Increasing evidence indicates that long non-coding RNAs (lncRNAs) play vital roles in the tumorigenesis and progression of cancers. However, the functions and regulatory mechanisms of lncRNAs in ...nasopharyngeal carcinoma (NPC) are still largely unknown. Our previous lncRNA expression profiles identified that LINC01503 was overexpressed in NPC. Here, we verified that LINC01503 was highly expressed in NPC and correlated with poor prognosis. LINC01503 promoted NPC cell proliferation, migration, and invasion in vitro, and facilitated tumor growth and metastasis in vivo. Mechanistically, LINC01503 recruited splicing factor proline-and glutamine-rich (SFPQ) to activate Fos like 1 (FOSL1) transcription, and ectopic expression of FOSL1 reversed the suppressive effect of LINC01503 knockdown on NPC progression. Moreover, androgen receptor (AR)-mediated transcription activation was responsible for the overexpression of LINC01503, and AR ligand-dependent cell growth, migration, and invasion in NPC cells. Taken together, our findings reveal that AR-induced LINC01503 can promote NPC progression through the SFPQ-FOSL1 axis, which represents a novel prognostic biomarker and therapeutic target for NPC patients.
Multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Therefore, combatting MDR is an important issue. Autophagy, a ...self-degradative system, universally arises during the treatment of sensitive and MDR cancer. Autophagy can be a double-edged sword for MDR tumors: it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive. Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells, facilitating MDR reversal. Therefore, research on the regulation of autophagy to combat MDR is expanding and is becoming increasingly important. We summarize advanced studies of autophagy in MDR tumors, including the variable role of autophagy in MDR cancer cells.
Understanding the dynamics and underlying mechanism of carbon exchange between terrestrial ecosystems and the atmosphere is one of the key issues in global change research. In this study, we ...quantified the carbon fluxes in different terrestrial ecosystems in China, and analyzed their spatial variation and environmental drivers based on the long‐term observation data of ChinaFLUX sites and the published data from other flux sites in China. The results indicate that gross ecosystem productivity (GEP), ecosystem respiration (ER), and net ecosystem productivity (NEP) of terrestrial ecosystems in China showed a significantly latitudinal pattern, declining linearly with the increase of latitude. However, GEP, ER, and NEP did not present a clear longitudinal pattern. The carbon sink functional areas of terrestrial ecosystems in China were mainly located in the subtropical and temperate forests, coastal wetlands in eastern China, the temperate meadow steppe in the northeast China, and the alpine meadow in eastern edge of Qinghai‐Tibetan Plateau. The forest ecosystems had stronger carbon sink than grassland ecosystems. The spatial patterns of GEP and ER in China were mainly determined by mean annual precipitation (MAP) and mean annual temperature (MAT), whereas the spatial variation in NEP was largely explained by MAT. The combined effects of MAT and MAP explained 79%, 62%, and 66% of the spatial variations in GEP, ER, and NEP, respectively. The GEP, ER, and NEP in different ecosystems in China exhibited ‘positive coupling correlation’ in their spatial patterns. Both ER and NEP were significantly correlated with GEP, with 68% of the per‐unit GEP contributed to ER and 29% to NEP. MAT and MAP affected the spatial patterns of ER and NEP mainly by their direct effects on the spatial pattern of GEP.
Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with extremely skewed ethnic and geographic distributions. Increasing evidence indicates that targeting the tumor microenvironment (TME) ...represents a promising therapeutic approach in NPC, highlighting an urgent need to deepen the understanding of the complex NPC TME. Here, we generated single-cell transcriptome profiles for 7581 malignant cells and 40,285 immune cells from fifteen primary NPC tumors and one normal sample. We revealed malignant signatures capturing intratumoral transcriptional heterogeneity and predicting aggressiveness of malignant cells. Diverse immune cell subtypes were identified, including novel subtypes such as CLEC9A
dendritic cells (DCs). We further revealed transcriptional regulators underlying immune cell diversity, and cell-cell interaction analyses highlighted promising immunotherapeutic targets in NPC. Moreover, we established the immune subtype-specific signatures, and demonstrated that the signatures of macrophages, plasmacytoid dendritic cells (pDCs), CLEC9A
DCs, natural killer (NK) cells, and plasma cells were significantly associated with improved survival outcomes in NPC. Taken together, our findings represent a unique resource providing in-depth insights into the cellular heterogeneity of NPC TME and highlight potential biomarkers for anticancer treatment and risk stratification, laying a new foundation for precision therapies in NPC.
