A Fluorescent Probe with Zwitterionic ESIPT Feature for Ratiometric Monitoring of Peroxynitrite In Vitro and In Vivo.

Peroxynitrite (ONOO-), as a short-term reactive biological oxidant, could lead to a series of effects in various physiological and pathological processes due to its subtle concentration changes. In vivo monitoring of ONOO- and relevant physiological processes is urgently required. Herein, we describe a novel fluorescent probe termed HBT-Fl-BnB for the ratiometric detection of ONOO- in vitro and in vivo. The probe consists of an HBT core with Fl groups at the ortho and para positions responding to the zwitterionic excited-state intramolecular proton-transfer (zwitterionic ESIPT) process and a boronic acid pinacol ester with dual roles that block the zwitterionic ESIPT and recognize ONOO-. Thanks to the specificity as well as low cytotoxicity, success in imaging of endogenous and exogenous ONOO- in living cells by HBT-Fl-BnB was obtained. Additionally, the applicability of HBT-Fl-BnB to tracking the abnormal expression of ONOO- in vivo induced by inactivated Escherichia coli was also explored. This is the first report of a fluorescent probe for ONOO- sensing via a zwitterionic ESIPT mechanism.

Genome-wide identification of GhRLCK-VII subfamily genes in Gossypium hirsutum and investigation of their functions in resistance to Verticillium wilt.

BACKGROUND: The receptor-like cytoplasmic kinases subfamily VII (RLCK-VII) is critical in regulating plant growth, development, and pattern-triggered immunity. However, a comprehensive exploration of these genes in the allotetraploid Gossypium hirsutum is still lacking. This study aimed to identify RLCK-VII genes in G. hirsutum and investigate their evolutionary history, structural features, expression patterns, and role in plant defense. RESULTS: Seventy-two RLCK-VII genes in the G. hirsutum genome were unveiled and classified into nine groups following their phylogenetic analysis with Arabidopsis thaliana. Group VII-1 was the largest, accounting for 28%, while Groups VII-2 and VII-3 had only one member each. The analysis using MCScanX revealed that these 72 genes formed 166 collinear gene pairs and were resided on 26 chromosomes of G. hirsutum, suggesting that they were derived from whole genome segmental duplication events. Their calculated Ka/Ks values were below one, implying the occurrence of purification selection during the evolution and inhibition of gene function differentiation/loss. All members of the RLCK-VII subfamily possessed two conserved domains, PKinase-Tyr and PKinase, and several conserved PBS1 kinase subdomains, individually included in one of the ten motifs identified using MEME. The RNA-Seq results showed that RLCK-VII genes exhibited different spatiotemporal expression, indicating their involvement in cotton growth, development, and defense responses to Verticillium dahliae. The transcription patterns of RLCK-VII genes found by RNA-Seq were further validated using qRT-PCR assays after inoculating "20B12" (cotton cultivar) with "V991" (V. dahliae). The virus-induced gene silencing (VIGS) assays uncovered that two RLCK-VII genes (Gohir.A13G227248 and Gohir.A10G219900) were essential to G. hirsutum resistance to Verticillium wilt. CONCLUSIONS: These observations offer valuable insight into the attributes and roles of RLCK-VII genes in G. hirsutum, potentially enable the breeding of new cotton cultivars with enhanced resistance to Verticillium wilt.

Synthesis of Chiral Diarylmethylamines by Cobalt-Catalyzed Enantioselective C-H Alkoxylation.

Chiral diarylmethylamines (DAMA) are important structural motifs widely present in pharmaceuticals, natural products, and chiral ligands. Herein, we reported a highly enantioselective synthesis of chiral DAMAs via cobalt-catalyzed enantioselective C-H alkoxylation strategy. The reaction features easy operation, the use of earth-abundant and cost-efficient cobalt(II) catalyst, and readily available ligand. A range of chiral DAMAs were efficiently synthesized in high yields with excellent enantioselectivities (up to 90 % yield and up to 99 % ee) through desymmetrization and parallel kinetic resolution. Moreover, this protocol was also compatible with the synthesis of chiral benzylamines via kinetic resolution.

