Publications by authors named "Jie Huang"

1,741 Publications

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[Community Composition and Assessment of the Aquatic Ecosystem of Periphytic Algae in the Yangtze River Basin].

Huan Jing Ke Xue 2022 Aug;43(8):3998-4007

Yangtze River Basin Ecological Environment Monitoring and Scientific Research Center, Yangtze River Basin Ecological Environment Supervision and Administration Bureau, Ministry of Ecology and Environment, Wuhan 430010, China.

To explore the periphytic algae community structure in the Yangtze River basin, samples were collected from 130 sampling sites, including the source to the estuary along the mainstream of the Yangtze River, eight primary tributaries, and the tributary of the Three Gorges area. The periphytic algae densities of different areas in the mainstream of the Yangtze River ranked from high to low were the upstream area, source area, middle and lower area, and the Jinsha River. The high periphytic algae density in the upstream area was associated with the shift in nutrition level, and the high periphytic algae density in the source area was associated with human activity. The spatial pattern of the periphytic algae community in the whole main stream from west to east presented the alternating dominance of Bacillariophyta and Cyanophyta; the Bacillariophyta () had a competitive advantage in the main stream, and the distribution of the periphytic algae community was driven by total nitrogen, total phosphorus, and pH. For the tributary of the Yangtze River, the periphytic algae density in the Three Gorges tributary area was far higher than those in the eight primary tributaries; the periphytic algae community was dominated by Cyanophyta (), which had a competitive advantage in the tributaries of the Yangtze River. The distribution of the periphytic community was driven by dissolved oxygen and pH. According to the diversity analysis and assessment, the periphytic algae community in the source area showed lower species richness and higher evenness, thus leading to a high -diversity and good assessment result (mesosaprobic zone). The middle and lower reaches of the Yangtze River also showed the same assessment result, the mesosaprobic zone. However, the community evenness of the middle and lower reaches was significantly lower than that of the source area, thus making the middle and lower reaches of the Yangtze River have a significantly lower -diversity than that of the source area. All areas of the Yangtze River showed good water quality assessment; however, different areas had different WQI index numbers, and the assessment results of the WQI index were inconsistent with the results of the aquatic assessment. Therefore, a comprehensive assessment of aquatic ecosystem health should use both aquatic assessments and water quality assessments.
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http://dx.doi.org/10.13227/j.hjkx.202111229DOI Listing
August 2022

Functional Au nanoparticles for engineering and long-term CT imaging tracking of mesenchymal stem cells in idiopathic pulmonary fibrosis treatment.

Biomaterials 2022 Aug 10:121731. Epub 2022 Aug 10.

CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China; School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei, 230026, China. Electronic address:

Idiopathic pulmonary fibrosis (IPF) therapy has always been a big and long-standing challenge in clinical practice due to the lack of miraculous medicine. Mesenchymal stem cells (MSCs)-based therapy has recently emerged as a promising candidate for redefining IPF therapy. Enhancing the therapeutic efficacy of MSCs and understanding of their growth, migration and differentiation in harsh lung microenviroments are two keys to improving the stem cell-based IPF treatment. Herein, a non-viral dual-functional nanocarrier is fabricated by a one-pot approach, using protamine sulfate stabilized Au nanoparticles (AuPS), to genetically engineer MSCs for simultaneous IPF treatment and monitoring the biological behavior of the MSCs. AuPS exhibits superior cellular uptake ability, which results in efficient genetic engineering of MSCs to overexpress hepatocyte growth factor for enhanced IPF therapy. In parallel, the intracellular accumulation of AuPS improves the CT imaging contrast of MSCs, allowing visual tracking of the therapeutic engineered MSCs up to 48 days. Overall, this work has described for the first time a novel strategy for enhanced therapeutic efficacy and long-term CT imaging tracking of transplanted MSCs in IPF therapy, providing great prospect for stem cell therapy of lung disease.
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http://dx.doi.org/10.1016/j.biomaterials.2022.121731DOI Listing
August 2022

A commentary on "Prognostic impact of neoadjuvant chemotherapy in patients with synchronous colorectal liver metastasis: A propensity score matching comparative study" (Int J Surg 2021;94:106106).

Int J Surg 2022 Aug 10:106810. Epub 2022 Aug 10.

Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650102, Yunnan, China. Electronic address:

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http://dx.doi.org/10.1016/j.ijsu.2022.106810DOI Listing
August 2022

ZC3H4 regulates infiltrating monocytes, attenuating pulmonary fibrosis through IL-10.

Respir Res 2022 Aug 12;23(1):204. Epub 2022 Aug 12.

Department of Physiology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Rd, Nanjing, 210009, Jiangsu, China.

Silicosis is a pulmonary fibrosis-associated disease caused by the inhalation of large amounts of free silicon dioxide (SiO) that mainly manifests as early inflammation and late pulmonary fibrosis. As macrophage precursors, monocytes accumulate in the lung during early inflammation, but their role in the development of silicosis is unclear. Single-cell sequencing (cell numbers = 25,002), Western blotting, quantitative real-time PCR, ELISA and cell functional experiments were used to explore the specific effects of monocytes on fibroblasts. The CRISPR/Cas9 system was used to specifically knock down ZC3H4, a novel member of the CCCH zinc finger protein family, and was combined with pharmacological methods to explore the mechanism by which ZC3H4 affects chemokine and cytokine secretion. The results indicated that (1) SiO induced an infiltrating phenotype in monocytes; (2) infiltrating monocytes inhibited the activation, viability and migration of fibroblasts by regulating IL-10 but not IL-8; and (3) SiO downregulated IL-10 via ZC3H4-induced autophagy. This study revealed that ZC3H4 regulated the secretion function of monocytes, which, in turn, inhibited fibroblast function in early inflammation through autophagy signaling, thereby reducing pulmonary fibrosis. These findings provide a new idea for the clinical treatment of silicosis.
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http://dx.doi.org/10.1186/s12931-022-02134-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375388PMC
August 2022

Resin glycoside extracts from Ipomoea aquatica retard lipid digestibility of high-fat food in vitro.

