Cushing's Syndrome in Pregnancy Secondary to Adrenocortical Adenoma: A Case Series and Review.

PURPOSE: To present a case series of Cushing's syndrome (CS) during pregnancy caused by adrenocortical adenomas, highlighting clinical features, hormonal assessments and outcomes. METHODS: We describe five pregnant women with CS, detailing clinical presentations and laboratory findings. RESULTS: Common clinical features included a full moon face, buffalo back and severe hypertension. Elevated blood cortisol levels with circadian rhythm disruption and suppressed adrenocorticotrophic hormone (ACTH) levels were observed. Imaging revealed unilateral adrenal tumours. Two cases underwent laparoscopic adrenalectomies during the second trimester, while three had postpartum surgery. All required hormone replacement therapy, with postoperative pathological confirmation of adrenocortical adenomas. CONCLUSION: Diagnosis of CS during pregnancy is challenging due to overlapping features with normal pregnancy: elevated blood cortisol levels and abnormal diurnal rhythm of blood cortisol, suppressed aid diagnosis. Treatment should be individualised due to a lack of explicit optimum therapeutic approaches. Laparoscopic adrenalectomy may be an optimal choice, along with multidisciplinary management including hormone replacement therapy.

Biting and thermal sensitivity relief of cracked tooth restored by occlusal veneer: A 12-to 24 months prospective clinical study.

OBJECTIVES: To analyze the relief time and risk factors of biting/thermal sensitivity in cracked tooth (CT) restored using occlusal veneer. METHODS: 63 CT were analyzed, and their demographic and clinical data and medical history were collected. Patients were followed-up to examine the relief of thermal/biting sensitivity. RESULTS: The maxillary first molar was the most prevalent (N = 25, 40%). The number of crack lines on the finish line ranged from 1 to 6 while the number of crack lines through preparation on the finish line from 0 to 4. Pain relief achieved steadily to 52% for thermal and 62% for biting at 1 week to over 90% for each by 3 months and was completely resolved (no pain) for each by 12 months. Painful of lateral percussion was related to a long period of thermal sensitivity (≥1 month) after restoration with occlusal veneer. The number of crack lines through preparation on the finish line >2 was correlated with biting sensitivity (≥1 month) post-treatment. CONCLUSIONS: Most patients (>90%) became asymptomatic of biting and thermal sensitivity within 3 months of CT restored by occlusal veneer. Lateral percussion and the number of crack lines through preparation on the finish line could be significant factors affecting postoperative symptoms. CLINICAL SIGNIFICANCE: Occlusal veneer is an ultrathin restoration and had no need for restricting clinical crown height, which could protect and relief the biting/thermal sensitivity of CT without preventive root canal therapy.

Management and prognosis of a vital cracked tooth by occlusal veneer for 14 months: A case report.

Key Clinical Message: An occlusal veneer is an ultrathin restoration method and a minimally invasive approach that can preserve more dental tissue and provide better aesthetic outcomes, thus increasing patient satisfaction. Abstract: An occlusal veneer is an ultrathin restoration method and a minimally invasive approach that can preserve more dental tissue and provide better aesthetic outcomes, thus increasing patient satisfaction; however, no previous studies reported on treating cracked teeth using occlusal veneer. Accordingly, we described the diagnosis and treatment process of a cracked tooth using occlusal veneer in a single case. A 29-year-old male presented at our dental clinic complaining of biting pain in the mandibular molar on the right-hand side. A routine oral examination with radiography was performed to evaluate the oral condition and treatment planning. The #16 tooth had a crack line surrounding the whole distal-lingual cusp from the occlusal surface. After discussing various therapeutic options with the patient, an occlusal veneer was performed. One week after treatment with occlusal veneer, the patient had no complaints. A 14-month follow-up showed promising clinical and radiographic outcomes. Occlusal veneer is an alternative treatment option for a cracked tooth, as it can preserve more dental tissue and potentially save pulp vitality.

