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xDeep-AcPEP: Deep Learning Method for Anticancer Peptide Activity Prediction Based on Convolutional Neural Network and Multitask Learning

Chen J, Cheong HH, Siu SWI

J Chem Inf Model, 2021 Aug 23;61(8):3789-3803.
PMID: 34327990 DOI: 10.1021/acs.jcim.1c00181

Cancer is one of the leading causes of death worldwide. Conventional cancer treatment relies on radiotherapy and chemotherapy, but both methods bring severe side effects to patients, as these therapies not only attack cancer cells but also damage normal cells. Anticancer peptides (ACPs) are a promising alternative as therapeutic agents that are efficient and selective against tumor cells. Here, we propose a deep learning method based on convolutional neural networks to predict biological activity (EC50, LC50, IC50, and LD50) against six tumor cells, including breast, colon, cervix, lung, skin, and prostate. We show that models derived with multitask learning achieve better performance than conventional single-task models. In repeated 5-fold cross validation using the CancerPPD data set, the best models with the applicability domain defined obtain an average mean squared error of 0.1758, Pearson's correlation coefficient of 0.8086, and Kendall's correlation coefficient of 0.6156. As a step toward model interpretability, we infer the contribution of each residue in the sequence to the predicted activity by means of feature importance weights derived from the convolutional layers of the model. The present method, referred to as xDeep-AcPEP, will help to identify effective ACPs in rational peptide design for therapeutic purposes. The data, script files for reproducing the experiments, and the final prediction models can be downloaded from http://github.com/chen709847237/xDeep-AcPEP. The web server to directly access this prediction method is at https://app.cbbio.online/acpep/home.
siRNA Silencing of FpVtg Induces Ovarian Cell Apoptosis in Redtail Prawn, Fenneropenaeus penicillatus

Tan K, Dong Y, Tan K, Lim LS, Waiho K, Chen J, et al.

Mar Biotechnol (NY), 2023 Dec;25(6):1176-1190.
PMID: 38010485 DOI: 10.1007/s10126-023-10269-6

Inadequate gonadal maturation and poor spawning performance increasingly threaten the sustainability of shrimp aquaculture. Unraveling the mechanisms regulating ovarian development and maturation hence is critical to address industry challenges. Vitellogenin (Vtg), a precursor of yolk protein found in the hepatopancreas and ovary of shrimp, plays a key role in facilitating shrimp's oocyte maturation and embryonic development after oviposition. This study found that FpVtg was specifically expressed in F. penicillatus hepatopancreas and ovary. FpVtg was localized predominantly in the oocyte cytoplasm and distributed uniformly in the hepatopancreas tissue. Silencing FpVtg led to apoptosis in both hepatopancreas and ovary tissues. Furthermore, FpVtg depletion upregulated the expression of ovarian peritrophin 1, ovarian peritrophin 2, serine proteinase inhibitor 6, and juvenile hormone esterase-like carboxylesterase 1, while downregulated that of vitellogenin, delta-9 desaturase, and insulin-like receptor. KEGG pathway analysis implicated such as PI3K-AKT signaling, RNA transport, ECM-receptor interaction, hippo signaling, oocyte meiosis, and apoptosis were enriched and involved in ovarian development. These findings have provided insights into the FpVtg's reproductive role and the associated regulatory genes and pathways in F. penicillatus. This knowledge can contribute to establishing strategies to improve the breeding and aquaculture production of F. penicillatus by elucidating its vitellogenesis regulation in redtail prawn and other penaeid species. Further characterization of the implicated pathways and genes will clarify the intricacies underlying ovarian maturation.
microRNAs expression profiles in Schistosoma japonicum of different sex 14 and 28 days post-infection

Ai L, Hu W, Zhang RL, Huang DN, Chen SH, Xu B, et al.

