[The evolution of approach in the resuscitation of neonates born with meconium-stained amniotic fluid: a tale of two countries, China and U.S.A., in the past 60 years]. / 羊水胎粪污染新生儿复苏的前世今生：过去60年中美两国的演变史.

Neonates born through meconium-stained amniotic fluid (MSAF) may develop complications including meconium aspiration syndrome, persistent pulmonary hypertension of newborn and death. The approach to the resuscitation of these neonates has significantly evolved for the past few decades. Initially, under direct visualization technique, neonates with MSAF were commonly suctioned below the vocal cords soon after delivery. Since 2015, Neonatal Resuscitation Program (NRP®) of the American Academy of Pediatrics has recommended against "routine" endotracheal suctioning of non-vigorous neonates with MSAF but favored immediate resuscitation with positive pressure ventilation via face-mask bagging. However, the China neonatal resuscitation 2021 guidelines continue to recommend routine endotracheal suctioning of non-vigorous neonates born with MSAF at birth. This review article discusses the differences and the rationales in the approach in the resuscitation of neonates with MSAF between Chinese and American NRP® guidelines over the past 60 years.

Engineering Hierarchical Architecture of Metal-Organic Frameworks for Highly Efficient Overall CO2 Photoreduction.

Previous studies on syntheses of metal-organic frameworks (MOFs) for photocatalytic CO2 reduction are mainly focused on the exquisite control over the net topology and the functionality of metal clusters/organic building blocks. This contribution demonstrates that the rational design of MOF-based photocatalyst can be further extended to the hierarchical structure at micrometer scales well beyond the conventional MOF design at the molecular level. By taking advantage of the disparity of two selective MOFs in nucleation kinetics, a hierarchical core-shell MOF@MOF structure is successfully constructed through a simple one-pot synthesis. Besides inheriting the high porosity, crystallinity, and robustness of parent MOFs, the obtained heterojunction exhibits extended photoresponse, optimized band alignment with large overpotential, and greatly enhanced photogenerated charge separation, which would be hardly realized by the merely molecular-level assembly. As a result, the challenging overall CO2 photoreduction is achieved, which generates a record high HCOOH production (146.0 µmol/g/h) without using any sacrificial reagents. Moreover, the core-shell structure exhibits a more effective use of photogenerated electrons than the individual MOFs. This work shows that harnessing the hierarchical architecture of MOFs present a new and effective alternative to tuning the photocatalytic performance at a mesoscopic level.

Resveratrol Triggered the Quick Self-Assembly of Gallic Acid into Therapeutic Hydrogels for Healing of Bacterially Infected Wounds.

Programing self-assembly of naturally bioactive molecules has been a wide topic of great significance for biomedical uses. Despite the fact that plant-derived polyphenols with catechol or pyrogallol moieties have been widely studied to construct nanocomplexes or nanocoatings via self-polymerization, there is no report on the self-assembly of these polyphenols into therapeutic hydrogels for potential applications. Here, we reported that adding a very small amount of resveratrol (Res) into the gallic acid (GA) aqueous solution could trigger the quick self-assembly of GA to form a fibrous hydrogel within 5 min through hydrogen bonds and π-π interactions. The length of GA/Res (GR) fibrils in gels varied from 100 to 1000 microns, with a diameter of around 1 µm. Notably, these GR hydrogels showed excellent colloid stability, providing better slow release and outstanding biocompatibility. Also, in vivo experiments indicated the hydrogels had high antibacterial effects and excellent wound healing capabilities in a total skin defect model via regulating the expression of inflammatory factors (IL-6, IL-1ß, and TNF-α) due to the release of therapeutic agents (GA and Res) into the matrix. Overall, our results provide a new strategy to accelerate self-assembly of GA by adding Res to form hydrogels, which is further proved as a promising therapeutic carrier for wound healing.

[Investigation and analysis of imported medicinal materials at Chinese border ports].

