circRUNX2.2, highly expressed in Marek's disease tumor tissues, functions in cis to regulate parental gene RUNX2 expression.

Marek's disease (MD), an immunosuppression disease induced by Marek's disease virus (MDV), is one of the significant diseases affecting the health and productive performance of poultry. The roles of circular RNAs (circRNAs) in MD development were poorly understood. In this study, we found a circRNA derived from exon 6 of RUNX family transcription factor 2 (RUNX2) gene, named circRUNX2.2, was highly expressed in chicken tumorous spleens (TS) induced by MDV. Through fluorescence in situ hybridization and nuclear-cytoplasmic separation assay, we determined circRUNX2.2 was mainly located in the nucleus. Knockout experiments confirmed that the flanking complementary sequences (RCMs) mediated its circularization. Gain of function assay and dual luciferase reporter gene assay revealed that circRUNX2.2 could promote the expression of RUNX2 via binding with its promoter region. RNA antisense purification assay and mass spectrometry assay showed circRUNX2.2 could recruit proteins such as CHD9 protein. Knocking down CHD9 expression decreased the expression of RUNX2 gene, which confirmed the positive regulation that circRUNX2.2 on RUNX2 expression was probably facilitated via recruiting CHD9 protein. Functional experiments showed that circRUNX2.2 promoted the proliferation of the MD lymphoma-derived chicken cell line, MDCC-MSB1, which confirmed the potential oncogenic role of circRNX2.2 in tumor development. In conclusion, we found that the RUNX2-derived circRUNX2.2 can positively regulate the transcription of the parental gene RUNX2 in a cis-acting manner. The high expression of circRUNX2.2 in MD tumor tissues indicated that it might mediate MD lymphoma progression.

Electrolyte Composition-Dependent Product Selectivity in CO2 Reduction with a Porphyrinic Metal-Organic Framework Catalyst.

A copper porphyrin-derived metal-organic framework electrocatalyst, FICN-8, was synthesized and its catalytic activity for CO2 reduction reaction (CO2RR) was investigated. FICN-8 selectively catalyzed electrochemical reduction of CO2 to CO in anhydrous acetonitrile electrolyte. However, formic acid became the dominant CO2RR product with the addition of a proton source to the system. Mechanistic studies revealed the change of major reduction pathway upon proton source addition, while catalyst-bound hydride (*H) species was proposed as the key intermediate for formic acid production. This work highlights the importance of electrolyte composition on CO2RR product selectivity.

Metal-Organic Framework-Induced Rh Monocoodination on Diphosphine Ligand Enables Catalytic Hydroformylation of Aliphatic Olefins at Room Temperature and Pressure.

Persistent challenges in hydroformylation of olefins include controlling regioselectivity, particularly for short aliphatic olefins and conducting reactions under ambient conditions.  We report here the synthesis of monophosphine-Rh complexes on a typical chelated diphosphine ligand mediated by a Zr-MOF through isolating a pair of phosphorus atoms. We demonstrate that single-crystal X-ray diffraction can elucidate the structural transformation of the Rh catalyst during olefin hydroformylation, providing valuable information on active site reconstruction during catalysis. The Rh-MOF catalyst demonstrates excellent catalytic and recyclable performance in the hydroformylation of short aliphatic olefins with linear to branched ratios of up to 99:1. Due to the framework's capacity to adsorb and concentrate gases, the catalytic reactions occur under room temperature and pressure, eliminating the need for the high temperature and pressures typically required in homogeneous systems. This study show that Zr-MOF can be a unique platform for synthesizing unusual catalytic species that cannot exist in solutions for meaningful chemical transformations and elucidate valuable structural information pertaining to metal-based catalysis.

[Mechanism of astragaloside â £ modulation of Nrf2/HO-1/GPX4 pathway to inhibit ferroptosis and ameliorate atherosclerosis in ApoE~(-/-) mice].

