Data on the associations between esophageal histological lesions and risk of esophageal squamous cell carcinoma (ESCC) in general populations are limited. We aimed to investigate these associations ...in a large Chinese general population to inform future Chinese ESCC screening guidelines.
We performed endoscopic screening of 21,111 participants aged 40-69 years from 3 high-risk areas of China in 2005-2009, and followed the cohort through 2016. Cumulative incidence and mortality rates of ESCC were calculated by baseline histological diagnosis, and hazard ratios of ESCC, overall and by age and sex, were assessed using the Cox proportional hazards models.
We identified 143 new ESCC cases (0.68%) and 62 ESCC deaths (0.29%) during a median follow-up of 8.5 years. Increasing grades of squamous dysplasia were associated with the increasing risk of ESCC incidence and mortality. The cumulative ESCC incidence rates for severe dysplasia/carcinoma in situ, moderate dysplasia (MD), and mild dysplasia were 15.5%, 4.5%, and 1.4%, respectively. Older individuals (50-69 years) had 3.1 times higher ESCC incidence than younger individuals (40-49 years), and men had 2.4 times higher ESCC incidence than women.
This study confirmed that increasing grades of squamous dysplasia are associated with increasing risk of ESCC and that severe dysplasia and carcinoma in situ require clinical treatment. This study suggests that in high-risk areas of China, patients with endoscopically worrisome MD should also receive therapy, the first screening can be postponed to 50 years, and endoscopic surveillance intervals for unremarkable MD and mild dysplasia can be lengthened to 3 and 5 years, respectively.
Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the ...perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis. Genetic depletion of pericytes in GBM xenografts enhances TMZ-induced cytotoxicity and prolongs survival of tumor-bearing mice. Mechanistically, C-C motif chemokine ligand 5 (CCL5) secreted by pericytes activates C-C motif chemokine receptor 5 (CCR5) on GBM cells to enable DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-mediated DDR upon TMZ treatment. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ. GBM patient-derived xenografts with high CCL5 expression benefit from combined treatment with TMZ and MVC. Our study reveals the role of pericytes as an extrinsic stimulator potentiating DDR signaling in GBM cells and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.
Recent studies suggest that perfluoroalkyl substances (PFAS) and PFAS alternatives can cross the placental barrier. However, little is known on the differential patterns of trans-placental transfer ...(TPT) among conventional PFAS and PFAS alternatives in epidemiological study.
We aimed to characterize comprehensive TPT patterns in conventional PFAS and PFAS alternatives using matched maternal-cord blood serum from a birth cohort.
A total of 424 mother-fetus pairs were recruited from the Maoming Birth Cohort during 2015–2018. We detected 20 PFAS in cord and maternal serum using an ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). TPT of PFAS was calculated via cord to maternal serum concentration ratios.
Both of PFOS alternatives (chlorinated polyfluorinated ether sulfonates, Cl-PFESAs) and PFOA short-chain alternative (perfluorobutanoic acid, PFBA) were widely detected in the cord and maternal serum. In cord serum, the predominant PFAS was PFOS (1.93 ng/mL), followed by PFBA (1.45 ng/mL), PFOA (0.75 ng/mL) and 6:2 Cl-PFESA (0.32 ng/mL). We found that the PFAS alternatives had higher TPT than PFOS and PFOA, such as PFBA vs. PFOA (median: 1.41 vs. 0.73, P < 0.001) and 8:2 Cl-PFESA vs. PFOS (median: 0.98 vs. 0.42, P < 0.001). Moreover, the TPT of 8:2 Cl-PFESA was higher than the precursor, linear and isomeric PFOS, respectively (P < 0.01). Furthermore, we found a U-shaped pattern for TPT in perfluorocarboxylic acid compounds (PFCAs) across different length of carbon chain.
Our findings suggest that PFAS alternatives may be more easily across the placenta than conventional PFAS. Given the widespread usage of PFAS alternatives, our results indicate that more research is needed to assess the potential health risks of prenatal exposure to PFAS alternatives in children.
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•Examined trans-placental transfer (TPT) of PFAS and the alternatives systematically•PFAS alternatives were widely detected in maternal and cord serum.•Higher TPT was observed in the PFAS alternatives than those in PFOS and PFOA.
