CRKL but not CRKII contributes to hemin-induced erythroid differentiation of CML.

Destruction of erythropoiesis process leads to various diseases, including thrombocytopenia, anaemia, and leukaemia. miR-429-CT10 regulation of kinase-like (CRKL) axis involved in development, progression and metastasis of cancers. However, the exact role of miR-429-CRKL axis in leukaemic cell differentiation are still unknown. The current work aimed to uncover the effect of miR-429-CRKL axis on erythropoiesis. In the present study, CRKL upregulation was negatively correlated with miR-429 downregulation in both chronic myeloid leukaemia (CML) patient and CR patient samples. Moreover, CRKL expression level was significantly decreased while miR-429 expression level was increased during the erythroid differentiation of K562 cells following hemin treatment. Functional investigations revealed that overexpression and knockdown of CRKL was remarkably effective in suppressing and promoting hemin-induced erythroid differentiation of K562 cells, whereas, miR-429 exhibited opposite effects to CRKL. Mechanistically, miR-429 regulates erythroid differentiation of K562 cells by downregulating CRKL via selectively targeting CRKL-3'-untranslated region (UTR) through Raf/MEK/ERK pathway. Conversely, CRKII had no effect on erythroid differentiation of K562 cells. Taken together, our data demonstrated that CRKL (but not CRKII) and miR-429 contribute to development, progression and erythropoiesis of CML, miR-429-CRKL axis regulates erythropoiesis of K562 cells via Raf/MEK/ERK pathway, providing novel insights into effective diagnosis and therapy for CML patients.

First Insight into Fetal Exposure to Legacy and Emerging Plasticizers Revealed by Infant Hair and Meconium: Occurrence, Biotransformation, and Accumulation.

Epidemiological studies have demonstrated the embryonic and developmental toxicity of plasticizers. Thus, understanding the in utero biotransformation and accumulation of plasticizers is essential to assessing their fate and potential toxicity in early life. In the present study, 311 infant hair samples and 271 paired meconium samples were collected at birth in Guangzhou, China, to characterize fetal exposure to legacy and emerging plasticizers and their metabolites. Results showed that most of the target plasticizers were detected in infant hair, with medians of 9.30, 27.6, and 0.145 ng/g for phthalate esters (PAEs), organic phosphate ester (OPEs), and alternative plasticizers (APs), and 1.44, 0.313, and 0.066 ng/g for the metabolites of PAEs, OPEs, and APs, respectively. Positive correlations between plasticizers and their corresponding primary metabolites, as well as correlations among the oxidative metabolites of bis(2-ethylhexyl) phthalate (DEHP) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), were observed, indicating that infant hair retained the major phase-I metabolism of the target plasticizers. While no positive correlations were found in parent compounds or their primary metabolites between paired infant hair and meconium, significant positive correlations were observed among secondary oxidative metabolites of DEHP and DINCH in hair and meconium, suggesting that the primary metabolites in meconium come from hydrolysis of plasticizers in the fetus but most of the oxidative metabolites come from maternal-fetal transmission. The parent compound/metabolite ratios in infant hair showed a decreasing trend across pregnancy, suggesting in utero accumulation and deposition of plasticizers. To the best of our knowledge, this study is the first to report in utero exposure to both parent compounds and metabolites of plasticizers by using paired infant hair and meconium as noninvasive biomonitoring matrices and provides novel insights into the fetal biotransformation and accumulation of plasticizers across pregnancy.

Network pharmacology prediction to discover the potential pharmacological action mechanism of Rhizoma Dioscoreae for liver regeneration.

Improving liver regeneration (LR) remains a medical issue, and there is currently a lack of safe and effective drugs for LR. Rhizoma Dioscoreae (SanYak, SY) is a traditional Chinese medicine. However, the underlying action mechanism of SY treatment for LR is yet to be fully elucidated. To explore the mechanism by which SY affects LR, we have conducted a series of methods for network pharmacological analysis, molecular docking, and in vivo experimental validation in mice. Overall, 9 compounds and 30 predicted target genes of SY were found to be associated with the therapeutic effects of LR. Compared with the model group, hematoxylin and eosin staining revealed that the mice with preoperative drug intervention possessed fewer postoperative hepatocyte bubbles and relatively regular morphology. Furthermore, the serum alanine transaminase and aspartate aminotransferase levels were reduced, immunohistochemistry revealed elevated proliferating cell nuclear antigen positivity rate, and Western blotting demonstrated that the phospho-protein kinase B (AKT)/AKT ratio was downregulated and that vascular endothelial growth factor A (VEGFA) expression levels were upregulated. This study explored dioscin, the main active ingredient of SY, and its potential therapeutic effects on LR. It repairs damaged liver following surgery and promotes liver cell proliferation. The action mechanism comprises reducing AKT phosphorylation levels and upregulating VEGFA expression levels. Thus, this study provides a new direction for further research on the mechanism of SY promoting LR.

