Prevotella copri exhausts intrinsic indole-3-pyruvic acid in the host to promote breast cancer progression: inactivation of AMPK via UHRF1-mediated negative regulation.

Emerging evidence has revealed the novel role of gut microbiota in the development of cancer. The characteristics of function and composition in the gut microbiota of patients with breast cancer patients has been reported, however the detailed causation between gut microbiota and breast cancer remains uncertain. In the present study, 16S rRNA sequencing revealed that Prevotella, particularly the dominant species Prevotella copri, is significantly enriched and prevalent in gut microbiota of breast cancer patients. Prior-oral administration of P. copri could promote breast cancer growth in specific pathogen-free mice and germ-free mice, accompanied with sharp reduction of indole-3-pyruvic acid (IPyA). Mechanistically, the present of excessive P. copri consumed a large amount of tryptophan (Trp), thus hampering the physiological accumulation of IPyA in the host. Our results revealed that IPyA is an intrinsic anti-cancer reagent in the host at physiological level. Briefly, IPyA directly suppressed the transcription of UHRF1, following by the declined UHRF1 and PP2A C in nucleus, thus inhibiting the phosphorylation of AMPK, which is just opposite to the cancer promoting effect of P. copri. Therefore, the exhaustion of IPyA by excessive P. copri strengthens the UHRF1-mediated negative control to inactivated the energy-controlling AMPK signaling pathway to promote tumor growth, which was indicated by the alternation in pattern of protein expression and DNA methylation. Our findings, for the first time, highlighted P. copri as a risk factor for the progression of breast cancer.

A phase-separated protein hub modulates resistance to Fusarium head blight in wheat.

Fusarium head blight (FHB) is a devastating wheat disease. Fhb1, the most widely applied genetic locus for FHB resistance, is conferred by TaHRC of an unknown mode of action. Here, we show that TaHRC alleles distinctly drive liquid-liquid phase separation (LLPS) within a proteinaceous complex, determining FHB susceptibility or resistance. TaHRC-S (susceptible) exhibits stronger LLPS ability than TaHRC-R (resistant), and this distinction is further intensified by fungal mycotoxin deoxynivalenol, leading to opposing FHB symptoms. TaHRC recruits a protein class with intrinsic LLPS potentials, referred to as an "HRC-containing hub." TaHRC-S drives condensation of hub components, while TaHRC-R comparatively suppresses hub condensate formation. The function of TaSR45a splicing factor, a hub member, depends on TaHRC-driven condensate state, which in turn differentially directs alternative splicing, switching between susceptibility and resistance to wheat FHB. These findings reveal a mechanism for FHB spread within a spike and shed light on the roles of complex condensates in controlling plant disease.

Self-Assembled Fe-Phenolic Acid Network Synergizes with Ferroptosis to Enhance Tumor Nanotherapy.

Natural polyphenolic compound rosmarinic acid (RA) has good antitumor activity. However, the distinctive tumor microenvironment, characterized by low pH and elevated levels of glutathione (GSH), enhances the tolerance of tumors to the singular anti-tumor treatment mode using RA, resulting in unsatisfactory therapeutic efficacy. Targeting nonapoptotic programmed cell death processes may provide another impetus to inhibit tumor growth. RA possesses the capability to coordinate with metal elements. To solve the effect restriction of the above single treatment mode, it is proposed to construct a self-assembled nanocomposite, Fe-RA. Under tumor microenvironment, Fe-RA nanocomposite exerts the characteristics of POD-like enzyme activity and depletion of GSH, producing a large amount of hydroxyl radical (·OH) while disrupting the antioxidant defense system of tumor cells. Moreover, due to the enhanced permeability and retention effect (EPR), Fe-RA can transport Fe2+ to a greater extent to tumor cells and increase intracellular iron content. Causing an imbalance in iron metabolism in tumor cells and promoting cell ferroptosis. The results of the synchrotron X-ray absorption spectroscopy (XAS) and high-resolution mass spectrometry (HRMS) prove the successful complexation of Fe-RA nanocomposite. Density functional theory (DFT) explains the efficient catalytic mechanism of its peroxide-like enzyme activity and the reaction principle with GSH.

Integrated analysis of m6A regulator-mediated RNA methylation modification patterns and immune characteristics in Sjögren's syndrome.