Food Res Int 2022 Sep 28;159:111552. Epub 2022 Jun 28.

Department of Food Science & Technology, National University of Singapore, 2 Science Drive 2, Singapore 117542, Singapore; National University of Singapore (Suzhou) Research Institute, 377 Lin Quan Street, Suzhou Industrial Park, Suzhou, Jiangsu 215123, PR China. Electronic address:

Due to the considerable increase in the prevalence of obesity, there is an increased interest in developing safe and effective anti-obesity treatments from fruits and vegetables. In this study, Ipomoea aquatica, commonly known as Kang Kong in Southeast Asia was first reported to contain potent pancreatic lipase (PL) inhibitors due to resin glycosides (RG). Ipomoea aquatica extract demonstrated a dose-dependent inhibitory activity against PL with an Orlistat equivalent (OE) value of 6.86 ± 0.51 × 10. In vitro lipolysis study showed that consuming RG in tandem with high-fat food (butter & salad dressing) was effective in delaying enzymatic fat digestion by inhibiting PL. Pre-incubation of PL with RG extract before substrate addition also significantly enhanced their inhibitory activity. However, RG was unstable when subjected to high heat treatments (90 °C). Overall, these results provided useful knowledge of RG as PL inhibitors for body weight management.
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http://dx.doi.org/10.1016/j.foodres.2022.111552DOI Listing
September 2022

Flavonoid Group of Roxb. Regulates the Anti-Tumor Immune Response Through the STAT3/HIF-1 Signaling Pathway.

Front Pharmacol 2022 22;13:918975. Epub 2022 Jul 22.

The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, China.

Roxb. (SGR) is a widely used traditional Chinese medicine, which has known effects of enhancing immunity. However, its anti-tumor effects and mechanism of action are still unclear. We selected MMTV-PyMT mice to determine the anti-tumor efficacy of SGR ethyl acetate (SGR-EA). First, flow cytometry was used to detect the number of immune cells in the mice tumor microenvironment. Furthermore, M2 polarization of macrophages was stimulated , and the expressions of macrophage M1/M2 surface markers and mRNA were as determined. Finally, we carried out a network pharmacology analysis on the active components of SGR-EA and experiments to verify that SGR-EA regulated the hypoxia-inducible factor (HIF)-1 signaling pathway to modulate the anti-tumor immune response by resetting M2 macrophages toward the M1 phenotype which inhibited tumor growth and lung metastasis in the mice. SGR-EA inhibited tumor growth and lung metastasis in the mice. Tumor-associated macrophages switched from M2 to the tumor-killing M1 phenotype and promoted the recruitment of CD4 and CD8 T cells in the tumor microenvironment. , SGR-EA significantly inhibited the polarization of macrophages into M2 macrophages and increased the number of M1 macrophages. In addition, following an intervention with SGR-EA, the expression of the HIF-1 signaling pathway-related proteins stimulated by interleukin-4 in macrophages was significantly inhibited. SGR-EA played an anti-tumor role by inhibiting the activation of the HIF-1 signaling pathway and response by resetting tumor-associated macrophages toward the M1 phenotype.
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http://dx.doi.org/10.3389/fphar.2022.918975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353186PMC
July 2022

GREM1/PPP2R3A expression in heterogeneous fibroblasts initiates pulmonary fibrosis.

Cell Biosci 2022 Aug 6;12(1):123. Epub 2022 Aug 6.

Department of Physiology, School of Medicine, Southeast University, 87 Dingjiaqiao Rd, Nanjing, 210009, Jiangsu, China.

Background: Fibroblasts have important roles in the synthesis and remodeling of extracellular matrix (ECM) proteins during pulmonary fibrosis. However, the spatiotemporal distribution of heterogeneous fibroblasts during disease progression remains unknown.

Results: In the current study, silica was used to generate a mouse model of pathological changes in the lung, and single-cell sequencing, spatial transcriptome sequencing and an analysis of markers of cell subtypes were performed to identify fibroblast subtypes. A group of heterogeneous fibroblasts that play an important role at the early pathological stage were identified, characterized based on the expression of inflammatory and proliferation genes (termed inflammatory-proliferative fibroblasts) and found to be concentrated in the lesion area. The expression of GREM1/protein phosphatase 2 regulatory subunit B''alpha (PPP2R3A) in inflammatory-proliferative fibroblasts was found to initiate early pulmonary pathological changes by increasing the viability, proliferation and migration of cells.

Conclusions: Inflammatory-proliferative fibroblasts play a key role in the early pathological changes that occur in silicosis, and during this process, GREM1 is the driving factor that targets PPP2R3A and initiates the inflammatory response, which is followed by irreversible fibrosis induced by SiO. The GREM1/PPP2R3A pathway may be a potential target in the early treatment of silicosis.
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http://dx.doi.org/10.1186/s13578-022-00860-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356444PMC
August 2022

Au-Pt nanozyme-based multifunctional hydrogel dressing for diabetic wound healing.

Biomater Adv 2022 Jun 17;137:212869. Epub 2022 May 17.

CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China. Electronic address:

Diabetic chronic wound healing is a critical clinical challenge due to the particularity of wound microenvironment, including hyperglycemia, excessive oxidative stress, hypoxia, and bacterial infection. Herein, we developed a multifunctional self-healing hydrogel dressing (defined as OHCN) to regulate the complex microenvironment of wound for accelerative diabetic wound repair. The OHCN hydrogel dressing was constructed by integrating Au-Pt alloy nanoparticles into a hydrogel (OHC) that formed through Schiff-base reaction between oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMCS). The dynamic cross-linking of OHA and antibacterial CMCS imparted the OHCN hydrogel dressing with excellent antibacterial and self-healing properties. Meanwhile, Au-Pt alloy nanoparticles endowed the OHCN hydrogel dressing with the functions of lowering blood glucose, alleviating oxidative damage, and providing O by simulating glucose oxidase and catalase. Through a synergistic combination of OHC hydrogel and Au-Pt alloy nanoparticles, the resulted OHCN hydrogel dressing significantly ameliorated the pathological microenvironment and accelerated the healing rate of diabetic wound. The proposed nanozyme-decorated multifunctional hydrogel offers an efficient strategy for the improved management of diabetic chronic wound.
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http://dx.doi.org/10.1016/j.bioadv.2022.212869DOI Listing
June 2022

RNF4 promotes tumorigenesis, therapy resistance of cholangiocarcinoma and affects cell cycle by regulating the ubiquitination degradation of p27kip1 in the nucleus.

Exp Cell Res 2022 Aug 2;419(1):113295. Epub 2022 Aug 2.

Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China. Electronic address:

Among the hallmarks of cholangiocarcinoma (CCA) progression and unresponsiveness to therapy is impaired ubiquitin-dependent degradation of nuclear tumor suppressor protein. In the previous stage, our research group found that as a key tumor suppressor, nuclear dysfunction of p27kip1 is closely related to chemotherapy resistance of CCA, but the specific mechanism is unclear. It was recently shown that p27kip1-driven tumors were strongly dependent on the SUMO pathway. RNF4, as the SUMO-targeted ubiquitin ligase (STUbL), identifies SUMOylated proteins as a substrate through sumo-interacting motifs (SIM) and causes its degradation via the ubiquitin proteasome pathway. Here we described that the expression of RNF4 was upregulated in CCA tissues and related to malignant features. Silencing RNF4 arrested human CCA cells at the G1 phase, which was associated with the upregulation of p27kip1 and the downregulation of its downstream cycle-related proteins. Silencing RNF4 inhibited cell proliferation and migration, increased cell apoptosis, and sensitized CCA cells to treatment of chemotherapeutic drugs in vitro. Immunofluorescence showed that p27kip1 and RNF4 were mainly co-located in the nucleus. Immunoprecipitation and Western blot showed that p27kip1 was a target protein for SUMOylation and high expression of RNF4 decreased the levels of nuclear p27kip1, enhanced the levels of ubiquitinated and SUMOylated p27kip1, indicating that RNF4 could regulate cell cycle progression via recognizing SUMOylated p27kip1 and facilitating its ubiquitination degradation. These data indicate that RNF4-mediated ubiquitination degradation of SUMOylated proteins is a novel regulatory mechanism of p27kip1 dysfunction and CCA tumorigenesis, which provides a potential option for therapeutic intervention of CCA.
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http://dx.doi.org/10.1016/j.yexcr.2022.113295DOI Listing
August 2022

Inhibition of miR-497 Attenuates Oral Submucous Fibrosis by Inhibiting Myofibroblast Transdifferentiation in Buccal Mucosal Fibroblasts.

Oral Health Prev Dent 2022 Jun;20(1):339-348

Purpose: Oral submucous fibrosis (OSF) is a common chronic condition with poor prognosis, and existing therapies for OSF are limited in effectiveness. This study was designed to explore the role of miR-497 in arecoline (AR)-induced OSF.

Materials And Methods: After miR-497 was silenced or overexpressed in buccal mucosa fibroblasts (BMFs), different concentrations of AR (5-200 μg/ml) were applied to incubate BMFs, and 50 μg/ml of AR was chosen for subsequent experiments. Thereafter, collagen gel contraction assay was used to detect the contractile capacity of BMFs. Transwell assay and wound healing assay were applied to detect migration and invasiveness of the cells. In addition, immunofluorescence staining, qRT-PCR and western blot were conducted to measure the expression of miR-497, collagen I and α-SMA, as well as the phosphorylation of Smad2 and Smad3.

Results: After successful inhibition or overexpression of miR-497 in AR-induced BMFs, the results showed that miR- 497 inhibition suppressed the contractility, migration and invasiveness of AR-induced BMFs, whereas overexpression of miR-497 produced the opposite. In addition, miR-497 inhibition down-regulated the expression level of collagen I and α-SMA in AR-exposed BMFs. Furthermore, TGF-β1 expression, Smad2 and Smad3 phosphorylation were also repressed in AR-induced BMFs after miR-497 inhibition. Correspondingly, overexpression of miR-497 reversed the expression of the aforementioned proteins.

Conclusion: miR-497 inhibition may attenuate OSF by inhibiting myofibroblast transdifferentiation in BMFs via the TGF-β1/Smads signaling pathway, indicating that miR-497 might represent an underlying target for treating OSF.
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http://dx.doi.org/10.3290/j.ohpd.b3276183DOI Listing
June 2022

The Application of Two-Stage Operation for High-Risk Patients with Oesophageal Cancer Following Gastrectomy.

J Gastrointest Surg 2022 Aug 1. Epub 2022 Aug 1.

Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Hubei Province, Jiefang Road 238, Wuhan City, 430060, People's Republic of China.

Background: Oesophageal replacement by colonic interposition remains a major challenge due to its complexity and high incidence of complications; here we applied the two-stage operation strategy to oesophageal replacement by colonic interposition in high-risk oesophageal cancer patients following gastrectomy.

Methods: We performed a retrospective analysis on the data of patients with a history of distal gastrectomy who underwent one-stage and two-stage oesophageal replacement by colonic interposition from February 2012 to February 2020, and explored the relationship between the staging strategy and postoperative outcomes.

Results: The clinical data of 93 patients were collected and analysed. There were no significant differences in the patients' characteristics between the two groups (all p > 0.05), except for comorbidities and Charlson Comorbidity Index (all p < 0.05). The Clavien-Dindo score between the two groups was also not significantly different (p > 0.05). The logistic regression models revealed that patients who had received preoperative therapy had a higher Clavien-Dindo score (p < 0.05), but the stage strategy did not (p > 0.05).