Gene expression patterns can be used as prognostic biomarkers in various types of cancers. We aimed to identify a gene expression pattern for individual distant metastatic risk assessment in patients ...with locoregionally advanced nasopharyngeal carcinoma.
In this multicentre, retrospective, cohort analysis, we included 937 patients with locoregionally advanced nasopharyngeal carcinoma from three Chinese hospitals: the Sun Yat-sen University Cancer Center (Guangzhou, China), the Affiliated Hospital of Guilin Medical University (Guilin, China), and the First People's Hospital of Foshan (Foshan, China). Using microarray analysis, we profiled mRNA gene expression between 24 paired locoregionally advanced nasopharyngeal carcinoma tumours from patients at Sun Yat-sen University Cancer Center with or without distant metastasis after radical treatment. Differentially expressed genes were examined using digital expression profiling in a training cohort (Guangzhou training cohort; n=410) to build a gene classifier using a penalised regression model. We validated the prognostic accuracy of this gene classifier in an internal validation cohort (Guangzhou internal validation cohort, n=204) and two external independent cohorts (Guilin cohort, n=165; Foshan cohort, n=158). The primary endpoint was distant metastasis-free survival. Secondary endpoints were disease-free survival and overall survival.
We identified 137 differentially expressed genes between metastatic and non-metastatic locoregionally advanced nasopharyngeal carcinoma tissues. A distant metastasis gene signature for locoregionally advanced nasopharyngeal carcinoma (DMGN) that consisted of 13 genes was generated to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter distant metastasis-free survival (hazard ratio HR 4·93, 95% CI 2·99–8·16; p<0·0001), disease-free survival (HR 3·51, 2·43–5·07; p<0·0001), and overall survival (HR 3·22, 2·18–4·76; p<0·0001) than patients with low-risk scores. The prognostic accuracy of DMGN was validated in the internal and external cohorts. Furthermore, among patients with low-risk scores in the combined training and internal cohorts, concurrent chemotherapy improved distant metastasis-free survival compared with those patients who did not receive concurrent chemotherapy (HR 0·40, 95% CI 0·19–0·83; p=0·011), whereas patients with high-risk scores did not benefit from concurrent chemotherapy (HR 1·03, 0·71–1·50; p=0·876). This was also validated in the two external cohorts combined. We developed a nomogram based on the DMGN and other variables that predicted an individual's risk of distant metastasis, which was strengthened by adding Epstein–Barr virus DNA status.
The DMGN is a reliable prognostic tool for distant metastasis in patients with locoregionally advanced nasopharyngeal carcinoma and might be able to predict which patients benefit from concurrent chemotherapy. It has the potential to guide treatment decisions for patients at different risk of distant metastasis.
The National Natural Science Foundation of China, the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period, the Natural Science Foundation of Guang Dong Province, the National Key Research and Development Program of China, the Innovation Team Development Plan of the Ministry of Education, the Health & Medical Collaborative Innovation Project of Guangzhou City, China, and the Program of Introducing Talents of Discipline to Universities.
Long noncoding RNAs (lncRNA) play important roles in the tumorigenesis and progression of cancers. However, the clinical significance of lncRNAs and their regulatory mechanisms in nasopharyngeal ...carcinogenesis (NPC) are largely unknown. Here, based on a microarray analysis, we identified 384 dysregulated lncRNAs, of which,
was one of the most upregulated lncRNAs in NPC.
significantly associated with poor survival in NPC. N(6)-Methyladenosine (m6A) was highly enriched within
and enhanced its RNA stability.
functioned as an oncogenic lncRNA that promoted NPC cell proliferation, migration, invasion, tumor growth, and metastasis. Mechanistically,
functioned as a competing endogenous RNA (ceRNA) for sponging miR-590-3p and miR-1275, leading to the upregulation of their target
(
), and the activation of FAK/PI3K/Akt signaling to promote NPC cell proliferation and invasion. In summary, our study reveals a potential ceRNA regulatory pathway in which
modulates
expression by binding to miR-590-3p and miR-1275, ultimately promoting tumorigenesis and metastasis in NPC. SIGNIFICANCE: These findings demonstrate the clinical significance of the lncRNA
in nasopharyngeal carcinoma (NPC) and the regulatory mechanism involved in NPC development and progression, providing a novel prognostic indicator and promising therapeutic target.