Imported medicinal materials are an important part of Chinese medicinal resources. To be specific, about 10% of the around 600 commonly used Chinese medicinal materials are from abroad, and the introduction of foreign medicinal materials has promoted the development of Chinese medicine. Amid the advancement of reform and opening up and the "Belt and Road" Initiative, major headway has been made in the cross-border trade in China, bringing opportunities for the import of medicinal materials from border ports. However, for a long time, there is a lack of systematic investigation on the types of exotic medicinal materials at border ports. In the fourth national census of traditional Chinese medicine resources, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, together with several organizations, investigated the nearly 40 border ports, Chinese medicinal material markets, and border trade markets in 6 provinces/autonomous regions in China for the first time and recorded the types, sources, circulation, and the transaction characteristics of imported medicinal materials. Moreover, they invited experts to identify the origins of the collected 237 medicinal materials. In addition, the status quo and the problems of the medicinal materials were summarized. This study is expected to lay a basis for clarifying the market and origins of imported medicinal materials as well as the scientific research on and supervision of them.

Spatially Directed Biosynthesis of Quantum Dots via Spidroin Templating in Escherichia coli.

Spatially directed synthesis of quantum dots (QDs) is intriguing yet challenging in organisms, due to the dispersed feature of templating biomolecules and precursors. Whether this task could be accomplished by biomolecular condensates, an emerging type of membraneless compartments in cells remains unknown. Here we report synthetic protein condensates for templated synthesis of QDs in bacterium Escherichia coli. This was realized by overexpression of spider silk protein to bind precursor ions and recruit other necessary components, which induced the spidroin to form more ß-sheet structures for assembly and maturation of the protein condensates. This in turn enabled formation and co-localization of the fluorescent QDs to "light up" the condensates, and alleviated cytotoxicity of the precursor heavy metal ions and resulting QDs. Thus, our results suggest a new strategy for nanostructure synthesis and deposition in subcellular compartments with great potential for in situ applications.

Salmonella infection may alter the expression of toll like receptor 4 and immune related cells in chicken bursa of Fabricius.

Toll like receptor 4 (TLR4), eosinophils and mast cells play significant role in host immunity during several pathogenic infections. However in vivo tissue expression of TLR4 and distribution pattern of eosinophils and mast cells in chicken bursa of Fabricius (BF) during Salmonella enterica serovar Typhimurium (STm) infection is poorly studied. Therefore, herein, following immunostaining, we found localization of TLR4 in follicular cortex and medulla and its expression was statistical increased after 36 h and 72 h of STm stimulation. Chromotrope 2R staining revealed that eosinophils were mostly distributed in follicular cortex, inter-follicular spaces and in or around blood vessels and their number in BF were statistical increased after 72 h of STm stimulation. The presence of eosinophils was confirmed using immunostaining with anti-rabbit eosinophil cationic protein antibody. Toluidine blue stained mast cells were mostly distributed in connective tissues between inter-follicular spaces while some were also present in follicular cortex of BF. However, STm stimulation illustrated non-significant effect on the number of mast cells or their de-granulation, instead their number were gradually decreased in BF with advancement in age of chickens. Hence, this study provided novel information about in vivo tissue distribution of TLR4, eosinophils and mast cells in BF during STm infection.

Lipopolysaccharide mediates immuno-pathological alterations in young chicken liver through TLR4 signaling.

