Phosphorylated FOXQ1, a novel substrate of JNK1, inhibits sorafenib-induced ferroptosis by activating ETHE1 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly heterogeneous and malignant cancer with poor overall survival. The application of sorafenib is a major breakthrough in the treatment of HCC. In our study, FOXQ1 was significantly overexpressed in sorafenib-resistant HCC cells and suppressed sorafenib-induced ferroptosis. We found that phosphorylation of FOXQ1 at serine 248 is critical for the suppression of sorafenib-induced ferroptosis. Furthermore, as the upstream phosphorylation kinase of FOXQ1, JNK1, which is activated by sorafenib, can directly phosphorylate the serine 248 site of FOXQ1. Then, the phosphorylated FOXQ1 got a high affinity for the promoter of ETHE1 and activates its transcription. Further flow cytometry results showed that ETHE1 reduced intracellular lipid peroxidation and iron levels. Collectively, our study implicated the JNK1-FOXQ1-ETHE1 axis in HCC ferroptosis induced by sorafenib, providing mechanistic insight into sensitivity to sorafenib therapy of HCC.

Preoperative prediction of perineural invasion of rectal cancer based on a magnetic resonance imaging radiomics model: A dual-center study.

BACKGROUND: Perineural invasion (PNI) has been used as an important pathological indicator and independent prognostic factor for patients with rectal cancer (RC). Preoperative prediction of PNI status is helpful for individualized treatment of RC. Recently, several radiomics studies have been used to predict the PNI status in RC, demonstrating a good predictive effect, but the results lacked generalizability. The preoperative prediction of PNI status is still challenging and needs further study. AIM: To establish and validate an optimal radiomics model for predicting PNI status preoperatively in RC patients. METHODS: This retrospective study enrolled 244 postoperative patients with pathologically confirmed RC from two independent centers. The patients underwent pre-operative high-resolution magnetic resonance imaging (MRI) between May 2019 and August 2022. Quantitative radiomics features were extracted and selected from oblique axial T2-weighted imaging (T2WI) and contrast-enhanced T1WI (T1CE) sequences. The radiomics signatures were constructed using logistic regression analysis and the predictive potential of various sequences was compared (T2WI, T1CE and T2WI + T1CE fusion sequences). A clinical-radiomics (CR) model was established by combining the radiomics features and clinical risk factors. The internal and external validation groups were used to validate the proposed models. The area under the receiver operating characteristic curve (AUC), DeLong test, net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curve, and decision curve analysis (DCA) were used to evaluate the model performance. RESULTS: Among the radiomics models, the T2WI + T1CE fusion sequences model showed the best predictive performance, in the training and internal validation groups, the AUCs of the fusion sequence model were 0.839 [95% confidence interval (CI): 0.757-0.921] and 0.787 (95%CI: 0.650-0.923), which were higher than those of the T2WI and T1CE sequence models. The CR model constructed by combining clinical risk factors had the best predictive performance. In the training and internal and external validation groups, the AUCs of the CR model were 0.889 (95%CI: 0.824-0.954), 0.889 (95%CI: 0.803-0.976) and 0.894 (95%CI: 0.814-0.974). Delong test, NRI, and IDI showed that the CR model had significant differences from other models (P < 0.05). Calibration curves demonstrated good agreement, and DCA revealed significant benefits of the CR model. CONCLUSION: The CR model based on preoperative MRI radiomics features and clinical risk factors can preoperatively predict the PNI status of RC noninvasively, which facilitates individualized treatment of RC patients.

The role of USP7-YY1 interaction in promoting colorectal cancer growth and metastasis.

