Chiral kagome superconductivity modulations with residual Fermi arcs.

Superconductivity involving finite-momentum pairing1 can lead to spatial-gap and pair-density modulations, as well as Bogoliubov Fermi states within the superconducting gap. However, the experimental realization of their intertwined relations has been challenging. Here we detect chiral kagome superconductivity modulations with residual Fermi arcs in KV3Sb5 and CsV3Sb5 using normal and Josephson scanning tunnelling microscopy down to 30 millikelvin with a resolved electronic energy difference at the microelectronvolt level. We observe a U-shaped superconducting gap with flat residual in-gap states. This gap shows chiral 2a × 2a spatial modulations with magnetic-field-tunable chirality, which align with the chiral 2a × 2a pair-density modulations observed through Josephson tunnelling. These findings demonstrate a chiral pair density wave (PDW) that breaks time-reversal symmetry. Quasiparticle interference imaging of the in-gap zero-energy states reveals segmented arcs, with high-temperature data linking them to parts of the reconstructed vanadium d-orbital states within the charge order. The detected residual Fermi arcs can be explained by the partial suppression of these d-orbital states through an interorbital 2a × 2a PDW and thus serve as candidate Bogoliubov Fermi states. In addition, we differentiate the observed PDW order from impurity-induced gap modulations. Our observations not only uncover a chiral PDW order with orbital selectivity but also show the fundamental space-momentum correspondence inherent in finite-momentum-paired superconductivity.

Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

Evidence for time-reversal symmetry-breaking kagome superconductivity.

Superconductivity and magnetism are often antagonistic in quantum matter, although their intertwining has long been considered in frustrated-lattice systems. Here we utilize scanning tunnelling microscopy and muon spin resonance to demonstrate time-reversal symmetry-breaking superconductivity in kagome metal Cs(V, Ta)3Sb5, where the Cooper pairing exhibits magnetism and is modulated by it. In the magnetic channel, we observe spontaneous internal magnetism in a fully gapped superconducting state. Under the perturbation of inverse magnetic fields, we detect a time-reversal asymmetrical interference of Bogoliubov quasi-particles at a circular vector. At this vector, the pairing gap spontaneously modulates, which is distinct from pair density waves occurring at a point vector and consistent with the theoretical proposal of an unusual interference effect under time-reversal symmetry breaking. The correlation between internal magnetism, Bogoliubov quasi-particles and pairing modulation provides a chain of experimental indications for time-reversal symmetry-breaking kagome superconductivity.

OsUVR8b, rather than OsUVR8a, plays a predominant role in rice UVR8-mediated UV-B response.

UV RESISTANCE LOCUS 8 (UVR8) has been identified in Arabidopsis thaliana as the receptor mediating responses to UV-B radiation. However, UVR8-mediated UV-B signaling pathways in rice, which possesses two proteins (UVR8a and UVR8b) with high identities to AtUVR8, remain largely unknown. Here, UVR8a/b were found to be predominantly expressed in rice leaves and leaf sheaths, while the levels of UVR8b transcript and UVR8b protein were both higher than those of UVR8a. Compared to wild-type (WT) plants, uvr8b and uvr8a uvr8b rice mutants exposed to UV-B showed reduced UV-B-induced growth inhibition and upregulation of CHS and HY5 transcripts alongside UV-B acclimation. However, uvr8a mutant was similar to WT plants and exhibited changes comparable with WT. Overexpressing OsUVR8a/b enhanced UV-B-induced growth inhibition and acclimation to UV-B. UV-B was able to enhance the interaction between E3 ubiquitin ligase OsCOP1 and OsUVR8a/b, whereas the interaction of the homologous protein of Arabidopsis REPRESSOR OF UV-B PHOTOMORPHOGENESIS2 (AtRUP2) in rice with OsUVR8a/b was independent of UV-B. Additionally, OsUVR8a/b proteins were also found in the nucleus and cytoplasm even in the absence of UV-B. The abundance of OsUVR8 monomer showed an invisible change in the leaves of rice seedlings transferred from white light to that supplemented with UV-B, even though UV-B was able to weaken the interactions between OsUVR8a and OsUVR8b homo and heterodimers. Therefore, both OsUVR8a and OsUVR8b, which have different localization and response patterns compared with AtUVR8, function in the response of rice to UV-B radiation, whereas OsUVR8b plays a predominant role in this process.