BACKGROUND: Lipopolysaccharide (LPS) induces acute liver injury and the complex mechanisms include the activation of toll like receptor 4 (TLR4) signaling pathway in many species. However, immuno-pathological changes during TLR4 signaling under LPS stress in acute liver injury is poorly understood in avian species. The present investigation was therefore carried out to evaluate these alterations in TLR4 signaling pathway during acute liver injury in young chickens. RESULTS: After intraperitoneal injection of LPS or saline, liver samples were harvested at 0, 2, 6, 12, 24, 36, 72 and 120 h (n = 6 at each time point) and the microstructures were analyzed by hematoxylin and eosin (H&E) staining. Alanine aminotransferase (ALT) and caspase-3 enzyme activity was assessed by enzyme-linked immunosorbent assay (ELISA). Proliferative cell nuclear antigen (PCNA), single stranded DNA (ssDNA) and TLR4 protein expressions were determined by immunohistochemistry. Gene expressions of PCNA, caspase-3, caspase-8, TLR4 and its downstream molecules were analyzed by quantitative polymerase chain reaction (qPCR). LPS injection induced significantly higher ALT activity, severe fatty degeneration, necrotic symptoms, ballooning degeneration, congestion, enhanced inflammatory cell infiltration in liver sinusoids, decreased proliferation, increased apoptosis and significant up-regulation in TLR4 and its downstream molecules (MyD88, NF-κB, TNF-α, IL-1ß and TGF-ß) expression at different time points. CONCLUSIONS: This study indicated that TLR4 signaling and its downstream molecules along with certain cytokines play a key role in acute liver injury in young chickens. Hence, our findings provided novel information about the histopathological, proliferative and apoptotic alterations along with changes in ALT and caspase-3 activities associated with acute liver injury induced by Salmonella LPS in avian species.

Effects of lipopolysaccharide on the histomorphology and expression of toll-like receptor 4 in the chicken trachea and lung.

Endotoxin or lipopolysaccharide (LPS) exposure can cause injury to the respiratory airways and in response, the respiratory epithelia express toll-like receptors (TLRs) in many species. However, its role in the innate immunity in the avian respiratory system is poorly understood. The aim of the present study was to evaluate the effects of LPS on the chicken trachea and lung. After intraperitoneal LPS or saline injection, the trachea and lungs were harvested at 0, 12, 36 and 72 h (n = 6 at each time point) and histopathologically analysed using haematoxylin and eosin and periodic acid-Schiff staining, while TLR4 expression was determined by immunohistochemistry and secretory Immunoglobulin A (SIgA) levels by enzyme-linked immunosorbent assay. After LPS stimulation, we observed a remarkable decrease in the number of goblet cells along with obvious disruption and desquamation of the ciliated epithelium in the trachea, blurring of the boundary between pulmonary lobules, narrowed or indistinguishable lumen of the pulmonary atria and leukostasis in the lungs. Following LPS stimulation, TLR4 protein expression was up-regulated in both the trachea and the lungs and was found on the ciliated columnar cells as well as in the submucosa of the trachea, and in the lungs on parenchymal and immune cells. However, SIgA levels were only up-regulated in the trachea at 12 h following LPS stimulation. Hence, this report provides novel information about the effects of LPS on the microstructure of the lower respiratory tract and it is concluded that its intra-peritoneal administration leads to TLR4-mediated destruction of the tracheal epithelium and pulmonary inflammation along with increased SIgA expression in the tracheal mucosa.

Immediate postpartum cessation of tenofovir did not increase risk of virological or clinical relapse in highly viremic pregnant mothers with chronic hepatitis B infection.