Ginsenoside-Rg1 combined with a conditioned medium from induced neuron-like hUCMSCs alleviated the apoptosis in a cell model of ALS through regulating the NF-κB/Bcl-2 pathway.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons in the brain and spinal cord. One important aspect of ALS pathogenesis is superoxide dismutase 1 (SOD1) mutant-mediated mitochondrial toxicity, leading to apoptosis in neurons. This study aimed to evaluate the neural protective synergistic effects of ginsenosides Rg1 (G-Rg1) and conditioned medium (CM) on a mutational SOD1 cell model, and to explore the underlying mechanisms. We found that the contents of nerve growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor significantly increased in CM after human umbilical cord mesenchymal stem cells (hUCMSCs) were exposed to neuron differentiation reagents for seven days. CM or G-Rg1 decreased the apoptotic rate of SOD1G93A-NSC34 cells to a certain extent, but their combination brought about the least apoptosis, compared with CM or G-Rg1 alone. Further research showed that the anti-apoptotic protein Bcl-2 was upregulated in all the treatment groups. Proteins associated with mitochondrial apoptotic pathways, such as Bax, caspase 9 (Cas-9), and cytochrome c (Cyt c), were downregulated. Furthermore, CM or G-Rg1 also inhibited the activation of the nuclear factor-kappa B (NF-κB) signaling pathway by reducing the phosphorylation of p65 and IκBα. CM/G-Rg1 or their combination also reduced the apoptotic rate induced by betulinic acid (BetA), an agonist of the NF-κB signaling pathway. In summary, the combination of CM and G-Rg1 effectively reduced the apoptosis of SOD1G93A-NSC34 cells through suppressing the NF-κB/Bcl-2 signaling pathway (Fig. 1 is a graphical representation of the abstract).

Comments on the Oyster Aquaculture Industry in China: 1985-2020.

Since the 1980s, China's oyster aquaculture has grown quickly in the past four decades, and it became the top mariculture species in China with an annual production of 5.23 million in 2019. Understanding the growth of oyster aquaculture in China is important to gain insights into successful long-term production. This paper attempts to decompose China's oyster aquaculture between trends and cycles by means of an HP filter, make a specific identification of the relevant factors according to the Cobb-Douglas production function, to summarize the objective law of yield fluctuations. Results suggest that from 1985 to 2011, China's oyster aquaculture experienced a development stage of "rapid rise - steady development". At this stage, it shows a slow growth trend, and the growth can persist for long periods of time. The improvement of consumption level driven by economic growth is the main facilitating factor to promote the oyster industry, export trade and oyster price are also critical, diseases and disasters did not exert much influence on the growth of China's oyster aquaculture. The biggest problem hindering sustainable development is the tragedy of the commons caused by the limitation of marine resources, the contradiction of development will become a thorny issue.

Dynamic adjustable metalens based on a stretchable substrate with a double-layer metal microstructure.

Based on the impedance-matching theory, a double-layer metal structure dynamical focusing cylindrical metalens with a stretchable substrate was designed at the operation frequency of 0.1 THz. The diameter, initial focal length, and NA of the metalens were 80 mm, 40 mm, and 0.7, respectively. The transmission phase of the unit cell structures could cover 0-2π by changing the size of the metal bars, and then the different unit cells were spatially arranged as the designed phase profile for the metalens. When the stretching range of the substrate was about 100%-140%, the focal length changed from 39.3 mm to 85.5 mm, the dynamic focusing range was about 117.6% of the minimum focal length, and the focusing efficiency decreases from 49.2% to 27.9%. Then, by rearranging the unit cell structures, a dynamically adjustable bifocal metalens was numerically realized. Using the same stretching ratio, compared to a single focus metalens, the bifocal metalens can provide a larger focal length control range.

Neutrophil membrane engineered HucMSC sEVs alleviate cisplatin-induced AKI by enhancing cellular uptake and targeting.

Human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (hucMSC-sEVs) have been demonstrated as a therapeutic agent to prevent and treat cisplatin-induced acute kidney injury (AKI). However, hucMSC-sEVs still face many problems and challenges in the repair and treatment of tissue injury, including short circulation time, insufficient targeting, and low therapeutic efficacy. Therefore, we constructed engineered hybrid vesicles fused with nanovesicles derived from human neutrophil membranes and hucMSC-sEVs, named neutrophil membrane engineered hucMSC-sEVs (NEX). NEX significantly enhanced the targeting of hucMSC-sEVs to injured kidney tissues, improved the impaired renal function via reducing pro-inflammatory cytokines expression, promoted the proliferation of renal tissue cells, and inhibited renal cell apoptosis in vivo. In addition, NEX enhanced hucMSC-sEVs uptake by NRK52E cells, but inhibited its uptake by RAW264.7 cells. Moreover, administration of NEX reduced cellular oxidative stress and promoted proliferation of NRK52E cells treated with cisplatin in vitro. In summary, our findings indicate that this design of a universal approach enhances the targeting and therapeutic efficacy of hucMSC-sEVs in kidney tissue regeneration, and provides new evidence promoting its clinical application.