Base-Promoted Electrochemical CoII -catalyzed Enantioselective C-H Oxygenation.

Metalla-electrocatalyzed C-H oxygenation represents one of the most straightforward and sustainable approaches to access valuable oxygenated molecules. Despite the significant advances, the development of enantioselective electrochemical C-H oxygenation reaction is very challenging and remains elusive. Herein, we described the first electrochemical CoII -catalyzed enantioselective C-H alkoxylation. A broad range of enantioenriched alkoxylated phosphinamides were obtained in good yields with excellent enantioselectivities (up to 98 % yield and >99 % ee). An unusual cobalt(III) alcohol complex was prepared and fully characterized, which was proven to be a key intermediate of this C-H alkoxylation reaction. Mechanistic studies revealed that the oxidation of CoIII to CoIV was facilitated by a base and the whole process proceeded through a cobalt(III/IV/II) catalytic cycle.

Synthesis of Axially Chiral Biaryls through Cobalt(II)-Catalyzed Atroposelective C-H Arylation.

Highly efficient synthesis of axially chiral biaryl amines through cobalt-catalyzed atroposelective C-H arylation using easily accessible cobalt(II) salt and salicyloxazoline ligand has been reported. This methodology provides a straightforward and sustainable access to a broad range of enantioenriched biaryl-2-amines in good yields (up to 99 %) with excellent enantioselectivities (up to 99 % ee). The synthetic utility of the unprecedented method is highlighted by its scalability and diverse transformations.

Cobalt/Salox-Catalyzed Enantioselective Dehydrogenative C-H Alkoxylation and Amination.

The past decade has witnessed a rapid progress in asymmetric C-H activation. However, the enantioselective C-H alkoxylation and amination with alcohols and free amines remains elusive. Herein, we disclose the first enantioselective dehydrogenative C-H alkoxylation and amination enabled by a simple cobalt/salicyloxazoline (Salox) catalysis. The use of cheap and readily available cobalt(II) salts as catalysts and Saloxs as chiral ligands provides an efficient method to access P-stereogenic compounds in excellent enantioselectivities (up to >99 % ee). The practicality of this protocol is demonstrated by gram-scale preparation and further derivatizations of the resulting P-stereogenic phosphinamides, which offering a flexible asymmetric alternative to access P-stereogenic mono- and diphosphine chiral ligands. Preliminary mechanistic studies on the enantioselective C-H alkoxylation reaction suggest that a cobalt(III/IV/II) catalytic cycle might be involved.

Multipartite quantum entanglement creation for distant stationary systems.

We present efficient protocols for creating multipartite Greenberger-Horne-Zeilinger (GHZ) and W states of distant stationary qubits. The system nonuniformity and/or the non-ideal single-photon scattering usually limit the performance of entanglement creation, and result in the decrease of the fidelity and the efficiency in practical quantum information processing. By using linear optical elements, errors caused by the system nonuniformity and non-ideal photon scattering can be converted into heralded loss in our protocols. Thus, the fidelity of generated multipartite entangled states keeps unchanged and only the efficiency decreases. The GHZ state of distant stationary qubits is created in a parallel way that its generation efficiency considerably increases. In the protocol for creating the W state of N distant stationary qubits, an input single photon is prepared in a superposition state and sent into N paths parallelly. We use the two-spatial-mode interferences to eliminate the "which path" single-photon scattering "knowledge". As a result, the efficiency of creating the N-qubit W state is independent of the number of stationary qubits rather than exponentially decreases.

Comparison of the short-term and long-term outcomes of surgical treatment versus endoscopic treatment for early esophageal squamous cell neoplasia larger than 2 cm: a retrospective study.

