gastrocnemius muscle from normal and model mice to identify differentially expressed genes and signal pathways related to skeletal muscle degeneration and fibrosis. RESULTS: Our results show that CXCL13 is highly expressed in chronically degenerating skeletal muscle. Furthermore, CXCL13-neutralising antibodies with therapeutic potential were observed to inhibit fibrosis and adipogenesis in vivo and in vitro. CONCLUSION: Our study reveals the underlying therapeutic implications of CXCL13 inhibition for clinical intervention in skeletal muscle degeneration, thereby improving patient prognosis.

Using ultrasonic-assisted sodium bicarbonate treatment to improve the gel and rheological properties of reduced-salt pork myofibrillar protein.

To study the impact of ultrasonic duration (0, 30, and 60 min) and sodium bicarbonate concentration (0% and 0.2%) on the gel properties of reduced-salt pork myofibrillar protein, the changes in cooking yield, colour, water retention, texture properties, and dynamic rheology were investigated. The findings revealed that added sodium bicarbonate significantly increased (P < 0.05) cooking yield, hardness, springiness, and strength of myofibrillar protein while reducing centrifugal loss. Furthermore, the incorporation of sodium bicarbonate led to a significant decrease in L⁎, a⁎, b⁎, and white values of cooked myofibrillar protein; these effects were further amplified with increasing ultrasonic duration (P < 0.05). Additionally, storage modulus (G') significantly increased for myofibrillar protein treated with ultrasonic-assisted sodium bicarbonate treatment resulting in a more compact gel structure post-cooking. In summary, the results demonstrated that ultrasonic-assisted sodium bicarbonate treatment could enhance the tightness of reduced-salt myofibrillar protein gel structure while improving the water retention and texture properties.