Diagnostic and Therapeutic Roles of Extracellular Vesicles in Aging-Related Diseases.

Aging shows a decline in overall physical function, and cellular senescence is the powerful catalyst leading to aging. Considering that aging will be accompanied with the emergence of various aging-related diseases, research on new antiaging drugs is still valuable. Extracellular vesicles (EVs), as tools for intercellular communication, are important components of the senescence-associated secretory phenotype (SASP), and they can play pathological roles in the process of cellular senescence. In addition, EVs are similar to their original cells in functions. Therefore, EVs derived from pathological tissues or body fluids may be closely related to the progression of diseases and become potential biomarkers, while those from healthy cells may have therapeutic effects. Moreover, EVs are satisfactory drug carriers. At present, numerous studies have supported the idea that engineered EVs could improve drug targeting ability and utilization efficiency. Here, we summarize the characteristics of EVs and cellular senescence and focus on the diagnostic and therapeutic potential of EVs in various aging-related diseases, including Alzheimer disease, osteoporosis, cardiovascular disease, diabetes mellitus and its complications, and skin aging.

Fertility Does Not Alter Disease Progression in ALS Patients of Childbearing Age: A Three Centers Retrospective Analysis in Southern China.

Background: Limited data exists on the clinical features of patients with amyotrophic lateral sclerosis (ALS) during reproductive ages. Objective: Our study characterized the clinical features of ALS and the effects of pregnancy on disease progression in patients with ALS. Methods: We performed a retrospective study of female patients with ALS in three ALS research centers in southern China from 2009 to 2021. Data regarding fertility status, and clinical and genetic features, were collected. Age-matched male patients with ALS served as controls. The patients were divided into the following two subgroups: patients with symptom onset within 1 year of pregnancy and patients with symptom onset over 1 year group after pregnancy. Results: A total of 52 female and 52 matched male patients were enrolled. There were no differences in female and male patients in the mean age of symptom onset, the mean baseline ALSFRS-R score, or median reduction of ALSFRS-R score (p > 0.05). The mean age of first pregnancy was 25.57 ± 4.40) years. The mean age of first pregnancy in the over 1 year group was lower than that in the within 1 year group (p= 0.01). There was no difference in the median reduction of ALSFRS-R between the two subgroups. In the univariate analysis, diagnostic delay was highly correlated with the disease progression, with short delay representing rapid progress. No multicollinearity was found among every variable. In addition, 40.38% patients carried ALS-related gene variants. The proportion with gene mutations in the within 1 year group was higher than that in the over 1 year group (p < 0.01). Furthermore, SETX was the most frequently mutated gene in this cohort (16.67%) including 4 uncertain mutation. Conclusion: Pregnancy and fertility were not associated with disease progression. Diagnostic delay was correlated with disease progression in this cohort. In addition, SETX might be a gene of concern for ALS patients of childbearing age.

The Effects and Underlying Mechanisms of Hepatitis B Virus X Gene Mutants on the Development of Hepatocellular Carcinoma.

We aimed to elucidate the mechanism by which hepatitis B virus X (HBx) mutations increase the occurrence of hepatocellular carcinoma (HCC) and identify novel putative therapeutic targets. Wild-type HBx (WT-HBx) and four HBx mutants (M1, A1762T/G1764A; M2, T1674G+T1753C+A1762T/G1764A; M3, C1653T+T1674G+A1762T/G1764A; and Ct-HBx, carboxylic acid-terminal truncated HBx) were delivered into Sleeping Beauty (SB) mouse models. The HCC incidence was higher in the M3-HBx- and Ct-HBx-injected SB mice. M3-HBx had a stronger capacity of upregulating inflammatory cytokines than other HBx variants. Ectopic expression of M3-HBx and Ct-HBx significantly increased proliferation and S phase proportion of HepG2 and HeLa cells, compared to WT-HBx. Plasminogen activator inhibitor-1 (PAI1) and cell division cycle 20 (CDC20) were identified as novel effectors by cDNA microarray analysis. M3-HBx and Ct-HBx significantly upregulated the expression of PAI1 and CDC20 in HepG2 and HeLa cells as well as the livers of SB mice. Silencing PAI1 attenuated the effects of M3-HBx and Ct-HBx on the growth of HepG2 and HeLa cells. PAI1, an important player bridging the HBx mutants and HCC, should be a promising candidate as a prognostic biomarker and therapeutic target in HBV-related HCC.