Electrocatalytic N
2
reduction reaction (NRR) represents a very promising route for ambient NH
3
synthesis, while the efficient NRR process necessitates active and robust catalysts. Herein, we ...explored the potential of In
2
O
3
as an NRR catalyst from both theoretical and experimental perspectives. Density functional theory calculations revealed that In
2
O
3
possessed the favorable N
2
adsorption, low reaction overpotential and suppressed hydrogen evolution reaction. As a proof-of-concept example, we prepared In
2
O
3
nanoparticle-reduced graphene oxide (In
2
O
3
/RGO) hybrid which exhibited attractive NRR performance with an NH
3
yield of 18.4 μg h
−1
mg
−1
and a Faradaic efficiency of 8.1% at − 0.6 V (RHE) in 0.1 M Na
2
SO
4
. Therefore, the combination of theoretical and experimental results demonstrated that In
2
O
3
-based materials could potentially serve as efficient NRR catalysts for electrocatalytic N
2
fixation.
We integrate the genomics, proteomics, and phosphoproteomics of 480 clinical tissues from 146 patients in a Chinese colorectal cancer (CRC) cohort, among which 70 had metastatic CRC (mCRC). Proteomic ...profiling differentiates three CRC subtypes characterized by distinct clinical prognosis and molecular signatures. Proteomic and phosphoproteomic profiling of primary tumors alone successfully distinguishes cases with metastasis. Metastatic tissues exhibit high similarities with primary tumors at the genetic but not the proteomic level, and kinase network analysis reveals significant heterogeneity between primary colorectal tumors and their liver metastases. In vivo xenograft-based drug tests using 31 primary and metastatic tumors show personalized responses, which could also be predicted by kinase-substrate network analysis no matter whether tumors carry mutations in the drug-targeted genes. Our study provides a valuable resource for better understanding of mCRC and has potential for clinical application.
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•A large-scale proteogenomics study of metastatic colorectal cancers•Phosphoproteomic pattern distinguishes metastasis and predicts drug response•A workflow from generation of large omics datasets to in vivo drug testing models•Improves the selection of treatment strategies for patients without druggable mutation
Li et al. provide a global proteogenomic landscape for metastatic colorectal cancer in a Chinese cohort. Proteomic and phosphoproteomic profiling of primary tumors successfully distinguishes cases with metastasis and, together with network analysis, accurately reflects the drug responses of primary and metastatic tumors.
•Mushrooms nutritional foods and source of compounds with medicinal properties.•We have updated latest date on contents of proximate composition and nutrition value.•Biodiversity of mushrooms make it ...possible to find more species of nutritional value.
In China, many species of edible wild-grown mushrooms are appreciated as food and also found use in traditional Chinese medicine. In this mini-review, for the first time, is summarized and discussed data available on chemical components of nutritional significance for wild-grown mushrooms collected from China. We aimed to update and discuss the latest data published on ash, fat, carbohydrates, fibre, proteins, essential amino acids and nonessential amino acids, some essential (P, K, Na, Ca, Mg, Fe, Mn, Zn, Cu) and toxic elements (As, Hg, Cd, Pb), vitamins (thiamine, riboflavin, niacin, tocopherol, vitamin D), flavour and taste compounds, antioxidants and also on less studied organic compounds (lectin, adustin, ribonuclease and nicotine) contents of wild-grown mushrooms.
How two subgenomes in allo-tetraploids adapt to coexistence and coordinate through structure and expression evolution requires extensive studies. In the present study, we report an improved genome ...assembly of allo-tetraploid common carp, an updated genome annotation of allo-tetraploid goldfish and the chromosome-scale assemblies of a progenitor-like diploid Puntius tetrazona and an outgroup diploid Paracanthobrama guichenoti. Parallel subgenome structure evolution in the allo-tetraploids was featured with equivalent chromosome components, higher protein identities, similar transposon divergence and contents, homoeologous exchanges, better synteny level, strong sequence compensation and symmetric purifying selection. Furthermore, we observed subgenome expression divergence processes in the allo-tetraploids, including inter-/intrasubgenome trans-splicing events, expression dominance, decreased expression levels, dosage compensation, stronger expression correlation, dynamic functionalization and balancing of differential expression. The potential disorders introduced by different progenitors in the allo-tetraploids were hypothesized to be alleviated by increasing structural homogeneity and performing versatile expression processes. Resequencing three common carp strains revealed two major ecotypes and uncovered candidate genes relevant to growth and survival rate.