Trop Biomed, 2020 Dec 01;37(4):947-962.
PMID: 33612748 DOI: 10.47665/tb.37.4.947

Different miRNAs are involved in the life cycles of Schistosoma japonicum. The aim of this study was to examine the expression profile of miRNAs in individual S. japonicum of different sex before and after pairing (18 and 24 dpi). The majority of differential expressed miRNAs were highly abundant at 14 dpi, except for sja-miR-125b and sja-miR-3505, in both male and female. Moreover, it was estimated that sja-miR-125b and sja-miR-3505 might be related to laying eggs. sja-miR-2a-5p and sja-miR-3484-5p were expressed at 14 dpi in males and were significantly clustered in DNA topoisomerase III, Rap guanine nucleotide exchange factor 1 and L-serine/L-threonine ammonia-lyase. Target genes of sja-miR-2d-5p, sja-miR-31- 5p and sja-miR-125a, which were expressed at 14 dpi in males but particularly females, were clustered in kelch-like protein 12, fructose-bisphosphate aldolase, class I, and heat shock protein 90 kDa beta. Predicted target genes of sja-miR-3483-3p (expressed at 28 dpi in females but not in males) were clustered in 26S proteasome regulatory subunit N1, ATPdependent RNA helicase DDX17. Predicted target genes of sja-miR-219-5p, which were differentially expressed at 28 dpi in females but particularly males, were clustered in DNA excision repair protein ERCC-6, protein phosphatase 1D, and ATPase family AAA domaincontaining protein 3A/B. Moreover, at 28 dpi, eight miRNAs were significantly up-regulated in females compared to males. The predicted target genes of these miRNAs were significantly clustered in heat shock protein 90 kDa beta, 26S proteasome regulatory subunit N1, and protein arginine N-methyltransferase 1. To sum up, differentially expressed miRNAs may have an essential role and provide necessary information on clarifying this trematode's growth, development, maturation, and infection ability to mammalian hosts in its complex life cycle, and may be helpful for developing new drug targets and vaccine candidates for schistosomiasis.
Viva-Asia Blood and Marrow Transplantation Groups - A Survey of Consortium Activity over a 12-year Period (2000 to 2011)

Tan AM, Ha C, Li CF, Chan GC, Lee V, Tan PL, et al.

Ann Acad Med Singap, 2016 Mar;45(3):106-9.
PMID: 27146463
Fulltext Under-recognized pertussis in adults from Asian countries: a cross-sectional seroprevalence study in Malaysia, Taiwan and Thailand

Koh MT, Liu CS, Chiu CH, Boonsawat W, Watanaveeradej V, Abdullah N, et al.

Epidemiol Infect, 2016 Apr;144(6):1192-200.
PMID: 26468043 DOI: 10.1017/S0950268815002393

Surveillance data on the burden of pertussis in Asian adults are limited. This cross-sectional study evaluated the prevalence of serologically confirmed pertussis in adults with prolonged cough in Malaysia, Taiwan and Thailand. Adults (⩾19 years) with cough lasting for ⩾14 days without other known underlying cause were enrolled from outpatient clinics of seven public and/or private hospitals. Single blood samples for anti-pertussis toxin antibodies (anti-PT IgG) were analysed and economic impact and health-related quality of life (EQ-5D) questionnaires assessed. Sixteen (5·13%) of the 312 chronically coughing adults had serological evidence of pertussis infection within the previous 12 months (anti-PT IgG titre ⩾62·5 IU/ml). Three of them were teachers. Longer duration of cough, paroxysms (75% seroconfirmed, 48% non-seroconfirmed) and breathlessness/chest pain (63% seroconfirmed, 36% non-seroconfirmed) were associated with pertussis (P < 0·04). Of the seroconfirmed patients, the median total direct medical cost per pertussis episode in public hospitals (including physician consultations and/or emergency room visits) was US$13 in Malaysia, US$83 in Taiwan (n = 1) and US$26 in Thailand. The overall median EQ-5D index score of cases was 0·72 (range 0·42-1·00). Pertussis should be considered in the aetiology of adults with a prolonged or paroxysmal cough, and vaccination programmes considered.
Study site in Malaysia: Klinik Kesihatan Seremban, Negeri Sembilan; Primary Care Clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases

Li JF, Dai YT, Lilljebjörn H, Shen SH, Cui BW, Bai L, et al.