Several studies have examined the functions of nucleic acids in small extracellular vesicles (sEVs). However, much less is known about the protein cargos of sEVs and their functions in recipient ...cells. This study demonstrates the presence of lysine‐specific demethylase 1 (LSD1), which is the first identified histone demethylase, in the culture medium of gastric cancer cells. We show that sEVs derived from gastric cancer cells and the plasma of patients with gastric cancer harbor LSD1. The shuttling of LSD1‐containing sEVs from donor cells to recipient gastric cancer cells promotes cancer cell stemness by positively regulating the expression of Nanog, OCT4, SOX2, and CD44. Additionally, sEV‐delivered LSD1 suppresses oxaliplatin response of recipient cells in vitro and in vivo, whereas LSD1‐depleted sEVs do not. Taken together, we demonstrate that LSD1‐loaded sEVs can promote stemness and chemoresistance to oxaliplatin. These findings suggest that the LSD1 content of sEV could serve as a biomarker to predict oxaliplatin response in gastric cancer patients.
Synopsis
Lysine specific demethylase 1 is not only a nuclear protein but is also secreted. Gastric cancer cells release sEVs that contain LSD1, thereby promoting cancer cell stemness and oxaliplatin resistance.
LSD1 is a component of small extracellular vesicles (sEVs) from gastric cancer cells and gastric cancer patient plasma.
LSD1‐containing sEVs increase the expression of Nanog, OCT4, SOX2 and CD44, and promote oxaliplatin resistance.
sEVs‐delivered LSD1 may serve as a potential biomarker to predict oxaliplatin response in the clinic.
Lysine specific demethylase 1 is not only a nuclear protein but is also secreted. Gastric cancer cells release sEVs that contain LSD1, thereby promoting cancer cell stemness and oxaliplatin resistance.
SUMMARY
Wheat yellow mosaic virus (WYMV) causes severe wheat viral disease in Asia. However, the viral suppressor of RNA silencing (VSR) encoded by WYMV has not been identified. Here, the P1 protein ...encoded by WYMV RNA2 was shown to suppress RNA silencing in Nicotiana benthamiana. Mutagenesis assays revealed that the alanine substitution mutant G175A of P1 abolished VSR activity and mutant Y10A VSR activity remained only in younger leaves. P1, but not G175A, interacted with gene silencing‐related protein, N. benthamiana calmodulin‐like protein (NbCaM), and calmodulin‐binding transcription activator 3 (NbCAMTA3), and Y10A interacted with NbCAMTA3 only. Competitive Bimolecular fluorescence complementation and co‐immunoprecipitation assays showed that the ability of P1 disturbing the interaction between NbCaM and NbCAMTA3 was stronger than Y10A, Y10A was stronger than G175A. In vitro transcript inoculation of infectious WYMV clones further demonstrated that VSR‐defective mutants G175A and Y10A reduced WYMV infection in wheat (Triticum aestivum L.), G175A had a more significant effect on virus accumulation in upper leaves of wheat than Y10A. Moreover, RNA silencing, temperature, and autophagy have significant effects on the accumulation of P1 in N. benthamiana. Taken together, WYMV P1 acts as VSR by interfering with calmodulin‐associated antiviral RNAi defense to facilitate virus infection in wheat, which has provided clear insights into the function of P1 in the process of WYMV infection.
Significance Statement
This study reveals that the wheat yellow mosaic virus (WYMV) P1 acts as VSR by interfering with calmodulin‐associated antiviral RNAi defense and facilitates virus infection in wheat. Results of our research provide clear insights and solutions for further understanding the role of P1 in process of WYMV infection.
Aims
To evaluate the effectiveness and safety of Xin Huang Pian skin patches for patients with acute gouty arthritis.
Background
In China, patients with acute gouty arthritis benefit from skin ...patcheses with herbal medicines. But the clinical effects of skin patches with Xin Huang Pian are rarely reported.
Design
A Randomized, Double‐Blind, Active‐Controlled Trial.
Methods
The trial was performed from January 2015–December 2018 at the First Affiliated Hospital of Sun Yat‐sen University in China. It was conducted with one intervention group (skin patches of Xin Huang Pian, N = 30) and one active control group (skin patches of Diclofenac Diethylamine Emulgel, N = 31). Participants and study investigators were both blinded to the treatment assignments. The primary outcomes were the improvement of joints' symptoms. The secondary outcomes were changes in white blood cells, erythrocyte sedimentation rate and C‐reactive protein.