The epigenetic modifier N6-methyladenosine (m6A), recognized as the most prevalent internal modification in messenger RNA (mRNA), has recently emerged as a pivotal player in immune regulation. Its dysregulation has been implicated in the pathogenesis of various autoimmune conditions. However, the implications of m6A modification within the immune microenvironment of Sjögren's syndrome (SS), a chronic autoimmune disorder characterized by exocrine gland dysfunction, remain unexplored. Herein, we leverage an integrative analysis combining public database resources and novel sequencing data to investigate the expression profiles of m6A regulatory genes in SS. Our cohort comprised 220 patients diagnosed with SS and 62 healthy individuals, enabling a comprehensive evaluation of peripheral blood at the transcriptomic level. We report a significant association between SS and altered expression of key m6A regulators, with these changes closely tied to the activation of CD4+ T cells. Employing a random forest (RF) algorithm, we identified crucial genes contributing to the disease phenotype, which facilitated the development of a robust diagnostic model via multivariate logistic regression analysis. Further, unsupervised clustering revealed two distinct m6A modification patterns, which were significantly associated with variations in immunocyte infiltration, immune response activity, and biological function enrichment in SS. Subsequently, we proceeded with a screening process aimed at identifying genes that were differentially expressed (DEGs) between the two groups distinguished by m6A modification. Leveraging these DEGs, we employed weight gene co-expression network analysis (WGCNA) to uncover sets of genes that exhibited strong co-variance and hub genes that were closely linked to m6A modification. Through rigorous analysis, we identified three critical m6A regulators - METTL3, ALKBH5, and YTHDF1 - alongside two m6A-related hub genes, COMMD8 and SRP9. These elements collectively underscore a complex but discernible pattern of m6A modification that appears to be integrally linked with SS's pathogenesis. Our findings not only illuminate the significant correlation between m6A modification and the immune microenvironment in SS but also lay the groundwork for a deeper understanding of m6A regulatory mechanisms. More importantly, the identification of these key regulators and hub genes opens new avenues for the diagnosis and treatment of SS, presenting potential targets for therapeutic intervention.

Traditional knowledge of animal-derived medicines used by Gelao community in Northern Guizhou, China.

INTRODUCTION: This study aims to document and preserve the traditional medicinal knowledge of the Gelao community in Northern Guizhou, China, providing valuable insights for modern pharmacological research and the development of these traditional remedies. METHODS: Our methodology encompassed a blend of literature review, community interviews, and participatory observation to delve into the traditional knowledge of animal-derived medicines among the Gelao community. We employed quantitative ethnological and ecological assessment techniques to evaluate the significance of these practices. Informed consent was secured before conducting interviews, with a focus on ascertaining the types of medicines familiar to the informants, including their local names, sources, methods of preparation, application techniques, diseases treated, frequency of use, and safety considerations. RESULTS: Our research cataloged 55 varieties of animal-derived medicines utilized by the Gelao people. Out of these, 34 originate from wild animals, mainly encompassing small insects, reptiles, and aquatic species; the remaining 21 are derived from domesticated animals, largely involving their tissues, organs, and various physiological or pathological by-products. These medicines are primarily applied in treating pediatric ailments (13 types), internal disorders (11 types), gynecological issues (3 types), dermatological problems (7 types), ENT conditions (3 types), trauma-related injuries (5 types), joint and bone ailments (5 types), infections (2 types), dental issues (2 types), and urolithiasis (1 type), with three types being used for other miscellaneous conditions. Commonly utilized medicines, such as honey, Blaps beetle, chicken gallstones, and snake-based products, are preferred for their availability, edibility, and safety within the Gelao communities. CONCLUSION: The Gelao community's traditional medicines represent a rich diversity of animal sources, showcasing extensive expertise and knowledge in their processing and clinical applications. This wealth of traditional knowledge offers novel perspectives for the contemporary pharmacological study and development of these remedies. Additionally, our research plays a crucial role in aiding the preservation and continuation of this invaluable cultural heritage.

Lysine acetyltransferase 6A maintains CD4+ T cell response via epigenetic reprogramming of glucose metabolism in autoimmunity.