Proc Natl Acad Sci U S A, 2018 12 11;115(50):E11711-E11720.
PMID: 30487223 DOI: 10.1073/pnas.1814397115

Most B cell precursor acute lymphoblastic leukemia (BCP ALL) can be classified into known major genetic subtypes, while a substantial proportion of BCP ALL remains poorly characterized in relation to its underlying genomic abnormalities. We therefore initiated a large-scale international study to reanalyze and delineate the transcriptome landscape of 1,223 BCP ALL cases using RNA sequencing. Fourteen BCP ALL gene expression subgroups (G1 to G14) were identified. Apart from extending eight previously described subgroups (G1 to G8 associated with MEF2D fusions, TCF3-PBX1 fusions, ETV6-RUNX1-positive/ETV6-RUNX1-like, DUX4 fusions, ZNF384 fusions, BCR-ABL1/Ph-like, high hyperdiploidy, and KMT2A fusions), we defined six additional gene expression subgroups: G9 was associated with both PAX5 and CRLF2 fusions; G10 and G11 with mutations in PAX5 (p.P80R) and IKZF1 (p.N159Y), respectively; G12 with IGH-CEBPE fusion and mutations in ZEB2 (p.H1038R); and G13 and G14 with TCF3/4-HLF and NUTM1 fusions, respectively. In pediatric BCP ALL, subgroups G2 to G5 and G7 (51 to 65/67 chromosomes) were associated with low-risk, G7 (with ≤50 chromosomes) and G9 were intermediate-risk, whereas G1, G6, and G8 were defined as high-risk subgroups. In adult BCP ALL, G1, G2, G6, and G8 were associated with high risk, while G4, G5, and G7 had relatively favorable outcomes. This large-scale transcriptome sequence analysis of BCP ALL revealed distinct molecular subgroups that reflect discrete pathways of BCP ALL, informing disease classification and prognostic stratification. The combined results strongly advocate that RNA sequencing be introduced into the clinical diagnostic workup of BCP ALL.
Traditional uses, phytochemistry, pharmacology and toxicology of the genus Gynura (Compositae): A comprehensive review

Meng X, Li J, Li M, Wang H, Ren B, Chen J, et al.

J Ethnopharmacol, 2021 Aug 10;276:114145.
PMID: 33932518 DOI: 10.1016/j.jep.2021.114145

ETHNOPHARMACOLOGICAL RELEVANCE: Gynura cass., belonging to the tribe Senecoineae of the family Compositae, contains more than 40 accepted species as annual or perennial herbs, mainly distributed in Asia, Africa and Australia. Among them, 11 species are distributed in China. Many of the Gynura species have been used as traditional herbal medicines for the treatment of diabetes mellitus, rheumatism, eruptive fever, gastric ulcer, bleeding, abscesses, bruises, burning pains, rashes and herpes zoster infection in tropical Asia countries such as China, Thailand, Indonesia, Malaysia, and Vietnam. Some of the species have been used as vegetables, tea beverage or ornamental plants by the local people.
AIM OF THE STUDY: A more comprehensive and in-depth review about the geographical distribution, traditional uses, chemical constituents and pharmacological activities as well as safe and toxicity of Gynura species has been summarized, hoping to provide a scientific basis for rational development and utilization as well as to foster further research of these important medicinal plant resources in the future.
MATERIALS AND METHODS: A review of the literature was performed based on the existing peer-reviewed researches by consulting scientific databases including Web of Science, PubMed, Elsevier, Google Scholar, SciFinder and China National Knowledge Infrastructure.
RESULTS: Many of the Gynura species have been phytochemically studied, which led to the isolation of more than 338 compounds including phenolics, flavonoids, alkaloids, terpenoids, steroids, cerebrosides, aliphatics and other compounds. Pharmacological studies in vitro and in vivo have also confirmed the various bioactive potentials of extracts or pure compounds from many Gynura plants, based on their claimed ethnomedicinal and anecdotal uses, including antioxidant, anti-inflammation, anticancer, antidiabetic, antihypertension, antibacterial and other activities. However, pyrrolizidine alkaloids (PAs) pose a threat to the medication safety and edible security of Gynura plants because of toxicity issues, requiring the need to pay great attention to this phenomenon.
CONCLUSION: The traditional uses, phytochemistry and pharmacology of Gynura species described in this review demonstrated that these plants contain a great number of active constituents and display a diversity of pharmacological activities. However, the mechanism of action, structure-activity relationship, potential synergistic effects and pharmacokinetics of these components need to be further elucidated. Moreover, further detailed research is urgently needed to explain the mechanisms of toxicity induced by PAs. In this respect, effective detoxification strategies need to be worked out, so as to support the safe and reasonable utilization of Gynura plant resources in the future.
The regulation of Cytochrome f by mannose treatment in broccoli and its relationship with programmed cell death in tobacco BY-2 cells