Electrochemical chemoselective hydrogenation of 1,4-enediones with HFIP as the hydrogen donor: scalable access to 1,4-diketones.

A straightforward electrochemical protocol for efficient hydrogenation of unsaturated CC bonds has been reported in an undivided cell. A series of versatile 1,4-diketones are smoothly generated under metal-free and external-reductant-free electrolytic conditions. Moreover, the tolerance of various functional groups and decagram-scale experiments have shown the practicability and potential applications of this methodology. Moreover, a range of heterocyclic compounds were easily prepared through follow-up procedures of 1,4-diketones.

Tissue-specific and stereoselective accumulation of Dechlorane Plus isomers in two predator fish in a laboratory feeding study.

The tissue-specific bioaccumulation of Dechlorane Plus (DP) isomers was investigated in two predator fish species (redtail catfish, RF; and oscar fish, OF) that were feeding on tiger barb (TB), which was exposed to syn-DP and anti-DP isomers. The biotransformation potential of DP isomers was examined by in vitro metabolism using fish liver microsomes. No difference in accumulation behaviors of DP isomers was observed between RF and OF, and the accumulation of both syn- and anti-DP isomers exhibiting a linear increase trend with the exposure time in all fish tissues. The assimilation efficiencies and depuration rates for syn-DP and anti-DP were determined to be the highest in the liver. Biomagnification factors (BMFs) for both syn-DP and anti-DP were higher than one in the serum and gastrointestinal tract of fish, whereas were less than one in the other tissues. The wet-weight concentrations of DP isomers in tissues were significantly correlated with the lipid contents in both fish species, indicating that the tissue distribution of DP isomers occurred through passive diffusion to the lipid compartments in vivo. Tissue-specific compositions of DP isomers were observed, with anti-DP selectively accumulating in the liver, gonad, serum, and gills, whilst syn-DP in the carcass and GI tract. However, after being normalized of all tissues, the fish showed no selective accumulation of DP isomers during the exposure period, and selective accumulation of syn-DP was observed during the depuration period. No potential DP metabolites were detected in the fish tissues and in vitro metabolism systems. The main cause of this stereoselective DP isomer accumulation could have been the selective excretion of anti-DP isomer through the fish feces.

Isolation and Anticancer Progression Evaluation of the Chemical Constituents from Bridelia balansae Tutcher.

The dichloromethane extract of the roots of Bridelia balansae Tutcher (Phyllanthaceae) was found to show potential anticancer activity against HCT116 colorectal cancer cell. Our bioassay-guided phytochemical investigation of the roots of B. balansae led to the identification of 14 compounds including seven lignans (1-7), three phenylbenzene derivatives (8-10), two flavanone (11-12), and two triterpenoids (13-14). Among them, 4'-demethyl-4-deoxypodophyllotoxin (1) is the first aryltetralin lignan compound identified from this plant species. In addition, the stereochemistry of 1 was validated by X-ray crystallography for the first time, and its distinguished cytotoxic effect on HCT116 cells with an IC50 value at 20 nM was induced via an apoptosis induction mechanism. Compound 1 could also significantly decrease the migration rate of HCT116 cells, indicating its potential application against cancer metastasis. The western blot analysis showed that 1 has the potential to inhibit cell proliferation and metastasis. Treatment of 1 resulted in the downregulation of matrix metalloproteinases 2 (MMP2) and p-Akt, while p21 was upregulated. Collectively, the present study on the phytochemical and biological profile of B. balansae has determined the plant as a useful source to produce promising anticancer lead compounds.

Comprehensive phylogenetic analyses of Orchidaceae using nuclear genes and evolutionary insights into epiphytism.