Insights into Advanced Neurological Dysfunction Mechanisms Following DBS Surgery in Parkinson's Patients: Neuroinflammation and Pyroptosis.

Parkinson's disease is a severe neurodegenerative disorder. Currently, deep brain electrical stimulation (DBS) is the first line of surgical treatment. However, serious neurological impairments such as speech disorders, disturbances of consciousness, and depression after surgery limit the efficacy of treatment. In this review, we summarize the recent experimental and clinical studies that have explored the possible causes of neurological deficits after DBS. Furthermore, we tried to identify clues from oxidative stress and pathological changes in patients that could lead to the activation of microglia and astrocytes in DBS surgical injury. Notably, reliable evidence supports the idea that neuroinflammation is caused by microglia and astrocytes, which may contribute to caspase-1 pathway-mediated neuronal pyroptosis. Finally, existing drugs and treatments may partially ameliorate the loss of neurological function in patients following DBS surgery by exerting neuroprotective effects.

Pediatric hypereosinophilic syndrome associated with liver damage, portal vein, splenic vein and superior mesenteric vein thromboses: a case report.

BACKGROUND: The hypereosinophilic syndrome (HES) is a group of rare blood disorders characterized by persistent eosinophilia and damage to multiple organs. HES can be either primary, secondary or idiopathic. Secondary HES are commonly caused by parasitic infections, allergic reactions or cancer. We described a pediatric case of HES associated with liver damage and multiple thrombi. A 12-year-old boy with eosinophilia was complicated with severe thrombocytopenia, liver damage, portal vein, splenic vein, and superior mesenteric vein thromboses. The thrombi recanalized after treatment with methylprednisolone succinate and low molecular weight heparin. No side effects appeared after 1-month. CONCLUSIONS: Corticosteroids should be used at an early stage of HES to prevent further damage to vital organs. Anticoagulants should be recommended only in cases with thrombosis which should be actively screened as a part of evaluation of end organ damage.

The rice germin-like protein OsGLP1 participates in acclimation to UV-B radiation.

Exposure to ultraviolet B radiation (UV-B) stress can have serious effects on the growth and development of plants. Germin-like proteins (GLPs) may be involved in different abiotic and biotic stress responses in different plants, but little is known about the role of GLPs in UV-B stress response and acclimation in plants. In the present study, knockout of GLP 8-14 (OsGLP1) using the CRISPR/Cas9 system resulted in mutant rice (Oryza sativa L.) plants (herein called glp1) that exhibited UV-B-dependent formation of lesion mimic in leaves. Moreover, glp1 grown under solar radiation (including UV-B) showed decreased plant height and increased leaf angle, but we observed no significant differences in phenotypes between wild-type (WT) plants and glp1 grown under artificial light lacking UV-B. Fv/Fm, Y (II) and the expression of many genes, based on RNA-seq analysis, related to photosynthesis were also only reduced in glp1, but not in WT, after transfer from a growth cabinet illuminated with artificial white light lacking UV-B to growth under natural sunlight. The genes-associated with flavonoid metabolism as well as UV resistance locus 8 (OsUVR8), phytochrome interacting factor-like 15-like (OsPIF3), pyridoxal 5'-phosphate synthase subunit PDX1.2 (OsPDX1.2), deoxyribodipyrimidine photolyase (OsPHR), and deoxyribodipyrimidine photolyase family protein-like (OsPHRL) exhibited lower expression levels, while higher expression levels of mitogen-activated protein kinase 5-like (OsMPK3), mitogen-activated protein kinase 13-like (OsMPK13), and transcription factor MYB4-like (OsMYB4) were observed in glp1 than in WT after transfer from a growth cabinet illuminated with artificial white light to growth under natural sunlight. Therefore, mutations in OsGLP1 resulted in rice plants more sensitive to UV-B and reduced expression of some genes for UV-B protection, suggesting that OsGLP1 is involved in acclimation to UV-B radiation.