Background & Aims: Peripartum prophylaxis (PP) with tenofovir disoproxil fumarate (TDF) is the standard of care to prevent mother-to-child transmission of chronic hepatitis B (CHB) infection in mothers who are highly viremic. We investigated the maternal and infant outcomes in a large Chinese cohort of TDF-treated CHB pregnant participants. Methods: In this prospective study, treatment-naive mothers with CHB and highly viremic (HBV DNA ≥200,000 IU/ml) but without cirrhosis were treated with TDF at 24-28 weeks of pregnancy. In accordance with Chinese CHB guidelines, TDF was stopped at delivery or ≥4 weeks postpartum. Serum HBV DNA and alanine aminotransferase were monitored every 6-8 weeks to determine virological relapse (VR). Infants received standard neonatal immunization, and HBV serology was checked at 7-12 months of age. Results: Among 330 participants recruited (median age 30, 82.7% HBeAg+, median HBV DNA 7.82 log IU/ml), TDF was stopped at delivery in 66.4% and at ≥4 weeks in 33.6%. VR was observed in 98.3%, among which 11.6% were retreated with TDF. Timing of TDF cessation did not alter the risk of VR (99.0 vs. 96.9%), clinical relapse (19.5 vs. 14.3%), or retreatment (12.6 vs. 10.1%) (all p > 0.05). A similar proportion of patients developed alanine aminotransferase flare five times (1.1 vs. 2.1%; p = 0.464) and 10 times (0.5 vs. 0%; p = 0.669) above the upper limit of normal (ULN) in the early withdrawal and late withdrawal groups, respectively. No infants developed HBsAg-positivity. Conclusions: PP-TDF and neonatal immunization were highly effective in preventing mother-to-child transmission of HBV in mothers who are highly viremic. Timing of cessation of PP-TDF did not affect the risk of VR or retreatment. Impact and Implications: In pregnant mothers with chronic hepatitis B infection who are started on peripartum tenofovir to prevent mother-to-child-transmission (MTCT), the optimal timing for antiviral withdrawal during the postpartum period remains unknown. This prospective study demonstrates that stopping tenofovir immediately at delivery, compared with longer treatment duration of tenofovir, did not lead to an increased risk of virological relapse, retreatment, or transmission of the virus to the baby. Shortening the duration of peripartum antiviral prophylaxis from 12 weeks to immediately after delivery can be considered. The immediate withdrawal of peripartum tenofovir, combined with standard neonatal immunization schemes, is 100% effective in preventing MTCT among pregnant mothers with CHB who are highly viremic, with a high rate of vaccine response in infants.

[Overview of current researches on Tibetan medicine "zuotai"].

"Zuotai" is one of the main raw material of many rare Tibetan medicine, and it plays a important role in the system of Tibetan medicine. There are some toxic heavy metals in "Zuotai", such as Hg, Au, Pb and so on. As a result, it's urgent to study the safety and effectiveness of "Zuotai" in depth. This paper will analyze and induce the resent progress of the study about "Zuotai". With constipation, "Zuotai" and "Zuotai" as key words, CNKI, CHINAINFO, CQVIP were retrieved, Springer were retrieved besides. Relevant 86 references were obtained. Twenty-two for reference were adopted through screening. The paper reviewed the resent progress of the study about "Zuotai" in chemical composition, pharmacodynamics and pharmacokinetics, toxicology and clinical application. This will establish the basis for further study.

Coassembly of Fiber Hydrogel with Antibacterial Activity for Wound Healing.

Wound healing remains a critical challenge due to its vulnerability to bacterial infection and the complicated inflammatory microenvironment. Herein, we report a novel antibacterial hydrogel constructed only by gallic acid (GA) and phycocyanin (PC), which is expected for the treatment of bacteria-infected wounds. These GA/PC hydrogels (GP) was found to coassemble into fibrous networks with a diameter of around 2 µm mainly through noncovalent interactions of hydrogen bonds, van der Waals force, and π interaction. Notably, these GP hydrogels showed excellent rheological properties (i.e., storage modulus of more than 9.0 × 104 Pa) and outstanding biocompatibility and antibacterial activities. Thanks to the incorporation of GA and PC, the GP hydrogels enabled adherence to the moist wound tissue and achieved a sustained release of GA and PC into the wound skin, therefore effectively attenuating inflammation and accelerating wound healing both in normal mice and bacteria-infected mice through regulating the expression of the tight junction protein and the alleviation of oxidative stress. Considering these results, these GP hydrogels are demonstrated to be a promising candidate for bacteria-infected wound healing.

Construction of high internal phase Pickering emulsions using cold plasma modified soy protein isolate-proanthocyanidin complex.