BACKGROUND: NCCN Guidelines of esophageal cancer recommend that endoscopic therapy is considered "preferred" for patients with limited early-stage disease less than or equal to 2 cm. However, there is currently no definite evidence to support either endoscopic therapy or esophagectomy for early esophageal cancer larger than 2 cm. We aimed to explore the optimal treatment for this condition. METHODS: From January 2010 to June 2016, 116 patients with early esophageal neoplasia [high-grade dysplasia (HGD), lamina propria and muscularis mucosae (T1a) cancer, selected superficial submucosa (T1b) cancer without lymph node metastases] larger than 2 cm and treated either surgically or endoscopically were included. RESULTS: Endoscopic therapy was performed in 69 patients and esophagectomy in 47 patients, respectively. The median follow-up time was 43.8 months in the endoscopic cohort and 49.4 months in the surgical cohort. The overall survival was similar between the two cohorts (97.1% vs. 91.5%, P = 0.18). Survival without readmission for treatment-related complicates was also similar. Minor and severe procedure-related complications occurred more often in the surgical cohort than in the endoscopic cohort (63.8% vs. 43.5% and 8.5% vs. 0 respectively, P < 0.05 for both). Four patients in the endoscopic cohort had to undergo additional esophagectomy and were alive during follow-up. There were no procedure-related deaths in the endoscopic cohort, whereas two deaths occurred in the surgical cohort. Recurrence occurred in nine patients in the endoscopic group (13%): six with local recurrence, one with residual neoplasia and two with metachronous neoplasia. None of them died after repeated endoscopic treatments. CONCLUSIONS: Efficacy was similar between endoscopic therapy and esophagectomy in the treatment of early esophageal squamous cell neoplasia larger than 2 cm and endoscopic therapy was associated with fewer and manageable complications. We recommend endoscopic treatment should be preferred selected for early esophageal neoplasia larger than 2 cm.

Feifukang ameliorates pulmonary fibrosis by inhibiting JAK-STAT signaling pathway.

BACKGROUND: Feifukang (FFK) is a traditional Chinese medicine composed of herbs that protect lung function. However, difficulty arises regarding the clinical application of FFK due to the complex mechanism of Chinese medicines. This study aimed to investigate the efficacy of FFK and explore its targeted genes and pathways. METHODS: Histopathological changes and collagen deposition were measured to evaluate the effect of FFK on bleomycin-induced pulmonary fibrosis in mice. The differentially expressed targeted genes and pathways were first screened using RNA sequencing. Then network pharmacology and other experiments were conducted to confirm RNA sequencing data. RESULTS: FFK treatment reduced the pathological score and collagen deposition, with a decrease in α-SMA and collagen. RNA sequencing and network pharmacology results all showed that FFK can ameliorate pulmonary fibrosis through multi-genes and multi-pathways. The targeted genes in JAK-STAT signaling pathway are some of the most notable components of these multi-genes and multi-pathways. Further experiments illustrated that FFK regulated phosphorylation of SMAD3, STAT3 and JAK1, and their co-expressed lncRNAs, which all are the important genes in JAK-STAT signaling pathway. CONCLUSION: FFK can ameliorate pulmonary fibrosis by inhibiting JAK-STAT signaling pathway and has potential therapeutic value for lung fibrosis treatment. Our study provides a new idea for the study of traditional Chinese medicine.

Long-term outcomes of endoscopic multiband mucosectomy for early esophageal squamous cell neoplasia: a retrospective, single-center study.