Effect of autoinduction and food on the pharmacokinetics of furmonertinib and its active metabolite characterized by a population pharmacokinetic model.

Furmonertinib (AST2818) is a novel third-generation irreversible EGFR TKI and recently has been approved in China for the treatment of non-small cell lung cancer (NSCLC) with EGFR-sensitizing and T790M resistance mutations. In the current study, we developed a semi-mechanistic population pharmacokinetic model to characterize the nonstationary pharmacokinetics (PK) of the furmonertinib and its active metabolite AST5902 simultaneously. The PK data of furmonertinib and AST5902 were obtained from 38 NSCLC patients and 16 healthy volunteers receiving 20-240 mg furmonertinib in three clinical trials. A nonlinear mixed-effects modeling approach was used to describe the PK data. The absorption process of furmonertinib was described by a transit compartment model. The disposition of both furmonertinib and AST5902 was described by a two-compartment model. An indirect response model accounted for the autoinduction of furmonertinib metabolism mediated by CYP3A4. The model-based simulation suggested that furmonertinib clearance was increased in one cycle of treatment (orally once daily for 21 days) compared to baseline, ranging from 1.1 to 1.8 fold corresponding to the dose range of 20-240 mg. The concentration of furmonertinib was decreased over time whereas that of AST5902 was increased. Interestingly, the concentration of the total active compounds (furmonertinib and AST5902) appeared to be stable. The food intake, serum alkaline phosphatase and body weight were identified as statistically significant covariates. The mechanism of food effect on PK was investigated, where the food intake might increase the bioavailability of furmonertinib via increasing the splanchnic blood flow. Overall, a population PK model was successfully developed to characterize the nonstationary PK of furmonertinib and AST5902 simultaneously. The concentrations of total active compounds were less affected by the autoinduction of furmonertinib metabolism.

Insight into the role of p62 in the cisplatin resistant mechanisms of ovarian cancer.

Cisplatin is a platinum-based first-line drug for treating ovarian cancer. However, chemotherapy tolerance has limited the efficacy of cisplatin for ovarian cancer patients. Research has demonstrated that cisplatin causes changes in cell survival and death signaling pathways through its interaction with macromolecules and organelles, which indicates that investigation into the DNA off-target effects of cisplatin may provide critical insights into the mechanisms underlying drug resistance. The multifunctional protein p62 works as a signaling hub in the regulation of pro-survival transcriptional factors NF-κB and Nrf2 and connects autophagy and apoptotic signals, which play important roles in maintaining cell homeostasis. In this review, we discuss the role of p62 in cisplatin resistance by exploring p62-associated signaling pathways based on current studies and our work. Insights into these resistance mechanisms may lead to more effective therapeutic strategies for ovarian cancer by targeting p62.

p62 aggregates mediated Caspase 8 activation is responsible for progression of ovarian cancer.

Increasing evidence suggests that p62/SQSTM1 functions as a signalling centre in cancer. However, the role of p62 in tumour development depends on the interacting factors it recruits and its precise regulatory mechanism remains unclear. In this study, we investigated the pro-death signalling recruitment of p62 with the goal of improving anti-tumour drug effects in ovarian cancer treatment. We found that p62 with Caspase 8 high expression is correlated with longer survival time compared with cases of low Caspase 8 expression in ovarian cancer. In vivo experiments suggested that insoluble p62 and ubiquitinated protein accumulation induced by autophagy impairment promoted the activation of Caspase 8 and increased cell sensitivity to cisplatin. Furthermore, p62 functional domain UBA and LIR mutants regulated autophagic flux and attenuated Caspase 8 activation, which indicates that autophagic degradation is involved in p62-mediated activation of Caspase 8 in ovarian cancer cells. Collectively, our study demonstrates that p62 promotes Caspase 8 activation through autophagy flux blockage with cisplatin treatment. We have provided evidence that autophagy induction followed by its blockade increases cell sensitivity to chemotherapy which is dependent on p62-Caspase 8 mediated apoptosis signalling. p62 exhibits pro-death functions through its interaction with Caspase 8. p62 and Caspase 8 may become novel prognostic biomarkers and oncotargets for ovarian cancer treatment.