Conclusions: The two-stage operation is feasible in high-risk patients who need to undergo colonic interposition for oesophageal replacement. At the same time, it lowers the technical threshold of colonic interposition for oesophageal replacement, increasing this surgical technique's acceptability.
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http://dx.doi.org/10.1007/s11605-022-05414-wDOI Listing
August 2022

Large-scale genome-wide association study of coronary artery disease in genetically diverse populations.

Nat Med 2022 Aug 1;28(8):1679-1692. Epub 2022 Aug 1.

Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.

We report a genome-wide association study (GWAS) of coronary artery disease (CAD) incorporating nearly a quarter of a million cases, in which existing studies are integrated with data from cohorts of white, Black and Hispanic individuals from the Million Veteran Program. We document near equivalent heritability of CAD across multiple ancestral groups, identify 95 novel loci, including nine on the X chromosome, detect eight loci of genome-wide significance in Black and Hispanic individuals, and demonstrate that two common haplotypes at the 9p21 locus are responsible for risk stratification in all populations except those of African origin, in which these haplotypes are virtually absent. Moreover, in the largest GWAS for angiographically derived coronary atherosclerosis performed to date, we find 15 loci of genome-wide significance that robustly overlap with established loci for clinical CAD. Phenome-wide association analyses of novel loci and polygenic risk scores (PRSs) augment signals related to insulin resistance, extend pleiotropic associations of these loci to include smoking and family history, and precisely document the markedly reduced transferability of existing PRSs to Black individuals. Downstream integrative analyses reinforce the critical roles of vascular endothelial, fibroblast, and smooth muscle cells in CAD susceptibility, but also point to a shared biology between atherosclerosis and oncogenesis. This study highlights the value of diverse populations in further characterizing the genetic architecture of CAD.
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http://dx.doi.org/10.1038/s41591-022-01891-3DOI Listing
August 2022

Multifunctional theranostic nanoplatform loaded with autophagy inhibitor for enhanced photothermal cancer therapy under mild near-infrared irradiation.

Biomater Adv 2022 Jul 24;138:212919. Epub 2022 May 24.

Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. Electronic address:

Photothermal therapy (PTT) usually causes hyperthermia and damages healthy tissues. Developing a PTT platform with enhanced therapeutic effects and reduced side effects to normal tissues attracts increasing attention. Herein, we developed a multifunctional theranostic nanoplatform using poly(lactic-co-glycolic acid) (PLGA) loaded with near-infrared (NIR) photothermal agent (new indocyanine green IR820), fluorescence imaging agent (ZnCdSe/ZnS quantum dots, QDs) and autophagy inhibitor (chloroquine, CQ). These PLGA/IR820/Fluorescence imaging agent/CQ co-loading nanoparticles (termed PIFC NPs) displayed photothermal effects, enhanced the stability of IR820 in vivo, and enabled QDs to have stable fluorescent signals in vitro and in vivo. The PIFC NPs with particle size around 240 nm aggregated to tumor sites through the high permeability and retention effects of solid tumors. The intracellular delivery of CQ molecules through PIFC NPs significantly attenuated the degradation of autophagic lysosomes in tumor cells and effectively inhibited the autophagy mediated repair of photothermal damaged cells. Under milder NIR irradiation conditions, PIFC NPs exhibited high antitumor effect. By regulating autophagy, PTT can be effectively sensitized, which will provide a new idea for future cancer treatment research.
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http://dx.doi.org/10.1016/j.bioadv.2022.212919DOI Listing
July 2022

Palladium-Catalyzed Three-Component Cross-Coupling of Conjugated Dienes with Indoles Using Ethynylbenziodazolones as Electrophilic Alkynylating Reagents.

Org Lett 2022 Aug 30;24(31):5777-5781. Epub 2022 Jul 30.

School of Chemistry and Chemical Engineering, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.

A palladium-catalyzed regioselective 1,2-alkynyl-carbonalization of conjugated dienes with ethynylbenziodazolone (EBZ) and indoles has been developed for the first time. Various molecules containing alkenyl, alkynyl, and indole groups were readily obtained. Moreover, the resulting products can be applied to various derivatizations. This protocol uses EBZ as an electrophilic alkynylating reagent, avoiding the byproduct of dimerization of alkynes.
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http://dx.doi.org/10.1021/acs.orglett.2c02275DOI Listing
August 2022

The alkynylative difunctionalization of alkenes.

Chemistry 2022 Aug 1. Epub 2022 Aug 1.

Shanghai Jiao Tong University, School of Chemistry and Chemical Engineering, 800 Dongchuan RD. Minhang District, 200240, Shanghai, CHINA.

Given alkynyl group is an important functional unit, a variety of efficient methods have been developed to construct alkynyl-containing compounds. Among them, the alkynylative difunctionalization of alkenes is one of the most straightforward and efficient strategies for preparing these compounds and so has made great progress in recent years, including the catalytic asymmetric manner. However, there is no comprehensive review to summarize these studies. This review is aimed at comprehensively summarizing the alkynylative difunctionalization of alkenes, which is presented in terms of alkynylation-initiated and alkynylation-terminated difunctionalization of alkenes. We hope that this review will help to encourage more researchers to further explore in this field.
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http://dx.doi.org/10.1002/chem.202201519DOI Listing
August 2022

Successful pregnancy via in vitro fertilization in a primary infertile woman with primary lymphoma of the fallopian tube after surgery: A case report and literature review.

Medicine (Baltimore) 2022 Jul 29;101(30):e29353. Epub 2022 Jul 29.

State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

Rationale: Primary extranodal marginal zone B-cell lymphomas of the fallopian tube is extremely rare. It is a great challenge for fertility and gynecology doctors to manage such cases and also fulfil the reproductive demands of these young women.