Zhao S, Chen J, Cao S, Wang H, Chen H, Wei Y, et al.

Plant Physiol Biochem, 2024 Mar;208:108480.
PMID: 38437751 DOI: 10.1016/j.plaphy.2024.108480

It is well established that programmed cell death (PCD) occurred in broccoli during postharvest senescence, but no studies have been conducted on the regulation of broccoli cytochrome f by mannose treatment and its relationship with PCD. In this study, we treated broccoli buds with mannose to investigate the changes in color, total chlorophyll content, gene expression related to chlorophyll metabolism, chloroplast structure, and cytochrome f determination during postharvest storage. In addition, to investigate the effect of cytochrome f on PCD, we extracted cytochrome f from broccoli and treated Nicotiana tabacum L. cv Bright Yellow 2 (BY-2) cells with extracted cytochrome f from broccoli at various concentrations. The results showed that cytochrome f can induce PCD in tobacco BY-2 cells, as evidenced by altered cell morphology, nuclear chromatin disintegration, DNA degradation, decreased cell viability, and increased caspase-3-like protease production. Taken together, our study indicated that mannose could effectively delay senescence of postharvest broccoli by inhibiting the expression of gene encoding cytochrome f which could induce PCD.
Fulltext The complete chloroplast genome of Walla Patta, Gyrinops walla (Thymelaeaceae), an agarwood-producing tree species from Sri Lanka

Chen J, Lee SY, Munugoda KD, Mohamed R, Subasinghe SMCUP, Liao W

Mitochondrial DNA B Resour, 2021 May 19;6(6):1699-1701.
PMID: 34104743 DOI: 10.1080/23802359.2021.1926362

Gyrinops walla is an important agarwood-producing tree and threatened species from Sri Lanka. Herein, we assembled and characterized the complete chloroplast (cp) genome of G. walla as a genomic resource for conservation purposes. The 175,130 bp long genome is comprised of 87,376 bp large single-copy (LSC) and 3316 bp small single-copy (SSC) regions, which are separated by two inverted repeat (IR) region, each with a size of 42,291 bp. A total of 140 genes were predicted for the cp genome, which includes 94 protein-coding, 38 tRNA, and eight rRNA genes. Phylogenetic analysis showed that G. walla is fully resolved in a sister position to Aquilaria in the family Thymelaeaceae. The data provided will be useful for study on the molecular phylogenetics and evolution of Thymelaeaceae in the future.
Fulltext The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data

Pastorello G, Trotta C, Canfora E, Chu H, Christianson D, Cheah YW, et al.

Sci Data, 2020 07 09;7(1):225.
PMID: 32647314 DOI: 10.1038/s41597-020-0534-3

The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.
The Extended Polydimensional Immunome Characterization (EPIC) web-based reference and discovery tool for cytometry data

Yeo JG, Wasser M, Kumar P, Pan L, Poh SL, Ally F, et al.

Nat Biotechnol, 2020 06;38(6):679-684.
PMID: 32440006 DOI: 10.1038/s41587-020-0532-1
Fulltext Singapore Genome Variation Project: a haplotype map of three Southeast Asian populations

Teo YY, Sim X, Ong RT, Tan AK, Chen J, Tantoso E, et al.

