Agomir-122-loaded nanoparticles coated with cell membrane of activated fibroblasts to treat frozen shoulder based on homologous targeting.

As a common musculoskeletal disorder, frozen shoulder is characterized by thickened joint capsule and limited range of motion, affecting 2-5% of the general population and more than 20% of patients with diabetes mellitus. Pathologically, joint capsule fibrosis resulting from fibroblast activation is the key event. The activated fibroblasts are proliferative and contractive, producing excessive collagen. Albeit high prevalence, effective anti-fibrosis modalities, especially fibroblast-targeting therapies, are still lacking. In this study, microRNA-122 was first identified from sequencing data as a potential therapeutic agent to antagonize fibroblast activation. Then, Agomir-122, an analog of microRNA-122, was loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Agomir-122@NP), a carrier with excellent biocompatibility for the agent delivery. Moreover, relying on the homologous targeting effect, we coated Agomir-122@NP with the cell membrane derived from activated fibroblasts (Agomir-122@MNP), with an attempt to inhibit the proliferation, contraction, and collagen production of abnormally activated fibroblasts. After confirming the targeting effect of Agomir-122@MNP on activated fibroblasts in vitro, we proved that Agomir-122@MNP effectively curtailed fibroblasts activation, ameliorated joint capsule fibrosis, and restored range of motion in mouse models both prophylactically and therapeutically. Overall, an effective targeted delivery method was developed with promising translational value against frozen shoulder.

Exploring the regulatory role of non-coding RNAs in fiber development and direct regulation of GhKCR2 in the fatty acid metabolic pathway in upland cotton.

Cotton fiber holds immense importance as the primary raw material for the textile industry. Consequently, comprehending the regulatory mechanisms governing fiber development is pivotal for enhancing fiber quality. Our study aimed to construct a regulatory network of competing endogenous RNAs (ceRNAs) and assess the impact of non-coding RNAs on gene expression throughout fiber development. Through whole transcriptome data analysis, we identified differentially expressed genes (DEGs) regulated by non-coding RNA (ncRNA) that were predominantly enriched in phenylpropanoid biosynthesis and the fatty acid elongation pathway. This analysis involved two contrasting phenotypic materials (J02-508 and ZRI015) at five stages of fiber development. Additionally, we conducted a detailed analysis of genes involved in fatty acid elongation, including KCS, KCR, HACD, ECR, and ACOT, to unveil the factors contributing to the variation in fatty acid elongation between J02-508 and ZRI015. Through the integration of histochemical GUS staining, dual luciferase assay experiments, and correlation analysis of expression levels during fiber development stages for lncRNA MSTRG.44818.23 (MST23) and GhKCR2, we elucidated that MST23 positively regulates GhKCR2 expression in the fatty acid elongation pathway. This identification provides valuable insights into the molecular mechanisms underlying fiber development, emphasizing the intricate interplay between non-coding RNAs and protein-coding genes.

Promising probiotic-fermented soymilk for alleviating acute diarrhea: insights into the microbiome and metabolomics.