Patient Concerns: A 30-year-old woman consulted for a 5-year primary infertility.

Diagnosis: According to the Ann Arbor staging system, a stage IE extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue lymphoma was diagnosed for this patient based on tumor pathology, bone marrow biopsy, hysteroscopy and whole-body positron emission tomography imaging. She also had endometriosis based on laparoscopy.

Interventions: The patient underwent a laparoscopic bilateral salpingostomy without additional surgery or radiotherapy and chemotherapy for fertility preservation, and received 5 months of long-acting gonadotropin releasing hormone agonist treatment for endometriosis.

Outcomes: Two years after the surgery, the patient delivered a healthy neonate through in vitro fertilization-embryo transfer procedures. The patient is now 3 years post-op and 1 year post-delivery, long-term follow-up suggested that the patient remained cancer-free up till now.

Lessons: More care should be taken when the newly diagnosed mass is combined with a rather high serum CA-125 level. Although endometriosis and ovarian cancer are more common, lymphoma cannot be ruled out.
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http://dx.doi.org/10.1097/MD.0000000000029353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333483PMC
July 2022

RGS6 suppresses TGF-β-induced epithelial-mesenchymal transition in non-small cell lung cancers via a novel mechanism dependent on its interaction with SMAD4.

Cell Death Dis 2022 Jul 28;13(7):656. Epub 2022 Jul 28.

Soochow University Laboratory of Cancer Molecular Genetics, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215123, China.

Regulator of G-protein signaling 6 (RGS6) is a newly discovered tumor suppressor that has been shown to be protective in development of various cancers such as breast cancer and bladder cancer. But the mechanisms underlying these tumor-suppressing functions of RGS6 are not fully understood. Here, we discover a novel function of RGS6 in suppressing TGF-β-induced epithelial-mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC) cells and in vivo NSCLC metastasis. Using both bioinformatics and experimental tools, we showed that RGS6 was downregulated in lung cancer tissues compared to noncancerous counterparts, and low expression of RGS6 was associated with poor survival of lung cancer patients. Overexpression of RGS6 suppressed TGF-β-induced EMT in vitro and TGF-β-promoted metastasis in vivo, by impairing gene expression of downstream effectors induced by the canonical TGF-β-SMAD signaling. The ability of RGS6 to suppress TGF-β-SMAD-mediated gene expression relied on its binding to SMAD4 to prevent complex formation between SMAD4 and SMAD2/3, but independent of its regulation of the G-protein signaling. Interaction between RGS6 and SMAD4 caused less nuclear entry of p-SMAD3 and SMAD4, resulting in inefficient SMAD3-mediated gene expression. Taken together, our findings reveal a novel and noncanonical role of RGS6 in regulation of TGF-β-induced EMT and metastasis of NSCLC and identify RGS6 as a prognostic marker and a potential novel target for NSCLC therapy.
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http://dx.doi.org/10.1038/s41419-022-05093-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334288PMC
July 2022

The Use of Thiocyanate Formulations to Create Manganese Porphyrin Antioxidants That Supplement Innate Immunity.

Antioxidants (Basel) 2022 Jun 25;11(7). Epub 2022 Jun 25.

Harmony Consulting, San Clemente, CA 92672, USA.

The innate immune response to infection results in inflammation and oxidative damage, creating a paradox where most anti-inflammatory and antioxidant therapies can further suppress an already inadequate immune response. We have previously reported the beneficial effects of the exogenous supplementation of innate immunity with small pseudohalide thiocyanate (SCN) in a mouse model of a cystic fibrosis (CF) lung infection and inflammation. The object of this study was to evaluate the use of SCN as a counter anion for cationic manganese porphyrin (MnP) catalytic antioxidants, which could increase the parent compound's antioxidant spectrum against hypohalous acids while supplementing innate immunity. The antioxidant activities of the parent compound were examined, as its chloride salt was compared with the SCN-anion exchanged compound, (MnP(SCN) versus MnP(Cl)). We measured the superoxide dismutase activity spectrophotometrically and performed hydrogen peroxide scavenging using oxygen and hydrogen peroxide electrodes. Peroxidase activity was measured using an amplex red assay. The inhibition of lipid peroxidation was assessed using a thiobarbituric acid reactive species (TBARS) assay. The effects of the MnP compounds on macrophage phagocytosis were assessed by flow cytometry. The abilities of the MnP(Cl) formulations to protect human bronchiolar epithelial cells against hypochlorite (HOCl) and glycine chloramine versus their MnP(SCN) formulations were assessed using a cell viability assay. We found that anions exchanging out the chloride for SCN improved the cellular bioavailability but did not adversely affect the cell viability or phagocytosis and that they switched hydrogen-peroxide scavenging from a dismutation reaction to a peroxidase reaction. In addition, the SCN formulations improved the ability of MnPs to protect human bronchiolar epithelial cells against hypochlorous acid (HOCl) and glycine chloramine toxicity. These novel types of antioxidants may be more beneficial in treating lung disease that is associated with chronic infections or acute infectious exacerbations.
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http://dx.doi.org/10.3390/antiox11071252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311894PMC
June 2022

Privacy-preserving state estimation with unreliable channels.

ISA Trans 2022 Jun 22. Epub 2022 Jun 22.

Department of Automation, Tsinghua University, Beijing 100084, PR China. Electronic address:

A co-design problem of privacy-preserving encoding and filtering is concerned in this paper. A remote legal user estimates states of a dynamic system by the received innovation messages. However, the communication channel is neither reliable nor secure. The messages may be missing during the transmission and have a risk of being intercepted by an eavesdropper. Therefore, in this work, an encoding scheme together with an MMSE estimation algorithm are designed for preserving information privacy and meanwhile guaranteeing estimation performance. We introduce a novel encoding approach using a weighted innovation with a public key to achieve privacy security as well as low computational expense. A filtering algorithm is designed under such an encoding mechanism. And the performance of the filter and the encoding method is analyzed. The feasibility of the encoding approach and the filtering algorithm is illustrated through numerical examples of an unstable system and a stable ballistic roll rate estimation system.
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http://dx.doi.org/10.1016/j.isatra.2022.05.035DOI Listing
June 2022

PMS2 Expression With Combination of PD-L1 and TILs for Predicting Survival of Esophageal Squamous Cell Carcinoma.