Protein-based high internal phase Pickering emulsions (HIPPEs) feature numerous multi-functionalities and widespread applications. However, the direct use of native proteins for the constructions of HIPPEs is limited since it is fragile under various conditions. Here, cold plasma was used to modify soy protein isolates (SPI) to improve their surficial properties. Meanwhile, proanthocyanidins (PA) were applied to interact with cold plasma-treated SPI to form complex. Furthermore, the well-prepared SPI-PA complex was used to construct novel HIPPEs. Results showed cold plasma treatment significantly improved the functionalities of SPI, which were confirmed by surface hydrophobicity (H0 ＜ 500), sulfhydryl (SH) groups and spectral analysis. Further, the emulsification and oxidation resistance of cold plasma treated SPI were enhanced after forming complex with PA. Soybean oils can be stabilized by SPI-PA complexes to form HIPPEs with a lipid oxidation inhibition rate of ＞ 65%, creaming index (CI) ＞ 80%, excellent rheological properties and better stability compared with conventional emulsion systems. Overall, this SPI-PA complexes provides a unique approach to improve the emulsification and oxidation resistance to engineer HIPPEs with versatile applications.

Mucoadhesive Hydrogel with Anti-gastric Acid and Sustained-Release Functions for Amelioration of DSS-Induced Ulcerative Colitis.

Mucoadhesive hydrogels with multifunctional properties such as gastric acid resistance and sustained drug release in the intestinal tract are highly desirable for the oral treatment of inflammatory bowel diseases (IBDs). Polyphenols are proven to have great efficacies compared with the first-line drugs for IBD treatments. We recently reported that gallic acid (GA) was capable of forming a hydrogel. However, this hydrogel is prone to easy degradation and poor adhesion in vivo. To tackle this problem, the current study introduced sodium alginate (SA) to form a gallic acid/sodium alginate hybrid hydrogel (GAS). As expected, the GAS hydrogel showed excellent antiacid, mucoadhesive, and sustained degradation properties in the intestinal tract. In vitro studies demonstrated that the GAS hydrogel significantly alleviated ulcerative colitis (UC) in mice. The colonic length of the GAS group (7.75 ± 0.38 cm) was significantly longer than that of the UC group (6.12 ± 0.25 cm). The disease activity index (DAI) value of the UC group was (5.5 ± 0.57), which was markedly higher than that of the GAS group (2.5 ± 0.65). The GAS hydrogel also could inhibit the expression of inflammatory cytokines, regulating macrophage polarization and improving the intestinal mucosal barrier functions. All these results indicated that the GAS hydrogel was an ideal candidate for oral treatment of UC.

Construction of an antibacterial hydrogel based on diammonium glycyrrhizinate and gallic acid for bacterial- infected wound healing.

The current antibacterial wound dressings with antibiotic substances or metal bactericidal agents may lead to severe multidrug resistance and poor biocompatibilities. Herein, we report an inherent antibacterial hydrogel constructed by only two naturally small molecules gallic acid (GA) and diammonium glycyrrhizinate (DG) for promoting Staphylococcus aureus (S. aureus)-infected wound healing. The resultant GAD hydrogel can be fabricated by co-assembly of these two materials through simple steps. Thanks to the incorporation of GA and DG, GAD hydrogel enabled a strong mechanical performance and great self-healing property with a sustained-release of drugs into skin wounds. Moreover, the cell viability assays showed that GAD hydrogel had good cytocompatibility by promoting cell proliferation and migration. In addition, GAD hydrogel had broad antibacterial efficiency against both Gram-positive and Gram-negative bacteria. Taken together, GAD hydrogel is a promising dressing to accelerate bacterial-infected wound healing through reconstructing an intact and thick epidermis without antibiotics or cytokines.

The differential associative relationship between early risk factors, neonatal morbidities and early neurodevelopmental outcome in preterm infants <29 weeks' gestation.