Fermented soymilk (FSM4) has attracted much attention due to its nutritional and health characteristics. Exploring FSM4 products to alleviate diarrhea can ensure their effectiveness as a therapeutic food for alleviating gastrointestinal disorders. However, the relationship between gut microbiota and gut metabolite production remains unknown during diarrheal episodes. Therefore, the diarrhea-alleviating role and mechanisms of FSM4 in diarrhea rats were investigated via biochemical, gut microbiota, and serum metabolite analyses. The findings showed that consuming FSM4 improved diarrhea symptoms and reduced systemic inflammation better than non-fermented soymilk (NFSM). It is worth noting that FSM4 promoted the diversity, richness, structure, and composition of gut microbiota. It increased the ability to reduce inflammation associated with harmful bacteria (Anaerofilum, Flavonifractor, Bilophila, Anaerostipes, [Ruminococcus]_torques_group, Clostridium_sensu_stricto_1, Turicibacter, Ruminococcus_1, Ruminiclostridium_6, Prevotellaceae_NK3B31_group and Fusicatenibacter), while stimulating the growth of healthy species (Lactobacillus, Ruminococcaceae_UCG-014, Oscillibacter, [Eubacterium]_coprostanoligenes_group, Negativibacillus, and Erysipelotrichaceae_UCG-003). Moreover, metabolomics analysis showed that lipid metabolites such as lysophosphatidylethanolamine (LysoPE) and sphingolipids were upregulated in the NG group, closely related to pro-inflammatory cytokines (IL-6, IL-1ß, TNF-α, and IFN-γ) and the aforementioned pathogenic bacteria. Notably, in treatment groups, especially FSM4, the accumulation of L-ornithine, aspartic acid, ursocholic acid, 18-oxooleate, and cyclopentanethiol was increased, which was robustly associated with the anti-inflammatory factor IL-10 and beneficial bacteria mentioned above. Therefore, it can be inferred that the amino acids, bile acid, 18-oxooleate, and cyclopentanethiol produced in the FSM4 group can serve as metabolic biomarkers, which synergistically act with the gut microbiota to help alleviate inflammation for diarrhea remission. Overall, FSM4 may provide a new alternative, as an anti-inflammatory diet, to alleviate diarrhea.

Probiotic-fermented tomato with hepatic lipid metabolism modulation effects: analysis of physicochemical properties, bioactivities, and potential bioactive compounds.

Lactiplantibacillus plantarum NCUH001046 (LP)-fermented tomatoes exhibited the potential to alleviate obesity in our previous study. This subsequent study further delves deeper into the effects of LP fermentation on the physicochemical properties, bioactivities, and hepatic lipid metabolism modulation of tomatoes, as well as the analysis of potential bioactive compounds exerting obesity-alleviating effects. Results showed that after LP fermentation, viable bacterial counts peaked at 9.11 log CFU mL-1 and sugar decreased, while organic acids, umami amino acids, total phenols, and total flavonoids increased. LP fermentation also improved the inhibition capacities of three digestive enzyme activities and Enterobacter cloacae growth, as well as antioxidant activities. Western blot results indicated that fermented tomatoes, especially live probiotic-fermented tomatoes (LFT), showed improved effects compared to unfermented tomatoes in reducing hepatic lipid accumulation by activating the AMPK signal pathway. UHPLC-Q-TOF/MS-based untargeted metabolomics analysis showed that chlorogenic acid, capsiate, tiliroside, irisflorentin, and homoeriodictyol levels increased after fermentation. Subsequent cell culture assays demonstrated that irisflorentin and homoeriodictyol reduced lipid accumulation via enhancing AMPK expression in oleic acid-induced hyperlipidemic HepG2 cells. Furthermore, Spearman's correlation analysis indicated that the five phenols were positively associated with hepatic AMPK pathway activation. Consequently, it could be inferred that the five phenols may be potential bioactive compounds in LFT to alleviate obesity and lipid metabolism disorders. In summary, these findings underscored the transformative potential of LP fermentation in enhancing the bioactive profile of tomatoes and augmenting its capacity to alleviate obesity and lipid metabolism disorders. This study furnished theoretical underpinnings for the functional investigation of probiotic-fermented plant-based foods.

Preparation of novel membranes with multiple hydrogen bonding sites and π-conjugated structure for high temperature proton exchange membrane fuel cells.

A novel poly(dibenzofuran isatin) (PBFI) with π conjugated structure was synthesized. Through the facile ring-opening reaction, flexible and hydrophilic side chains with hydroxyl and quaternary ammounium groups were grafted into PBFI. Obtained PBFI-x%GTA membranes with twisted polymer structure and multiple hydrogen bonding sites displayed high HT-PEMFC performance.

100-Phones: A Large VI-SLAM Dataset for Augmented Reality Towards Mass Deployment on Mobile Phones.