Orchidaceae (with >28,000 orchid species) are one of the two largest plant families, with economically and ecologically important species, and occupy global and diverse niches with primary distribution in rainforests. Among orchids, 70% grow on other plants as epiphytes; epiphytes contribute up to ~50% of the plant diversity in rainforests and provide food and shelter for diverse animals and microbes, thereby contributing to the health of these ecosystems. Orchids account for over two-thirds of vascular epiphytes and provide an excellent model for studying evolution of epiphytism. Extensive phylogenetic studies of Orchidaceae and subgroups have ;been crucial for understanding relationships among many orchid lineages, although some uncertainties remain. For example, in the largest subfamily Epidendroideae with nearly all epiphytic orchids, relationships among some tribes and many subtribes are still controversial, hampering evolutionary analyses of epiphytism. Here we obtained 1,450 low-copy nuclear genes from 610 orchid species, including 431 with newly generated transcriptomes, and used them for the reconstruction of robust Orchidaceae phylogenetic trees with highly supported placements of tribes and subtribes. We also provide generally well-supported phylogenetic placements of 131 genera and 437 species that were not sampled by previous plastid and nuclear phylogenomic studies. Molecular clock analyses estimated the Orchidaceae origin at ~132 million years ago (Ma) and divergences of most subtribes from 52 to 29 Ma. Character reconstruction supports at least 14 parallel origins of epiphytism; one such origin was placed at the most recent common ancestor of ~95% of epiphytic orchids and linked to modern rainforests. Ten occurrences of rapid increase in the diversification rate were detected within Epidendroideae near and after the K-Pg boundary, contributing to ~80% of the Orchidaceae diversity. This study provides a robust and the largest family-wide Orchidaceae nuclear phylogenetic tree thus far and new insights into the evolution of epiphytism in vascular plants.

Clinical experience in laparoscopic treatment of gallbladder perforation.

Aim: We herein present our clinical experience in laparoscopic surgery for gallbladder perforation (GBP). Materials and Methods: Retrospective analysis was performed on the clinical data of 44 patients who diagnosed with GBP from January 2015 to November 2020. Results: The mean age of the 44 patients was 64.0 years and the female-to-male ratio was 20:24. The most common type of GBP was Type II, followed by Type I and Type III (31:9:4). 72.7% of the patients were diagnosed with GBP at the time of surgery. Laparoscopic surgery was performed for 38 (86.4%) patients, with a conversion rate of 13.2%. The mean length of hospital stays was 7.8 days. The mortality and morbidity rates were 2.3% and 11.4%, respectively. Conclusions: Pre-operative diagnosis of GBP is difficult. Laparoscopic surgery is safe, feasible and effective for patients with GBP.

OrchidBase 5.0: updates of the orchid genome knowledgebase.

Containing the largest number of species, the orchid family provides not only materials for studying plant evolution and environmental adaptation, but economically and culturally important ornamental plants for human society. Previously, we collected genome and transcriptome information of Dendrobium catenatum, Phalaenopsis equestris, and Apostasia shenzhenica which belong to two different subfamilies of Orchidaceae, and developed user-friendly tools to explore the orchid genetic sequences in the OrchidBase 4.0. The OrchidBase 4.0 offers the opportunity for plant science community to compare orchid genomes and transcriptomes and retrieve orchid sequences for further study.In the year 2022, two whole-genome sequences of Orchidoideae species, Platanthera zijinensis and Platanthera guangdongensis, were de novo sequenced, assembled and analyzed. In addition, systemic transcriptomes from these two species were also established. Therefore, we included these datasets to develop the new version of OrchidBase 5.0. In addition, three new functions including synteny, gene order, and miRNA information were also developed for orchid genome comparisons and miRNA characterization.OrchidBase 5.0 extended the genetic information to three orchid subfamilies (including five orchid species) and provided new tools for orchid researchers to analyze orchid genomes and transcriptomes. The online resources can be accessed at https://cosbi.ee.ncku.edu.tw/orchidbase5/.

ETV6 Regulates Hemin-Induced Erythroid Differentiation of K562 Cells through Mediating the Raf/MEK/ERK Pathway.