Front Oncol 2022 5;12:897527. Epub 2022 Jul 5.

Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: DNA mismatch repair (MMR) deficiency (dMMR) has been recognized as an important biomarker for immunotherapy in esophageal squamous cell carcinoma (ESCC), along with programmed death ligand 1 (PD-L1) expression and/or tumor-infiltrated lymphocytes (TILs). However, in ESCC, MMR protein assessment has not been well studied at present.

Methods: A total of 484 ESCC tissues treated between 2007 and 2010, in our hospital, were enrolled. Immunohistochemical expression of MLH1, MSH2, MSH6, PMS2, and PD-L1 on tissue microarray specimens and clinicopathological features, including TILs, were analyzed retrospectively.

Results: Out of the 484 studied cases, loss of MLH1, MSH2, MSH6, and PMS2 expression were found in 6.8%, 2.1%, 8.7%, and 4.8% patients, respectively. dMMR was found in 65 patients, 37 cases involved in one MMR protein, 17 cases involved in two proteins, 7 cases involved in three proteins, and 4 cases involved in four proteins. There was no significant survival difference between pMMR (MMR-proficient) and dMMR patients (>0.05). However, 224 patients with low PMS2 expression had better DFS and OS than 260 patients with high PMS2 expression (=0.006 for DFS and 0.008 for OS), which was identified as an independent prognostic factor in multivariate analyses. Positive PD-L1 expression was detected in 341 (70.5%) samples. In stage I-II disease, patients with PD-L1 expression had better DFS and OS than those without PD-L1 expression(<0.05), which was not found in stage III-IV disease. With the ITWG system, 40.1% of cases were classified as high TILs. Patients in the high-TILs group tended to have better DFS (=0.055) and OS (=0.070) than those in the low-TILs group and the differences were statistically significant in pMMR, high MSH6, or PMS2 expression cases (<0.05). Also, high PMS2 expression patients with both PD-L1 expression and high TILs, had similar DFS and OS compared with low PMS2 expression patients (>0.05), which were much better than other high PMS2 expression patients.

Conclusion: The expression level of MMR proteins could also be used as a prognostic factor in ESCC and PMS2 expression outperformed other MMR proteins for predicting survival. The combination of PD-L1 expression and TILs may lead to more efficient risk stratification of ESCC.
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http://dx.doi.org/10.3389/fonc.2022.897527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294642PMC
July 2022

EGCG exposure during pregnancy affects uterine histomorphology in F1 female mice and the underlying mechanisms.

Food Chem Toxicol 2022 Sep 19;167:113306. Epub 2022 Jul 19.

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, PR China. Electronic address:

Although epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been shown to have many benefits, the effect of EGCG exposure in utero on adult uterine development is unclear. In this study, pregnant C57BL/6 mice were exposed to 1 mg/kg body weight (bw) EGCG dissolved in drinking water from gestational days 0.5-16.5. A significant decrease in uterine weight was observed in the adult female mice, accompanied by uterine atrophy, inflammation, and fibrosis in the endometrium. Uterine atrophy was attributed to the thinning of the endometrial stromal layer and a significant reduction in endometrial cell proliferation. The expression levels of related proteins in the NF-κB and RAF/MEK/ERK signaling pathways were significantly increased, which might be responsible for the occurrence of inflammation. Activation of the transforming growth factor beta (TGF-β1)/Smad signaling pathway might be involved in the development of endometrial fibrosis. The changes in the expression of estrogen receptor α, β (ERα, ERβ), progesterone receptor (PGR), and androgen receptor (AR) might lead to changes in the aforementioned signaling pathways. The promoter region methylation level of Esr2 was increased, and the expression of DNMT3A was evaluated. Our study indicates a risk of EGCG intake during pregnancy affecting uterine development in offspring.
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http://dx.doi.org/10.1016/j.fct.2022.113306DOI Listing
September 2022

Acetylation of p62 regulates base excision repair through interaction with APE1.

Cell Rep 2022 Jul;40(3):111116

Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address:

p62, a well-known adaptor of autophagy, plays multiple functions in response to various stresses. Here, we report a function for p62 in base excision repair that is distinct from its known functions. Loss of p62 impairs base excision repair capacity and increases the sensitivity of cancer cells to alkylating and oxidizing agents. In response to alkylative and oxidative damage, p62 is accumulated in the nucleus,acetylated by hMOF,and deacetylated by SIRT7, and acetylated p62 is recruited to chromatin. The chromatin-enriched p62 directly interacts with APE1, a key enzyme of the BER pathway, and promotes its endonuclease activity, which facilitates BER and cell survival. Collectively, our findings demonstrate that p62 is a regulator of BER and provide further rationale for targeting p62 as a cancer therapeutic strategy.
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http://dx.doi.org/10.1016/j.celrep.2022.111116DOI Listing
July 2022

Ferromagnetic Vortex Iron Oxide Nanorings Modified with Integrin 1 Antibody for Targeted MRI Tracking of Human Mesenchymal Stem Cells.

J Biomed Nanotechnol 2022 Apr;18(4):1044-1051

Chinese Academy of Sciences Key Laboratory of Nano-Bio Interface, Division of Nano Biomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.