Augmented CD4+ T cell response in autoimmunity is characterized by extensive metabolic reprogramming. However, the epigenetic molecule that drives the metabolic adaptation of CD4+ T cells remains largely unknown. Here, we show that lysine acetyltransferase 6A (KAT6A), an epigenetic modulator that is clinically associated with autoimmunity, orchestrates the metabolic reprogramming of glucose in CD4+ T cells. KAT6A is required for the proliferation and differentiation of proinflammatory CD4+ T cell subsets in vitro, and mice with KAT6A-deficient CD4+ T cells are less susceptible to experimental autoimmune encephalomyelitis and colitis. Mechanistically, KAT6A orchestrates the abundance of histone acetylation at the chromatin where several glycolytic genes are located, thus affecting glucose metabolic reprogramming and subsequent CD4+ T cell responses. Treatment with KAT6A small-molecule inhibitors in mouse models shows high therapeutic value for targeting KAT6A in autoimmunity. Our study provides novel insights into the epigenetic programming of immunometabolism and suggests potential therapeutic targets for patients with autoimmunity.

Efficacy and Safety of Human Urinary Kallidinogenase for Acute Ischemic Stroke: A Retrospective Single-Center Study.

BACKGROUND: The aim of this study was to investigate the outcomes of human urinary kallidinogenase (HUK) after recombinant tissue-type plasminogen activator treatment in patients with acute ischemic stroke (AIS). METHODS: In this retrospective study conducted from December 2018 to August 2020, 313 patients with AIS patients who received recombinant tissue-type plasminogen activator treatment were enrolled. Among them, 148 patients received basic therapy, and 165 patients received HUK treatment. Demographics and clinical characteristics were analyzed after treatment, and patients were monitored for stroke recurrence for 12 months. National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale scores were used to assess the efficacy of treatment. Logistic regression analysis was used to identify risk factors for recurrence. RESULTS: There were no differences in baseline clinical characteristics between the 2 groups in the database. After 14 days of treatment, the HUK group had significantly lower NIHSS and modified Rankin Scale scores than the control group ( P <0.01). The recurrence rates in the HUK and control groups were 12.84% and 21.82%, respectively, with patients treated with HUK having better outcomes ( P <0.001). Logistic analysis indicated that high homocysteine levels and high NIHSS scores at diagnosis were risk factors for AIS recurrence. In addition, HUK treatment was found to reduce the risk of recurrence. CONCLUSION: Treatment with HUK after intravenous thrombolysis can significantly improve the neurological function of AIS patients and reduce stroke recurrence.

Physical activity and its fluctuations in relation to depressive symptoms: A national longitudinal study among Chinese adults.

BACKGROUND: Physical activity (PA) may prevent depressive symptoms, however, PA fluctuations may have different effects. Using three waves of nationally representative data, this study aimed to examine the effects of PA fluctuations on depressive symptoms. METHODS: Participants comprised 7633 adults free of depressive symptoms at the first two waves (Mage = 45.26, 54.70 % males). They completed the China Family Panel Study in 2016 (T1), 2018 (T2), and 2020 (T3), respectively. Depressive symptoms were measured by the Center for Epidemiologic Studies Depression (CES-D) scale using a cutoff of 16. Participants' PA levels were split into regular PA or infrequent PA groups. Changes in PA levels between T1 and T2 were classified into four groups: maintained infrequent PA, initiated regular PA, ceased regular PA, and persisted regular PA. RESULTS: The incidence of depressive symptoms was 20.22 % (19.05 % possible and 1.17 % severe depression). After multivariate adjustment, Poisson regression showed that persistent regular PA had 17.8 % (95 % CI: 0.724, 0.934) lower risks of incident depressive symptoms compared to maintained infrequent PA. And adults who ceased regular PA were more likely to experience depressive symptoms than those who persisted in regular PA (RR = 1.188, 95 % CI: 1.010, 1.398). LIMITATIONS: All items were self-reported. CES-D only examined self-diagnosed depressive symptoms, not medical diagnoses. CONCLUSION: Adults who persisted in regular PA may have a lower possibility of developing depressive symptoms. The finding might serve as an empirical reference to depression prevention.

A novel multimodal prediction model based on DNA methylation biomarkers and low-dose computed tomography images for identifying early-stage lung cancer.