Visual-inertial SLAM (VI-SLAM) is a key technology for Augmented Reality (AR), which allows the AR device to recover its 6-DoF motion in real-time in order to render the virtual content with the corresponding pose. Nowadays, smartphones are still the mainstream devices for ordinary users to experience AR. However the current VI-SLAM methods, although performing well on high-end phones, still face robustness challenges when deployed on a larger stock of mid- and low-end phones. Existing VI-SLAM datasets use either very ideal sensors or only a limited number of devices for data collection, which cannot reflect the capability gaps that VI-SLAM methods need to solve when deployed on a large variety of phone models. This work proposes 100-Phones. the first VI-SLAM dataset covering a wide range of mainstream phones in the market. The dataset consists of 350 sequences collected by 100 different models of phones. Through analysis and experiments on the collected data, we conclude that the quality of visual-inertial data vary greatly among the mainstream phones, and the current open source VI-SLAM methods still have serious robustness issues when it comes to mass deployment on mobile phones. We release the dataset to facilitate the robustness improvement of VI-SLAM and to promote the mass popularization of AR. Project page: https://github.com/zju3dv/100-Phones.

Exercise potentially prevents colorectal cancer liver metastases by suppressing tumor epithelial cell stemness via RPS4X downregulation.

Background: Colorectal cancer (CRC) is the third most prevalent tumor globally. The liver is the most common site for CRC metastasis, and the involvement of the liver is a common cause of death in patients with late-stage CRC. Consequently, mitigating CRC liver metastasis (CRLM) is key to improving CRC prognosis and increasing survival. Exercise has been shown to be an effective method of improving the prognosis of many tumor types. However, the ability of exercise to inhibit CRLM is yet to be thoroughly investigated. Methods: The GSE157600 and GSE97084 datasets were used for analysis. A pan-cancer dataset which was uniformly normalized was downloaded and analyzed from the UCSC database: TCGA, TARGET, GTEx (PANCAN, n = 19,131, G = 60,499). Several advanced bioinformatics analyses were conducted, including single-cell sequencing analysis, correlation algorithm, and prognostic screen. CRC tumor microarray (TMA) as well as cell/animal experiments are used to further validate the results of the analysis. Results: The greatest variability was found in epithelial cells from the tumor group. RPS4X was generally upregulated in all types of CRC, while exercise downregulated RPS4X expression. A lowered expression of RPS4X may prolong tumor survival and reduce CRC metastasis. RPS4X and tumor stemness marker-CD44 were highly positively correlated and knockdown of RPS4X expression reduced tumor stemness both in vitro and in vivo. Conclusion: RPS4X upregulation may enhance CRC stemness and increase the odds of metastasis. Exercise may reduce CRC metastasis through the regulation of RPS4X.

Identification and characterization of candidate genes for primary root length in Asiatic cotton (Gossypium arboreum L.).

KEY MESSAGE: One major gene controlling primary root length (PRL) in Gossypium arboreum is identified and this research provides a theoretical basis for root development for cotton. Primary root elongation is an essential process in plant root system structure. Here, we investigated the primary root length (PRL) of 215 diploid cotton (G. arboreum) accessions at 5, 8, 10, 15 days after sowing. A Genome-wide association study was performed for the PRL, resulting in 49 significant SNPs associated with 32 putative candidate genes. The SNP with the strongest signal (Chr07_8047530) could clearly distinguish the PRLs between accessions with two haplotypes. GamurG is the only gene that showed higher relative expression in the long PRL genotypes than the short PRL genotypes, which indicated it was the most likely candidate gene for regulating PRL. Moreover, the GamurG-silenced cotton seedlings showed a shorter PRL, while the GamurG-overexpressed Arabidopsis exhibited a significantly longer PRL. Our findings provide insight into the regulation mechanism of cotton root growth and will facilitate future breeding programs to optimize the root system structure in cotton.

Exploring Impact of Probiotic-Fermented Soymilk on Dextran-Sulfate-Sodium-Induced Ulcerative Colitis via Modulating Inflammation and Gut Microbiota Profile.