Mesenchymal stem cells (MSCs) have demonstrated great potential for tissue engineering and regenerative medicine applications. Noninvasive and real-term tracking of transplanted MSCs is crucial for studying the distribution and migration of MSCs, and their role in tissue injury repair. This study reports on the use of ferrimagnetic vortex iron oxide (FVIO) nanorings modified with anti-human integrin 1 for specific recognition and magnetic resonance imaging (MRI) tracking of human MSCs (hMSCs). Integrin 1 is highly expressed at all stem cell proliferation and differentiation stages. Therefore, the anti-integrin 1 antibody (Ab) introduced in FVIO targets integrin 1, thus enabling FVIO to target stem cells at any stage. This is unlike the traditional MRI-based monitoring of transplanted stem cells, which usually requires pre-labeling the stem cells with tracers before injection. Because of the ability to recognize hMSCs, the Ab-modified FVIO nanotracers (FVIO-Ab) have the advantage of not requiring pre-labeling before stem cell transplantation. Furthermore, the FVIO-Ab nanotracers have high T₂ contrast resulting from the unique magnetic properties of FVIO which can improve the MRI tracking efficiency of stem cells. This work may provide a new way for stem cell labeling and MRI tracking, thus reducing the risks associated with stem cell transplantation and promoting clinical translation.
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http://dx.doi.org/10.1166/jbn.2022.3319DOI Listing
April 2022

Proteomic analysis reveals key differences between squamous cell carcinomas and adenocarcinomas across multiple tissues.

Nat Commun 2022 07 18;13(1):4167. Epub 2022 Jul 18.

Department of Pathology, Zhongshan Hospital, State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Fudan University, Shanghai, China.

Squamous cell carcinoma (SCC) and adenocarcinoma (AC) are two main histological subtypes of solid cancer; however, SCCs are derived from different organs with similar morphologies, and it is challenging to distinguish the origin of metastatic SCCs. Here we report a deep proteomic analysis of 333 SCCs of 17 organs and 69 ACs of 7 organs. Proteomic comparison between SCCs and ACs identifies distinguishable pivotal pathways and molecules in those pathways play consistent adverse or opposite prognostic roles in ACs and SCCs. A comparison between common and rare SCCs highlights lipid metabolism may reinforce the malignancy of rare SCCs. Proteomic clusters reveal anatomical features, and kinase-transcription factor networks indicate differential SCC characteristics, while immune subtyping reveals diverse tumor microenvironments across and within diagnoses and identified potential druggable targets. Furthermore, tumor-specific proteins provide candidates with differentially diagnostic values. This proteomics architecture represents a public resource for researchers seeking a better understanding of SCCs and ACs.
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http://dx.doi.org/10.1038/s41467-022-31719-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293992PMC
July 2022

Nuclear TIGAR mediates an epigenetic and metabolic autoregulatory loop NRF2 in cancer therapeutic resistance.

Acta Pharm Sin B 2022 Apr 21;12(4):1871-1884. Epub 2021 Oct 21.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

Metabolic and epigenetic reprogramming play important roles in cancer therapeutic resistance. However, their interplays are poorly understood. We report here that elevated TIGAR (TP53-induced glycolysis and apoptosis regulator), an antioxidant and glucose metabolic regulator and a target of oncogenic histone methyltransferase NSD2 (nuclear receptor binding SET domain protein 2), is mainly localized in the nucleus of therapeutic resistant tumor cells where it stimulates NSD2 expression and elevates global H3K36me2 mark. Mechanistically, TIGAR directly interacts with the antioxidant master regulator NRF2 and facilitates chromatin recruitment of NRF2, H3K4me3 methylase MLL1 and elongating Pol-II to stimulate the expression of both new (NSD2) and established (, and ) targets of , independent of its enzymatic activity. Nuclear TIGAR confers cancer cell resistance to chemotherapy and hormonal therapy and in tumors through effective maintenance of redox homeostasis. In addition, nuclear accumulation of TIGAR is positively associated with NSD2 expression in clinical tumors and strongly correlated with poor survival. These findings define a nuclear TIGAR-mediated epigenetic autoregulatory loop in redox rebalance for tumor therapeutic resistance.
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http://dx.doi.org/10.1016/j.apsb.2021.10.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279715PMC
April 2022

How Does the Social Support Influence Junior College Students' Occupational Identity in Pre-school Education?

Front Psychol 2022 30;13:884606. Epub 2022 Jun 30.

School of Education, Wenzhou University, Wenzhou, China.

Objective: This study aimed to investigate the multiple mediating effects of achievement motivation and subjective wellbeing between social support and individual occupational identity.

Methods: Questionnaire method was used in this study. 565 junior college students majoring in pre-school education were tested by social support scale, achievement motivation scale, subjective wellbeing scale, and occupational identity scale.

Results: (1) There isn't significant relationship between perceptions of social support and individual occupational identity. (2) Achievement motivation and subjective wellbeing individually play a mediating role between social support and individual occupational identity. (3) Achievement motivation and subjective wellbeing play a chain mediating effect between elf-efficacy and individual occupational identity.

Conclusion: Social support can indirectly predict professional identity of pre-school "would-be teachers" through the mediating effect of achievement motivation, subjective wellbeing and the chain mediating effect of achievement motivation and subjective wellbeing.
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http://dx.doi.org/10.3389/fpsyg.2022.884606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280683PMC
June 2022

Study on pharmacokinetic interactions between SHR2554 and itraconazole in healthy subjects: A single-center, open-label phase I trial.

Cancer Med 2022 Jul 16. Epub 2022 Jul 16.

Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China.

Background: SHR2554, a novel oral Enhancer of Zeste Homolog 2 inhibitor, shows broad-spectrum anti-tumor efficacy in preclinical studies. As SHR2554 is mainly metabolized by CYP3A4, it is helpful to conduct research on the effects of itraconazole, a strong inhibitor of CYP3A4-metabolizing enzymes, on the pharmacokinetic characteristics and safety of SHR2554.