Results
Skin patches of Xin Huang Pian showed quick effect on decreasing joint pain at 3rd day of treatment. Wherever only at 7th day, Diclofenac Diethylamine Emulgel markedly lowered joint pain. Xin Huang Pian also showed superior effect than Diclofenac Diethylamine Emulgel on improving joint swelling and range of motion and decreasing the levels of C‐reactive protein and erythrocyte sedimentation rate. No adverse reactions were observed in skin patches of Xin Huang Pian treatment.
Conclusion
Skin patches of Xin Huang Pian appeared to be safe and efficacious for relieving joint symptoms in patients with acute gouty arthritis. The mechanism might be associated with the decreased levels of C‐reactive protein and erythrocyte sedimentation rate.
Impact
Skin‐patcheses with Xin Huang Pian are more effective than Diclofenac Diethylamine Emulgel on improving joint pain, swelling and range of motion. Xin Huang Pian treatment showed superior effects compared with Diclofenac Diethylamine Emulgel on decreasing levels of C‐reactive protein and erythrocyte sedimentation rate. Patients with acute gouty arthritis may benefit from skin patches of Xin Huang Pian for effective relief from joint pain and swelling.
Chinese Clinical Trial Registration: ChiCTR‐TRC‐1300 4122.
目的
评估新癀片贴剂治疗急性痛风性关节炎的有效性和安全性。
背景
在中国,患有急性痛风性关节炎的患者可使用草药药贴。但关于新癀片贴剂临床疗效的报道较少。
设计
随机、双盲、阳性对照试验。
方法
于2015年1月至2018年12月在中国中山大学附属第一医院开展此项试验。该试验分为干预组1例(新癀片贴剂,N=30)和阳性对照组1例(双氯芬酸二乙胺乳胶剂贴剂,N=31)。在治疗任务中,随机分配受试者和研究人员。主要研究结果是发现关节症状得到改善,其次是白细胞、红细胞沉降率和C反应蛋白的变化。
结果
治疗第3天,新癀片贴剂对缓解关节疼痛有明显疗效。而双氯芬酸二乙胺乳胶剂贴剂仅在治疗第7天发现对缓解关节疼痛有明显疗效。在改善关节肿胀和活动度以及降低C反应蛋白水平和红细胞沉降率方面,新癀片疗效优于双氯芬酸二乙胺乳胶剂。使用新癀片贴剂未见不良反应。
结论
新癀片贴剂在治疗急性痛风性关节炎方面安全有效,其作用机制可能与C反应蛋白水平和红细胞沉降率降低有关。
影响
在改善关节疼痛、肿胀和活动度方面,新癀片疗效优于双氯芬酸二乙胺乳胶剂。与双氯芬酸二乙胺乳胶剂相比,新癀片在降低C反应蛋白水平和红细胞沉降率方面的作用更为明显。急性痛风性关节炎患者可使用新癀片贴剂有效缓解关节疼痛和肿胀。
中国临床试验注册中心
ChiCTR‐TRC‐1300 4122
Abstract
Lithium garnets have been widely studied as promising electrolytes that could enable the next-generation all-solid-state lithium batteries. However, upon exposure to atmospheric moisture and ...carbon dioxide, insulating lithium carbonate forms on the surface and deteriorates the interfaces within electrodes. Here, we report a scalable solid sintering method, defined by lithium donor reaction that allows for complete decarbonation of Li
6.4
La
3
Zr
1.4
Ta
0.6
O
12
(LLZTO) and yields an active LiCoO
2
layer for each garnet particle. The obtained LiCoO
2
coated garnets composite is stable against air without any Li
2
CO
3
. Once working in a solid-state lithium battery, the LiCoO
2
-LLZTO@LiCoO
2
composite cathode maintains 81% of the initial capacity after 180 cycles at 0.1 C. Eliminating CO
2
evolution above 4.0 V is confirmed experimentally after transforming Li
2
CO
3
into LiCoO
2
. These results indicate that Li
2
CO
3
is no longer an obstacle, but a trigger of the intimate solid-solid interface. This strategy has been extended to develop a series of LLZTO@active layer materials.
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