SCOPE: Lactic acid bacteria with probiotic functions and their fermentation products play a role in regulating ulcerative colitis (UC). This study investigates the potential role of fermented soymilk (FSM4) rich in isoflavones on DSS-induced UC. METHODS AND RESULTS: Mice received 3% DSS and are supplemented daily once for 1 week by NFSM and FSM4. DSS usually causes intestinal inflammation and alters the gut microbiota. FSM4 intervention improves the UC-related inflammation and gut microbiota alteration. It considerably decreases pro-inflammatories such as TNF-α, IL-1ß, and IL-6 in serum and COX-2 and MPO in colon tissues and pathogenic bacteria (Escherichia-Shigella). This facilitates gut-healthy bacteria growth. These healthy bacteria negatively correlat with pro-inflammatory factors but positively associated with acetic acid, butyric acid, and propionic acid, which may act for PPAR-γ pathway activating and NF-κB p65 pathway inhibiting, lowering the risk of UC. Overall, FSM4 might alleviate UC and significantly reverse the dysbiosis of gut microbiota via the PPAR-γ activation. It could be a good alternative for developing functional food to protect against UC. CONCLUSION: FSM4 attenuates intestinal inflammation and modulates the SCFA-producing bacteria growth, which enable the PPAR-γ activation to alleviate the UC target, which could be a dietary intervention strategy for gut health.

Gut Distribution, Impact Factor, and Action Mechanism of Bacteriocin-Producing Beneficial Microbes as Promising Antimicrobial Agents in Gastrointestinal Infection.

Gastrointestinal (GI) infection by intestinal pathogens poses great threats to human health, and the therapeutic use of antibiotics has reached a bottleneck due to drug resistance. The developments of antimicrobial peptides produced by beneficial bacteria have drawn attention by virtue of effective, safe, and not prone to developing resistance. Though bacteriocin as antimicrobial agent in gut infection has been intensively investigated and reviewed, reviews on that of bacteriocin-producing beneficial microbes are very rare. It is important to explicitly state the prospect of bacteriocin-producing microbes in prevention of gastrointestinal infection towards their application in host. This review discusses the potential of gut as an appropriate resource for mining targeted bacteriocin-producing microbes. Then, host-related factors affecting the bacteriocin production and activity of bacteriocin-producing microbes in the gut are summarized. Accordingly, the multiple mechanisms (direct inhibition and indirect inhibition) behind the preventive effects of bacteriocin-producing microbes on gut infection are discussed. Finally, we propose several targeted strategies for the manipulation of bacteriocin-producing beneficial microbes to improve their performance in antimicrobial outcomes. We anticipate an upcoming emergence of developments and applications of bacteriocin-producing beneficial microbes as antimicrobial agent in gut infection induced by pathogenic bacteria.

Microstructure and Friction Properties of AlCrTiVNbx High-Entropy Alloys via Annealing Manufactured by Vacuum Arc Melting.

To enhance the friction and wear properties of alloys, AlCrTiVNbx high-entropy alloys (HEAs) with various Nb contents were prepared using the arc melting technique and then annealed at 1000 °C for 2 h. The microstructure and hardness changes in the AlCrTiVNbx (x = 0.3, 0.4, and 0.5) HEAs after casting and annealing were studied via scanning electron microscopy, X-ray diffractometry, optical microscopy and the Vickers hardness test. The MFT-EC400 ball disc reciprocating friction and wear tester was used to investigate the wear resistance of the HEAs before and after annealing. The results show that the annealed AlCrTiVNbx HEAs changed from a single-phase structure to a multi-phase structure, and the content of the face-center cubic (FCC) phase and hexagonal close-packed (HCP) phase further increases with the increase in Nb content. The hardness value of the annealed HEAs is greatly enhanced compared with the casting state, and the hardness of the Nb0.5 HEA is increased from 543 HV to 725 HV after annealing. The wear resistance of the alloys after the annealing treatment is also greatly improved, among which Nb0.5 has the best wear resistance. The average friction coefficient of Nb0.5 is 0.154 and the wear rate is 2.117 × 10-5 mm3/(N·m). We believe that the precipitation strengthening after the annealing treatment and the lubrication effect of the FCC phase are the reasons for the significant improvement in wear resistance. The morphology of the samples indicates that the wear mechanism of the alloy includes adhesive wear, abrasive wear and a certain degree of oxidation wear.

Manipulation of aurophilicity in constructed clusters of gold(I) complexes with boosted luminescence and smart responsiveness.