Colorectal cancer (CRC) remains a significant global health issue with high incidence and mortality. Yin Yang 1 (YY1) is a powerful transcription factor that acts dual roles in gene activation and repression. High expression level of YY1 has been reported in CRC, indicating the existence of stable factors of YY1 in CRC cells. We aimed to identify the key molecules and underlying mechanisms responsible for stabilizing YY1 expression in CRC. Mass spectrometry analysis was utilized to identify USP7 as a potential molecule that interacted with YY1. Mechanically, USP7 stabilizes YY1 expression at the protein level by interfering its K63 linkage ubiquitination. YY1 exerts its oncogenic function through transcriptionally activating TRIAP1 but suppressing LC3B. In addition, at the pathological level, there is a positive correlation between the expression of YY1 and the budding of CRC. This study has revealed the intricate interplay between YY1 and USP7 in CRC, suggesting that they could serve as novel therapeutic targets or predictive biomarkers for CRC patients.

The demethylase ALKBH5 mediates ZKSCAN3 expression through the m6A modification to activate VEGFA transcription and thus participates in MNNG-induced gastric cancer progression.

N-Nitroso compounds (NOCs) are recognized as important factors that promote gastric cancer development, but the specific effects and potential mechanisms by which NOC exposure promotes gastric cancer are still poorly understood. In this study, we explored the effects and potential molecular mechanisms of NOCs on the promotion of gastric cancer using methylnitronitrosoguanidine (MNNG), a classical direct carcinogen of NOC. The results of in vivo and in vitro experiments showed that chronic and low-concentration MNNG exposure significantly promoted the malignant progression of tumors, including cell migration, cell invasion, vasculogenic mimicry (VM) formation, cell spheroid formation, stem cell-like marker expression, and gastric cancer growth and metastasis. Mechanistically, we revealed that demethylase ALKBH5 regulated the level of the N6­methyladenosine (m6A) modification in the 3'UTR and CDS region of the ZKSCAN3 mRNA to promote ZKSCAN3 expression, mediated the binding of ZKSCAN3 to the VEGFA promoter region to regulate VEGFA transcription, and participated in MNNG-induced gastric cancer cell migration, invasion, VM formation, cell spheroid formation, stem cell-like marker expression and ultimately gastric cancer progression. In addition, our study revealed that ALKBH5-ZKSCAN3-VEGFA signaling was significantly activated during MNNG-induced gastric carcinogenesis, and further studies in gastric cancer patients showed that ALKBH5, ZKSCAN3, and VEGFA expression were upregulated in cancers compared with paired gastric mucosal tissues, that ALKBH5, ZKSCAN3, and VEGFA could serve as important biomarkers for determining patient prognosis, and that the molecular combination showed greater prognostic value. These findings provide a theoretical basis for developing gastric cancer interventions for NOCs and for determining gastric cancer progression.

First-Principles Predictions of MoS2-WS2 In-Plane Heterostructures for Sensing Dissolved Gas Species in Oil-Immersed Transformers.

This work from first-principles insight uses a MoS2-WS2 in-plane heterostructure as a potential sensing material for detection of CO and C2H2, two typical dissolved gases in oil-immersed transformers, in order to evaluate the operation status. The adsorption performance of the MoS2-WS2 heterostructure upon two gas species is assessed via three adsorption sites and compared with isolated MoS2 and WS2. Results indicate that MoS2-WS2 performs with a much stronger binding force and charge-transfer for adsorptions of CO and C2H2 in comparison to the isolated counterpart, which gives rise to more obvious deformation in the electronic property of MoS2-WS2 as well as a much larger resistance-based sensing response. The recovery time of MoS2-WS2 for desorption of CO and C2H2 molecules is also appropriate to allow the reusability of such a sensor. The findings in this work uncover the admirable sensing potential of transition metal dichalcogenides (TMDs)-based heterostructures upon oil dissolved gases, which opens up a new way to explore novel 2D nanomaterials as resistive gas sensors for dissolved gas analysis in electrical oil-immersed transformers.

Functionalized PLGA Microsphere Loaded with Fusion Peptide for Therapy of Bone Defects.