Genome Res, 2009 Nov;19(11):2154-62.
PMID: 19700652 DOI: 10.1101/gr.095000.109

The Singapore Genome Variation Project (SGVP) provides a publicly available resource of 1.6 million single nucleotide polymorphisms (SNPs) genotyped in 268 individuals from the Chinese, Malay, and Indian population groups in Southeast Asia. This online database catalogs information and summaries on genotype and phased haplotype data, including allele frequencies, assessment of linkage disequilibrium (LD), and recombination rates in a format similar to the International HapMap Project. Here, we introduce this resource and describe the analysis of human genomic variation upon agglomerating data from the HapMap and the Human Genome Diversity Project, providing useful insights into the population structure of the three major population groups in Asia. In addition, this resource also surveyed across the genome for variation in regional patterns of LD between the HapMap and SGVP populations, and for signatures of positive natural selection using two well-established metrics: iHS and XP-EHH. The raw and processed genetic data, together with all population genetic summaries, are publicly available for download and browsing through a web browser modeled with the Generic Genome Browser.
Fulltext Shape Optimization for Additive Manufacturing of Removable Partial Dentures--A New Paradigm for Prosthetic CAD/CAM

Chen J, Ahmad R, Suenaga H, Li W, Sasaki K, Swain M, et al.

PLoS One, 2015;10(7):e0132552.
PMID: 26161878 DOI: 10.1371/journal.pone.0132552

With ever-growing aging population and demand for denture treatments, pressure-induced mucosa lesion and residual ridge resorption remain main sources of clinical complications. Conventional denture design and fabrication are challenged for its labor and experience intensity, urgently necessitating an automatic procedure. This study aims to develop a fully automatic procedure enabling shape optimization and additive manufacturing of removable partial dentures (RPD), to maximize the uniformity of contact pressure distribution on the mucosa, thereby reducing associated clinical complications. A 3D heterogeneous finite element (FE) model was constructed from CT scan, and the critical tissue of mucosa was modeled as a hyperelastic material from in vivo clinical data. A contact shape optimization algorithm was developed based on the bi-directional evolutionary structural optimization (BESO) technique. Both initial and optimized dentures were prototyped by 3D printing technology and evaluated with in vitro tests. Through the optimization, the peak contact pressure was reduced by 70%, and the uniformity was improved by 63%. In vitro tests verified the effectiveness of this procedure, and the hydrostatic pressure induced in the mucosa is well below clinical pressure-pain thresholds (PPT), potentially lessening risk of residual ridge resorption. This proposed computational optimization and additive fabrication procedure provides a novel method for fast denture design and adjustment at low cost, with quantitative guidelines and computer aided design and manufacturing (CAD/CAM) for a specific patient. The integration of digitalized modeling, computational optimization, and free-form fabrication enables more efficient clinical adaptation. The customized optimal denture design is expected to minimize pain/discomfort and potentially reduce long-term residual ridge resorption.
Search for top squark and Higgsino production using diphoton Higgs boson decays

Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, et al.

Phys Rev Lett, 2014 Apr 25;112(16):161802.
PMID: 24815637

Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top quark (the top squark) and the Higgs boson (Higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 fb-1 of proton-proton collision data at s=8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the top squark mass below 360 to 410 GeV, depending on the Higgsino mass.
Search for invisible decays of Higgs bosons in the vector boson fusion and associated ZH production modes

Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, et al.