Glide path enlargement of curved molar canals using HyFlex EDM glide path file versus PathFile: a comparative study of preparation time and postoperative pain.

BACKGROUND: This randomized clinical trial aimed to compare the preparation time and severity of postoperative pain between HyFlex Electric Discharge Machine (EDM) glide path file (GPF) and PathFile. METHODS: Eighty patients whose molar teeth had at least one severely curved canal were treated by the same specialist. After access cavity preparation, the patients were randomly assigned to receive glide path enlargement with either HyFlex EDM GPF or PathFile. ProTaper Next X1 and X2 files were used to prepare the canals. The time of preparation was assessed and the severity of postoperative pain over the next 7 days was recorded. The preparation time and the postoperative pain scores were compared using the Linear Mixed Models (P ≤ 0.05). RESULTS: Glide path enlargement time was significantly shorter with HyFlex EDM GPF (27.828 ± 2.345 s) than with PathFile (48.942 ± 2.864 s) (P < 0.001). The highest postoperative pain score was recorded on the first day and the pain decreased over time in both groups. HyFlex EDM GPF group patients reported significantly less postoperative pain than PathFile group patients overall (P < 0.001). CONCLUSIONS: Postoperative pain and glide path preparation time could be reduced by using HyFlex EDM GPF system. Trial registration PKUSSNCT, PKUSSNCT-17B12, Registered 24 October 2017.

One-dimensional terahertz dielectric gradient metasurface for broadband spoof surface plasmon polaritons couplers: publisher's note.

This publisher's note contains corrections to Opt. Lett.46, 290 (2021)OPLEDP0146-959210.1364/OL.412229.

One-dimensional terahertz dielectric gradient metasurface for broadband spoof surface plasmon polaritons couplers.

At present, most of the gradient metasurfaces used to construct surface plasmon polaritons (SPPs)/spoof SPPs (SSPs) couplers are usually compact metal antennas working under reflection and transmission. In reflection mode, meta-couplers link propagating waves and surface waves (SWs), and SWs will undergo significant scattering before coupling to an Eigen SPP in the target system. In transmission mode, metal meta-couplers will encounter complex multilayer designing at the microwave/terahertz region and metal absorption loss at optical frequencies. In this Letter, to the best of our knowledge, a novel design using dielectric gradient metasurfaces instead of metal metasurface couplers is proposed to excite broadband SSPs on the metal groove array. We demonstrate that the well-designed phase dielectric gradient metasurface converts the normal incident terahertz wave to the predetermined angle in the dielectric substrate and then excites the broadband SSPs with the transmission coupling between the dielectric meta-coupler and SSPs surface. This research may open up new avenues in simple and broadband plane dielectric meta-couplers for SSPs in ultra-thin and compact functional devices for versatile applications.

Phase transformation behaviors and mechanical properties of NiTi endodontic files after gold heat treatment and blue heat treatment.

WaveOne Gold, ProTaper Gold, Reciproc Blue, ProTaper Next, WaveOne and ProTaper files were selected to compare the phase transformation behaviors and mechanical properties of nickel-titanium (NiTi) rotary files after gold heat and blue heat treatments. The reverse transformation finishing point temperatures of WaveOne Gold, ProTaper Gold, ProTaper Next and WaveOne were higher than those of the other two instruments investigated. At a deflection of 0.5 mm, the loads were significantly varied except for ProTaper Next and ProTaper Gold. At a deflection of 3.0 mm, the loads of Reciproc Blue and WaveOne Gold were significantly varied compared to WaveOne and ProTaper. Cycles to failure were reduced in the order of WaveOne Gold, Reciproc Blue, ProTaper Gold, ProTaper Next, WaveOne and ProTaper. NiTi instruments after gold heat and blue heat treatments exhibited significantly higher bending properties and cyclic fatigue resistances, representing an improved performance over traditional and M-wire instruments.

FHA2 is a plant-specific ISWI subunit responsible for stamen development and plant fertility.