The challenges in the treatment of extensive bone defects are infection control and bone regeneration. Bone tissue engineering is currently one of the most promising strategies. In this study, a short biopeptide with specific osteogenic ability is designed by fusion peptide technology and encapsulated with chitosan-modified poly(lactic acid-glycolic acid) (PLGA) microspheres. The fusion peptide (FP) mainly consists of an osteogenic functional sequence (P-15) and a bone-specific binding sequence (Asp-6), which can regulate bone formation accurately and efficiently. Chitosan-modified PLGA with antimicrobial and pro-healing effects is used to achieve the sustained release of fusion peptides. In the early stage, the antimicrobial and soft tissue healing effects can stop the wound infection as soon as possible, which is relevant for the subsequent bone regeneration process. Our data show that CS-PLGA@FP microspheres have antibacterial and pro-cell migration effects in vitro and excellent pro-wound-healing effects in vivo. In addition, CS-PLGA@FP microspheres promote the expression of osteogenic-related factors and show excellent bone regeneration in a rat defect model. Therefore, CS-PLGA@FP microspheres are an efficient biomaterial that can accelerate the recovery of bone defects.

Nifuroxazide suppresses PD-L1 expression and enhances the efficacy of radiotherapy in hepatocellular carcinoma.

Radiation therapy is a primary treatment for hepatocellular carcinoma (HCC), but its effectiveness can be diminished by various factors. The over-expression of PD-L1 has been identified as a critical reason for radiotherapy resistance. Previous studies have demonstrated that nifuroxazide exerts antitumor activity by damaging the Stat3 pathway, but its efficacy against PD-L1 has remained unclear. In this study, we investigated whether nifuroxazide could enhance the efficacy of radiotherapy in HCC by reducing PD-L1 expression. Our results showed that nifuroxazide significantly increased the sensitivity of tumor cells to radiation therapy by inhibiting cell proliferation and migration while increasing apoptosis in vitro. Additionally, nifuroxazide attenuated the up-regulation of PD-L1 expression induced by irradiation, which may be associated with increased degradation of PD-L1 through the ubiquitination-proteasome pathway. Furthermore, nifuroxazide greatly enhanced the efficacy of radiation therapy in H22-bearing mice by inhibiting tumor growth, improving survival, boosting the activation of T lymphocytes, and decelerating the ratios of Treg cells in spleens. Importantly, nifuroxazide limited the increased expression of PD-L1 in tumor tissues induced by radiation therapy. This study confirms, for the first time, that nifuroxazide can augment PD-L1 degradation to improve the efficacy of radiation therapy in HCC-bearing mice.

The CT-guided percutaneous drainage of pancreatic pseudocyst accompanied by pseudoaneurysm: A case report.

RATIONALE: This case report discusses the CT-guided percutaneous drainage of a pancreatic pseudocyst accompanied by a pseudoaneurysm. Pancreatic pseudocysts can erode the peripancreatic artery and produce pseudoaneurysms. This is rare, but it can be life-threatening. PATIENT CONCERNS: The case presented involves a 58-year-old female who was diagnosed with pancreatic cancer and underwent surgical treatment. She presented with hematochezia, dizziness, and hypodynamic findings with no obvious cause. Imaging revealed a pancreatic pseudocyst and small arterial aneurysms. To reduce the risk of aneurysm rupture, the patient underwent transcatheter arterial coil embolization. Three days later, CT-guided catheter drainage was performed to reduce the erosion of the arterial wall caused by pancreatic fluid. DIAGNOSES: The contrast-enhanced-CT imaging showed a round, slightly high-density lesion in the cyst, suggesting the presence of a pseudoaneurysm. INTERVENTIONS: The patient was sent for another transcatheter arterial embolization with coils and n-butyl-2-cyanoacrylate. OUTCOMES: After receiving the transcatheter arterial embolization, the patient had no serious bleeding or other complications. LESSONS: Early detection and accurate assessment of pseudoaneurysms are essential for appropriate management. This case shows that contrast-enhanced CT is necessary before CT-guided percutaneous drainage of pancreatic pseudocysts. It also shows that, due to the many complications that pancreatic pseudocysts may cause, appropriate treatment of pseudocysts complicated with pseudoaneurysm has important clinical significance.