BACKGROUND AND AIMS: Endoscopic multiband mucosectomy (EMBM) has been used to treat early Barrett's esophagus and esophagogastric junction neoplasia, yet it is seldom reported for the treatment of early esophageal squamous cell neoplasia. Here we retrospectively evaluated the feasibility, safety, and efficacy of EMBM for early esophageal squamous cell neoplasia. METHODS: A total of 125 patients were included in the study. Lesions were delineated using electrocoagulation and resected using the EMBM technique. The primary outcomes were local recurrence and adverse events. Secondary outcomes were histology of the endoscopic resection specimens, specimen area, and speed of resection. All patients were followed up endoscopically. RESULTS: There were 135 esophageal lesions, of which 40 were pathologically diagnosed as low-grade intraepithelial neoplasia, 57 as high-grade intraepithelial neoplasia, 34 as early esophageal cancer, and 4 as squamous epithelium without neoplasia. No severe adverse events were observed, except for 1 perforation, which was treated by application of clips. The median follow-up was 27.75 months. Three patients had local recurrence and were endoscopically treated again. Local recurrence rate was 2.4% (3/125). No deaths occurred during the follow-up. All specimens were visible with a dividing rule, and the mean specimen area was 4.63 cm2. Mean operation time was 31.2 ± 17.4 minutes. Mean speed of resection was 6.74 min/cm2. CONCLUSIONS: EMBM seems to be effective and safe for patients with early esophageal squamous cell neoplasia. The long-term recurrence rate is low.

Genetic Screening and Analysis of LKB1 Gene in Chinese Patients with Peutz-Jeghers Syndrome.

BACKGROUND Peutz-Jeghers syndrome (PJS) is an autosomal dominant genetic disease. It severely decreases patient quality of life and leads elevated cancer risk. Germline mutation of LKB1 is the leading cause of familial PJS. MATERIAL AND METHODS To characterize the germline mutation of LKB1 gene in Chinese familial and sporadic PJS patients, 14 PJS families, 5 sporadic PJS patients, and 250 healthy adults were collected and genomic DNAs of peripheral blood were extracted. Mutation screenings of LKB1 were performed using MLPA (multiplex ligation-dependent probe amplification), PCR, direct sequencing, and PCR-DHPLC (denaturing high-performance liquid chromatography). RESULTS A total of 12 kinds of germline mutations were found in 9 familial PJS patients, most of which were point mutations (7/12); 4 large deletions of LKB1 were also observed. Of the 12 mutations, 7 were pathogenic (2 were de novo), 4 were just polymorphisms, and 1 was indefinitely pathogenic. No pathogenic mutation in exons of the LKB1 gene was detected in the 5 sporadic PJS patients. The mutation detection rate for the LKB1 gene was 85.7% in our Chinese familial PJS and 63.2% in all Chinese PJS patients. Eight familial PJS patients were identified with pathogenic germline mutations in 14 unrelated families (57.1%). Further methylation detection and analysis showed promoter methylation in carcinomatous polyps. CONCLUSIONS LKB1 gene germline mutation with pathogenic effect is a common cause of familial PJS in Chinese patients; however, it is not the only molecular pathogen of PJS. Methylation in the LKB1 gene promoter region may cause carcinomatous change in intestinal polyps.

Scutellarin Suppressed Proliferation and Induced Apoptosis in Gastric Cancer via Wnt/ß-catenin Signaling Pathway.

BACKGROUND: Scutellarin exerts anticancer effects on diverse malignancies. However, its function in gastric cancer has not been explored. OBJECTIVE: This study aimed to examine the anticancer effect and molecular mechanism of scutellarin in gastric cancer. MATERIALS AND METHODS: Gastric cancer cells were treated with scutellarin and transfected with the Wnt1 overexpression plasmid. Cell viability, proliferation, toxicity, and apoptosis were determined by cell counting kit-8 (CCK-8), colony formation, lactate dehydrogenase (LDH) activity, TdT-mediated dUTP Nick-End Labeling (TUNEL), and flow cytometry assays. Expressions of apoptosis-related and Wnt/ß-catenin signaling pathway- related proteins were examined by western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: Scutellarin concentration dependently restrained cell viability. Scutellarin (20 and 80 µmol/L) suppressed proliferation and promoted LDH release and apoptosis. Moreover, scutellarin elevated Bax and Cytochrome C levels but diminished the levels of Bcl-2, Wnt1, cytoplasmic ß-catenin, and basal cytoplasmic ß- catenin. However, the above-mentioned regulatory effects of scutellarin were all reversed by Wnt1 overexpression. CONCLUSION: Scutellarin suppressed gastric cancer cell proliferation and promoted apoptosis by inhibition of the Wnt/ß-catenin pathway.