Cisplatin (CDDP) treatment is one of the most predominant chemotherapeutic strategies for patients with gastric cancer (GC). A better understanding of the mechanisms of CDDP resistance can greatly ...improve therapeutic efficacy in patients with GC. Circular RNAs (circRNAs) are a class of noncoding RNAs whose functions are related to the pathogenesis of cancer, but, in CDDP resistance of GC remains unknown.
circAKT3 (hsa_circ_0000199, a circRNA originating from exons 8, 9, 10, and 11 of the AKT3 gene) was identified by RNA sequencing and verified by quantitative reverse transcription PCR. The role of circAKT3 in CDDP resistance in GC was assessed both in vitro and in vivo. Luciferase reporter assay, biotin-coupled RNA pull-down and fluorescence in situ hybridization (FISH) were conducted to evaluate the interaction between circAKT3 and miR-198. Functional experiments were measured by western blotting, a cytotoxicity assay, clonogenic assay and flow cytometry.
The expression of circAKT3 was higher in CDDP-resistant GC tissues and cells than in CDDP-sensitive samples. The upregulation of circAKT3 in GC patients receiving CDDP therapy was significantly associated with aggressive characteristics and was an independent risk factor for disease-free survival (DFS). Our data indicated that circAKT3 promotes DNA damage repair and inhibits the apoptosis of GC cells in vivo and in vitro. Mechanistically, we verified that circAKT3 could promote PIK3R1 expression by sponging miR-198.
circAKT3 plays an important role in the resistance of GC to CDDP. Thus, our results highlight the potential of circAKT3 as a therapeutic target for GC patients receiving CDDP therapy.
Irritable bowel syndrome (IBS) is a common disorder in gastrointestinal system and impairs the quality of life of the patients. Clostridium butyricum (CB) is a probiotics that has been used in ...several gastrointestinal diseases. The efficacy of CB in treating IBS is still unknown. This prospective, multi-centre, randomized, double-blind, placebo-controlled trial aimed to assess the efficacy and safety of CB in treating diarrhea-predominant IBS (IBS-D) and analyze the fecal microbiota after treatment. Two hundred patients with IBS-D were recruited and were given CB or placebo for 4 weeks. End points included change from baseline in IBS symptoms, quality of life, stool consistency and frequency. Compared with placebo, CB is effective in improving the overall IBS-D symptoms (-62.12 ± 74.00 vs. -40.74 ± 63.67, P = 0.038) as well as quality of life (7.232 ± 14.06 vs. 3.159 ± 11.73, P = 0.032) and stool frequency (-1.602 ± 1.416 vs. -1.086 ± 1.644, P = 0.035). The responder rates are found higher in CB compared with the placebo (44.76% vs. 30.53%, P = 0.042). The change in fecal microbiota was analyzed and function pathways of CB in treating IBS-D were predicted. In conclusion, CB improves overall symptoms, quality of life and stool frequency in IBS-D patients and is considered to be used as a probiotics in treating IBS-D clinically.
Aqueous zinc‐ion batteries (ZIBs) are promising energy storage solutions with low cost and superior safety, but they suffer from chemical and electrochemical degradations closely related to the ...electrolyte. Here, a new zinc salt design and a drop‐in solution for long cycle‐life aqueous ZIBs are reported. The salt Zn(BBI)2 with a rationally designed anion group, N‐(benzenesulfonyl)benzenesulfonamide (BBI−), has a special amphiphilic molecular structure, which combines the benefits of hydrophilic and hydrophobic groups to properly tune the solubility and interfacial condition. This new zinc salt does not contain fluorine and is synthesized via a high‐yield and low‐cost method. It is shown that 1 m Zn(BBI)2 aqueous electrolyte with a widened cathodic stability window effectively stabilizes Zn metal/H2O interface, mitigates chemical and electrochemical degradations, and enables both symmetric and full cells using a zinc‐metal electrode.
A new aqueous Zn salt with an anion group, N‐(benzenesulfonyl)benzenesulfonamide C12H10N(SO2)2−, (BBI−) is designed and synthesized. The 1 m Zn(BBI)2 electrolyte decreases the decomposition activity of H2O molecules, suppresses the hydrogen evolution reaction, enables compact and uniform zinc deposition, and improves the cycling and calendar stabilities of aqueous Zn batteries.
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