The intervention effect of astragaloside Ⅳ(AS-Ⅳ) on atherosclerosis in apolipoprotein E gene knockout(ApoE)~(-/-) mice was observed based on the nuclear factor erythroid-2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4) signaling pathway to explore the potential mechanism of AS-Ⅳ in improving ferroptosis in atherosclerotic mice. This study established an atherosclerosis mouse model by feeding them a high-fat diet. After modeling for 8 weeks, ApoE~(-/-) mice were randomly divided into the model group, AS-Ⅳ group, AS-Ⅳ+Nrf2 inhibitor(ML385) group, and ferrostatin-1(Fer-1) group. Additionally, a blank control group was also established. Corresponding drugs were administered via intraperitoneal injection, with the control group receiving an equivalent amount of normal saline injection as the model group. After the experiment, serum biochemical levels were measured using an automatic blood lipid analyzer, hematoxylin-eosin(HE) staining was used to observe morphological changes in aortic sinus tissues, colorimetric methods were used to detect levels of ferrous ion(Fe~(2+)), malondialdehyde(MDA), glutathione(GSH), and superoxide dismutase(SOD) in mouse serum, immunofluorescence was used to observe the expressions of ferritin heavy chain 1(FTH1) and ferritin light chain(FTL) proteins in the aortic sinus of mice, Western blot was used to detect the protein levels of Nrf2, HO-1, and GPX4 in mouse aortic tissues, and transmission electron microscopy was used to observe ultrastructural changes in aortic tissues. RESULTS:: showed that compared to the control group, the model group of mice had significantly increased calcification and plaque deposition areas in the aortic sinus, increased mitochondrial membrane density, decreased or disappeared mitochondrial cristae, elevated levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), Fe~(2+), and MDA, decreased levels of high-density lipoprotein cholesterol(HDL-C), SOD, and GSH, and significant inhibition of Nrf2, HO-1, GPX4 proteins, as well as iron storage proteins FTH1 and FTL expressions in the aorta. Compared to the model group, AS-Ⅳ treatment resulted in decreased serum TC, TG, LDL-C, Fe~(2+), and MDA levels, increased HDL-C, SOD, and GSH levels, increased expressions of Nrf2, HO-1, and GPX4 proteins, and iron storage proteins FTH1 and FTL, and significant improvement in aortic tissue morphology. Compared to the AS-Ⅳ group, the Nrf2 inhibitor ML385 could reverse the therapeutic effect of AS-Ⅳ on atherosclerosis mice. These findings suggest that AS-Ⅳ can inhibit ferroptosis and improve atherosclerosis in ApoE~(-/-) mice, and its mechanism of action may be related to the regulation of the Nrf2/HO-1/GPX4 signaling pathway.

The 3,3'-dimethoxy-4,4'-dihydroxy-stilbene Triazole (STT) Inhibits Liver Cancer Cell Growth by Targeting Akt/mTOR Pathway.

The present study was aimed to investigate the proliferation inhibitory ability of 3,3'-dimethoxy-4,4'-dihydroxy-stilbene triazole (STT) on SNU449 and Huh7 cells. Moreover, the mechanism associated with the suppression of liver cancer cell proliferation by STT was also studied. The results revealed that STT suppresses proliferation of SNU449 and Huh7 cells to 28 and 21%, respectively treatment with 20 µM. The clonogenic survival of SNU449 and Huh7 cells was also significantly reduced after incubation with STT compared to the control cultures. In comparison to the control, STT treatment significantly decreased the invasive potential of SNU449 cells. Treatment with STT led to a prominent suppression in p62 and increase in LC3B protein expression in SNU449 cells compared to the control cells. The STT treatment dramatically decreased p-Akt and p-mTOR protein expression in SNU449 cells. Docking study revealed that STT interacts via traditional hydrogen bonding with the glutamine, phenylalanine, leucine, serine, arginine, aspartic acid, and lysine residues of Akt protein. In summary, the current study demonstrates that STT effectively suppresses the viability of SNU449 and Huh7 liver cancer cells. Moreover, STT treatment of the liver cancer cells also significantly reduces the clonogenic survival and invasive potential of SNU449 cells. Treatment of liver cancer cells with STT increases the expression of autophagic, targets anti-autophagic protein expression and down-regulates Akt/mTOR pathway to inhibit cancer growth and proliferation. Thus, STT exhibits prominent anticancer effect and needs to be investigated further as a potential candidate for the treatment of liver cancer.

Proteomics and its application in the research of acupuncture: An updated review.