BACKGROUND: Very preterm infants of <29 weeks' gestation are at high risk for adverse neurodevelopment due to multiple risk factors in the early stages of life. There is little information regarding the associative effects of risk factors in early life, neonatal morbidities and subsequent neurodevelopmental outcomes. AIMS: Investigate the association of early neurodevelopmental outcomes, neonatal complications and the risk factors in the early hours of life in a cohort of preterm infants <29 weeks' gestational age. METHODS: We enrolled all surviving preterm neonates born at gestation <29 weeks between January 2015 and June 2021 in the University of Hong Kong-Shenzhen Hospital. Demographic and clinical characteristics were collected from a database of the neonatal intensive care unit. Neurodevelopmental outcomes of the survivors were evaluated using the Ages and Stages Questionnaire (ASQ-3) which were measured at the adjusted age of 12 to 18 months. The multivariate linear regression model was used to determine correlation presented as ß coefficient (ß) with 95 % confidence intervals (CI). RESULTS: In this cohort of 56 survivors <29 weeks' gestation, urine output within the first 12 h of life and Apgar score at 5 min were positively associated with different domains of ASQ-3 score, however male sex and highest fraction of inspired oxygen (FiO2) in the first 12 h of life were negatively related with at least one of neurocognitive domains of ASQ-3 at adjusted age of 12 to 18 months. During hospitalization, in addition to the frequency of packed red cell transfusions, the development of severe necrotizing enterocolitis was inversely associated with both neuromotor and neurocognitive skills (gross motor domain: ß = -16.93, CI: -32.04, -1.82; fine motor domain: ß = -16.42, CI: -28.82, -4.02; problem solving domain: ß = -13.14, CI: -24.45, -1.83; all P < 0.05), whereas severe intraventricular hemorrhage had adverse effects on gross motor only (ß = -13.04, CI: -24.42, -1.65; P = 0.03). Bronchopulmonary dysplasia and retinopathy of prematurity were not related with ASQ-3. CONCLUSIONS: In this small cohort study of very preterm neonates born at <29 weeks' gestation, risk factors in the early hours of life and neonatal morbidities during hospitalization had differential associative relationships with ASQ-3 at 12-18 months adjusted age. This information may be important for parental counseling and management including early diagnosis and intervention.

A Family-Centered, Multidisciplinary Clinic for Early Diagnosis of Neurodevelopmental Impairment and Cerebral Palsy in China-A Pilot Observation.

Background: Comprehensive multidisciplinary assessment of neurodevelopmental outcomes of high-risk neonates may have significant challenges in low- and middle-income countries, in addition to socio-cultural barriers. We aimed to compare the time to diagnosis of neurodevelopmental impairment (NDI) and cerebral palsy (CP) in preterm neonates (<29 weeks) at a multidisciplinary assessment and care (MDAC) clinic with that of a conventional high-risk infant follow-up clinic in China. Methods: All eligible surviving very preterm neonates born at <29 weeks gestation at the University of Hong Kong-Shenzhen Hospital between January 2015 and December 2019 were followed up in conventional (2015-2017) and MDAC (2018-2020) clinics up to 2 years corrected age with clinical demographic information collected in a prospective database. The MDAC team used standardized developmental assessments. The rates and timing of diagnosing NDI and CP in two epochs were compared. Results: The rates of NDI and CP were not different in two epochs [NDI: 12 (50%) vs. 12 (41%); CP: 3 (12%) vs. 2 (7%) of 24 and 29 surviving infants assessed in conventional and MDAC clinics, respectively]. Infants in the MDAC clinic were diagnosed with NDI and CP earlier than those in the pre-MDAC epoch (6 vs. 14 months corrected age, respectively, P < 0.05). Conclusion: High-risk preterm neonates can be followed more effectively in a family-centered, child-friendly multidisciplinary clinic, leading to an earlier diagnosis of NDI and CP. Early counseling and interventions could be implemented accordingly.

Construction of a sustained-release hydrogel using gallic acid and lysozyme with antimicrobial properties for wound treatment.