As a member of transcription factor E-Twenty Six (ETS) family, ETS variant 6 (ETV6) plays significant role in hematopoiesis and embryonic development. ETV6 dysexpression also involved in the occurrence, development and progression of cancers and leukemia. In current work, we hypothesized that ETV6 plays a role in erythroid differentiation of chronic myeloid leukemia (CML). We found the protein expression level of ETV6 was significantly upregulated during hemin-induced erythroid differentiation of K562 cells. Moreover, overexpression of ETV6 inhibited erythroid differentiation in hemin-induced K562 cells with decreased numbers of benzidine-positive cells and decreased expression levels of erythroid differentiation specific markers glycophorin (GPA), CD71, hemoglobin A (HBA), α-globin, γ-globin and ε-globin. Conversely, ETV6 knockdown promoted erythroid differentiation in hemin-induced K562 cells. Furthermore, ETV6 expression level slightly positively with the proliferation capacity of K562 cells treated with hemin. Mechanistically, ETV6 overexpression inhibited fibrosarcoma/mitogen activated extracellular signal-regulated kinase/extracellular regulated protein kinase (Raf/MEK/ERK) pathway, ETV6 knockdown activated the Raf/MEK/ERK pathway. Collectively, the current work demonstrates that ETV6 plays an inhibitory role in the regulation of K562 cell erythroid differentiation via Raf/MEK/ERK pathway, it would be a potentially therapeutic target for dyserythropoiesis.

CRKL promotes hepatocarcinoma through enhancing glucose metabolism of cancer cells via activating PI3K/Akt.

Abnormal glucose metabolism may contribute to cancer progression. As a member of the CRK (v-crk sarcoma virus CT10 oncogene homologue) adapter protein family, CRKL (CRK-like) associated with the development and progression of various tumours. However, the exact role and underlying mechanism of CRKL on energy metabolism remain unknown. In this study, we investigated the effect of CRKL on glucose metabolism of hepatocarcinoma cells. CRKL and PI3K were found to be overexpressed in both hepatocarcinoma cells and tissues; meanwhile, CRKL up-regulation was positively correlated with PI3K up-regulation. Functional investigations revealed that CRKL overexpression promoted glucose uptake, lactate production and glycogen synthesis of hepatocarcinoma cells by up-regulating glucose transporters 1 (GLUT1), hexokinase II (HKII) expression and down-regulating glycogen synthase kinase 3ß (GSK3ß) expression. Mechanistically, CRKL promoted glucose metabolism of hepatocarcinoma cells via enhancing the CRKL-PI3K/Akt-GLUT1/HKII-glucose uptake, CRKL-PI3K/Akt-HKII-glucose-lactate production and CRKL-PI3K/Akt-Gsk3ß-glycogen synthesis. We demonstrate CRKL facilitates HCC malignancy via enhancing glucose uptake, lactate production and glycogen synthesis through PI3K/Akt pathway. It provides interesting fundamental clues to CRKL-related carcinogenesis through glucose metabolism and offers novel therapeutic strategies for hepatocarcinoma.

Plastid phylogenomics improves resolution of phylogenetic relationship in the Cheirostylis and Goodyera clades of Goodyerinae (Orchidoideae, Orchidaceae).

Goodyerinae are one of phylogenetically unresolved groups of Orchidaceae. The lack of resolution achieved through the analyses of previous molecular sequences from one or a few markers has long confounded phylogenetic estimation and generic delimitation. Here, we present large-scale phylogenomic data to compare the plastome structure of the two main clades (Goodyera and Cheirostylis) in this subtribe and further adopt two strategies, combining plastid coding sequences and the whole plastome, to investigate phylogenetic relationships. A total of 46 species in 16 genera were sampled, including 39 species in 15 genera sequenced in this study. The plastomes of heterotrophic species are not drastically reduced in overall size, but display a pattern congruent with a loss of photosynthetic function. The plastomes of autotrophic species ranged from 147 to 165 kb and encoded from 132 to 137 genes. Three unusual structural features were detected: a 1.0-kb inversion in the large single-copy region of Goodyera schlechtendaliana; the loss and/or pseudogenization of ndh genes only in two species, Cheirostylis chinensis and C. montana; and the expansion of inverted repeat regions and contraction of small single-copy region in Hetaeria oblongifolia. Phylogenomic analyses provided improved resolution for phylogenetic relationships. All genera were recovered as monophyletic, except for Goodyera and Hetaeria, which were each recovered as non-monophyletic. Nomenclatural changes are needed until the broader sampling and biparental inherited markers. This study provides a phylogenetic framework of Goodyerinae and insight into plastome evolution of Orchidaceae.