As a complementary and alternative therapy, acupuncture is widely used in the prevention and treatment of various diseases. However, the understanding of the mechanism of acupuncture effects is still limited due to the lack of systematic biological validation. Notably, proteomics technologies in the field of acupuncture are rapidly evolving, and these advances are greatly contributing to the research of acupuncture. In this study, we review the progress of proteomics research in analyzing the molecular mechanisms of acupuncture for neurological disorders, pain, circulatory disorders, digestive disorders, and other diseases, with an in-depth discussion around acupoint prescription and acupuncture manipulation modalities. The study found that proteomics has great potential in understanding the mechanisms of acupuncture. This study will help explore the mechanisms of acupuncture from a proteomic perspective and provide information to support future clinical decisions.

Citrus polymethoxyflavones degrade estrogen receptor-alpha (ERα) and combine with tamoxifen for the treatment of estrogen receptor-positive breast cancer.

Estrogen receptor-positive (ER+) breast cancer seriously endangers the women's physical and mental health worldwide and ER targeting therapy is vital. Here, we found that a citrus polymethoxyflavones (PMFs)-rich hydrolysate (C-H) and its major components (nobiletin and 3-methoxynobiletin) potently degrade ERα protein via the ubiquitin-proteasome pathway, thereby impairing the proliferation of ER+ breast cancer cells. Moreover, our study exhibited that C-H combined with tamoxifen (TAM) inhibited the cell proliferation of ER+ breast cancer in vitro. It was further confirmed that C-H decreased tumor growth of ER+ breast cancer in tumor-bearing 129 mice in vivo and improved the efficacy of tamoxifen. Our study revealed that the citrus PMFs have potential applications as pharmaceutical and healthcare products in breast cancer treatment by targeting ERα protein degradation.

Expression and function identification of senescence-associated genes under continuous drought treatment in grapevine (Vitis vinifera L.) leaves.

Natural leaf senescence is critical for plant fitness. Drought-induced premature leaf senescence affects grape yield and quality. However, reports on the regulatory mechanisms underlying premature leaf senescence under drought stress are limited. In this study, two-year-old potted 'Muscat Hamburg' grape plants were subjected to continuous natural drought treatment until mature leaves exhibited senescence symptoms. Physiological and biochemical indices related to drought stress and senescence were monitored. Transcriptome and transgenic Arabidopsis were used to perform expression analyses and functional identification of drought-induced senescence-associated genes. Twelve days of continuous drought stress was sufficient to cause various physiological disruptions and visible senescence symptoms in mature 'Muscat Hamburg' leaves. These disruptions included malondialdehyde and H2O2 accumulation, and decreased catalase activity and chlorophyll (Chl) levels. Transcriptome analysis revealed that most genes involved in photosynthesis and Chl synthesis were downregulated after 12 d of drought treatment. Three key Chl catabolic genes (SGR, NYC1, and PAO) were significantly upregulated. Overexpression of VvSGR in wild Arabidopsis further confirmed that SGR directly promoted early yellowing of cotyledons and leaves. In addition, drought treatment decreased expression of gibberellic acid signaling repressors (GAI and GAI1) and cytokinin signal components (AHK4, AHK2, RR22, RR9-1, RR9-2, RR6, and RR4) but significantly increased the expression of abscisic acid, jasmonic acid, and salicylic acid signaling components and responsive transcription factors (bZIP40/ABF2, WRKY54/75/70, ANAC019, and MYC2). Moreover, some NAC members (NAC0002, NAC019, and NAC048) may also be drought-induced senescence-associated genes. These results provide extensive information on candidate genes involved in drought-induced senescence in grape leaves. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01465-2.

Study on the mechanism of macrophages activated by phosphoesterified rehmanniae polysaccharide on human gastric cancer cells.