Objective: DNA methylation alterations are early events in carcinogenesis and immune signalling in lung cancer. This study aimed to develop a model based on short stature homeobox 2 gene (SHOX2)/prostaglandin E receptor 4 gene (PTGER4) DNA methylation in plasma, appearance subtype of pulmonary nodules (PNs) and low-dose computed tomography (LDCT) images to distinguish early-stage lung cancers. Methods: We developed a multimodal prediction model with a training set of 257 individuals. The performance of the multimodal prediction model was further validated in an independent validation set of 42 subjects. In addition, we explored the association between SHOX2/PTGER4 DNA methylation and driver gene mutations in lung cancer based on data from The Cancer Genome Atlas (TCGA) portal. Results: There were significant differences between the early-stage lung cancers and benign groups in the methylation levels. The area under a receiver operator characteristic curve (AUC) of SHOX2 in patients with solid nodules, mixed ground-glass opacity nodules and pure ground-glass opacity nodules were 0.693, 0.497 and 0.864, respectively, while the AUCs of PTGER4 were 0.559, 0.739 and 0.619, respectively. With the highest AUC of 0.894, the novel multimodal prediction model outperformed the Mayo Clinic model (0.519) and LDCT-based deep learning model (0.842) in the independent validation set. Database analysis demonstrated that patients with SHOX2/PTGER4 DNA hypermethylation were enriched in TP53 mutations. Conclusions: The present multimodal prediction model could more efficiently distinguish early-stage lung cancer from benign PNs. A prognostic index based on DNA methylation and lung cancer driver gene alterations may separate the patients into groups with good or poor prognosis.

Lactate-induced mtDNA Accumulation Activates cGAS-STING Signaling and the Inflammatory Response in Sjögren's Syndrome.

Acinar epithelial cell atrophy in secretory glands is a hallmark of primary Sjögren's syndrome (pSS), the cause of which is far from elucidated. We examined the role of acinar atrophy by focusing on the metabolism of glandular epithelial cells and mitochondria in the pSS environment. After confirming the presence of a high-lactate environment in the labial glands of human pSS patients, we used the A253 cell line and NOD/Ltj mice as models to investigate the metabolic changes in salivary gland epithelial cells in a high-lactate environment in vitro and in vivo. We found that epithelial cells produced high levels of IL-6, IL-8, IFN-α, IFN-ß and TNF-α and exhibited significant NF-κB and type I IFN-related pathway activation. The results confirmed that lactate damaged mitochondrial DNA (mtDNA) and led to its leakage, which subsequently activated the cGAS-STING pathway. Inflammatory cytokine production and pathway activation were inhibited in vivo and in vitro by the lactate scavenger sodium dichloroacetate (DCA). Our study provides new insights into the etiology and treatment of pSS from the perspective of cell metabolism.

Population structure and mixed reproductive strategies in Bipolaris maydis from single and multiple corn cultivars in Fujian Province, China.

Bipolaris maydis is the pathogenic microorganism of southern corn leaf blight, a persistent biotic constraint responsible for substantial yield losses of corn worldwide. In the present study, 96 isolates from six representative fields growing single and multiple sweet corn cultivars in Pingnan, Fuqing, and Jian'ou in Fujian Province, which are characterized by different geographical characteristics and cropping patterns, were genetically analyzed using inter-simple sequence repeat (ISSR) markers to assess the impact of geographical origins and corn cultivars on B. maydis population differentiation. B. maydis isolates originated from diverse regions possessed higher genetic variety than those from single and multiple sweet corn cultivars. Phylogenetic analysis showed that the isolates from single and multiple sweet corn cultivars were randomly grouped into different clusters, with those from the same location tending to form clusters. A greater genetic differentiation among different geographical populations than between those from single and multiple sweet corn cultivars was observed by pairwise comparison. Hierarchical analysis indicated that among-population variation was higher when comparatively analyzed B. maydis populations from different locations than in those from single and multiple sweet corn cultivars. In conclusion, these results suggest that geographical origin acts a more considerable role in genetic differentiation of B. maydis than corn cultivar. Two divided genetic clusters were detected in the B. maydis populations from single and multiple sweet corn cultivars at the three locations in Fujian Province, with major genetic variation being derived within populations. The high haplotypic diversity and expected mating type ratio of 1:1 in combination with significant linkage disequilibrium suggested that a mixed reproductive strategy occurs in the B. maydis population in Fujian Province. This study will enrich the information on the role that geographical origins and corn cultivars play in the population structure of the pathogen as well as the reproductive strategies in B. maydis population in Fujian Province.