Methods: We conducted a single-center, open-label pharmacokinetic study of itraconazole on SHR2554 in 18 healthy Chinese subjects. Subjects were orally administrated SHR2554 50 mg on Day 1, itraconazole 200 mg Quaque Die (QD) from Days 4 to 7, SHR2554 50 mg co-administrated with itraconazole 200 mg on Day 8, and itraconazole 200 mg QD from Days 9 to 12. Then, 4 ml of venous blood was collected at predetermined time points. Plasma SHR2554 concentrations were analyzed using a validated high-performance liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters were calculated using Phoenix WinNonlin v8.1.

Results: The C of SHR2554 alone and in combination was 10.197 ± 7.0262 ng·ml versus 70.538 ± 25.0219 ng·ml , AUC was 50.99 ± 19.358 h·ng·ml versus 641.53 ± 319.538 h·ng·ml , and AUC was 28.70 ± 18.913 h·ng·ml versus 612.13 ± 315.720 h·ng·ml . Co-administration of SHR2554 and itraconazole caused 7.73-, 12.47-, and 23.75-fold adjusted geometric mean ratios increases in SHR2554 C , AUC and AUC respectively. The co-administration regimen was well tolerated and had a good safety profile.

Conclusions: Compared with a single dose of SHR2554 50 mg, the exposure of SHR2554 in vivo was significantly affected by the combined administration of itraconazole.
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http://dx.doi.org/10.1002/cam4.5028DOI Listing
July 2022

Single-cell transcriptomic landscape of the sheep rumen provides insights into physiological programming development and adaptation of digestive strategies.

Zool Res 2022 Jul;43(4):634-647

School of Ecology and Environment, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China. E-mail:

As an important evolutionary innovation and unique organ, the rumen has played a crucial role in ruminant adaptation to complex ecological environments. However, the cellular basis of its complex morphology and function remains largely unknown. In this study, we identified eight major cell types from seven representative prenatal and postnatal rumen samples using ~56 600 single-cell transcriptomes. We captured the dynamic changes and high heterogeneity in cellular and molecular profiles before, during, and after the appearance of keratinized stratified squamous epithelium with neatly arranged papillae and functional maturity. Basal cells, keratinocytes, differentiating keratinocytes, terminally differentiated keratinocytes, and special spinous cells provided the cellular basis for rumen epithelium formation. Notably, we obtained clear evidence of two keratinization processes involved in early papillogenesis and papillae keratinization and identified as a potential marker gene. Importantly, enriched stratum spinosum cells played crucial roles in volatile fatty acid (VFA) metabolism and immune response. Our results provide a comprehensive transcriptional landscape of rumen development at single-cell resolution, as well as valuable insight into the interactions between dietary metabolism and the rumen.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2022.086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9336438PMC
July 2022

Transcriptional Proposition for Uniquely Developed Protocorm Flowering in Three Orchid Species: Resources for Innovative Breeding.

Front Plant Sci 2022 28;13:942591. Epub 2022 Jun 28.

Key Laboratory of National Forestry and Grassland Administration for Orchid Conservation and Utilization at College of Landscape Architecture, Fujian Agriculture and Forestry University, Fuzhou, China.

During orchid seed culture, seeds germinate as protocorms, and protocorms normally develop into plant with leaves and roots. Orchids require many years of vegetative development for flowering. However, under a certain combination of growth cultures, we observed that protocorms can directly flower without leaves and roots. Therefore, we performed comparative transcriptome analysis to identify the different transcriptional regulators of two types of protocorms of , , and . Zinc finger, MYB, AP2, and bHLH were the most abundant transcription factor (TF) families in the transcriptome. Weighted gene coexpression network analysis (WGCNA) was performed to identify hub genes related to leaf and flower development. The key hubs included , , , , , , , , , , , and . The hub genes were further validated through statistical tools to propose the roles of key TFs. Therefore, this study initiates to answer that why there is no leaf initiation and root development and how can protocorm bypass the vegetative phase to flower? The outcomes can direct future research on short-span flowering in orchids through protocorms.
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http://dx.doi.org/10.3389/fpls.2022.942591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275812PMC
June 2022

Induction of Trained Immunity Protects Neonatal Mice Against Microbial Sepsis by Boosting Both the Inflammatory Response and Antimicrobial Activity.

J Inflamm Res 2022 7;15:3829-3845. Epub 2022 Jul 7.

Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, People's Republic of China.

Background: Neonates are susceptible to a wide range of microbial infection and at a high risk to develop severe sepsis and septic shock. Emerged evidence has shown that induction of trained immunity triggers a much stronger inflammatory response in adult monocytes/macrophages, thereby conferring protection against microbial infection.

Methods: This study was carried out to examine whether trained immunity is inducible and exerts its protection against microbial sepsis in neonates.

Results: Induction of trained immunity by Bacillus Calmette-Guerin (BCG) plus bacterial lipoprotein (BLP) protected neonatal mice against cecal slurry peritonitis-induced polymicrobial sepsis, and this protection is associated with elevated circulating inflammatory cytokines, increased neutrophil recruitment, and accelerated bacterial clearance. In vitro stimulation of neonatal murine macrophages with BCG+BLP augmented both inflammatory response and antimicrobial activity. Notably, BCG+BLP stimulation resulted in epigenetic remodeling characterized by histone modifications with enhanced H3K4me3, H3K27Ac, and suppressed H3K9me3 at the promoters of the targeted inflammatory and antimicrobial genes. Critically, BCG+BLP stimulation led to a shift in cellular metabolism with increased glycolysis, which is the prerequisite for subsequent BCG+BLP-triggered epigenetic reprogramming and augmented inflammatory response and antimicrobial capacity.

Conclusion: These results illustrate that BCG+BLP induces trained immunity in neonates, thereby protecting against microbial infection by boosting both inflammatory and antimicrobial responses.
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http://dx.doi.org/10.2147/JIR.S363995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273902PMC
July 2022
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