Gastric cancer(GC)is one of the most common gastrointestinal malignant tumors in the world, requiring the development of novel therapeutic agents with reduced toxicity. Rehmannia polysaccharide (RPS) possesses immunomodulatory and anti-tumor properties, yet its efficacy is suboptimal. To enhance its biological activity, we subjected RPS to molecular modifications, resulting in phosphorylated Rehmannia polysaccharides (P-RPS). Using the mixed phosphate method, we synthesized P-RPS and optimized the synthesis conditions through a combination of single-factor and response surface methodologies. In vitro studies on P-RPS's anti-tumor activity showed no direct influence on the viability of GC cells. However, P-RPS induced the transformation of PMA-activated THP-1 cells into the M1 phenotype. We collected conditioned medium (CM) of THP-1 cells to stimulate gastric cancer cells and CM-P-RPS significantly promoted apoptosis of gastric cancer cells and inhibited cell proliferation, and reduced cell migration. Mechanistically, CM-P-RPS inhibits the Wnt/ß-catenin signaling pathway through LGR6, leading to the suppression of tumor growth. Furthermore, P-RPS demonstrated a significant inhibitory effect on tumor growth in vivo, suggesting its potential as a promising therapeutic agent for GC treatment.

Biliary atresia and cholestasis plasma non-targeted metabolomics unravels perturbed metabolic pathways and unveils a diagnostic model for biliary atresia.

The clinical diagnosis of biliary atresia (BA) poses challenges, particularly in distinguishing it from cholestasis (CS). Moreover, the prognosis for BA is unfavorable and there is a dearth of effective non-invasive diagnostic models for detection. Therefore, the aim of this study is to elucidate the metabolic disparities among children with BA, CS, and normal controls (NC) without any hepatic abnormalities through comprehensive metabolomics analysis. Additionally, our objective is to develop an advanced diagnostic model that enables identification of BA. The plasma samples from 90 children with BA, 48 children with CS, and 47 NC without any liver abnormalities children were subjected to metabolomics analysis, revealing significant differences in metabolite profiles among the 3 groups, particularly between BA and CS. A total of 238 differential metabolites were identified in the positive mode, while 89 differential metabolites were detected in the negative mode. Enrichment analysis revealed 10 distinct metabolic pathways that differed, such as lysine degradation, bile acid biosynthesis. A total of 18 biomarkers were identified through biomarker analysis, and in combination with the exploration of 3 additional biomarkers (LysoPC(18:2(9Z,12Z)), PC (22:5(7Z,10Z,13Z,16Z,19Z)/14:0), and Biliverdin-IX-α), a diagnostic model for BA was constructed using logistic regression analysis. The resulting ROC area under the curve was determined to be 0.968. This study presents an innovative and pioneering approach that utilizes metabolomics analysis to develop a diagnostic model for BA, thereby reducing the need for unnecessary invasive examinations and contributing to advancements in diagnosis and prognosis for patients with BA.

Ag-Catalyzed Selective C-C Bond Activation of Cyclopropenones to Access α-Alkylidene Lactones.

A novel Ag-catalyzed ring opening of unsymmetric cyclopropenones for the stereoselective synthesis of a diverse range of α-alkylidene lactones has been developed. In this protocol, two different C-C(O) bonds were distinguished, demonstrating selective C-C bond activation. This reaction features a wide substrate scope, good functional group compatibility, and high atom economy, providing a versatile and general approach to the construction of α-alkylidene lactones.

Specific CD4+ T cell phenotypes associate with bacterial control in people who 'resist' infection with Mycobacterium tuberculosis.

A subset of individuals exposed to Mycobacterium tuberculosis (Mtb) that we refer to as 'resisters' (RSTR) show evidence of IFN-γ- T cell responses to Mtb-specific antigens despite serially negative results on clinical testing. Here we found that Mtb-specific T cells in RSTR were clonally expanded, confirming the priming of adaptive immune responses following Mtb exposure. RSTR CD4+ T cells showed enrichment of TH17 and regulatory T cell-like functional programs compared to Mtb-specific T cells from individuals with latent Mtb infection. Using public datasets, we showed that these TH17 cell-like functional programs were associated with lack of progression to active tuberculosis among South African adolescents with latent Mtb infection and with bacterial control in nonhuman primates. Our findings suggested that RSTR may successfully control Mtb following exposure and immune priming and established a set of T cell biomarkers to facilitate further study of this clinical phenotype.

Melatonin partially rescues defects induced by tranexamic acid exposure during oocyte maturation in mice.