MADS8 is indispensable for female reproductive development at high ambient temperatures in cereal crops.

Temperature is a major factor that regulates plant growth and phenotypic diversity. To ensure reproductive success at a range of temperatures, plants must maintain developmental stability of their sexual organs when exposed to temperature fluctuations. However, the mechanisms integrating plant floral organ development and temperature responses are largely unknown. Here, we generated barley and rice loss-of-function mutants in the SEPALLATA-like MADS-box gene MADS8. The mutants in both species form multiple carpels that lack ovules at high ambient temperatures. Tissue-specific markers revealed that HvMADS8 is required to maintain floral meristem determinacy and ovule initiation at high temperatures, and transcriptome analyses confirmed that temperature-dependent differentially expressed genes in Hvmads8 mutants predominantly associate with floral organ and meristem regulation. HvMADS8 temperature-responsive activity relies on increased binding to promoters of downstream targets, as revealed by a cleavage under targets and tagmentation (CUT&Tag) analysis. We also demonstrate that HvMADS8 directly binds to 2 orthologs of D-class floral homeotic genes to activate their expression. Overall, our findings revealed a new, conserved role for MADS8 in maintaining pistil number and ovule initiation in cereal crops, extending the known function of plant MADS-box proteins in floral organ regulation.

Metagenomic next-generation sequencing for the diagnosis of oral and maxillofacial space infections.

Background/purpose: Metagenomic next-generation sequencing (mNGS) has been widely used for the detection of pathogens causing infectious diseases. This study aimed to evaluate the potential ability of mNGS to detect pathogens causing oral and maxillofacial space infection (OMSI) and compare the results with those of the traditional diagnostic microbial culture method. Materials and methods: We retrospectively reviewed the data of 218 patients diagnosed with OMSI who underwent microbial culture and mNGS at the Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, from July 2020 to January 2022. Results: The positivity rate of mNGS (216 cases) was significantly higher than that of microbial culture (123 cases). The most frequently detected bacteria were different between these two detection methods. Streptococcus constellatus (16.05%, 35), Streptococcus anginosus (15.69%, 34) and Klebsiella pneumoniae (6.88%, 15) were the most commonly isolated bacteria by culture. However, Peptostreptococcus stomatis (61.47%, 134), Parvimonas micra (68.35%, 149) and Streptococcus constellatus (57.34%, 125) were the most commonly detected bacteria by mNGS. mNGS also has advantages in diagnosing viral infections. The optimal numbers of diagnostic reads were 1162 and 588 for the diagnosis of Streptococcus anginosus and Streptococcus constellatus infections, respectively. Read numbers were significantly correlated with C-reactive protein (CRP), procalcitonin (PCT), and blood glucose levels and neutrophil percentage (NEUT%). Conclusion: For pathogens causing OMSI, mNGS had a higher rate of microbial pathogen detection and remarkable advantages in identifying coinfections involving viruses and fungi. The read numbers for mNGS are important for diagnostic accuracy and disease severity evaluation.

HvSL1 and HvMADS16 promote stamen identity to restrict multiple ovary formation in barley.

Correct floral development is the result of a sophisticated balance of molecular cues. Floral mutants provide insight into the main genetic determinants that integrate these cues, as well as providing opportunities to assess functional variation across species. In this study, we characterize the barley (Hordeum vulgare) multiovary mutants mov2.g and mov1, and propose causative gene sequences: a C2H2 zinc-finger gene HvSL1 and a B-class gene HvMADS16, respectively. In the absence of HvSL1, florets lack stamens but exhibit functional supernumerary carpels, resulting in multiple grains per floret. Deletion of HvMADS16 in mov1 causes homeotic conversion of lodicules and stamens into bract-like organs and carpels that contain non-functional ovules. Based on developmental, genetic, and molecular data, we propose a model by which stamen specification in barley is defined by HvSL1 acting upstream of HvMADS16. The present work identifies strong conservation of stamen formation pathways with other cereals, but also reveals intriguing species-specific differences. The findings lay the foundation for a better understanding of floral architecture in Triticeae, a key target for crop improvement.

The molecular chaperone mtHSC70-1 interacts with DjA30 to regulate female gametophyte development and fertility in Arabidopsis.