The purpose of this study is to provide a new strategy for constructing a temperature-controlled hydrogel as a promising agent for wound healing using natural products through physical co-assembly. Herein, the temperature-controlled physically assembled hydrogel consisting of gallic acid and lysozyme (GL) could be co-assembled into a regular fibrous structure accompanied by strong blue fluorescence with three-dimensional networks at micron levels through hydrophobic interactions, π-π interactions and hydrogen bonding. This GL hydrogel has excellent temperature sensitivity and self-healing properties, as proved by cycle high-low temperature tests. In addition, it possesses stable rheological properties, great sustained release ability, and could realize the spatiotemporal delivery of gallic acid and lysozyme. Biocompatibility and antibacterial tests proved that this well-assembled GL hydrogel has no cytotoxicity but excellent antibacterial activity. Both in vitro and in vivo experiments demonstrated that the GL hydrogel has excellent anti-inflammation efficiency and promotes the healing of chronic wounds by suppressing the expression of pro-inflammatory related genes. Tests using an E. coli-infected wound model confirmed that the GL hydrogel could terminate the inflammatory phase early and ultimately promote the healing of wounds infected by E. coli. This study provides a promising strategy for the effective treatment of wounds through a physical self-assembled hydrogel.

Photocatalytic CO2-to-Ethylene Conversion over Bi2S3/CdS Heterostructures Constructed via Facile Cation Exchange.

Solar-driven CO2 conversion to multicarbon (C2+) products has emerged as a key challenge, yet this calls for a systematic investigation on the overall reaction process and mechanism at an atomic level based on the rational design of highly selective photocatalysts. Herein, we report the synthesis of compact Bi2S3/CdS heterostructures via facile cation exchange, by which a unique pathway of CO2-to-C2H4 photoconversion is achieved. Specifically, the BCS-30 shows an optimal C2H4 production rate of 3.49 µmol h-1 g-1 based on the regulation of band structures and energy levels of photocatalysts by controlled growth of Bi2S3 at CdS surface. Both experimental and theoretical results (DFT calculations) identify Bi atoms as new catalytic sites for the adsorption of CO* and formation of *CO-*CO dimers that further hydrogenate to produce ethylene. Overall, this work demonstrates vast potentials of delicately designed heterostructures for CO2 conversion towards C2+ products under mild photocatalytic conditions.

Integrative analysis reveals a lineage-specific circular RNA landscape for adipo-osteogenesis of human mesenchymal stem cells.

BACKGROUND: The balance between osteogenesis and adipogenesis of mesenchymal stem cells (MSCs) is critical to skeletal development and diseases. As a research hotspot, circular RNAs (circRNAs) have expanded our understanding of a hidden layer of the transcriptome. Yet, their roles during adipo-osteogenesis remain poorly described. METHODS: The identity of human MSCs derived from bone marrow and adipose were first determined by flow cytometry, cellular staining, and quantitative polymerase chain reaction (qPCR). Multi-strategic RNA-sequencing was performed using Poly A, RiboMinus and RiboMinus/RNase R methods. Integrative analysis was performed to identify lineage-specific expressed circRNAs. The structural and expressional characteristics were identified by Sanger sequencing and qPCR, respectively. The regulatory effects of adipogenesis-specific circ-CRLF1 were confirmed using siRNA transcfection and qPCR. RESULTS: We generated a whole transcriptome map during adipo-osteogenesis based on 10 Poly A, 20 RiboMinus and 20 RiboMinus/ RNase R datasets. A total of 31,326 circRNAs were identified and quantified from ~ 3.4 billion paired-end reads. Furthermore, the integrative analysis revealed that 1166 circRNA genes exhibited strong lineage-specific expression patterns. Their host genes were enriched in distinct biological functions, such as cell adhesion, cytokine signaling, and cell division. We randomly selected and validated the back-spliced junction sites and expression patterns of 12 lineage-specific circRNAs. Functional analysis indicated that circ-CRLF1 negatively regulated adipogenesis. CONCLUSIONS: Our integrative analysis reveals an accurate and generally applicable lineage-specific circRNA landscape for adipo-osteogenesis of MSCs and provides a potential therapeutic target, circ-CRLF1, for the treatment of skeleton-related disease.