SIRT3 aggravates metformin-induced energy stress and apoptosis in ovarian cancer cells.

Increasing evidence suggests that mitochondrial respiratory chain complex I participates in carcinogenesis and cancer progression by providing energy and maintaining mitochondrial function. However, the role of complex I in ovarian cancer is largely unknown. In this study we showed that metformin, considered to be an inhibitor of complex I, simultaneously inhibited cell growth and induced mitochondrial-related apoptosis in human ovarian cancer cells. Metformin interrupted cellular energy metabolism mainly by causing damage to complex I that impacted mitochondrial function. Additionally, treatment with metformin increased the activation of sirtuin 3 (SIRT3), a mitochondrial deacetylase. We demonstrated that SIRT3 overexpression aggravated metformin-induced apoptosis, energy stress and mitochondrial dysfunction. Moreover, treatment with metformin or SIRT3 overexpression increased activation of AMP-activated protein kinase (AMPK), a major sensor of cellular energy status. AMPK compensated for energy loss by increasing glycolysis. The impact of this was assessed by reducing glucose levels in the media or by using inhibitors (2-deoxyglucose, Compound C) of glycolysis and AMPK. The combination of these factors with metformin intensified cytotoxicity through further downregulation of ATP. Our study outlines an important role for SIRT3 in the antitumor effect of mitochondrial complex I inhibitors in human ovarian cancer cells. This effect appears to be mediated by induction of energy stress and apoptosis. Strategies that target the mitochondria could be enhanced by modulating glycolysis to further aggravate energy stress that may increase the antitumor effect.

p62/SQSTM1 as an oncotarget mediates cisplatin resistance through activating RIP1-NF-κB pathway in human ovarian cancer cells.

Platinum-based therapeutic strategies have been widely used in ovarian cancer treatment. However, drug resistance has greatly limited therapeutic efficacy. Recently, tolerance to cisplatin has been attributed to other factors unrelated to DNA. p62 (also known as SQSTM1) functions as a multifunctional hub participating in tumorigenesis and may be a therapeutic target. Our previous study showed that p62 was overexpressed in drug-resistant ovarian epithelial carcinoma and its inhibition increased the sensitivity to cisplatin. In this study, we demonstrate that the activity of the NF-κB signaling pathway and K63-linked ubiquitination of RIP1 was higher in cisplatin-resistant ovarian (SKOV3/DDP) cells compared with parental cells. In addition, cisplatin resistance could be reversed by inhibiting the expression of p62 using siRNA. Furthermore, deletion of the ZZ domain of p62 that interacts with RIP1 in SKOV3 cells markedly decreased K63-linked ubiquitination of RIP1 and inhibited the activation of the NF-κB signaling pathway. Moreover, loss of the ZZ domain from p62 led to poor proliferative capacity and high levels of apoptosis in SKOV3 cells and made them more sensitive to cisplatin treatment. Collectively, we provide evidence that p62 is implicated in the activation of NF-κB signaling that is partly dependent on RIP1. p62 promotes cell proliferation and inhibits apoptosis thus mediating drug resistance in ovarian cancer cells.

Cytoprotective Effect of the UCP2-SIRT3 Signaling Pathway by Decreasing Mitochondrial Oxidative Stress on Cerebral Ischemia-Reperfusion Injury.

Recovered blood supply after cerebral ischemia for a certain period of time fails to restore brain function, with more severe dysfunctional problems developing, called cerebral ischemia-reperfusion injury (CIR). CIR involves several extremely complex pathophysiological processes in which the interactions between key factors at various stages have not been fully elucidated. Mitochondrial dysfunction is one of the most important mechanisms of CIR. The mitochondrial deacetylase, sirtuin 3 (SIRT3), can inhibit mitochondrial oxidative stress by deacetylation, to maintain mitochondrial stability. Uncoupling protein 2 (UCP2) regulates ATP (Adenosine triphosphate) and reactive oxygen species production by affecting the mitochondrial respiratory chain, which may play a protective role in CIR. Finally, we propose that UCP2 regulates the activity of SIRT3 through sensing the energy level and, in turn, maintaining the mitochondrial steady state, which demonstrates a cytoprotective effect on CIR.