Controllable Regulation of Ag2 S Quantum-Dot-Mediated Protein Nanoassemblies for Imaging-Guided Synergistic PDT/PTT/Chemotherapy against Hypoxic Tumor.

The combination of phototherapy and chemotherapy holds great potential for cancer treatment, while hypoxia in tumor as well as unexpected drug release largely restricts anticancer therapy. Inspired by the natural intelligence, herein, for the first time, a "bottom-up" protein self-assembly strategy mediated by near-infrared (NIR) quantum dots (QDs) with multicharged electrostatic interactions is presented to develop a tumor microenvironment (TME)-responsive theranostic nanoplatform for imaging-guided synergistic photodynamic therapy (PDT)/photothermal therapy (PTT)/chemotherapy. Catalase (CAT) possesses diverse surface charge distribution under different pH conditions. After modification by chlorin e6 (Ce6), the formulated CAT-Ce6 with patchy negative charges can be assembled with NIR Ag2 S QDs by regulating their electrostatic interactions, allowing for effective incorporation of specific anticancer drug oxaliplatin (Oxa). Such Ag2 S@CAT-Ce6@Oxa nanosystems are able to visualize nanoparticle (NP) accumulation to guide subsequent phototherapy, together with significant alleviation of tumor hypoxia to further enhance PDT. Moreover, the acidic TME triggers controllable disassembly through weakening the CAT surface charge to disrupt electrostatic interactions, allowing for sustained drug release. Both in vitro and in vivo results demonstrate remarkable inhibition of colorectal tumor growth with a synergistic effect. Overall, this multicharged electrostatic protein self-assembly strategy provides a versatile platform for realizing TME-specific theranostics with high efficiency and safety, promising for clinical translation.

Hypermethylation of adenomatous polyposis coli gene promoter is associated with novel Wnt signaling pathway in gastric adenomas.

BACKGROUND AND AIM: Gastric adenomas (GAs) are considered as premalignant lesions of gastric adenocarcinoma. The role of Wnt signaling pathway in GAs is rarely identified. In the present study, we aimed to determine whether Wnt signaling plays a role in the pathogenesis of GAs, and to clarify the mechanism of Wnt signaling in GAs. METHODS: The study investigated the relationship between clinicopathological characteristics, Helicobacter pylori (Hp) infection, adenomatous polyposis coli (APC) promoter methylation, APC and ß-catenin immunohistochemistry expression and mutation status, compared with 38 gastric adenoma and periadenomatous tissues (PTs). RESULTS: The abnormal expression of ß-catenin in PTs, low-grade adenomas (LGAs) and high-grade adenomas (HGAs) was 0%, 9.09% and 81.25%. For APC, immunoreactive score (IRS) was 5.50 ± 0.5 in PTs, 3.59 ± 1.4 in LGAs and 1.8 ± 2.0 in HGAs. The scores in LGAs and HGAs were significantly lower than those in PTs (P = 0.000). IRS reflected significantly reduced expression of APC in HGAs (P = 0.002). The absent expression of APC had a correlation with the expression of ß-catenin (P = 0.000). Four LGAs (18.18%) and nine HGAs (56.25%) had methylation of APC. APC promoter methylation correlated with the grade (P = 0.014) and the expression of ß-catenin and APC (P = 0.000). Genes mutation was detected in only two adenomas (5.3%). The presence of Hp in HGAs (43.8%) was significantly higher than in LGAs (13.6%) (P = 0.038). But there was no statistical correlation to growth pattern, size, APC hypermethylation and gene mutation. CONCLUSION: Hypermethylation of APC promoter, instead of mutations involving APC and ß-catenin, may play a role in the development and progression of GAs contributing to moderate activation of Wnt signaling. Helicobacter pylori may accelerate the progress of gastric adenoma, but the pathogenesis needs further research.