SDCBP modulates tumor microenvironment, tumor progression and anti-PD1 efficacy in colorectal cancer.

Anti-programmed cell death 1 (aPD1) therapy has yielded limited success in patients with colorectal cancer (CRC). Syndecan binding protein (SDCBP), encodes a PDZ domain-containing protein that is essential for cellular processes, including cell adhesion, migration, and signal transduction. Here, we investigated the effect of SDCBP on tumor progression, immunotherapy, and the tumor microenvironment (TME) in CRC. High expression of SDCBP is associated with non-response to immunotherapy and correlated with poorer disease-free survival (DFS) in CRC patients. Inhibiting SDCBP by transfecting shRNA or using its inhibitor zinc pyrithione (ZnPT) hindered proliferation and metastasis while enhancing the efficacy of aPD1 treatment in a mouse xenograft model and liver metastasis model. The TME of CRC was significantly altered following ZnPT treatment characterized by a reduced amount of M2 macrophages and a heightened percentage of M1 macrophages. The co-culture system of CRC cells and macrophages provided evidence that SDCBP silencing promoted the repolarisation of M2 macrophages into M1. SDCBP promotes the proliferation, metastasis, and immunotherapy resistance of CRC. Thus, ZnPT represents an effective SDCBP inhibitor and exhibits considerable potential for combination with aPD1 to enhance immunotherapy efficacy.

gp120-derived amyloidogenic peptides form amyloid fibrils that increase HIV-1 infectivity.

Apart from mediating viral entry, the function of the free HIV-1 envelope protein (gp120) has yet to be elucidated. Our group previously showed that EP2 derived from one ß-strand in gp120 can form amyloid fibrils that increase HIV-1 infectivity. Importantly, gp120 contains ~30 ß-strands. We examined whether gp120 might serve as a precursor protein for the proteolytic release of amyloidogenic fragments that form amyloid fibrils, thereby promoting viral infection. Peptide array scanning, enzyme degradation assays, and viral infection experiments in vitro confirmed that many ß-stranded peptides derived from gp120 can indeed form amyloid fibrils that increase HIV-1 infectivity. These gp120-derived amyloidogenic peptides, or GAPs, which were confirmed to form amyloid fibrils, were termed gp120-derived enhancers of viral infection (GEVIs). GEVIs specifically capture HIV-1 virions and promote their attachment to target cells, thereby increasing HIV-1 infectivity. Different GAPs can cross-interact to form heterogeneous fibrils that retain the ability to increase HIV-1 infectivity. GEVIs even suppressed the antiviral activity of a panel of antiretroviral agents. Notably, endogenous GAPs and GEVIs were found in the lymphatic fluid, lymph nodes, and cerebrospinal fluid (CSF) of AIDS patients in vivo. Overall, gp120-derived amyloid fibrils might play a crucial role in the process of HIV-1 infectivity and thus represent novel targets for anti-HIV therapeutics.

Melanoma extracellular vesicles inhibit tumor growth and metastasis by stimulating CD8 T cells.

Tumor cell-derived extracellular vesicles (EVs) play a crucial role in mediating immune responses by carrying and presenting tumor antigens. Here, we suggested that melanoma EVs triggered cytotoxic CD8 T cell-mediated inhibition of tumor growth and metastasis. Our results indicated that immunization of mice with melanoma EVs inhibited melanoma growth and metastasis while increasing CD8 T cells and serum interferon γ (IFN-γ) in vivo. In vitro experiments showed that melanoma EV stimulates dendritic cells (DCs) maturation, and mature dendritic cells induce T lymphocyte activation. Thus, tumor cell-derived EVs can generate anti-tumor immunity in a prophylactic setting and may be potential candidates for cell-free tumor vaccines.

FBXO22 promotes glioblastoma malignant progression by mediating VHL ubiquitination and degradation.