Quantum frequency conversion from ultraviolet to visible band through waveguides in a period-poled MgO:LiTaO3 crystal.

In research on hybrid quantum networks, visible or near-infrared frequency conversion has been realized. However, technical limitations mean that there have been few studies involving the ultraviolet band, and unfortunately the wavelengths of the rare-earth or alkaline-earth metal atoms or ions that are used widely in research on quantum information are often in the UV band. Therefore, frequency conversion of the ultraviolet band is very important. In this paper, we demonstrate a quantum frequency conversion between ultraviolet and visible wavelengths by fabricating waveguides in a period-poled MgO:LiTaO3 crystal with a laser writing system, which will be used to connect the wavelength of the dipole transition of 171Yb+ at 369.5 nm and the absorption wavelength of Eu3+ at 580 nm in a solid-state quantum memory system. An external conversion efficiency of 0.85% and a signal-to-noise ratio of greater than 500 are realized with a pumping power of 3.28 W at 1018 nm. Furthermore, we complete frequency conversion of the classical polarization state by means of a symmetric optical setup based on the fabricated waveguide, and the process fidelity of the conversion is (96.13 ± 0.021)%. This converter paves the way for constructing a hybrid quantum network and realizing a quantum router in the ultraviolet band in the future.

Large-tuning-range frequency stabilization of an ultraviolet laser by an open-loop piezoelectric ceramic controlled Fabry-Pérot cavity.

We demonstrate a laser frequency stabilization method with large tuning range to stabilize a UV laser by installing piezoelectric ceramic actuators into a Fabry-Pérot cavity with an ultra-low expansion spacer. To suppress piezoelectric drift, a two-layer symmetrical structure is adopted for the piezoelectric actuator, and a 14.7 GHz tuning range is achieved. The short-term drift of the piezoelectric ceramics caused by temperature and creep is eliminated, and the long-term drift is 0.268 MHz/h when the Fabry-Pérot cavity is sealed in a chamber without a vacuum environment. The long-term frequency drift is mainly caused by stress release and is eliminated by compensating the cavity voltage with an open loop. Without the need for an external reference or a vacuum environment, the laser frequency stabilization system is greatly simplified, and it can be extended to wavelengths ranging from ultraviolet to infrared. Owing to its simplicity, stability, and large tuning range, it is applicable in cold atom and trapped ion experiments.

Super-resolved Imaging of a Single Cold Atom on a Nanosecond Timescale.

In cold atomic systems, fast and high-resolution microscopy of individual atoms is crucial, since it can provide direct information on the dynamics and correlations of the system. Here, we demonstrate nanosecond-scale two-dimensional stroboscopic pictures of a single trapped ion beyond the optical diffraction limit, by combining the main idea of ground-state depletion microscopy with quantum-state transition control in cold atoms. We achieve a spatial resolution up to 175 nm using a NA=0.1 objective in the experiment, which represents a more than tenfold improvement compared with direct fluorescence imaging. To show the potential of this method, we apply it to observe the secular motion of the trapped ion; we demonstrate a temporal resolution up to 50 ns with a displacement detection sensitivity of 10 nm. Our method provides a powerful tool for probing particle positions, momenta, and correlations, as well as their dynamics in cold atomic systems.

Discovery of an Oxidative System for Radical Generation from Csp3-H Bonds: A Synthesis of Functionalized Oxindoles.

A facile and versatile method for generating radicals from Csp3-H bonds under metal-free and organic-peroxide-free conditions was developed. By combining safe persulfate and low-toxic quaternary ammonium salt, a wide variety of Csp3-H compounds including ethers, (hetero)aromatic/aliphatic ketones, alkylbenzenes, alkylheterocycles, cycloalkanes, and haloalkanes were selectively activated to generate the corresponding C-centered radicals, which could be further captured by N-arylacrylamides to deliver the valuable functionalized oxindoles. Good functional group tolerance was demonstrated. The useful polycarbonyl compound and esters were also modified with the strategy. Moreover, the combination can also be applied to the practical coupling between simple haloalkanes and N-hydroxyphthalimide (NHPI).