Antifungal Activity of Phloroglucinol Derivatives against Botrytis cinerea and Monilinia fructicola.

Naturally derived compounds show promise as treatments for microbial infections. Polyphenols, abundantly found in various plants, fruits, and vegetables, are noted for their physiological benefits including antimicrobial effects. This study introduced a new set of acylated phloroglucinol derivatives, synthesized and tested for their antifungal activity in vitro against seven different pathogenic fungi. The standout compound, 3-methyl-1-(2,4,6-trihydroxyphenyl) butan-1-one (2b), exhibited remarkable fungicidal strength, with EC50 values of 1.39 µg/mL against Botrytis cinerea and 1.18 µg/mL against Monilinia fructicola, outperforming previously screened phenolic compounds. When tested in vivo, 2b demonstrated effective antifungal properties, with cure rates of 76.26% for brown rot and 83.35% for gray mold at a concentration of 200 µg/mL, rivaling the commercial fungicide Pyrimethanil in its efficacy against B. cinerea. Preliminary research suggests that 2b's antifungal mechanism may involve the disruption of spore germination, damage to the fungal cell membrane, and leakage of cellular contents. These results indicate that compound 2b has excellent fungicidal properties against B. cinerea and holds potential as a treatment for gray mold.

[Spatiotemporal Distribution Characteristics of Ground-level-ozone and Its Relationship with Meteorological Conditions in a Representative City in the Bohai Rim from 2017 to 2022].

In recent years, ground-level-ozone（O3） pollution in urban areas in the Bohai Rim has attracted wide attention. Based on the analysis of the spatiotemporal distribution characteristics of O3 concentration in Dongying, a representative city in the Bohai Rim from 2017 to 2022, the effects of meteorological factors and sea-land breeze circulation on O3 concentration were evaluated. The results showed that： ① From 2017 to 2022, the annual assessment value of O3 concentration in Dongying showed a fluctuating upward trend, and the pollution days with O3 as the primary pollutant increased. O3 pollution mainly occurred in spring, summer, and autumn, with the most severe O3 pollution episodes typically occurring in May and June, and the duration of O3 pollution season tended to be longer. The monthly variation in the daily maximum 8-h average ozone （MDA8 O3） presented a bimodal distribution, with significant increases in the 5th and 25th percentiles, and the spatial distribution was "high in the north and south, low in the middle." In addition, the nocturnal O3 concentration in recent years in Dongying also showed a significant increase trend. ② Meteorological factors greatly influenced O3 concentration in Dongying. When the temperature was greater than 30℃, the relative humidity was less than 50%, and the wind direction was south-southwest or east-northeast, a high O3 value was more likely to occur. Meteorological factors contributed 30% of the MDA8 O3 variation in Dongying during the study period. In the case of moderate and severe O3 pollution, the contribution of meteorological factors to the change in MDA8 O3 could be as high as 40%. ③ To some extent, sea-land breeze contributed to the occurrence of MDA8 O3 exceeding the secondary standard limit value of the National Ambient Air Quality Standard. In the afternoon, the hourly concentration of O3 during the sea-land breeze days was approximately 20 µg·m-3 higher than that during the non-sea-land breeze days. On the days of moderate and severe O3 pollution, the O3 concentration during the sea-land breeze days from 10：00 to 16：00 was higher than that during non-sea-land breeze days, and the O3 concentration was also at a high level from 20：00 to 23：00 on sea-land breeze days. In the O3 pollution season, the sea-land breeze could significantly affect the O3 level in coastal cities, which could bring significant challenges for O3 pollution prevention and control in this region. In the future, cities in the Bohai Rim need to further strengthen regional joint prevention and control of O3 pollution and increase emission reduction efforts of nitrogen oxides and volatile organic compounds. This strategy could effectively lower pollutant concentrations within the land breeze air mass, consequently reducing the impact of the sea breeze air mass on air quality in cities in the Bohai Rim.