Glioblastoma (GBM) is the most common malignant primary brain tumor. Despite comprehensive treatment with traditional surgery, radiotherapy, and chemotherapy, the median survival rate is <14.6% and the 5-year survival rate is only 5%. FBXO22, a substrate receptor of the SCF ubiquitin ligases, has been reported to play a promoting role in melanoma, liver cancer, cervical cancer, and other cancers. However, the function of FBXO22 in GBM has not been reported. In the present study, we demonstrate that FBXO22 is highly expressed in glioma and is positively correlated with worse pathological features and shorter survival of GBM patients. We revealed that FBXO22 promotes GBM cell proliferation, angiogenesis, migration, and tumorigenesis in vitro and in vivo. In terms of mechanism, we reveal that FBXO22 decreases VHL expression by directly mediating VHL ubiquitination degradation, which ultimately increases HIF-1α and VEGFA expression. In addition, our data confirm that there are positive correlations among FBXO22, HIF-1α, and VEGFA expression, and there is a negative correlation between FBXO22 and VHL protein expression in glioma patients. Our study strongly indicates that FBXO22 is a promising diagnostic marker and therapeutic target for glioma patients.

The crucial role of transient tri-coordinated oxygen in the flow of silicate melts.

The transport properties of high-temperature silicate melts control magma flow and are crucial for a wide variety of industrial processes involving minerals. However, anomalous melt properties have been observed that cannot be explained by the traditional polymerization degree theory, which was derived based on quenched melts. Ab initio molecular dynamics (AIMD) simulations were conducted to investigate the flow mechanism of CaO-Al2O3-SiO2 melts under high temperature atmospheric conditions. By analyzing the dynamic structure of melted silicates and employing molecular orbital theory, we gained a fundamental understanding of the flow mechanism from a chemistry perspective. Transient tri-coordinated oxygen (TO) bonded with one Si and two Al atoms (SiOAl2) was found to be a pivotal intermediate in melt flow and atomic diffusion processes. Frequent chemical transition between TO in SiOAl2 and bridging oxygen (BO) dominated the fluidity of melted silicates. The presence of such transitions is facilitated by the unstable nature of [SiAlO2] 4-membered rings, which are susceptible to instability due to the intense repulsion between the O 2p lone pairs and the excessively bent O-Al-O angle. Additionally, the density of SiOAl2 type TO motif could serve as an indicator to determine the relationship between structure and fluidity. Our results challenge the traditional polymerization degree theory and suggest the need to reassess high-temperature liquid properties that govern processes in the Earth and industry by monitoring transient motifs.

circEPB41L2 blocks the progression and metastasis in non-small cell lung cancer by promoting TRIP12-triggered PTBP1 ubiquitylation.

The metastasis of non-small cell lung cancer (NSCLC) is the leading death cause of NSCLC patients, which requires new biomarkers for precise diagnosis and treatment. Circular RNAs (circRNAs), the novel noncoding RNA, participate in the progression of various cancers as microRNA or protein sponges. We revealed the mechanism by which circEPB41L2 (hsa_circ_0077837) blocks the aerobic glycolysis, progression and metastasis of NSCLC through modulating protein metabolism of PTBP1 by the E3 ubiquitin ligase TRIP12. With ribosomal RNA-depleted RNA seq, 57 upregulated and 327 downregulated circRNAs were identified in LUAD tissues. circEPB41L2 was selected due to its dramatically reduced levels in NSCLC tissues and NSCLC cells. Interestingly, circEPB41L2 blocked glucose uptake, lactate production, NSCLC cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, acting as a scaffold, circEPB41L2 bound to the RRM1 domain of the PTBP1 and the E3 ubiquitin ligase TRIP12 to promote TRIP12-mediated PTBP1 polyubiquitylation and degradation, which could be reversed by the HECT domain mutation of TRIP12 and circEPB41L2 depletion. As a result, circEPB41L2-induced PTBP1 inhibition led to PTBP1-induced PKM2 and Vimentin activation but PKM1 and E-cadherin inactivation. These findings highlight the circEPB41L2-dependent mechanism that modulates the "Warburg Effect" and EMT to inhibit NSCLC development and metastasis, offering an inhibitory target for NSCLC treatment.