Tranexamic acid (TXA) is widely used among young women because of its ability to whiten skin and treat menorrhagia. Nevertheless, its potential effects on oocyte maturation and quality have not yet been clearly clarified. Melatonin (MT) is an endogenous hormone released by the pineal gland and believed to protect cells from oxidative stress injury. In the present study, we used in vitro maturation model to investigate the toxicity of TXA and the protective role of MT in mouse oocyte. Compared with the control group, TXA-exposed group had significantly lower nuclear maturation (57.72% vs. 94.08%, P < 0.001) and early embryo cleavage rates (38.18% vs. 87.66%, P < 0.001). Further study showed that spindle organization (52.56% vs. 18.77%, P < 0.01) and chromosome alignment (33.23% vs. 16.66%, P < 0.01) were also disrupted after TXA treatment. Mechanistically, we have demonstrated that TXA induced early apoptosis of oocytes (P < 0.001) by raising the level of ROS (P < 0.001), which was consistent with an increase in mitochondrial damage (P < 0.01). Fortunately, all these effects except the spindle defect were successfully rescued by an appropriate level of MT. Collectively, our findings indicate that MT could partially reverse TXA-induced oocyte quality deterioration in mouse by effectively improving mitochondrial function and reducing oxidative stress-mediated apoptosis.

Study on the preparation of CdS/TiO2 corn straw biochar composite materials for photocatalytic reduction of CO2 and collaborative H2 production.

A thermal synthesis method was employed in this work to prepare CdS/TiO2 corn straw biochar photocatalytic composite materials suitable for synergistic hydrogen production with the photocatalytic reduction of CO2. The structure and synergistic reaction of these composite materials were characterized by its photogenerated electron transfer process. Compared with pure TiO2, the energy band gap of the optimal CdS/TiO2 corn straw biochar composite material was reduced to 2.89 eV. The heterostructure coupling between TiO2 and CdS in the biochar accelerated the transfer of photogenerated electrons and reduced the recombination rate of photogenerated electrons and holes. Under visible light irradiation, the photocatalytic H2 yield of this CdS/TiO2 corn straw-derived biochar composite material was 1200 µmol·h-1·g-1, the CO yield was 150 µmol·h-1·g-1, and the CH4 yield was 55 µmol·h-1·g-1. The key to this synergistic reaction is the formation of heterojunctions between CdS and TiO2 as well as the rapid oxidation of holes in the composite material caused by the doping of biochar.

Morphological and physiological investigations reveal the regulatory effect of exogenous paclobutrazol on flowering promotion by winter warming in Chaenomeles speciosa 'Changshouguan'.

The application of exogenous paclobutrazol (PP333) can improve the ability of winter warming to promote flowering in Chaenomeles speciosa, but the underlying mechanism is unclear. In this study, the cultivar 'Changshouguan' was sprayed with different concentrations of PP333 during flower bud differentiation, and the changes in the anatomical structures and physiological characteristics of the flower buds during the differentiation process, as well as the growth state of the flower buds and the effect on flowering promotion after winter warming treatment, were comprehensively investigated. The results showed that different concentrations of PP333 could advance the flowering time of 'Changshouguan' by 15-24 d under the warming treatment and increase the flowering duration to 17 d compared with those under the warming treatment alone (CK), and 1000 mg/L was the best treatment. Compared with the CK treatment, the PP333 treatment decreased the contents of indole acetic acid (IAA) and gibberellic acid (GAs) and increased the contents of zeatin ribosides (ZRs) and abscisic acid (ABA), thus changing the balance of hormones during flower bud differentiation. The inflection point (low point) of the curve shapes of the ZRs/GAs and ZRs/IAA ratios appeared significantly earlier, which showed a pattern consistent with soluble sugar and protein content and antioxidant activity. Interestingly, the above changes also corresponded to earlier flowering times during the warming process. Taken together, these results indicate that spraying an appropriate concentration of PP333 in the early stage of 'Changshouguan' flower bud differentiation promotes the early differentiation of flower buds and early flowering under winter warming treatment by altering their endogenous hormone content and homeostasis and changing their physiological state. The key to maintaining a relatively long flowering period in plants in the PP333 treatment group after flowering promotion was the increased accumulation of sugars and proteins.

Laparoscopic spleen-preserving total pancreatectomy for the treatment of low-grade malignant pancreatic tumors: Two case reports and review of literature.