High-performance luminescent gold(I) complexes have attracted considerable attention due to their potential applications in various fields, but their construction is a significantly challenging task. Herein, we designed and synthesized a series of novel dinuclear gold(I) complexes 1-4 based on 1,2-bis(diphenylphosphino)benzene and 1,4-bis(diphenylphosphino)benzene frameworks, where para-substitutions of benzene ring were employed for comparison and bulky t-butyl groups were introduced into carbazole ligands to assist flexibly regulating the aurophilicity. Among them, the structure of complex 1 was confirmed by single-crystal X-ray diffraction, and all the complexes exhibited typical aggregation-induced emission characteristics. Due to the construction of intramolecular aurophilicity and the formation of molecular clusters, noticeable enhancement of the luminescent efficiency was achieved for the core complex 1. Together with the introduction of flexible t-butyl groups, good responsiveness towards external mechanical force and solvent vapors were also realized. Moreover, the specific bioimaging ability of complex 1 towards cancer cells was demonstrated. Thus, this work presents the crucial capability of aurophilic manipulation in tuning the luminescence and smart behaviors of gold complexes, and it will open a new route to developing high-performance luminescent materials.

Macrophage-Myofibroblast Transition as a Potential Origin for Skeletal Muscle Fibrosis After Injury via Complement System Activation.

Background: Acute skeletal muscle injury is common in sports. The injured muscle cannot fully recover due to fibrosis resulting from myofibroblasts. Understanding the origin of fibroblasts is, therefore, important for the development of anti-fibrotic therapies. Accumulating evidence shows that a mechanism called macrophage-myofibroblast transition (MMT) can lead to tissue or organ fibrosis, yet it is still unclear whether MMT exists in skeletal muscle and the exact mechanisms. Methods: Single-cell transcriptome of mice skeletal muscle after acute injury was analyzed with a specific attention on the process of MMT. Cell-cell interaction network, pseudotime trajectory analysis, Gene Ontology (GO), and Kyoto Genome Encyclopedia (KEGG) were conducted. A series of experiments in vivo and in vitro were launched for verification. Results: Single cell transcriptomic analysis indicated that, following acute injury, there were much interactions between macrophages and myofibroblasts. A detailed analysis on macrophages indicated that, CD68+α-SMA+ cells, which represented the status of MMT, mainly appeared at five days post-injury. KEGG/GO analysis underlined the involvement of complement system, within which C3ar1, C1qa, C1qb, and C1qc were up-regulated. Trajectory analysis also confirmed a potential shift from macrophages to myofibroblasts. These findings were verified by histological study in mice skeletal muscle, that there were much MMT cells at five days, declined gradually, and vanished 14 days after trauma, when there was remarkable fibrosis formation within the injured muscle. Moreover, C3a stimulation could directly induce MMT in BMDMs. Conclusion: Fibrosis following acute injury is disastrous to skeletal muscle, but the origin of myofibroblasts remains unclear. We proved that, following acute injury, macrophage-myofibroblast transition happened in skeletal muscle, which may contribute to fibrosis formation. This phenomenon mainly occurred at five days post-injury. The complement system can activate MMT. More evidence is needed to directly support the pro-fibrotic role of MMT in skeletal muscle fibrosis after acute injury.

Screening of probiotic Lactobacillus to reduce peanut allergy and with potential anti-allergic activity.

BACKGROUND: Peanut is a significant source of nutrition and a valuable oilseed crop. It is also a serious allergy source, which poses a threat to 1.1% of the population. This study aimed to screen lactic acid bacteria (LAB) with the capacity to alleviate peanut allergenicity and exhibit anti-allergic properties. RESULT: The results show that LAB can make use of substances in peanuts to reduce the pH of peanut milk from 6.603 to 3.593-4.500 by acid production and that it can utilize the protein in peanuts to reduce the allergenic content (especially Ara h 1) and improve biological activity in peanut pulp. The content of Ara h 1 peanut-sensitizing protein was reduced by 74.65% after fermentation. The protein extracted from fermented peanut pulp is more readily digestible by gastrointestinal juices. The inhibitory activity assay of hyaluronidase (an enzyme with strong correlation to allergy) increased from 46.65% to a maximum of 90.57% to reveal that LAB fermentation of peanut pulp exhibited a robust anti-allergic response. CONCLUSION: The strains identified in this study exhibited the ability to mitigate peanut allergenicity partially and to possess potential anti-allergic properties. Lactobacillus plantarum P1 and Lactobacillus salivarius C24 were identified as the most promising strains and were selected for further research. © 2023 Society of Chemical Industry.