PRMT1-mediated PGK1 arginine methylation promotes colorectal cancer glycolysis and tumorigenesis.

Many types of cancer cells, including colorectal cancer cells (CRC), can simultaneously enhance glycolysis and repress the mitochondrial tricarboxylic acid (TCA) cycle, which is called the Warburg effect. However, the detailed mechanisms of abnormal activation of the glycolysis pathway in colorectal cancer are largely unknown. In this study, we reveal that the protein arginine methyltransferase 1 (PRMT1) promotes glycolysis, proliferation, and tumorigenesis in CRC cells. Mechanistically, PRMT1-mediated arginine asymmetric dimethylation modification of phosphoglycerate kinase 1 (PGK1, the first ATP-producing enzyme in glycolysis) at R206 (meR206-PGK1) enhances the phosphorylation level of PGK1 at S203 (pS203-PGK1), which inhibits mitochondrial function and promotes glycolysis. We found that PRMT1 and meR206-PGK1 expression were positively correlated with pS203-PGK1 expression in tissues from colorectal cancer patients. Furthermore, we also confirmed that meR206-PGK1 expression is positively correlated with the poor survival of patients with colorectal cancer. Our findings show that PRMT1 and meR206-PGK1 may become promising predictive biomarkers for the prognosis of patients with CRC and that arginine methyltransferase inhibitors have great potential in colorectal cancer treatment.

Polypyrimidine tract-binding protein 3/insulin-like growth factor 2 mRNA-binding proteins 3/high-mobility group A1 axis promotes renal cancer growth and metastasis.

Polypyrimidine tract-binding protein 3 (PTBP3) plays an important role in the post-transcriptional regulation of gene expression, including mRNA splicing, translation, and stability. Increasing evidence has shown that PTBP3 promotes cancer progression in several tumor types. However, the molecular mechanisms of PTBP3 in renal cell carcinoma (RCC) remain unknown. Here, tissue microarrays (TMAs) suggested that PTBP3 expression was increased in human RCC and that high PTBP3 expression was correlated with poor five-year overall survival and disease-free survival. We also showed that PTBP3 binds with HMGA1 mRNA in the 3'UTR region and let-7 miRNAs. PTBP3 interacted with IGF2BP3, and the PTBP3/IGF2BP3 axis prevented let-7 mediated HMGA1 mRNA silencing. PTBP3 promotes renal cancer cell growth and metastasis in vitro and in vivo. Taken together, our findings indicate PTBP3 serves as a regulator of HMGA1 and suggest its potential as a therapeutic agent for RCC.

Recent progress in critical electrode and electrolyte materials for flexible zinc-ion batteries.

With the increasing popularity of flexible and wearable electronic devices, the demand for power supplies that can be easily bent or worn is also rapidly growing. However, traditional lithium ion batteries are difficult to adapt to complex wearable devices because of their unsatisfactory flexibility and thickness as well as safety issues. Zinc-ion batteries have several advantages, including low redox potential, high theoretical capacity, high safety, and abundant reserves. These features make flexible zinc-ion batteries (FZIBs) an ideal wearable energy storage device candidate. The electrochemical performance and mechanical deformability of FZIBs were pivotally determined based on the properties of their electrode and electrolyte. Herein, we summarize some recent advances from 2015 to 2023 in the design and preparation of various electrode and electrolyte materials for FZIBs with controllable morphology and structure, excellent mechanical property, and enhanced electrochemical performance. Moreover, efforts to explore the potential practical applications of FZIBs have also been considered. Finally, we present and discuss current challenges and opportunities for the development of high-performance FZIBs.

Bioaerosols in deodorization covers of wastewater treatment plants: Emission characteristics and health risks.