The potential role of miR-124-3p in tumorigenesis and other related diseases.

MicroRNAs (miRNAs) are a class of single-stranded noncoding and endogenous RNA molecules with a length of 18-25 nucleotides. Previous work has shown that miR-124-3p leads to malignant progression of cancer including cell apoptosis, migration, invasion, drug resistance, and also recovers neural function, affects adipogenic differentiation, facilitates wound healing through control of various target genes. miR-124-3p has been mainly previously characterized as a tumor suppressor regulating tumorigenesis and progression in several cancers, such as hepatocellular carcinoma (HCC), gastric cancer (GC), bladder cancer, ovarian cancer (OC), and leukemia, as a tumor promotor in breast cancer (BC), and it has been also widely studied in a variety of neurological diseases, like Parkinson's disease (PD), dementia and Alzheimer's disease (AD), and cardiovascular diseases, ulcerative colitis (UC), acute respiratory distress syndrome (ARDS). To lay the groundwork for future therapeutic strategies, in this review we mainly focus on the most recent years of literature on the functions of miR-124-3p in related major cancers, as well as its downstream target genes. Although current work as yet provides an incomplete picture, miR-124-3p is still worthy of more attention as a practical and effective clinical biomarker.

A path-based computational model for long non-coding RNA-protein interaction prediction.

Recently, lncRNAs have attracted accumulating attentions because more and more experimental researches have shown lncRNA can play critical roles in many biological processes. Predicting potential interactions between lncRNAs and proteins are key to understand the lncRNAs biological functions. But traditional biological experiments are expensive and time-consuming, network similarity methods provide a powerful solution to computationally predict lncRNA-protein interactions. In this work, a novel path-based lncRNA-protein interaction (PBLPI) prediction model is proposed by integrating protein semantic similarity, lncRNA functional similarity, known human lncRNA-protein interactions, and Gaussian interaction profile kernel similarity. PBLPI model utilizes three interlinked sub-graphs to construct a heterogeneous graph, and then infers potential lncRNA-protein interactions through depth-first search algorithm. Consequently, PBLPI achieves reliable performance in the frameworks of 5-fold cross validation (average AUC is 0.9244 and AUPR is 0.6478). In the case study, we use "Mus musculus" data to further validate the reliability of PBLPI method. It is anticipated that PBLPI would become a useful tool to identify potential lncRNA-protein interactions.

Divergent syntheses of okaramines C, J, L, and S-U.

The total synthesis of six novel okaramines (C, J, L, and S-U) was accomplished with a precise synthesis scheme involving a few steps and a practical yield of 6.7%-23% was obtained. The significance of this study includes the design of a successful and convenient synthesis method for preparation of 3a-hydroxy-pyrrolo[2,3-b]-indole and C-7 prenylated l-tryptophan derivatives using a nucleophilic attack of cyclopropylazetoindoline and an aza-Claisen rearrangement of N-reverse-prenyl tryptophan, respectively.

A Systematic Review on Cloud Storage Mechanisms Concerning e-Healthcare Systems.

As the expenses of medical care administrations rise and medical services experts are becoming rare, it is up to medical services organizations and institutes to consider the implementation of medical Health Information Technology (HIT) innovation frameworks. HIT permits health associations to smooth out their considerable cycles and offer types of assistance in a more productive and financially savvy way. With the rise of Cloud Storage Computing (CSC), an enormous number of associations and undertakings have moved their healthcare data sources to distributed storage. As the information can be mentioned whenever universally, the accessibility of information becomes an urgent need. Nonetheless, outages in cloud storage essentially influence the accessibility level. Like the other basic variables of cloud storage (e.g., reliability quality, performance, security, and protection), availability also directly impacts the data in cloud storage for e-Healthcare systems. In this paper, we systematically review cloud storage mechanisms concerning the healthcare environment. Additionally, in this paper, the state-of-the-art cloud storage mechanisms are critically reviewed for e-Healthcare systems based on their characteristics. In short, this paper summarizes existing literature based on cloud storage and its impact on healthcare, and it likewise helps researchers, medical specialists, and organizations with a solid foundation for future studies in the healthcare environment.