Arabidopsis mitochondria-targeted heat shock protein 70 (mtHSC70-1) plays important roles in the establishment of cytochrome c oxidase-dependent respiration and redox homeostasis during the vegetative growth of plants. Here, we report that knocking out the mtHSC70-1 gene led to a decrease in plant fertility; the fertility defect of the mutant was completely rescued by introducing the mtHSC70-1 gene. mtHSC70-1 mutants also showed defects in female gametophyte (FG) development, including delayed mitosis, abnormal nuclear position, and ectopic gene expression in the embryo sacs. In addition, we found that an Arabidopsis mitochondrial J-protein gene (DjA30) mutant, j30+/- , had defects in FG development and fertility similar to those of mtHSC70-1 mutant. mtHSC70-1 and DjA30 had similar expression patterns in FGs and interacted in vivo, suggesting that these two proteins might cooperate during female gametogenesis. Further, respiratory chain complex IV activity in mtHSC70-1 and DjA30 mutant embryo sacs was markedly downregulated; this led to the accumulation of mitochondrial reactive oxygen species (ROS). Scavenging excess ROS by introducing Mn-superoxide dismutase 1 or catalase 1 gene into the mtHSC70-1 mutant rescued FG development and fertility. Altogether, our results suggest that mtHSC70-1 and DjA30 are essential for the maintenance of ROS homeostasis in the embryo sacs and provide direct evidence for the roles of ROS homeostasis in embryo sac maturation and nuclear patterning, which might determine the fate of gametic and accessory cells.

Investigating the Resistance Mechanism of Wheat Varieties to Fusarium Head Blight Using Comparative Metabolomics.

Fusarium head blight (FHB) is primarily caused by Fusarium graminearum and severely reduces wheat yield, causing mycotoxin contamination in grains and derived products. F. graminearum-secreted chemical toxins stably accumulate in plant cells, disturbing host metabolic homeostasis. We determined the potential mechanisms underlying FHB resistance and susceptibility in wheat. Three representative wheat varieties (Sumai 3, Yangmai 158, and Annong 8455) were inoculated with F. graminearum and their metabolite changes were assessed and compared. In total, 365 differentiated metabolites were successfully identified. Amino acids and derivatives, carbohydrates, flavonoids, hydroxycinnamate derivatives, lipids, and nucleotides constituted the major changes in response to fungal infection. Changes in defense-associated metabolites, such as flavonoids and hydroxycinnamate derivatives, were dynamic and differed among the varieties. Nucleotide and amino acid metabolism and the tricarboxylic acid cycle were more active in the highly and moderately resistant varieties than in the highly susceptible variety. We demonstrated that two plant-derived metabolites, phenylalanine and malate, significantly suppressed F. graminearum growth. The genes encoding the biosynthetic enzymes for these two metabolites were upregulated in wheat spike during F. graminearum infection. Thus, our findings uncovered the metabolic basis of resistance and susceptibility of wheat to F. graminearum and provided insights into engineering metabolic pathways to enhance FHB resistance in wheat.

Ovule cell wall composition is a maternal determinant of grain size in barley.

In cereal species, grain size is influenced by growth of the ovule integuments (seed coat), the spikelet hull (lemma and palea) and the filial endosperm. Whether a highly conserved ovule tissue, the nucellus, has any impact on grain size has remained unclear. Immunolabelling revealed that the barley nucellus comprises two distinct cell types that differ in terms of cell wall homogalacturonan (HG) accumulation. Transcriptional profiling of the nucellus identified two pectin methylesterase (PME) genes, OVULE PECTIN MODIFIER 1 (OPM1) and OPM2, which are expressed in the unfertilized ovule but absent from the seed. Ovules from an opm1 opm2 mutant and plants expressing an ovule-specific pectin methylesterase inhibitor (PMEI), exhibit reduced HG accumulation. This results in changes to ovule cell size and shape and ovules that are longer than wild-type (WT) controls. At grain maturity, this is manifested as significantly longer grain. These findings indicate that cell wall composition during ovule development acts to limit ovule and seed growth. The investigation of ovule PME and PMEI activity reveals an unexpected role of maternal tissues in controlling grain growth before fertilization, one that has been lacking from models exploring improvements in grain size.

3D-Printed Porous Tantalum Scaffold Improves Muscle Attachment via Integrin-ß1-Activated AKT/MAPK Signaling Pathway.