[Mutation screening of LKB1 gene in familial Peutz-Jeghers syndrome patients].

OBJECTIVE: To screen for potential mutations of LKB1 gene in Chinese familial Peutz-Jeghers syndrome (PJS) patients and analyze their clinical manifestations. METHODS: Eleven PJS families were collected and genomic DNA of peripheral blood was extracted. Typically mucosal pigmentation and hamartomatous polyps were present in all 11 probands. Mutation screening of the probands were carried out by PCR and direct sequencing. Two hundred and fifty healthy adults were enrolled as normal controls, for whom genomic DNA of peripheral blood was also extracted. PCR-denaturing high performance liquid chromatography was carried out to verify the mutation identified in the patients. RESULTS: Nine germline mutations were identified in eight PJS patients, which included 7 point mutations, 1 deletion and 1 insertion. Among these, 4 were considered to be pathogenic, of which 2 were de novel, 4 were considered to be polymorphism, and 1 was uncertain. CONCLUSION: LKB1 gene mutations with pathogenic effect are a common cause of familial PJS in Chinese patients. Most mutations are point mutations.

Comparative Transcriptome Analysis Reveals Genes Associated with the Gossypol Synthesis and Gland Morphogenesis in Gossypium hirsutum.

Gossypium hirsutum is an important source of natural textile fibers. Gossypol, which is a sesquiterpenoid compound mainly existing in the cotton pigment glands, can facilitate resistance to the stress from diseases and pests. The level of gossypol in the cotton is positively correlated to the quantity of pigment glands. However, the underlying regulatory mechanisms of gossypol synthesis and gland morphogenesis are still poorly understood, especially from a transcriptional perspective. The transcripts of young leaves and ovules at 30 DPA of the glanded plants and glandless plants were studied by RNA-Seq and 865 million clean reads were obtained. A total of 34,426 differentially expressed genes (DEGs) were identified through comparative transcriptome analysis. Genes related to gossypol synthesis or gland morphogenesis displayed significant differential expression between the two cultivars. Functional annotation revealed that the candidate genes related to catalytic activity, the biosynthesis of secondary metabolites, and biomolecular decomposition processes. Our work herein unveiled several potential candidate genes related to gossypol synthesis or gland morphogenesis and may provide useful clues for a breeding program of cotton cultivars with low cottonseed gossypol contents.

Spatial Differentiation and Influencing Factors of Poverty Alleviation Performance Under the Background of Sustainable Development: A Case Study of Contiguous Destitute Areas in Hunan Province, China.

Poverty eradication is a realistic requirement for the addressing of the urban-rural development imbalance. It consolidates the achievements of the poverty alleviation, and accelerates the realization of the United Nations Sustainable Development Goals. In research that deals with poverty, qualitative analysis is often used to study the connection between a single influencing factor and poverty reduction, and to solve regional poverty through government measures. However, these studies usually ignore the multidimensional nature of poverty, and the fact that poverty alleviation also needs to be approached from multiple perspectives. By constructing a theoretical framework of poverty alleviation performance from the perspective of sustainable development, this study selects contiguous poverty-stricken areas in the Hunan Province, China as the empirical study area, constructs an evaluation index system from the three dimensions of economic development, infrastructure and people's livelihood security, and selects influencing factors from three aspects of 'population', 'land' and 'industry'. The spatial differentiation characteristics and influencing factors of poverty alleviation performance in poverty-stricken areas were studied by using the methods of entropy weight method and geodetector. The results show: firstly, in the concentrated and contiguous poverty-stricken areas of the Hunan Province, the performance of poverty alleviation in the economic development makes little difference, showing a 'high-medium-low' cross-distribution pattern. The poverty alleviation performance of the infrastructure presents a distribution pattern of 'low in the middle and high on both sides. The poverty alleviation performance of people's livelihood security has significant spatial differentiation characteristics, which all present a reunion distribution. The overall poverty alleviation performance varies greatly, showing a funnel-shaped distribution in space. Secondly, the spatial differentiation of poverty alleviation performance in the concentrated and contiguous poverty-stricken areas of the Hunan Province is the result of the combined effects of multiple factors. 'Population' is the dominant factor affecting the performance of poverty alleviation, 'land' is the basic factor that causes the spatial differentiation of poverty alleviation performance, and 'industry' is the key factor for the improvement of the poverty alleviation ability.