A radiomics-based interpretable model to predict the pathological grade of pancreatic neuroendocrine tumors.

OBJECTIVES: To develop a computed tomography (CT) radiomics-based interpretable machine learning (ML) model to predict the pathological grade of pancreatic neuroendocrine tumors (pNETs) in a non-invasive manner. METHODS: Patients with pNETs who underwent contrast-enhanced abdominal CT between 2010 and 2022 were included in this retrospective study. Radiomics features were extracted, and five radiomics-based ML models, namely logistic regression (LR), random forest (RF), support vector machine (SVM), XGBoost, and GaussianNB, were developed. The performance of these models was evaluated using a time-independent testing set, and metrics such as sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve (AUC) were calculated. The accuracy of the radiomics model was compared to that of needle biopsy. The Shapley Additive Explanation (SHAP) tool and the correlation between radiomics and biological features were employed to explore the interpretability of the model. RESULTS: A total of 122 patients (mean age: 50 ± 14 years; 53 male) were included in the training set, whereas 100 patients (mean age: 48 ± 13 years; 50 male) were included in the testing set. The AUCs for LR, SVM, RF, XGBoost, and GaussianNB were 0.758, 0.742, 0.779, 0.744, and 0.745, respectively, with corresponding accuracies of 73.0%, 70.0%, 77.0%, 71.9%, and 72.9%. The SHAP tool identified two features of the venous phase as the most significant, which showed significant differences among the Ki-67 index or mitotic count subgroups (p < 0.001). CONCLUSIONS: An interpretable radiomics-based RF model can effectively differentiate between G1 and G2/3 of pNETs, demonstrating favorable interpretability. CLINICAL RELEVANCE STATEMENT: The radiomics-based interpretable model developed in this study has significant clinical relevance as it offers a non-invasive method for assessing the pathological grade of pancreatic neuroendocrine tumors and holds promise as an important complementary tool to traditional tissue biopsy. KEY POINTS: • A radiomics-based interpretable model was developed to predict the pathological grade of pNETs and compared with preoperative needle biopsy in terms of accuracy. • The model, based on CT radiomics, demonstrated favorable interpretability. • The radiomics model holds potential as a valuable complementary technique to preoperative needle biopsy; however, it should not be considered a replacement for biopsy.

PCB126 impairs human sperm functions by affecting post-translational modifications and mitochondrial functions.

Over the past few decades, there has been a consistent decline in semen quality across the globe, with environmental pollution being identified as the primary cause. Among the various contaminants present in the environment, persistent organic pollutants (POPs) have garnered significant attention due to their high toxicity, slow degradation, bio-accumulation, and long-range migration. PCBs, which include 210 congeners, are a crucial type of POPs that are known to have harmful effects on the environment and human health. Among the various PCB congeners, 3,3',4,4',5-pentachlorobiphenyl (PCB126) is a typical environmental endocrine-disrupting chemical that is widely distributed and has been associated with several health hazards. However, the impact and mechanism of PCB126 on human sperm function has not been fully elucidated. We aimed to investigate the effects of different concentrations of PCB126 (0.01, 0.1, 1, 10 µg/mL) on sperm motility, viability, hyperactivation, and acrosome reaction after incubation for different periods (1 and 2 h), delving deeper into the molecular mechanism of human sperm dysfunction caused by PCB126. First, we investigated the link between PCB126 treatment and the occurrence of protein modifications that are critical to sperm function regulation, such as tyrosine phosphorylation and lysine glutarylation. Second, we examined the potential impact of PCB126 on different parameters related to mitochondrial function, including reactive oxygen species, malondialdehyde levels, mitochondrial membrane potential, mitochondria respiration and adenosine triphosphate generation. Our findings indicate that exposure to environmental pollutants such as PCB126 in vitro may have a negative impact on human sperm functions by interfering with post-translational modifications and mitochondrial functions.