Eur Phys J C Part Fields, 2014;74(8):2980.
PMID: 25814906

A search for invisible decays of Higgs bosons is performed using the vector boson fusion and associated ZH production modes. In the ZH mode, the Z boson is required to decay to a pair of charged leptons or a [Formula: see text] quark pair. The searches use the 8┬á[Formula: see text] pp collision dataset collected by the CMS detector at the LHC, corresponding to an integrated luminosity of up to 19.7┬á[Formula: see text]. Certain channels include data from 7┬á[Formula: see text] collisions corresponding to an integrated luminosity of 4.9┬á[Formula: see text]. The searches are sensitive to non-standard-model invisible decays of the recently observed Higgs boson, as well as additional Higgs bosons with similar production modes and large invisible branching fractions. In all channels, the observed data are consistent with the expected standard model backgrounds. Limits are set on the production cross section times invisible branching fraction, as a function of the Higgs boson mass, for the vector boson fusion and ZH production modes. By combining all channels, and assuming standard model Higgs boson cross sections and acceptances, the observed (expected) upper limit on the invisible branching fraction at [Formula: see text]┬á[Formula: see text] is found to be 0.58┬á(0.44) at 95┬á% confidence level. We interpret this limit in terms of a Higgs-portal model of dark matter interactions.
Safety and efficacy of endoscopic submucosal dissection of large (≥3 cm) subepithelial tumors located in the cardia

Li J, Tang J, Lua GW, Chen J, Shi X, Liu F, et al.

Surg Endosc, 2017 12;31(12):5183-5191.
PMID: 28597288 DOI: 10.1007/s00464-017-5585-y

BACKGROUND: Upper gastrointestinal subepithelial tumors (SETs) may harbor potential malignancy. Although it is well recognized that large SETs should be resected, the treatment strategy remains controversial. Compared to surgical resection, endoscopic resection has many advantages such as less invasive, shorter hospital stay, lower costs, and better quality of life. However, Endoscopic resection of large SETs in the cardia is challenging. The purpose of this study was to evaluate the safety and efficacy of endoscopic submucosal dissection (ESD) in the treatment of such SETs.
METHODS: A total of 41 patients with large SETs (≥3 cm in diameter) located in the cardia were involved in the study. All patients underwent ESD. Data on therapeutic outcomes and follow-up were collected, for analysis of risk factors of complication rates.
RESULTS: The average tumor size was 4.7 ± 1.7 cm. The average procedure time was 69.3 ± 32.7 min and the average postoperative hospital stay was 3.5 ± 1.1 days. A total of 41 tumors were removed successfully, in which 35 were leiomyomas, three were gastrointestinal stromal tumors, two were lipomas, and one was gastritis cystica profunda. The en bloc resection rate was 90.2%, and was significantly higher for tumors with a round or oval shape (100%) than for those with an irregular shape (75.0%) (P
Fulltext Reversible structure manipulation by tuning carrier concentration in metastable Cu2S

Tao J, Chen J, Li J, Mathurin L, Zheng JC, Li Y, et al.

Proc Natl Acad Sci U S A, 2017 09 12;114(37):9832-9837.
PMID: 28855335 DOI: 10.1073/pnas.1709163114

The optimal functionalities of materials often appear at phase transitions involving simultaneous changes in the electronic structure and the symmetry of the underlying lattice. It is experimentally challenging to disentangle which of the two effects--electronic or structural--is the driving force for the phase transition and to use the mechanism to control material properties. Here we report the concurrent pumping and probing of Cu2S nanoplates using an electron beam to directly manipulate the transition between two phases with distinctly different crystal symmetries and charge-carrier concentrations, and show that the transition is the result of charge generation for one phase and charge depletion for the other. We demonstrate that this manipulation is fully reversible and nonthermal in nature. Our observations reveal a phase-transition pathway in materials, where electron-induced changes in the electronic structure can lead to a macroscopic reconstruction of the crystal structure.
Fulltext Regulation of hepatic insulin signaling and glucose homeostasis by sphingosine kinase 2

Aji G, Huang Y, Ng ML, Wang W, Lan T, Li M, et al.