Advanced treatment of secondary effluent organic matters (EfOM) from an industrial park wastewater treatment plant by Fenton oxidation combining with biological aerated filter.

This study investigated the advanced treatment of secondary effluent organic matters (EfOM) from an industrial park wastewater treatment plant (IPWTP) by Fenton oxidation process and its combination with biological aerated filter (BAF). The constituents of EfOM were characterized by using fluorescence excitation-emission matrix, and the results showed that the major components included aromatic proteins, soluble microbial products, humic and fulvic acid-like substances, and compounds associated with fluorescent region of Ex 250-300 nm/Em 600-700 nm. The EfOM was strongly resistant to biodegradation (biochemical oxygen demand (BOD5):chemical oxygen demand (COD) ratio at 0.11), resulting in less than 15% dissolved organic carbon (DOC) removal efficiency by the BAF reactor. The advanced treatment of EfOM by Fenton oxidation process led to maximum ~50% mineralization efficiency of EfOM under the optimal conditions of 2.0 mM FeII, 10 mM H2O2, pH 3.0 and 3.0 h of the reaction time. Particularly, Fenton oxidation treatment effectively improved the biodegradability of EfOM in the IPWTP secondary effluents, e.g., increasing the BOD5:COD ratio from 0.11 to 0.42. A synergistic combination of Fenton oxidation process with the BAF reactor offered desirable mineralization efficiencies of EfOM (>70%) at lower dosages of Fenton's reagents. The present results suggest that Fenton oxidation process combining with the BAF reactor can be a promising strategy for the advanced treatment of EfOM in IPWTP secondary effluents. This study provides guidance for the characterization and advanced treatment of EfOM in IPWTP secondary effluents for practical purpose.

Crosstalk of mRNA, miRNA, lncRNA, and circRNA and Their Regulatory Pattern in Pulmonary Fibrosis.

Noncoding RNAs (ncRNAs), such as microRNA (miRNA), long ncRNA (lncRNA), and circular RNA (circRNA), are regulators of important biological functions. Therefore, understanding their crosstalk and regulatory patterns can provide treatment for diseases. In this study, differentially expressed RNA transcripts were obtained by RNA sequencing in bleomycin-induced pulmonary fibrosis in mice. Four miRNAs, 10 lncRNAs, and two circRNAs were tested to validate the sequencing. There were differentially expressed 585 mRNAs, 236 miRNAs, 272 lncRNAs, and 74 circRNAs in pulmonary fibrosis. Their location on chromosome, length varieties, interaction, and host genes were analyzed. lnc949, circ949, and circ057 were chosen to explore the detailed crosstalk and regulatory pattern, which were measured by using RNA-FISH, dual-luciferase reporter assay, real-time cell analysis and rescue experiment, co-localization analysis, RNA immunoprecipitation, and RNA pull down. The data showed that the three ncRNAs were predominant in the cytoplasm, and their regulatory patterns were focused on post-transcription. The fibrotic function of lnc949 depended on its host gene FKBP5. circ949 and circ057 formed a regulatory network with lnc865 and lnc556 to simultaneously regulate miR-29b-2-5p targeting STAT3 phosphorylation. Collectively, different RNAs can crosstalk with each other to regulate pulmonary fibrosis through different regulatory patterns. We hope these data can provide a full concept of RNA transcripts, leading to a new treatment for pulmonary fibrosis.