Imitation Switch (ISWI) chromatin remodelers are known to function in diverse multi-subunit complexes in yeast and animals. However, the constitution and function of ISWI complexes in Arabidopsis thaliana remain unclear. In this study, we identified forkhead-associated domain 2 (FHA2) as a plant-specific subunit of an ISWI chromatin-remodeling complex in Arabidopsis. By in vivo and in vitro analyses, we demonstrated that FHA2 directly binds to RLT1 and RLT2, two redundant subunits of the ISWI complex in Arabidopsis. The stamen filament is shorter in the fha2 and rlt1/2 mutants than in the wild type, whereas their pistil lengths are comparable. The shorter filament, which is due to reduced cell size, results in insufficient pollination and reduced fertility. The rlt1/2 mutant shows an early-flowering phenotype, whereas the phenotype is not shared by the fha2 mutant. Consistent with the functional specificity of FHA2, our RNA-seq analysis indicated that the fha2 mutant affects a subset of RLT1/2-regulated genes that does not include genes involved in the regulation of flowering time. This study demonstrates that FHA2 functions as a previously uncharacterized subunit of the Arabidopsis ISWI complex and is exclusively involved in regulating stamen development and plant fertility.

A plant-specific SWR1 chromatin-remodeling complex couples histone H2A.Z deposition with nucleosome sliding.

Deposition of H2A.Z in chromatin is known to be mediated by a conserved SWR1 chromatin-remodeling complex in eukaryotes. However, little is known about whether and how the SWR1 complex cooperates with other chromatin regulators. Using immunoprecipitation followed by mass spectrometry, we found all known components of the Arabidopsis thaliana SWR1 complex and additionally identified the following three classes of previously uncharacterized plant-specific SWR1 components: MBD9, a methyl-CpG-binding domain-containing protein; CHR11 and CHR17 (CHR11/17), ISWI chromatin remodelers responsible for nucleosome sliding; and TRA1a and TRA1b, accessory subunits of the conserved NuA4 histone acetyltransferase complex. MBD9 directly interacts with CHR11/17 and the SWR1 catalytic subunit PIE1, and is responsible for the association of CHR11/17 with the SWR1 complex. MBD9, TRA1a, and TRA1b function as canonical components of the SWR1 complex to mediate H2A.Z deposition. CHR11/17 are not only responsible for nucleosome sliding but also involved in H2A.Z deposition. These results indicate that the association of the SWR1 complex with CHR11/17 may facilitate the coupling of H2A.Z deposition with nucleosome sliding, thereby co-regulating gene expression, development, and flowering time.

Analysis of Transcriptome in Enterococcus faecalis Treated with Silver Nanoparticles.

Silver nanoparticles can be used to effectively disinfect Enterococcus faecalis (E. faecalis) in dental root canal therapy, of which the mechanism remains unclear. In the current study, we explored the effect of silver nanoparticles on bacterial growth and changes in the transcriptome of E. faecalis using RNA-sequencing technology. Results showed that silver nanoparticles significantly inhibited growth of E. faecalis by prolonging the lag phase in a dose dependent manner. A total of 100 differentially expressed genes (DEGs) including 3 upregulated and 97 downregulated DEGs were obtained in E. faecalis after treatment with silver nanoparticles. We performed Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses on these DEGs. Functional annotation of DEGs showed that transport and metabolism, such as carbohydrate metabolic process, peptide transport, and amide transport were most significantly enriched. Dysregulated genes were significantly enriched in pathways related to carbohydrate and energy metabolism, and the TCA cycle may be a major mechanism for E. faecalis with silver nanoparticle treatment. These data indicated changes in the transcriptome of E. faecalis after silver nanoparticle treatment, thus providing a mechanism for supporting application of silver nanoparticles for disinfection of E. faecalis during and after root canal therapy.

Genetic Polymorphisms Predisposing the Interleukin 6-Induced APOBEC3B-UNG Imbalance Increase HCC Risk via Promoting the Generation of APOBEC-Signature HBV Mutations.