ACT001 improved cardiovascular function in septic mice by inhibiting the production of proinflammatory cytokines and the expression of JAK-STAT signaling pathway.

Sepsis is a life-threatening multiple organ dysfunction syndrome (MODS) caused by a microbial infection that leads to high morbidity and mortality worldwide. Sepsis-induced cardiomyopathy (SIC) and coagulopathy promote the progression of adverse outcomes in sepsis. Here, we reported that ACT001, a modified compound of parthenolide, improved the survival of sepsis mice. In this work, we used cecal ligation and puncture (CLP) model to induce SIC. Transthoracic echocardiography and HE staining assays were adopted to evaluate the influence of ACT001 on sepsis-induced cardiac dysfunction. Our results showed that ACT001 significantly improved heart function and reduced SIC. Coagulation accelerates organ damage in sepsis. We found that ACT001 decreased blood clotting in the FeCl3-induced carotid artery thrombosis experiment. ACT001 also reduced the production of neutrophil extracellular traps (NETs). RNA-sequencing of heart tissues revealed that ACT001 significantly downregulated the expression of pro-inflammatory cytokines and the JAK-STAT signaling pathway. These results were confirmed with real-time PCR and ELISA. In summary, we found ACT001 rescued mice from septic shock by protecting the cardiovascular system. This was partially mediated by inhibiting pro-inflammatory cytokine production and down-regulating the JAK-STAT signaling.

Melatonin-Mediated Enhancement of Photosynthetic Capacity and Photoprotection Improves Salt Tolerance in Wheat.

The role of melatonin in plant growth and response to environmental stress has been widely demonstrated. However, the physiological and molecular regulation of salt tolerance in wheat seedlings by melatonin remains unclear. In this study, we investigated changes in phenotype, physiology, photosynthetic parameters, and transcript levels in wheat seedlings to reveal the role of melatonin in the regulation of salt tolerance in wheat. The results indicate that the application of exogenous melatonin significantly alleviates growth inhibition, reactive oxygen species accumulation, and membrane oxidative damage induced by salt stress in wheat. Additionally, exogenous melatonin increased antioxidant enzyme activity and regulated photosynthetic gas exchange. Transcriptomic data showed a significant up-regulation of genes encoding light-harvesting chlorophyll protein complex proteins in photosynthesis and genes related to chlorophyll and carotenoid biosynthesis under the influence of melatonin. These results suggest that exogenous melatonin improves salt tolerance in wheat seedlings by enhancing the antioxidant, photoprotective, and photosynthesis activities.

[Gene Mutation Types of Thalassemia in Chongzuo Childbearing-age Population of Guangxi Zhuang Autonomous Region of China].