BACKGROUND: Function-preserving pancreatectomy can improve the long-term quality of life of patients with benign or low-grade malignant tumors, such as intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms. However, there is limited literature on laparoscopic spleen-preserving total pancreatectomy (L-SpTP) due to technical difficulties. CASE SUMMARY: Patient 1 was a 51-year-old male diagnosed with IPMN based on preoperative imaging, showing solid nodules in the pancreatic head and diffuse dilation of the main pancreatic duct with atrophy of the distal pancreas. We performed L-SpTP with preservation of the splenic vessels, and the postoperative pathology report revealed IPMN with invasive carcinoma. Patient 2 was a 60-year-old male with multiple cystic lesions in the pancreatic head and body. L-SpTP was performed, and intraoperatively, the splenic vein was injured and required ligation. Postoperative pathology revealed a mucinous cystic tumor of the pancreas with low-grade dysplasia. Both patients were discharged on postoperative day 7, and there were no major complications during the perioperative period. CONCLUSION: We believe that L-SpTP is a safe and feasible treatment for low-grade malignant pancreatic tumors, but more case studies are needed to evaluate its safety, efficacy, and long-term outcomes.

A double-negative feedback loop mediated by non-coding RNAs contributes to tooth morphogenesis.

Tooth morphogenesis is a critically ordered process manipulated by a range of signaling factors. Particularly, the involvement of fine-tuned signaling mediated by non-coding RNAs has been of longstanding interest. Here, we revealed a double-negative feedback loop acted by a long non-coding RNA (LOC102159588) and a microRNA (miR-133b) that modulated tooth morphogenesis of miniature swine. Mechanistically, miR-133b repressed the transcription of LOC102159588 through downstream target Sp1. Conversely, LOC102159588 not only inhibited the transport of pre-miR-133b from the nucleus to the cytoplasm by regulating exportin-5 but also served as a sponge in the cytoplasm, suppressing functional miR-133b. Together, the double-negative feedback loop maintained normal tooth morphogenesis by modulating endogenous apoptosis. Related disruptions would lead to an arrest of tooth development and may result in tooth malformations.

Dysregulated RNA editing of EIF2AK2 in polycystic ovary syndrome: clinical relevance and functional implications.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive ages. Our previous study has implicated a possible link between RNA editing and PCOS, yet the actual role of RNA editing, its association with clinical features, and the underlying mechanisms remain unclear. METHODS: Ten RNA-Seq datasets containing 269 samples of multiple tissue types, including granulosa cells, T helper cells, placenta, oocyte, endometrial stromal cells, endometrium, and adipose tissues, were retrieved from public databases. Peripheral blood samples were collected from twelve PCOS and ten controls and subjected to RNA-Seq. Transcriptome-wide RNA-Seq data analysis was conducted to identify differential RNA editing (DRE) between PCOS and controls. The functional significance of DRE was evaluated by luciferase reporter assays and overexpression in human HEK293T cells. Dehydroepiandrosterone and lipopolysaccharide were used to stimulate human KGN granulosa cells to evaluate gene expression. RESULTS: RNA editing dysregulations across multiple tissues were found to be associated with PCOS in public datasets. Peripheral blood transcriptome analysis revealed 798 DRE events associated with PCOS. Through weighted gene co-expression network analysis, our results revealed a set of hub DRE events in PCOS blood. A DRE event in the eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2:chr2:37,100,559) was associated with PCOS clinical features such as luteinizing hormone (LH) and the ratio of LH over follicle-stimulating hormone. Luciferase assays, overexpression, and knockout of RNA editing enzyme adenosine deaminase RNA specific (ADAR) showed that the ADAR-mediated editing cis-regulated EIF2AK2 expression. EIAF2AK2 showed a higher expression after dehydroepiandrosterone and lipopolysaccharide stimulation, triggering changes in the downstrean MAPK pathway. CONCLUSIONS: Our study presented the first evidence of cross-tissue RNA editing dysregulation in PCOS and its clinical associations. The dysregulation of RNA editing mediated by ADAR and the disrupted target EIF2AK2 may contribute to PCOS development via the MPAK pathway, underlining such epigenetic mechanisms in the disease.