3D-printed porous titanium (Ti) alloy scaffolds have been reported for facilitating muscle attachment in our previous study. However, the anti-avulsion ability needs to be improved. In this study, we used 3D-printed porous tantalum (Ta) scaffolds to improve muscle attachment. The differences in chemical and physical characteristics and muscle adhesion between the two scaffolds were tested and compared in the gene and protein level both in vitro and in vivo. The possible molecular mechanism was analyzed and further proved. The results showed that compared with the porous Ti alloy, porous Ta had better cell proliferation, differentiation, migration, and adhesion via the integrin-ß1 (Itgb1)-activated AKT/MAPK signaling pathway in L6 rat myoblasts. When artificially down-regulated the expression of Itgb1, cell adhesion and myogenesis differentiation were affected and the phosphorylation of the AKT/MAPK signaling pathway was suppressed. In rat intramuscular implantation, porous Ta had a significantly higher muscle ingrowth rate (85.63% ± 4.97 vs 65.98% ± 4.52, p < 0.01) and larger avulsion force (0.972 vs 0.823 N/mm2, p < 0.05) than the porous Ti alloy. These findings demonstrate that the 3D-printed porous Ta scaffold is beneficial for further clinical application of muscle attachment.

Characteristics and pollution risks of potentially toxic elements and nematode community structure on farm soil near coal mines.

As one of the most important coal-producing provinces of China, Shanxi Province has been concerned about soil potentially toxic elements (PTEs) contamination in recent years. The study aimed to determine the status and sources of PTEs contamination and evaluate the quality of the soil ecology. This study investigated the degree of 13 PTEs contamination. The sources and contributions of PTEs were traced by the absolute principal component score followed by a multiple linear regression model (APCS-MLR). And the status of the soil ecosystem was verified by evaluating the soil nematode community around the coal mining areas in Jinzhong. The results showed that the mean PTEs concentration of 5 trace elements were higher than the background values of Shanxi, and safe to considerable was indicated by the pollution and ecological risk values. Soil Hg was the most contaminated element, followed by Cd. The distribution of PTEs was determined by coal mining activities (44.72%) followed by agricultural practice (32.37%) and coal transportation (21.37%). The nematode genera Acrobeloides (4.01%), Aphelenchus (20.30%), Meloidogyne (11.95%) and Aporcelaimus (2.74%) could be regarded as bioindicators of soil PTEs contamination by their tolerance. Concentrations of soil Cr, Mn, Ti and Cd showed remarkable influences on the total nematode abundance, maturity index, enrichment index, structural index, Shannon-Wiener diversity index and Pielou index of soil nematode. It is an appropriate method to evaluate the status of soil PTEs contamination combining the response of a single nematode genus and the nematode community evaluation index.

The effect of Tianjiang Xueshuantong Wan pills on ischemia-reperfusion injury after thrombolysis in acute cerebral infarction.

OBJECTIVE: The aim of this study is to investigate the effect of Tianjiang Xueshuantong Wan pills on reperfusion injury after venous thrombolysis in acute cerebral infarction. METHODS: The strategy used in this study is a randomised controlled clinical trial. In total, 72 cases were included, with 36 in the trial group and 36 in the control group, with a 1:1 ratio. Both groups were given standardised treatment for acute cerebral infarction. Based on the rt-PA intravenous thrombolysis, the test group took Tianjiang Xueshuantong Wan pills orally, whereas the control group solely utilised rt-PA for intravenous thrombolysis and did not take the test medicine orally. The patients' intracranial hemorrhage was clarified by head CT scan, and the occurrence of reperfusion injury was recorded during the entire trial. RESULTS: There were no significant differences in serum IL-6, MDA, SOD and TNF concentrations and NIHSS scores between the two groups before therapy (P > 0.05). After treatment, the serum concentrations of IL-6, MDA and TNF in the experimental group were significantly decreased compared with the control group, while the serum concentrations of SOD were significantly increased compared with the control group, with statistical significance (P > 0.05). After seven days of treatment, the total effective rate in the experimental group was 88.89%, while the data in the control group was 75%. There was a statistically significant difference between the experimental and control groups. CONCLUSION: Tianjiang Xueshuantong Wan pills can effectively prevent reperfusion injury following intravenous thrombolysis in individuals with cerebral infarction while improving patients' neurological deficits.