OBJECTIVE: To investigate the gene mutation and genotype distribution of thalassemia in the population of childbearing age in Chongzuo area of Guangxi. METHODS: Six α-thalassemia and 17 ß-thalassemia gene mutations common in Chinese were detected by gap-polymerase chain reaction (gap-PCR) combined with agarose gel eletrophoresis and reserve dot bolt hybridization in 29 266 cases of child-bearing age suspected of thalassemia. RESULTS: A total of 19 128 (65.36%) cases were identified with thalassemia. The detection rate of α-thalassemia, ß-thalassemia and α-combining ß-thalassemia was 45.25% (13 242/29 266), 15.47% (4 526/29 266) and 4.65% (1 360/29 266), respectively. A total carrying rate of 8 kinds of α-thalassemia gene mutations was 26.74% (15 649/58 532), including 12.51% for --SEA, followed by 5.70% for -α3.7, and 0.24% for --Thai. Among 32 α-thalassemia genotypes, the most common five were --SEA/αα, -α3.7/αα, αCSα/αα, -α4.2/αα and αWSα/αα, accounting for 47.27%, 18.31%, 8.56%, 8.52% and 7.91%, respectively, as well as 0.97% for --Thai/αα. A total carrying rate of 13 kinds of ß-thalassemia gene mutations was 10.07% (5 897/58 532), including 3.63% for CD41-42, followed by 2.55% for CD17, and 0.003% for -50 (G>A). Among 17 ß-thalassemia genotypes, the most common six were CD41-42/N, CD17/N, CD71-72/N, CD26/N, 28/N and IVSI-1/N, accounting for 36.15%, 25.81%, 9.43%, 8.18%, 8.09% and 7.75%. The homozygous genotype CD26/CD26 [hemoglobin (Hb): 121 g/L] and -28/-28 (Hb: 56 g/L) were respectively detected in one case, and double heterozygous genotype were detected in 5 cases, including 3 cases of CD41-42/CD26 (Hb: 41 g/L, 51 g/L, 63 g/L, respectively), 1 case of -28/IVSI-1 (Hb: 53 g/L), and 1 case of CD71-72/CD26 (Hb: 89 g/L), in which patients with moderate or severe anemia had a history of blood transfusion. Among 104 α-combining ß-thalassemia genotypes, the most common were --SEA/αα, -α3.7/αα combining CD41-42/N and --SEA/αα combining CD17/N, accounting for 12.13%, 9.63% and 9.26%, respectively. In addition, 1 case of --SEA/-α3.7 combining -28/IVSI-1 (Hb: 83 g/L) and 1 case of -α3.7/αα combining CD41-42/ CD41-42 (Hb: 110 g/L) were detected without history of blood transfusion, while 1 case of αWSα/αα combining CD41-42/CD17 (Hb: 79 g/L) and 1 case of --SEA/αα combining CD17/-28 (Hb: 46 g/L) were detected with history. CONCLUSIONS: The detection rate of thalassemia genes is high and the mutations are diverse in the population of childbearing age in Chongzuo area of Guangxi. The common deletion genotype is --SEA/αα in α-thalassemia and CD41-42/N in ß-thalassemia, and deletion genotype --Thai is not rare. There is a certain incidence of intermediate and severe ß-thalassemia, and most patients require transfusion therapy. The results are beneficial for genetic consultation and intervention of thalassemia.

[Analysis of HKαα Genotype and Hematological Characteristics in South Guangxi].

OBJECTIVE: To investigate the detection rate and hematologic phenotype of HKαα thalassemia in south Guangxi, in order to provide reference for the prevention and control of thalassemia and prenatal and postnatal care consultation in this region. METHODS: Gene testing was performed on pre-marital medical examinations, pre-pregnancy eugenic health examinations, prenatal examinations and hospitalized thalassemia-positive persons in south of Guangxi, and the results were analyzed. RESULTS: A total of 183 190 thalassemia patients were included in this study, the age was mainly concentrated in 26-35 years old (101 709 cases, accounting for 55.521%), and 40 HKαα mutations were detected, detection rate was 0.022%, including 5 cases in Nanning, 22 cases in Qinzhou, 2 cases in Fangchenggang, 11 cases in Beihai. A total of 29 ethnic groups were included in the survey, but HKαα gene was observed only in Han nationality (0.0380%) and Zhuang nationality (0.0068%). A total of 8 genotypes carrying HKαα mutations were detected in this study ( HKαα/--SEA, ßN/ ßN, HKαα/αα, ß-28/ ßN, HKαα/αα, ß-50/ ßN, HKαα/αα, ßCD17/ ßN, HKαα/αα, ßCD27/28/ß N, HKαα/αα, ßCD41-42/ ßN, HKαα/αα, ßCD71-72/ ßN, and HKαα/αα, ßN/ ßN). Except for most cases with HKαα/αα, ßN/ ßN genotypes with no significant changes in the hematological indexes, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) of other genotypes were decreased, showing microcytic hypochromic performance, mild anemia or no anemia. CONCLUSION: HKαα carrier is often misdiagnosed as -α3.7 carrier, which easily leads to missed diagnosis or misdiagnosis. Therefore, it is necessary to continuously improve the diagnostic level of laboratory testing personnels and genetic counselors to avoid unnecessary interventional puncture operations and birth of children with moderate and severe thalassemia.