Peplau's interpersonal relationship theory combined with bladder function training on patients with prostate cancer.

BACKGROUND: Prostate cancer is a major disease impacting men's health worldwide. Peplau, who is known as "the mother of psychiatric society," developed an interpersonal relationship theory for nursing. Implementation of this theory in practice has been shown to positively impact patients' quality of life and reduce adverse symptoms after surgery. AIM: To investigate the effects of a nursing model based on Peplau's interpersonal relationship theory combined with bladder function training on patients with prostate cancer. METHODS: Eighty-nine patients with prostate cancer who underwent transurethral resection of the prostate (TURP) participated in this study. These patients were admitted to The First Affiliated Hospital of Soochow University or Dushu Lake Hospital Affiliated to Soochow University between January 2020 and April 2021. Patients were randomized into either the Peplau nursing group (n = 44) or a routine nursing group (n = 45). The routine nursing group received routine care and bladder function training, while the Peplau care group received care that integrated concepts from the Peplau interpersonal relationship theory as well as bladder function training. The urinary incontinence symptoms of the two groups were recorded, and the respective International Prostate Symptom Scores (IPSS), Functional Assessment of Chronic Illness Therapy- Spiritual Well-Being (FACIT-Sp) scores, and quality of life (QOL) scores for each group were compared before and after three months of nursing intervention. RESULTS: During the intervention period, the duration of urinary incontinence, frequency, number and amount of urinary incontinence were significantly greater in the routine nursing group compared to the Peplau care group (P < 0.05). The indicators of the routine nursing group were 7.13 ± 2.42 days, 8.23 ± 2.75 times, and 1.24 ± 0.42 L, while those of the Peplau care group were 4.74 ± 1.85 d, 4.21 ± 1.26 times, and 0.56 ± 0.11 L, respectively. After three months of intervention, the mean IPSS score of the routine nursing group was significantly reduced (P < 0.05), while the mean FACIT-Sp and QOL scores were significantly increased (P < 0.05). The mean IPSS score in the Peplau nursing group was significantly lower compared to the routine nursing group, while the FACIT-Sp and QOL scores were higher (P < 0.05). CONCLUSION: A nursing model based on Peplau's interpersonal relationship theory combined with bladder function training can significantly improve prostate function and urinary symptoms, resulting in the restoration of physiological function and improvement in the QOL of patients with prostate cancer following TURP.

What is responsible for acute myocardial infarction in combination with aplastic anemia? A case report and literature review.

BACKGROUND: Aplastic anemia (AA) complicated with myocardial infarction (MI) is rare and associated with poor prognosis. Here, we present a case of AA with recurrent acute MI (AMI) in a patient treated with cyclosporine A (CsA) and stanozolol. In this patient, we suspect the long-term use of medication linked to platelets hyperfunction. CASE SUMMARY: In 2017, a 45-year-old man was rushed to the emergency department of China-Japan Union Hospital due to precordial pain for 5 h. Based on his symptoms, medical history, blood tests, and findings from coronary angiography (CAG), the patient was diagnosed with acute anterior wall, ST-segment elevated MI, Killip II grade, AA, and dyslipidemia. In 2021, the patient was readmitted to the hospital for 2 h due to chest pain. Because the patient's platelet count was 30 × 109/L and he had severe thrombocytopenia, we performed CAG following platelet transfusion. Optical coherence tomography revealed lipid plaque and thrombus mass in his right coronary artery. The antithrombotic approach was adjusted to employ only anticoagulants (factor Xa inhibitors) and adenosine diphosphate inhibitors (clopidogrel) after assessing the risk of bleeding/thrombotic events. Long-term follow-up revealed that the patient had made a good recovery. CONCLUSION: Patients with AA should be closely monitored for the risk of thrombosis and cardiovascular events, particularly when taking stanozolol or CsA for an extended period of time.

Simultaneous quantification of three iridoids in rat plasma after oral administration of Zhi-zi-chi decoction using LC-MS.