Proc Natl Acad Sci U S A, 2020 09 29;117(39):24434-24442.
PMID: 32917816 DOI: 10.1073/pnas.2007856117

Sphingolipid dysregulation is often associated with insulin resistance, while the enzymes controlling sphingolipid metabolism are emerging as therapeutic targets for improving insulin sensitivity. We report herein that sphingosine kinase 2 (SphK2), a key enzyme in sphingolipid catabolism, plays a critical role in the regulation of hepatic insulin signaling and glucose homeostasis both in vitro and in vivo. Hepatocyte-specific Sphk2 knockout mice exhibit pronounced insulin resistance and glucose intolerance. Likewise, SphK2-deficient hepatocytes are resistant to insulin-induced activation of the phosphoinositide 3-kinase (PI3K)-Akt-FoxO1 pathway and elevated hepatic glucose production. Mechanistically, SphK2 deficiency leads to the accumulation of sphingosine that, in turn, suppresses hepatic insulin signaling by inhibiting PI3K activation in hepatocytes. Either reexpressing functional SphK2 or pharmacologically inhibiting sphingosine production restores insulin sensitivity in SphK2-deficient hepatocytes. In conclusion, the current study provides both experimental findings and mechanistic data showing that SphK2 and sphingosine in the liver are critical regulators of insulin sensitivity and glucose homeostasis.
Recent advances in nanomaterials for water protection and monitoring

Das R, Vecitis CD, Schulze A, Cao B, Ismail AF, Lu X, et al.

Chem Soc Rev, 2017 Sep 29.
PMID: 28959815 DOI: 10.1039/c6cs00921b

The efficient handling of wastewater pollutants is a must, since they are continuously defiling limited fresh water resources, seriously affecting the terrestrial, aquatic, and aerial flora and fauna. Our vision is to undertake an exhaustive examination of current research trends with a focus on nanomaterials (NMs) to considerably improve the performance of classical wastewater treatment technologies, e.g. adsorption, catalysis, separation, and disinfection. Additionally, NM-based sensor technologies are considered, since they have been significantly used for monitoring water contaminants. We also suggest future directions to inform investigators of potentially disruptive NM technologies that have to be investigated in more detail. The fate and environmental transformations of NMs, which need to be addressed before large-scale implementation of NMs for water purification, are also highlighted.
Fulltext Random plasma glucose levels and cause-specific mortality among Chinese adults without known diabetes: an 11-year prospective study of 450,000 people

Vermunt J, Bragg F, Halsey J, Yang L, Chen Y, Guo Y, et al.

BMJ Open Diabetes Res Care, 2021 11;9(2).
PMID: 34728472 DOI: 10.1136/bmjdrc-2021-002495

INTRODUCTION: We examined the associations between long-term usual random plasma glucose (RPG) levels and cause-specific mortality risks among adults without known diabetes in China.
RESEARCH DESIGN AND METHODS: The China Kadoorie Biobank recruited 512,891 adults (59% women) aged 30-79 from 10 regions of China during 2004-2008. At baseline survey, and subsequent resurveys of a random subset of survivors, participants were interviewed and measurements collected, including on-site RPG testing. Cause of death was ascertained via linkage to local mortality registries. Cox regression yielded adjusted HR for all-cause and cause-specific mortality associated with usual levels of RPG.
RESULTS: During median 11 years' follow-up, 37,214 deaths occurred among 452,993 participants without prior diagnosed diabetes or other chronic diseases. There were positive log-linear relationships between RPG and all-cause, cardiovascular disease (CVD) (n=14,209) and chronic kidney disease (CKD) (n=432) mortality down to usual RPG levels of at least 5.1 mmol/L. At RPG <11.1 mmol/L, each 1.0 mmol/L higher usual RPG was associated with adjusted HRs of 1.14 (95% CI 1.12 to 1.16), 1.16 (1.12 to 1.19) and 1.44 (1.22 to 1.70) for all-cause, CVD and CKD mortality, respectively. Usual RPG was positively associated with chronic liver disease (n=547; 1.45 (1.26 to 1.66)) and cancer (n=12,680; 1.12 (1.09 to 1.16)) mortality, but with comparably lower risks at baseline RPG ≥11.1 mmol/L. These associations persisted after excluding participants who developed diabetes during follow-up.
CONCLUSIONS: Among Chinese adults without diabetes, higher RPG levels were associated with higher mortality risks from several major diseases, with no evidence of apparent thresholds below the cut-points for diabetes diagnosis.

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