PURPOSE: APOBEC3-UNG imbalance contributes to hepatitis B virus (HBV) inhibition and somatic mutations. We aimed to explore the associations between hepatocellular carcinoma (HCC) risk and genetic polymorphisms predisposing the imbalance.Experimental Design: Genetic polymorphisms at APOBEC3 promoter and UNG enhancer regions were genotyped in 5,621 participants using quantitative PCR. HBV mutations (nt.1600-nt.1945, nt.2848-nt.155) were determined by Sanger sequencing. Dual-luciferase reporter assay was applied to detect the transcriptional activity. Effects of APOBEC3B/UNG SNPs and expression levels on HCC prognosis were evaluated with a cohort of 400 patients with HCC and public databases, respectively. RESULTS: APOBEC3B rs2267401-G allele and UNG rs3890995-C allele significantly increased HCC risk. rs2267401-G allele was significantly associated with the generation of APOBEC-signature HBV mutation whose frequency consecutively increased from asymptomatic HBV carriers to patients with HCC. Multiplicative interaction of rs2267401-G allele with rs3890995-C allele increased HCC risk, with an adjusted OR (95% confidence interval) of 1.90 (1.34-2.81). rs2267401 T-to-G and rs3890995 T-to-C conferred increased activities of APOBEC3B promoter and UNG enhancer, respectively. IL6 significantly increased APOBEC3B promoter activity and inhibited UNG enhancer activity, and these effects were more evident in those carrying rs2267401-G and rs3890995-C, respectively. APOBEC3B rs2267401-GG genotype, higher APOBEC3B expression, and higher APOBEC3B/UNG expression ratio in HCCs indicated poor prognosis. APOBEC-signature somatic mutation predicts poor prognosis in HBV-free HCCs rather than in HBV-positive ones. CONCLUSIONS: Polymorphic genotypes predisposing the APOBEC3B-UNG imbalance in IL6-presenting microenvironment promote HCC development, possibly via promoting the generation of high-risk HBV mutations. This can be transformed into specific prophylaxis of HBV-caused HCC.

The PEAT protein complexes are required for histone deacetylation and heterochromatin silencing.

In eukaryotes, heterochromatin regions are typically subjected to transcriptional silencing. DNA methylation has an important role in such silencing and has been studied extensively. However, little is known about how methylated heterochromatin regions are subjected to silencing. We conducted a genetic screen and identified an epcr (enhancer of polycomb-related) mutant that releases heterochromatin silencing in Arabidopsis thaliana We demonstrated that EPCR1 functions redundantly with its paralog EPCR2 and interacts with PWWP domain-containing proteins (PWWPs), AT-rich interaction domain-containing proteins (ARIDs), and telomere repeat binding proteins (TRBs), thus forming multiple functionally redundant protein complexes named PEAT (PWWPs-EPCRs-ARIDs-TRBs). The PEAT complexes mediate histone deacetylation and heterochromatin condensation and thereby facilitate heterochromatin silencing. In heterochromatin regions, the production of small interfering RNAs (siRNAs) and DNA methylation is repressed by the PEAT complexes. The study reveals how histone deacetylation, heterochromatin condensation, siRNA production, and DNA methylation interplay with each other and thereby maintain heterochromatin silencing.

Follistatin-like protein 1 plays a tumor suppressor role in clear-cell renal cell carcinoma.

BACKGROUND: We previously showed that the expression of follistatin-like protein 1 (FSTL1) was significantly down-regulated in metastatic clear-cell renal cell carcinoma (ccRCC). In this study, we aimed to characterize the role of FSTL1 in the development of ccRCC. METHODS: The effects of FSTL1 on cell activity and cell cycle were investigated in ccRCC cell lines with altered FSTL1 expression. Gene expression microarray assays were performed to identify the major signaling pathways affected by FSTL1 knockdown. The expression of FSTL1 in ccRCC and its effect on postoperative prognosis were estimated in a cohort with 89 patients. RESULTS: FSTL1 knockdown promoted anchorage-independent growth, migration, invasion, and cell cycle of ccRCC cell lines, whereas FSTL1 overexpression attenuated cell migration. FSTL1 knockdown up-regulated nuclear factor-κB (NF-κB) and hypoxia-inducible factor (HIF) signaling pathways, increased epithelial-to-mesenchymal transition, up-regulated interleukin-6 expression, and promoted tumor necrosis factor-α-induced degradation of NF-κB inhibitor (IκBα) in ccRCC cell lines. FSTL1 immunostaining was selectively positive in epithelial cytoplasm in the loop of Henle, and positive rate of FSTL1 was significantly lower in ccRCC tissues than in adjacent renal tissues (P < 0.001). The multivariate Cox regression analysis showed that the intratumoral FSTL1 expression conferred a favorable independent prognosis with a hazard ratio of 0.325 (95% confidence interval 0.118-0.894). HIF-2α expression was negatively correlated with FSTL1 expression in ccRCC specimens (r = - 0.229, P = 0.044). Intratumoral expression of HIF-2α, rather than HIF-1α, significantly predicted an unfavorable prognosis in ccRCC (log-rank, P = 0.038). CONCLUSIONS: FSTL1 plays a tumor suppression role possibly via repressing the NF-κB and HIF-2α signaling pathways. To increase FSTL1 expression might be a candidate therapeutic strategy for metastatic ccRCC.