Wastewater treatment plants (WWTPs) are the main source of bioaerosol emissions. The cover of deodorization within WWTPs serves not only to manage odors but also to limit the dispersion of bioaerosols. This study investigated the emission characteristics and exposure risks of bioaerosols inside deodorization covers from a WWTP in Northern China. The results revealed that the concentration of bacteria in bioaerosols ranged from 96 ± 8 to 706 ± 45 CFU/m3, with the highest concentration observed in the biochemical reaction tank. The predominant bacterial genera in bioaerosols within the odor control covers were Cetobacterium, Romboutsia, Bacteroides, Lactobacillus, and Tubricibacter, while the dominant fungal genera included Aspergillus, Alternaria, Fusarium, and Cladosporium. The main water-soluble ions in the air were NH4+, Ca2+, SO42-, and Cl-. SO42- was found to promote the survival of Cetobacterium, Brevibacterium, Fusarium, Penicillium, and Filobasidium, while Cl- exhibited inhibitory effects on most microorganisms in bioaerosols. Source tracker analysis indicated that wastewater was the primary source of bioaerosols in the biochemical reaction tank. The non-carcinogenic risk associated with bioaerosols within deodorization covers was less than 1 (2.34 × 10-9 to 3.08 × 10-2). FunGuild fungal functional prediction suggested that the abundance of animal pathogens was highest in the bioaerosols from the anaerobic sedimentation tank. BugBase phenotypic prediction showed that the abundance of potential pathogens in secondary sedimentation tank bioaerosols was the highest. This study effectively revealed the characteristics and sources of bioaerosols in the sewage and sludge treatment area under the deodorization cover, which provided a theoretical basis for enhancing the management and control of bioaerosols.

Misdiagnosis of ß-Thalassemia Major Due to Chinese Gγ+(Aγδß)0-Thalassemia Combined with ß0-Thalassemia.

δß-thalassemia is a rare type of thalassemia characterized by increased Hb F levels, including mainly Chinese Gγ(Aγδß)0-thalassemia, Yunnanese Gγ(Aγδß)0-thalassemia, Cantonese Gγ(Aγδß)0-thalassemia in China. Due to the low rate of δß-thalassemia carriers, there are few reports of δß-thalassemia combined with ß-thalassemia causing ß-thalassemia major. Herein, we described the combination of Chinese Gγ(Aγδß)0-thalassemia and ß-thalassemia leading to ß-thalassemia major in a Chinese patient. Hemoglobin analysis was performed by capillary electrophoresis (CE). Routine genetic analysis was carried out by gap-polymerase chain reaction (Gap-PCR) and PCR and reverse dot blot (PCR-RDB). Multiple ligation-dependent probe amplification (MLPA) was used to detect the large deletion, and Gap-PCR confirmed the deletion. A CE result showed an elevated Hb F level of 98.7% and 11.7% in the proband and her mother, but the proband was diagnosed with ßCD17M/ßCD17M using routine genetic analysis. However, her father was heterozygous for CD17 in ß-globin, and her mother was detected as SEA heterozygous. The further analysis presented that the proband had actually missed the diagnosis of Chinese Gγ(Aγδß)0-thalassemia by MLPA and PCR-RDB. Finally, the genotype of the proband was corrected from ßCD17M/ßCD17M to ßCD17M/ßGγ(Aγδß)0. This is the first report of Chinese Gγ(Aγδß)0-thalassemia combined with ß-thalassemia resulting in ß-thalassemia major in China. Screening for δß-thalassemia by Hb analysis could be an effective method.

Steroidal saponins from the roots of Paris verticillata and their anti-proliferative and anti-inflammatory activities.

Thirteen previously undescribed steroidal saponins, named parisverticilloside A-M (1-13) and twenty known steroidal saponins (14-33) were isolated from ethanol extract of the roots of Paris verticillata. Their structures were identified by a series of spectroscopic methods, including 1D and 2D NMR, HR-ESI-MS, optical rotatory dispersion and chemical processes. The anti-proliferative activities of all compounds against LN229, HepG2, MDA-MB-231 and 4T1 cell lines were evaluated using the CCK8 assay with cisplatin or capecitabine as the positive control. The anti-inflammatory activities of all compounds were measured by inhibition of LPS-induced NO release from BV2 cell lines, with dexamethasone as the positive control.