A sensitive and efficient liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for the simultaneous determination of geniposide, 6α-hydroxygeniposide, and genipin gentiobioside in rat plasma. After the addition of internal standard (I.S.) salidroside and acidification (formic acid, 0.1%), plasma samples were carried out by protein precipitation with acetonitrile and separated on a Kromasil C(18) column (200 mm × 4.6 mm, 5 µm) within a runtime of 15.0 min. The linear ranges were 2-250 ng/mL for both 6α-hydroxygeniposide and genipin gentiobioside and 2-2000 ng/mL for geniposide, respectively. The lower limit of quantification (LLOQ) was 2 ng/mL for all the analytes. The validated method was successfully applied to the pharmacokinetics study of geniposide, 6α-hydroxygeniposide, and genipin gentiobioside in rats after oral administration of Zhi-zi-chi decoction.

The LINC00365/SCGB2A1 (Mammaglobin B) Axis Down-Regulates NF-κB Signaling and Is Associated with the Progression of Gastric Cancer.

PURPOSE: A lack of early diagnostic biomarkers and therapeutic targets has led to poor prognosis for gastric cancer patients. However, the analysis of cancer-associated genomic data has been shown to be effective in identifying potential markers. Recently, the long non-coding RNA LINC00365 and SCGB2A1 gene (as known as mammaglobin B) were predicted to be co-expressed in gastric cancer based on the Gene Expression Omnibus database. However, their precise role in gastric cancer tumors is still not clear. METHODS: The expressions of LINC00365 and SCGB2A1 in gastric cancer tissues were investigated using qPCR and their expressions were detected in a gastric cancer tissue microarray by in situ hybridization and immunohistochemical staining. The functions of LINC00365 in BGC-823 and MGC-803 gastric cancer cells were tested using the MTT assay, flow cytometry, colony formation assay, EDU staining, immunofluorescence and luciferase assay. RESULTS: We found that LINC00365 and SCGB2A1 mRNA were both expressed at low levels in 30 cases of gastric cancer. Gastric cancer tissue microarray analysis indicated that LINC00365 and SCGB2A1 were expressed at low levels in tumor tissue, and low expression of both factors correlated with shorter survival time. Functional studies showed that LINC00365 overexpression significantly inhibited gastric cancer cell viability through the impairment of proliferation rather than the promotion of apoptosis. Furthermore, overexpressed LINC00365 upregulated SCGB2A1 in gastric cancer cell lines. Immuno-fluorescence and luciferase assay analysis indicated that LINC00365 overexpression inhibited the NF-κB pro-survival signaling pathway. Consistent with the effects of LINC00365, SCGB2A1 upregulation also reduced cell survival and inactivated NF-κB. CONCLUSION: Collectively, our findings revealed that SCGB2A1 may be the target coding protein regulated by LINC00365 in gastric cancer. LINC00365 and SCGB2A1 may function as tumor suppressors and may serve as potential prognostic and therapeutic markers in gastric cancer treatment.

p62 Suppressed VK3-induced Oxidative Damage Through Keap1/Nrf2 Pathway In Human Ovarian Cancer Cells.

Imbalance of redox homeostasis may be responsible for the resistance of cancer to chemotherapy. Currently, increasing studies demonstrated that vitamin K3 (VK3), which promoted the production of ROS, had potential to be developed as an anti-tumor agent. We found SKOV3/DDP cells with high levels of p62 were insensitive to VK3 compared with SKOV3 cells. Furthermore, Nrf2 downstream antioxidant genes such as HO-1(heme oxygenase 1) and NQO1 (NAD (P) H: quinone oxidoreductase 1) were upregulated in SKOV3/DDP cells with VK3 treatment, which indicated VK3 activated Nrf2 signaling in SKOV3/DDP cells. Moreover, co-localization of p62 and Keap1 was also observed. Suppression of p62 expression increased the apoptosis induced by VK3, and the expression of Nrf2, HO-1 and NQO1 were all downregulated in SKOV3/DDP cells. Our results suggested that overexpressed p62 may protect cells from oxidative damage caused by VK3 through activating Keap1/Nrf2 signaling in ovarian cancer.